PT J
AU Jin, LY
   Pahuja, KB
   Wickliffe, KE
   Gorur, A
   Baumgärtel, C
   Schekman, R
   Rape, M
AF Jin, Lingyan
   Pahuja, Kanika Bajaj
   Wickliffe, Katherine E.
   Gorur, Amita
   Baumgaertel, Christine
   Schekman, Randy
   Rape, Michael
TI Ubiquitin-dependent regulation of COPII coat size and function
SO NATURE
LA English
DT Article
ID reticulum exit sites; collagen secretion; mammalian-cells; ligase; cargo; identification; proteins; adapters; organization; degradation
AB Packaging of proteins from the endoplasmic reticulum into COPII vesicles is essential for secretion. In cells, most COPII vesicles are approximately 60-80 nm in diameter, yet some must increase their size to accommodate 300-400 nm procollagen fibres or chylomicrons. Impaired COPII function results in collagen deposition defects, craniolenticulo-sutural dysplasia, or chylomicron retention disease, but mechanisms to enlarge COPII coats have remained elusive. Here, we identified the ubiquitin ligase CUL3-KLHL12 as a regulator of COPII coat formation. CUL3-KLHL12 catalyses the monoubiquitylation of the COPII-component SEC31 and drives the assembly of large COPII coats. As a result, ubiquitylation by CUL3-KLHL12 is essential for collagen export, yet less important for the transport of small cargo. We conclude that monoubiquitylation controls the size and function of a vesicle coat.
C1 [Jin, Lingyan; Pahuja, Kanika Bajaj; Wickliffe, Katherine E.; Gorur, Amita; Baumgaertel, Christine; Schekman, Randy; Rape, Michael] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA.
   [Pahuja, Kanika Bajaj; Gorur, Amita; Schekman, Randy] Univ Calif Berkeley, Howard Hughes Med Inst, Berkeley, CA 94720 USA.
C3 University of California System; University of California Berkeley; Howard Hughes Medical Institute; University of California System; University of California Berkeley
RP Rape, M (corresponding author), Univ Calif Berkeley, Dept Mol & Cell Biol, 229 Stanley Hall, Berkeley, CA 94720 USA.
EM mrape@berkeley.edu
FU Pew Foundation; NIH (NIGMS); Howard Hughes Medical Institute; CIRM
NR 41
TC 270
Z9 346
U1 2
U2 48
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 23
PY 2012
VL 482
IS 7386
BP 495
EP U213
DI 10.1038/nature10822
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 898VM
UT WOS:000300770500044
PM 22358839
DA 2026-03-09
ER

PT J
AU Liu, GH
   Qu, J
   Suzuki, K
   Nivet, E
   Li, M
   Montserrat, N
   Yi, F
   Xu, XL
   Ruiz, S
   Zhang, WQ
   Wagner, U
   Kim, A
   Ren, B
   Li, Y
   Goebl, A
   Kim, J
   Soligalla, RD
   Dubova, I
   Thompson, J
   Yates, J
   Esteban, CR
   Sancho-Martinez, I
   Belmonte, JCI
AF Liu, Guang-Hui
   Qu, Jing
   Suzuki, Keiichiro
   Nivet, Emmanuel
   Li, Mo
   Montserrat, Nuria
   Yi, Fei
   Xu, Xiuling
   Ruiz, Sergio
   Zhang, Weiqi
   Wagner, Ulrich
   Kim, Audrey
   Ren, Bing
   Li, Ying
   Goebl, April
   Kim, Jessica
   Soligalla, Rupa Devi
   Dubova, Ilir
   Thompson, James
   Yates, John, III
   Esteban, Concepcion Rodriguez
   Sancho-Martinez, Ignacio
   Izpisua Belmonte, Juan Carlos
TI Progressive degeneration of human neural stem cells caused by pathogenic LRRK2
SO NATURE
LA English
DT Article
ID homologous recombination; kinase-activity; 14-3-3 binding; disease; inhibition; mutations; efficient; expression; nucleus
AB Nuclear-architecture defects have been shown to correlate with the manifestation of a number of human diseases as well as ageing(1-4). It is therefore plausible that diseases whose manifestations correlate with ageing might be connected to the appearance of nuclear aberrations over time. We decided to evaluate nuclear organization in the context of ageing-associated disorders by focusing on a leucine-rich repeat kinase 2 (LRRK2) dominant mutation (G2019S; glycine-to-serine substitution at amino acid 2019), which is associated with familial and sporadic Parkinson's disease as well as impairment of adult neurogenesis in mice(5). Here we report on the generation of induced pluripotent stem cells (iPSCs) derived from Parkinson's disease patients and the implications of LRRK2 (G2019S) mutation in human neural-stem-cell (NSC) populations. Mutant NSCs showed increased susceptibility to proteasomal stress as well as passage-dependent deficiencies in nuclear-envelope organization, clonal expansion and neuronal differentiation. Disease phenotypes were rescued by targeted correction of the LRRK2 (G2019S) mutation with its wild-type counterpart in Parkinson's disease iPSCs and were recapitulated after targeted knock-in of the LRRK2(G2019S) mutation in human embryonic stem cells. Analysis of human brain tissue showed nuclear-envelope impairment in clinically diagnosed Parkinson's disease patients. Together, our results identify the nucleus as a previously unknown cellular organelle in Parkinson's disease pathology and may help to open new avenues for Parkinson's disease diagnoses as well as for the potential development of therapeutics targeting this fundamental cell structure.
C1 [Liu, Guang-Hui; Qu, Jing; Suzuki, Keiichiro; Nivet, Emmanuel; Li, Mo; Yi, Fei; Ruiz, Sergio; Goebl, April; Kim, Jessica; Soligalla, Rupa Devi; Dubova, Ilir; Esteban, Concepcion Rodriguez; Sancho-Martinez, Ignacio; Izpisua Belmonte, Juan Carlos] Salk Inst Biol Studies, Gene Express Lab, La Jolla, CA 92037 USA.
   [Liu, Guang-Hui; Qu, Jing; Xu, Xiuling; Zhang, Weiqi; Li, Ying] Chinese Acad Sci, Inst Biophys, Natl Lab Biomacromol, Beijing 100101, Peoples R China.
   [Montserrat, Nuria; Izpisua Belmonte, Juan Carlos] Ctr Regenerat Med Barcelona, Barcelona 08003, Spain.
   [Wagner, Ulrich; Kim, Audrey; Ren, Bing] Univ Calif San Diego, Sch Med, Ludwig Inst Canc Res, Dept Cellular & Mol Med, La Jolla, CA 92093 USA.
   [Thompson, James; Yates, John, III] Scripps Res Inst, Dept Cell Biol, La Jolla, CA 92037 USA.
C3 Salk Institute; Chinese Academy of Sciences; Institute of Biophysics, CAS; Institut d'Investigacio Biomedica de Bellvitge (IDIBELL); Centro de Medicina Regenerativa de Barcelona; University of Barcelona; Ludwig Institute for Cancer Research; University of California System; University of California San Diego; Scripps Research Institute
RP Belmonte, JCI (corresponding author), Salk Inst Biol Studies, Gene Express Lab, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA.
EM ghliu@ibp.ac.cn; belmonte@salk.edu
FU Thousand Young Talents program of China; National Laboratory of Biomacromolecules; Chinese Academy of Sciences; National Natural Science Foundation of China (NSFC) [81271266, 31222039]; Beijing Municipal Natural Science Foundation; AFAR/Ellison Medical Foundation; Uehara Memorial Foundation; F.M. Kirby Foundation; NSFC [31201111]; US National Institute of Health (NIH) [ES017166]; Ludwig Institute for Cancer Research; NIH [P41 RR011823]; Glenn Foundation; G. Harold and Leila Y. Mathers Charitable Foundation; Sanofi; California Institute of Regenerative Medicine; Ellison Medical Foundation; Helmsley Charitable Trust; ERA-Net Neuron; MINECO; Fundacion Cellex; (G. Gaslini Institute)-Telethon Genetic Biobank Network [GTB07001]
NR 30
TC 289
Z9 329
U1 0
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 22
PY 2012
VL 491
IS 7425
BP 603
EP 607
DI 10.1038/nature11557
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 040RE
UT WOS:000311339800054
PM 23075850
DA 2026-03-09
ER

PT J
AU Antonica, F
   Kasprzyk, DF
   Opitz, R
   Iacovino, M
   Liao, XH
   Dumitrescu, AM
   Refetoff, S
   Peremans, K
   Manto, M
   Kyba, M
   Costagliola, S
AF Antonica, Francesco
   Kasprzyk, Dominika Figini
   Opitz, Robert
   Iacovino, Michelina
   Liao, Xiao-Hui
   Dumitrescu, Alexandra Mihaela
   Refetoff, Samuel
   Peremans, Kathelijne
   Manto, Mario
   Kyba, Michael
   Costagliola, Sabine
TI Generation of functional thyroid from embryonic stem cells
SO NATURE
LA English
DT Article
ID in-vitro; 3-dimensional culture; follicular cells; hormone-receptor; gland; differentiation; progenitors; system; lung; hypothyroidism
AB The primary function of the thyroid gland is to metabolize iodide by synthesizing thyroid hormones, which are critical regulators of growth, development and metabolism in almost all tissues. So far, research on thyroid morphogenesis has been missing an efficient stem-cell model system that allows for the in vitro recapitulation of the molecular and morphogenic events regulating thyroid follicular-cell differentiation and subsequent assembly into functional thyroid follicles. Here we report that a transient overexpression of the transcription factors NKX2-1 and PAX8 is sufficient to direct mouse embryonic stem-cell differentiation into thyroid follicular cells that organize into three-dimensional follicular structures when treated with thyrotropin. These in vitro-derived follicles showed appreciable iodide organification activity. Importantly, when grafted in vivo into athyroid mice, these follicles rescued thyroid hormone plasma levels and promoted subsequent symptomatic recovery. Thus, mouse embryonic stem cells can be induced to differentiate into thyroid follicular cells in vitro and generate functional thyroid tissue.
C1 [Antonica, Francesco; Kasprzyk, Dominika Figini; Opitz, Robert; Costagliola, Sabine] Univ Libre Bruxelles, Inst Interdisciplinary Res Mol Human Biol IRIBHM, B-1070 Brussels, Belgium.
   [Iacovino, Michelina; Kyba, Michael] Univ Minnesota, Lillehei Heart Inst, Minneapolis, MN 55455 USA.
   [Iacovino, Michelina; Kyba, Michael] Univ Minnesota, Dept Pediat, Minneapolis, MN 55455 USA.
   [Liao, Xiao-Hui; Dumitrescu, Alexandra Mihaela; Refetoff, Samuel] Univ Chicago, Dept Med, Chicago, IL 60637 USA.
   [Refetoff, Samuel] Univ Chicago, Dept Pediat, Chicago, IL 60637 USA.
   [Refetoff, Samuel] Univ Chicago, Dept Genet, Chicago, IL 60637 USA.
   [Peremans, Kathelijne] Univ Ghent, Fac Vet Med, Dept Vet Med Imaging & Small Anim Orthopaed, B-9820 Merelbeke, Belgium.
   [Manto, Mario] Univ Libre Bruxelles, FNRS, ERASME, B-1070 Brussels, Belgium.
C3 Universite Libre de Bruxelles; University of Minnesota System; University of Minnesota Twin Cities; University of Minnesota System; University of Minnesota Twin Cities; University of Chicago; University of Chicago; University of Chicago; Ghent University; Universite Libre de Bruxelles
RP Costagliola, S (corresponding author), Univ Libre Bruxelles, Inst Interdisciplinary Res Mol Human Biol IRIBHM, 808 Route Lennik, B-1070 Brussels, Belgium.
EM scostag@ulb.ac.be
FU National Institutes of Health [DK15070, DK91016]; Belgian Fonds de la Recherche Scientifique Medicale [FRSM[2]3_4_557_08, [3]3_4598_12]; Action de Recherche Concertee de la Communaute Francaise de Belgique (ARC) [AUWB-08/13-ULB10]; Fonds d'Encouragement a la Recherche; Belgian National Fund for Scientific Research (FNRS)
NR 33
TC 238
Z9 248
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 1
PY 2012
VL 491
IS 7422
BP 66
EP U170
DI 10.1038/nature11525
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 028PM
UT WOS:000310434500031
DA 2026-03-09
ER

PT J
AU Barouch, DH
   Liu, JY
   Li, HL
   Maxfield, LF
   Abbink, P
   Lynch, DM
   Iampietro, MJ
   SanMiguel, A
   Seaman, MS
   Ferrari, G
   Forthal, DN
   Ourmanov, I
   Hirsch, VM
   Carville, A
   Mansfield, KG
   Stablein, D
   Pau, MG
   Schuitemaker, H
   Sadoff, JC
   Billings, EA
   Rao, M
   Robb, ML
   Kim, JH
   Marovich, MA
   Goudsmit, J
   Michael, NL
AF Barouch, Dan H.
   Liu, Jinyan
   Li, Hualin
   Maxfield, Lori F.
   Abbink, Peter
   Lynch, Diana M.
   Iampietro, M. Justin
   SanMiguel, Adam
   Seaman, Michael S.
   Ferrari, Guido
   Forthal, Donald N.
   Ourmanov, Ilnour
   Hirsch, Vanessa M.
   Carville, Angela
   Mansfield, Keith G.
   Stablein, Donald
   Pau, Maria G.
   Schuitemaker, Hanneke
   Sadoff, Jerald C.
   Billings, Erik A.
   Rao, Mangala
   Robb, Merlin L.
   Kim, Jerome H.
   Marovich, Mary A.
   Goudsmit, Jaap
   Michael, Nelson L.
TI Vaccine protection against acquisition of neutralization-resistant SIV challenges in rhesus monkeys
SO NATURE
LA English
DT Article
ID cellular immune-responses; low-dose challenge; infection; antibody; macaques; vectors; memory; breadth
AB Preclinical studies of human immunodeficiency virus type 1 (HIV-1) vaccine candidates have typically shown post-infection virological control, but protection against acquisition of infection has previously only been reported against neutralization-sensitive virus challenges(1-3). Here we demonstrate vaccine protection against acquisition of fully heterologous, neutralization-resistant simian immunodeficiency virus (SIV) challenges in rhesus monkeys. Adenovirus/poxvirus and adenovirus/adenovirus-vector-based vaccines expressing SIVSME543 Gag, Pol and Env antigens resulted in an 80% or greater reduction in the per-exposure probability of infection(4,5) against repetitive, intrarectal SIVMAC251 challenges in rhesus monkeys. Protection against acquisition of infection showed distinct immunological correlates compared with post-infection virological control and required the inclusion of Env in the vaccine regimen. These data demonstrate the proof-of-concept that optimized HIV-1 vaccine candidates can block acquisition of stringent, heterologous, neutralization-resistant virus challenges in rhesus monkeys.
C1 [Barouch, Dan H.; Liu, Jinyan; Li, Hualin; Maxfield, Lori F.; Abbink, Peter; Lynch, Diana M.; Iampietro, M. Justin; SanMiguel, Adam; Seaman, Michael S.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Vaccine Res, Boston, MA 02215 USA.
   [Barouch, Dan H.] Ragon Inst MGH MIT & Harvard, Boston, MA 02114 USA.
   [Ferrari, Guido] Duke Univ, Med Ctr, Durham, NC 27710 USA.
   [Forthal, Donald N.] Univ Calif Irvine, Sch Med, Irvine, CA 92717 USA.
   [Ourmanov, Ilnour; Hirsch, Vanessa M.] NIAID, Bethesda, MA 20892 USA.
   [Carville, Angela; Mansfield, Keith G.] New England Primate Res Ctr, Southborough, MA 01772 USA.
   [Stablein, Donald] EMMES Corp, Rockville, MD 20850 USA.
   [Pau, Maria G.; Schuitemaker, Hanneke; Sadoff, Jerald C.; Goudsmit, Jaap] Crucell Holland BV, NL-2301 CA Leiden, Netherlands.
   [Billings, Erik A.; Rao, Mangala; Robb, Merlin L.; Kim, Jerome H.; Marovich, Mary A.; 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; Duke University; University of California System; University of California Irvine; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID); Emmes Corporation; Johnson & Johnson; Johnson & Johnson Netherlands; Walter Reed Army Institute of Research (WRAIR); United States Department of Defense; United States Army
RP Barouch, DH (corresponding author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Vaccine Res, Boston, MA 02215 USA.
EM dbarouch@bidmc.harvard.edu
FU US Military Research and Material Command; US Military HIV Research Program [W81XWH-07-2-0067]; Ragon Institute of MGH, MIT and Harvard; National Institutes of Health [AI066924, AI078526, AI084794, AI095985, AI060354, AI002642, RR000168]; Bill and Melinda Gates Foundation; National Cancer Institute; National Institute of Allergy and Infectious Diseases; National Institute of Diabetes and Digestive and Kidney Diseases; National Institute of Dental and Craniofacial Research; National Heart Lung and Blood Institute; National Institute on Aging; National Institute on Drug Abuse; National Institute of Nursing Research; Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Institute on Minority Health and Health Disparities [P30AI060354] Funding Source: NIH RePORTER
NR 30
TC 404
Z9 467
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 2
PY 2012
VL 482
IS 7383
BP 89
EP U115
DI 10.1038/nature10766
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 884RN
UT WOS:000299726000041
PM 22217938
DA 2026-03-09
ER

PT J
AU Martincorena, I
   Seshasayee, ASN
   Luscombe, NM
AF Martincorena, Inigo
   Seshasayee, Aswin S. N.
   Luscombe, Nicholas M.
TI Evidence of non-random mutation rates suggests an evolutionary risk management strategy
SO NATURE
LA English
DT Article
ID escherichia-coli; enterobacterial genes; dna-repair; transcription; selection; genome; sequences; spectrum; increase; site
AB A central tenet in evolutionary theory is that mutations occur randomly with respect to their value to an organism; selection then governs whether they are fixed in a population. This principle has been challenged by long-standing theoretical models predicting that selection could modulate the rate of mutation itself(1,2). However, our understanding of how the mutation rate varies between different sites within a genome has been hindered by technical difficulties in measuring it. Here we present a study that overcomes previous limitations by combining phylogenetic and population genetic techniques. Upon comparing 34 Escherichia coli genomes, we observe that the neutral mutation rate varies by more than an order of magnitude across 2,659 genes, with mutational hot and cold spots spanning several kilobases. Importantly, the variation is not random: we detect a lower rate in highly expressed genes and in those undergoing stronger purifying selection. Our observations suggest that the mutation rate has been evolutionarily optimized to reduce the risk of deleterious mutations. Current knowledge of factors influencing the mutation rate-including transcription-coupled repair and context-dependent mutagenesis-do not explain these observations, indicating that additional mechanisms must be involved. The findings have important implications for our understanding of evolution and the control of mutations.
C1 [Martincorena, Inigo; Seshasayee, Aswin S. N.; Luscombe, Nicholas M.] EMBL European Bioinformat Inst, Cambridge CB10 1SD, England.
   [Luscombe, Nicholas M.] Okinawa Inst Sci & Technol, Onna Son, Okinawa 9040495, Japan.
   [Luscombe, Nicholas M.] UCL, Dept Genet Environm & Evolut, UCL Genet Inst, London WC1E 6BT, England.
   [Luscombe, Nicholas M.] Canc Res UK London Res Inst, London WC2A 3LY, England.
C3 European Molecular Biology Laboratory (EMBL); European Bioinformatics Institute; Okinawa Institute of Science & Technology Graduate University; University of London; University College London; Cancer Research UK
RP Martincorena, I (corresponding author), EMBL European Bioinformat Inst, Wellcome Trust Genome Campus, Cambridge CB10 1SD, England.
EM martinco@ebi.ac.uk; luscombe@ebi.ac.uk
FU EMBL; Spanish Ministry of Science and Innovation; Caja Madrid Foundation; Biotechnology and Biological Sciences Research Council [BB/E01075X/1] Funding Source: researchfish; Cancer Research UK [16358] Funding Source: researchfish; BBSRC [BB/E01075X/1] Funding Source: UKRI
NR 30
TC 140
Z9 163
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 MAY 3
PY 2012
VL 485
IS 7396
BP 95
EP 98
DI 10.1038/nature10995
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 934NV
UT WOS:000303451900041
PM 22522932
DA 2026-03-09
ER

PT J
AU Qu, Y
   Misaghi, S
   Izrael-Tomasevic, A
   Newton, K
   Gilmour, LL
   Lamkanfi, M
   Louie, S
   Kayagaki, N
   Liu, JF
   Kömüves, L
   Cupp, JE
   Arnott, D
   Monack, D
   Dixit, VM
AF Qu, Yan
   Misaghi, Shahram
   Izrael-Tomasevic, Anita
   Newton, Kim
   Gilmour, Laurie L.
   Lamkanfi, Mohamed
   Louie, Salina
   Kayagaki, Nobuhiko
   Liu, Jinfeng
   Koemueves, Laszlo
   Cupp, James E.
   Arnott, David
   Monack, Denise
   Dixit, Vishva M.
TI Phosphorylation of NLRC4 is critical for inflammasome activation
SO NATURE
LA English
DT Article
ID innate immune recognition; iii secretion apparatus; protein-kinase-c; francisella-tularensis; aim2 inflammasome; host-defense; ipaf; caspase-1; flagellin; salmonella
AB NLRC4 is a cytosolic member of the NOD-like receptor family that is expressed in innate immune cells. It senses indirectly bacterial flagellin and type III secretion systems, and responds by assembling an inflammasome complex that promotes caspase-1 activation and pyroptosis(1-6). Here we use knock-in mice expressing NLRC4 with a carboxy-terminal 3xFlag tag to identify phosphorylation of NLRC4 on a single, evolutionarily conserved residue, Ser 533, following infection of macrophages with Salmonella enterica serovar Typhimurium (also known as Salmonella typhimurium). Western blotting with a NLRC4 phospho-Ser 533 antibody confirmed that this post-translational modification occurs only in the presence of stimuli known to engage NLRC4 and not the related protein NLRP3 or AIM2. Nlrc4(-/-) macrophages reconstituted with NLRC4 mutant S533A, unlike those reconstituted with wild-type NLRC4, did not activate caspase-1 and pyroptosis in response to S. typhimurium, indicating that S533 phosphorylation is critical for NLRC4 inflammasome function. Conversely, phosphomimetic NLRC4 S533D caused rapid macrophage pyroptosis without infection. Biochemical purification of the NLRC4-phosphorylating activity and a screen of kinase inhibitors identified PRKCD (PKC delta) as a candidate NLRC4 kinase. Recombinant PKC delta phosphorylated NLRC4 S533 in vitro, immunodepletion of PKC delta from macrophage lysates blocked NLRC4 S533 phosphorylation in vitro, and Prkcd(-/-) macrophages exhibited greatly attenuated caspase-1 activation and IL-1 beta secretion specifically in response to S. typhimurium. Phosphorylation-defective NLRC4 S533A failed to recruit procaspase-1 and did not assemble inflammasome specks(7) during S. typhimurium infection, so phosphorylation of NLRC4 S533 probably drives conformational changes necessary for NLRC4 inflammasome activity and host innate immunity.
C1 [Qu, Yan; Newton, Kim; Kayagaki, Nobuhiko; Dixit, Vishva M.] Genentech Inc, Dept Physiol Chem, San Francisco, CA 94080 USA.
   [Misaghi, Shahram; Louie, Salina] Genentech Inc, Dept Early Stage Cell Culture, San Francisco, CA 94080 USA.
   [Izrael-Tomasevic, Anita; Arnott, David] Genentech Inc, Dept Prot Chem, San Francisco, CA 94080 USA.
   [Gilmour, Laurie L.; Cupp, James E.] Genentech Inc, Dept Immunol, San Francisco, CA 94080 USA.
   [Lamkanfi, Mohamed] VIB, Dept Med Prot Res, B-9000 Ghent, Belgium.
   [Lamkanfi, Mohamed] Univ Ghent, Dept Biochem, B-9000 Ghent, Belgium.
   [Liu, Jinfeng] Genentech Inc, Dept Bioinformat & Computat Biol, San Francisco, CA 94080 USA.
   [Koemueves, Laszlo] Genentech Inc, Dept Pathol, San Francisco, CA 94080 USA.
   [Monack, Denise] Stanford Sch Med, Dept Microbiol & Immunol, Stanford, CA 94305 USA.
C3 Roche Holding; Genentech; Roche Holding USA; Roche Holding; Genentech; Roche Holding USA; Roche Holding; Genentech; Roche Holding USA; Roche Holding; Roche Holding USA; Genentech; Flanders Institute for Biotechnology (VIB); Ghent University; Roche Holding; Genentech; Roche Holding USA; Roche Holding; Genentech; Roche Holding USA; Stanford University
RP Dixit, VM (corresponding author), Genentech Inc, Dept Physiol Chem, 1 DNA Way, San Francisco, CA 94080 USA.
EM dixit@gene.com
NR 22
TC 245
Z9 298
U1 0
U2 86
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD OCT 25
PY 2012
VL 490
IS 7421
BP 539
EP +
DI 10.1038/nature11429
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 025NK
UT WOS:000310196200042
PM 22885697
DA 2026-03-09
ER

PT J
AU Huang, CS
   Ge, P
   Zhou, ZH
   Tong, L
AF Huang, Christine S.
   Ge, Peng
   Zhou, Z. Hong
   Tong, Liang
TI An unanticipated architecture of the 750-kDa α6β6 holoenzyme of 3-methylcrotonyl-CoA carboxylase
SO NATURE
LA English
DT Article
ID aureus pyruvate-carboxylase; coenzyme-a; crystal-structure; substrate-specificity; coa carboxylases; molecular-basis; mccb mutations; deficiency; mechanism; software
AB 3-Methylcrotonyl-CoA carboxylase (MCC), a member of the biotin-dependent carboxylase superfamily, is essential for the metabolism of leucine, and deficient mutations in this enzyme are linked to methylcrotonylglycinuria (MCG) and other serious diseases in humans(1-8). MCC has strong sequence conservation with propionyl-CoA carboxylase (PCC), and their holoenzymes are both 750-kilodalton (kDa) alpha(6)beta(6) dodecamers. Therefore the architecture of the MCC holoenzyme is expected to be highly similar to that of PCC9. Here we report the crystal structures of the Pseudomonas aeruginosa MCC (PaMCC) holoenzyme, alone and in complex with coenzyme A. Surprisingly, the structures show that the architecture and overall shape of PaMCC are markedly different when compared to PCC. The alpha-subunits show trimeric association in the PaMCC holoenzyme, whereas they have no contacts with each other in PCC. Moreover, the positions of the two domains in the beta-subunit of PaMCC are swapped relative to those in PCC. This structural information establishes a foundation for understanding the disease-causing mutations of MCC and provides new insights into the catalytic mechanism and evolution of biotin-dependent carboxylases. The large structural differences between MCC and PCC also have general implications for the relationship between sequence conservation and structural similarity.
C1 [Huang, Christine S.; Tong, Liang] Columbia Univ, Dept Biol Sci, New York, NY 10027 USA.
   [Ge, Peng; Zhou, Z. Hong] Univ Calif Los Angeles, Dept Microbiol Immunol & Mol Genet, Calif NanoSyst Inst, Los Angeles, CA 90095 USA.
C3 Columbia University; University of California System; University of California Los Angeles
RP Tong, L (corresponding author), Columbia Univ, Dept Biol Sci, New York, NY 10027 USA.
EM ltong@columbia.edu
FU National Institutes of Health (NIH) [DK067238, GM071940, GM08281]; National Institute of General Medical Sciences [R01GM071940] Funding Source: NIH RePORTER
NR 33
TC 39
Z9 53
U1 2
U2 20
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JAN 12
PY 2012
VL 481
IS 7380
BP 219
EP +
DI 10.1038/nature10691
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 874TO
UT WOS:000298981200043
PM 22158123
DA 2026-03-09
ER

PT J
AU Lau, WCY
   Rubinstein, JL
AF Lau, Wilson C. Y.
   Rubinstein, John L.
TI Subnanometre-resolution structure of the intact Thermus thermophilus H+-driven ATP synthase
SO NATURE
LA English
DT Article
ID rotor ring; v-atpase; membrane topology; crystal-structure; central stalk; na+-atpase; subunit-c; translocation; architecture; maps
AB Ion-translocating rotary ATPases serve either as ATP synthases, using energy from a transmembrane ion motive force to create the cell's supply of ATP, or as transmembrane ion pumps that are powered by ATP hydrolysis(1). The members of this family of enzymes each contain two rotary motors: one that couples ion translocation to rotation and one that couples rotation to ATP synthesis or hydrolysis. During ATP synthesis, ion translocation through the membrane-bound region of the complex causes rotation of a central rotor that drives conformational changes and ATP synthesis in the catalytic region of the complex. There are no structural models available for the intact membrane region of any ion-translocating rotary ATPase. Here we present a 9.7 angstrom resolution map of the H+-driven ATP synthase from Thermus thermophilus obtained by electron cryomicroscopy of single particles in ice. The 600-kilodalton complex has an overall subunit composition of A(3)B(3)CDE(2)FG(2)IL(12). The membrane-bound motor consists of a ring of L subunits and the carboxy-terminal region of subunit I, which are equivalent to the c and a subunits of most other rotary ATPases, respectively. The map shows that the ring contains 12 L subunits(2) and that the I subunit has eight transmembrane helices(3). The L-12 ring and I subunit have a surprisingly small contact area in the middle of the membrane, with helices from the I subunit making contacts with two different L subunits. The transmembrane helices of subunit I form bundles that could serve as half-channels across the membrane, with the first half-channel conducting protons from the periplasm to the L-12 ring and the second half-channel conducting protons from the L-12 ring to the cytoplasm. This structure therefore suggests the mechanism by which a transmembrane proton motive force is converted to rotation in rotary ATPases.
C1 [Lau, Wilson C. Y.; Rubinstein, John L.] Hosp Sick Children, Mol Struct & Funct Program, Res Inst, Toronto, ON M5G 1X8, Canada.
   [Lau, Wilson C. Y.; Rubinstein, John L.] Univ Toronto, Dept Biochem, Toronto, ON M5S 1A8, Canada.
   [Rubinstein, John L.] Univ Toronto, Dept Med Biophys, Toronto, ON M5G 2M9, Canada.
C3 University of Toronto; Hospital for Sick Children (SickKids); University of Toronto; University of Toronto
RP Rubinstein, JL (corresponding author), Hosp Sick Children, Mol Struct & Funct Program, Res Inst, 555 Univ Ave, Toronto, ON M5G 1X8, Canada.
EM john.rubinstein@utoronto.ca
FU Ontario Graduate Scholarship; Ontario Ministry of Research and Innovation; Canadian Institutes of Health Research [MOP 81294]
NR 41
TC 97
Z9 108
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 JAN 12
PY 2012
VL 481
IS 7380
BP 214
EP +
DI 10.1038/nature10699
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 874TO
UT WOS:000298981200042
PM 22178924
DA 2026-03-09
ER

PT J
AU Pani, AM
   Mullarkey, EE
   Aronowicz, J
   Assimacopoulos, S
   Grove, EA
   Lowe, CJ
AF Pani, Ariel M.
   Mullarkey, Erin E.
   Aronowicz, Jochanan
   Assimacopoulos, Stavroula
   Grove, Elizabeth A.
   Lowe, Christopher J.
TI Ancient deuterostome origins of vertebrate brain signalling centres
SO NATURE
LA English
DT Article
ID hemichordate saccoglossus-kowalevskii; nervous-system; forebrain development; transcription factors; cell fate; fgf8; amphioxus; hedgehog; evolutionary; expression
AB Neuroectodermal signalling centres induce and pattern many novel vertebrate brain structures but are absent, or divergent, in invertebrate chordates. This has led to the idea that signalling-centre genetic programs were first assembled in stem vertebrates and potentially drove morphological innovations of the brain. However, this scenario presumes that extant cephalochordates accurately represent ancestral chordate characters, which has not been tested using close chordate outgroups. Here we report that genetic programs homologous to three vertebrate signalling centres-the anterior neural ridge, zona limitans intrathalamica and isthmic organizer-are present in the hemichordate Saccoglossus kowalevskii. Fgf8/17/18 (a single gene homologous to vertebrate Fgf8, Fgf17 and Fgf18), sfrp1/5, hh and wnt1 are expressed in vertebrate-like arrangements in hemichordate ectoderm, and homologous genetic mechanisms regulate ectodermal patterning in both animals. We propose that these genetic programs were components of an unexpectedly complex, ancient genetic regulatory scaffold for deuterostome body patterning that degenerated in amphioxus and ascidians, but was retained to pattern divergent structures in hemichordates and vertebrates.
C1 [Pani, Ariel M.; Lowe, Christopher J.] Univ Chicago, Comm Evolut Biol, Chicago, IL 60637 USA.
   [Pani, Ariel M.; Lowe, Christopher J.] Stanford Univ, Hopkins Marine Stn, Dept Biol, Pacific Grove, CA 93950 USA.
   [Mullarkey, Erin E.; Grove, Elizabeth A.] Univ Chicago, Comm Neurobiol, Chicago, IL 60637 USA.
   [Aronowicz, Jochanan; Grove, Elizabeth A.; Lowe, Christopher J.] Univ Chicago, Dept Organismal Biol & Anat, Chicago, IL 60637 USA.
   [Assimacopoulos, Stavroula; Grove, Elizabeth A.] Univ Chicago, Dept Neurobiol, Chicago, IL 60637 USA.
C3 University of Chicago; Stanford University; University of Chicago; University of Chicago; University of Chicago
RP Lowe, CJ (corresponding author), Univ Chicago, Comm Evolut Biol, 1025 E 57th St, Chicago, IL 60637 USA.
EM clowe@stanford.edu
FU Searle Kinship Foundation; Brain Research Foundation; National Science Foundation [1049106]; National Institutes of Health [R01 HD42330]; University of Chicago; Marine Biological Laboratory Frank R. Lillie Fellowship; National Institute of Child Health and Development [1T32HD055164-01A1]; National Institute of Neurological Disorders and Stroke [1F31NS074738-01A1]; National Science and Engineering Research Council of Canada; Eunice Kennedy Shriver National Institute of Child Health and Human Development [T32HD055164, T32HD007009] Funding Source: NIH RePORTER; Direct For Biological Sciences; Division Of Integrative Organismal Systems [1049106] Funding Source: National Science Foundation
NR 50
TC 202
Z9 221
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 MAR 15
PY 2012
VL 483
IS 7389
BP 289
EP U79
DI 10.1038/nature10838
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 908HP
UT WOS:000301481800040
PM 22422262
DA 2026-03-09
ER

PT J
AU Hansen, LN
   Zimmerman, ME
   Kohlstedt, DL
AF Hansen, L. N.
   Zimmerman, M. E.
   Kohlstedt, D. L.
TI Laboratory measurements of the viscous anisotropy of olivine aggregates
SO NATURE
LA English
DT Article
ID lattice-preferred orientation; oceanic upper-mantle; mechanical anisotropy; seismic anisotropy; simple shear; deformation; viscosity; strain; flow
AB A marked anisotropy in viscosity develops in Earth's mantle as deformation strongly aligns the crystallographic axes of the individual grains that comprise the rocks. On the basis of geodynamic simulations, processes significantly affected by viscous anisotropy include post-glacial rebound(1,2), foundering of lithosphere(3) and melt production above subduction zones(4). However, an estimate of the magnitude of viscous anisotropy based on the results of deformation experiments on single crystals(5) differs by three orders of magnitude from that obtained by grain-scale numerical models of deforming aggregates with strong crystallographic alignment(6-8). Complicating matters, recent experiments indicate that deformation of the uppermost mantle is dominated by dislocation-accommodated grain-boundary sliding(9), a mechanism not activated in experiments on single crystals and not included in numerical models. Here, using direct measurements of the viscous anisotropy of highly deformed polycrystalline olivine, we demonstrate a significant directional dependence of viscosity. Specifically, shear viscosities measured in high-strain torsion experiments are 15 times smaller than normal viscosities measured in subsequent tension tests performed parallel to the torsion axis. This anisotropy is approximately an order of magnitude larger than that predicted by grain-scale simulations. These results indicate that dislocation-accommodated grain-boundary sliding produces an appreciable anisotropy in rock viscosity. We propose that crystallographic alignment imparts viscous anisotropy because the rate of deformation is limited by the movement of dislocations through the interiors of the crystallographically aligned grains. The maximum degree of anisotropy is reached at geologically low shear strain (of about ten) such that deforming regions of the upper mantle will exhibit significant viscous anisotropy.
C1 [Hansen, L. N.; Zimmerman, M. E.; Kohlstedt, D. L.] Univ Minnesota, Dept Earth Sci, Minneapolis, MN 55455 USA.
C3 University of Minnesota System; University of Minnesota Twin Cities
RP Hansen, LN (corresponding author), Stanford Univ, Dept Geol & Environm Sci, 450 Serra Mall,Bldg 320, Stanford, CA 94305 USA.
EM lars.norman.hansen@gmail.com
FU NSF [EAR1214876]; NSF through the NNIN programme; Division Of Earth Sciences; Directorate For Geosciences [1015343, 1214876] Funding Source: National Science Foundation
NR 30
TC 81
Z9 93
U1 2
U2 84
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD DEC 20
PY 2012
VL 492
IS 7429
BP 415
EP +
DI 10.1038/nature11671
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 056KQ
UT WOS:000312488200053
PM 23257885
DA 2026-03-09
ER

PT J
AU Yao, XC
   Wang, TX
   Chen, HZ
   Gao, WB
   Fowler, AG
   Raussendorf, R
   Chen, ZB
   Liu, NL
   Lu, CY
   Deng, YJ
   Chen, YA
   Pan, JW
AF Yao, Xing-Can
   Wang, Tian-Xiong
   Chen, Hao-Ze
   Gao, Wei-Bo
   Fowler, Austin G.
   Raussendorf, Robert
   Chen, Zeng-Bing
   Liu, Nai-Le
   Lu, Chao-Yang
   Deng, You-Jin
   Chen, Yu-Ao
   Pan, Jian-Wei
TI Experimental demonstration of topological error correction
SO NATURE
LA English
DT Article
ID quantum; codes
AB Scalable quantum computing can be achieved only if quantum bits are manipulated in a fault-tolerant fashion. Topological error correction-a method that combines topological quantum computation with quantum error correction-has the highest known tolerable error rate for a local architecture. The technique makes use of cluster states with topological properties and requires only nearest-neighbour interactions. Here we report the experimental demonstration of topological error correction with an eight-photon cluster state. We show that a correlation can be protected against a single error on any quantum bit. Also, when all quantum bits are simultaneously subjected to errors with equal probability, the effective error rate can be significantly reduced. Our work demonstrates the viability of topological error correction for fault-tolerant quantum information processing.
C1 [Yao, Xing-Can; Wang, Tian-Xiong; Chen, Hao-Ze; Gao, Wei-Bo; Chen, Zeng-Bing; Liu, Nai-Le; Lu, Chao-Yang; Deng, You-Jin; Chen, Yu-Ao; Pan, Jian-Wei] Univ Sci & Technol China, Natl Lab Phys Sci Microscale, Shanghai Branch, Shanghai 201315, Peoples R China.
   [Yao, Xing-Can; Wang, Tian-Xiong; Chen, Hao-Ze; Gao, Wei-Bo; Chen, Zeng-Bing; Liu, Nai-Le; Lu, Chao-Yang; Deng, You-Jin; Chen, Yu-Ao; Pan, Jian-Wei] Univ Sci & Technol China, Dept Modern Phys, Shanghai 201315, Peoples R China.
   [Fowler, Austin G.] Univ Melbourne, Sch Phys, CQC2T, Melbourne, Vic 3010, Australia.
   [Raussendorf, Robert] Univ British Columbia, Dept Phys & Astron, Vancouver, BC V6T 1Z1, Canada.
C3 Chinese Academy of Sciences; University of Science & Technology of China, CAS; Chinese Academy of Sciences; University of Science & Technology of China, CAS; University of Melbourne; University of British Columbia
RP Chen, YA (corresponding author), Univ Sci & Technol China, Natl Lab Phys Sci Microscale, Shanghai Branch, Shanghai 201315, Peoples R China.
EM yuaochen@ustc.edu.cn; pan@ustc.edu.cn
FU NNSF of China; CAS; National Fundamental Research Program [2011CB921300]; NSERC
NR 43
TC 179
Z9 197
U1 2
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 FEB 23
PY 2012
VL 482
IS 7386
BP 489
EP 494
DI 10.1038/nature10770
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 898VM
UT WOS:000300770500043
PM 22358838
DA 2026-03-09
ER

PT J
AU Zuber, MT
   Head, JW
   Smith, DE
   Neumann, GA
   Mazarico, E
   Torrence, MH
   Aharonson, O
   Tye, AR
   Fassett, CI
   Rosenburg, MA
   Melosh, HJ
AF Zuber, Maria T.
   Head, James W.
   Smith, David E.
   Neumann, Gregory A.
   Mazarico, Erwan
   Torrence, Mark H.
   Aharonson, Oded
   Tye, Alexander R.
   Fassett, Caleb I.
   Rosenburg, Margaret A.
   Melosh, H. Jay
TI Constraints on the volatile distribution within Shackleton crater at the lunar south pole
SO NATURE
LA English
DT Article
ID ice
AB Shackleton crater is nearly coincident with the Moon's south pole. Its interior receives almost no direct sunlight and is a perennial cold trap(1,2), making Shackleton a promising candidate location in which to seek sequestered volatiles(3). However, previous orbital and Earth-based radar mapping(4-8) and orbital optical imaging(9) have yielded conflicting interpretations about the existence of volatiles. Here we present observations from the Lunar Orbiter Laser Altimeter on board the Lunar Reconnaissance Orbiter, revealing Shackleton to be an ancient, unusually well-preserved simple crater whose interior walls are fresher than its floor and rim. Shackleton floor deposits are nearly the same age as the rim, suggesting that little floor deposition has occurred since the crater formed more than three billion years ago. At a wavelength of 1,064 nanometres, the floor of Shackleton is brighter than the surrounding terrain and the interiors of nearby craters, but not as bright as the interior walls. The combined observations are explicable primarily by downslope movement of regolith on the walls exposing fresher underlying material. The relatively brighter crater floor is most simply explained by decreased space weathering due to shadowing, but a one-micrometre-thick layer containing about 20 per cent surficial ice is an alternative possibility.
C1 [Zuber, Maria T.; Smith, David E.; Mazarico, Erwan] MIT, Dept Earth Atmospher & Planetary Sci, Cambridge, MA 02139 USA.
   [Head, James W.; Tye, Alexander R.; Fassett, Caleb I.] Brown Univ, Dept Geol Sci, Providence, RI 02912 USA.
   [Neumann, Gregory A.] NASA, Solar Syst Explorat Div, Goddard Space Flight Ctr, Greenbelt, MD 20771 USA.
   [Torrence, Mark H.] Stinger Ghaffarian Technol, Greenbelt, MD 20770 USA.
   [Aharonson, Oded; Rosenburg, Margaret A.] CALTECH, Div Geol & Planetary Sci, Pasadena, CA 91125 USA.
   [Melosh, H. Jay] Purdue Univ, Dept Earth & Atmospher Sci, W Lafayette, IN 47907 USA.
C3 Massachusetts Institute of Technology (MIT); Brown University; National Aeronautics & Space Administration (NASA); NASA Goddard Space Flight Center; Stinger Ghaffarian Technologies, Inc. (SGT); California Institute of Technology; Purdue University System; Purdue University
RP Zuber, MT (corresponding author), MIT, Dept Earth Atmospher & Planetary Sci, Cambridge, MA 02139 USA.
EM zuber@mit.edu
FU Lunar Reconnaissance Orbiter Mission under NASA's Exploration Systems Mission Directorate; Lunar Reconnaissance Orbiter Mission under NASA's Science Mission Directorate
NR 31
TC 138
Z9 163
U1 2
U2 40
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 21
PY 2012
VL 486
IS 7403
BP 378
EP +
DI 10.1038/nature11216
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 961LV
UT WOS:000305466800038
PM 22722197
DA 2026-03-09
ER

PT J
AU Prindle, A
   Samayoa, P
   Razinkov, I
   Danino, T
   Tsimring, LS
   Hasty, J
AF Prindle, Arthur
   Samayoa, Phillip
   Razinkov, Ivan
   Danino, Tal
   Tsimring, Lev S.
   Hasty, Jeff
TI A sensing array of radically coupled genetic 'biopixels'
SO NATURE
LA English
DT Article
ID escherichia-coli; superoxide-dismutase; cell communication; synthetic biology; bacteria; networks; circuits; design; system; noise
AB Although there has been considerable progress in the development of engineering principles for synthetic biology, a substantial challenge is the construction of robust circuits in a noisy cellular environment. Such an environment leads to considerable intercellular variability in circuit behaviour, which can hinder functionality at the colony level. Here we engineer the synchronization of thousands of oscillating colony 'biopixels' over centimetre-length scales through the use of synergistic intercellular coupling involving quorum sensing within a colony and gas-phase redox signalling between colonies. We use this platform to construct a liquid crystal display (LCD)-like macroscopic clock that can be used to sense arsenic via modulation of the oscillatory period. Given the repertoire of sensing capabilities of bacteria such as Escherichia coli, the ability to coordinate their behaviour over large length scales sets the stage for the construction of low cost genetic biosensors that are capable of detecting heavy metals and pathogens in the field.
C1 [Prindle, Arthur; Razinkov, Ivan; Danino, Tal; Hasty, Jeff] Univ Calif San Diego, Dept Bioengn, La Jolla, CA 92093 USA.
   [Samayoa, Phillip; Hasty, Jeff] Univ Calif San Diego, Bioinformat Program, 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; 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 Institutes of Health and General Medicine [R01GM69811]; San Diego Center for Systems Biology [P50GM085764]; DoD NDSEG; NSF; Office of Naval Research [MURI N00014-07-0741]; National Institute of General Medical Sciences [R01GM069811] Funding Source: NIH RePORTER
NR 50
TC 296
Z9 393
U1 1
U2 215
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JAN 5
PY 2012
VL 481
IS 7379
BP 39
EP 44
DI 10.1038/nature10722
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 872VD
UT WOS:000298836900024
PM 22178928
DA 2026-03-09
ER

PT J
AU Teanby, NA
   Irwin, PGJ
   Nixon, CA
   de Kok, R
   Vinatier, S
   Coustenis, A
   Sefton-Nash, E
   Calcutt, SB
   Flasar, FM
AF Teanby, Nicholas A.
   Irwin, Patrick G. J.
   Nixon, Conor A.
   de Kok, Remco
   Vinatier, Sandrine
   Coustenis, Athena
   Sefton-Nash, Elliot
   Calcutt, Simon B.
   Flasar, F. Michael
TI Active upper-atmosphere chemistry and dynamics from polar circulation reversal on Titan
SO NATURE
LA English
DT Article
ID composite infrared spectrometer; cassini/cirs data; temperatures; model; mesosphere
AB Saturn's moon Titan has a nitrogen atmosphere comparable to Earth's, with a surface pressure of 1.4 bar. Numerical models reproduce the tropospheric conditions very well but have trouble explaining the observed middle-atmosphere temperatures, composition and winds(1,2). The top of the middle-atmosphere circulation has been thought to lie at an altitude of 450 to 500 kilometres, where there is a layer of haze that appears to be separated from the main haze deck(3). This 'detached' haze was previously explained as being due to the co-location of peak haze production and the limit of dynamical transport by the circulation's upper branch(4). Here we report a build-up of trace gases over the south pole approximately two years after observing the 2009 post-equinox circulation reversal, from which we conclude that middle-atmosphere circulation must extend to an altitude of at least 600 kilometres. The primary drivers of this circulation are summer-hemisphere heating of haze by absorption of solar radiation and winter-hemisphere cooling due to infrared emission by haze and trace gases(5); our results therefore imply that these effects are important well into the thermosphere (altitudes higher than 500 kilometres). This requires both active upper-atmosphere chemistry, consistent with the detection of high-complexity molecules and ions at altitudes greater than 950 kilometres(6,7), and an alternative explanation for the detached haze, such as a transition in haze particle growth from monomers to fractal structures(8).
C1 [Teanby, Nicholas A.; Sefton-Nash, Elliot] Univ Bristol, Sch Earth Sci, Bristol BS8 1RJ, Avon, England.
   [Irwin, Patrick G. J.; Calcutt, Simon B.] Univ Oxford, Dept Phys, Clarendon Lab, Oxford OX1 3PU, England.
   [Nixon, Conor A.; Flasar, F. Michael] NASA, Planetary Syst Lab, Goddard Space Flight Ctr, Greenbelt, MD 20771 USA.
   [de Kok, Remco] SRON, Netherlands Inst Space Res, NL-3584 CA Utrecht, Netherlands.
   [Vinatier, Sandrine; Coustenis, Athena] Univ Paris Diderot, LESIA Observ Paris, CNRS, Univ Paris 06, F-92195 Meudon, France.
   [Sefton-Nash, Elliot] Univ Calif Los Angeles, Dept Earth & Space Sci, Los Angeles, CA 90095 USA.
C3 University of Bristol; University of Oxford; National Aeronautics & Space Administration (NASA); NASA Goddard Space Flight Center; Universite Paris Cite; Universite PSL; Observatoire de Paris; Centre National de la Recherche Scientifique (CNRS); Sorbonne Universite; University of California System; University of California Los Angeles
RP Teanby, NA (corresponding author), Univ Bristol, Sch Earth Sci, Wills Mem Bldg,Queens Rd, Bristol BS8 1RJ, Avon, England.
EM n.teanby@bristol.ac.uk
FU UK Science and Technology Facilities Council; Leverhulme Trust; NASA Cassini mission; Science and Technology Facilities Council [PP/D000866/1, ST/F007957/2, ST/I001948/1, ST/I001018/1] Funding Source: researchfish; UK Space Agency [ST/J004545/1] Funding Source: researchfish; STFC [ST/I001948/1, PP/D000866/1, ST/I001018/1, ST/F007957/2] Funding Source: UKRI
NR 30
TC 82
Z9 89
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 NOV 29
PY 2012
VL 491
IS 7426
BP 732
EP 735
DI 10.1038/nature11611
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 044FY
UT WOS:000311606000039
PM 23192150
DA 2026-03-09
ER

PT J
AU Andrault, D
   Petitgirard, S
   Lo Nigro, G
   Devidal, JL
   Veronesi, G
   Garbarino, G
   Mezouar, M
AF Andrault, Denis
   Petitgirard, Sylvain
   Lo Nigro, Giacomo
   Devidal, Jean-Luc
   Veronesi, Giulia
   Garbarino, Gaston
   Mezouar, Mohamed
TI Solid-liquid iron partitioning in Earth's deep mantle
SO NATURE
LA English
DT Article
ID post-perovskite; silicate perovskite; melting experiments; magma ocean; peridotite; constraints; signature; boundary; elements; system
AB Melting processes in the deep mantle have important implications for the origin of the deep-derived plumes believed to feed hotspot volcanoes such as those in Hawaii(1). They also provide insight into how the mantle has evolved, geochemically and dynamically, since the formation of Earth(2). Melt production in the shallow mantle is quite well understood, but deeper melting near the core-mantle boundary remains controversial. Modelling the dynamic behaviour of deep, partially molten mantle requires knowledge of the density contrast between solid and melt fractions. Although both positive and negative melt buoyancies can produce major chemical segregation between different geochemical reservoirs, each type of buoyancy yields drastically different geodynamical models. Ascent or descent of liquids in a partially molten deep mantle should contribute to surface volcanism or production of a deep magma ocean, respectively. We investigated phase relations in a partially molten chondritic-type material under deep-mantle conditions. Here we show that the iron partition coefficient between aluminium-bearing (Mg,Fe)SiO3 perovskite and liquid is between 0.45 and 0.6, so iron is not as incompatible with deep-mantle minerals as has been reported previously(3). Calculated solid and melt density contrasts suggest that melt generated at the core-mantle boundary should be buoyant, and hence should segregate upwards. In the framework of the magma oceans induced by large meteoritic impacts on early Earth, our results imply that the magma crystallization should push the liquids towards the surface and form a deep solid residue depleted in incompatible elements.
C1 [Andrault, Denis; Lo Nigro, Giacomo; Devidal, Jean-Luc] Univ Blaise Pascal, CNRS, IRD, Lab Magmas & Volcans, F-63038 Clermont Ferrand, France.
   [Petitgirard, Sylvain; Veronesi, Giulia; Garbarino, Gaston; Mezouar, Mohamed] European Synchrotron Radiat Facil, F-38043 Grenoble, France.
C3 Institut de Recherche pour le Developpement (IRD); Universite Clermont Auvergne (UCA); Centre National de la Recherche Scientifique (CNRS); European Synchrotron Radiation Facility (ESRF)
RP Andrault, D (corresponding author), Univ Blaise Pascal, CNRS, IRD, Lab Magmas & Volcans, F-63038 Clermont Ferrand, France.
EM d.andrault@opgc.univ-bpclermont.fr
FU French National Centre for Scientific Research's National Institute for Earth Sciences and Astronomy; ESRF; European C2C programme
NR 40
TC 138
Z9 151
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 JUL 19
PY 2012
VL 487
IS 7407
BP 354
EP +
DI 10.1038/nature11294
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 975JB
UT WOS:000306506500040
PM 22810700
DA 2026-03-09
ER

PT J
AU Vegetti, S
   Lagattuta, DJ
   McKean, JP
   Auger, MW
   Fassnacht, CD
   Koopmans, LVE
AF Vegetti, S.
   Lagattuta, D. J.
   McKean, J. P.
   Auger, M. W.
   Fassnacht, C. D.
   Koopmans, L. V. E.
TI Gravitational detection of a low-mass dark satellite galaxy at cosmological distance
SO NATURE
LA English
DT Article
ID milky-way; matter substructure; lenses; haloes; statistics; subhaloes; b1938+666; evolution; scale
AB The mass function of dwarf satellite galaxies that are observed around Local Group galaxies differs substantially from simulations(1-5) based on cold dark matter: the simulations predict many more dwarf galaxies than are seen. The Local Group, however, may be anomalous in this regard(6,7). A massive dark satellite in an early-type lens galaxy at a redshift of 0.222 was recently found(8) using a method based on gravitational lensing(9,10), suggesting that the mass fraction contained in substructure could be higher than is predicted from simulations. The lack of very low-mass detections, however, prohibited any constraint on their mass function. Here we report the presence of a (1.9 +/- 0.1) x 10(8)M(circle dot) dark satellite galaxy in the Einstein ring system JVAS B1938+666 (ref. 11) at a redshift of 0.881, where M(circle dot) denotes the solar mass. This satellite galaxy has a mass similar to that of the Sagittarius(12) galaxy, which is a satellite of the Milky Way. We determine the logarithmic slope of the mass function for substructure beyond the local Universe to be 1.1(-0.4)(+0.6), with an average mass fraction of 3.3(-1.8)(+3.6) per cent, by combining data on both of these recently discovered galaxies. Our results are consistent with the predictions from cold dark matter simulations(13-15) at the 95 per cent confidence level, and therefore agree with the view that galaxies formed hierarchically in a Universe composed of cold dark matter.
C1 [Vegetti, S.] MIT, Kavli Inst Astrophys & Space Res, Cambridge, MA 02139 USA.
   [Lagattuta, D. J.; Fassnacht, C. D.] Univ Calif Davis, Dept Phys, Davis, CA 95616 USA.
   [McKean, J. P.] ASTRON, NL-7991 PD Dwingeloo, Netherlands.
   [Auger, M. W.] Univ Calif Santa Barbara, Dept Phys, Santa Barbara, CA 93106 USA.
   [Koopmans, L. V. E.] Univ Groningen, Kapteyn Astron Inst, NL-9700 AV Groningen, Netherlands.
C3 Massachusetts Institute of Technology (MIT); University of California System; University of California Davis; University of California System; University of California Santa Barbara; University of Groningen; Kapteyn Astronomical Institute
RP Vegetti, S (corresponding author), MIT, Kavli Inst Astrophys & Space Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
EM svegetti@space.mit.edu
FU Massachusetts Institute of Technology; NWO-VIDI; National Science Foundation; Science and Technology Facilities Council [ST/J001538/1, ST/H00243X/1] Funding Source: researchfish; STFC [ST/J001538/1] Funding Source: UKRI
NR 28
TC 321
Z9 367
U1 0
U2 5
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JAN 19
PY 2012
VL 481
IS 7381
BP 341
EP 343
DI 10.1038/nature10669
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 877VK
UT WOS:000299210600037
PM 22258612
DA 2026-03-09
ER

PT J
AU Larivière, L
   Plaschka, C
   Seizl, M
   Wenzeck, L
   Kurth, F
   Cramer, P
AF Lariviere, Laurent
   Plaschka, Clemens
   Seizl, Martin
   Wenzeck, Larissa
   Kurth, Fabian
   Cramer, Patrick
TI Structure of the Mediator head module
SO NATURE
LA English
DT Article
ID rna-polymerase-ii; transcription initiation; preinitiation complex; maximum-likelihood; yeast; recruitment; protein; ctd; architecture; holoenzyme
AB Gene transcription by RNA polymerase (Pol) II requires the coactivator complex Mediator. Mediator connects transcriptional regulators and Pol II, and is linked to human disease(1-4). Mediator from the yeast Saccharomyces cerevisiae has a molecular mass of 1.4 megadaltons and comprises 25 subunits that form the head, middle, tail and kinase modules(5-7). The head module constitutes one-half of the essential Mediator core(8), and comprises the conserved(9) subunits Med6, Med8, Med11, Med17, Med18, Med20 and Med22. Recent X-ray analysis of the S. cerevisiae head module at 4.3 angstrom resolution led to a partial architectural model with three submodules called neck, fixed jaw and moveable jaw(10). Here we determine de novo the crystal structure of the head module from the fission yeast Schizosaccharomyces pombe at 3.4 angstrom resolution. Structure solution was enabled by new structures of Med6 and the fixed jaw, and previous structures of the moveable jaw(11) and part of the neck(12), and required deletion of Med20. The S. pombe head module resembles the head of a crocodile with eight distinct elements, of which at least four are mobile. The fixed jaw comprises tooth and nose domains, whereas the neck submodule contains a helical spine and one limb, with shoulder, arm and finger elements. The arm and the essential shoulder contact other parts of Mediator. The jaws and a central joint are implicated in interactions with Pol II and its carboxy-terminal domain, and the joint is required for transcription in vitro. The S. pombe head module structure leads to a revised model of the S. cerevisiae module, reveals a high conservation and flexibility, explains knownmutations, and provides the basis for unravelling a central mechanism of gene regulation.
C1 [Lariviere, Laurent; Plaschka, Clemens; Seizl, Martin; Wenzeck, Larissa; Kurth, Fabian; Cramer, Patrick] Univ Munich, Gene Ctr, D-81377 Munich, Germany.
   [Lariviere, Laurent; Plaschka, Clemens; Seizl, Martin; Wenzeck, Larissa; Kurth, Fabian; Cramer, Patrick] Univ Munich, CIPSM, Dept Biochem, D-81377 Munich, Germany.
C3 University of Munich; University of Munich
RP Larivière, L (corresponding author), Univ Munich, Gene Ctr, Feodor Lynen Str 25, D-81377 Munich, Germany.
EM larivier@genzentrum.lmu.de; cramer@genzentrum.lmu.de
FU Boehringer Ingelheim fellowship; Elite Network of Bavaria; Deutsche Forschungsgemeinschaft [SFB646, TR5, GraKo1721, SFB960]; CIPSM; NIM; European Research Council; LMU innovativ project Bioimaging Network; Vallee Foundation; Jung-Stiftung
NR 48
TC 87
Z9 96
U1 1
U2 61
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 20
PY 2012
VL 492
IS 7429
BP 448
EP +
DI 10.1038/nature11670
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 056KQ
UT WOS:000312488200060
PM 23123849
DA 2026-03-09
ER

PT J
AU Fei, Z
   Rodin, AS
   Andreev, GO
   Bao, W
   McLeod, AS
   Wagner, M
   Zhang, LM
   Zhao, Z
   Thiemens, M
   Dominguez, G
   Fogler, MM
   Castro Neto, AH
   Lau, CN
   Keilmann, F
   Basov, DN
AF Fei, Z.
   Rodin, A. S.
   Andreev, G. O.
   Bao, W.
   McLeod, A. S.
   Wagner, M.
   Zhang, L. M.
   Zhao, Z.
   Thiemens, M.
   Dominguez, G.
   Fogler, M. M.
   Castro Neto, A. H.
   Lau, C. N.
   Keilmann, F.
   Basov, D. N.
TI Gate-tuning of graphene plasmons revealed by infrared nano-imaging
SO NATURE
LA English
DT Article
ID metamaterials; spectroscopy; optics
AB Surface plasmons are collective oscillations of electrons in metals or semiconductors that enable confinement and control of electromagnetic energy at subwavelength scales(1-5). Rapid progress in plasmonics has largely relied on advances in device nano-fabrication(5-7), whereas less attention has been paid to the tunable properties of plasmonic media. One such medium-graphene-is amenable to convenient tuning of its electronic and optical properties by varying the applied voltage(8-11). Here, using infrared nano-imaging, we show that common graphene/SiO2/Si back-gated structures support propagating surface plasmons. The wavelength of graphene plasmons is of the order of 200 nanometres at technologically relevant infrared frequencies, and they can propagate several times this distance. We have succeeded in altering both the amplitude and the wavelength of these plasmons by varying the gate voltage. Using plasmon interferometry, we investigated losses in graphene by exploring real-space profiles of plasmon standing waves formed between the tip of our nano-probe and the edges of the samples. Plasmon dissipation quantified through this analysis is linked to the exotic electrodynamics of graphene(10). Standard plasmonic figures of merit of our tunable graphene devices surpass those of common metal-based structures.
C1 [Fei, Z.; Rodin, A. S.; Andreev, G. O.; McLeod, A. S.; Wagner, M.; Fogler, M. M.; Basov, D. N.] Univ Calif San Diego, Dept Phys, La Jolla, CA 92093 USA.
   [Bao, W.; Zhao, Z.; Lau, C. N.] Univ Calif Riverside, Dept Phys & Astron, Riverside, CA 92521 USA.
   [Bao, W.] Univ Maryland, Mat Res Sci & Engn Ctr, College Pk, MD 20742 USA.
   [Zhang, L. M.] Boston Univ, Dept Phys, Boston, MA 02215 USA.
   [Thiemens, M.] Univ Calif San Diego, Dept Chem & Biochem, La Jolla, CA 92093 USA.
   [Dominguez, G.] Calif State Univ, Dept Phys, San Marcos, CA 92096 USA.
   [Castro Neto, A. H.] Natl Univ Singapore, Graphene Res Ctr, Singapore 117542, Singapore.
   [Castro Neto, A. H.] Natl Univ Singapore, Dept Phys, Singapore 117542, Singapore.
   [Keilmann, F.] Max Planck Inst Quantum Opt, D-85714 Garching, Germany.
   [Keilmann, F.] Ctr Nanosci, D-85714 Garching, Germany.
C3 University of California System; University of California San Diego; University of California System; University of California Riverside; University System of Maryland; University of Maryland College Park; Boston University; University of California System; University of California San Diego; California State University System; California State University San Marcos; National University of Singapore; National University of Singapore; Max Planck Society
RP Basov, DN (corresponding author), Univ Calif San Diego, Dept Phys, La Jolla, CA 92093 USA.
EM dbasov@physics.ucsd.edu
FU AFOSR; ONR [N00014-09-1-0724]; DARPA; DOE-BES [DE-FG02-00ER45799]; NSF [DMR/1106358, PHY11-25915]; ONR/DMEA [H94003-10-2-1003]; FENA Focus Center; NASA; UCOP; NRF-CRP [R-144-000-295-281]; DOE [DE-FG02-08ER46512]; Alexander von Humboldt Foundation; Deutsche Forschungsgemeinschaft through the Cluster of Excellence Munich Centre for Advanced Photonics; U.S. Department of Energy (DOE) [DE-FG02-00ER45799] Funding Source: U.S. Department of Energy (DOE); Direct For Mathematical & Physical Scien [0748910, 1106358] Funding Source: National Science Foundation; Division Of Materials Research [0748910, 1106358] Funding Source: National Science Foundation
NR 29
TC 1891
Z9 2110
U1 20
U2 1122
PU NATURE PUBLISHING 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 5
PY 2012
VL 487
IS 7405
BP 82
EP 85
DI 10.1038/nature11253
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 968LM
UT WOS:000305982900054
PM 22722866
DA 2026-03-09
ER

PT J
AU Yan, J
   Bloom, M
   Bae, SC
   Luijten, E
   Granick, S
AF Yan, Jing
   Bloom, Moses
   Bae, Sung Chul
   Luijten, Erik
   Granick, Steve
TI Linking synchronization to self-assembly using magnetic Janus colloids
SO NATURE
LA English
DT Article
AB Synchronization occurs widely in the natural and technological worlds, from the rhythm of applause and neuron firing(1) to the quantum mechanics of coupled Josephson junctions(2), but has not been used to produce new spatial structures. Our understanding of self-assembly has evolved independently in the fields of chemistry and materials, and with a few notable exceptions(3,4) has focused on equilibrium rather than dynamical systems. Here we combine these two phenomena to create synchronization-selected microtubes of Janus colloids, micron-sized spherical particles with different surface chemistry on their opposing hemispheres, which we study using imaging and computer simulation. A thin nickel film coats one hemisphere of each silica particle to generate a discoid magnetic symmetry, such that in a precessing magnetic field its dynamics retain crucial phase freedom. Synchronizing their motion, these Janus spheres self-organize into micrometre-scale tubes in which the constituent particles rotate and oscillate continuously. In addition, the microtube must be tidally locked to the particles, that is, the particles must maintain their orientation within the rotating microtube. This requirement leads to a synchronization-induced structural transition that offers various applications based on the potential to form, disintegrate and fine-tune self-assembled in-motion structures in situ. Furthermore, it offers a generalizable method of controlling structure using dynamic synchronization criteria rather than static energy minimization, and of designing new field-driven microscale devices in which components do not slavishly follow the external field.
C1 [Bloom, Moses; Luijten, Erik] Northwestern Univ, Dept Mat Sci & Engn, Evanston, IL 60208 USA.
   [Yan, Jing; Bae, Sung Chul; Granick, Steve] Univ Illinois, Dept Mat Sci & Engn, Urbana, IL 61801 USA.
   [Luijten, Erik] Northwestern Univ, Dept Engn Sci & Appl Math, Evanston, IL 60208 USA.
   [Granick, Steve] Univ Illinois, Dept Phys, Urbana, IL 61801 USA.
   [Granick, Steve] Univ Illinois, Dept Chem, Urbana, IL 61801 USA.
C3 Northwestern University; University of Illinois System; University of Illinois Urbana-Champaign; Northwestern University; University of Illinois System; University of Illinois Urbana-Champaign; University of Illinois System; University of Illinois Urbana-Champaign
RP Luijten, E (corresponding author), Northwestern Univ, Dept Mat Sci & Engn, Evanston, IL 60208 USA.
EM luijten@northwestern.edu; sgranick@uiuc.edu
FU US Army Research Office [W911NF-10-1-0518]; National Science Foundation [DMR-1006430, CBET-0853737]; US Department of Energy, Division of Materials Science through Frederick Seitz Materials Research Laboratory at the University of Illinois at Urbana-Champaign [DE-FG02-07ER46471]; Division Of Materials Research; Direct For Mathematical & Physical Scien [1006430] Funding Source: National Science Foundation; Div Of Chem, Bioeng, Env, & Transp Sys; Directorate For Engineering [0853737] Funding Source: National Science Foundation
NR 30
TC 369
Z9 435
U1 0
U2 614
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 22
PY 2012
VL 491
IS 7425
BP 578
EP +
DI 10.1038/nature11619
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 040RE
UT WOS:000311339800048
PM 23172215
DA 2026-03-09
ER

PT J
AU Ma, XY
   Hou, XG
   Edgecombe, GD
   Strausfeld, NJ
AF Ma, Xiaoya
   Hou, Xianguang
   Edgecombe, Gregory D.
   Strausfeld, Nicholas J.
TI Complex brain and optic lobes in an early Cambrian arthropod
SO NATURE
LA English
DT Article
ID ground pattern; nervous-system; sister group; evolution; crustacean; insects; head; view; organization; fuxianhuia
AB The nervous system provides a fundamental source of data for understanding the evolutionary relationships between major arthropod groups(1,2). Fossil arthropods rarely preserve neural tissue. As a result, inferring sensory and motor attributes of Cambrian taxa has been limited to interpreting external features, such as compound eyes(3) or sensilla decorating appendages(4), and early-diverging arthropods have scarcely been analysed in the context of nervous system evolution. Here we report exceptional preservation of the brain and optic lobes of a stem-group arthropod from 520 million years ago (Myr ago), Fuxianhuia protensa(5), exhibiting the most compelling neuroanatomy known from the Cambrian. The protocerebrum of Fuxianhuia is supplied by optic lobes evidencing traces of three nested optic centres serving forward-viewing eyes. Nerves from uniramous antennae define the deutocerebrum, and a stout pair of more caudal nerves indicates a contiguous tritocerebral component. Fuxianhuia shares a tripartite pre-stomodeal brain and nested optic neuropils with extant Malacostraca and Insecta(2,6), demonstrating that these characters were present in some of the earliest derived arthropods. The brain of Fuxianhuia impacts molecular analyses that advocate either a branchiopod-like ancestor of Hexapoda(7,8) or remipedes and possibly cephalocarids as sister groups of Hexapoda(9,10). Resolving arguments about whether the simple brain of a branchiopod approximates an ancestral insect brain or whether it is the result of secondary simplification has until now been hindered by lack of fossil evidence. The complex brain of Fuxianhuia accords with cladistic analyses on the basis of neural characters, suggesting that Branchiopoda derive from a malacostracan-like ancestor but underwent evolutionary reduction and character reversal of brain centres that are common to hexapods and malacostracans(2). The early origin of sophisticated brains provides a probable driver for versatile visual behaviours, a view that accords with compound eyes from the early Cambrian that were, in size and resolution, equal to those of modern insects and malacostracans(3).
C1 [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 Ma, XY (corresponding author), Yunnan Univ, Yunnan Key Lab Palaeobiol, Kunming 650091, Peoples R China.
EM x.ma@nhm.ac.uk
FU National Natural Science Foundation of China [40730211]; Leverhulme Trust [F/00 696/T]; Center for Insect Science, University of Arizona
NR 30
TC 159
Z9 176
U1 5
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 OCT 11
PY 2012
VL 490
IS 7419
BP 258
EP +
DI 10.1038/nature11495
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 019IY
UT WOS:000309733300049
PM 23060195
DA 2026-03-09
ER

PT J
AU Hagberg, CE
   Mehlem, A
   Falkevall, A
   Muhl, L
   Fam, BC
   Ortsäter, H
   Scotney, P
   Nyqvist, D
   Samén, E
   Lu, L
   Stone-Elander, S
   Proietto, J
   Andrikopoulos, S
   Sjöholm, Å
   Nash, A
   Eriksson, U
AF Hagberg, Carolina E.
   Mehlem, Annika
   Falkevall, Annelie
   Muhl, Lars
   Fam, Barbara C.
   Ortsater, Henrik
   Scotney, Pierre
   Nyqvist, Daniel
   Samen, Erik
   Lu, Li
   Stone-Elander, Sharon
   Proietto, Joseph
   Andrikopoulos, Sofianos
   Sjoholm, Ake
   Nash, Andrew
   Eriksson, Ulf
TI Targeting VEGF-B as a novel treatment for insulin resistance and type 2 diabetes
SO NATURE
LA English
DT Article
ID growth-factor-b; oxidative-phosphorylation; glucose-production; skeletal-muscle; metabolism; tolerance; isoforms
AB The prevalence of type 2 diabetes is rapidly increasing, with severe socioeconomic impacts(1,2). Excess lipid deposition in peripheral tissues impairs insulin sensitivity and glucose uptake, and has been proposed to contribute to the pathology of type 2 diabetes(3-5). However, few treatment options exist that directly target ectopic lipid accumulation(6). Recently it was found that vascular endothelial growth factor B (VEGF-B) controls endothelial uptake and transport of fatty acids in heart and skeletal muscle(7). Here we show that decreased VEGF-B signalling in rodent models of type 2 diabetes restores insulin sensitivity and improves glucose tolerance. Genetic deletion of Vegfb in diabetic db/db mice prevented ectopic lipid deposition, increased-muscle glucose uptake and maintained normoglycaemia. Pharmacological inhibition of VEGF-B signalling by antibody administration to db/db mice enhanced glucose tolerance, preserved pancreatic islet architecture, improved beta-cell function and ameliorated dyslipidaemia, key elements of type 2 diabetes and the metabolic syndrome. The potential use of VEGF-B neutralization in type 2 diabetes was further elucidated in rats fed a high-fat diet, in which it normalized insulin sensitivity and increased glucose uptake in skeletal muscle and heart. Our results demonstrate that the vascular endothelium can function as an efficient barrier to excess muscle lipid uptake even under conditions of severe obesity and type 2 diabetes, and that this barrier can be maintained by inhibition of VEGF-B signalling. We propose VEGF-B antagonism as a novel pharmacological approach for type 2 diabetes, targeting the lipid-transport properties of the endothelium to improve muscle insulin sensitivity and glucose disposal.
C1 [Hagberg, Carolina E.; Mehlem, Annika; Falkevall, Annelie; Muhl, Lars; Nyqvist, Daniel; Eriksson, Ulf] Karolinska Inst, Dept Med Biochem & Biophys, Div Vasc Biol, Tissue Biol Grp, SE-17177 Stockholm, Sweden.
   [Hagberg, Carolina E.; Falkevall, Annelie; Muhl, Lars] Karolinska Inst, Stockholm Branch, Ludwig Inst Canc Res Ltd, SE-17177 Stockholm, Sweden.
   [Fam, Barbara C.; Proietto, Joseph; Andrikopoulos, Sofianos] Univ Melbourne, Dept Med AH, Heidelberg, Vic 3091, Australia.
   [Ortsater, Henrik; Sjoholm, Ake] Karolinska Inst, Dept Clin Sci & Educ, Diabet Res Unit, SE-11883 Stockholm, Sweden.
   [Scotney, Pierre; Nash, Andrew] CSL Ltd, Parkville, Vic 3052, Australia.
   [Samen, Erik; Lu, Li; Stone-Elander, Sharon] Karolinska Univ Hosp, Dept Neuroradiol, SE-17176 Stockholm, Sweden.
   [Samen, Erik; Lu, Li; Stone-Elander, Sharon] Karolinska Univ Hosp, Karolinska Expt Res & Imaging Ctr, SE-17176 Stockholm, Sweden.
   [Samen, Erik; Stone-Elander, Sharon] Karolinska Inst, SE-17176 Stockholm, Sweden.
C3 Karolinska Institutet; Ludwig Institute for Cancer Research; Karolinska Institutet; University of Melbourne; Karolinska Institutet; CSL; Karolinska Institutet; Karolinska University Hospital; Karolinska Institutet; Karolinska University Hospital; Karolinska Institutet
RP Eriksson, U (corresponding author), Karolinska Inst, Dept Med Biochem & Biophys, Div Vasc Biol, Tissue Biol Grp, SE-17177 Stockholm, Sweden.
EM ulf.pe.eriksson@ki.se
FU Frans Wilhelm och Waldemar von Frenckells Fond; Wilhelm och Else Stockmanns Stiftelse; Swedish Society for Medical Research; Ludwig Institute for Cancer Research; Novo Nordisk Foundation; Swedish Cancer Foundation; Swedish Research Council; Torsten och Ragnar Soderbergs Stiftelser; Dr Peter Wallenbergs Foundation for Economics and Technology; Swedish Heart and Lung Foundation; Diabetes Foundation; Karolinska Institutet
NR 38
TC 242
Z9 275
U1 2
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 OCT 18
PY 2012
VL 490
IS 7420
BP 426
EP +
DI 10.1038/nature11464
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 021XI
UT WOS:000309918500051
PM 23023133
DA 2026-03-09
ER

PT J
AU Tidow, H
   Poulsen, LR
   Andreeva, A
   Knudsen, M
   Hein, KL
   Wiuf, C
   Palmgren, MG
   Nissen, P
AF Tidow, Henning
   Poulsen, Lisbeth R.
   Andreeva, Antonina
   Knudsen, Michael
   Hein, Kim L.
   Wiuf, Carsten
   Palmgren, Michael G.
   Nissen, Poul
TI A bimodular mechanism of calcium control in eukaryotes
SO NATURE
LA English
DT Article
ID membrane ca2+ pump; structure validation; regulatory domain; binding domain; calmodulin; plant; ca2+-atpase; activation; diversity; proteins
AB Calcium ions (Ca2+) have an important role as secondary messengers in numerous signal transduction processes(1-4), and cells invest much energy in controlling and maintaining a steep gradient between intracellular (similar to 0.1-micromolar) and extracellular (similar to 2-millimolar) Ca2+ concentrations(1). Calmodulin-stimulated calcium pumps, which include the plasma-membrane Ca2+-ATPases (PMCAs), are key regulators of intracellular Ca2+ in eukaryotes(5-8). They contain a unique amino- or carboxy-terminal regulatory domain responsible for autoinhibition, and binding of calcium-loaded calmodulin to this domain releases autoinhibition and activates the pump. However, the structural basis for the activation mechanism is unknown and a key remaining question is how calmodulin-mediated PMCA regulation can cover both basal Ca2+ levels in the nanomolar range as well as micromolar-range Ca2+ transients generated by cell stimulation(7). Here we present an integrated study combining the determination of the high-resolution crystal structure of a PMCA regulatory-domain/calmodulin complex with in vivo characterization and biochemical, biophysical and bioinformatics data that provide mechanistic insights into a two-step PMCA activation mechanism mediated by calcium-loaded calmodulin. The structure shows the entire PMCA regulatory domain and reveals an unexpected 2: 1 stoichiometry with two calcium-loaded calmodulin molecules binding to different sites on a long helix. A multifaceted characterization of the role of both sites leads to a general structural-model for calmodulin-mediated regulation of PMCAs that allows stringent, highly responsive control of intracellular calcium in eukaryotes, making it possible to maintain a stable, basal level at a threshold Ca2+ concentration, where steep activation occurs.
C1 [Tidow, Henning; Poulsen, Lisbeth R.; Knudsen, Michael; Hein, Kim L.; Palmgren, Michael G.; Nissen, Poul] Aarhus Univ, Ctr Membrane Pumps Cells & Dis PUMPKIN, DK-8000 Aarhus C, Denmark.
   [Tidow, Henning; Hein, Kim L.; Nissen, Poul] Aarhus Univ, Dept Mol Biol & Genet, DK-8000 Aarhus C, Denmark.
   [Poulsen, Lisbeth R.; Palmgren, Michael G.] Univ Copenhagen, Dept Plant Biol & Biotechnol, DK-1871 Frederiksberg C, Denmark.
   [Andreeva, Antonina] MRC Lab Mol Biol, Cambridge CB2 0QH, England.
   [Knudsen, Michael] Aarhus Univ, Bioinformat Res Ctr, DK-8000 Aarhus C, Denmark.
   [Wiuf, Carsten] Univ Copenhagen, Dept Math Sci, DK-2100 Copenhagen, Denmark.
C3 Aarhus University; Aarhus University; University of Copenhagen; MRC Laboratory Molecular Biology; Aarhus University; University of Copenhagen
RP Palmgren, MG (corresponding author), Aarhus Univ, Ctr Membrane Pumps Cells & Dis PUMPKIN, Gustav Wieds Vej 10C, DK-8000 Aarhus C, Denmark.
EM palmgren@life.ku.dk; pn@mb.au.dk
FU EMBO Long-Term Fellowship; Marie-Curie Intra-European Fellowship; HFSP Long-Term Fellowship; ERC advanced grant (BIOMEMOS); MRC [MC_U105192716] Funding Source: UKRI; Medical Research Council [MC_U105192716] Funding Source: researchfish
NR 48
TC 107
Z9 114
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 NOV 15
PY 2012
VL 491
IS 7424
BP 468
EP +
DI 10.1038/nature11539
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 036MY
UT WOS:000311031600051
PM 23086147
DA 2026-03-09
ER

PT J
AU Muzny, DM
   Bainbridge, MN
   Chang, K
   Dinh, HH
   Drummond, JA
   Fowler, G
   Kovar, CL
   Lewis, LR
   Morgan, MB
   Newsham, IF
   Reid, JG
   Santibanez, J
   Shinbrot, E
   Trevino, LR
   Wu, YQ
   Wang, M
   Gunaratne, P
   Donehower, LA
   Creighton, CJ
   Wheeler, DA
   Gibbs, RA
   Lawrence, MS
   Voet, D
   Jing, R
   Cibulskis, K
   Sivachenko, A
   Stojanov, P
   McKenna, A
   Lander, ES
   Gabriel, S
   Getz, G
   Ding, L
   Fulton, RS
   Koboldt, DC
   Wylie, T
   Walker, J
   Dooling, DJ
   Fulton, L
   Delehaunty, KD
   Fronick, CC
   Demeter, R
   Mardis, ER
   Wilson, RK
   Chu, A
   Chun, HJE
   Mungall, AJ
   Pleasance, E
   Robertson, AG
   Stoll, D
   Balasundaram, M
   Birol, I
   Butterfield, YSN
   Chuah, E
   Coope, RJN
   Dhalla, N
   Guin, R
   Hirst, C
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   Holt, RA
   Lee, D
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   Mayo, M
   Moore, RA
   Schein, JE
   Slobodan, JR
   Tam, A
   Thiessen, N
   Varhol, R
   Zeng, T
   Zhao, Y
   Jones, SJM
   Marra, MA
   Bass, AJ
   Ramos, AH
   Saksena, G
   Cherniack, AD
   Schumacher, SE
   Tabak, B
   Carter, SL
   Pho, NH
   Nguyen, H
   Onofrio, RC
   Crenshaw, A
   Ardlie, K
   Beroukhim, R
   Winckler, W
   Getz, G
   Meyerson, M
   Protopopov, A
   Zhang, J
   Hadjipanayis, A
   Lee, E
   Xi, R
   Yang, L
   Ren, X
   Zhang, H
   Sathiamoorthy, N
   Shukla, S
   Chen, PC
   Haseley, P
   Xiao, Y
   Lee, S
   Seidman, J
   Chin, L
   Park, PJ
   Kucherlapati, R
   Auman, JT
   Hoadley, KA
   Du, Y
   Wilkerson, MD
   Shi, Y
   Liquori, C
   Meng, S
   Li, L
   Turman, YJ
   Topal, MD
   Tan, D
   Waring, S
   Buda, E
   Walsh, J
   Jones, CD
   Mieczkowski, PA
   Singh, D
   Wu, J
   Gulabani, A
   Dolina, P
   Bodenheimer, T
   Hoyle, AP
   Simons, JV
   Soloway, M
   Mose, LE
   Jefferys, SR
   Balu, S
   O'Connor, BD
   Prins, JF
   Chiang, DY
   Hayes, DN
   Perou, CM
   Hinoue, T
   Weisenberger, DJ
   Maglinte, DT
   Pan, F
   Berman, BP
   Van den Berg, DJ
   Shen, H
   Triche, T
   Baylin, SB
   Laird, PW
   Getz, G
   Noble, M
   Voet, D
   Saksena, G
   Gehlenborg, N
   DiCara, D
   Zhang, J
   Zhang, H
   Wu, CJ
   Liu, SY
   Shukla, S
   Lawrence, MS
   Zhou, L
   Sivachenko, A
   Lin, P
   Stojanov, P
   Jing, R
   Park, RW
   Nazaire, MD
   Robinson, J
   Thorvaldsdottir, H
   Mesirov, J
   Park, PJ
   Chin, L
   Thorsson, V
   Reynolds, SM
   Bernard, B
   Kreisberg, R
   Lin, J
   Iype, L
   Bressler, R
   Erkkilä, T
   Gundapuneni, M
   Liu, Y
   Norberg, A
   Robinson, T
   Da Yang
   Zhang, W
   Shmulevich, I
   De Ronde, JJ
   Schultz, N
   Cerami, E
   Ciriello, G
   Goldberg, AP
   Gross, B
   Jacobsen, A
   Gao, J
   Kaczkowski, B
   Sinha, R
   Aksoy, BA
   Antipin, Y
   Reva, B
   Shen, R
   Taylor, BS
   Chan, TA
   Ladanyi, M
   Sander, C
   Akbani, R
   Zhang, N
   Broom, BM
   Casasent, T
   Unruh, A
   Wakefield, C
   Hamilton, SR
   Cason, RC
   Baggerly, KA
   Weinstein, JN
   Haussler, D
   Benz, CC
   Stuart, JM
   Benz, SC
   Sanborn, JZ
   Vaske, CJ
   Zhu, J
   Szeto, C
   Scott, GK
   Yau, C
   Ng, S
   Goldstein, T
   Ellrott, K
   Collisson, E
   Cozen, AE
   Zerbino, D
   Wilks, C
   Craft, B
   Spellman, P
   Penny, R
   Shelton, T
   Hatfield, M
   Morris, S
   Yena, P
   Shelton, C
   Sherman, M
   Paulauskis, J
   Gastier-Foster, JM
   Bowen, J
   Ramirez, NC
   Black, A
   Pyatt, R
   Wise, L
   White, P
   Bertagnolli, M
   Brown, J
   Chan, TA
   Chu, GC
   Czerwinski, C
   Denstman, F
   Dhir, R
   Doerner, A
   Fuchs, CS
   Guillem, JG
   Iacocca, M
   Juhl, H
   Kaufman, A
   Kohl, B
   Van Le, X
   Mariano, MC
   Medina, EN
   Meyers, M
   Nash, GM
   Paty, PB
   Petrelli, N
   Rabeno, B
   Richards, WG
   Solit, D
   Swanson, P
   Temple, L
   Tepper, JE
   Thorp, R
   Vakiani, E
   Weiser, MR
   Willis, JE
   Witkin, G
   Zeng, Z
   Zinner, MJ
   Zornig, C
   Jensen, MA
   Sfeir, R
   Kahn, AB
   Chu, AL
   Kothiyal, P
   Wang, Z
   Snyder, EE
   Pontius, J
   Pihl, TD
   Ayala, B
   Backus, M
   Walton, J
   Whitmore, J
   Baboud, J
   Berton, DL
   Nicholls, MC
   Srinivasan, D
   Raman, R
   Girshik, S
   Kigonya, PA
   Alonso, S
   Sanbhadti, RN
   Barletta, SP
   Greene, JM
   Pot, DA
   Shaw, KRM
   Dillon, LAL
   Buetow, K
   Davidsen, T
   Demchok, JA
   Eley, G
   Ferguson, M
   Fielding, P
   Schaefer, C
   Sheth, M
   Yang, L
   Guyer, MS
   Ozenberger, BA
   Palchik, JD
   Peterson, J
   Sofia, HJ
   Thomson, E
AF Muzny, Donna M.
   Bainbridge, Matthew N.
   Chang, Kyle
   Dinh, Huyen H.
   Drummond, Jennifer A.
   Fowler, Gerald
   Kovar, Christie L.
   Lewis, Lora R.
   Morgan, Margaret B.
   Newsham, Irene F.
   Reid, Jeffrey G.
   Santibanez, Jireh
   Shinbrot, Eve
   Trevino, Lisa R.
   Wu, Yuan-Qing
   Wang, Min
   Gunaratne, Preethi
   Donehower, Lawrence A.
   Creighton, Chad J.
   Wheeler, David A.
   Gibbs, Richard A.
   Lawrence, Michael S.
   Voet, Douglas
   Jing, Rui
   Cibulskis, Kristian
   Sivachenko, Andrey
   Stojanov, Petar
   McKenna, Aaron
   Lander, Eric S.
   Gabriel, Stacey
   Getz, Gad
   Ding, Li
   Fulton, Robert S.
   Koboldt, Daniel C.
   Wylie, Todd
   Walker, Jason
   Dooling, David J.
   Fulton, Lucinda
   Delehaunty, Kim D.
   Fronick, Catrina C.
   Demeter, Ryan
   Mardis, Elaine R.
   Wilson, Richard K.
   Chu, Andy
   Chun, Hye-Jung E.
   Mungall, Andrew J.
   Pleasance, Erin
   Robertson, A. Gordon
   Stoll, Dominik
   Balasundaram, Miruna
   Birol, Inanc
   Butterfield, Yaron S. N.
   Chuah, Eric
   Coope, Robin J. N.
   Dhalla, Noreen
   Guin, Ranabir
   Hirst, Carrie
   Hirst, Martin
   Holt, Robert A.
   Lee, Darlene
   Li, Haiyan I.
   Mayo, Michael
   Moore, Richard A.
   Schein, Jacqueline E.
   Slobodan, Jared R.
   Tam, Angela
   Thiessen, Nina
   Varhol, Richard
   Zeng, Thomas
   Zhao, Yongjun
   Jones, Steven J. M.
   Marra, Marco A.
   Bass, Adam J.
   Ramos, Alex H.
   Saksena, Gordon
   Cherniack, Andrew D.
   Schumacher, Stephen E.
   Tabak, Barbara
   Carter, Scott L.
   Pho, Nam H.
   Nguyen, Huy
   Onofrio, Robert C.
   Crenshaw, Andrew
   Ardlie, Kristin
   Beroukhim, Rameen
   Winckler, Wendy
   Getz, Gad
   Meyerson, Matthew
   Protopopov, Alexei
   Zhang, Juinhua
   Hadjipanayis, Angela
   Lee, Eunjung
   Xi, Ruibin
   Yang, Lixing
   Ren, Xiaojia
   Zhang, Hailei
   Sathiamoorthy, Narayanan
   Shukla, Sachet
   Chen, Peng-Chieh
   Haseley, Psalm
   Xiao, Yonghong
   Lee, Semin
   Seidman, Jonathan
   Chin, Lynda
   Park, Peter J.
   Kucherlapati, Raju
   Auman, J. Todd
   Hoadley, Katherine A.
   Du, Ying
   Wilkerson, Matthew D.
   Shi, Yan
   Liquori, Christina
   Meng, Shaowu
   Li, Ling
   Turman, Yidi J.
   Topal, Michael D.
   Tan, Donghui
   Waring, Scot
   Buda, Elizabeth
   Walsh, Jesse
   Jones, Corbin D.
   Mieczkowski, Piotr A.
   Singh, Darshan
   Wu, Junyuan
   Gulabani, Anisha
   Dolina, Peter
   Bodenheimer, Tom
   Hoyle, Alan P.
   Simons, Janae V.
   Soloway, Matthew
   Mose, Lisle E.
   Jefferys, Stuart R.
   Balu, Saianand
   O'Connor, Brian D.
   Prins, Jan F.
   Chiang, Derek Y.
   Hayes, D. Neil
   Perou, Charles M.
   Hinoue, Toshinori
   Weisenberger, Daniel J.
   Maglinte, Dennis T.
   Pan, Fei
   Berman, Benjamin P.
   Van den Berg, David J.
   Shen, Hui
   Triche, Timothy, Jr.
   Baylin, Stephen B.
   Laird, Peter W.
   Getz, Gad
   Noble, Michael
   Voet, Doug
   Saksena, Gordon
   Gehlenborg, Nils
   DiCara, Daniel
   Zhang, Juinhua
   Zhang, Hailei
   Wu, Chang-Jiun
   Liu, Spring Yingchun
   Shukla, Sachet
   Lawrence, Michael S.
   Zhou, Lihua
   Sivachenko, Andrey
   Lin, Pei
   Stojanov, Petar
   Jing, Rui
   Park, Richard W.
   Nazaire, Marc-Danie
   Robinson, Jim
   Thorvaldsdottir, Helga
   Mesirov, Jill
   Park, Peter J.
   Chin, Lynda
   Thorsson, Vesteinn
   Reynolds, Sheila M.
   Bernard, Brady
   Kreisberg, Richard
   Lin, Jake
   Iype, Lisa
   Bressler, Ryan
   Erkkilae, Timo
   Gundapuneni, Madhumati
   Liu, Yuexin
   Norberg, Adam
   Robinson, Tom
   Da Yang
   Zhang, Wei
   Shmulevich, Ilya
   De Ronde, Jorma J.
   Schultz, Nikolaus
   Cerami, Ethan
   Ciriello, Giovanni
   Goldberg, Arthur P.
   Gross, Benjamin
   Jacobsen, Anders
   Gao, Jianjiong
   Kaczkowski, Bogumil
   Sinha, Rileen
   Aksoy, B. Arman
   Antipin, Yevgeniy
   Reva, Boris
   Shen, Ronglai
   Taylor, Barry S.
   Chan, Timothy A.
   Ladanyi, Marc
   Sander, Chris
   Akbani, Rehan
   Zhang, Nianxiang
   Broom, Bradley M.
   Casasent, Tod
   Unruh, Anna
   Wakefield, Chris
   Hamilton, Stanley R.
   Cason, R. Craig
   Baggerly, Keith A.
   Weinstein, John N.
   Haussler, David
   Benz, Christopher C.
   Stuart, Joshua M.
   Benz, Stephen C.
   Sanborn, J. Zachary
   Vaske, Charles J.
   Zhu, Jingchun
   Szeto, Christopher
   Scott, Gary K.
   Yau, Christina
   Ng, Sam
   Goldstein, Ted
   Ellrott, Kyle
   Collisson, Eric
   Cozen, Aaron E.
   Zerbino, Daniel
   Wilks, Christopher
   Craft, Brian
   Spellman, Paul
   Penny, Robert
   Shelton, Troy
   Hatfield, Martha
   Morris, Scott
   Yena, Peggy
   Shelton, Candace
   Sherman, Mark
   Paulauskis, Joseph
   Gastier-Foster, Julie M.
   Bowen, Jay
   Ramirez, Nilsa C.
   Black, Aaron
   Pyatt, Robert
   Wise, Lisa
   White, Peter
   Bertagnolli, Monica
   Brown, Jen
   Chan, Timothy A.
   Chu, Gerald C.
   Czerwinski, Christine
   Denstman, Fred
   Dhir, Rajiv
   Doerner, Arnulf
   Fuchs, Charles S.
   Guillem, Jose G.
   Iacocca, Mary
   Juhl, Hartmut
   Kaufman, Andrew
   Kohl, Bernard, III
   Van Le, Xuan
   Mariano, Maria C.
   Medina, Elizabeth N.
   Meyers, Michael
   Nash, Garrett M.
   Paty, Phillip B.
   Petrelli, Nicholas
   Rabeno, Brenda
   Richards, William G.
   Solit, David
   Swanson, Pat
   Temple, Larissa
   Tepper, Joel E.
   Thorp, Richard
   Vakiani, Efsevia
   Weiser, Martin R.
   Willis, Joseph E.
   Witkin, Gary
   Zeng, Zhaoshi
   Zinner, Michael J.
   Zornig, Carsten
   Jensen, Mark A.
   Sfeir, Robert
   Kahn, Ari B.
   Chu, Anna L.
   Kothiyal, Prachi
   Wang, Zhining
   Snyder, Eric E.
   Pontius, Joan
   Pihl, Todd D.
   Ayala, Brenda
   Backus, Mark
   Walton, Jessica
   Whitmore, Jon
   Baboud, Julien
   Berton, Dominique L.
   Nicholls, Matthew C.
   Srinivasan, Deepak
   Raman, Rohini
   Girshik, Stanley
   Kigonya, Peter A.
   Alonso, Shelley
   Sanbhadti, Rashmi N.
   Barletta, Sean P.
   Greene, John M.
   Pot, David A.
   Shaw, Kenna R. Mills
   Dillon, Laura A. L.
   Buetow, Ken
   Davidsen, Tanja
   Demchok, John A.
   Eley, Greg
   Ferguson, Martin
   Fielding, Peter
   Schaefer, Carl
   Sheth, Margi
   Yang, Liming
   Guyer, Mark S.
   Ozenberger, Bradley A.
   Palchik, Jacqueline D.
   Peterson, Jane
   Sofia, Heidi J.
   Thomson, Elizabeth
TI Comprehensive molecular characterization of human colon and rectal cancer
SO NATURE
LA English
DT Article
ID somatic mutations; human breast; gene; differentiation; wtx; sequences; oncogene; network; sox9; igf2
AB To characterize somatic alterations in colorectal carcinoma, we conducted a genome-scale analysis of 276 samples, analysing exome sequence, DNA copy number, promoter methylation and messenger RNA and microRNA expression. A subset of these samples (97) underwent low-depth-of-coverage whole-genome sequencing. In total, 16% of colorectal carcinomas were found to be hypermutated: three-quarters of these had the expected high microsatellite instability, usually with hypermethylation and MLH1 silencing, and one-quarter had somatic mismatch-repair gene and polymerase e (POLE) mutations. Excluding the hypermutated cancers, colon and rectum cancers were found to have considerably similar patterns of genomic alteration. Twenty-four genes were significantly mutated, and in addition to the expected APC, TP53, SMAD4, PIK3CA and KRAS mutations, we found frequent mutations in ARID1A, SOX9 and FAM123B. Recurrent copy-number alterations include potentially drug-targetable amplifications of ERBB2 and newly discovered amplification of IGF2. Recurrent chromosomal translocations include the fusion of NAV2 and WNT pathway member TCF7L1. Integrative analyses suggest new markers for aggressive colorectal carcinoma and an important role for MYC-directed transcriptional activation and repression.
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   [Gunaratne, Preethi] Univ Houston, Dept Biol & Biochem, Houston, TX 77204 USA.
   [Lawrence, Michael S.; Voet, Douglas; Jing, Rui; Cibulskis, Kristian; Stojanov, Petar; McKenna, Aaron; Lander, Eric S.; Gabriel, Stacey; Getz, Gad; Bass, Adam J.; Ramos, Alex H.; Saksena, Gordon; Cherniack, Andrew D.; Schumacher, Stephen E.; Tabak, Barbara; Carter, Scott L.; Pho, Nam H.; Nguyen, Huy; Onofrio, Robert C.; Crenshaw, Andrew; Ardlie, Kristin; Beroukhim, Rameen; Winckler, Wendy; Meyerson, Matthew; Chin, Lynda; Noble, Michael; Voet, Doug; Gehlenborg, Nils; DiCara, Daniel; Zhang, Juinhua; Zhang, Hailei; Wu, Chang-Jiun; Liu, Spring Yingchun; Shukla, Sachet; Zhou, Lihua; Sivachenko, Andrey; Lin, Pei; Nazaire, Marc-Danie; Robinson, Jim; Thorvaldsdottir, Helga; Mesirov, Jill] MIT, Eli & Edythe L Broad Inst, Cambridge, MA 02142 USA.
   [Voet, Douglas; Jing, Rui; Cibulskis, Kristian; Stojanov, Petar; McKenna, Aaron; Lander, Eric S.; Gabriel, Stacey; Getz, Gad; Bass, Adam J.; Ramos, Alex H.; Saksena, Gordon; Cherniack, Andrew D.; Schumacher, Stephen E.; Tabak, Barbara; Carter, Scott L.; Pho, Nam H.; Nguyen, Huy; Onofrio, Robert C.; Crenshaw, Andrew; Ardlie, Kristin; Beroukhim, Rameen; Winckler, Wendy; Meyerson, Matthew; Chin, Lynda; Noble, Michael; Voet, Doug; Gehlenborg, Nils; DiCara, Daniel; Zhang, Juinhua; Zhang, Hailei; Wu, Chang-Jiun; Liu, Spring Yingchun; Shukla, Sachet; Zhou, Lihua; Sivachenko, Andrey; Lin, Pei; Nazaire, Marc-Danie; Robinson, Jim; Thorvaldsdottir, Helga; Mesirov, Jill] Harvard Univ, Cambridge, MA 02142 USA.
   [Lander, Eric S.] MIT, Dept Biol, Cambridge, MA 02142 USA.
   [Lander, Eric S.] Harvard Univ, Dept Syst Biol, Boston, MA 02115 USA.
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   [Meyerson, Matthew] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
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   Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA.
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   [Haussler, David; Stuart, Joshua M.; Benz, Stephen C.; Sanborn, J. Zachary; Vaske, Charles J.; Zhu, Jingchun; Szeto, Christopher; Ng, Sam; Goldstein, Ted; Ellrott, Kyle; Cozen, Aaron E.; Zerbino, Daniel; Wilks, Christopher; Craft, Brian] Univ Calif Santa Cruz, Dept Biomol Engn, Santa Cruz, CA 95064 USA.
   [Haussler, David] Univ Calif Santa Cruz, Howard Hughes Med Inst, Santa Cruz, CA 95064 USA.
   [Benz, Christopher C.; Scott, Gary K.; Yau, Christina] Buck Inst Age Res, Novato, CA 94945 USA.
   [Collisson, Eric] Univ Calif San Francisco, Div Hematol Oncol, San Francisco, CA 94143 USA.
   [Spellman, Paul] Oregon Hlth & Sci Univ, Dept Mol & Med Genet, Portland, OR 97239 USA.
   [Penny, Robert; Shelton, Troy; Hatfield, Martha; Morris, Scott; Yena, Peggy; Shelton, Candace; Sherman, Mark; Paulauskis, Joseph] Int Genom Consortium, Phoenix, AZ 85004 USA.
   [Gastier-Foster, Julie M.; Bowen, Jay; Ramirez, Nilsa C.; Black, Aaron; Pyatt, Robert; Wise, Lisa; White, Peter] Nationwide Childrens Hosp, Res Inst, Nationwide Childrens Hosp Biospecimen Core Resour, Columbus, OH 43205 USA.
   [Gastier-Foster, Julie M.; Ramirez, Nilsa C.; Pyatt, Robert; White, Peter] Ohio State Univ, Coll Med, Dept Pathol, Columbus, OH 43205 USA.
   [Gastier-Foster, Julie M.; White, Peter] Ohio State Univ, Dept Pediat, Coll Med, Columbus, OH 43205 USA.
   [Bertagnolli, Monica] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA.
   [Brown, Jen; Czerwinski, Christine; Iacocca, Mary; Rabeno, Brenda; Swanson, Pat; Witkin, Gary] Christiana Care Hlth Syst, Dept Pathol, Newark, DE 19718 USA.
   [Chu, Gerald C.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Brookline, MA 02115 USA.
   [Denstman, Fred; Petrelli, Nicholas] Helen F Graham Canc Ctr Christiana Care, Dept Surg, Newark, DC 19718 USA.
   [Dhir, Rajiv] Univ Pittsburgh, Dept Pathol, Pittsburgh, PA 15213 USA.
   [Doerner, Arnulf] Krankenhaus Alten Eichen, Chirurg Klin, D-22527 Hamburg, Germany.
   [Fuchs, Charles S.] Dana Farber Canc Inst, Dept Med Oncol, Brookline, MA 02115 USA.
   [Fuchs, Charles S.] Brigham & Womens Hosp, Dept Med, Brookline, MA 02115 USA.
   [Guillem, Jose G.; Nash, Garrett M.; Paty, Phillip B.; Weiser, Martin R.; Zeng, Zhaoshi] Mem Sloan Kettering Canc Ctr, Dept Surg, New York, NY 10065 USA.
   [Juhl, Hartmut] Indivumed Inc, Kensington, MD 20895 USA.
   [Kohl, Bernard, III; Van Le, Xuan; Thorp, Richard] ILSbio LLC, Chestertown, MD 21620 USA.
   [Tepper, Joel E.] Univ N Carolina, Dept Radiat Oncol, Chapel Hill, NC 27599 USA.
   [Solit, David] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10065 USA.
   [Willis, Joseph E.] Case Med Ctr, Dept Pathol, Cleveland, OH 44106 USA.
   [Zornig, Carsten] Israelit Krankenhaus, Chirurg Klin, D-22297 Hamburg, Germany.
   [Jensen, Mark A.; Sfeir, Robert; Kahn, Ari B.; Chu, Anna L.; Kothiyal, Prachi; Wang, Zhining; Snyder, Eric E.; Pontius, Joan; Pihl, Todd D.; Ayala, Brenda; Backus, Mark; Walton, Jessica; Whitmore, Jon; Baboud, Julien; Berton, Dominique L.; Nicholls, Matthew C.; Srinivasan, Deepak; Raman, Rohini; Girshik, Stanley; Kigonya, Peter A.; Alonso, Shelley; Sanbhadti, Rashmi N.; Barletta, Sean P.; Greene, John M.; Pot, David A.] SRA Int, Fairfax, VA 22033 USA.
   [Shaw, Kenna R. Mills; Dillon, Laura A. L.; Demchok, John A.; Fielding, Peter; Sheth, Margi; Yang, Liming] NCI, Canc Genome Atlas Program Off, NIH, Bethesda, MD 20892 USA.
   [Buetow, Ken; Davidsen, Tanja; Schaefer, Carl] NCI, Ctr Biomed Informat & Informat Technol CBIIT, NIH, Rockville, MD 20852 USA.
   [Eley, Greg] Scimentis LLC, Statham, GA 30666 USA.
   [Ferguson, Martin] MLF Consulting, Arlington, MA 02474 USA.
   [Guyer, Mark S.; Ozenberger, Bradley A.; Palchik, Jacqueline D.; Peterson, Jane; Sofia, Heidi J.; Thomson, Elizabeth] NHGRI, NIH, Bethesda, MD 20892 USA.
C3 Harvard University; Harvard Medical School; Baylor College of Medicine; University of Houston System; University of Houston; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Harvard University; Massachusetts Institute of Technology (MIT); Harvard University; Washington University (WUSTL); Washington University (WUSTL); Washington University (WUSTL); Siteman Cancer Center; British Columbia Cancer Agency; Harvard University; Harvard Medical School; 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 University Medical Affiliates; Boston Children's Hospital; Harvard University; Harvard Medical School; 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; 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 Southern California; Johns Hopkins University; Johns Hopkins Medicine; Institute for Systems Biology (ISB); University of Texas System; UTMD Anderson Cancer Center; Memorial Sloan Kettering Cancer Center; Netherlands Cancer Institute; Memorial Sloan Kettering Cancer Center; Memorial Sloan Kettering Cancer Center; University of Texas System; UTMD Anderson Cancer Center; University of Texas System; UTMD Anderson Cancer Center; 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; Buck Institute for Research on Aging; University of California System; University of California San Francisco; Oregon Health & Science University; International Genomics Consortium; University System of Ohio; Ohio State University; Nationwide Childrens Hospital; Research Institute at Nationwide Children's Hospital; International Genomics Consortium; University System of Ohio; Ohio State University; University System of Ohio; Ohio State University; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard Medical School; Christiana Care Health System; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Helen F. Graham Cancer Center & Research Institute; Christiana Care Health System; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Memorial Sloan Kettering Cancer Center; University of North Carolina; University of North Carolina Chapel Hill; Memorial Sloan Kettering Cancer Center; University System of Ohio; Case Western Reserve University; SRA International; International Genomics Consortium; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); Center for Cancer Genomics (CCG); 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 Kucherlapati, R (corresponding author), Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
EM rkucherlapati@partners.org
FU National Institutes of Health [U24CA143799, U24CA143835, U24CA143840, U24CA143843, U24CA143845, U24CA143848, U24CA143858, U24CA143866, U24CA143867, U24CA143882, U24CA143883, U24CA144025, U54HG003067, U54HG003079, U54HG003273]; National Cancer Institute [P30CA016672, P30CA016086] Funding Source: NIH RePORTER; Direct For Biological Sciences; Emerging Frontiers [0850237] Funding Source: National Science Foundation
NR 44
TC 5579
Z9 5926
U1 11
U2 11
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 19
PY 2012
VL 487
IS 7407
BP 330
EP 337
DI 10.1038/nature11252
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 975JB
UT WOS:000306506500035
PM 22810696
DA 2026-03-09
ER

PT J
AU Fu, M
   Yu, XZ
   Lu, J
   Zuo, Y
AF Fu, Min
   Yu, Xinzhu
   Lu, Ju
   Zuo, Yi
TI Repetitive motor learning induces coordinated formation of clustered dendritic spines in vivo
SO NATURE
LA English
DT Article
ID structural plasticity; synaptic plasticity; pyramidal neurons; cortex; memory; circuits; stability; mice; ltp
AB Many lines of evidence suggest that memory in the mammalian brain is stored with distinct spatiotemporal patterns(1,2). Despite recent progresses in identifying neuronal populations involved in memory coding(3-5), the synapse-level mechanism is still poorly understood. Computational models and electrophysiological data have shown that functional clustering of synapses along dendritic branches leads to nonlinear summation of synaptic inputs and greatly expands the computing power of a neural network(6-10). However, whether neighbouring synapses are involved in encoding similar memory and how task-specific cortical networks develop during learning remain elusive. Using transcranial two-photon microscopy(11), we followed apical dendrites of layer 5 pyramidal neurons in the motor cortex while mice practised novel forelimb skills. Here we show that a third of new dendritic spines (postsynaptic structures of most excitatory synapses) formed during the acquisition phase of learning emerge in clusters, and that most such clusters are neighbouring spine pairs. These clustered new spines are more likely to persist throughout prolonged learning sessions, and even long after training stops, than non-clustered counterparts. Moreover, formation of new spine clusters requires repetition of the same motor task, and the emergence of succedent new spine(s) accompanies the strengthening of the first new spine in the cluster. We also show that under control conditions new spines appear to avoid existing stable spines, rather than being uniformly added along dendrites. However, succedent new spines in clusters overcome such a spatial constraint and form in close vicinity to neighbouring stable spines. Our findings suggest that clustering of new synapses along dendrites is induced by repetitive activation of the cortical circuitry during learning, providing a structural basis for spatial coding of motor memory in the mammalian brain.
C1 [Fu, Min; Yu, Xinzhu; Zuo, Yi] Univ Calif Santa Cruz, Dept Mol Cell & Dev Biol, Santa Cruz, CA 95064 USA.
   [Lu, Ju] Stanford Univ, Dept Biol Sci, Stanford, CA 94305 USA.
   [Lu, Ju] Stanford Univ, James H Clark Ctr, Stanford, CA 94305 USA.
C3 University of California System; University of California Santa Cruz; Stanford University; Stanford University
RP Zuo, Y (corresponding author), Univ Calif Santa Cruz, Dept Mol Cell & Dev Biol, Santa Cruz, CA 95064 USA.
EM yizuo@ucsc.edu
FU DANA Foundation; National Institutes of Mental Health
NR 32
TC 356
Z9 436
U1 1
U2 70
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD MAR 1
PY 2012
VL 483
IS 7387
BP 92
EP U135
DI 10.1038/nature10844
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 900HP
UT WOS:000300877900051
PM 22343892
DA 2026-03-09
ER

PT J
AU Johnston, DT
   Macdonald, FA
   Gill, BC
   Hoffman, PF
   Schrag, DP
AF Johnston, D. T.
   Macdonald, F. A.
   Gill, B. C.
   Hoffman, P. F.
   Schrag, D. P.
TI Uncovering the Neoproterozoic carbon cycle
SO NATURE
LA English
DT Article
ID snowball-earth; grand-canyon; chuar group; ocean; glaciation; history; constraints; initiation; oxidation; mongolia
AB Interpretations of major climatic and biological events in Earth history are, in large part, derived from the stable carbon isotope records of carbonate rocks and sedimentary organic matter(1,2). Neoproterozoic carbonate records contain unusual and large negative isotopic anomalies within long periods (10-100 million years) characterized by delta C-13 in carbonate (delta C-13(carb)) enriched to more than 15 per mil. Classically, delta C-13(carb) is interpreted as a metric of the relative fraction of carbon buried as organic matter in marine sediments(2-4), which can be linked to oxygen accumulation through the stoichiometry of primary production(3,5). If a change in the isotopic composition of marine dissolved inorganic carbon is responsible for these excursions, it is expected that records of delta C-13(carb) and delta C-13 in organic carbon (delta C-13(org)) will covary, offset by the fractionation imparted by primary production(5). The documentation of several Neoproterozoic delta C-13(carb) excursions that are decoupled from delta C-13(org), however, indicates that other mechanisms(6-8) may account for these excursions. Here we present delta C-13 data from Mongolia, northwest Canada and Namibia that capture multiple large-amplitude (over 10 per mil) negative carbon isotope anomalies, and use these data in a new quantitative mixing model to examine the behaviour of the Neoproterozoic carbon cycle. We find that carbonate and organic carbon isotope data from Mongolia and Canada are tightly coupled through multiple delta C-13(carb) excursions, quantitatively ruling out previously suggested alternative explanations, such as diagenesis(7,8) or the presence and terminal oxidation of a large marine dissolved organic carbon reservoir(6). Our data from Namibia, which do not record isotopic covariance, can be explained by simple mixing with a detrital flux of organic matter. We thus interpret delta C-13(carb) anomalies as recording a primary perturbation to the surface carbon cycle. This interpretation requires the revisiting of models linking drastic isotope excursions to deep ocean oxygenation and the opening of environments capable of supporting animals(9-11).
C1 [Johnston, D. T.; Macdonald, F. A.; Gill, B. C.; Hoffman, P. F.; Schrag, D. P.] Harvard Univ, Dept Earth & Planetary Sci, Cambridge, MA 02138 USA.
   [Hoffman, P. F.] Univ Victoria, Sch Earth & Ocean Sci, Victoria, BC V8W 2Y2, Canada.
C3 Harvard University; University of Victoria
RP Johnston, DT (corresponding author), Harvard Univ, Dept Earth & Planetary Sci, 20 Oxford St, Cambridge, MA 02138 USA.
EM johnston@eps.harvard.edu
FU Yukon Geological Survey; NSF [EAR-IF 0949227]; KINSC; ESEP; Harvard University; NASA NAI
NR 30
TC 180
Z9 212
U1 2
U2 180
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 15
PY 2012
VL 483
IS 7389
BP 320
EP U110
DI 10.1038/nature10854
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 908HP
UT WOS:000301481800046
PM 22388817
DA 2026-03-09
ER

PT J
AU Schneider, T
   Graves, SDB
   Schaller, EL
   Brown, ME
AF Schneider, T.
   Graves, S. D. B.
   Schaller, E. L.
   Brown, M. E.
TI Polar methane accumulation and rainstorms on Titan from simulations of the methane cycle
SO NATURE
LA English
DT Article
ID midlatitude clouds; lakes; atmosphere; tropics; storms
AB Titan has a methane cycle akin to Earth's water cycle. It has lakes in polar regions(1,2), preferentially in the north(3); dry low latitudes with fluvial features(4,5) and occasional rainstorms(6,7); and tropospheric clouds mainly (so far) in southern middle latitudes and polar regions(8-15). Previous models have explained the low-latitude dryness as a result of atmospheric methane transport into middle and high latitudes(16). Hitherto, no model has explained why lakes are found only in polar regions and preferentially in the north; how low-latitude rainstorms arise; or why clouds cluster in southern middle and high latitudes. Here we report simulations with a three-dimensional atmospheric model coupled to a dynamic surface reservoir of methane. We find that methane is cold-trapped and accumulates in polar regions, preferentially in the north because the northern summer, at aphelion, is longer and has greater net precipitation than the southern summer. The net precipitation in polar regions is balanced in the annual mean by slow along-surface methane transport towards mid-latitudes, and subsequent evaporation. In low latitudes, rare but intense storms occur around the equinoxes, producing enough precipitation to carve surface features. Tropospheric clouds form primarily in middle and high latitudes of the summer hemisphere, which until recently has been the southern hemisphere. We predict that in the northern polar region, prominent clouds will form within about two (Earth) years and lake levels will rise over the next fifteen years.
C1 [Schneider, T.; Graves, S. D. B.; Brown, M. E.] CALTECH, Pasadena, CA 91125 USA.
   [Schaller, E. L.] Natl Suborbital Educ & Res Ctr, NASA Dryden Aircraft Operat Facil, Palmdale, CA 93550 USA.
C3 California Institute of Technology; National Aeronautics & Space Administration (NASA)
RP Schneider, T (corresponding author), CALTECH, Pasadena, CA 91125 USA.
EM tapio@caltech.edu
FU NASA; David and Lucile Packard Fellowship
NR 30
TC 112
Z9 132
U1 0
U2 23
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JAN 5
PY 2012
VL 481
IS 7379
BP 58
EP 61
DI 10.1038/nature10666
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 872VD
UT WOS:000298836900028
PM 22222747
DA 2026-03-09
ER

PT J
AU McLaughlin, RN
   Poelwijk, FJ
   Raman, A
   Gosal, WS
   Ranganathan, R
AF McLaughlin, Richard N., Jr.
   Poelwijk, Frank J.
   Raman, Arjun
   Gosal, Walraj S.
   Ranganathan, Rama
TI The spatial architecture of protein function and adaptation
SO NATURE
LA English
DT Article
ID pdz domain; activation; transcription; determinants; information; robustness; mechanism; network; fitness; units
AB Statistical analysis of protein evolution suggests a design for natural proteins in which sparse networks of coevolving amino acids (termed sectors) comprise the essence of three-dimensional structure and function(1-5). However, proteins are also subject to pressures deriving from the dynamics of the evolutionary process itself-the ability to tolerate mutation and to be adaptive to changing selection pressures(6-10). To understand the relationship of the sector architecture to these properties, we developed a high-throughput quantitative method for a comprehensive single-mutation study in which every position is substituted individually to every other amino acid. Using a PDZ domain (PSD95(pdz3)) model system, we show that sector positions are functionally sensitive to mutation, whereas non-sector positions are more tolerant to substitution. In addition, we find that adaptation to a new binding specificity initiates exclusively through variation within sector residues. A combination of just two sector mutations located near and away from the ligand-binding site suffices to switch the binding specificity of PSD95(pdz3) quantitatively towards a class-switching ligand. The localization of functional constraint and adaptive variation within the sector has important implications for understanding and engineering proteins.
C1 [McLaughlin, Richard N., Jr.; Poelwijk, Frank J.; Raman, Arjun; Gosal, Walraj S.; Ranganathan, Rama] Univ Texas SW Med Ctr Dallas, Green Ctr Syst Biol, Dallas, TX 75390 USA.
   [McLaughlin, Richard N., Jr.; Poelwijk, Frank J.; Raman, Arjun; Gosal, Walraj S.; Ranganathan, Rama] Univ Texas SW Med Ctr Dallas, Dept Pharmacol, Dallas, TX 75390 USA.
C3 University of Texas System; University of Texas Southwestern Medical Center; University of Texas System; University of Texas Southwestern Medical Center
RP Ranganathan, R (corresponding author), Univ Texas SW Med Ctr Dallas, Green Ctr Syst Biol, Dallas, TX 75390 USA.
EM rama.ranganathan@utsouthwestern.edu
FU University of Texas Southwestern Graduate School and Pharmacology Training Grant; Helen Hay Whitney Fellowship program; National Institutes of Health [R01EY018720-05]; Robert A. Welch Foundation [I-1366]; Green Center for Systems Biology
NR 35
TC 346
Z9 420
U1 2
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 NOV 1
PY 2012
VL 491
IS 7422
BP 138
EP U163
DI 10.1038/nature11500
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 028PM
UT WOS:000310434500046
PM 23041932
DA 2026-03-09
ER

PT J
AU Verhagen, E
   Deléglise, S
   Weis, S
   Schliesser, A
   Kippenberg, TJ
AF Verhagen, E.
   Deleglise, S.
   Weis, S.
   Schliesser, A.
   Kippenberg, T. J.
TI Quantum-coherent coupling of a mechanical oscillator to an optical cavity mode
SO NATURE
LA English
DT Article
ID ground-state; optomechanics; resonator
AB Optical laser fields have been widely used to achieve quantum control over the motional and internal degrees of freedom of atoms and ions(1,2), molecules and atomic gases. A route to controlling the quantum states of macroscopic mechanical oscillators in a similar fashion is to exploit the parametric coupling between optical and mechanical degrees of freedom through radiation pressure in suitably engineered optical cavities(3-6). If the optomechanical coupling is 'quantum coherent'-that is, if the coherent coupling rate exceeds both the optical and the mechanical decoherence rate-quantum states are transferred from the optical field to the mechanical oscillator and vice versa. This transfer allows control of the mechanical oscillator state using the wide range of available quantum optical techniques. So far, however, quantum-coherent coupling of micromechanical oscillators has only been achieved using microwave fields at millikelvin temperatures(7,8). Optical experiments have not attained this regime owing to the large mechanical decoherence rates(9) and the difficulty of overcoming optical dissipation(10). Here we achieve quantum-coherent coupling between optical photons and a micromechanical oscillator. Simultaneously, coupling to the cold photon bath cools the mechanical oscillator to an average occupancy of 1.7 +/- 0.1 motional quanta. Excitation with weak classical light pulses reveals the exchange of energy between the optical light field and the micromechanical oscillator in the time domain at the level of less than one quantum on average. This optomechanical system establishes an efficient quantum interface between mechanical oscillators and optical photons, which can provide decoherence-free transport of quantum states through optical fibres. Our results offer a route towards the use of mechanical oscillators as quantum transducers or in microwave-to-optical quantum links(11-15).
C1 [Verhagen, E.; Deleglise, S.; Weis, S.; Schliesser, A.; Kippenberg, T. J.] Ecole Polytech Fed Lausanne, CH-1015 Lausanne, Switzerland.
   [Weis, S.; Schliesser, A.; Kippenberg, T. J.] Max Planck Inst Quantum Opt, D-85748 Garching, Germany.
C3 Swiss Federal Institutes of Technology Domain; Ecole Polytechnique Federale de Lausanne; Max Planck Society
RP Kippenberg, TJ (corresponding author), Ecole Polytech Fed Lausanne, CH-1015 Lausanne, Switzerland.
EM tobias.kippenberg@epfl.ch
FU ERC; DARPA/MTO ORCHID through the AFOSR; NCCR Quantum Science and Technology; Swiss National Science Foundation; Netherlands Organization for Scientific Research (NWO); Marie Curie Cofund Action; Marie Curie Individual Fellowship
NR 30
TC 782
Z9 856
U1 6
U2 325
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD FEB 2
PY 2012
VL 482
IS 7383
BP 63
EP 67
DI 10.1038/nature10787
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 884RN
UT WOS:000299726000035
PM 22297970
DA 2026-03-09
ER

PT J
AU Sterzik, MF
   Bagnulo, S
   Palle, E
AF Sterzik, Michael F.
   Bagnulo, Stefano
   Palle, Enric
TI Biosignatures as revealed by spectropolarimetry of Earthshine
SO NATURE
LA English
DT Article
ID extrasolar planets; vegetation signature; polarization; spectrum; search; atmospheres; skylight; clouds; life
AB Low-resolution intensity spectra of Earth's atmosphere obtained from space reveal strong signatures of life ('biosignatures'), such as molecular oxygen and methane with abundances far from chemical equilibrium, as well as the presence of a 'red edge' (a sharp increase of albedo for wavelengths longer than 700 nm) caused by surface vegetation(1). Light passing through the atmosphere is strongly linearly polarized by scattering (from air molecules, aerosols and cloud particles) and by reflection (from oceans and land(2)). Spectropolarimetric observations of local patches of Earth's sky light from the ground contain signatures of oxygen, ozone and water, and are used to characterize the properties of clouds and aerosols(3,4). When applied to exoplanets, ground-based spectropolarimetry can better constrain properties of atmospheres and surfaces than can standard intensity spectroscopy(5-9). Here we report disk-integrated linear polarization spectra of Earthshine, which is sunlight that has been first reflected by Earth and then reflected back to Earth by the Moon(10-13). The observations allow us to determine the fractional contribution of clouds and ocean surface, and are sensitive to visible areas of vegetation as small as 10 per cent. They represent a benchmark for the diagnostics of the atmospheric composition, mean cloud height and surfaces of exoplanets.
C1 [Sterzik, Michael F.] European So Observ, Santiago, Chile.
   [Bagnulo, Stefano] Armagh Observ, Armagh BT61 9DG, North Ireland.
   [Palle, Enric] Inst Astrofis Canarias, E-38205 Tenerife, Spain.
C3 European Southern Observatory; Instituto de Astrofisica de Canarias
RP Sterzik, MF (corresponding author), European So Observ, Alonso de Cordova 3107, Santiago, Chile.
EM msterzik@eso.org
FU Spanish MICIIN [CGL2009-10641]
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NR 23
TC 100
Z9 108
U1 2
U2 33
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD MAR 1
PY 2012
VL 483
IS 7387
BP 64
EP 66
DI 10.1038/nature10778
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 900HP
UT WOS:000300877900044
PM 22382980
DA 2026-03-09
ER

PT J
AU Xu, X
   Wang, KB
   Zhang, K
   Ma, QY
   Xing, LD
   Sullivan, C
   Hu, DY
   Cheng, SQ
   Wang, S
AF Xu, Xing
   Wang, Kebai
   Zhang, Ke
   Ma, Qingyu
   Xing, Lida
   Sullivan, Corwin
   Hu, Dongyu
   Cheng, Shuqing
   Wang, Shuo
TI A gigantic feathered dinosaur from the Lower Cretaceous of China
SO NATURE
LA English
DT Article
ID tyrannosauroid dinosaur; north-america; theropoda; age
AB Numerous feathered dinosaur specimens have recently been recovered from the Middle-Upper Jurassic and Lower Cretaceous deposits of northeastern China, but most of them represent small animals(1). Here we report the discovery of a gigantic new basal tyrannosauroid, Yutyrannus huali gen. et sp. nov., based on three nearly complete skeletons representing two distinct ontogenetic stages from the Lower Cretaceous Yixian Formation of Liaoning Province, China. Y. huali shares some features, particularly of the cranium, with derived tyrannosauroids(2,3), but is similar to other basal tyrannosauroids(4-12) in possessing a three-fingered manus and a typical theropod pes. Morphometric analysis suggests that Y. huali differed from tyrannosaurids in its growth strategy(13,14). Most significantly, Y. huali bears long filamentous feathers, thus providing direct evidence for the presence of extensively feathered gigantic dinosaurs and offering new insights into early feather evolution.
C1 [Xu, Xing; Ma, Qingyu; Sullivan, Corwin; Wang, Shuo] Chinese Acad Sci, Inst Vertebrate Paleontol & Paleoanthropol, Key Lab Evolutionary Systemat Vertebrates, Beijing 100044, Peoples R China.
   [Xu, Xing; Hu, Dongyu] Shenyang Normal Univ, Liaoning Paleontol Museum, Shenyang 110034, Peoples R China.
   [Wang, Kebai; Cheng, Shuqing] Zhucheng Dinosaur Museum, Zhucheng 262200, Shandong, Peoples R China.
   [Zhang, Ke] China Univ Geosci, Sch Earth Sci & Resources, Beijing 100083, Peoples R China.
   [Xing, Lida] Univ Alberta, Dept Biol Sci, Edmonton, AB T6G 2E9, Canada.
   [Wang, Shuo] Chinese Acad Sci, Grad Univ, Beijing 100049, Peoples R China.
C3 Chinese Academy of Sciences; Institute of Vertebrate Paleontology & Paleoanthropology, CAS; Shenyang Normal University; China University of Geosciences; University of Alberta; Chinese Academy of Sciences; University of Chinese Academy of Sciences, CAS
RP Xu, X (corresponding author), Chinese Acad Sci, Inst Vertebrate Paleontol & Paleoanthropol, Key Lab Evolutionary Systemat Vertebrates, 142 Xiwai St, Beijing 100044, Peoples R China.
EM xingxu@vip.sina.com
FU Zhucheng Municipal Government; Erlianhaote Municipal Government; National Natural Science Foundation of China; Special Funds For Major State Basic Research Projects of China
NR 30
TC 116
Z9 146
U1 8
U2 151
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 5
PY 2012
VL 484
IS 7392
BP 92
EP 95
DI 10.1038/nature10906
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 919QN
UT WOS:000302343400040
PM 22481363
DA 2026-03-09
ER

PT J
AU Pfeffer, C
   Larsen, S
   Song, J
   Dong, MD
   Besenbacher, F
   Meyer, RL
   Kjeldsen, KU
   Schreiber, L
   Gorby, YA
   El-Naggar, MY
   Leung, KM
   Schramm, A
   Risgaard-Petersen, N
   Nielsen, LP
AF Pfeffer, Christian
   Larsen, Steffen
   Song, Jie
   Dong, Mingdong
   Besenbacher, Flemming
   Meyer, Rikke Louise
   Kjeldsen, Kasper Urup
   Schreiber, Lars
   Gorby, Yuri A.
   El-Naggar, Mohamed Y.
   Leung, Kar Man
   Schramm, Andreas
   Risgaard-Petersen, Nils
   Nielsen, Lars Peter
TI Filamentous bacteria transport electrons over centimetre distances
SO NATURE
LA English
DT Article
ID microsensor; reduction; nanowires; sediment
AB Oxygen consumption in marine sediments is often coupled to the oxidation of sulphide generated by degradation of organic matter in deeper, oxygen-free layers. Geochemical observations have shown that this coupling can be mediated by electric currents carried by unidentified electron transporters across centimetre-wide zones. Here we present evidence that the native conductors are long, filamentous bacteria. They abounded in sediment zones with electric currents and along their length they contained strings with distinct properties in accordance with a function as electron transporters. Living, electrical cables add a new dimension to the understanding of interactions in nature and may find use in technology development.
C1 [Pfeffer, Christian; Kjeldsen, Kasper Urup; Schreiber, Lars; Schramm, Andreas; Risgaard-Petersen, Nils; Nielsen, Lars Peter] Aarhus Univ, Dept Biosci, Ctr Geomicrobiol, DK-8000 Aarhus C, Denmark.
   [Larsen, Steffen; Meyer, Rikke Louise; Schramm, Andreas; Nielsen, Lars Peter] Aarhus Univ, Dept Biosci, Microbiol Sect, DK-8000 Aarhus C, Denmark.
   [Song, Jie; Dong, Mingdong; Besenbacher, Flemming; Meyer, Rikke Louise] Aarhus Univ, Ctr DNA Nanotechnol CDNA, Interdisciplinary Nanosci Ctr INANO, DK-8000 Aarhus C, Denmark.
   [Gorby, Yuri A.; Leung, Kar Man] Univ So Calif, Dept Biol Sci, Los Angeles, CA 90089 USA.
   [El-Naggar, Mohamed Y.; Leung, Kar Man] Univ So Calif, Dept Phys & Astron, Los Angeles, CA 90089 USA.
C3 Aarhus University; Aarhus University; Aarhus University; University of Southern California; University of Southern California
RP Risgaard-Petersen, N (corresponding author), Aarhus Univ, Dept Biosci, Ctr Geomicrobiol, DK-8000 Aarhus C, Denmark.
EM nils.risgaard-petersen@biology.au.dk; biolpn@biology.au.dk
FU European Research Council; Danish National Research Foundation; Danish Council for Independent Research \ Natural Sciences (FNU); German Max Planck Society; Villum Foundation; Villum Fonden [00007194] Funding Source: researchfish
NR 20
TC 444
Z9 541
U1 13
U2 732
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD NOV 8
PY 2012
VL 491
IS 7423
BP 218
EP 221
DI 10.1038/nature11586
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 033DP
UT WOS:000310774300036
PM 23103872
DA 2026-03-09
ER

PT J
AU Hammerman, PS
   Lawrence, MS
   Voet, D
   Jing, R
   Cibulskis, K
   Sivachenko, A
   Stojanov, P
   McKenna, A
   Lander, ES
   Gabriel, S
   Getz, G
   Sougnez, C
   Imielinski, M
   Helman, E
   Hernandez, B
   Pho, NH
   Meyerson, M
   Chu, A
   Chun, HJE
   Mungall, AJ
   Pleasance, E
   Robertson, AG
   Sipahimalani, P
   Stoll, D
   Balasundaram, M
   Birol, I
   Butterfield, YSN
   Chuah, E
   Coope, RJN
   Corbett, R
   Dhalla, N
   Guin, R
   Hirst, AC
   Hirst, M
   Holt, RA
   Lee, D
   Li, HI
   Mayo, M
   Moore, RA
   Mungall, K
   Nip, KM
   Olshen, A
   Schein, JE
   Slobodan, JR
   Tam, A
   Thiessen, N
   Varhol, R
   Zeng, T
   Zhao, Y
   Jones, SJM
   Marra, MA
   Saksena, G
   Cherniack, AD
   Schumacher, SE
   Tabak, B
   Carter, SL
   Pho, NH
   Nguyen, H
   Onofrio, RC
   Crenshaw, A
   Ardlie, K
   Beroukhim, R
   Winckler, W
   Hammerman, PS
   Getz, G
   Meyerson, M
   Protopopov, A
   Zhang, JH
   Hadjipanayis, A
   Lee, S
   Xi, RB
   Yang, LX
   Ren, XJ
   Zhang, HL
   Shukla, S
   Chen, PC
   Haseley, P
   Lee, E
   Chin, L
   Park, PJ
   Kucherlapati, R
   Socci, ND
   Liang, YP
   Schultz, N
   Borsu, L
   Lash, AE
   Viale, A
   Sander, C
   Ladanyi, M
   Auman, JT
   Hoadley, KA
   Wilkerson, MD
   Shi, Y
   Liquori, C
   Meng, SW
   Li, L
   Turman, YJ
   Topal, MD
   Tan, DH
   Waring, S
   Buda, E
   Walsh, J
   Jones, CD
   Mieczkowski, PA
   Singh, D
   Wu, J
   Gulabani, A
   Dolina, P
   Bodenheimer, T
   Hoyle, AP
   Simons, JV
   Soloway, MG
   Mose, LE
   Jefferys, SR
   Balu, S
   O'Connor, BD
   Prins, JF
   Liu, J
   Chiang, DY
   Hayes, DN
   Perou, CM
   Cope, L
   Danilova, L
   Weisenberger, DJ
   Maglinte, DT
   Pan, F
   den Berg, DJ
   Triche, T
   Herman, JG
   Baylin, SB
   Laird, PW
   Getz, G
   Noble, M
   Voet, D
   Saksena, G
   Gehlenborg, N
   DiCara, D
   Zhang, JH
   Zhang, HL
   Wu, CJ
   Liu, SY
   Lawrence, MS
   Zou, LH
   Sivachenko, A
   Lin, P
   Stojanov, P
   Jing, R
   Cho, J
   Nazaire, MD
   Robinson, J
   Thorvaldsdottir, H
   Mesirov, J
   Park, PJ
   Chin, L
   Schultz, N
   Sinha, R
   Ciriello, G
   Cerami, E
   Gross, B
   Jacobsen, A
   Gao, J
   Aksoy, BA
   Weinhold, N
   Ramirez, R
   Taylor, BS
   Antipin, Y
   Reva, B
   Shen, RL
   Mo, Q
   Seshan, V
   Paik, PK
   Ladanyi, M
   Sander, C
   Akbani, R
   Zhang, NX
   Broom, BM
   Casasent, T
   Unruh, A
   Wakefield, C
   Cason, RC
   Baggerly, KA
   Weinstein, JN
   Haussler, D
   Benz, CC
   Stuart, JM
   Zhu, JC
   Szeto, C
   Scott, GK
   Yau, C
   Ng, S
   Goldstein, T
   Waltman, P
   Sokolov, A
   Ellrott, K
   Collisson, EA
   Zerbino, D
   Wilks, C
   Ma, S
   Craft, B
   Wilkerson, MD
   Auman, JT
   Hoadley, KA
   Du, Y
   Cabanski, C
   Walter, V
   Singh, D
   Wu, JY
   Gulabani, A
   Bodenheimer, T
   Hoyle, AP
   Simons, JV
   Soloway, MG
   Mose, LE
   Jefferys, SR
   Balu, S
   Marron, JS
   Liu, Y
   Wang, K
   Liu, J
   Prins, JF
   Hayes, DN
   Perou, CM
   Creighton, CJ
   Zhang, YQ
   Travis, WD
   Rekhtman, N
   Yi, J
   Aubry, MC
   Cheney, R
   Dacic, S
   Flieder, D
   Funkhouser, W
   Illei, P
   Myers, J
   Tsao, MS
   Penny, R
   Mallery, D
   Shelton, T
   Hatfield, M
   Morris, S
   Yena, P
   Shelton, C
   Sherman, M
   Paulauskis, J
   Meyerson, M
   Baylin, SB
   Govindan, R
   Akbani, R
   Azodo, I
   Beer, D
   Bose, R
   Byers, LA
   Carbone, D
   Chang, LW
   Chiang, D
   Chu, A
   Chun, E
   Collisson, E
   Cope, L
   Creighton, CJ
   Danilova, L
   Ding, L
   Getz, G
   Hammerman, PS
   Hayes, DN
   Hernandez, B
   Herman, JG
   Heymach, J
   Ida, C
   Imielinski, M
   Johnson, B
   Jurisica, I
   Kaufman, J
   Kosari, F
   Kucherlapati, R
   Kwiatkowski, D
   Ladanyi, M
   Lawrence, MS
   Maher, CA
   Mungall, A
   Ng, S
   Pao, W
   Peifer, M
   Penny, R
   Robertson, G
   Rusch, V
   Sander, C
   Schultz, N
   Shen, RL
   Siegfried, J
   Sinha, R
   Sivachenko, A
   Sougnez, C
   Stoll, D
   Stuart, J
   Thomas, RK
   Tomaszek, S
   Tsao, MS
   Travis, WD
   Vaske, C
   Weinstein, JN
   Weisenberger, D
   Wheeler, D
   Wigle, DA
   Wilkerson, MD
   Wilks, C
   Yang, P
   Zhang, JJ
   Jensen, MA
   Sfeir, R
   Kahn, AB
   Chu, AL
   Kothiyal, P
   Wang, Z
   Snyder, EE
   Pontius, J
   Pihl, TD
   Ayala, B
   Backus, M
   Walton, J
   Baboud, J
   Berton, DL
   Nicholls, MC
   Srinivasan, D
   Raman, R
   Girshik, S
   Kigonya, PA
   Alonso, S
   Sanbhadti, RN
   Barletta, SP
   Greene, JM
   Pot, DA
   Tsao, MS
   Bandarchi-Chamkhaleh, B
   Boyd, J
   Weaver, J
   Wigle, DA
   Azodo, IA
   Tomaszek, SC
   Aubry, MC
   Ida, CM
   Yang, P
   Kosari, F
   Brock, MV
   Rogers, K
   Rutledge, M
   Brown, T
   Lee, B
   Shin, J
   Trusty, D
   Dhir, R
   Siegfried, JM
   Potapova, O
   Fedosenko, KV
   Nemirovich-Danchenko, E
   Rusch, V
   Zakowski, M
   Iacocca, MV
   Brown, J
   Rabeno, B
   Czerwinski, C
   Petrelli, N
   Fan, Z
   Todaro, N
   Eckman, J
   Myers, J
   Rathmell, WK
   Thorne, LB
   Huang, M
   Boice, L
   Hill, A
   Penny, R
   Mallery, D
   Curley, E
   Shelton, C
   Yena, P
   Morrison, C
   Gaudioso, C
   Bartlett, JS
   Kodeeswaran, S
   Zanke, B
   Sekhon, H
   David, K
   Juhl, H
   Van Le, X
   Kohl, B
   Thorp, R
   Tien, NV
   Van Bang, N
   Sussman, H
   Phu, BD
   Hajek, R
   PhiHung, N
   Khan, KZ
   Muley, T
   Shaw, KRM
   Sheth, M
   Yang, L
   Buetow, K
   Davidsen, T
   Demchok, JA
   Eley, G
   Ferguson, M
   Dillon, LAL
   Schaefer, C
   Guyer, MS
   Ozenberger, BA
   Palchik, JD
   Peterson, J
   Sofia, HJ
   Thomson, E
   Meyerson, M
AF Hammerman, Peter S.
   Lawrence, Michael S.
   Voet, Douglas
   Jing, Rui
   Cibulskis, Kristian
   Sivachenko, Andrey
   Stojanov, Petar
   McKenna, Aaron
   Lander, Eric S.
   Gabriel, Stacey
   Getz, Gad
   Sougnez, Carrie
   Imielinski, Marcin
   Helman, Elena
   Hernandez, Bryan
   Pho, Nam H.
   Meyerson, Matthew
   Chu, Andy
   Chun, Hye-Jung E.
   Mungall, Andrew J.
   Pleasance, Erin
   Robertson, A. Gordon
   Sipahimalani, Payal
   Stoll, Dominik
   Balasundaram, Miruna
   Birol, Inanc
   Butterfield, Yaron S. N.
   Chuah, Eric
   Coope, Robin J. N.
   Corbett, Richard
   Dhalla, Noreen
   Guin, Ranabir
   Hirst, Anhe Carrie
   Hirst, Martin
   Holt, Robert A.
   Lee, Darlene
   Li, Haiyan I.
   Mayo, Michael
   Moore, Richard A.
   Mungall, Karen
   Nip, Ka Ming
   Olshen, Adam
   Schein, Jacqueline E.
   Slobodan, Jared R.
   Tam, Angela
   Thiessen, Nina
   Varhol, Richard
   Zeng, Thomas
   Zhao, Yongjun
   Jones, Steven J. M.
   Marra, Marco A.
   Saksena, Gordon
   Cherniack, Andrew D.
   Schumacher, Stephen E.
   Tabak, Barbara
   Carter, Scott L.
   Pho, Nam H.
   Nguyen, Huy
   Onofrio, Robert C.
   Crenshaw, Andrew
   Ardlie, Kristin
   Beroukhim, Rameen
   Winckler, Wendy
   Hammerman, Peter S.
   Getz, Gad
   Meyerson, Matthew
   Protopopov, Alexei
   Zhang, Jianhua
   Hadjipanayis, Angela
   Lee, Semin
   Xi, Ruibin
   Yang, Lixing
   Ren, Xiaojia
   Zhang, Hailei
   Shukla, Sachet
   Chen, Peng-Chieh
   Haseley, Psalm
   Lee, Eunjung
   Chin, Lynda
   Park, Peter J.
   Kucherlapati, Raju
   Socci, Nicholas D.
   Liang, Yupu
   Schultz, Nikolaus
   Borsu, Laetitia
   Lash, Alex E.
   Viale, Agnes
   Sander, Chris
   Ladanyi, Marc
   Auman, J. Todd
   Hoadley, Katherine A.
   Wilkerson, Matthew D.
   Shi, Yan
   Liquori, Christina
   Meng, Shaowu
   Li, Ling
   Turman, Yidi J.
   Topal, Michael D.
   Tan, Donghui
   Waring, Scot
   Buda, Elizabeth
   Walsh, Jesse
   Jones, Corbin D.
   Mieczkowski, Piotr A.
   Singh, Darshan
   Wu, Junyuan
   Gulabani, Anisha
   Dolina, Peter
   Bodenheimer, Tom
   Hoyle, Alan P.
   Simons, Janae V.
   Soloway, Matthew G.
   Mose, Lisle E.
   Jefferys, Stuart R.
   Balu, Saianand
   O'Connor, Brian D.
   Prins, Jan F.
   Liu, Jinze
   Chiang, Derek Y.
   Hayes, D. Neil
   Perou, Charles M.
   Cope, Leslie
   Danilova, Ludmila
   Weisenberger, Daniel J.
   Maglinte, Dennis T.
   Pan, Fei
   Van den Berg, David J.
   Triche, Timothy
   Herman, James G.
   Baylin, Stephen B.
   Laird, Peter W.
   Getz, Gad
   Noble, Michael
   Voet, Doug
   Saksena, Gordon
   Gehlenborg, Nils
   DiCara, Daniel
   Zhang, Jinhua
   Zhang, Hailei
   Wu, Chang-Jiun
   Liu, Spring Yingchun
   Lawrence, Michael S.
   Zou, Lihua
   Sivachenko, Andrey
   Lin, Pei
   Stojanov, Petar
   Jing, Rui
   Cho, Juok
   Nazaire, Marc-Danie
   Robinson, Jim
   Thorvaldsdottir, Helga
   Mesirov, Jill
   Park, Peter J.
   Chin, Lynda
   Schultz, Nikolaus
   Sinha, Rileen
   Ciriello, Giovanni
   Cerami, Ethan
   Gross, Benjamin
   Jacobsen, Anders
   Gao, Jianjiong
   Aksoy, B. Arman
   Weinhold, Nils
   Ramirez, Ricardo
   Taylor, Barry S.
   Antipin, Yevgeniy
   Reva, Boris
   Shen, Ronglai
   Mo, Qianxing
   Seshan, Venkatraman
   Paik, Paul K.
   Ladanyi, Marc
   Sander, Chris
   Akbani, Rehan
   Zhang, Nianxiang
   Broom, Bradley M.
   Casasent, Tod
   Unruh, Anna
   Wakefield, Chris
   Cason, R. Craig
   Baggerly, Keith A.
   Weinstein, John N.
   Haussler, David
   Benz, Christopher C.
   Stuart, Joshua M.
   Zhu, Jingchun
   Szeto, Christopher
   Scott, Gary K.
   Yau, Christina
   Ng, Sam
   Goldstein, Ted
   Waltman, Peter
   Sokolov, Artem
   Ellrott, Kyle
   Collisson, Eric A.
   Zerbino, Daniel
   Wilks, Christopher
   Ma, Singer
   Craft, Brian
   Wilkerson, Matthew D.
   Auman, J. Todd
   Hoadley, Katherine A.
   Du, Ying
   Cabanski, Christopher
   Walter, Vonn
   Singh, Darshan
   Wu, Junyuan
   Gulabani, Anisha
   Bodenheimer, Tom
   Hoyle, Alan P.
   Simons, Janae V.
   Soloway, Matthew G.
   Mose, Lisle E.
   Jefferys, Stuart R.
   Balu, Saianand
   Marron, J. S.
   Liu, Yufeng
   Wang, Kai
   Liu, Jinze
   Prins, Jan F.
   Hayes, D. Neil
   Perou, Charles M.
   Creighton, Chad J.
   Zhang, Yiqun
   Travis, William D.
   Rekhtman, Natasha
   Yi, Joanne
   Aubry, Marie C.
   Cheney, Richard
   Dacic, Sanja
   Flieder, Douglas
   Funkhouser, William
   Illei, Peter
   Myers, Jerome
   Tsao, Ming-Sound
   Penny, Robert
   Mallery, David
   Shelton, Troy
   Hatfield, Martha
   Morris, Scott
   Yena, Peggy
   Shelton, Candace
   Sherman, Mark
   Paulauskis, Joseph
   Meyerson, Matthew
   Baylin, Stephen B.
   Govindan, Ramaswamy
   Akbani, Rehan
   Azodo, Ijeoma
   Beer, David
   Bose, Ron
   Byers, Lauren A.
   Carbone, David
   Chang, Li-Wei
   Chiang, Derek
   Chu, Andy
   Chun, Elizabeth
   Collisson, Eric
   Cope, Leslie
   Creighton, Chad J.
   Danilova, Ludmila
   Ding, Li
   Getz, Gad
   Hammerman, Peter S.
   Hayes, D. Neil
   Hernandez, Bryan
   Herman, James G.
   Heymach, John
   Ida, Cristiane
   Imielinski, Marcin
   Johnson, Bruce
   Jurisica, Igor
   Kaufman, Jacob
   Kosari, Farhad
   Kucherlapati, Raju
   Kwiatkowski, David
   Ladanyi, Marc
   Lawrence, Michael S.
   Maher, Christopher A.
   Mungall, Andy
   Ng, Sam
   Pao, William
   Peifer, Martin
   Penny, Robert
   Robertson, Gordon
   Rusch, Valerie
   Sander, Chris
   Schultz, Nikolaus
   Shen, Ronglai
   Siegfried, Jill
   Sinha, Rileen
   Sivachenko, Andrey
   Sougnez, Carrie
   Stoll, Dominik
   Stuart, Joshua
   Thomas, Roman K.
   Tomaszek, Sandra
   Tsao, Ming-Sound
   Travis, William D.
   Vaske, Charles
   Weinstein, John N.
   Weisenberger, Daniel
   Wheeler, David
   Wigle, Dennis A.
   Wilkerson, Matthew D.
   Wilks, Christopher
   Yang, Ping
   Zhang, Jianjua John
   Jensen, Mark A.
   Sfeir, Robert
   Kahn, Ari B.
   Chu, Anna L.
   Kothiyal, Prachi
   Wang, Zhining
   Snyder, Eric E.
   Pontius, Joan
   Pihl, Todd D.
   Ayala, Brenda
   Backus, Mark
   Walton, Jessica
   Baboud, Julien
   Berton, Dominique L.
   Nicholls, Matthew C.
   Srinivasan, Deepak
   Raman, Rohini
   Girshik, Stanley
   Kigonya, Peter A.
   Alonso, Shelley
   Sanbhadti, Rashmi N.
   Barletta, Sean P.
   Greene, John M.
   Pot, David A.
   Tsao, Ming-Sound
   Bandarchi-Chamkhaleh, Bizhan
   Boyd, Jeff
   Weaver, JoEllen
   Wigle, Dennis A.
   Azodo, Ijeoma A.
   Tomaszek, Sandra C.
   Aubry, Marie Christine
   Ida, Christiane M.
   Yang, Ping
   Kosari, Farhad
   Brock, Malcolm V.
   Rogers, Kristen
   Rutledge, Marian
   Brown, Travis
   Lee, Beverly
   Shin, James
   Trusty, Dante
   Dhir, Rajiv
   Siegfried, Jill M.
   Potapova, Olga
   Fedosenko, Konstantin V.
   Nemirovich-Danchenko, Elena
   Rusch, Valerie
   Zakowski, Maureen
   Iacocca, Mary V.
   Brown, Jennifer
   Rabeno, Brenda
   Czerwinski, Christine
   Petrelli, Nicholas
   Fan, Zhen
   Todaro, Nicole
   Eckman, John
   Myers, Jerome
   Rathmell, W. Kimryn
   Thorne, Leigh B.
   Huang, Mei
   Boice, Lori
   Hill, Ashley
   Penny, Robert
   Mallery, David
   Curley, Erin
   Shelton, Candace
   Yena, Peggy
   Morrison, Carl
   Gaudioso, Carmelo
   Bartlett, Johnm. S.
   Kodeeswaran, Sugy
   Zanke, Brent
   Sekhon, Harman
   David, Kerstin
   Juhl, Hartmut
   Van Le, Xuan
   Kohl, Bernard
   Thorp, Richard
   Tien, Nguyen Viet
   Van Bang, Nguyen
   Sussman, Howard
   Phu, Bui Duc
   Hajek, Richard
   PhiHung, Nguyen
   Khan, Khurram Z.
   Muley, Thomas
   Shaw, Kenna R. Mills
   Sheth, Margi
   Yang, Liming
   Buetow, Ken
   Davidsen, Tanja
   Demchok, John A.
   Eley, Greg
   Ferguson, Martin
   Dillon, Laura A. L.
   Schaefer, Carl
   Guyer, Mark S.
   Ozenberger, Bradley A.
   Palchik, Jacqueline D.
   Peterson, Jane
   Sofia, Heidi J.
   Thomson, Elizabeth
   Meyerson, Matthew
TI Comprehensive genomic characterization of squamous cell lung cancers
SO NATURE
LA English
DT Article
ID copy-number alteration; therapeutic target; mutations; gene; carcinoma; amplification; sensitivity; landscape; gefitinib; oncogene
AB Lung squamous cell carcinoma is a common type of lung cancer, causing approximately 400,000 deaths per year worldwide. Genomic alterations in squamous cell lung cancers have not been comprehensively characterized, and no molecularly targeted agents have been specifically developed for its treatment. As part of The Cancer Genome Atlas, here we profile 178 lung squamous cell carcinomas to provide a comprehensive landscape of genomic and epigenomic alterations. We show that the tumour type is characterized by complex genomic alterations, with a mean of 360 exonic mutations, 165 genomic rearrangements, and 323 segments of copy number alteration per tumour. We find statistically recurrent mutations in 11 genes, including mutation of TP53 in nearly all specimens. Previously unreported loss-of-function mutations are seen in the HLA-A class I major histocompatibility gene. Significantly altered pathways included NFE2L2 and KEAP1 in 34%, squamous differentiation genes in 44%, phosphatidylinositol-3-OH kinase pathway genes in 47%, and CDKN2A and RB1 in 72% of tumours. We identified a potential therapeutic target in most tumours, offering new avenues of investigation for the treatment of squamous cell lung cancers.
C1 [Sivachenko, Andrey; McKenna, Aaron; Cherniack, Andrew D.; Crenshaw, Andrew; Hadjipanayis, Angela; Chen, Peng-Chieh; Kucherlapati, Raju] MIT, Eli & Edythe L Broad Inst, Cambridge, MA 02142 USA.
   [Hammerman, Peter S.; Meyerson, Matthew; Beroukhim, Rameen; Hammerman, Peter S.; Meyerson, Matthew; Johnson, Bruce] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA.
   [Lander, Eric S.] MIT, Dept Biol, Cambridge, MA 02142 USA.
   [Lander, Eric S.; Sougnez, Carrie] Harvard Univ, Dept Syst Biol, Boston, MA 02115 USA.
   [Gabriel, Stacey; Getz, Gad; Sougnez, Carrie; Onofrio, Robert C.; Ardlie, Kristin] Harvard Univ, Genet Anal Platform, Cambridge, MA 02142 USA.
   [Imielinski, Marcin; Meyerson, Matthew; Meyerson, Matthew; Imielinski, Marcin] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
   [Chu, Andy; Chun, Hye-Jung E.; Mungall, Andrew J.; Pleasance, Erin; Robertson, A. Gordon; Sipahimalani, Payal; Stoll, Dominik; Balasundaram, Miruna; Birol, Inanc; Chuah, Eric; Guin, Ranabir; Hirst, Anhe Carrie; Hirst, Martin; Lee, Darlene; Li, Haiyan I.; Mayo, Michael; Mungall, Karen; Nip, Ka Ming; Schein, Jacqueline E.; Slobodan, Jared R.; Thiessen, Nina; Marra, Marco A.; Chun, Elizabeth; Mungall, Andy; Robertson, Gordon] BC Canc Agcy, Canadas Michael Smith Genome Sci Ctr, Vancouver, BC V5Z, Canada.
   [Olshen, Adam] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
   [Olshen, Adam] Dana Farber Canc Inst, Boston, MA 02115 USA.
   [Protopopov, Alexei; Zhang, Jianhua; Ren, Xiaojia; Zhang, Hailei; Shukla, Sachet; Zhang, Jinhua; Chin, Lynda] Univ Texas MD Anderson Canc Ctr, Inst Appl Canc Sci, Dept Genom Med, Houston, TX 77030 USA.
   [Hadjipanayis, Angela; Ren, Xiaojia; Chen, Peng-Chieh; Haseley, Psalm; Lee, Eunjung; Park, Peter J.; Kucherlapati, Raju] Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA.
   [Lee, Semin; Xi, Ruibin; Yang, Lixing; Haseley, Psalm; Lee, Eunjung; Gehlenborg, Nils] Harvard Univ, Ctr Biomed Informat, Sch Med, Boston, MA 02115 USA.
   [Park, Peter J.] Childrens Hosp, Informat Program, Boston, MA 02115 USA.
   [Socci, Nicholas D.; Liang, Yupu; Schultz, Nikolaus; Borsu, Laetitia; Lash, Alex E.; Viale, Agnes; Sander, Chris; Sinha, Rileen; Ciriello, Giovanni; Cerami, Ethan; Gross, Benjamin; Jacobsen, Anders; Gao, Jianjiong; Aksoy, B. Arman; Weinhold, Nils; Ramirez, Ricardo; Taylor, Barry S.; Antipin, Yevgeniy; Reva, Boris] Mem Sloan Kettering Canc Ctr, Computat Biol Ctr, New York, NY 10065 USA.
   [Ladanyi, Marc; Ladanyi, Marc] Mem Sloan Kettering Canc Ctr, Dept Mol Oncol, New York, NY 10065 USA.
   [Ladanyi, Marc; Ladanyi, Marc] Mem Sloan Kettering Canc Ctr, Dept Pathol & Human Oncol, New York, NY 10065 USA.
   [Auman, J. Todd] Univ N Carolina, Eshelman Sch Pharm, Chapel Hill, NC 27599 USA.
   [Auman, J. Todd; Zerbino, Daniel; Auman, J. Todd] Univ N Carolina, Inst Pharmacogenet & Individualized Therapy, Chapel Hill, NC 27599 USA.
   [Hoadley, Katherine A.; Mieczkowski, Piotr A.; Chiang, Derek Y.] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA.
   [Hoadley, Katherine A.; Mose, Lisle E.; Jefferys, Stuart R.; Perou, Charles M.] Univ N Carolina, Dept Pathol & Lab Med, Chapel Hill, NC 27599 USA.
   [Hoadley, Katherine A.; Wilkerson, Matthew D.; Liquori, Christina; Li, Ling; Buda, Elizabeth; Walsh, Jesse; Singh, Darshan; Wu, Junyuan; Gulabani, Anisha; Dolina, Peter; Hoyle, Alan P.; Simons, Janae V.; Soloway, Matthew G.; Collisson, Eric A.; Craft, Brian; Cabanski, Christopher; Prins, Jan F.; Chiang, Derek; Hayes, D. Neil] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA.
   [Tan, Donghui; Liu, Yufeng] Univ N Carolina, Carolina Ctr Genome Sci, Chapel Hill, NC 27599 USA.
   [Jones, Corbin D.; Hayes, D. Neil] Univ N Carolina, Dept Biol, Chapel Hill, NC 27599 USA.
   [Balu, Saianand; Prins, Jan F.] Univ N Carolina, Dept Comp Sci, Chapel Hill, NC 27599 USA.
   [Liu, Jinze] Univ Kentucky, Dept Comp Sci, Lexington, KY 40506 USA.
   [Hayes, D. Neil] Univ N Carolina, Dept Internal Med, Div Med Oncol, Chapel Hill, NC 27599 USA.
   [Cope, Leslie; Danilova, Ludmila; Herman, James G.; Baylin, Stephen B.] Johns Hopkins Univ, Canc Biol Div, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21231 USA.
   [Weisenberger, Daniel J.; Maglinte, Dennis T.; Pan, Fei; Van den Berg, David J.; Triche, Timothy; Laird, Peter W.; Weisenberger, Daniel; Wilks, Christopher] Univ So Calif, Calif Epigenome Ctr, Los Angeles, CA 90033 USA.
   [Akbani, Rehan; Zhang, Nianxiang; Broom, Bradley M.; Unruh, Anna; Wakefield, Chris; Baggerly, Keith A.; Weinstein, John N.; Weinstein, John N.] Univ Texas MD Anderson Canc Ctr, Dept Bioinformat & Computat Biol, Houston, TX 77030 USA.
   [Cason, R. Craig] Univ Texas MD Anderson Canc Ctr, Div Pathol & Lab Med, Houston, TX 77030 USA.
   [Weinstein, John N.] Univ Texas MD Anderson Canc Ctr, Dept Syst Biol, Houston, TX 77030 USA.
   [Haussler, David; Stuart, Joshua M.; Zhu, Jingchun; Szeto, Christopher; Ng, Sam; Waltman, Peter; Sokolov, Artem; Ellrott, Kyle; Stuart, Joshua; Vaske, Charles] Univ Calif Santa Cruz, Dept Biomol Engn, Santa Cruz, CA 95064 USA.
   [Haussler, David; Stuart, Joshua M.; Zhu, Jingchun; Szeto, Christopher; Goldstein, Ted; Waltman, Peter; Sokolov, Artem; Ellrott, Kyle; Stuart, Joshua; Vaske, Charles] Univ Calif Santa Cruz, Ctr Biomol Sci & Engn, Santa Cruz, CA 95064 USA.
   Univ Calif Santa Cruz, Howard Hughes Med Inst, Santa Cruz, CA 95064 USA.
   [Benz, Christopher C.; Scott, Gary K.; Yau, Christina] Buck Inst Age Res, Novato, CA 94945 USA.
   [Collisson, Eric] Univ Calif San Francisco, Div Hematol Oncol, San Francisco, CA 94143 USA.
   [Marron, J. S.] Univ N Carolina, Dept Stat & Operat Res, Chapel Hill, NC 27599 USA.
   [Creighton, Chad J.; Zhang, Yiqun] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA.
   [Zhang, Yiqun] Baylor Coll Med, Dan L Duncan Canc Ctr, Div Biostat, Houston, TX 77030 USA.
   [Travis, William D.; Rekhtman, Natasha] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10065 USA.
   [Yi, Joanne; Aubry, Marie C.; Ida, Cristiane] Mayo Clin, Dept Pathol, Rochester, MN 55905 USA.
   [Cheney, Richard; Shelton, Candace; Yena, Peggy; Morrison, Carl; Gaudioso, Carmelo] Roswell Pk Canc Inst, Dept Pathol, Buffalo, NY 14263 USA.
   [Dacic, Sanja] Univ Pittsburgh, Dept Pathol, Pittsburgh, PA 15213 USA.
   [Flieder, Douglas; Boyd, Jeff; Weaver, JoEllen] Fox Chase Canc Ctr, Dept Pathol, Philadelphia, PA 19111 USA.
   [Funkhouser, William] Univ N Carolina, Dept Pathol, Med Ctr, Chapel Hill, NC 27599 USA.
   [Illei, Peter] Johns Hopkins Univ, Dept Pathol, Sch Med, Baltimore, MD 21287 USA.
   [Myers, Jerome] Penrose St Francis Hlth Syst, Dept Pathol, Colorado Springs, CO 80907 USA.
   [Tsao, Ming-Sound; Bandarchi-Chamkhaleh, Bizhan] Ontario Canc Inst, Dept Pathol & Med Biophys, Toronto, ON M5G 2MY, Canada.
   [Tsao, Ming-Sound; Bandarchi-Chamkhaleh, Bizhan] Princess Margaret Hosp, Toronto, ON M5G 2MY, Canada.
   [Penny, Robert; Mallery, David; Shelton, Troy; Hatfield, Martha; Morris, Scott; Yena, Peggy; Shelton, Candace; Sherman, Mark; Paulauskis, Joseph; Hill, Ashley; Curley, Erin] Int Genom Consortium, Phoenix, AZ 85004 USA.
   [Govindan, Ramaswamy; Bose, Ron; Chang, Li-Wei; Ding, Li; Maher, Christopher A.] Washington Univ, Dept Med, Div Oncol, Sch Med, St Louis, MO 63110 USA.
   [Beer, David] Univ Michigan, Dept Surg, Ann Arbor, MI 48109 USA.
   [Carbone, David; Kaufman, Jacob; Pao, William] Vanderbilt Univ, Dept Hematol, Nashville, TN 37232 USA.
   [Jurisica, Igor; Brock, Malcolm V.] IBM Life Sci Discovery Ctr, Ontario Canc Inst, Toronto, ON M5G 1L7, Canada.
   [Peifer, Martin; Thomas, Roman K.] Univ Cologne, Dept Translat Genom, D-50931 Cologne, Germany.
   [Rusch, Valerie] Mem Sloan Kettering Canc Ctr, Dept Surg, New York, NY 10065 USA.
   [Siegfried, Jill; Siegfried, Jill M.] Univ Pittsburgh, Dept Pharmacol & Chem Biol, Med Ctr, Pittsburgh, PA 15232 USA.
   [Thomas, Roman K.] Univ Cologne, Dept Translat Canc Genom, Ctr Integrated Oncol, D-50924 Cologne, Germany.
   [Wheeler, David] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA.
   [Ida, Christiane M.] Mayo Clin, Dept Lab Med, Rochester, MN 55905 USA.
   [Yang, Ping] Mayo Clin, Dept Hlth Sci Res, Rochester, MN 55905 USA.
   [Rogers, Kristen; Brown, Travis] Johns Hopkins Sch Med, Dept Surg, Baltimore, MD 21287 USA.
   [Rutledge, Marian; Lee, Beverly] Johns Hopkins Sch Med, Dept Oncol, Baltimore, MD 21287 USA.
   [Shin, James; Trusty, Dante] Johns Hopkins Sch Med, Dept Pathol, Baltimore, MD 21287 USA.
   [Dhir, Rajiv] Univ Pittsburgh, Dept Pathol, Pittsburgh, PA 15213 USA.
   [Potapova, Olga; Nemirovich-Danchenko, Elena] Cureline, San Francisco, CA 94080 USA.
   [Fedosenko, Konstantin V.] City Clin Oncol Dispensary, St Petersburg 197022, Russia.
   [Zakowski, Maureen] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10065 USA.
   [Iacocca, Mary V.; Brown, Jennifer; Rabeno, Brenda; Czerwinski, Christine; Petrelli, Nicholas] Helen F Graham Canc Ctr, Newark, DE 19713 USA.
   [Fan, Zhen; Todaro, Nicole; Huang, Mei] St Joseph Med Ctr, Towson, MD 21204 USA.
   [Thorne, Leigh B.] UNC Lineberger Canc Ctr, UNC Tissue Procurement Facil, Dept Pathol, Chapel Hill, NC 27599 USA.
   [Kodeeswaran, Sugy; Zanke, Brent] Ontario Inst Canc Res, Ontario Tumour Bank, Toronto, ON M5G 0A3, Canada.
   [David, Kerstin] Indivumed GmbH, D-20251 Hamburg, Germany.
   [Juhl, Hartmut] Indivumed Inc, Kensington, MD 20895 USA.
   [Van Le, Xuan; Kohl, Bernard; Thorp, Richard] ILSBio LLC, Chestertown, MD 21620 USA.
   [Tien, Nguyen Viet] Minist Hlth, Hanoi, Vietnam.
   [Van Bang, Nguyen] Hue Cent Hosp, Hue City, Vietnam.
   [Sussman, Howard] Stanford Univ, Med Ctr, Stanford, CA 94305 USA.
   [Hajek, Richard] Univ Texas MD Anderson Canc Ctr, Ctr Minor Hlth Res, Houston, TX 77030 USA.
   [Phu, Bui Duc; PhiHung, Nguyen] Natl Canc Inst, Hanoi, Vietnam.
   [Khan, Khurram Z.] ILSBio LLC, Chestertown, MD 21620 USA.
   [Muley, Thomas] Univ Heidelberg Hosp, ThoraxKlin, D-69126 Heidelberg, Germany.
   [Shaw, Kenna R. Mills; Sheth, Margi; Yang, Liming; Demchok, John A.; Dillon, Laura A. L.] NCI, Canc Genome Atlas Program Off, Bethesda, MD 20892 USA.
   [Buetow, Ken; Davidsen, Tanja; Eley, Greg; Schaefer, Carl] NCI, CBIIT, NIH, Rockville, MD 20852 USA.
   [Guyer, Mark S.; Ozenberger, Bradley A.; Palchik, Jacqueline D.; Peterson, Jane; Sofia, Heidi J.; Thomson, Elizabeth] NHGRI, NIH, Bethesda, MD 20892 USA.
C3 Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Massachusetts Institute of Technology (MIT); Harvard University; Harvard University; Harvard University; Harvard Medical School; British Columbia Cancer Agency; University of California System; University of California San Francisco; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; University of Texas System; UTMD Anderson Cancer Center; 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; Memorial Sloan Kettering Cancer Center; Memorial Sloan Kettering Cancer Center; 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; 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; University of Kentucky; University of North Carolina; University of North Carolina Chapel Hill; Johns Hopkins University; Johns Hopkins Medicine; University of Southern California; 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 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; Buck Institute for Research on Aging; University of California System; University of California San Francisco; University of North Carolina; University of North Carolina Chapel Hill; Baylor College of Medicine; Baylor College of Medicine; Memorial Sloan Kettering Cancer Center; Mayo Clinic; Roswell Park Comprehensive Cancer Center; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh; Fox Chase Cancer Center; University of North Carolina; University of North Carolina Chapel Hill; Johns Hopkins University; University of Toronto; University Health Network Toronto; University of Toronto; University Health Network Toronto; Princess Margaret Cancer Centre; International Genomics Consortium; Washington University (WUSTL); University of Michigan System; University of Michigan; Vanderbilt University; University of Toronto; University Health Network Toronto; University of Cologne; Memorial Sloan Kettering Cancer Center; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh; University of Cologne; Baylor College of Medicine; Mayo Clinic; Mayo Clinic; Johns Hopkins University; Johns Hopkins Medicine; Johns Hopkins University; Johns Hopkins Medicine; Johns Hopkins University; Johns Hopkins Medicine; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh; Memorial Sloan Kettering Cancer Center; Helen F. Graham Cancer Center & Research Institute; Ontario Institute for Cancer Research; University of Toronto; Stanford University; University of Texas System; UTMD Anderson Cancer Center; Ruprecht Karls University Heidelberg; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); Center for Cancer Genomics (CCG); International Genomics Consortium; 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), MIT, 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 CA126563, U24 CA126544, U24 CA143845, U24 CA143858, U24 CA144025, U24 CA143882, U24 CA143866, U24 CA143867, U24 CA143848, U24 CA143840, U24 CA143835, U24 CA143799, U24 CA143883, U24 CA143843, U54 HG003067, U54 HG003079, U54 HG003273]; Direct For Biological Sciences [0850237] Funding Source: National Science Foundation; Emerging Frontiers [0850237] Funding Source: National Science Foundation; National Cancer Institute [P30CA016086, P30CA016672, T32CA009172] Funding Source: NIH RePORTER
NR 46
TC 3086
Z9 3439
U1 3
U2 373
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 27
PY 2012
VL 489
IS 7417
BP 519
EP 525
DI 10.1038/nature11404
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 011LT
UT WOS:000309167100041
PM 22960745
DA 2026-03-09
ER

PT J
AU Macfarlan, TS
   Gifford, WD
   Driscoll, S
   Lettieri, K
   Rowe, HM
   Bonanomi, D
   Firth, A
   Singer, O
   Trono, D
   Pfaff, SL
AF Macfarlan, Todd S.
   Gifford, Wesley D.
   Driscoll, Shawn
   Lettieri, Karen
   Rowe, Helen M.
   Bonanomi, Dario
   Firth, Amy
   Singer, Oded
   Trono, Didier
   Pfaff, Samuel L.
TI Embryonic stem cell potency fluctuates with endogenous retrovirus activity
SO NATURE
LA English
DT Article
ID gene-expression; muerv-l; transposable elements; mouse; evolution; differentiation; trophectoderm; establishment; repression; generation
AB Embryonic stem (ES) cells are derived from blastocyst-stage embryos and are thought to be functionally equivalent to the inner cell mass, which lacks the ability to produce all extraembryonic tissues. Here we identify a rare transient cell population within mouse ES and induced pluripotent stem (iPS) cell cultures that expresses high levels of transcripts found in two-cell (2C) embryos in which the blastomeres are totipotent. We genetically tagged these 2C-like ES cells and show that they lack the inner cell mass pluripotency proteins Oct4 (also known as Pou5f1), Sox2 and Nanog, and have acquired the ability to contribute to both embryonic and extraembryonic tissues. We show that nearly all ES cells cycle in and out of this privileged state, which is partially controlled by histone-modifying enzymes. Transcriptome sequencing and bioinformatic analyses showed that many 2C transcripts are initiated from long terminal repeats derived from endogenous retroviruses, suggesting this foreign sequence has helped to drive cell-fate regulation in placental mammals.
C1 [Macfarlan, Todd S.; Gifford, Wesley D.; Driscoll, Shawn; Lettieri, Karen; Bonanomi, Dario; Pfaff, Samuel L.] Salk Inst Biol Studies, Howard Hughes Med Inst, Gene Express Lab, La Jolla, CA 92037 USA.
   [Rowe, Helen M.; Trono, Didier] Ecole Polytech Fed Lausanne, Sch Life Sci, CH-1015 Lausanne, Switzerland.
   [Firth, Amy; Singer, Oded] Salk Inst Biol Studies, Genet Lab, La Jolla, CA 92037 USA.
C3 Salk Institute; Howard Hughes Medical Institute; Swiss Federal Institutes of Technology Domain; Ecole Polytechnique Federale de Lausanne; Swiss School of Public Health (SSPH+); Salk Institute
RP Pfaff, SL (corresponding author), Salk Inst Biol Studies, Howard Hughes Med Inst, Gene Express Lab, 10010 N Torrey Pines, La Jolla, CA 92037 USA.
EM pfaff@salk.edu
FU National Institute of Neurological Disorders and Stroke [R37NS037116]; Marshall Heritage Foundation; California Institute for Regenerative Medicine; Eunice Kennedy Shriver National Institute of Child Health and Human Development [ZIAHD008933] Funding Source: NIH RePORTER
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NR 42
TC 894
Z9 1004
U1 6
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 JUL 5
PY 2012
VL 487
IS 7405
BP 57
EP +
DI 10.1038/nature11244
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 968LM
UT WOS:000305982900049
PM 22722858
DA 2026-03-09
ER

PT J
AU Law, DR
   Shapley, AE
   Steidel, CC
   Reddy, NA
   Christensen, CR
   Erb, DK
AF Law, David R.
   Shapley, Alice E.
   Steidel, Charles C.
   Reddy, Naveen A.
   Christensen, Charlotte R.
   Erb, Dawn K.
TI High velocity dispersion in a rare grand-design spiral galaxy at redshift z=2.18
SO NATURE
LA English
DT Article
ID star-forming galaxy; ultra deep field; similar-to 2; adaptive optics; sins survey; spectroscopy; evolution; disks; kinematics; simulations
AB Although grand-design spiral galaxies are relatively common in the local Universe, only one has been spectroscopically confirmed(1) to lie at redshift z > 2 (HDFX 28; z = 2.011); and it may prove to be a major merger that simply resembles a spiral in projection. The rarity of spirals has been explained as a result of disks being dynamically 'hot' at z > 2 (refs 2-5), which may instead favour the formation of commonly observed clumpy structures(6-10). Alternatively, current instrumentation may simply not be sensitive enough to detect spiral structures comparable to those in the modern Universe(11). At z < 2, the velocity dispersion of disks decreases(12), and spiral galaxies are more numerous by z approximate to 1 (refs 7, 13-15). Here we report observations of the grand-design spiral galaxy Q2343-BX442 at z = 2.18. Spectroscopy of ionized gas shows that the disk is dynamically hot, implying an uncertain origin for the spiral structure. The kinematics of the galaxy are consistent with a thick disk undergoing a minor merger, which can drive the formation of short-lived spiral structure(16-18). A duty cycle of <100 Myr for such tidally induced spiral structure in a hot massive disk is consistent with its rarity.
C1 [Law, David R.] Univ Toronto, Dunlap Inst Astron & Astrophys, Toronto, ON M5S 3H4, Canada.
   [Shapley, Alice E.] Univ Calif Los Angeles, Dept Phys & Astron, Los Angeles, CA 90095 USA.
   [Steidel, Charles C.] CALTECH, Pasadena, CA 91125 USA.
   [Reddy, Naveen A.] Univ Calif Riverside, Dept Phys & Astron, Riverside, CA 92521 USA.
   [Christensen, Charlotte R.] Steward Observ, Tucson, AZ 85721 USA.
   [Erb, Dawn K.] Univ Wisconsin, Dept Phys, Milwaukee, WI 53211 USA.
C3 University of Toronto; University of California System; University of California Los Angeles; California Institute of Technology; University of California System; University of California Riverside; University of Wisconsin System; University of Wisconsin Milwaukee
RP Law, DR (corresponding author), Univ Toronto, Dunlap Inst Astron & Astrophys, 50 St George St, Toronto, ON M5S 3H4, Canada.
EM drlaw@di.utoronto.ca
FU Space Telescope Science Institute [GO-11694]; NASA [NAS 5-26555]; David and Lucile Packard Foundation; US National Science Foundation [AST-1009452]; Direct For Mathematical & Physical Scien; Division Of Astronomical Sciences [0908805, 1009452] Funding Source: National Science Foundation
NR 30
TC 74
Z9 83
U1 0
U2 3
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUL 19
PY 2012
VL 487
IS 7407
BP 338
EP 340
DI 10.1038/nature11256
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 975JB
UT WOS:000306506500036
PM 22810697
DA 2026-03-09
ER

PT J
AU Schlappa, J
   Wohlfeld, K
   Zhou, KJ
   Mourigal, M
   Haverkort, MW
   Strocov, VN
   Hozoi, L
   Monney, C
   Nishimoto, S
   Singh, S
   Revcolevschi, A
   Caux, JS
   Patthey, L
   Ronnow, HM
   van den Brink, J
   Schmitt, T
AF Schlappa, J.
   Wohlfeld, K.
   Zhou, K. J.
   Mourigal, M.
   Haverkort, M. W.
   Strocov, V. N.
   Hozoi, L.
   Monney, C.
   Nishimoto, S.
   Singh, S.
   Revcolevschi, A.
   Caux, J. -S.
   Patthey, L.
   Ronnow, H. M.
   van den Brink, J.
   Schmitt, T.
TI Spin-orbital separation in the quasi-one-dimensional Mott insulator Sr2CuO3
SO NATURE
LA English
DT Article
ID x-ray-scattering; charge separation
AB When viewed as an elementary particle, the electron has spin and charge. When binding to the atomic nucleus, it also acquires an angular momentum quantum number corresponding to the quantized atomic orbital it occupies. Even if electrons in solids form bands and delocalize from the nuclei, in Mott insulators they retain their three fundamental quantum numbers: spin, charge and orbital(1). The hallmark of one-dimensional physics is a breaking up of the elementary electron into its separate degrees of freedom(2). The separation of the electron into independent quasi-particles that carry either spin (spinons) or charge (holons) was first observed fifteen years ago(3). Here we report observation of the separation of the orbital degree of freedom (orbiton) using resonant inelastic X-ray scattering on the one-dimensional Mott insulator Sr2CuO3. We resolve an orbiton separating itself from spinons and propagating through the lattice as a distinct quasi-particle with a substantial dispersion in energy over momentum, of about 0.2 electronvolts, over nearly one Brillouin zone.
C1 [Schlappa, J.; Zhou, K. J.; Strocov, V. N.; Monney, C.; Patthey, L.; Schmitt, T.] Paul Scherrer Inst, Swiss Light Source, CH-5232 Villigen, Switzerland.
   [Schlappa, J.] Helmholtz Zentrum Berlin Mat & Energie GmbH, Inst Methoden & Instrumentierung Forsch Synchrotr, D-12489 Berlin, Germany.
   [Wohlfeld, K.; Hozoi, L.; Nishimoto, S.; van den Brink, J.] IFW Dresden, Inst Theoret Solid State Phys, D-01069 Dresden, Germany.
   [Mourigal, M.; Ronnow, H. M.] Ecole Polytech Fed Lausanne, CH-1015 Lausanne, Switzerland.
   [Haverkort, M. W.] Max Planck Inst Solid State Res, D-70569 Stuttgart, Germany.
   [Singh, S.; Revcolevschi, A.] Univ Paris 11, ICMMO UMR 8182, F-91405 Orsay, France.
   [Caux, J. -S.] Univ Amsterdam, Inst Theoret Phys, NL-1090 GL Amsterdam, Netherlands.
   [Patthey, L.] SwissFEL, CH-5232 Villigen, Switzerland.
C3 Swiss Federal Institutes of Technology Domain; Paul Scherrer Institute; Helmholtz Association; Helmholtz-Zentrum fuer Materialien und Energie GmbH (HZB); Institute for Integrative Nanosciences (IIN); Leibniz Association; Leibniz Institute for Solid State & Materials Research Dresden; Swiss Federal Institutes of Technology Domain; Ecole Polytechnique Federale de Lausanne; Max Planck Society; Universite Paris Saclay; Centre National de la Recherche Scientifique (CNRS); CNRS - Institute of Chemistry (INC); University of Amsterdam
RP Schlappa, J (corresponding author), Paul Scherrer Inst, Swiss Light Source, CH-5232 Villigen, Switzerland.
EM justine.schlappa@helmholtz-berlin.de; thorsten.schmitt@psi.ch
FU Swiss National Science Foundation and its NCCR MaNEP; Alexander von Humboldt foundation; Foundation for Fundamental Research on Matter; Netherlands Organisation for Scientific Research; European contract NOVMAG; Division of Materials Science and Engineering, US Department of Energy [DE-SC0007091]; U.S. Department of Energy (DOE) [DE-SC0007091] Funding Source: U.S. Department of Energy (DOE)
NR 30
TC 279
Z9 303
U1 0
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 3
PY 2012
VL 485
IS 7396
BP 82
EP U108
DI 10.1038/nature10974
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 934NV
UT WOS:000303451900038
PM 22522933
DA 2026-03-09
ER

PT J
AU Li, Y
   Lu, H
   Cheng, PL
   Ge, SY
   Xu, HT
   Shi, SH
   Dan, Y
AF Li, Ye
   Lu, Hui
   Cheng, Pei-lin
   Ge, Shaoyu
   Xu, Huatai
   Shi, Song-Hai
   Dan, Yang
TI Clonally related visual cortical neurons show similar stimulus feature selectivity
SO NATURE
LA English
DT Article
ID circuit formation; receptive-fields; in-vivo; cortex; neocortex; networks; specification; neurogenesis; patterns; connexin
AB A fundamental feature of the mammalian neocortex is its columnar organization(1). In the visual cortex, functional columns consisting of neurons with similar orientation preferences have been characterized extensively(2-4), but how these columns are constructed during development remains unclear(5). The radial unit hypothesis(6) posits that the ontogenetic columns formed by clonally related neurons migrating along the same radial glial fibre during corticogenesis(7) provide the basis for functional columns in adult neocortex(1). However, a direct correspondence between the ontogenetic and functional columns has not been demonstrated(8). Here we show that, despite the lack of a discernible orientation map in mouse visual cortex(4,9,10), sister neurons in the same radial clone exhibit similar orientation preferences. Using a retroviral vector encoding green fluorescent protein to label radial clones of excitatory neurons, and in vivo two-photon calcium imaging to measure neuronal response properties, we found that sister neurons preferred similar orientations whereas nearby non-sister neurons showed no such relationship. Interestingly, disruption of gap junction coupling by viral expression of a dominant-negative mutant of Cx26 (also known as Gjb2) or by daily administration of a gap junction blocker, carbenoxolone, during the first postnatal week greatly diminished the functional similarity between sister neurons, suggesting that the maturation of ontogenetic into functional columns requires intercellular communication through gap junctions. Together with the recent finding of preferential excitatory connections among sister neurons(11), our results support the radial unit hypothesis and unify the ontogenetic and functional columns in the visual cortex.
C1 [Li, Ye; Lu, Hui; Cheng, Pei-lin; Dan, Yang] Univ Calif Berkeley, Helen Wills Neurosci Inst, Dept Mol & Cell Biol, Div Neurobiol, Berkeley, CA 94720 USA.
   [Li, Ye; Lu, Hui; Dan, Yang] Univ Calif Berkeley, Howard Hughes Med Inst, Berkeley, CA 94720 USA.
   [Ge, Shaoyu] SUNY Stony Brook, Dept Neurobiol & Behav, Stony Brook, NY 11794 USA.
   [Xu, Huatai; Shi, Song-Hai] Mem Sloan Kettering Canc Ctr, Dev Biol Program, New York, NY 10065 USA.
C3 University of California System; University of California Berkeley; Howard Hughes Medical Institute; University of California System; University of California Berkeley; State University of New York (SUNY) System; Stony Brook University; Memorial Sloan Kettering Cancer Center
RP Dan, Y (corresponding author), Univ Calif Berkeley, Helen Wills Neurosci Inst, Dept Mol & Cell Biol, Div Neurobiol, Berkeley, CA 94720 USA.
EM ydan@berkeley.edu
FU National Institutes of Health (NIH) [R01 EY018861, R01 DA024681, R21NS072483]; NSF [22250400-42533]; Emerging Frontiers & Multidisciplinary Activities; Directorate For Engineering [0835878] Funding Source: National Science Foundation
NR 33
TC 188
Z9 220
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 7
PY 2012
VL 486
IS 7401
BP 118
EP U144
DI 10.1038/nature11110
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 953GD
UT WOS:000304854000039
PM 22678292
DA 2026-03-09
ER

PT J
AU Cook, DJ
   Teves, L
   Tymianski, M
AF Cook, Douglas J.
   Teves, Lucy
   Tymianski, Michael
TI Treatment of stroke with a PSD-95 inhibitor in the gyrencephalic primate brain
SO NATURE
LA English
DT Article
ID acute ischemic-stroke; protein interactions; neuroprotection; translation; evolution; diffusion; trials; model; recommendations; prediction
AB All attempts at treating strokes by pharmacologically reducing the human brain's vulnerability to ischaemia have failed, leaving stroke as a leading cause of death, disability and massive socioeconomic loss worldwide(1). Over decades, research has failed to translate over 1,000 experimental treatments from discovery in cells and rodents to use in humans(2-4), a scientific crisis that gave rise to the prevailing belief that pharmacological neuroprotection is not feasible or practicable in higher-order brains. To provide a strategy for advancing stroke therapy, we used higher-order gyrencephalic non-human primates, which bear genetic, anatomical and behavioural similarities to humans(5,6) and tested neuroprotection by PSD-95 inhibitors-promising compounds that uncouple postsynaptic density protein PSD-95 from neurotoxic signalling pathways(7-10). Here we show that stroke damage can be prevented in non-human primates in which a PSD-95 inhibitor is administered after stroke onset in clinically relevant situations. This treatment reduced infarct volumes as gauged by magnetic resonance imaging and histology, preserved the capacity of ischaemic cells to maintain gene transcription in genome-wide screens of ischaemic brain tissue, and significantly preserved neurological function in neuro-behavioural assays. The degree of tissue neuroprotection by magnetic resonance imaging corresponded strongly to the preservation of neurological function, supporting the intuitive but unproven dictum that integrity of brain tissue can reflect functional outcome. Our findings establish that tissue neuroprotection and improved functional outcome after stroke is unequivocally achievable in gyrencephalic non-human primates treated with PSD-95 inhibitors. Efforts must ensue to translate these findings to humans.
C1 [Cook, Douglas J.; Teves, Lucy; Tymianski, Michael] Toronto Western Hosp, Res Inst, Toronto, ON M5T 2S8, Canada.
   [Tymianski, Michael] Univ Toronto, Dept Physiol, Toronto, ON M5S 1A8, Canada.
   [Tymianski, Michael] Univ Toronto, Inst Med Sci, Toronto, ON M5S 1A8, Canada.
   [Tymianski, Michael] Univ Toronto, Dept Surg, Toronto, ON M5S 1A8, Canada.
C3 University of Toronto; University Health Network Toronto; University of Toronto; University of Toronto; University of Toronto
RP Tymianski, M (corresponding author), Toronto Western Hosp, Res Inst, Toronto, ON M5T 2S8, Canada.
EM mike.tymianski@uhn.ca
FU Canadian Stroke Network; Heart and Stroke Foundation of Ontario [NA 6988]; Canada Research Chair
NR 37
TC 362
Z9 429
U1 1
U2 96
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD MAR 8
PY 2012
VL 483
IS 7388
BP 213
EP U112
DI 10.1038/nature10841
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 904DT
UT WOS:000301174900039
PM 22388811
DA 2026-03-09
ER

PT J
AU Pearson, RA
   Barber, AC
   Rizzi, M
   Hippert, C
   Xue, T
   West, EL
   Duran, Y
   Smith, AJ
   Chuang, JZ
   Azam, SA
   Luhmann, UFO
   Benucci, A
   Sung, CH
   Bainbridge, JW
   Carandini, M
   Yau, KW
   Sowden, JC
   Ali, RR
AF Pearson, R. A.
   Barber, A. C.
   Rizzi, M.
   Hippert, C.
   Xue, T.
   West, E. L.
   Duran, Y.
   Smith, A. J.
   Chuang, J. Z.
   Azam, S. A.
   Luhmann, U. F. O.
   Benucci, A.
   Sung, C. H.
   Bainbridge, J. W.
   Carandini, M.
   Yau, K. -W.
   Sowden, J. C.
   Ali, R. R.
TI Restoration of vision after transplantation of photoreceptors
SO NATURE
LA English
DT Article
ID retinitis-pigmentosa; visual-acuity; cone vision; wild-type; mouse; mice; precursors; adult; cells; integration
AB Cell transplantation is a potential strategy for treating blindness caused by the loss of photoreceptors. Although transplanted rod-precursor cells are able to migrate into the adult retina and differentiate to acquire the specialized morphological features of mature photoreceptor cells(1), the fundamental question remains whether transplantation of photoreceptor cells can actually improve vision. Here we provide evidence of functional rod-mediated vision after photoreceptor transplantation in adult Gnat1(-/-) mice, which lack rod function and are a model of congenital stationary night blindness(2). We show that transplanted rod precursors form classic triad synaptic connections with second-order bipolar and horizontal cells in the recipient retina. The newly integrated photoreceptor cells are light-responsive with dim-flash kinetics similar to adult wild-type photoreceptors. By using intrinsic imaging under scotopic conditions we demonstrate that visual signals generated by transplanted rods are projected to higher visual areas, including V1. Moreover, these cells are capable of driving optokinetic head tracking and visually guided behaviour in the Gnat1(-/-) mouse under scotopic conditions. Together, these results demonstrate the feasibility of photoreceptor transplantation as a therapeutic strategy for restoring vision after retinal degeneration.
C1 [Pearson, R. A.; Barber, A. C.; Rizzi, M.; Hippert, C.; West, E. L.; Duran, Y.; Smith, A. J.; Azam, S. A.; Luhmann, U. F. O.; Bainbridge, J. W.; Ali, R. R.] UCL, Dept Genet, UCL Inst Ophthalmol, London EC1V 9EL, England.
   [Benucci, A.; Carandini, M.] UCL, UCL Inst Ophthalmol, Dept Visual Neurosci, London EC1V 9EL, England.
   [Xue, T.; Yau, K. -W.] Johns Hopkins Univ, Sch Med, Solomon H Snyder Dept Neurosci, Baltimore, MD 21205 USA.
   [Chuang, J. Z.; Sung, C. H.] Cornell Univ, Weill Med Coll, Dept Cell & Dev Biol, Dyson Vision Res Inst,Dept Ophthalmol, New York, NY 10021 USA.
   [Sowden, J. C.] UCL, UCL Inst Child Hlth, Dev Biol Unit, London WC1N 1EH, England.
   [Ali, R. R.] UCL, UCL Inst Child Hlth, Mol Immunol Unit, London WC1N 1EH, England.
C3 University of London; University College London; University of London; University College London; Johns Hopkins University; Cornell University; Weill Cornell Medicine; University of London; University College London; University of London; University College London
RP Pearson, RA (corresponding author), UCL, Dept Genet, UCL Inst Ophthalmol, 11-43 Bath St, London EC1V 9EL, England.
EM rachael.pearson@ucl.ac.uk; r.ali@ucl.ac.uk
FU Medical Research Council UK [G03000341]; Wellcome Trust [082217]; Royal Society [RG080398]; British Retinitis Pigmentosa Society [GR566]; Miller's Trust; Department of Health's National Institute for Health Research Biomedical Research Centre at Moorfields Eye Hospital; Alcon Research Institute; Great Ormond Street Hospital Children's Charity; US National Institutes of Health [EY06837]; Antonio Champalimaud Vision Award (Portugal); Research to Prevent Blindness [EY11307, EY016805]; European Research Council; Fight for Sight [1351/52, 1779/80] Funding Source: researchfish; Great Ormond Street Hospital Childrens Charity [V1221, V1257] Funding Source: researchfish; Medical Research Council [MR/J004553/1, G0901550, G0800791, G0700438] Funding Source: researchfish; National Institute for Health Research [NF-SI-0508-10130, NIHR-RP-011-003] Funding Source: researchfish; MRC [G0901550, G0800791, MR/J004553/1, G0700438] Funding Source: UKRI
NR 22
TC 392
Z9 453
U1 0
U2 125
PU NATURE PUBLISHING 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 3
PY 2012
VL 485
IS 7396
BP 99
EP 103
DI 10.1038/nature10997
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 934NV
UT WOS:000303451900042
PM 22522934
DA 2026-03-09
ER

PT J
AU Vanin, S
   Bhutani, S
   Montelli, S
   Menegazzi, P
   Green, EW
   Pegoraro, M
   Sandrelli, F
   Costa, R
   Kyriacou, CP
AF Vanin, Stefano
   Bhutani, Supriya
   Montelli, Stefano
   Menegazzi, Pamela
   Green, Edward W.
   Pegoraro, Mirko
   Sandrelli, Federica
   Costa, Rodolfo
   Kyriacou, Charalambos P.
TI Unexpected features of Drosophila circadian behavioural rhythms under natural conditions
SO NATURE
LA English
DT Article
ID endogenous clock; temperature; light; melanogaster; neurons; entrainment; oscillators; moonlight; favors; allele
AB Circadian clocks have evolved to synchronize physiology, metabolism and behaviour to the 24-h geophysical cycles of the Earth(1). Drosophila melanogaster's rhythmic locomotor behaviour provides the main phenotype for the identification of higher eukaryotic clock genes(2,3). Under laboratory light-dark cycles, flies show enhanced activity before lights on and off signals(4,5), and these anticipatory responses have defined the neuronal sites of the corresponding morning (M) and evening (E) oscillators(6,7). However, the natural environment provides much richer cycling environmental stimuli than the laboratory, so we sought to examine fly locomotor rhythms in the wild. Here we show that several key laboratory-based assumptions about circadian behaviour are not supported by natural observations. These include the anticipation of light transitions, the midday 'siesta', the fly's crepuscular activity, its nocturnal behaviour under moonlight, and the dominance of light stimuli over temperature. We also observe a third major locomotor component in addition to M and E, which we term 'A' (afternoon). Furthermore, we show that these natural rhythm phenotypes can be observed in the laboratory by using realistic temperature and light cycle simulations. Our results suggest that a comprehensive re-examination of circadian behaviour and its molecular readouts under simulated natural conditions will provide a more authentic interpretation of the adaptive significance of this important rhythmic phenotype. Such studies should also help to clarify the underlying molecular and neuroanatomical substrates of the clock under natural protocols.
C1 [Vanin, Stefano; Montelli, Stefano; Menegazzi, Pamela; Pegoraro, Mirko; Sandrelli, Federica; Costa, Rodolfo] Univ Padua, Dept Biol, I-35131 Padua, Italy.
   [Bhutani, Supriya; Green, Edward W.; Pegoraro, Mirko; Kyriacou, Charalambos P.] Univ Leicester, Dept Genet, Leicester LE1 7RH, Leics, England.
C3 University of Padua; University of Leicester
RP Costa, R (corresponding author), Univ Padua, Dept Biol, I-35131 Padua, Italy.
EM rodolfo.costa@unipd.it
FU European Community [018741]; Biotechnology and Biological Sciences Research Council; National Environmental Research Council; Royal Society; Medical Research Council; Italian Space Agency (DCMC); Ministero dell'Universita e delle Ricerca (MIUR); BBSRC [BB/J005169/1, BB/F008988/1] Funding Source: UKRI; Biotechnology and Biological Sciences Research Council [BB/F008988/1, BB/J005169/1] Funding Source: researchfish
NR 30
TC 220
Z9 241
U1 0
U2 95
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD APR 19
PY 2012
VL 484
IS 7394
BP 371
EP U108
DI 10.1038/nature10991
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 927YM
UT WOS:000302946500032
PM 22495312
DA 2026-03-09
ER

PT J
AU Lin, YY
   Kiihl, S
   Suhail, Y
   Liu, SY
   Chou, YH
   Kuang, Z
   Lu, JY
   Khor, CN
   Lin, CL
   Bader, JS
   Irizarry, R
   Boeke, JD
AF Lin, Yu-yi
   Kiihl, Samara
   Suhail, Yasir
   Liu, Shang-Yun
   Chou, Yi-hsuan
   Kuang, Zheng
   Lu, Jin-ying
   Khor, Chin Ni
   Lin, Chi-Long
   Bader, Joel S.
   Irizarry, Rafael
   Boeke, Jef D.
TI RETRACTED: Functional dissection of lysine deacetylases reveals that HDAC1 and p300 regulate AMPK (Retracted article. See vol. 503, 2013)
SO NATURE
LA English
DT Article; Retracted Publication
ID activated protein-kinase; histone acetylation; cellular-metabolism; essential genes; cancer-cells; inhibitors; complexes; identification; panther; yeast
AB First identified as histone-modifying proteins, lysine acetyltransferases (KATs) and deacetylases (KDACs) antagonize each other through modification of the side chains of lysine residues in histone proteins(1). Acetylation of many non-histone proteins involved in chromatin, metabolism or cytoskeleton regulation were further identified in eukaryotic organisms(2-6), but the corresponding enzymes and substrate-specific functions of the modifications are unclear. Moreover, mechanisms underlying functional specificity of individual KDACs(7) remain enigmatic, and the substrate spectra of each KDAC lack comprehensive definition. Here we dissect the functional specificity of 12 critical human KDACs using a genome-wide synthetic lethality screen(8-13) in cultured human cells. The genetic interaction profiles revealed enzyme-substrate relationships between individual KDACs and many important substrates governing a wide array of biological processes including metabolism, development and cell cycle progression. We further confirmed that acetylation and deacetylation of the catalytic subunit of the adenosine monophosphate-activated protein kinase (AMPK), a critical cellular energy-sensing protein kinase complex, is controlled by the opposing catalytic activities of HDAC1 and p300. Deacetylation of AMPK enhances physical interaction with the upstream kinase LKB1, leading to AMPK phosphorylation and activation, and resulting in lipid breakdown in human liver cells. These findings provide new insights into previously underappreciated metabolic regulatory roles of HDAC1 in coordinating nutrient availability and cellular responses upstream of AMPK, and demonstrate the importance of high-throughput genetic interaction profiling to elucidate functional specificity and critical substrates of individual human KDACs potentially valuable for therapeutic applications.
C1 [Lin, Yu-yi; Liu, Shang-Yun; Chou, Yi-hsuan] Natl Taiwan Univ, Inst Biochem & Mol Biol, Coll Med, Taipei 100, Taiwan.
   [Lin, Yu-yi; Lu, Jin-ying] Natl Taiwan Univ Hosp, Dept Internal Med, Taipei 100, Taiwan.
   [Lin, Yu-yi] Natl Taiwan Univ Hosp, Dept Oncol, Taipei 100, Taiwan.
   [Kiihl, Samara; Irizarry, Rafael] Sch Publ Hlth, Dept Biostat, Baltimore, MD 21231 USA.
   [Suhail, Yasir; Bader, Joel S.] Johns Hopkins Univ, Dept Biomed Engn, Baltimore, MD 21218 USA.
   [Kuang, Zheng; Boeke, Jef D.] Johns Hopkins Univ, Dept Mol Biol & Genet, Sch Med, Baltimore, MD 21205 USA.
   [Kuang, Zheng; Boeke, Jef D.] Johns Hopkins Univ, High Throughput Biol Ctr, Sch Med, Baltimore, MD 21205 USA.
   [Lu, Jin-ying] Natl Taiwan Univ Hosp, Dept Lab Med, Taipei 100, Taiwan.
   [Khor, Chin Ni; Lin, Chi-Long] Acad Sinica, Inst Mol Biol, Natl RNAi Core Facil, Taipei 115, Taiwan.
C3 National Taiwan University; National Taiwan University; National Taiwan University Hospital; National Taiwan University; National Taiwan University Hospital; Johns Hopkins University; Johns Hopkins University; Johns Hopkins University; National Taiwan University; National Taiwan University Hospital; Academia Sinica - Taiwan
RP Lin, YY (corresponding author), Natl Taiwan Univ, Inst Biochem & Mol Biol, Coll Med, Taipei 100, Taiwan.
EM yuyilin@ntu.edu.tw; jboeke1@jhmi.edu
FU National Science Council [NSC 98-2320-B-002-057-, NSC 99-2320-B-002-057-, NSC 100-2325-002-044]; National Taiwan University Frontier and Innovative Research [99R71424]; National Taiwan University College of Medicine; National Taiwan University Hospital Excellent Translational Medicine Research [99C101-603]; National Health Research Institutes [NHRI-EX100-10017BC]; Liver Disease Prevention and Treatment Research Foundation; NIH [U54 RR 020839]
NR 38
TC 78
Z9 98
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 FEB 9
PY 2012
VL 482
IS 7384
BP 251
EP U149
DI 10.1038/nature10804
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 888HI
UT WOS:000299994100045
PM 22318606
DA 2026-03-09
ER

PT J
AU Liu, C
   Plaçais, PY
   Yamagata, N
   Pfeiffer, BD
   Aso, Y
   Friedrich, AB
   Siwanowicz, I
   Rubin, GM
   Preat, T
   Tanimoto, H
AF Liu, Chang
   Placais, Pierre-Yves
   Yamagata, Nobuhiro
   Pfeiffer, Barret D.
   Aso, Yoshinori
   Friedrich, Anja B.
   Siwanowicz, Igor
   Rubin, Gerald M.
   Preat, Thomas
   Tanimoto, Hiromu
TI A subset of dopamine neurons signals reward for odour memory in Drosophila
SO NATURE
LA English
DT Article
ID targeted gene-expression; mushroom body; brain; fly; hydroxylase; octopamine; serotonin; behavior; reveals; arousal
AB Animals approach stimuli that predict a pleasant outcome(1). After the paired presentation of an odour and a reward, Drosophila melanogaster can develop a conditioned approach towards that odour(2,3). Despite recent advances in understanding the neural circuits for associative memory and appetitive motivation(4), the cellular mechanisms for reward processing in the fly brain are unknown. Here we show that a group of dopamine neurons in the protocerebral anterior medial (PAM) cluster signals sugar reward by transient activation and inactivation of target neurons in intact behaving flies. These dopamine neurons are selectively required for the reinforcing property of, but not a reflexive response to, the sugar stimulus. In vivo calcium imaging revealed that these neurons are activated by sugar ingestion and the activation is increased on starvation. The output sites of the PAM neurons are mainly localized to the medial lobes of the mushroom bodies (MBs), where appetitive olfactory associative memory is formed(5,6). We therefore propose that the PAM cluster neurons endow a positive predictive value to the odour in the MBs. Dopamine in insects is known to mediate aversive reinforcement signals(5,7-11). Our results highlight the cellular specificity underlying the various roles of dopamine and the importance of spatially segregated local circuits within the MBs.
C1 [Liu, Chang; Yamagata, Nobuhiro; Aso, Yoshinori; Friedrich, Anja B.; Siwanowicz, Igor; Tanimoto, Hiromu] Max Planck Inst Neurobiol, D-82152 Martinsried, Germany.
   [Liu, Chang] Chinese Acad Sci, Kunming Inst Zool, Lab Primate Cognit Neurosci, Kunming 650223, Yunnan, Peoples R China.
   [Liu, Chang] Chinese Acad Sci, Grad Univ, Beijing 100049, Peoples R China.
   [Placais, Pierre-Yves; Preat, Thomas] Ecole Super Phys & Chim Ind Ville Paris, CNRS, Neurobiol Unit, F-75005 Paris, France.
   [Pfeiffer, Barret D.; Aso, Yoshinori; Rubin, Gerald M.] Howard Hughes Med Inst, Ashburn, VA 20147 USA.
C3 Max Planck Society; Chinese Academy of Sciences; Kunming Institute of Zoology, CAS; Chinese Academy of Sciences; University of Chinese Academy of Sciences, CAS; Centre National de la Recherche Scientifique (CNRS); Universite PSL; Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI); Howard Hughes Medical Institute
RP Tanimoto, H (corresponding author), Max Planck Inst Neurobiol, D-82152 Martinsried, Germany.
EM hiromut@neuro.mpg.de
FU Max-Planck-Gesellschaft; Chinese Academy of Sciences; Deutscher Akademischer Austausch Dienst; Alexander von Humboldt Foundation; Region Ile-de-France; Agence Nationale pour la Recherche; Howard Hughes Medical Institute; Bundesministerium fur Bildung und Forschung
NR 37
TC 423
Z9 485
U1 2
U2 160
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD AUG 23
PY 2012
VL 488
IS 7412
BP 512
EP +
DI 10.1038/nature11304
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 992FS
UT WOS:000307761600037
PM 22810589
DA 2026-03-09
ER

PT J
AU Chung, I
   Lee, B
   He, JQ
   Chang, RPH
   Kanatzidis, MG
AF Chung, In
   Lee, Byunghong
   He, Jiaqing
   Chang, Robert P. H.
   Kanatzidis, Mercouri G.
TI All-solid-state dye-sensitized solar cells with high efficiency
SO NATURE
LA English
DT Article
ID redox electrolyte; performance
AB Dye-sensitized solar cells based on titanium dioxide (TiO2) are promising low-cost alternatives to conventional solid-state photovoltaic devices based on materials such as Si, CdTe and CuIn1-xGaxSe2 (refs 1, 2). Despite offering relatively high conversion efficiencies for solar energy, typical dye-sensitized solar cells suffer from durability problems that result from their use of organic liquid electrolytes containing the iodide/tri-iodide redox couple, which causes serious problems such as electrode corrosion and electrolyte leakage(3). Replacements for iodine-based liquid electrolytes have been extensively studied, but the efficiencies of the resulting devices remain low(3-9). Here we show that the solution-processable p-type direct bandgap semiconductor CsSnI3 can be used for hole conduction in lieu of a liquid electrolyte. The resulting solid-state dye-sensitized solar cells consist of CsSnI2.95F0.05 doped with SnF2, nanoporous TiO2 and the dye N719, and show conversion efficiencies of up to 10.2 per cent (8.51 per cent with a mask). With a bandgap of 1.3 electronvolts, CsSnI3 enhances visible light absorption on the red side of the spectrum to outperform the typical dye-sensitized solar cells in this spectral region.
C1 [Chung, In; He, Jiaqing; Kanatzidis, Mercouri G.] Northwestern Univ, Dept Chem, Evanston, IL 60208 USA.
C3 Northwestern University
RP Kanatzidis, MG (corresponding author), Northwestern Univ, Dept Chem, 2145 Sheridan Rd, Evanston, IL 60208 USA.
EM m-kanatzidis@northwestern.edu
FU NSF-DMR [0843962]; DOE Energy Frontier Research Center, ANSER [DE-SC0001059]; Initiative for Energy and Sustainability at Northwestern (ISEN); Direct For Mathematical & Physical Scien; Division Of Materials Research [0843962] Funding Source: National Science Foundation
NR 20
TC 1647
Z9 1839
U1 6
U2 1726
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD MAY 24
PY 2012
VL 485
IS 7399
BP 486
EP U94
DI 10.1038/nature11067
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 946IH
UT WOS:000304344500039
PM 22622574
DA 2026-03-09
ER

PT J
AU Sahoo, SK
   Planavsky, NJ
   Kendall, B
   Wang, XQ
   Shi, XY
   Scott, C
   Anbar, AD
   Lyons, TW
   Jiang, GQ
AF Sahoo, Swapan K.
   Planavsky, Noah J.
   Kendall, Brian
   Wang, Xinqiang
   Shi, Xiaoying
   Scott, Clint
   Anbar, Ariel D.
   Lyons, Timothy W.
   Jiang, Ganqing
TI Ocean oxygenation in the wake of the Marinoan glaciation
SO NATURE
LA English
DT Article
ID evolution; molybdenum; oxidation; vanadium
AB Metazoans are likely to have their roots in the Cryogenian period(1-3), but there is a marked increase in the appearance of novel animal and algae fossils shortly after the termination of the late Cryogenian (Marinoan) glaciation about 635 million years ago(4-6). It has been suggested that an oxygenation event in the wake of the severe Marinoan glaciation was the driving factor behind this early diversification of metazoans and the shift in ecosystem complexity(7,8). But there is little evidence for an increase in oceanic or atmospheric oxygen following the Marinoan glaciation, or for a direct link between early animal evolution and redox conditions in general(9). Models linking trends in early biological evolution to shifts in Earth system processes thus remain controversial(10). Here we report geochemical data from early Ediacaran organic-rich black shales (similar to 635-630 million years old) of the basal Doushantuo Formation in South China. High enrichments of molybdenum and vanadium and low pyrite sulphur isotope values (Delta S-34 values >= 65 per mil) in these shales record expansion of the oceanic inventory of redox-sensitive metals and the growth of the marine sulphate reservoir in response to a widely oxygenated ocean. The data provide evidence for an early Ediacaran oxygenation event, which pre-dates the previous estimates for post-Marinoan oxygenation(11-13) by more than 50 million years. Our findings seem to support a link between the most severe glaciations in Earth's history, the oxygenation of the Earth's surface environments, and the earliest diversification of animals.
C1 [Sahoo, Swapan K.; Jiang, Ganqing] Univ Nevada, Dept Geosci, Las Vegas, NV 89154 USA.
   [Planavsky, Noah J.; Lyons, Timothy W.] Univ Calif Riverside, Dept Earth Sci, Riverside, CA 92521 USA.
   [Kendall, Brian; Anbar, Ariel D.] Arizona State Univ, Sch Earth & Space Explorat, Tempe, AZ 85287 USA.
   [Wang, Xinqiang; Shi, Xiaoying] China Univ Geosci, Sch Earth Sci & Resources, Beijing 10008, Peoples R China.
   [Scott, Clint] McGill Univ, Dept Earth & Planetary Sci, Montreal, PQ H3A 2A7, Canada.
   [Anbar, Ariel D.] Arizona State Univ, Dept Chem & Biochem, Tempe, AZ 85287 USA.
C3 Nevada System of Higher Education (NSHE); University of Nevada Las Vegas; University of California System; University of California Riverside; Arizona State University; Arizona State University-Tempe; China University of Geosciences; McGill University; Arizona State University; Arizona State University-Tempe
RP Jiang, GQ (corresponding author), Univ Nevada, Dept Geosci, Las Vegas, NV 89154 USA.
EM Ganqing.Jiang@unlv.edu
FU National Science Foundation Division of Earth Science; NASA Astrobiology programme; National Natural Science Foundation of China; Directorate For Geosciences; Division Of Earth Sciences [0746035] Funding Source: National Science Foundation; Division Of Earth Sciences; Directorate For Geosciences [0745825] Funding Source: National Science Foundation
NR 32
TC 465
Z9 555
U1 11
U2 360
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 27
PY 2012
VL 489
IS 7417
BP 546
EP 549
DI 10.1038/nature11445
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 011LT
UT WOS:000309167100046
PM 23018964
DA 2026-03-09
ER

PT J
AU Huang, DY
   Engel, MS
   Cai, CY
   Wu, H
   Nel, A
AF Huang, Diying
   Engel, Michael S.
   Cai, Chenyang
   Wu, Hao
   Nel, Andre
TI Diverse transitional giant fleas from the Mesozoic era of China
SO NATURE
LA English
DT Article
ID phylogenetic implications; head morphology; mecoptera; siphonaptera; insecta
AB Fleas are one of the major lineages of ectoparasitic insects and are now highly specialized for feeding on the blood of birds or mammals(1). This has isolated them among holometabolan insect orders, although they derive from the Antliophora (scorpionflies and true flies). Like most ectoparasitic lineages, their fossil record is meagre and confined to Cenozoic-era representatives of modern families(1), so that we lack evidence of the origins of fleas in the Mesozoic era. The origins of the first recognized Cretaceous stem-group flea, Tarwinia, remains highly controversial(1). Here we report fossils of the oldest definitive fleas-giant forms from the Middle Jurassic and Early Cretaceous periods of China. They exhibit many defining features of fleas but retain primitive traits such as non-jumping hindlegs. More importantly, all have stout and elongate sucking siphons for piercing the hides of their hosts, implying that these fleas may be rooted among the pollinating 'long siphonate' scorpionflies of the Mesozoic. Their special morphology suggests that their earliest hosts were hairy or feathered 'reptilians', and that they radiated to mammalian and bird hosts later in the Cenozoic.
C1 [Huang, Diying; Cai, Chenyang; Wu, Hao] Chinese Acad Sci, Nanjing Inst Geol & Palaeontol, State Key Lab Palaeobiol & Stratig, Nanjing 210008, Peoples R China.
   [Engel, Michael S.] Univ Kansas, Nat Hist Museum, Div Entomol, Lawrence, KS 66049 USA.
   [Engel, Michael S.] Univ Kansas, Dept Ecol & Evolutionary Biol, Lawrence, KS 66049 USA.
   [Nel, Andre] Museum Natl Hist Nat, CNRS, UMR 7205, F-75005 Paris, France.
C3 Chinese Academy of Sciences; University of Kansas; University of Kansas; Centre National de la Recherche Scientifique (CNRS); CNRS - Institute of Ecology & Environment (INEE); Sorbonne Universite; Museum National d'Histoire Naturelle (MNHN)
RP Huang, DY (corresponding author), Chinese Acad Sci, Nanjing Inst Geol & Palaeontol, State Key Lab Palaeobiol & Stratig, Nanjing 210008, Peoples R China.
EM huangdiying@sina.com; anel@mnhn.fr
FU National Natural Science Foundation of China; National Basic Research Program of China [2012CB821900]; Chinese Academy of Sciences [KZCX2-YW-QN104]; US National Science Foundation [DEB-0542909]
NR 23
TC 64
Z9 73
U1 0
U2 63
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD MAR 8
PY 2012
VL 483
IS 7388
BP 201
EP 204
DI 10.1038/nature10839
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 904DT
UT WOS:000301174900036
DA 2026-03-09
ER

PT J
AU Rücklin, M
   Donoghue, PCJ
   Johanson, Z
   Trinajstic, K
   Marone, F
   Stampanoni, M
AF Ruecklin, Martin
   Donoghue, Philip C. J.
   Johanson, Zerina
   Trinajstic, Kate
   Marone, Federica
   Stampanoni, Marco
TI Development of teeth and jaws in the earliest jawed vertebrates
SO NATURE
LA English
DT Article
ID evolutionary origins; pharyngeal denticles; placoderms; dentition; skeleton; growth; fish
AB Teeth and jaws constitute a model of the evolutionary developmental biology concept of modularity(1) and they have been considered the key innovations underpinning a classic example of adaptive radiation(2). However, their evolutionary origins are much debated. Placoderms comprise an extinct sister clade(3) or grade(4,5) to the clade containing chondrichthyans and osteichthyans, and although they clearly possess jaws, previous studies have suggested that they lack teeth(6-8), that they possess convergently evolved tooth-like structures(9-11) or that they possess true teeth(12). Here we use synchrotron radiation X-ray tomographic microscopy (SRXTM)(13) of a developmental series of Compagopiscis croucheri (Arthrodira) to show that placoderm jaws are composed of distinct cartilages and gnathal ossifications in both jaws, and a dermal element in the lower jaw. The gnathal ossification is a composite of distinct teeth that developed in succession, polarized along three distinct vectors, comparable to tooth families. The teeth are composed of dentine and bone, and show a distinct pulp cavity that is infilled centripetally as development proceeds. This pattern is repeated in other placoderms, but differs from the structure and development of tooth-like structures in the postbranchial lamina and dermal skeleton of Compagopiscis and other placoderms. We interpret this evidence to indicate that Compagopiscis and other arthrodires possessed teeth, but that tooth and jaw development was not developmentally or structurally integrated in placoderms. Teeth did not evolve convergently among the extant and extinct classes of early jawed vertebrates but, rather, successional teeth evolved within the gnathostome stem-lineage soon after the origin of jaws. The chimaeric developmental origin of this model of modularity reflects the distinct evolutionary origins of teeth and of component elements of the jaws.
C1 [Ruecklin, Martin; Donoghue, Philip C. J.] Univ Bristol, Sch Earth Sci, Bristol BS8 1RJ, Avon, England.
   [Johanson, Zerina] Nat Hist Museum, London SW7 5BD, England.
   [Trinajstic, Kate] Curtin Univ Technol, Dept Chem, Bentley, WA 6102, Australia.
   [Trinajstic, Kate] Western Australian Museum, Dept Earth & Planetary Sci, Welshpool 6106, Australia.
   [Marone, Federica; Stampanoni, Marco] Paul Scherrer Inst, Swiss Light Source, CH-5232 Villigen, Switzerland.
   [Stampanoni, Marco] Univ Zurich, Inst Biomed Engn, CH-8092 Zurich, Switzerland.
   [Stampanoni, Marco] ETH, CH-8092 Zurich, Switzerland.
C3 University of Bristol; Natural History Museum London; Curtin University; Western Australian Museum; Swiss Federal Institutes of Technology Domain; Paul Scherrer Institute; University of Zurich; Swiss Federal Institutes of Technology Domain; ETH Zurich
RP Rücklin, M (corresponding author), Univ Bristol, Sch Earth Sci, Wills Mem Bldg,Queens Rd, Bristol BS8 1RJ, Avon, England.
EM m.ruecklin@bristol.ac.uk; phil.donoghue@bristol.ac.uk
FU EU; Australian Research Council [DP 110101127]; Natural Environment Research Council [NE/G016623/1]; Paul Scherrer Institut; NERC [NE/G016623/1, NE/G020264/1] Funding Source: UKRI; Natural Environment Research Council [NE/G020264/1, NE/G016623/1] Funding Source: researchfish
NR 29
TC 95
Z9 111
U1 1
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 29
PY 2012
VL 491
IS 7426
BP 748
EP +
DI 10.1038/nature11555
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 044FY
UT WOS:000311606000043
PM 23075852
DA 2026-03-09
ER

PT J
AU O'Neill, HS
   Jenner, FE
AF O'Neill, Hugh St C.
   Jenner, Frances E.
TI The global pattern of trace-element distributions in ocean floor basalts
SO NATURE
LA English
DT Article
ID midocean ridge basalts; geochemical evolution; phase-equilibria; crystallization; beneath; constraints; melt; plagioclase; earth; systematics
AB The magmatic layers of the oceanic crust are created at constructive plate margins by partial melting of the mantle as it wells up. The chemistry of ocean floor basalts, the most accessible product of this magmatism, is studied for the insights it yields into the compositional heterogeneity of the mantle and its thermal structure. However, before eruption, parental magma compositions are modified at crustal pressures by a process that has usually been assumed to be fractional crystallization. Here we show that the global distributions of trace elements in ocean floor basalts describe a systematic pattern that cannot be explained by simple fractional crystallization alone, but is due to cycling of magma through the global ensemble of magma chambers. Variability in both major and incompatible trace-element contents about the average global pattern is due to fluctuations in the magma fluxes into and out of the chambers, and their depth, as well as to differences in the composition of the parental magmas.
C1 [O'Neill, Hugh St C.; Jenner, Frances E.] Australian Natl Univ, Res Sch Earth Sci, Canberra, ACT 2600, Australia.
   [Jenner, Frances E.] Carnegie Inst Sci, Dept Terr Magnetism, Washington, DC 20015 USA.
C3 Australian National University; Carnegie Institution for Science
RP O'Neill, HS (corresponding author), Australian Natl Univ, Res Sch Earth Sci, GPO Box 4, Canberra, ACT 2600, Australia.
EM hugh.oneill@anu.edu.au
FU Australian National University
NR 45
TC 148
Z9 162
U1 4
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 NOV 29
PY 2012
VL 491
IS 7426
BP 698
EP +
DI 10.1038/nature11678
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 044FY
UT WOS:000311606000033
PM 23192147
DA 2026-03-09
ER

PT J
AU Shin, HN
   Iwasaki, A
AF Shin, Haina
   Iwasaki, Akiko
TI A vaccine strategy that protects against genital herpes by establishing local memory T cells
SO NATURE
LA English
DT Article
ID replication-defective mutant; simplex-virus type-2; immune-responses; dendritic cells; viral-infection; resident memory; rm cells; migration; mucosal; hsv-2
AB Most successful existing vaccines rely on neutralizing antibodies, which may not require specific anatomical localization of B cells. However, efficacious vaccines that rely on T cells for protection have been difficult to develop, as robust systemic memory T-cell responses do not necessarily correlate with host protection(1). In peripheral sites, tissue-resident memory T cells provide superior protection compared to circulating memory T cells(2,3). Here we describe a simple and non-inflammatory vaccine strategy that enables the establishment of a protective memory T-cell pool within peripheral tissue. The female genital tract, which is a portal of entry for sexually transmitted infections, is an immunologically restrictive tissue that prevents entry of activated T cells in the absence of inflammation or infection(4). To overcome this obstacle, we developed a vaccine strategy that we term 'prime and pull' to establish local tissue-resident memory T cells at a site of potential viral exposure. This approach relies on two steps: conventional parenteral vaccination to elicit systemic T-cell responses (prime), followed by recruitment of activated T cells by means of topical chemokine application to the restrictive genital tract (pull), where such T cells establish a long-term niche and mediate protective immunity. In mice, prime and pull protocol reduces the spread of infectious herpes simplex virus 2 into the sensory neurons and prevents development of clinical disease. These results reveal a promising vaccination strategy against herpes simplex virus 2, and potentially against other sexually transmitted infections such as human immunodeficiency virus.
C1 [Shin, Haina; Iwasaki, Akiko] Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT 06520 USA.
C3 Yale University
RP Iwasaki, A (corresponding author), Yale Univ, Sch Med, Dept Immunobiol, 300 Cedar St, New Haven, CT 06520 USA.
EM akiko.iwasaki@yale.edu
FU NIAID [F32AI091024]; NIH [AI054359, AI062428]
NR 30
TC 510
Z9 622
U1 1
U2 84
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 15
PY 2012
VL 491
IS 7424
BP 463
EP +
DI 10.1038/nature11522
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 036MY
UT WOS:000311031600050
PM 23075848
DA 2026-03-09
ER

PT J
AU Yumoto, N
   Kim, N
   Burden, SJ
AF Yumoto, Norihiro
   Kim, Natalie
   Burden, Steven J.
TI Lrp4 is a retrograde signal for presynaptic differentiation at neuromuscular synapses
SO NATURE
LA English
DT Article
ID in-vivo; organizing molecules; neural development; skeletal-muscle; receptor; junction; agrin; musk; form; neurotransmitter
AB Motor axons receive retrograde signals from skeletal muscle that are essential for the differentiation and stabilization of motor nerve terminals(1). Identification of these retrograde signals has proved elusive, but their production by muscle depends on the receptor tyrosine kinase, MuSK (muscle, skeletal receptor tyrosine-protein kinase), and Lrp4 (low-density lipoprotein receptor (LDLR)-related protein 4), an LDLR family member that forms a complex with MuSK, binds neural agrin and stimulates MuSK kinase activity(2-5). Here we show that Lrp4 also functions as a direct muscle-derived retrograde signal for early steps in presynaptic differentiation. We demonstrate that Lrp4 is necessary, independent of MuSK activation, for presynaptic differentiation in vivo, and we show that Lrp4 binds to motor axons and induces clustering of synaptic-vesicle and active-zone proteins. Thus, Lrp4 acts bidirectionally and coordinates synapse formation by binding agrin, activating MuSK and stimulating postsynaptic differentiation, and functioning in turn as a muscle-derived retrograde signal that is necessary and sufficient for presynaptic differentiation.
C1 [Yumoto, Norihiro; Kim, Natalie; Burden, Steven J.] NYU, Sch Med, Mol Neurobiol Program,Skirball Inst Biomol Med, Helen L & Martin S Kimmel Ctr Biol & Med, New York, NY 10012 USA.
C3 New York University
RP Burden, SJ (corresponding author), NYU, Sch Med, Mol Neurobiol Program,Skirball Inst Biomol Med, Helen L & Martin S Kimmel Ctr Biol & Med, 540 1st Ave, New York, NY 10012 USA.
EM burden@saturn.med.nyu.edu
FU New York University Cancer Institute Center Support Grant (National Institutes of Health (NIH)/National Cancer Institute (NCI)) [5 P30CA16087-31]; National Institutes of Health [NS36193]; Skirball Institute; New York State Stem Cell Science (NYSTEM); National Cancer Institute [P30CA016087] Funding Source: NIH RePORTER
NR 29
TC 158
Z9 185
U1 0
U2 24
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD SEP 20
PY 2012
VL 489
IS 7416
BP 438
EP U130
DI 10.1038/nature11348
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 007AK
UT WOS:000308860900047
PM 22854782
DA 2026-03-09
ER

PT J
AU Allen, RJ
   Sherwood, SC
   Norris, JR
   Zender, CS
AF Allen, Robert J.
   Sherwood, Steven C.
   Norris, Joel R.
   Zender, Charles S.
TI Recent Northern Hemisphere tropical expansion primarily driven by black carbon and tropospheric ozone
SO NATURE
LA English
DT Article
AB Observational analyses have shown the width of the tropical belt increasing in recent decades as the world has warmed(1). This expansion is important because it is associated with shifts in large-scale atmospheric circulation(2-4) and major climate zones(5,6). Although recent studies have attributed tropical expansion in the Southern Hemisphere to ozone depletion(7-10), the drivers of Northern Hemisphere expansion are not well known and the expansion has not so far been reproduced by climate models(11). Here we use a climate model with detailed aerosol physics to show that increases in heterogeneous warming agents-including black carbon aerosols and tropospheric ozone-are noticeably better than greenhouse gases at driving expansion, and can account for the observed summertime maximum in tropical expansion. Mechanistically, atmospheric heating from black carbon and tropospheric ozone has occurred at the mid-latitudes, generating a poleward shift of the tropospheric jet(12), thereby relocating the main division between tropical and temperate air masses. Although we still underestimate tropical expansion, the true aerosol forcing is poorly known and could also be underestimated. Thus, although the insensitivity of models needs further investigation, black carbon and tropospheric ozone, both of which are strongly influenced by human activities, are the most likely causes of observed Northern Hemisphere tropical expansion.
C1 [Allen, Robert J.] Univ Calif Riverside, Dept Earth Sci, Riverside, CA 92521 USA.
   [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.
   [Norris, Joel R.] Univ Calif San Diego, Scripps Inst Oceanog, San Diego, CA 92093 USA.
   [Zender, Charles S.] Univ Calif Irvine, Irvine, CA 92697 USA.
C3 University of California System; University of California Riverside; University of New South Wales Sydney; University of New South Wales Sydney; ARC Centre of Excellence for Climate System Science; University of California System; University of California San Diego; Scripps Institution of Oceanography; University of California System; University of California Irvine
RP Allen, RJ (corresponding author), Univ Calif Riverside, Dept Earth Sci, Riverside, CA 92521 USA.
EM rjallen@ucr.edu
FU University of California at Riverside
NR 43
TC 212
Z9 234
U1 2
U2 153
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 17
PY 2012
VL 485
IS 7398
BP 350
EP U93
DI 10.1038/nature11097
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 943CW
UT WOS:000304099100038
PM 22596159
DA 2026-03-09
ER

PT J
AU Matsushita, H
   Vesely, MD
   Koboldt, DC
   Rickert, CG
   Uppaluri, R
   Magrini, VJ
   Arthur, CD
   White, JM
   Chen, YS
   Shea, LK
   Hundal, J
   Wendl, MC
   Demeter, R
   Wylie, T
   Allison, JP
   Smyth, MJ
   Old, LJ
   Mardis, ER
   Schreiber, RD
AF Matsushita, Hirokazu
   Vesely, Matthew D.
   Koboldt, Daniel C.
   Rickert, Charles G.
   Uppaluri, Ravindra
   Magrini, Vincent J.
   Arthur, Cora D.
   White, J. Michael
   Chen, Yee-Shiuan
   Shea, Lauren K.
   Hundal, Jasreet
   Wendl, Michael C.
   Demeter, Ryan
   Wylie, Todd
   Allison, James P.
   Smyth, Mark J.
   Old, Lloyd J.
   Mardis, Elaine R.
   Schreiber, Robert D.
TI Cancer exome analysis reveals a T-cell-dependent mechanism of cancer immunoediting
SO NATURE
LA English
DT Article
ID adaptive immunity; tumor escape; ifn-gamma; genome; breast; gene; resolution; mutations; responses; melanoma
AB Cancer immunoediting, the process by which the immune system controls tumour outgrowth and shapes tumour immunogenicity, is comprised of three phases: elimination, equilibrium and escape(1-5). Although many immune components that participate in this process are known, its underlying mechanisms remain poorly defined. A central tenet of cancer immunoediting is that T-cell recognition of tumour antigens drives the immunological destruction or sculpting of a developing cancer. However, our current understanding of tumour antigens comes largely from analyses of cancers that develop in immunocompetent hosts and thus may have already been edited. Little is known about the antigens expressed in nascent tumour cells, whether they are sufficient to induce protective antitumour immune responses or whether their expression is modulated by the immune system. Here, using massively parallel sequencing, we characterize expressed mutations in highly immunogenic methylcholanthrene-induced sarcomas derived from immunodeficient Rag2(-/-) mice that phenotypically resemble nascent primary tumour cells(1,3,5). Using class I prediction algorithms, we identify mutant spectrin-beta 2 as a potential rejection antigen of the d42m1 sarcoma and validate this prediction by conventional antigen expression cloning and detection. We also demonstrate that cancer immunoediting of d42m1 occurs via a T-cell-dependent immunoselection process that promotes outgrowth of pre-existing tumour cell clones lacking highly antigenic mutant spectrin-beta 2 and other potential strong antigens. These results demonstrate that the strong immunogenicity of an unedited tumour can be ascribed to expression of highly antigenic mutant proteins and show that outgrowth of tumour cells that lack these strong antigens via a T-cell-dependent immunoselection process represents one mechanism of cancer immunoediting.
C1 [Matsushita, Hirokazu; Vesely, Matthew D.; Rickert, Charles G.; Arthur, Cora D.; White, J. Michael; Chen, Yee-Shiuan; Shea, Lauren K.; Schreiber, Robert D.] Washington Univ, Dept Pathol & Immunol, Sch Med, St Louis, MO 63110 USA.
   [Koboldt, Daniel C.; Magrini, Vincent J.; Hundal, Jasreet; Wendl, Michael C.; Demeter, Ryan; Wylie, Todd; Mardis, Elaine R.] Washington Univ, Sch Med, Genome Inst, St Louis, MO 63110 USA.
   [Uppaluri, Ravindra] Washington Univ, Sch Med, Dept Otolaryngol, St Louis, MO 63110 USA.
   [Magrini, Vincent J.; Wendl, Michael C.] Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA.
   [Allison, James P.] Mem Sloan Kettering Canc Ctr, Dept Immunol, Ludwig Ctr Canc Immunotherapy, New York, NY 10021 USA.
   [Allison, James P.] Mem Sloan Kettering Canc Ctr, Howard Hughes Med Inst, New York, NY 10021 USA.
   [Smyth, Mark J.] Peter MacCallum Canc Ctr, Canc Immunol Program, Melbourne, Vic 3002, Australia.
   [Smyth, Mark J.] Univ Melbourne, Dept Pathol, Parkville, Vic 2010, Australia.
   [Old, Lloyd J.] Mem Sloan Kettering Canc Ctr, Ludwig Inst Canc Res, New York Branch, New York, NY 10021 USA.
C3 Washington University (WUSTL); Washington University (WUSTL); Washington University (WUSTL); Washington University (WUSTL); Memorial Sloan Kettering Cancer Center; Memorial Sloan Kettering Cancer Center; Howard Hughes Medical Institute; Peter Maccallum Cancer Center; University of Melbourne; Ludwig Institute for Cancer Research; Memorial Sloan Kettering Cancer Center
RP Schreiber, RD (corresponding author), Washington Univ, Dept Pathol & Immunol, Sch Med, 660 S Euclid Ave, St Louis, MO 63110 USA.
EM schreiber@immunology.wustl.edu
FU National Cancer Institute; Ludwig Institute for Cancer Research; Cancer Research Institute; WWWW Foundation; National Human Genome Research Institute; Howard Hughes Medical Institute; Ludwig Center for Cancer Immunotherapy; National Health and Medical Research Council of Australia (NHMRC); Association for International Cancer Research
NR 36
TC 1027
Z9 1248
U1 1
U2 150
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD FEB 16
PY 2012
VL 482
IS 7385
BP 400
EP U149
DI 10.1038/nature10755
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 892LG
UT WOS:000300287100046
PM 22318521
DA 2026-03-09
ER

PT J
AU Weber, T
   Deutsch, C
AF Weber, Thomas
   Deutsch, Curtis
TI Oceanic nitrogen reservoir regulated by plankton diversity and ocean circulation
SO NATURE
LA English
DT Article
ID to-phosphorus stoichiometry; marine prochlorococcus; elemental composition; community structure; nutrient ratios; southern-ocean; phytoplankton; fixation; denitrification; iron
AB The average nitrogen-to-phosphorus ratio of marine phytoplankton (16N:1P) is closely matched to the nutrient content of mean ocean waters (14.3N:1P). This condition is thought to arise from biological control over the ocean's nitrogen budget, in which removal of bioavailable nitrogen by denitrifying bacteria ensures widespread selection for diazotrophic phytoplankton that replenish this essential nutrient when it limits the growth of other species(1-3). Here we show that in the context of a realistic ocean circulation model, and a uniform N:P ratio of plankton biomass, this feedback mechanism yields an oceanic nitrate deficit more than double its observed value. The critical missing phenomenon is diversity in the metabolic N: P requirement of phytoplankton, which has recently been shown to exhibit large-scale patterns associated with species composition(4). When we model these variations, such that diazotrophs compete with high N: P communities in subtropical regions, the ocean nitrogen inventory rises and may even exceed the average N: P ratio of plankton. The latter condition, previously considered impossible, is prevented in the modern ocean by shallow circulations that communicate stoichiometric signals from remote biomes dominated by diatoms with low N: P ratios. Large-scale patterns of plankton diversity and the circulation pathways connecting them are thus key factors determining the availability of fixed nitrogen in the ocean.
C1 [Weber, Thomas; Deutsch, Curtis] Univ Calif Los Angeles, Los Angeles, CA 90095 USA.
C3 University of California System; University of California Los Angeles
RP Weber, T (corresponding author), Univ Calif Los Angeles, Los Angeles, CA 90095 USA.
EM tweber@atmos.ucla.edu
FU NASA Earth Systems Science Fellowship; Gordon and Betty Moore Foundation; Division Of Ocean Sciences; Directorate For Geosciences [0851483] Funding Source: National Science Foundation
NR 38
TC 91
Z9 105
U1 0
U2 201
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD SEP 20
PY 2012
VL 489
IS 7416
BP 419
EP U105
DI 10.1038/nature11357
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 007AK
UT WOS:000308860900042
PM 22996557
DA 2026-03-09
ER

PT J
AU Welsh, WF
   Orosz, JA
   Carter, JA
   Fabrycky, DC
   Ford, EB
   Lissauer, JJ
   Prsa, A
   Quinn, SN
   Ragozzine, D
   Short, DR
   Torres, G
   Winn, JN
   Doyle, LR
   Barclay, T
   Batalha, N
   Bloemen, S
   Brugamyer, E
   Buchhave, LA
   Caldwell, C
   Caldwell, DA
   Christiansen, JL
   Ciardi, DR
   Cochran, WD
   Endl, M
   Fortney, JJ
   Gautier, TN
   Gilliland, RL
   Haas, MR
   Hall, JR
   Holman, MJ
   Howard, AW
   Howell, SB
   Isaacson, H
   Jenkins, JM
   Klaus, TC
   Latham, DW
   Li, J
   Marcy, GW
   Mazeh, T
   Quintana, EV
   Robertson, P
   Shporer, A
   Steffen, JH
   Windmiller, G
   Koch, DG
   Borucki, WJ
AF Welsh, William F.
   Orosz, Jerome A.
   Carter, Joshua A.
   Fabrycky, Daniel C.
   Ford, Eric B.
   Lissauer, Jack J.
   Prsa, Andrej
   Quinn, Samuel N.
   Ragozzine, Darin
   Short, Donald R.
   Torres, Guillermo
   Winn, Joshua N.
   Doyle, Laurance R.
   Barclay, Thomas
   Batalha, Natalie
   Bloemen, Steven
   Brugamyer, Erik
   Buchhave, Lars A.
   Caldwell, Caroline
   Caldwell, Douglas A.
   Christiansen, Jessie L.
   Ciardi, David R.
   Cochran, William D.
   Endl, Michael
   Fortney, Jonathan J.
   Gautier, Thomas N., III
   Gilliland, Ronald L.
   Haas, Michael R.
   Hall, Jennifer R.
   Holman, Matthew J.
   Howard, Andrew W.
   Howell, Steve B.
   Isaacson, Howard
   Jenkins, Jon M.
   Klaus, Todd C.
   Latham, David W.
   Li, Jie
   Marcy, Geoffrey W.
   Mazeh, Tsevi
   Quintana, Elisa V.
   Robertson, Paul
   Shporer, Avi
   Steffen, Jason H.
   Windmiller, Gur
   Koch, David G.
   Borucki, William J.
TI Transiting circumbinary planets Kepler-34 b and Kepler-35 b
SO NATURE
LA English
DT Article
ID hierarchical triple; eclipsing binary; stellar; stability; catalog
AB Most Sun-like stars in the Galaxy reside in gravitationally bound pairs of stars(1,2) (binaries). Although long anticipated(3-8), the existence of a 'circumbinary planet' orbiting such a pair of normal stars was not definitively established until the discovery(9) of the planet transiting (that is, passing in front of) Kepler-16. Questions remained, however, about the prevalence of circumbinary planets and their range of orbital and physical properties. Here we report two additional transiting circumbinary planets: Kepler-34 (AB)b and Kepler-35 (AB)b, referred to here as Kepler-34 b and Kepler-35 b, respectively. Each is a low-density gas-giant planet on an orbit closely aligned with that of its parent stars. Kepler-34 b orbits two Sun-like stars every 289 days, whereas Kepler-35 b orbits a pair of smaller stars (89% and 81% of the Sun's mass) every 131 days. The planets experience large multi-periodic variations in incident stellar radiation arising from the orbital motion of the stars. The observed rate of circumbinary planets in our sample implies that more than similar to 1% of close binary stars have giant planets in nearly coplanar orbits, yielding a Galactic population of at least several million.
C1 [Welsh, William F.; Orosz, Jerome A.; Short, Donald R.; Windmiller, Gur] San Diego State Univ, Dept Astron, San Diego, CA 92182 USA.
   [Fabrycky, Daniel C.] Univ Calif Santa Cruz, Lick Observ, UCO, Santa Cruz, CA 95064 USA.
   [Ford, Eric B.] Univ Florida, Bryant Space Sci Ctr 211, Gainesville, FL 32611 USA.
   [Lissauer, Jack J.; Barclay, Thomas; Batalha, Natalie; Christiansen, Jessie L.; Haas, Michael R.; Howell, Steve B.; Jenkins, Jon M.; Li, Jie; Quintana, Elisa V.; Koch, David G.; Borucki, William J.] NASA, Ames Res Ctr, Moffett Field, CA 94035 USA.
   [Carter, Joshua A.; Quinn, Samuel N.; Ragozzine, Darin; Torres, Guillermo; Holman, Matthew J.; Latham, David W.] Harvard Smithsonian Ctr Astrophys, Cambridge, MA 02138 USA.
   [Prsa, Andrej] Villanova Univ, Dept Astron & Astrophys, Villanova, PA 19085 USA.
   [Quinn, Samuel N.] Georgia State Univ, Dept Phys & Astron, Atlanta, GA 30302 USA.
   [Winn, Joshua N.] MIT, Dept Phys, Cambridge, MA 02139 USA.
   [Winn, Joshua N.] MIT, Kavli Inst Astrophys & Space Res, Cambridge, MA 02139 USA.
   [Doyle, Laurance R.; Caldwell, Douglas A.; Christiansen, Jessie L.; Jenkins, Jon M.; Li, Jie; Quintana, Elisa V.] SETI Inst, Carl Sagan Ctr Study Life Universe, Mountain View, CA 94043 USA.
   [Barclay, Thomas] Bay Area Environm Res Inst Inc, Sonoma, CA 95476 USA.
   [Batalha, Natalie] San Jose State Univ, Dept Phys & Astron, San Jose, CA 95192 USA.
   [Bloemen, Steven] Katholieke Univ Leuven, Inst Sterrenkunde, B-3001 Louvain, Belgium.
   [Buchhave, Lars A.] Univ Copenhagen, Ctr Star & Planet Format, Nat Hist Museum Denmark, DK-1350 Copenhagen, Denmark.
   [Brugamyer, Erik; Cochran, William D.; Endl, Michael] Univ Texas Austin, McDonald Observ, Austin, TX 78712 USA.
   [Buchhave, Lars A.] Univ Copenhagen, Niels Bohr Inst, DK-2100 Copenhagen, Denmark.
   [Ciardi, David R.] CALTECH, NASA Exoplanet Sci Inst, Pasadena, CA 91125 USA.
   [Fortney, Jonathan J.] Univ Calif Santa Cruz, Dept Astron & Astrophys, Santa Cruz, CA 95064 USA.
   [Gautier, Thomas N., III] Jet Prop Lab, Pasadena, CA 91109 USA.
   [Gilliland, Ronald L.] Space Telescope Sci Inst, Baltimore, MD 21218 USA.
   [Klaus, Todd C.] NASA, Orbital Sci Corp, Ames Res Ctr, Moffett Field, CA 94035 USA.
   [Marcy, Geoffrey W.] Univ Calif Berkeley, Dept Astron, Berkeley, CA 94720 USA.
   [Mazeh, Tsevi] Tel Aviv Univ, Sch Phys & Astron, IL-69978 Tel Aviv, Israel.
   [Shporer, Avi] Las Cumbres Observ, Global Telescope Network, Santa Barbara, CA 93117 USA.
   [Shporer, Avi] Univ Calif Santa Barbara, Dept Phys, Santa Barbara, CA 93106 USA.
   [Steffen, Jason H.] Fermilab Ctr Particle Astrophys, Batavia, IL 60510 USA.
C3 California State University System; San Diego State University; University of California System; University of California Santa Cruz; State University System of Florida; University of Florida; National Aeronautics & Space Administration (NASA); NASA Ames Research Center; Smithsonian Astrophysical Observatory; Smithsonian Institution; Harvard University; Villanova University; University System of Georgia; Georgia State University; Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); SETI Institute; California State University System; San Jose State University; KU Leuven; University of Copenhagen; University of Texas System; University of Texas Austin; University of Copenhagen; Niels Bohr Institute; California Institute of Technology; National Aeronautics & Space Administration (NASA); University of California System; University of California Santa Cruz; National Aeronautics & Space Administration (NASA); NASA Jet Propulsion Laboratory (JPL); Space Telescope Science Institute; Orbital Sciences Corporation; National Aeronautics & Space Administration (NASA); NASA Ames Research Center; University of California System; University of California Berkeley; Tel Aviv University; University of California System; University of California Santa Barbara
RP Welsh, WF (corresponding author), San Diego State Univ, Dept Astron, 5500 Campanile Dr, San Diego, CA 92182 USA.
EM wfw@sciences.sdsu.edu; jacarter@cfa.harvard.edu
FU NASA's Science Mission Directorate; Kepler Participating Scientist Program; NSF; NASA; STScI; European Research Council under the European Community; Research Council of KU Leuven; FAS Science Division Research Computing Group at Harvard University; Direct For Mathematical & Physical Scien; Division Of Astronomical Sciences [1109928] Funding Source: National Science Foundation; Division Of Astronomical Sciences; Direct For Mathematical & Physical Scien [1007992] Funding Source: National Science Foundation
NR 22
TC 351
Z9 390
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 JAN 26
PY 2012
VL 481
IS 7382
BP 475
EP U85
DI 10.1038/nature10768
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 881GY
UT WOS:000299471800033
PM 22237021
DA 2026-03-09
ER

PT J
AU Ichimura, A
   Hirasawa, A
   Poulain-Godefroy, O
   Bonnefond, A
   Hara, T
   Yengo, L
   Kimura, I
   Leloire, A
   Liu, N
   Iida, K
   Choquet, H
   Besnard, P
   Lecoeur, C
   Vivequin, S
   Ayukawa, K
   Takeuchi, M
   Ozawa, K
   Tauber, M
   Maffeis, C
   Morandi, A
   Buzzetti, R
   Elliott, P
   Pouta, A
   Jarvelin, MR
   Körner, A
   Kiess, W
   Pigeyre, M
   Caiazzo, R
   Van Hul, W
   Van Gaal, L
   Horber, F
   Balkau, B
   Lévy-Marchal, C
   Rouskas, K
   Kouvatsi, A
   Hebebrand, J
   Hinney, A
   Scherag, A
   Pattou, F
   Meyre, D
   Koshimizu, T
   Wolowczuk, I
   Tsujimoto, G
   Froguel, P
AF Ichimura, Atsuhiko
   Hirasawa, Akira
   Poulain-Godefroy, Odile
   Bonnefond, Amelie
   Hara, Takafumi
   Yengo, Loic
   Kimura, Ikuo
   Leloire, Audrey
   Liu, Ning
   Iida, Keiko
   Choquet, Helene
   Besnard, Philippe
   Lecoeur, Cecile
   Vivequin, Sidonie
   Ayukawa, Kumiko
   Takeuchi, Masato
   Ozawa, Kentaro
   Tauber, Maithe
   Maffeis, Claudio
   Morandi, Anita
   Buzzetti, Raffaella
   Elliott, Paul
   Pouta, Anneli
   Jarvelin, Marjo-Riitta
   Koerner, Antje
   Kiess, Wieland
   Pigeyre, Marie
   Caiazzo, Roberto
   Van Hul, Wim
   Van Gaal, Luc
   Horber, Fritz
   Balkau, Beverley
   Levy-Marchal, Claire
   Rouskas, Konstantinos
   Kouvatsi, Anastasia
   Hebebrand, Johannes
   Hinney, Anke
   Scherag, Andre
   Pattou, Francois
   Meyre, David
   Koshimizu, Taka-aki
   Wolowczuk, Isabelle
   Tsujimoto, Gozoh
   Froguel, Philippe
TI Dysfunction of lipid sensor GPR120 leads to obesity in both mouse and human
SO NATURE
LA English
DT Article
ID pancreatic beta-cells; chain fatty-acids; insulin-resistance; body-mass; childhood obesity; protein function; early-onset; receptor; population; mutations
AB Free fatty acids provide an important energy source as nutrients, and act as signalling molecules in various cellular processes(1-4). Several G-protein-coupled receptors have been identified as free-fatty-acid receptors important in physiology as well as in several diseases(3,5-13). GPR120 (also known as O3FAR1) functions as a receptor for unsaturated long-chain free fatty acids and has a critical role in various physiological homeostasis mechanisms such as adipogenesis, regulation of appetite and food preference(5,6,14-16). Here we show that GPR120-deficient mice fed a high-fat diet develop obesity, glucose intolerance and fatty liver with decreased adipocyte differentiation and lipogenesis and enhanced hepatic lipogenesis. Insulin resistance in such mice is associated with reduced insulin signalling and enhanced inflammation in adipose tissue. In human, we show that GPR120 expression in adipose tissue is significantly higher in obese individuals than in lean controls. GPR120 exon sequencing in obese subjects reveals a deleterious non-synonymous mutation (p.R270H) that inhibits GPR120 signalling activity. Furthermore, the p.R270H variant increases the risk of obesity in European populations. Overall, this study demonstrates that the lipid sensor GPR120 has a key role in sensing dietary fat and, therefore, in the control of energy balance in both humans and rodents.
C1 [Poulain-Godefroy, Odile; Bonnefond, Amelie; Yengo, Loic; Leloire, Audrey; Choquet, Helene; Lecoeur, Cecile; Vivequin, Sidonie; Morandi, Anita; Rouskas, Konstantinos; Meyre, David; Wolowczuk, Isabelle; Froguel, Philippe] Lille Pasteur Inst, CNRS, UMR 8199, F-59000 Lille, France.
   [Ichimura, Atsuhiko; Hirasawa, Akira; Hara, Takafumi; Kimura, Ikuo; Liu, Ning; Iida, Keiko; Ayukawa, Kumiko; Takeuchi, Masato; Ozawa, Kentaro; Tsujimoto, Gozoh] Kyoto Univ, Grad Sch Pharmaceut Sci, Dept Genom Drug Discovery Sci, Sakyo Ku, Kyoto 6068501, Japan.
   [Pigeyre, Marie; Caiazzo, Roberto; Pattou, Francois] Lille Nord France Univ, INSERM, U859, F-59000 Lille, France.
   [Besnard, Philippe] Univ Bourgogne, INSERM, UMR U866, AgroSup Dijon, F-21078 Dijon, France.
   [Tauber, Maithe] Ctr Hosp Univ, Childrens Hosp, INSERM, U563, F-31000 Toulouse, France.
   [Maffeis, Claudio; Morandi, Anita] Reg Ctr Juvenile Diabet Obes & Clin Nutr, I-37134 Verona, Italy.
   [Maffeis, Claudio] Univ Verona, Dept Mother & Child, Paediat Sect, I-37134 Verona, Italy.
   [Buzzetti, Raffaella] Univ Roma La Sapienza, Dept Clin Sci, I-00161 Rome, Italy.
   [Elliott, Paul; Jarvelin, Marjo-Riitta] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Epidemiol & Biostat, HPA Ctr Environm & Hlth,MRC, London W2 1PG, England.
   [Pouta, Anneli; Jarvelin, Marjo-Riitta] Univ Oulu, Natl Publ Hlth Inst, Bioctr Oulu, SF-90220 Oulu, Finland.
   [Pouta, Anneli] Univ Oulu, Inst Clin Med Obstet & Gynecol, SF-90220 Oulu, Finland.
   [Jarvelin, Marjo-Riitta] Univ Oulu, Inst Hlth Sci, SF-90220 Oulu, Finland.
   [Koerner, Antje; Kiess, Wieland] Univ Leipzig, Ctr Pediat Res, Dept Womens & Child Hlth, D-04317 Leipzig, Germany.
   [Pigeyre, Marie; Caiazzo, Roberto; Pattou, Francois] Lille Univ Hosp, F-59000 Lille, France.
   [Van Hul, Wim] Univ Antwerp, Dept Med Genet, B-2610 Antwerp, Belgium.
   [Van Gaal, Luc] Univ Antwerp Hosp, Dept Endocrinol, B-2650 Antwerp, Belgium.
   [Horber, Fritz] Clin Lindberg, Dept Med, Dept Surg & Internal Med, CH-8400 Winterthur, Switzerland.
   [Horber, Fritz] Univ Bern, CH-3011 Bern, Switzerland.
   [Balkau, Beverley] Ctr Res Epidemiol & Populat Hlth CRESP, INSERM, U780, F-94800 Villejuif, France.
   [Balkau, Beverley] Univ Paris 11, F-91405 Orsay, France.
   [Levy-Marchal, Claire] Hop Robert Debre, INSERM, U690, F-75935 Paris, France.
   [Rouskas, Konstantinos; Kouvatsi, Anastasia] Aristotle Univ Thessaloniki, Sch Biol, Dept Genet Dev & Mol Biol, Thessaloniki 54124, Greece.
   [Hebebrand, Johannes; Hinney, Anke] Univ Duisburg Essen, Dept Child & Adolescent Psychiat, D-45147 Essen, Germany.
   [Scherag, Andre] Univ Duisburg Essen, Inst Med Informat Biometry & Epidemiol, D-45122 Essen, Germany.
   [Meyre, David] McMaster Univ, Hamilton, ON L8S 4L8, Canada.
   [Koshimizu, Taka-aki] Jichi Med Univ, Div Mol Pharmacol, Dept Pharmacol, Shimotsuke, Tochigi 3290498, Japan.
   [Froguel, Philippe] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, Sch Publ Hlth, Dept Genom Common Dis, London W12 0NN, England.
C3 Pasteur Network; Universite de Lille; Institut Pasteur Lille; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB); Kyoto University; Institut National de la Sante et de la Recherche Medicale (Inserm); Universite de Lille; Institut Agro; Institut Agro Dijon; Universite Bourgogne Europe; Institut National de la Sante et de la Recherche Medicale (Inserm); Universite de Toulouse; Universite Toulouse III - Paul Sabatier; Centre National de la Recherche Scientifique (CNRS); Institut National de la Sante et de la Recherche Medicale (Inserm); CHU de Toulouse; University of Verona; Sapienza University Rome; Imperial College London; Finland National Institute for Health & Welfare; University of Oulu; University of Oulu; University of Oulu; Leipzig University; Universite de Lille; CHU Lille; University of Antwerp; University of Antwerp; University of Bern; Institut National de la Sante et de la Recherche Medicale (Inserm); Universite Paris Saclay; Universite Paris Cite; Assistance Publique Hopitaux Paris (APHP); Hopital Universitaire Robert-Debre - APHP; Institut National de la Sante et de la Recherche Medicale (Inserm); Aristotle University of Thessaloniki; University of Duisburg Essen; University of Duisburg Essen; McMaster University; Jichi Medical University; Imperial College London
RP Froguel, P (corresponding author), Lille Pasteur Inst, CNRS, UMR 8199, F-59000 Lille, France.
EM gtsuji@pharm.kyoto-u.ac.jp; p.froguel@imperial.ac.uk
FU Japan Society for the Promotion of Science; Ministry of Education, Culture, Sports, Science and Technology of Japan; Japan Science and Technology Agency; Funding Program for World-Leading Innovative R&D on Science and Technology (FIRST Program); Conseil Regional Nord Pas de Calais/FEDER; Agence Nationale de la Recherche; Academy of Finland; University Hospital of Oulu (Finland); University of Oulu (Finland); European Commission (EURO-BLCS) [QLG1-CT-2000-01643]; Medical Research Council [G0500539, G0600705]; Grants-in-Aid for Scientific Research [20117008, 23890019, 24590327, 21390021] Funding Source: KAKEN; Medical Research Council [G1002084, G0801056B, G0600705] Funding Source: researchfish; MRC [G0600705, G1002084] Funding Source: UKRI
NR 48
TC 553
Z9 645
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 MAR 15
PY 2012
VL 483
IS 7389
BP 350
EP U149
DI 10.1038/nature10798
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 908HP
UT WOS:000301481800053
PM 22343897
DA 2026-03-09
ER

PT J
AU Mancusso, R
   Gregorio, GG
   Liu, Q
   Wang, DN
AF Mancusso, Romina
   Gregorio, G. Glenn
   Liu, Qun
   Wang, Da-Neng
TI Structure and mechanism of a bacterial sodium-dependent dicarboxylate transporter
SO NATURE
LA English
DT Article
ID coupled citrate transporter; crystal-structure; na+/dicarboxylate cotransporter; anomalous diffraction; carrier protein; membrane; expression; system; residues; insights
AB In human cells, cytosolic citrate is a chief precursor for the synthesis of fatty acids, triacylglycerols, cholesterol and low-density lipoprotein. Cytosolic citrate further regulates the energy balance of the cell by activating the fatty-acid-synthesis pathway while downregulating both the glycolysis and fatty-acid beta-oxidation pathways(1-4). The rate of fatty-acid synthesis in liver and adipose cells, the two main tissue types for such synthesis, correlates directly with the concentration of citrate in the cytosol(2-5), with the cytosolic citrate concentration partially depending on direct import across the plasma membrane through the Na+-dependent citrate transporter (NaCT)(6,7). Mutations of the homologous fly gene (Indy; I'm not dead yet) result in reduced fat storage through calorie restriction(8). More recently, Nact (also known as Slc13a5)-knockout mice have been found to have increased hepatic mitochondrial biogenesis, higher lipid oxidation and energy expenditure, and reduced lipogenesis, which taken together protect the mice from obesity and insulin resistance(9). To understand the transport mechanism of NaCT and INDY proteins, here we report the 3.2 angstrom crystal structure of a bacterial INDY homologue. One citrate molecule and one sodium ion are bound per protein, and their binding sites are defined by conserved amino acid motifs, forming the structural basis for understanding the specificity of the transporter. Comparison of the structures of the two symmetrical halves of the transporter suggests conformational changes that propel substrate translocation.
C1 [Mancusso, Romina; Gregorio, G. Glenn; Wang, Da-Neng] NYU, Sch Med, Skirball Inst Biomol Med, Helen L & Martin S Kimmel Ctr Biol & Med, New York, NY 10016 USA.
   [Mancusso, Romina] NYU, Sch Med, Mol Biophys Grad Program, New York, NY 10016 USA.
   [Liu, Qun] Brookhaven Natl Lab, NSLS X4, New York Struct Biol Ctr, Upton, NY 11973 USA.
   [Wang, Da-Neng] NYU, Sch Med, Dept Cell Biol, New York, NY 10016 USA.
C3 New York University; New York University; United States Department of Energy (DOE); Brookhaven National Laboratory; New York University
RP Wang, DN (corresponding author), NYU, Sch Med, Skirball Inst Biomol Med, Helen L & Martin S Kimmel Ctr Biol & Med, 540 1st Ave, New York, NY 10016 USA.
EM wang@saturn.med.nyu.edu
FU National Institutes of Health [U54-GM075026, R01-DK073973, R01-GM093825, R01-MH083840]
NR 49
TC 154
Z9 171
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 NOV 22
PY 2012
VL 491
IS 7425
BP 622
EP +
DI 10.1038/nature11542
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 040RE
UT WOS:000311339800058
PM 23086149
DA 2026-03-09
ER

PT J
AU Iizuka, Y
   Uemura, R
   Motoyama, H
   Suzuki, T
   Miyake, T
   Hirabayashi, M
   Hondoh, T
AF Iizuka, Yoshinori
   Uemura, Ryu
   Motoyama, Hideaki
   Suzuki, Toshitaka
   Miyake, Takayuki
   Hirabayashi, Motohiro
   Hondoh, Takeo
TI Sulphate-climate coupling over the past 300,000 years in inland Antarctica
SO NATURE
LA English
DT Article
ID ice-core; sea-salt; oceanic phytoplankton; aerosol; sulfur; dust; period; cycle
AB Sulphate aerosols, particularly micrometre-sized particles of sulphate salt and sulphate-adhered dust, can act as cloud condensation nuclei, leading to increased solar scattering that cools Earth's climate(1,2). Evidence for such a coupling may lie in the sulphate record from polar ice cores, but previous analyses of melted ice-core samples have provided only sulphate ion concentrations, which may be due to sulphuric acid(3). Here we present profiles of sulphate salt and sulphate-adhered dust fluxes over the past 300,000 years from the Dome Fuji ice core in inland Antarctica. Our results show a nearly constant flux of sulphate-adhered dust through glacial and interglacial periods despite the large increases in total dust flux during glacial maxima(4). The sulphate salt flux, however, correlates inversely with temperature, suggesting a climatic coupling between particulate sulphur and temperature. For example, the total sulphate salt flux during the Last Glacial Maximum averages 5.78 mg m(-2) yr(-1), which is almost twice the Holocene value. Although it is based on a modern analogue with considerable uncertainties when applied to the ice-core record, this analysis indicates that the glacial-to-interglacial decrease in sulphate would lessen the aerosol indirect effects on cloud lifetime and albedo, leading to an Antarctic warming of 0.1 to 5 kelvin.
C1 [Iizuka, Yoshinori; Hondoh, Takeo] Hokkaido Univ, Inst Low Temp Sci, Sapporo, Hokkaido 0600819, Japan.
   [Uemura, Ryu] Univ Ryukyus, Fac Sci, Dept Chem Biol & Marine Sci, Okinawa 9030213, Japan.
   [Motoyama, Hideaki; Miyake, Takayuki; Hirabayashi, Motohiro] Natl Inst Polar Res, Tokyo 1908518, Japan.
   [Suzuki, Toshitaka] Yamagata Univ, Dept Earth & Environm Sci, Fac Sci, Yamagata 9908560, Japan.
C3 Hokkaido University; University of the Ryukyus; Research Organization of Information & Systems (ROIS); National Institute of Polar Research (NIPR) - Japan; Yamagata University
RP Iizuka, Y (corresponding author), Hokkaido Univ, Inst Low Temp Sci, Sapporo, Hokkaido 0600819, Japan.
EM iizuka@lowtem.hokudai.ac.jp
FU Ministry of Education, Culture, Sports, Science and Technology(MEXT) [14GS0202, 23680001, 21221002]; Japan Society for the Promotion of Science (JSPS); Institute of Low Temperature Science, Hokkaido University; Grants-in-Aid for Scientific Research [21221002, 23681001, 23680001] Funding Source: KAKEN
NR 28
TC 31
Z9 33
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 OCT 4
PY 2012
VL 490
IS 7418
BP 81
EP 84
DI 10.1038/nature11359
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 015LG
UT WOS:000309446800036
PM 23038469
DA 2026-03-09
ER

PT J
AU Jin, MS
   Oldham, ML
   Zhang, QJ
   Chen, J
AF Jin, Mi Sun
   Oldham, Michael L.
   Zhang, Qiuju
   Chen, Jue
TI Crystal structure of the multidrug transporter P-glycoprotein from Caenorhabditis elegans
SO NATURE
LA English
DT Article
ID drug-binding pocket; atpase activity; alternating access; nucleotide-binding; membrane; resistance; mutations; mutants; cells; purification
AB P-glycoprotein (P-gp) is an ATP-binding cassette transporter that confers multidrug resistance in cancer cells(1,2). It also affects the absorption, distribution and clearance of cancer-unrelated drugs and xenobiotics. For these reasons, the structure and function of P-gp have been studied extensively for decades(3). Here we present biochemical characterization of P-gp from Caenorhabditis elegans and its crystal structure at a resolution of 3.4 angstroms. We find that the apparent affinities of P-gp for anticancer drugs actinomycin D and paclitaxel are approximately 4,000 and 100 times higher, respectively, in the membrane bilayer than in detergent. This affinity enhancement highlights the importance of membrane partitioning when a drug accesses the transporter in the membrane(4). Furthermore, the transporter in the crystal structure opens its drug pathway at the level of the membrane's inner leaflet. In the helices flanking the opening to the membrane, we observe extended loops that may mediate drug binding, function as hinges to gate the pathway or both. We also find that the interface between the transmembrane and nucleotide-binding domains, which couples ATP hydrolysis to transport, contains a ball-and-socket joint and salt bridges similar to the ATP-binding cassette importers(5), suggesting that ATP-binding cassette exporters and importers may use similar mechanisms to achieve alternating access for transport. Finally, a model of human P-gp derived from the structure of C. elegans P-gp not only is compatible with decades of biochemical analysis(6-12), but also helps to explain perplexing functional data regarding the Phe335Ala mutant(13,14). These results increase our understanding of the structure and function of this important molecule.
C1 [Jin, Mi Sun; Chen, Jue] Purdue Univ, Dept Biol Sci, W Lafayette, IN 47907 USA.
   [Oldham, Michael L.; Zhang, Qiuju; Chen, Jue] Howard Hughes Med Inst, W Lafayette, IN 47907 USA.
C3 Purdue University System; Purdue University; Howard Hughes Medical Institute
RP Chen, J (corresponding author), Purdue Univ, Dept Biol Sci, W Lafayette, IN 47907 USA.
EM chenjue@purdue.edu
FU Howard Hughes Medical Institute; Purdue Center for Cancer Research [NCI CCSG CA23168]; National Research Foundation of Korea; International Human Frontier Science Program; National Cancer Institute [P30CA023168] Funding Source: NIH RePORTER
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   Zolnerciks JK, 2007, FASEB J, V21, P3937, DOI 10.1096/fj.07-8610com
NR 35
TC 405
Z9 476
U1 1
U2 156
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD OCT 25
PY 2012
VL 490
IS 7421
BP 566
EP +
DI 10.1038/nature11448
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 025NK
UT WOS:000310196200048
PM 23000902
DA 2026-03-09
ER

PT J
AU Peters, BA
   Kermani, BG
   Sparks, AB
   Alferov, O
   Hong, P
   Alexeev, A
   Jiang, Y
   Dahl, F
   Tang, YT
   Haas, J
   Robasky, K
   Zaranek, AW
   Lee, JH
   Ball, MP
   Peterson, JE
   Perazich, H
   Yeung, G
   Liu, J
   Chen, LS
   Kennemer, MI
   Pothuraju, K
   Konvicka, K
   Tsoupko-Sitnikov, M
   Pant, KP
   Ebert, JC
   Nilsen, GB
   Baccash, J
   Halpern, AL
   Church, GM
   Drmanac, R
AF Peters, Brock A.
   Kermani, Bahram G.
   Sparks, Andrew B.
   Alferov, Oleg
   Hong, Peter
   Alexeev, Andrei
   Jiang, Yuan
   Dahl, Fredrik
   Tang, Y. Tom
   Haas, Juergen
   Robasky, Kimberly
   Zaranek, Alexander Wait
   Lee, Je-Hyuk
   Ball, Madeleine Price
   Peterson, Joseph E.
   Perazich, Helena
   Yeung, George
   Liu, Jia
   Chen, Linsu
   Kennemer, Michael I.
   Pothuraju, Kaliprasad
   Konvicka, Karel
   Tsoupko-Sitnikov, Mike
   Pant, Krishna P.
   Ebert, Jessica C.
   Nilsen, Geoffrey B.
   Baccash, Jonathan
   Halpern, Aaron L.
   Church, George M.
   Drmanac, Radoje
TI Accurate whole-genome sequencing and haplotyping from 10 to 20 human cells
SO NATURE
LA English
DT Article
ID open-access database; jaspar
AB Recent advances in whole-genome sequencing have brought the vision of personal genomics and genomic medicine closer to reality. However, current methods lack clinical accuracy and the ability to describe the context (haplotypes) in which genome variants co-occur in a cost-effective manner. Here we describe a low-cost DNA sequencing and haplotyping process, long fragment read (LFR) technology, which is similar to sequencing long single DNA molecules without cloning or separation of metaphase chromosomes. In this study, ten LFR libraries were made using only similar to 100 picograms of human DNA per sample. Up to 97% of the heterozygous single nucleotide variants were assembled into long haplotype contigs. Removal of false positive single nucleotide variants not phased by multiple LFR haplotypes resulted in a final genome error rate of 1 in 10 megabases. Cost-effective and accurate genome sequencing and haplotyping from 10-20 human cells, as demonstrated here, will enable comprehensive genetic studies and diverse clinical applications.
C1 [Peters, Brock A.; Kermani, Bahram G.; Sparks, Andrew B.; Alferov, Oleg; Hong, Peter; Alexeev, Andrei; Jiang, Yuan; Dahl, Fredrik; Tang, Y. Tom; Haas, Juergen; Peterson, Joseph E.; Perazich, Helena; Yeung, George; Liu, Jia; Chen, Linsu; Kennemer, Michael I.; Pothuraju, Kaliprasad; Konvicka, Karel; Tsoupko-Sitnikov, Mike; Pant, Krishna P.; Ebert, Jessica C.; Nilsen, Geoffrey B.; Baccash, Jonathan; Halpern, Aaron L.; Drmanac, Radoje] Complete Genom Inc, Mountain View, CA 94043 USA.
   [Robasky, Kimberly; Zaranek, Alexander Wait; Lee, Je-Hyuk; Ball, Madeleine Price; Church, George M.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
   [Robasky, Kimberly] Boston Univ, Program Bioinformat, Boston, MA 02215 USA.
   [Lee, Je-Hyuk] Harvard Univ, Sch Med, Wyss Inst Biologically Inspired Engn, Cambridge, MA 02115 USA.
C3 Harvard University; Harvard Medical School; Boston University; Harvard University
RP Peters, BA (corresponding author), Complete Genom Inc, 2071 Stierlin Court, Mountain View, CA 94043 USA.
EM bpeters@completegenomics.com; rdrmanac@completegenomics.com
FU US Department of Commerce; National Institute of Standards and Technology [70NANB7H7027]; National Institutes of Health [P50HG005550]
NR 37
TC 175
Z9 372
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 12
PY 2012
VL 487
IS 7406
BP 190
EP 195
DI 10.1038/nature11236
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 972LP
UT WOS:000306278900030
PM 22785314
DA 2026-03-09
ER

PT J
AU Chen, Z
   Cheng, K
   Walton, Z
   Wang, YC
   Ebi, H
   Shimamura, T
   Liu, Y
   Tupper, T
   Ouyang, J
   Li, J
   Gao, P
   Woo, MS
   Xu, CX
   Yanagita, M
   Altabef, A
   Wang, SM
   Lee, C
   Nakada, Y
   Peña, CG
   Sun, YP
   Franchetti, Y
   Yao, C
   Saur, A
   Cameron, MD
   Nishino, M
   Hayes, DN
   Wilkerson, MD
   Roberts, PJ
   Lee, CB
   Bardeesy, N
   Butaney, M
   Chirieac, LR
   Costa, DB
   Jackman, D
   Sharpless, NE
   Castrillon, DH
   Demetri, GD
   Jänne, PA
   Pandolfi, PP
   Cantley, LC
   Kung, AL
   Engelman, JA
   Wong, KK
AF Chen, Zhao
   Cheng, Katherine
   Walton, Zandra
   Wang, Yuchuan
   Ebi, Hiromichi
   Shimamura, Takeshi
   Liu, Yan
   Tupper, Tanya
   Ouyang, Jing
   Li, Jie
   Gao, Peng
   Woo, Michele S.
   Xu, Chunxiao
   Yanagita, Masahiko
   Altabef, Abigail
   Wang, Shumei
   Lee, Charles
   Nakada, Yuji
   Pena, Christopher G.
   Sun, Yanping
   Franchetti, Yoko
   Yao, Catherine
   Saur, Amy
   Cameron, Michael D.
   Nishino, Mizuki
   Hayes, D. Neil
   Wilkerson, Matthew D.
   Roberts, Patrick J.
   Lee, Carrie B.
   Bardeesy, Nabeel
   Butaney, Mohit
   Chirieac, Lucian R.
   Costa, Daniel B.
   Jackman, David
   Sharpless, Norman E.
   Castrillon, Diego H.
   Demetri, George D.
   Jaenne, Pasi A.
   Pandolfi, Pier Paolo
   Cantley, Lewis C.
   Kung, Andrew L.
   Engelman, Jeffrey A.
   Wong, Kwok-Kin
TI A murine lung cancer co-clinical trial identifies genetic modifiers of therapeutic response
SO NATURE
LA English
DT Article
ID standardized uptake value; volume measurement; mouse models; survival; metaanalysis; gefitinib; docetaxel; adenocarcinoma; arry-142886; activation
AB Targeted therapies have demonstrated efficacy against specific subsets of molecularly defined cancers(1-4). Although most patients with lung cancer are stratified according to a single oncogenic driver, cancers harbouring identical activating genetic mutations show large variations in their responses to the same targeted therapy(1,3). The biology underlying this heterogeneity is not well understood, and the impact of co-existing genetic mutations, especially the loss of tumour suppressors(5-) (9), has not been fully explored. Here we use genetically engineeredmousemodels to conduct a ` co-clinical' trial that mirrors an ongoing human clinical trial in patients with KRAS-mutant lung cancers. This trial aims to determine if the MEK inhibitor selumetinib (AZD6244)(10) increases the efficacy of docetaxel, a standard of care chemotherapy. Our studies demonstrate that concomitant loss of either p53 (also known as Tp53) or Lkb1 (also known as Stk11), two clinically relevant tumour suppressors(6,9,11,12), markedly impaired the response of Kras-mutant cancers to docetaxel monotherapy. We observed that the addition of selumetinib provided substantial benefit for mice with lung cancer caused by Kras and Kras and p53 mutations, but mice with Kras and Lkb1 mutations had primary resistance to this combination therapy. Pharmacodynamic studies, including positron-emission tomography (PET) and computed tomography (CT), identified biological markers in mice and patients that provide a rationale for the differential efficacy of these therapies in the different genotypes. These co-clinical results identify predictive genetic biomarkers that should be validated by interrogating samples from patients enrolled on the concurrent clinical trial. These studies also highlight the rationale for synchronous co-clinical trials, not only to anticipate the results of ongoing human clinical trials, but also to generate clinically relevant hypotheses that can inform the analysis and design of human studies.
C1 [Chen, Zhao; Ebi, Hiromichi; Liu, Yan; Xu, Chunxiao; Jaenne, Pasi A.; Engelman, Jeffrey A.; Wong, Kwok-Kin] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.
   [Chen, Zhao; Cheng, Katherine; Walton, Zandra; Liu, Yan; Ouyang, Jing; Gao, Peng; Woo, Michele S.; Xu, Chunxiao; Yanagita, Masahiko; Altabef, Abigail; Yao, Catherine; Butaney, Mohit; Jackman, David; Jaenne, Pasi A.; Wong, Kwok-Kin] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
   [Chen, Zhao; Cheng, Katherine; Walton, Zandra; Liu, Yan; Gao, Peng; Xu, Chunxiao; Demetri, George D.; Wong, Kwok-Kin] Dana Farber Canc Inst, Harvard Canc Ctr, Ludwig Ctr Dana Farber, Boston, MA 02115 USA.
   [Wang, Yuchuan; Tupper, Tanya; Sun, Yanping; Saur, Amy; Kung, Andrew L.] Dana Farber Canc Inst, Lurie Family Imaging Ctr, Boston, MA 02115 USA.
   [Wang, Yuchuan; Sun, Yanping; Nishino, Mizuki] Dana Farber Canc Inst, Dept Imaging, Boston, MA 02115 USA.
   [Wang, Yuchuan; Nishino, Mizuki] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA.
   [Ebi, Hiromichi; Bardeesy, Nabeel; Engelman, Jeffrey A.] Massachusetts Gen Hosp, Ctr Canc, Dept Med Oncol, Boston, MA 02114 USA.
   [Shimamura, Takeshi] Loyola Univ Chicago, Stritch Sch Med, Inst Oncol, Dept Mol Pharmacol & Therapeut, Maywood, IL 60153 USA.
   [Li, Jie] Iowa State Univ, Dept Stat & Stat Lab, Ctr Survey Stat & Methodol, Ames, IA 50010 USA.
   [Wang, Shumei; Lee, Charles; Chirieac, Lucian R.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
   [Nakada, Yuji; Pena, Christopher G.; Castrillon, Diego H.] Univ Texas SW Med Ctr Dallas, Dept Pathol, Dallas, TX 75390 USA.
   [Nakada, Yuji; Pena, Christopher G.; Castrillon, Diego H.] Univ Texas SW Med Ctr Dallas, Simmons Comprehens Canc Ctr, Dallas, TX 75390 USA.
   [Franchetti, Yoko] Harvard Univ, Sch Publ Hlth, Dept Biostat & Computat Biol, Dana Farber Canc Inst,Dept Biostat, Boston, MA 02115 USA.
   [Cameron, Michael D.] Scripps Res Inst, Translat Res Inst, Jupiter, FL 33458 USA.
   [Hayes, D. Neil; Wilkerson, Matthew D.; Roberts, Patrick J.; Lee, Carrie B.; Sharpless, Norman E.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA.
   [Costa, Daniel B.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Boston, MA 02115 USA.
   [Jaenne, Pasi A.; Wong, Kwok-Kin] Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA.
   [Pandolfi, Pier Paolo] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Canc Genet Program,Dept Med & Pathol, Boston, MA 02115 USA.
   [Cantley, Lewis C.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA.
   [Cantley, Lewis C.] Beth Israel Deaconess Med Ctr, Div Signal Transduct, Boston, MA 02115 USA.
   [Kung, Andrew L.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
   [Kung, Andrew L.] Childrens Hosp, Boston, MA 02115 USA.
C3 Harvard University; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; 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 University Medical Affiliates; Massachusetts General Hospital; Loyola University Chicago; Iowa State University; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; University of Texas System; University of Texas Southwestern Medical Center; University of Texas System; University of Texas Southwestern Medical Center; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard T.H. Chan School of Public Health; State University System of Florida; University of Florida; Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology; University of North Carolina; University of North Carolina Chapel Hill; Harvard University; Harvard University Medical Affiliates; Beth Israel Deaconess Medical Center; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard University Medical Affiliates; Beth Israel Deaconess Medical Center; 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; Dana-Farber Cancer Institute; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital
RP Wong, KK (corresponding author), Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.
EM andrew_kung@dfci.harvard.edu; jengelman@partners.org; kwong1@partners.org
FU National Institutes of Health [CA122794, CA140594, CA137181, CA137008, CA147940, CA137008-01, 1U01CA141576, Lung SPORE P50CA090578]; United against Lung Cancer Foundation; American Lung Association; Susan Spooner Research Fund; National Cancer Institute [R01CA166480, P01CA120964, R01CA137008, P30CA016086] Funding Source: NIH RePORTER
NR 30
TC 385
Z9 434
U1 0
U2 76
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD MAR 29
PY 2012
VL 483
IS 7391
BP 613
EP 617
DI 10.1038/nature10937
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 915EF
UT WOS:000302006100042
PM 22425996
DA 2026-03-09
ER

PT J
AU Mebrahtu, HT
   Borzenets, IV
   Liu, DE
   Zheng, HX
   Bomze, YV
   Smirnov, AI
   Baranger, HU
   Finkelstein, G
AF Mebrahtu, Henok T.
   Borzenets, Ivan V.
   Liu, Dong E.
   Zheng, Huaixiu
   Bomze, Yuriy V.
   Smirnov, Alex I.
   Baranger, Harold U.
   Finkelstein, Gleb
TI Quantum phase transition in a resonant level coupled to interacting leads
SO NATURE
LA English
DT Article
ID coulomb-blockade; tunnel-junctions; luttinger liquid
AB A Luttinger liquid is an interacting one-dimensional electronic system, quite distinct from the 'conventional' Fermi liquids formed by interacting electrons in two and three dimensions(1). Some of the most striking properties of Luttinger liquids are revealed in the process of electron tunnelling. For example, as a function of the applied bias voltage or temperature, the tunnelling current exhibits a non-trivial power-law suppression(2,3). (There is no such suppression in a conventional Fermi liquid.) Here, using a carbon nanotube connected to resistive leads, we create a system that emulates tunnelling in a Luttinger liquid, by controlling the interaction of the tunnelling electron with its environment. We further replace a single tunnelling barrier with a double-barrier, resonant-level structure and investigate resonant tunnelling between Luttinger liquids. At low temperatures, we observe perfect transparency of the resonant level embedded in the interacting environment, and the width of the resonance tends to zero. We argue that this behaviour results from many-body physics of interacting electrons, and signals the presence of a quantum phase transition(4,5). Given that many parameters, including the interaction strength, can be precisely controlled in our samples, this is an attractive model system for studying quantum critical phenomena in general, with wide-reaching implications for understanding quantum phase transitions in more complex systems, such as cold atoms(6) and strongly correlated bulk materials(7).
C1 [Mebrahtu, Henok T.; Borzenets, Ivan V.; Liu, Dong E.; Zheng, Huaixiu; Bomze, Yuriy V.; Baranger, Harold U.; Finkelstein, Gleb] Duke Univ, Dept Phys, Durham, NC 27708 USA.
   [Smirnov, Alex I.] N Carolina State Univ, Dept Chem, Raleigh, NC 27695 USA.
C3 Duke University; North Carolina State University
RP Finkelstein, G (corresponding author), Duke Univ, Dept Phys, Durham, NC 27708 USA.
EM gleb@phy.duke.edu
FU US DOE [DE-SC0002765, DE-SC0005237, DE-FG02-02ER15354]; U.S. Department of Energy (DOE) [DE-SC0002765, DE-SC0005237] Funding Source: U.S. Department of Energy (DOE)
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NR 30
TC 74
Z9 79
U1 0
U2 44
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD AUG 2
PY 2012
VL 488
IS 7409
BP 61
EP 64
DI 10.1038/nature11265
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 981ZE
UT WOS:000307010700032
PM 22859201
DA 2026-03-09
ER

PT J
AU Firestone, AJ
   Weinger, JS
   Maldonado, M
   Barlan, K
   Langston, LD
   O'Donnell, M
   Gelfand, VI
   Kapoor, TM
   Chen, JK
AF Firestone, Ari J.
   Weinger, Joshua S.
   Maldonado, Maria
   Barlan, Kari
   Langston, Lance D.
   O'Donnell, Michael
   Gelfand, Vladimir I.
   Kapoor, Tarun M.
   Chen, James K.
TI Small-molecule inhibitors of the AAA plus ATPase motor cytoplasmic dynein
SO NATURE
LA English
DT Article
ID primary cilium; in-vitro; dynactin; kinetochore; organization; centrosm; transport; proteins; motility; kinesin
AB The conversion of chemical energy into mechanical force by AAA+ (ATPases associated with diverse cellular activities) ATPases is integral to cellular processes, including DNA replication, protein unfolding, cargo transport and membrane fusion(1). The AAA+ ATPase motor cytoplasmic dynein regulates ciliary trafficking(2), mitotic spindle formation(3) and organelle transport(4), and dissecting its precise functions has been challenging because of its rapid timescale of action and the lack of cell-permeable, chemical modulators. Here we describe the discovery of ciliobrevins, the first specific small-molecule antagonists of cytoplasmic dynein. Ciliobrevins perturb protein trafficking within the primary cilium, leading to their malformation and Hedgehog signalling blockade. Ciliobrevins also prevent spindle pole focusing, kinetochore-microtubule attachment, melanosome aggregation and peroxisome motility in cultured cells. We further demonstrate the ability of ciliobrevins to block dynein-dependent microtubule gliding and ATPase activity in vitro. Ciliobrevins therefore will be useful reagents for studying cellular processes that require this microtubule motor and may guide the development of additional AAA+ ATPase superfamily inhibitors.
C1 [Firestone, Ari J.; Chen, James K.] Stanford Univ, Sch Med, Dept Chem & Syst Biol, Stanford, CA 94305 USA.
   [Weinger, Joshua S.; Maldonado, Maria; Langston, Lance D.; O'Donnell, Michael; Kapoor, Tarun M.] Rockefeller Univ, Lab Chem & Cell Biol, New York, NY 10021 USA.
   [Barlan, Kari; Gelfand, Vladimir I.] Northwestern Univ, Sch Med, Dept Cell & Mol Biol, Chicago, IL 60611 USA.
C3 Stanford University; Rockefeller University; Northwestern University
RP Chen, JK (corresponding author), Stanford Univ, Sch Med, Dept Chem & Syst Biol, Stanford, CA 94305 USA.
EM kapoor@rockefeller.edu; jameschen@stanford.edu
FU National Institutes of Health [R01 CA136574, R01 GM65933, R01 GM71772, R01 GM52111]
NR 30
TC 314
Z9 375
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 APR 5
PY 2012
VL 484
IS 7392
BP 125
EP 129
DI 10.1038/nature10936
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 919QN
UT WOS:000302343400047
PM 22425997
DA 2026-03-09
ER

PT J
AU Gräff, J
   Rei, D
   Guan, JS
   Wang, WY
   Seo, J
   Hennig, KM
   Nieland, TJF
   Fass, DM
   Kao, PF
   Kahn, M
   Su, SC
   Samiei, A
   Joseph, N
   Haggarty, SJ
   Delalle, I
   Tsai, LH
AF Graeff, Johannes
   Rei, Damien
   Guan, Ji-Song
   Wang, Wen-Yuan
   Seo, Jinsoo
   Hennig, Krista M.
   Nieland, Thomas J. F.
   Fass, Daniel M.
   Kao, Patricia F.
   Kahn, Martin
   Su, Susan C.
   Samiei, Alireza
   Joseph, Nadine
   Haggarty, Stephen J.
   Delalle, Ivana
   Tsai, Li-Huei
TI An epigenetic blockade of cognitive functions in the neurodegenerating brain
SO NATURE
LA English
DT Article
ID long-term-memory; alzheimers-disease; synaptic plasticity; clinical-implications; transgenic mice; remote memory; cdk5; phosphorylation; expression; chromatin
AB Cognitive decline is a debilitating feature of most neurodegenerative diseases of the central nervous system, including Alzheimer's disease(1). The causes leading to such impairment are only poorly understood and effective treatments are slow to emerge(2). Here we show that cognitive capacities in the neurodegenerating brain are constrained by an epigenetic blockade of gene transcription that is potentially reversible. This blockade is mediated by histone deacetylase 2, which is increased by Alzheimer's-disease-related neurotoxic insults in vitro, in two mouse models of neurodegeneration and in patients with Alzheimer's disease. Histone deacetylase 2 associates with and reduces the histone acetylation of genes important for learning and memory, which show a concomitant decrease in expression. Importantly, reversing the build-up of histone deacetylase 2 by short-hairpin-RNA-mediated knockdown unlocks the repression of these genes, reinstates structural and synaptic plasticity, and abolishes neurodegeneration-associated memory impairments. These findings advocate for the development of selective inhibitors of histone deacetylase 2 and suggest that cognitive capacities following neurodegeneration are not entirely lost, but merely impaired by this epigenetic blockade.
C1 [Graeff, Johannes; Rei, Damien; Guan, Ji-Song; Wang, Wen-Yuan; Seo, Jinsoo; Kahn, Martin; Su, Susan C.; Samiei, Alireza; Joseph, Nadine; Tsai, Li-Huei] MIT, Dept Brain & Cognit Sci, Picower Inst Learning & Memory, Cambridge, MA 02139 USA.
   [Graeff, Johannes; Rei, Damien; Guan, Ji-Song; Wang, Wen-Yuan; Seo, Jinsoo; Su, Susan C.; Joseph, Nadine; Tsai, Li-Huei] MIT, Howard Hughes Med Inst, Cambridge, MA 02139 USA.
   [Graeff, Johannes; Guan, Ji-Song; Wang, Wen-Yuan; Hennig, Krista M.; Nieland, Thomas J. F.; Fass, Daniel M.; Joseph, Nadine; Haggarty, Stephen J.; Tsai, Li-Huei] Broad Inst Harvard Univ & Massachusetts Inst Tech, Stanley Ctr Psychiat Res, Cambridge, MA 02142 USA.
   [Hennig, Krista M.; Fass, Daniel M.; Haggarty, Stephen J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
   [Kao, Patricia F.; Delalle, Ivana] Boston Univ, Sch Med, Dept Pathol & Lab Med, Boston, MA 02118 USA.
C3 Massachusetts Institute of Technology (MIT); Howard Hughes Medical Institute; Massachusetts Institute of Technology (MIT); Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard Medical School; Boston University
RP Tsai, LH (corresponding author), MIT, Dept Brain & Cognit Sci, Picower Inst Learning & Memory, E25-618, Cambridge, MA 02139 USA.
EM lhtsai@mit.edu
FU Stanley Medical Research Institution; National Institutes of Health/National Institute on Drug Abuse [RO1DA028301]; National Institutes of Health/National Institute of Neurological Disorders and Stroke [RO1NS078839]; Bard Richmond fellowship; Swiss National Science Foundation; Simons Foundation; Theodor und Ida Herzog-Egli foundation
NR 38
TC 704
Z9 809
U1 0
U2 176
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 8
PY 2012
VL 483
IS 7388
BP 222
EP U123
DI 10.1038/nature10849
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 904DT
UT WOS:000301174900041
PM 22388814
DA 2026-03-09
ER

PT J
AU Allan, RS
   Zueva, E
   Cammas, F
   Schreiber, HA
   Masson, V
   Belz, GT
   Roche, D
   Maison, C
   Quivy, JP
   Almouzni, G
   Amigorena, S
AF Allan, Rhys S.
   Zueva, Elina
   Cammas, Florence
   Schreiber, Heidi A.
   Masson, Vanessa
   Belz, Gabrielle T.
   Roche, Daniele
   Maison, Christele
   Quivy, Jean-Pierre
   Almouzni, Genevieve
   Amigorena, Sebastian
TI An epigenetic silencing pathway controlling T helper 2 cell lineage commitment
SO NATURE
LA English
DT Article
ID obstructive pulmonary-disease; cd4(+) t-cells; histone h3; interferon-gamma; dynamic changes; cytokine genes; hp1 proteins; lysine 9; heterochromatin; differentiation
AB During immune responses, naive CD4(+) T cells differentiate into several T helper (T-H) cell subsets under the control of lineage-specifying genes. These subsets (T(H)1, T(H)2 and T(H)17 cells and regulatory T cells) secrete distinct cytokines and are involved in protection against different types of infection. Epigenetic mechanisms are involved in the regulation of these developmental programs, and correlations have been drawn between the levels of particular epigenetic marks and the activity or silencing of specifying genes during differentiation(1-3). Nevertheless, the functional relevance of the epigenetic pathways involved in T-H cell subset differentiation and commitment is still unclear. Here we explore the role of the SUV39H1-H3K9me3-HP1 alpha silencing pathway in the control of T(H)2 lineage stability. This pathway involves the histone methylase SUV39H1, which participates in the trimethylation of histone H3 on lysine 9 (H3K9me3), a modification that provides binding sites for heterochromatin protein 1 alpha (HP1 alpha)(4,5) and promotes transcriptional silencing. This pathway was initially associated with heterochromatin formation and maintenance(6) but can also contribute to the regulation of euchromatic genes(7-9). We now propose that the SUV39H1-H3K9me3-HP1 alpha pathway participates in maintaining the silencing of T(H)1 loci, ensuring T(H)2 lineage stability. In T(H)2 cells that are deficient in SUV39H1, the ratio between trimethylated and acetylated H3K9 is impaired, and the binding of HP1 alpha at the promoters of silenced T(H)1 genes is reduced. Despite showing normal differentiation, both SUV39H1-deficient T(H)2 cells and HP1 alpha-deficient T(H)2 cells, in contrast to wild-type cells, expressed T(H)1 genes when recultured under conditions that drive differentiation into T(H)1 cells. In a mouse model of T(H)2-driven allergic asthma, the chemical inhibition or loss of SUV39H1 skewed T-cell responses towards T(H)1 responses and decreased the lung pathology. These results establish a link between the SUV39H1-H3K9me3-HP1 alpha pathway and the stability of T(H)2 cells, and they identify potential targets for therapeutic intervention in T(H)2-cell-mediated inflammatory diseases.
C1 [Allan, Rhys S.; Belz, Gabrielle T.] Walter & Eliza Hall Inst Med Res, Div Mol Immunol, Parkville, Vic 3052, Australia.
   [Allan, Rhys S.; Zueva, Elina; Schreiber, Heidi A.; Masson, Vanessa; Amigorena, Sebastian] Inst Curie Res Ctr, INSERM, U932, F-75248 Paris 05, France.
   [Cammas, Florence] Inst Rech Canc Montpellier, CRLC Val dAurelle Paul Lamarque, F-34298 Montpellier 5, France.
   [Roche, Daniele; Maison, Christele; Quivy, Jean-Pierre; Almouzni, Genevieve] Inst Curie Res Ctr, CNRS, UMR218, F-75248 Paris 05, France.
C3 Walter & Eliza Hall Institute; Universite PSL; UNICANCER; Institut Curie; Institut National de la Sante et de la Recherche Medicale (Inserm); UNICANCER; Universite de Montpellier; Institut Regional du Cancer Montpellier / Val d'Aurelle (ICM); Universite PSL; UNICANCER; Institut Curie; Centre National de la Recherche Scientifique (CNRS)
RP Allan, RS (corresponding author), Walter & Eliza Hall Inst Med Res, Div Mol Immunol, Parkville, Vic 3052, Australia.
EM rallan@wehi.edu.au; sebastian.amigorena@curie.fr
FU ANR [2010 1326 03, 2009 BLAN-0021 EPIGO, 2010 BLAN-1326 01]; European Commission Network of Excellence EpiGeneSys [HEALTH-F4-2010-257082]; Ligue National de Lutte contre le Cancer; Fellowship of the Institut Curie (Paris); Australian National Health and Medical Research Council-INSERM [461286];  [ANR-09-BLAN-0257]; National Health and Medical Research Council (NHMRC) [461286] Funding Source: National Health and Medical Research Council (NHMRC)
NR 29
TC 164
Z9 172
U1 0
U2 34
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUL 12
PY 2012
VL 487
IS 7406
BP 249
EP U137
DI 10.1038/nature11173
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 972LP
UT WOS:000306278900043
DA 2026-03-09
ER

PT J
AU Tomioka, K
   Yoshimura, M
   Fukui, T
AF Tomioka, Katsuhiro
   Yoshimura, Masatoshi
   Fukui, Takashi
TI A III-V nanowire channel on silicon for high-performance vertical transistors
SO NATURE
LA English
DT Article
ID field-effect transistors; growth
AB Silicon transistors are expected to have new gate architectures, channel materials and switching mechanisms in ten years' time(1-4). The trend in transistor scaling has already led to a change in gate structure from two dimensions to three, used in fin field-effect transistors, to avoid problems inherent in miniaturization such as high off-state leakage current and the short-channel effect. At present, planar and fin architectures using III-V materials, specifically InGaAs, are being explored as alternative fast channels on silicon(5-9) because of their high electron mobility and high-quality interface with gate dielectrics(10). The idea of surrounding-gate transistors(11), in which the gate is wrapped around a nanowire channel to provide the best possible electrostatic gate control, using InGaAs channels on silicon, however, has been less well investigated(12,13) because of difficulties in integrating free-standing InGaAs nanostructures on silicon. Here we report the position-controlled growth of vertical InGaAs nanowires on silicon without any buffering technique and demonstrate surrounding-gate transistors using InGaAs nanowires and InGaAs/InP/InAlAs/InGaAs core-multishell nanowires as channels. Surrounding-gate transistors using core-multishell nanowire channels with a six-sided, high-electron-mobility transistor structure greatly enhance the on-state current and transconductance while keeping good gate controllability. These devices provide a route to making vertically oriented transistors for the next generation of field-effect transistors and may be useful as building blocks for wireless networks on silicon platforms.
C1 [Tomioka, Katsuhiro; Yoshimura, Masatoshi; Fukui, Takashi] Hokkaido Univ, Grad Sch Informat Sci & Technol, Sapporo, Hokkaido 0608628, Japan.
   [Tomioka, Katsuhiro; Yoshimura, Masatoshi; Fukui, Takashi] Hokkaido Univ, RCIQE, Sapporo, Hokkaido 0608628, Japan.
   [Tomioka, Katsuhiro] Japan Sci & Technol Agcy PRESTO, Kawaguchi, Saitama 3320012, Japan.
C3 Hokkaido University; Hokkaido University
RP Tomioka, K (corresponding author), Hokkaido Univ, Grad Sch Informat Sci & Technol, Kita 13 Nishi 8, Sapporo, Hokkaido 0608628, Japan.
EM tomioka@rciqe.hokudai.ac.jp
FU MEXT; Japan Science and Technology Agency - PRESTO programme; Grants-in-Aid for Scientific Research [23221007] Funding Source: KAKEN
NR 28
TC 653
Z9 721
U1 2
U2 476
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 9
PY 2012
VL 488
IS 7410
BP 189
EP +
DI 10.1038/nature11293
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 985LE
UT WOS:000307267000028
PM 22854778
DA 2026-03-09
ER

PT J
AU Ding, L
   Ley, TJ
   Larson, DE
   Miller, CA
   Koboldt, DC
   Welch, JS
   Ritchey, JK
   Young, MA
   Lamprecht, T
   McLellan, MD
   McMichael, JF
   Wallis, JW
   Lu, C
   Shen, D
   Harris, CC
   Dooling, DJ
   Fulton, RS
   Fulton, LL
   Chen, K
   Schmidt, H
   Kalicki-Veizer, J
   Magrini, VJ
   Cook, L
   McGrath, SD
   Vickery, TL
   Wendl, MC
   Heath, S
   Watson, MA
   Link, DC
   Tomasson, MH
   Shannon, WD
   Payton, JE
   Kulkarni, S
   Westervelt, P
   Walter, MJ
   Graubert, TA
   Mardis, ER
   Wilson, RK
   DiPersio, JF
AF Ding, Li
   Ley, Timothy J.
   Larson, David E.
   Miller, Christopher A.
   Koboldt, Daniel C.
   Welch, John S.
   Ritchey, Julie K.
   Young, Margaret A.
   Lamprecht, Tamara
   McLellan, Michael D.
   McMichael, Joshua F.
   Wallis, John W.
   Lu, Charles
   Shen, Dong
   Harris, Christopher C.
   Dooling, David J.
   Fulton, Robert S.
   Fulton, Lucinda L.
   Chen, Ken
   Schmidt, Heather
   Kalicki-Veizer, Joelle
   Magrini, Vincent J.
   Cook, Lisa
   McGrath, Sean D.
   Vickery, Tammi L.
   Wendl, Michael C.
   Heath, Sharon
   Watson, Mark A.
   Link, Daniel C.
   Tomasson, Michael H.
   Shannon, William D.
   Payton, Jacqueline E.
   Kulkarni, Shashikant
   Westervelt, Peter
   Walter, Matthew J.
   Graubert, Timothy A.
   Mardis, Elaine R.
   Wilson, Richard K.
   DiPersio, John F.
TI Clonal evolution in relapsed acute myeloid leukaemia revealed by whole-genome sequencing
SO NATURE
LA English
DT Article
ID acute myelogenous leukemia; stem-cell transplantation; lymphoblastic-leukemia; mismatched hla; mutations; metastasis; resolution; cancer
AB Most patients with acute myeloid leukaemia (AML) die from progressive disease after relapse, which is associated with clonal evolution at the cytogenetic level(1,2). To determine the mutational spectrum associated with relapse, we sequenced the primary tumour and relapse genomes from eight AML patients, and validated hundreds of somatic mutations using deep sequencing; this allowed us to define clonality and clonal evolution patterns precisely at relapse. In addition to discovering novel, recurrently mutated genes (for example, WAC, SMC3, DIS3, DDX41 and DAXX) in AML, we also found two major clonal evolution patterns during AML relapse: (1) the founding clone in the primary tumour gained mutations and evolved into the relapse clone, or (2) a subclone of the founding clone survived initial therapy, gained additional mutations and expanded at relapse. In all cases, chemotherapy failed to eradicate the founding clone. The comparison of relapse-specific versus primary tumour mutations in all eight cases revealed an increase in transversions, probably due to DNA damage caused by cytotoxic chemotherapy. These data demonstrate that AML relapse is associated with the addition of new mutations and clonal evolution, which is shaped, in part, by the chemotherapy that the patients receive to establish and maintain remissions.
C1 [Ding, Li; Ley, Timothy J.; Larson, David E.; Miller, Christopher A.; Koboldt, Daniel C.; McLellan, Michael D.; McMichael, Joshua F.; Wallis, John W.; Lu, Charles; Shen, Dong; Harris, Christopher C.; Dooling, David J.; Fulton, Robert S.; Fulton, Lucinda L.; Chen, Ken; Schmidt, Heather; Kalicki-Veizer, Joelle; Magrini, Vincent J.; Cook, Lisa; McGrath, Sean D.; Vickery, Tammi L.; Wendl, Michael C.; Mardis, Elaine R.; Wilson, Richard K.] Washington Univ, Genome Inst, St Louis, MO 63108 USA.
   [Ding, Li; Wallis, John W.; Dooling, David J.; Fulton, Robert S.; Fulton, Lucinda L.; Chen, Ken; Magrini, Vincent J.; Wendl, Michael C.; Kulkarni, Shashikant; Mardis, Elaine R.; Wilson, Richard K.] Washington Univ, Dept Genet, St Louis, MO 63110 USA.
   [Ley, Timothy J.; Welch, John S.; Ritchey, Julie K.; Young, Margaret A.; Lamprecht, Tamara; Heath, Sharon; Link, Daniel C.; Tomasson, Michael H.; Westervelt, Peter; Walter, Matthew J.; Graubert, Timothy A.; DiPersio, John F.] Washington Univ, Dept Internal Med, Div Oncol, St Louis, MO 63110 USA.
   [Ley, Timothy J.; Link, Daniel C.; Tomasson, Michael H.; Kulkarni, Shashikant; Westervelt, Peter; Walter, Matthew J.; Graubert, Timothy A.; Mardis, Elaine R.; Wilson, Richard K.; DiPersio, John F.] Washington Univ, Siteman Canc Ctr, St Louis, MO 63110 USA.
   [Watson, Mark A.; Payton, Jacqueline E.; Kulkarni, Shashikant] Washington Univ, Dept Pathol & Immunol, St Louis, MO 63110 USA.
   [Shannon, William D.] Washington Univ, Div Biostat, St Louis, MO 63110 USA.
C3 Washington University (WUSTL); Washington University (WUSTL); Washington University (WUSTL); Siteman Cancer Center; Washington University (WUSTL); Washington University (WUSTL); Washington University (WUSTL)
RP Ley, TJ (corresponding author), Washington Univ, Genome Inst, St Louis, MO 63108 USA.
EM timley@wustl.edu
FU Washington University Cancer Genome Initiative; National Human Genome Research Institute (NHGRI) [U54 HG003079]; National Cancer Institute [PO1 CA101937]; Barnes-Jewish Hospital Foundation [00335-0505-02]; National Cancer Institute [P01CA101937] Funding Source: NIH RePORTER
NR 28
TC 1636
Z9 1999
U1 3
U2 212
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JAN 26
PY 2012
VL 481
IS 7382
BP 506
EP 510
DI 10.1038/nature10738
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 881GY
UT WOS:000299471800040
PM 22237025
DA 2026-03-09
ER

PT J
AU Gomes, KK
   Mar, W
   Ko, W
   Guinea, F
   Manoharan, HC
AF Gomes, Kenjiro K.
   Mar, Warren
   Ko, Wonhee
   Guinea, Francisco
   Manoharan, Hari C.
TI Designer Dirac fermions and topological phases in molecular graphene
SO NATURE
LA English
DT Article
AB The observation of massless Dirac fermions in monolayer graphene has generated a new area of science and technology seeking to harness charge carriers that behave relativistically within solid-state materials(1). Both massless and massive Dirac fermions have been studied and proposed in a growing class of Dirac materials that includes bilayer graphene, surface states of topological insulators and iron-based high-temperature superconductors. Because the accessibility of this physics is predicated on the synthesis of new materials, the quest for Dirac quasi-particles has expanded to artificial systems such as lattices comprising ultracold atoms(2-4). Here we report the emergence of Dirac fermions in a fully tunable condensed-matter system-molecular graphene-assembled by atomic manipulation of carbon monoxide molecules over a conventional two-dimensional electron system at a copper surface(5). Using low-temperature scanning tunnelling microscopy and spectroscopy, we embed the symmetries underlying the two-dimensional Dirac equation into electron lattices, and then visualize and shape the resulting ground states. These experiments show the existence within the system of linearly dispersing, massless quasi-particles accompanied by a density of states characteristic of graphene. We then tune the quantum tunnelling between lattice sites locally to adjust the phase accrual of propagating electrons. Spatial texturing of lattice distortions produces atomically sharp p-n and p-n-p junction devices with two-dimensional control of Dirac fermion density and the power to endow Dirac particles with mass(6-8). Moreover, we apply scalar and vector potentials locally and globally to engender topologically distinct ground states and, ultimately, embedded gauge fields(9-12), wherein Dirac electrons react to 'pseudo' electric and magnetic fields present in their reference frame but absent from the laboratory frame. We demonstrate that Landau levels created by these gauge fields can be taken to the relativistic magnetic quantum limit, which has so far been inaccessible in natural graphene. Molecular graphene provides a versatile means of synthesizing exotic topological electronic phases in condensed matter using tailored nanostructures.
C1 [Gomes, Kenjiro K.; Manoharan, Hari C.] Stanford Univ, Dept Phys, Stanford, CA 94305 USA.
   [Gomes, Kenjiro K.; Mar, Warren; Ko, Wonhee; Manoharan, Hari C.] SLAC Natl Accelerator Lab, Stanford Inst Mat & Energy Sci, Menlo Pk, CA 94025 USA.
   [Mar, Warren] Stanford Univ, Dept Elect Engn, Stanford, CA 94305 USA.
   [Ko, Wonhee] Stanford Univ, Dept Appl Phys, Stanford, CA 94305 USA.
   [Guinea, Francisco] CSIC, Inst Ciencia Mat Madrid, E-28049 Madrid, Spain.
C3 Stanford University; Stanford University; United States Department of Energy (DOE); SLAC National Accelerator Laboratory; Stanford University; Stanford University; Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Instituto de Ciencia de Materiales de Madrid (ICMM)
RP Manoharan, HC (corresponding author), Stanford Univ, Dept Phys, Stanford, CA 94305 USA.
EM manoharan@stanford.edu
FU US Department of Energy, Office of Basic Energy Sciences, Division of Materials Sciences and Engineering [DE-AC02-76SF00515]; MICINN (Spain) [FIS2008-00124, CSD2007-00010]; US National Science Foundation
NR 30
TC 654
Z9 738
U1 2
U2 476
PU NATURE PUBLISHING 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 15
PY 2012
VL 483
IS 7389
BP 306
EP 310
DI 10.1038/nature10941
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 908HP
UT WOS:000301481800043
PM 22422264
DA 2026-03-09
ER

PT J
AU Harvey, CD
   Coen, P
   Tank, DW
AF Harvey, Christopher D.
   Coen, Philip
   Tank, David W.
TI Choice-specific sequences in parietal cortex during a virtual-navigation decision task
SO NATURE
LA English
DT Article
ID hippocampal place cells; prefrontal cortex; working-memory; cellular resolution; perceptual decisions; spatial information; activity patterns; neural activity; visual-cortex; dynamics
AB The posterior parietal cortex (PPC) has an important role in many cognitive behaviours; however, the neural circuit dynamics underlying PPC function are not well understood. Here we optically imaged the spatial and temporal activity patterns of neuronal populations in mice performing a PPC-dependent task that combined a perceptual decision and memory-guided navigation in a virtual environment. Individual neurons had transient activation staggered relative to one another in time, forming a sequence of neuronal activation spanning the entire length of a task trial. Distinct sequences of neurons were triggered on trials with opposite behavioural choices and defined divergent, choice-specific trajectories through a state space of neuronal population activity. Cells participating in the different sequences and at distinct time points in the task were anatomically intermixed over microcircuit length scales (<100 micrometres). During working memory decision tasks, the PPC may therefore perform computations through sequence-based circuit dynamics, rather than long-lived stable states, implemented using anatomically intermingled microcircuits.
C1 [Harvey, Christopher D.; Coen, Philip; Tank, David W.] Princeton Univ, Princeton Neurosci Inst, Princeton, NJ 08544 USA.
   [Tank, David W.] Princeton Univ, Bezos Ctr Neural Circuit Dynam, Princeton, NJ 08544 USA.
   [Harvey, Christopher D.; Tank, David W.] Princeton Univ, Lewis Sigler Inst Integrat Genom, Princeton, NJ 08544 USA.
   [Harvey, Christopher D.; Coen, Philip; Tank, David W.] Princeton Univ, Dept Mol Biol, Princeton, NJ 08544 USA.
C3 Princeton University; Princeton University; Princeton University; Princeton University
RP Harvey, CD (corresponding author), Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA.
EM christopher_harvey@hms.harvard.edu; dwtank@princeton.edu
FU NIH [R01-MH083686, RC1-NS068148]; Helen Hay Whitney Foundation; Burroughs Wellcome Fund Career Award at the Scientific Interface
NR 50
TC 670
Z9 835
U1 1
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 APR 5
PY 2012
VL 484
IS 7392
BP 62
EP 68
DI 10.1038/nature10918
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 919QN
UT WOS:000302343400034
PM 22419153
DA 2026-03-09
ER

PT J
AU Curtis, C
   Shah, SP
   Chin, SF
   Turashvili, G
   Rueda, OM
   Dunning, MJ
   Speed, D
   Lynch, AG
   Samarajiwa, S
   Yuan, YY
   Gräf, S
   Ha, G
   Haffari, G
   Bashashati, A
   Russell, R
   McKinney, S
   Langerod, A
   Green, A
   Provenzano, E
   Wishart, G
   Pinder, S
   Watson, P
   Markowetz, F
   Murphy, L
   Ellis, I
   Purushotham, A
   Borresen-Dale, AL
   Brenton, JD
   Tavaré, S
   Caldas, C
   Aparicio, S
AF Curtis, Christina
   Shah, Sohrab P.
   Chin, Suet-Feung
   Turashvili, Gulisa
   Rueda, Oscar M.
   Dunning, Mark J.
   Speed, Doug
   Lynch, Andy G.
   Samarajiwa, Shamith
   Yuan, Yinyin
   Graef, Stefan
   Ha, Gavin
   Haffari, Gholamreza
   Bashashati, Ali
   Russell, Roslin
   McKinney, Steven
   Langerod, Anita
   Green, Andrew
   Provenzano, Elena
   Wishart, Gordon
   Pinder, Sarah
   Watson, Peter
   Markowetz, Florian
   Murphy, Leigh
   Ellis, Ian
   Purushotham, Arnie
   Borresen-Dale, Anne-Lise
   Brenton, James D.
   Tavare, Simon
   Caldas, Carlos
   Aparicio, Samuel
TI The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups
SO NATURE
LA English
DT Article
ID gene-expression; cancer; protein; suppressor; carcinoma; subtype
AB The elucidation of breast cancer subgroups and their molecular drivers requires integrated views of the genome and transcriptome from representative numbers of patients. We present an integrated analysis of copy number and gene expression in a discovery and validation set of 997 and 995 primary breast tumours, respectively, with long-term clinical follow-up. Inherited variants (copy number variants and single nucleotide polymorphisms) and acquired somatic copy number aberrations (CNAs) were associated with expression in similar to 40% of genes, with the landscape dominated by cis-and trans-acting CNAs. By delineating expression outlier genes driven in cis by CNAs, we identified putative cancer genes, including deletions in PPP2R2A, MTAP and MAP2K4. Unsupervised analysis of paired DNA-RNA profiles revealed novel subgroups with distinct clinical outcomes, which reproduced in the validation cohort. These include a high-risk, oestrogen-receptor-positive 11q13/14 cis-acting subgroup and a favourable prognosis subgroup devoid of CNAs. Trans-acting aberration hotspots were found to modulate subgroup-specific gene networks, including a TCR deletion-mediated adaptive immune response in the 'CNA-devoid' subgroup and a basal-specific chromosome 5 deletion-associated mitotic network. Our results provide a novel molecular stratification of the breast cancer population, derived from the impact of somatic CNAs on the transcriptome.
C1 [Curtis, Christina; Chin, Suet-Feung; Rueda, Oscar M.; Lynch, Andy G.; Samarajiwa, Shamith; Yuan, Yinyin; Graef, Stefan; Markowetz, Florian; Tavare, Simon; Caldas, Carlos] Univ Cambridge, Dept Oncol, Cambridge CB2 2XZ, England.
   [Curtis, Christina; Chin, Suet-Feung; Rueda, Oscar M.; Dunning, Mark J.; Speed, Doug; Lynch, Andy G.; Samarajiwa, Shamith; Yuan, Yinyin; Graef, Stefan; Russell, Roslin; Markowetz, Florian; Brenton, James D.; Tavare, Simon; Caldas, Carlos] Canc Res UK, Cambridge Res Inst, Li Ka Shing Ctr, Cambridge CB2 0RE, England.
   [Shah, Sohrab P.; Turashvili, Gulisa; Ha, Gavin; Haffari, Gholamreza; Bashashati, Ali; McKinney, Steven; Watson, Peter; Aparicio, Samuel] Univ British Columbia, Dept Pathol & Lab Med, Vancouver, BC V6T 2B5, Canada.
   [Shah, Sohrab P.; Turashvili, Gulisa; McKinney, Steven; Watson, Peter; Aparicio, Samuel] British Columbia Canc Res Ctr, Vancouver, BC V5Z 1L3, Canada.
   [Speed, Doug; Tavare, Simon] Univ Cambridge, Dept Appl Math & Theoret Phys, Ctr Math Sci, Cambridge CB3 0WA, England.
   [Langerod, Anita; Borresen-Dale, Anne-Lise] Radiumhosp, Dept Genet, Inst Canc Res, Oslo Univ Hosp, N-0310 Oslo, Norway.
   [Green, Andrew; Ellis, Ian] Univ Nottingham, Dept Histopathol, Sch Mol Med Sci, Nottingham NG5 1PB, England.
   [Provenzano, Elena; Wishart, Gordon; Caldas, Carlos] Cambridge Univ Hosp NHS Fdn Trust, Cambridge Breast Unit, Addenbrookes Hosp, Cambridge CB2 2QQ, England.
   [Pinder, Sarah; Purushotham, Arnie] Kings Coll London, Breakthrough Breast Canc Res Unit, London WC2R 2LS, England.
   [Pinder, Sarah; Borresen-Dale, Anne-Lise] NIHR Cambridge Biomed Res Ctr, London WC2R 2LS, England.
   [Watson, Peter; Murphy, Leigh] Univ Manitoba, Manitoba Inst Cell Biol, Winnipeg, MB R3E 0V9, Canada.
   [Purushotham, Arnie] Guys & St Thomas NHS Fdn Trust, NIHR Comprehens Biomed Res Ctr, London WC2R 2LS, England.
   [Borresen-Dale, Anne-Lise] Univ Oslo, Inst Clin Med, Fac Med, N-0316 Oslo, Norway.
   [Brenton, James D.; Caldas, Carlos] Cambridge Expt Canc Med Ctr, Cambridge CB2 0RE, England.
   [Tavare, Simon] Univ So Calif, Mol & Computat Biol Program, Los Angeles, CA 90089 USA.
C3 University of Cambridge; University of Cambridge; Cancer Research UK; CRUK Cambridge Institute; University of British Columbia; British Columbia Cancer Agency; University of Cambridge; University of Oslo; University of Nottingham; Cambridge University Hospitals NHS Foundation Trust; Addenbrooke's Hospital; University of Cambridge; University of London; King's College London; University of Manitoba; Guy's & St Thomas' NHS Foundation Trust; University of Oslo; University of Southern California
RP Caldas, C (corresponding author), Univ Cambridge, Dept Oncol, Hills Rd, Cambridge CB2 2XZ, England.
EM carlos.caldas@cancer.org.uk; saparicio@bccrc.ca
FU Cancer Research UK; British Columbia Cancer Foundation; Canadian Breast Cancer Foundation BC/Yukon; University of Cambridge; Hutchinson Whampoa; NIHR Cambridge Biomedical Research Centre; Cambridge Experimental Cancer Medicine Centre; Centre for Translational Genomics (CTAG) Vancouver; BCCA Breast Cancer Outcomes Unit; Canada Research Chair; National Institutes of Health Centers of Excellence in Genomics Science [P50 HG02790]; Cancer Research UK [19556, 15601] Funding Source: researchfish; National Institute for Health Research [ACF-2012-14-006, NF-SI-0611-10154] Funding Source: researchfish
NR 29
TC 4611
Z9 5365
U1 2
U2 488
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUN 21
PY 2012
VL 486
IS 7403
BP 346
EP 352
DI 10.1038/nature10983
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 961LV
UT WOS:000305466800033
PM 22522925
DA 2026-03-09
ER

PT J
AU Aharonian, FA
   Bogovalov, SV
   Khangulyan, D
AF Aharonian, F. A.
   Bogovalov, S. V.
   Khangulyan, D.
TI Abrupt acceleration of a 'cold' ultrarelativistic wind from the Crab pulsar
SO NATURE
LA English
DT Article
ID magnetic-field; x-ray; nebula; radiation; model
AB Pulsars are thought to eject electron-positron winds that energize the surrounding environment, with the formation of a pulsar wind nebula(1). The pulsar wind originates close to the light cylinder, the surface at which the pulsar co-rotation velocity equals the speed of light, and carries away much of the rotational energy lost by the pulsar. Initially the wind is dominated by electromagnetic energy (Poynting flux) but later this is converted to the kinetic energy of bulk motion(2). It is unclear exactly where this takes place and to what speed the wind is accelerated. Although some preferred models imply a gradual acceleration over the entire distance from the magnetosphere to the point at which the wind terminates(3,4), a rapid acceleration close to the light cylinder cannot be excluded(5,6). Here we report that the recent observations of pulsed, very high-energy gamma-ray emission from the Crab pulsar(7-9) are explained by the presence of a cold (in the sense of the low energy of the electrons in the frame of the moving plasma) ultrarelativistic wind dominated by kinetic energy. The conversion of the Poynting flux to kinetic energy should take place abruptly in the narrow cylindrical zone of radius between 20 and 50 light-cylinder radii centred on the axis of rotation of the pulsar, and should accelerate the wind to a Lorentz factor of (0.5-1.0) x 10(6). Although the ultrarelativistic nature of the wind does support the general model of pulsars, the requirement of the very high acceleration of the wind in a narrow zone not far from the light cylinder challenges current models.
C1 [Aharonian, F. A.] Dublin Inst Adv Studies, Sch Cosm Phys, Dublin 2, Ireland.
   [Aharonian, F. A.] Max Planck Inst Nucl Phys, D-69117 Heidelberg, Germany.
   [Bogovalov, S. V.] Natl Res Nucl Univ MEPhI, Moscow 115409, Russia.
   [Khangulyan, D.] Inst Space & Astronaut Sci JAXA, Chuo Ku, Sagamihara, Kanagawa 2525210, Japan.
C3 Dublin Institute for Advanced Studies; Max Planck Society; National Research Nuclear University MEPhI (Moscow Engineering Physics Institute); Japan Aerospace Exploration Agency (JAXA); Institute of Space & Astronautical Science (ISAS)
RP Aharonian, FA (corresponding author), Dublin Inst Adv Studies, Sch Cosm Phys, 31 Fitzwilliam Pl, Dublin 2, Ireland.
EM felix.aharonian@dias.ie
NR 23
TC 107
Z9 114
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 23
PY 2012
VL 482
IS 7386
BP 507
EP 509
DI 10.1038/nature10793
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 898VM
UT WOS:000300770500046
PM 22343893
DA 2026-03-09
ER

PT J
AU Timmann, C
   Thye, T
   Vens, M
   Evans, J
   May, J
   Ehmen, C
   Sievertsen, J
   Muntau, B
   Ruge, G
   Loag, W
   Ansong, D
   Antwi, S
   Asafo-Adjei, E
   Nguah, SB
   Kwakye, KO
   Akoto, AOY
   Sylverken, J
   Brendel, M
   Schuldt, K
   Loley, C
   Franke, A
   Meyer, CG
   Agbenyega, T
   Ziegler, A
   Horstmann, RD
AF Timmann, Christian
   Thye, Thorsten
   Vens, Maren
   Evans, Jennifer
   May, Juergen
   Ehmen, Christa
   Sievertsen, Juergen
   Muntau, Birgit
   Ruge, Gerd
   Loag, Wibke
   Ansong, Daniel
   Antwi, Sampson
   Asafo-Adjei, Emanuel
   Nguah, Samuel Blay
   Kwakye, Kingsley Osei
   Akoto, Alex Osei Yaw
   Sylverken, Justice
   Brendel, Michael
   Schuldt, Kathrin
   Loley, Christina
   Franke, Andre
   Meyer, Christian G.
   Agbenyega, Tsiri
   Ziegler, Andreas
   Horstmann, Rolf D.
TI Genome-wide association study indicates two novel resistance loci for severe malaria
SO NATURE
LA English
DT Article
ID cerebral malaria; activation; diseases
AB Malaria causes approximately one million fatalities per year, mostly among African children(1). Although highlighted by the strong protective effect of the sickle-cell trait(2,3), the full impact of human genetics on resistance to the disease remains largely unexplored(4). Genome-wide association (GWA) studies are designed to unravel relevant genetic variants comprehensively; however, in malaria, as in other infectious diseases, these studies have been only partly successful(5). Here we identify two previously unknown loci associated with severe falciparum malaria in patients and controls from Ghana, West Africa. We applied the GWA approach to the diverse clinical syndromes of severe falciparum malaria, thereby targeting human genetic variants influencing any step in the complex pathogenesis of the disease. One of the loci was identified on chromosome 1q32 within the ATP2B4 gene, which encodes the main calcium pump of erythrocytes(6), the host cells of the pathogenic stage of malaria parasites. The second was indicated by an intergenic single nucleotide polymorphism on chromosome 16q22.2, possibly linked to a neighbouring gene encoding the tight-junction protein MARVELD3. The protein is expressed on endothelial cells(7) and might therefore have a role in microvascular damage caused by endothelial adherence of parasitized erythrocytes. We also confirmed previous reports on protective effects of the sickle-cell trait and blood group O-5,O-8,O-9. Our findings underline the potential of the GWA approach to provide candidates for the development of control measures against infectious diseases in humans.
C1 [Timmann, Christian; Thye, Thorsten; Evans, Jennifer; Ehmen, Christa; Sievertsen, Juergen; Muntau, Birgit; Ruge, Gerd; Brendel, Michael; Schuldt, Kathrin; Meyer, Christian G.; Horstmann, Rolf D.] Bernhard Nocht Inst Trop Med, Dept Mol Med, D-20359 Hamburg, Germany.
   [Timmann, Christian; Thye, Thorsten; Vens, Maren; Brendel, Michael; Loley, Christina; Ziegler, Andreas] Med Univ Lubeck, Inst Med Biometry & Stat, D-23562 Lubeck, Germany.
   [Evans, Jennifer] Kumasi Ctr Collaborat Res Trop Med, Kumasi, Ghana.
   [May, Juergen; Loag, Wibke] Bernhard Nocht Inst Trop Med, Infect Dis Epidemiol Grp, D-20359 Hamburg, Germany.
   [Ansong, Daniel; Antwi, Sampson; Asafo-Adjei, Emanuel; Nguah, Samuel Blay; Kwakye, Kingsley Osei; Akoto, Alex Osei Yaw; Sylverken, Justice; Agbenyega, Tsiri] Kwame Nkrumah Univ Sci & Technol, Sch Med Sci, Kumasi, Ghana.
   [Franke, Andre] Univ Kiel, Inst Clin Mol Biol, D-24105 Kiel, Germany.
C3 Leibniz Association; Bernhard Nocht Institut fur Tropenmedizin; University of Lubeck; Kumasi Center for Collaborative Research; Leibniz Association; Bernhard Nocht Institut fur Tropenmedizin; Kwame Nkrumah University Science & Technology; University of Kiel
RP Timmann, C (corresponding author), Bernhard Nocht Inst Trop Med, Dept Mol Med, Bernhard Nocht Str 74, D-20359 Hamburg, Germany.
EM timmann@bnitm.de
FU National Genome Research Network of the German Ministry for Education and Research (BMBF) [NGFN1, NGFN2]; Wellcome Trust [WT077383/Z/05/Z]; Foundation for the National Institutes of Health, Bill & Melinda Gates' Grand Challenges in Global Health Initiative [566]
NR 27
TC 195
Z9 217
U1 0
U2 59
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 20
PY 2012
VL 489
IS 7416
BP 443
EP 446
DI 10.1038/nature11334
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 007AK
UT WOS:000308860900048
PM 22895189
DA 2026-03-09
ER

PT J
AU Ye, Y
   Blaser, G
   Horrocks, MH
   Ruedas-Rama, MJ
   Ibrahim, S
   Zhukov, AA
   Orte, A
   Klenerman, D
   Jackson, SE
   Komander, D
AF Ye, Yu
   Blaser, Georg
   Horrocks, Mathew H.
   Ruedas-Rama, Maria J.
   Ibrahim, Shehu
   Zhukov, Alexander A.
   Orte, Angel
   Klenerman, David
   Jackson, Sophie E.
   Komander, David
TI Ubiquitin chain conformation regulates recognition and activity of interacting proteins
SO NATURE
LA English
DT Article
ID fluorescence coincidence spectroscopy; linear polyubiquitin chains; kappa-b activation; single-molecule; structural basis; diubiquitin; binding; nmr; e2
AB Mechanisms of protein recognition have been extensively studied for single-domain proteins(1), but are less well characterized for dynamic multidomain systems. Ubiquitin chains represent a biologically important multidomain system that requires recognition by structurally diverse ubiquitin-interacting proteins(2,3). Ubiquitin chain conformations in isolation are often different from conformations observed in ubiquitin-interacting protein complexes, indicating either great dynamic flexibility or extensive chain remodelling upon binding. Using single-molecule fluorescence resonance energy transfer, we show that Lys 63-, Lys 48- and Met 1-linked diubiquitin exist in several distinct conformational states in solution. Lys 63- and Met 1-linked diubiquitin adopt extended 'open' and more compact 'closed' conformations, and ubiquitin-binding domains and deubiquitinases (DUBs) select pre-existing conformations. By contrast, Lys 48-linked diubiquitin adopts predominantly compact conformations. DUBs directly recognize existing conformations, but may also remodel ubiquitin chains to hydrolyse the isopeptide bond. Disruption of the Lys 48-diubiquitin interface changes conformational dynamics and affects DUB activity. Hence, conformational equilibria in ubiquitin chains provide an additional layer of regulation in the ubiquitin system, and distinct conformations observed in differently linked polyubiquitin may contribute to the specificity of ubiquitin-interacting proteins.
C1 [Ye, Yu; Komander, David] MRC, Mol Biol Lab, Div Prot & Nucle Acids Chem, Cambridge CB2 0QH, England.
   [Blaser, Georg; Horrocks, Mathew H.; Ibrahim, Shehu; Zhukov, Alexander A.; Klenerman, David; Jackson, Sophie E.] Univ Cambridge, Dept Chem, Cambridge CB2 1EW, England.
   [Ruedas-Rama, Maria J.; Orte, Angel] Univ Granada, Fac Pharm, Dept Phys Chem, E-18071 Granada, Spain.
C3 MRC Laboratory Molecular Biology; University of Cambridge; University of Granada
RP Komander, D (corresponding author), MRC, Mol Biol Lab, Div Prot & Nucle Acids Chem, Cambridge CB2 0QH, England.
EM dk10012@cam.ac.uk; sej13@cam.ac.uk; dk@mrc-lmb.cam.ac.uk
FU Medical Research Council [U105192732]; EMBO Young Investigator Program; BBSRC; Newton Trust; EMBO YIP small grant; EPSRC; Biotechnology and Biological Sciences Research Council [BB/F00219X/1] Funding Source: researchfish; Medical Research Council [MC_U105192732] Funding Source: researchfish; BBSRC [BB/F00219X/1] Funding Source: UKRI; MRC [MC_U105192732] Funding Source: UKRI
NR 29
TC 157
Z9 197
U1 1
U2 111
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD DEC 13
PY 2012
VL 492
IS 7428
BP 266
EP 270
DI 10.1038/nature11722
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 053GM
UT WOS:000312259300045
PM 23201676
DA 2026-03-09
ER

PT J
AU Uoyama, H
   Goushi, K
   Shizu, K
   Nomura, H
   Adachi, C
AF Uoyama, Hiroki
   Goushi, Kenichi
   Shizu, Katsuyuki
   Nomura, Hiroko
   Adachi, Chihaya
TI Highly efficient organic light-emitting diodes from delayed fluorescence
SO NATURE
LA English
DT Article
ID exciton formation; electroluminescence; singlet; states
AB The inherent flexibility afforded by molecular design has accelerated the development of a wide variety of organic semiconductors over the past two decades. In particular, great advances have been made in the development of materials for organic light-emitting diodes (OLEDs), from early devices based on fluorescent molecules(1) to those using phosphorescent molecules(2,3). In OLEDs, electrically injected charge carriers recombine to form singlet and triplet excitons in a 1:3 ratio(1); the use of phosphorescent metal-organic complexes exploits the normally non-radiative triplet excitons and so enhances the overall electroluminescence efficiency(2,3). Here we report a class of metal-free organic electroluminescent molecules in which the energy gap between the singlet and triplet excited states is minimized by design(4), thereby promoting highly efficient spin up-conversion from non-radiative triplet states to radiative singlet states while maintaining high radiative decay rates, of more than 10(6) decays per second. In other words, these molecules harness both singlet and triplet excitons for light emission through fluorescence decay channels, leading to an intrinsic fluorescence efficiency in excess of 90 per cent and a very high external electroluminescence efficiency, of more than 19 per cent, which is comparable to that achieved in high-efficiency phosphorescence-based OLEDs(3).
C1 [Uoyama, Hiroki; Goushi, Kenichi; Shizu, Katsuyuki; Nomura, Hiroko; Adachi, Chihaya] Kyushu Univ, Ctr Organ Photon & Elect Res, Nishi Ku, Fukuoka 8190395, Japan.
   [Goushi, Kenichi; Adachi, Chihaya] Kyushu Univ, Int Inst Carbon Neutral Energy Res WPI I2CNER, Nishi Ku, Fukuoka 8190395, Japan.
C3 Kyushu University; Kyushu University
RP Adachi, C (corresponding author), Kyushu Univ, Ctr Organ Photon & Elect Res, Nishi Ku, 744 Motooka, Fukuoka 8190395, Japan.
EM adachi@opera.kyushu-u.ac.jp
FU Funding Program for World-Leading Innovative R&D on Science and Technology (FIRST); International Institute for Carbon Neutral Energy Research (WPI-I2CNER); Japanese Ministry of Education, Culture, Sports, Science and Technology
NR 30
TC 7028
Z9 7822
U1 108
U2 4427
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 13
PY 2012
VL 492
IS 7428
BP 234
EP +
DI 10.1038/nature11687
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 053GM
UT WOS:000312259300038
PM 23235877
DA 2026-03-09
ER

PT J
AU Pascoli, V
   Turiault, M
   Lüscher, C
AF Pascoli, Vincent
   Turiault, Marc
   Luescher, Christian
TI Reversal of cocaine-evoked synaptic potentiation resets drug-induced adaptive behaviour
SO NATURE
LA English
DT Article
ID rat nucleus-accumbens; ampa receptors; plasticity; dopamine; activation; addiction; erk; sensitization; cascade; responses
AB Drug-evoked synaptic plasticity is observed at many synapses and may underlie behavioural adaptations in addiction(1). Mechanistic investigations start with the identification of the molecular drug targets. Cocaine, for example, exerts its reinforcing(2) and early neuroadaptive effects(3) by inhibiting the dopamine transporter, thus causing a strong increase in mesolimbic dopamine. Among the many signalling pathways subsequently engaged, phosphorylation of the extracellular signal-regulated kinase (ERK) in the nucleus accumbens(4) is of particular interest because it has been implicated in NMDA-receptor and type 1 dopamine (D1)-receptor-dependent synaptic potentiation(5) as well as in several behavioural adaptations(6-8). A causal link between drug-evoked plasticity at identified synapses and behavioural adaptations, however, is missing, and the benefits of restoring baseline transmission have yet to be demonstrated. Here we find that cocaine potentiates excitatory transmission in D1-receptor-expressing medium-sized spiny neurons (D1R-MSNs) in mice via ERK signalling with a time course that parallels locomotor sensitization. Depotentiation of cortical nucleus accumbens inputs by optogenetic stimulation in vivo efficiently restored normal transmission and abolished cocaine-induced locomotor sensitization. These findings establish synaptic potentiation selectively in D1R-MSNs as a mechanism underlying a core component of addiction, probably by creating an imbalance between distinct populations of MSNs in the nucleus accumbens. Our data also provide proof of principle that reversal of cocaine-evoked synaptic plasticity can treat behavioural alterations caused by addictive drugs and may inspire novel therapeutic approaches involving deep brain stimulation or transcranial magnetic stimulation.
C1 [Pascoli, Vincent; Turiault, Marc; Luescher, Christian] Univ Geneva, Fac Med, Dept Basic Neurosci, CH-1211 Geneva, Switzerland.
   [Luescher, Christian] Univ Hosp Geneva, Dept Clin Neurosci, Clin Neurol, CH-1211 Geneva, Switzerland.
C3 University of Geneva; 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; "Synapsy", a National Competence Center in Research (NCCR) of the Swiss Confederation on the synaptic basis of mental disorders
NR 34
TC 305
Z9 359
U1 0
U2 52
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JAN 5
PY 2012
VL 481
IS 7379
BP 71
EP U76
DI 10.1038/nature10709
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 872VD
UT WOS:000298836900031
PM 22158102
DA 2026-03-09
ER

PT J
AU Kretzschmar, T
   Kohlen, W
   Sasse, J
   Borghi, L
   Schlegel, M
   Bachelier, JB
   Reinhardt, D
   Bours, R
   Bouwmeester, HJ
   Martinoia, E
AF Kretzschmar, Tobias
   Kohlen, Wouter
   Sasse, Joelle
   Borghi, Lorenzo
   Schlegel, Markus
   Bachelier, Julien B.
   Reinhardt, Didier
   Bours, Ralph
   Bouwmeester, Harro J.
   Martinoia, Enrico
TI A petunia ABC protein controls strigolactone-dependent symbiotic signalling and branching
SO NATURE
LA English
DT Article
ID cassette-type transporter; arbuscular mycorrhiza; medicago-truncatula; gene family; plant; auxin; arabidopsis; acid; pcr; germination
AB Strigolactones were originally identified as stimulators of the germination of root-parasitic weeds(1) that pose a serious threat to resource-limited agriculture(2). They are mostly exuded from roots and function as signalling compounds in the initiation of arbuscular mycorrhizae(3), which are plant-fungus symbionts with a global effect on carbon and phosphate cycling(4). Recently, strigolactones were established to be phytohormones that regulate plant shoot architecture by inhibiting the outgrowth of axillary buds(5,6). Despite their importance, it is not known how strigolactones are transported. ATP-binding cassette (ABC) transporters, however, are known to have functions in phytohormone translocation(7-9). Here we show that the Petunia hybrida ABC transporter PDR1 has a key role in regulating the development of arbuscular mycorrhizae and axillary branches, by functioning as a cellular strigolactone exporter. P. hybrida pdr1 mutants are defective in strigolactone exudation from their roots, resulting in reduced symbiotic interactions. Above ground, pdr1 mutants have an enhanced branching phenotype, which is indicative of impaired strigolactone allocation. Overexpression of Petunia axillaris PDR1 in Arabidopsis thaliana results in increased tolerance to high concentrations of a synthetic strigolactone, consistent with increased export of strigolactones from the roots. PDR1 is the first known component in strigolactone transport, providing new opportunities for investigating and manipulating strigolactone-dependent processes.
C1 [Kretzschmar, Tobias; Sasse, Joelle; Borghi, Lorenzo; Schlegel, Markus; Bachelier, Julien B.; Martinoia, Enrico] Univ Zurich, Inst Plant Biol, CH-8008 Zurich, Switzerland.
   [Kohlen, Wouter; Bours, Ralph; Bouwmeester, Harro J.] Wageningen Univ, Lab Plant Physiol, NL-6700 AR Wageningen, Netherlands.
   [Reinhardt, Didier] Univ Fribourg, Dept Biol, CH-1700 Fribourg, Switzerland.
   [Bouwmeester, Harro J.] Ctr Biosyst Genom, NL-6700 AB Wageningen, Netherlands.
C3 University of Zurich; Wageningen University & Research; University of Fribourg; Centre for BioSystems Genomics
RP Kretzschmar, T (corresponding author), Univ Zurich, Inst Plant Biol, Zollikerstr 107, CH-8008 Zurich, Switzerland.
EM t.kretzschmar@irri.org
FU Swiss National Foundation within the NCCR; Netherlands Organization for Scientific Research (NWO) [865.06.002, 834.08.001]; Centre for BioSystems Genomics (CBSG)
NR 49
TC 451
Z9 510
U1 6
U2 370
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 15
PY 2012
VL 483
IS 7389
BP 341
EP U135
DI 10.1038/nature10873
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 908HP
UT WOS:000301481800051
PM 22398443
DA 2026-03-09
ER

PT J
AU Heurlin, M
   Magnusson, MH
   Lindgren, D
   Ek, M
   Wallenberg, LR
   Deppert, K
   Samuelson, L
AF Heurlin, Magnus
   Magnusson, Martin H.
   Lindgren, David
   Ek, Martin
   Wallenberg, L. Reine
   Deppert, Knut
   Samuelson, Lars
TI Continuous gas-phase synthesis of nanowires with tunable properties
SO NATURE
LA English
DT Article
ID growth; nanoparticles
AB Semiconductor nanowires are key building blocks for the next generation of light-emitting diodes(1), solar cells(2) and batteries(3). To fabricate functional nanowire-based devices on an industrial scale requires an efficient methodology that enables the mass production of nanowires with perfect crystallinity, reproducible and controlled dimensions and material composition, and low cost. So far there have been no reports of reliable methods that can satisfy all of these requirements. Here we show how aerotaxy, an aerosol-based growth method(4), can be used to grow nanowires continuously with controlled nanoscale dimensions, a high degree of crystallinity and at a remarkable growth rate. In our aerotaxy approach, catalytic size-selected Au aerosol particles induce nucleation and growth of GaAs nanowires with a growth rate of about 1 micrometre per second, which is 20 to 1,000 times higher than previously reported for traditional, substrate-based growth of nanowires made of group III-V materials(5-7). We demonstrate that the method allows sensitive and reproducible control of the nanowire dimensions and shape-and, thus, controlled optical and electronic properties-through the variation of growth temperature, time and Au particle size. Photoluminescence measurements reveal that even as-grown nanowires have good optical properties and excellent spectral uniformity. Detailed transmission electron microscopy investigations show that our aerotaxy-grown nanowires form along one of the four equivalent < 111 > B crystallographic directions in the zincblende unit cell, which is also the preferred growth direction for III-V nanowires seeded by Au particles on a single-crystal substrate. The reported continuous and potentially high-throughput method can be expected substantially to reduce the cost of producing high-quality nanowires and may enable the low-cost fabrication of nanowire-based devices on an industrial scale.
C1 [Heurlin, Magnus; Lindgren, David; Deppert, Knut; Samuelson, Lars] Lund Univ, Div Solid State Phys, S-22100 Lund, Sweden.
   [Magnusson, Martin H.] Sol Volta AB, S-22370 Lund, Sweden.
   [Ek, Martin; Wallenberg, L. Reine] Lund Univ, Div Polymer & Mat Chem, S-22100 Lund, Sweden.
C3 Lund University; Lund University
RP Samuelson, L (corresponding author), Lund Univ, Div Solid State Phys, S-22100 Lund, Sweden.
EM lars.samuelson@ftf.lth.se
FU Swedish Research Council; Swedish Foundation for Strategic Research; Knut and Alice Wallenberg Foundation; VINNOVA
NR 33
TC 152
Z9 175
U1 0
U2 386
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 6
PY 2012
VL 492
IS 7427
BP 90
EP +
DI 10.1038/nature11652
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 048EQ
UT WOS:000311893400051
PM 23201685
DA 2026-03-09
ER

PT J
AU Jiang, XD
   Clark, RA
   Liu, LZ
   Wagers, AJ
   Fuhlbrigge, RC
   Kupper, TS
AF Jiang, Xiaodong
   Clark, Rachael A.
   Liu, Luzheng
   Wagers, Amy J.
   Fuhlbrigge, Robert C.
   Kupper, Thomas S.
TI Skin infection generates non-migratory memory CD8+ TRM cells providing global skin immunity
SO NATURE
LA English
DT Article
ID migration; trafficking; effector; resident; heterogeneity; activation; selectin; tissue
AB Protective T-cell memory has long been thought to reside in blood and lymph nodes, but recently the concept of immune memory in peripheral tissues mediated by resident memory T (T-RM) cells has been proposed(1-5). Here we show in mice that localized vaccinia virus (VACV) skin infection generates long-lived non-recirculating CD8(+) skin T-RM cells that reside within the entire skin. These skin T-RM cells are potent effector cells, and are superior to circulating central memory T (T-CM) cells at providing rapid long-term protection against cutaneous re-infection. We find that CD8(+) T cells are rapidly recruited to skin after acute VACV infection. CD8(+) T-cell recruitment to skin is independent of CD4(+) T cells and interferon-c, but requires the expression of E-and P-selectin ligands by CD8(+) T cells. Using parabiotic mice, we further show that circulating CD8(+) T-CM and CD8(+) skin T-RM cells are both generated after skin infection; however, CD8(+) T-CM cells recirculate between blood and lymph nodes whereas T-RM cells remain in the skin. Cutaneous CD8(+) T-RM cells produce effector cytokines and persist for at least 6 months after infection. Mice with CD8(+) skin T-RM cells rapidly cleared a subsequent re-infection with VACV whereas mice with circulating T-CM but no skin T-RM cells showed greatly impaired viral clearance, indicating that T-RM cells provide superior protection. Finally, we show that T-RM cells generated as a result of localized VACV skin infection reside not only in the site of infection, but also populate the entire skin surface and remain present for many months. Repeated re-infections lead to progressive accumulation of highly protective T-RM cells in non-involved skin. These findings have important implications for our understanding of protective immune memory at epithelial interfaces with the environment, and suggest novel strategies for vaccines that protect against tissue tropic organisms.
C1 [Jiang, Xiaodong; Clark, Rachael A.; Liu, Luzheng; Fuhlbrigge, Robert C.; Kupper, Thomas S.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 USA.
   [Jiang, Xiaodong; Clark, Rachael A.; Liu, Luzheng; Fuhlbrigge, Robert C.; Kupper, Thomas S.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Harvard Skin Dis Res Ctr, Boston, MA 02115 USA.
   [Wagers, Amy J.] Harvard Univ, Howard Hughes Med Inst, Dept Stem Cell & Regenerat Biol, Harvard Stem Cell Inst,Joslin Diabet Ctr, Boston, MA 02115 USA.
C3 Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Joslin Diabetes Center, Inc.; Howard Hughes Medical Institute
RP Kupper, TS (corresponding author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 USA.
EM tkupper@partners.org
FU National Institutes of Health (NIH) [R01AI041707, R37AI025082, TR01AI097128]; National Institute of Arthritis and Musculoskeletal and Skin Diseases [R01AR065807] Funding Source: NIH RePORTER
NR 30
TC 723
Z9 883
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 MAR 8
PY 2012
VL 483
IS 7388
BP 227
EP U129
DI 10.1038/nature10851
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 904DT
UT WOS:000301174900042
PM 22388819
DA 2026-03-09
ER

PT J
AU Page, MJ
   Symeonidis, M
   Vieira, JD
   Altieri, B
   Amblard, A
   Arumugam, V
   Aussel, H
   Babbedge, T
   Blain, A
   Bock, J
   Boselli, A
   Buat, V
   Castro-Rodríguez, N
   Cava, A
   Chanial, P
   Clements, DL
   Conley, A
   Conversi, L
   Cooray, A
   Dowell, CD
   Dubois, EN
   Dunlop, JS
   Dwek, E
   Dye, S
   Eales, S
   Elbaz, D
   Farrah, D
   Fox, M
   Franceschini, A
   Gear, W
   Glenn, J
   Griffin, M
   Halpern, M
   Hatziminaoglou, E
   Ibar, E
   Isaak, K
   Ivison, RJ
   Lagache, G
   Levenson, L
   Lu, N
   Madden, S
   Maffei, B
   Mainetti, G
   Marchetti, L
   Nguyen, HT
   O'Halloran, B
   Oliver, SJ
   Omont, A
   Panuzzo, P
   Papageorgiou, A
   Pearson, CP
   Pérez-Fournon, I
   Pohlen, M
   Rawlings, JI
   Rigopoulou, D
   Riguccini, L
   Rizzo, D
   Rodighiero, G
   Roseboom, IG
   Rowan-Robinson, M
   Portal, MS
   Schulz, B
   Scott, D
   Seymour, N
   Shupe, DL
   Smith, AJ
   Stevens, JA
   Trichas, M
   Tugwell, KE
   Vaccari, M
   Valtchanov, I
   Viero, M
   Vigroux, L
   Wang, L
   Ward, R
   Wright, G
   Xu, CK
   Zemcov, M
AF Page, M. J.
   Symeonidis, M.
   Vieira, J. D.
   Altieri, B.
   Amblard, A.
   Arumugam, V.
   Aussel, H.
   Babbedge, T.
   Blain, A.
   Bock, J.
   Boselli, A.
   Buat, V.
   Castro-Rodriguez, N.
   Cava, A.
   Chanial, P.
   Clements, D. L.
   Conley, A.
   Conversi, L.
   Cooray, A.
   Dowell, C. D.
   Dubois, E. N.
   Dunlop, J. S.
   Dwek, E.
   Dye, S.
   Eales, S.
   Elbaz, D.
   Farrah, D.
   Fox, M.
   Franceschini, A.
   Gear, W.
   Glenn, J.
   Griffin, M.
   Halpern, M.
   Hatziminaoglou, E.
   Ibar, E.
   Isaak, K.
   Ivison, R. J.
   Lagache, G.
   Levenson, L.
   Lu, N.
   Madden, S.
   Maffei, B.
   Mainetti, G.
   Marchetti, L.
   Nguyen, H. T.
   O'Halloran, B.
   Oliver, S. J.
   Omont, A.
   Panuzzo, P.
   Papageorgiou, A.
   Pearson, C. P.
   Perez-Fournon, I.
   Pohlen, M.
   Rawlings, J. I.
   Rigopoulou, D.
   Riguccini, L.
   Rizzo, D.
   Rodighiero, G.
   Roseboom, I. G.
   Rowan-Robinson, M.
   Sanchez Portal, M.
   Schulz, B.
   Scott, D.
   Seymour, N.
   Shupe, D. L.
   Smith, A. J.
   Stevens, J. A.
   Trichas, M.
   Tugwell, K. E.
   Vaccari, M.
   Valtchanov, I.
   Viero, M.
   Vigroux, L.
   Wang, L.
   Ward, R.
   Wright, G.
   Xu, C. K.
   Zemcov, M.
TI The suppression of star formation by powerful active galactic nuclei
SO NATURE
LA English
DT Article
ID black-holes; galaxy formation; agn; outflows; feedback; catalogs; quasars; fields; growth; model
AB The old, red stars that constitute the bulges of galaxies, and the massive black holes at their centres, are the relics of a period in cosmic history when galaxies formed stars at remarkable rates and active galactic nuclei (AGN) shone brightly as a result of accretion onto black holes. It is widely suspected, but unproved, that the tight correlation between the mass of the black hole and the mass of the stellar bulge(1) results from the AGN quenching the surrounding star formation as it approaches its peak luminosity(2-4). X-rays trace emission from AGN unambiguously(5), whereas powerful star-forming galaxies are usually dust-obscured and are brightest at infrared and submillimetre wavelengths(6). Here we report submillimetre and X-ray observations that show that rapid star formation was common in the host galaxies of AGN when the Universe was 2-6 billion years old, but that the most vigorous star formation is not observed around black holes above an X-ray luminosity of 10(44) ergs per second. This suppression of star formation in the host galaxy of a powerful AGN is a key prediction of models in which the AGN drives an outflow(7-9), expelling the interstellar medium of its host and transforming the galaxy's properties in a brief period of cosmic time.
C1 [Page, M. J.; Symeonidis, M.; Rawlings, J. I.; Seymour, N.; Tugwell, K. E.] Univ Coll London, Mullard Space Sci Lab, Dorking RH5 6NT, Surrey, England.
   [Altieri, B.; Conversi, L.; Sanchez Portal, M.; Valtchanov, I.] European Space Astron Ctr, Herschel Sci Ctr, Madrid 28691, Spain.
   [Amblard, A.] NASA, Ames Res Ctr, Moffett Field, CA 94035 USA.
   [Arumugam, V.; Dunlop, J. S.; Ivison, R. J.; Roseboom, I. G.] Univ Edinburgh, Inst Astron, Royal Observ, Edinburgh EH9 3HJ, Midlothian, Scotland.
   [Aussel, H.; Chanial, P.; Elbaz, D.; Madden, S.; Panuzzo, P.; Riguccini, L.] Univ Paris Diderot, CE Saclay, CEA DSM IRFU, CNRS,Lab AIM Paris Saclay, F-91191 Gif Sur Yvette, France.
   [Babbedge, T.; Clements, D. L.; Fox, M.; O'Halloran, B.; Rizzo, D.; Rowan-Robinson, M.] Univ London Imperial Coll Sci Technol & Med, Blackett Lab, Astrophys Grp, London SW7 2AZ, England.
   [Blain, A.] Univ Leicester, Dept Phys & Astron, Leicester LE1 7RH, Leics, England.
   [Bock, J.; Dowell, C. D.; Levenson, L.; Nguyen, H. T.; Zemcov, M.] CALTECH, Jet Prop Lab, Pasadena, CA 91109 USA.
   [Boselli, A.; Buat, V.] Univ Aix Marseille, CNRS, OAMP, Lab Astrophys Marseille, F-13388 Marseille 13, France.
   [Castro-Rodriguez, N.; Perez-Fournon, I.] Inst Astrofis Canarias, E-38200 San Cristobal la Laguna, Tenerife, Spain.
   [Castro-Rodriguez, N.; Perez-Fournon, I.] Univ La Laguna, Dept Astrofis, E-38205 Tenerife, Spain.
   [Cava, A.] Univ Complutense Madrid, Fac CC Fis, Dept Astrofis, E-28040 Madrid, Spain.
   [Conley, A.; Glenn, J.] Univ Colorado, Ctr Astrophys & Space Astron UCB 389, Boulder, CO 80309 USA.
   [Cooray, A.] Univ Calif Irvine, Dept Phys & Astron, Irvine, CA 92697 USA.
   [Dubois, E. N.; Farrah, D.; Oliver, S. J.; Roseboom, I. G.; Smith, A. J.; Wang, L.; Ward, R.] Univ Sussex, Dept Phys & Astron, Ctr Astron, Brighton BN1 9QH, E Sussex, England.
   [Dwek, E.] NASA, Goddard Space Flight Ctr, Observat Cosmol Lab, Greenbelt, MD 20771 USA.
   [Dye, S.] Univ Nottingham, Sch Phys & Astron, Nottingham NG7 2RD, England.
   [Eales, S.; Gear, W.; Griffin, M.; Papageorgiou, A.; Pohlen, M.] Cardiff Univ, Sch Phys & Astron, Cardiff CF24 3AA, S Glam, Wales.
   [Franceschini, A.; Mainetti, G.; Marchetti, L.; Rodighiero, G.; Vaccari, M.] Univ Padua, Dipartimento Astron, I-35122 Padua, Italy.
   [Glenn, J.] Univ Colorado, Dept Astrophys & Planetary Sci, CASA UCB 389, Boulder, CO 80309 USA.
   [Halpern, M.; Scott, D.] Univ British Columbia, Dept Phys & Astron, Vancouver, BC V6T 1Z1, Canada.
   [Hatziminaoglou, E.] ESO, D-85748 Garching, Germany.
   [Ibar, E.; Ivison, R. J.; Wright, G.] Royal Observ, UK Astron Technol Ctr, Edinburgh EH9 3HJ, Midlothian, Scotland.
   [Isaak, K.] European Space Res & Technol Ctr ESTEC, NL-2201 AZ Noordwijk, Netherlands.
   [Lagache, G.] Univ Paris 11, IAS, F-91405 Orsay, France.
   [Lagache, G.] CNRS, UMR 8617, F-91405 Orsay, France.
   [Lu, N.; Schulz, B.; Shupe, D. L.; Xu, C. K.] CALTECH, JPL, Ctr Infrared Proc & Anal, Pasadena, CA 91125 USA.
   [Maffei, B.] Univ Manchester, Sch Phys & Astron, Manchester M13 9PL, Lancs, England.
   [Omont, A.; Vigroux, L.] Univ Paris 06, CNRS, UMR 7095, Inst Astrophys Paris, F-75014 Paris, France.
   [Pearson, C. P.; Rigopoulou, D.] Rutherford Appleton Lab, RAL Space, Didcot OX11 0QX, Oxon, England.
   [Pearson, C. P.] Univ Lethbridge, Inst Space Imaging Sci, Lethbridge, AB T1K 3M4, Canada.
   [Rigopoulou, D.] Univ Oxford, Dept Astrophys, Oxford OX1 3RH, England.
   [Seymour, N.] CSIRO Astron & Space Sci, Epping, NSW 1710, Australia.
   [Stevens, J. A.] Univ Hertfordshire, Ctr Astrophys Res, Hatfield AL10 9AB, Herts, England.
   [Trichas, M.] Harvard Smithsonian Ctr Astrophys, Cambridge, MA 02138 USA.
C3 University of London; University College London; European Space Agency; European Space Astronomy Center; National Aeronautics & Space Administration (NASA); NASA Ames Research Center; University of Edinburgh; CEA; Centre National de la Recherche Scientifique (CNRS); Universite Paris Cite; Universite Paris Saclay; Imperial College London; University of Leicester; National Aeronautics & Space Administration (NASA); NASA Jet Propulsion Laboratory (JPL); California Institute of Technology; Aix-Marseille Universite; Centre National de la Recherche Scientifique (CNRS); Instituto de Astrofisica de Canarias; Universidad de la Laguna; Complutense University of Madrid; University of Colorado System; University of Colorado Boulder; University of California System; University of California Irvine; University of Sussex; National Aeronautics & Space Administration (NASA); NASA Goddard Space Flight Center; University of Nottingham; Cardiff University; University of Padua; University of Colorado System; University of Colorado Boulder; University of British Columbia; University of Edinburgh; European Space Agency; European Space Research & Technology Centre; Universite Paris Saclay; Universite Paris Saclay; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Earth Sciences & Astronomy (INSU); National Aeronautics & Space Administration (NASA); NASA Jet Propulsion Laboratory (JPL); California Institute of Technology; University of Manchester; Sorbonne Universite; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Earth Sciences & Astronomy (INSU); UK Research & Innovation (UKRI); Science & Technology Facilities Council (STFC); STFC Rutherford Appleton Laboratory; University of Lethbridge; University of Oxford; Commonwealth Scientific & Industrial Research Organisation (CSIRO); CSIRO Astronomy & Space; University of Hertfordshire; Smithsonian Institution; Smithsonian Astrophysical Observatory; Harvard University
RP Page, MJ (corresponding author), Univ Coll London, Mullard Space Sci Lab, Holmbury St Mary, Dorking RH5 6NT, Surrey, England.
EM mjp@mssl.ucl.ac.uk
FU CSA (Canada); NAOC (China); CEA (France); CNES (France); CNRS (France); ASI (Italy); MCINN(Spain); SNSB(Sweden); STFC (UK); UKSA (UK); NASA (USA); STFC [ST/H00260X/1, ST/G002630/1, ST/I005765/1, ST/H002456/1, ST/H001530/1, ST/I001212/1, ST/J001449/1, ST/G001979/1, ST/J001562/1, ST/I000976/1, ST/F007019/1] Funding Source: UKRI; Science and Technology Facilities Council [ST/I001212/1, ST/H002456/1, ST/I000976/1, ST/J001562/1, ST/G002630/1, ST/H001530/1, ST/H00260X/1, ST/F007019/1, ST/I005765/1, ST/J001449/1, ST/G001979/1] Funding Source: researchfish; UK Space Agency [ST/G003874/1, ST/F012373/1, ST/J004812/1] Funding Source: researchfish; Direct For Mathematical & Physical Scien; Division Of Astronomical Sciences [0909159] Funding Source: National Science Foundation
NR 29
TC 187
Z9 212
U1 0
U2 11
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD MAY 10
PY 2012
VL 485
IS 7397
BP 213
EP 216
DI 10.1038/nature11096
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 939HJ
UT WOS:000303799800035
PM 22575961
DA 2026-03-09
ER

PT J
AU Russell, JK
   Porritt, LA
   Lavallée, Y
   Dingwell, DB
AF Russell, James K.
   Porritt, Lucy A.
   Lavallee, Yan
   Dingwell, Donald B.
TI Kimberlite ascent by assimilation-fuelled buoyancy
SO NATURE
LA English
DT Article
ID system cao-mgo-al2o3-sio2-co2; slave craton; constraints; magma; dissolution; lherzolite; peridotite; xenoliths; petrology; carbonate
AB Kimberlite magmas have the deepest origin of all terrestrial magmas and are exclusively associated with cratons(1-3). During ascent, they travel through about 150 kilometres of cratonic mantle lithosphere and entrain seemingly prohibitive loads (more than 25 per cent by volume) of mantle-derived xenoliths and xenocrysts (including diamond)(4,5). Kimberlite magmas also reputedly have higher ascent rates(6-9) than other xenolith-bearing magmas(10,11). Exsolution of dissolved volatiles (carbon dioxide and water) is thought to be essential to provide sufficient buoyancy for the rapid ascent of these dense, crystal-rich magmas. The cause and nature of such exsolution, however, remains elusive and is rarely specified(6,9). Here we use a series of high-temperature experiments to demonstrate a mechanism for the spontaneous, efficient and continuous production of this volatile phase. This mechanism requires parental melts of kimberlite to originate as carbonatite-like melts. In transit through the mantle lithosphere, these silica-undersaturated melts assimilate mantle minerals, especially orthopyroxene, driving the melt to more silicic compositions, and causing a marked drop in carbon dioxide solubility. The solubility drop manifests itself immediately in a continuous and vigorous exsolution of a fluid phase, thereby reducing magma density, increasing buoyancy, and driving the rapid and accelerating ascent of the increasingly kimberlitic magma. Our model provides an explanation for continuous ascent of magmas laden with high volumes of dense mantle cargo, an explanation for the chemical diversity of kimberlite, and a connection between kimberlites and cratons.
C1 [Russell, James K.; Porritt, Lucy A.] Univ British Columbia, Volcanol & Petrol Lab, Vancouver, BC V6T 1Z4, Canada.
   [Lavallee, Yan; Dingwell, Donald B.] Univ Munich, Dept Earth & Environm Sci, D-80333 Munich, Germany.
C3 University of British Columbia; University of Munich
RP Russell, JK (corresponding author), Univ British Columbia, Volcanol & Petrol Lab, Vancouver, BC V6T 1Z4, Canada.
EM krussell@eos.ubc.ca
FU Natural Sciences and Engineering Research Council; Marie Curie outbound fellowship; ERC
NR 36
TC 263
Z9 293
U1 6
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 JAN 19
PY 2012
VL 481
IS 7381
BP 352
EP U133
DI 10.1038/nature10740
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 877VK
UT WOS:000299210600040
PM 22258614
DA 2026-03-09
ER

PT J
AU Zikherman, J
   Parameswaran, R
   Weiss, A
AF Zikherman, Julie
   Parameswaran, Ramya
   Weiss, Arthur
TI Endogenous antigen tunes the responsiveness of naive B cells but not T cells
SO NATURE
LA English
DT Article
ID self-tolerance; expression; cd45; activation; resolution; selection; anergy; mouse
AB In humans, up to 75% of newly generated B cells and about 30% of mature B cells show some degree of autoreactivity(1). Yet, how B cells establish and maintain tolerance in the face of autoantigen exposure during and after development is not certain. Studies of model B-cell antigen receptor (BCR) transgenic systems have highlighted the critical role of functional unresponsiveness or 'anergy'(2,3). Unlike T cells, evidence suggests that receptor editing and anergy, rather than deletion, account for much of B-cell tolerance(4,5). However, it remains unclear whether the mature diverse B-cell repertoire of mice contains anergic autoreactive B cells, and if so, whether antigen was encountered during or after their development. By taking advantage of a reporter mouse in which BCR signalling rapidly and robustly induces green fluorescent protein expression under the control of the Nur77 regulatory region, antigen-dependent and antigen-independent BCR signalling events in vivo during B-cell maturation were visualized. Here we show that B cells encounter antigen during development in the spleen, and that this antigen exposure, in turn, tunes the responsiveness of BCR signalling in B cells at least partly by downmodulating expression of surface IgM but not IgD BCRs, and by modifying basal calcium levels. By contrast, no analogous process occurs in naive mature T cells. Our data demonstrate not only that autoreactive B cells persist in the mature repertoire, but that functional unresponsiveness or anergy exists in the mature B-cell repertoire along a continuum, a fact that has long been suspected, but never yet shown. These results have important implications for understanding how tolerance in T and B cells is differently imposed, and how these processes might go awry in disease.
C1 [Zikherman, Julie; Parameswaran, Ramya; Weiss, Arthur] Univ Calif San Francisco, Rosalind Russell Med Res Ctr Arthrit, Dept Med, Div Rheumatol, San Francisco, CA 94143 USA.
   [Weiss, Arthur] Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94143 USA.
C3 University of California System; University of California San Francisco; Howard Hughes Medical Institute; University of California System; University of California San Francisco
RP Weiss, A (corresponding author), Univ Calif San Francisco, Rosalind Russell Med Res Ctr Arthrit, Dept Med, Div Rheumatol, San Francisco, CA 94143 USA.
EM aweiss@medicine.ucsf.edu
FU Rosalind Russell Medical Research Foundation Bechtel Award; American College of Rheumatology REF Rheumatology Investigator Award; Arthritis National Research Foundation; National Institutes of Health [K08 AR059723]; Howard Hughes Medical Institute
NR 29
TC 261
Z9 317
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 SEP 6
PY 2012
VL 489
IS 7414
BP 160
EP U185
DI 10.1038/nature11311
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 999WW
UT WOS:000308347000055
PM 22902503
DA 2026-03-09
ER

PT J
AU Tarruell, L
   Greif, D
   Uehlinger, T
   Jotzu, G
   Esslinger, T
AF Tarruell, Leticia
   Greif, Daniel
   Uehlinger, Thomas
   Jotzu, Gregor
   Esslinger, Tilman
TI Creating, moving and merging Dirac points with a Fermi gas in a tunable honeycomb lattice
SO NATURE
LA English
DT Article
ID quantum phase-transition; optical lattices; mott insulator; atoms; physics
AB Dirac points are central to many phenomena in condensed-matter physics, from massless electrons in graphene to the emergence of conducting edge states in topological insulators(1,2). At a Dirac point, two energy bands intersect linearly and the electrons behave as relativistic Dirac fermions. In solids, the rigid structure of the material determines the mass and velocity of the electrons, as well as their interactions. A different, highly flexible means of studying condensed-matter phenomena is to create model systems using ultracold atoms trapped in the periodic potential of interfering laser beams(3,4). Here we report the creation of Dirac points with adjustable properties in a tunable honeycomb optical lattice. Using momentum-resolved interband transitions, we observe a minimum bandgap inside the Brillouin zone at the positions of the two Dirac points. We exploit the unique tunability of our lattice potential to adjust the effective mass of the Dirac fermions by breaking inversion symmetry. Moreover, changing the lattice anisotropy allows us to change the positions of the Dirac points inside the Brillouin zone. When the anisotropy exceeds a critical limit, the two Dirac points merge and annihilate each other-a situation that has recently attracted considerable theoretical interest(5-9) but that is extremely challenging to observe in solids(10). We map out this topological transition in lattice parameter space and find excellent agreement with ab initio calculations. Our results not only pave the way to model materials in which the topology of the band structure is crucial, but also provide an avenue to exploring many-body phases resulting from the interplay of complex lattice geometries with interactions(11-13).
C1 [Tarruell, Leticia; Greif, Daniel; Uehlinger, Thomas; Jotzu, Gregor; 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-MaNEP; NCCR-QSIT; NAME-QUAM (EU, FET open); SQMS; ESF (POLATOM)
NR 30
TC 841
Z9 903
U1 1
U2 257
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 15
PY 2012
VL 483
IS 7389
BP 302
EP +
DI 10.1038/nature10871
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 908HP
UT WOS:000301481800042
PM 22422263
DA 2026-03-09
ER

PT J
AU Erler, J
   Birge, N
   Kortelainen, M
   Nazarewicz, W
   Olsen, E
   Perhac, AM
   Stoitsov, M
AF Erler, Jochen
   Birge, Noah
   Kortelainen, Markus
   Nazarewicz, Witold
   Olsen, Erik
   Perhac, Alexander M.
   Stoitsov, Mario
TI The limits of the nuclear landscape
SO NATURE
LA English
DT Article
ID ground-state property
AB In 2011, 100 new nuclides were discovered(1). They joined the approximately 3,000 stable and radioactive nuclides that either occur naturally on Earth or are synthesized in the laboratory(2,3). Every atomic nucleus, characterized by a specific number of protons and neutrons, occupies a spot on the chart of nuclides, which is bounded by 'drip lines' indicating the values of neutron and proton number at which nuclear binding ends. The placement of the neutron drip line for the heavier elements is based on theoretical predictions using extreme extrapolations, and so is uncertain. However, it is not known how uncertain it is or how many protons and neutrons can be bound in a nucleus. Here we estimate these limits of the nuclear 'landscape' and provide statistical and systematic uncertainties for our predictions. We use nuclear density functional theory, several Skyrme interactions and high-performance computing, and find that the number of bound nuclides with between 2 and 120 protons is around 7,000. We find that extrapolations for drip-line positions and selected nuclear properties, including neutron separation energies relevant to astrophysical processes, are very consistent between the models used.
C1 [Erler, Jochen; Birge, Noah; Kortelainen, Markus; Nazarewicz, Witold; Olsen, Erik; Perhac, Alexander M.; Stoitsov, Mario] Univ Tennessee, Dept Phys & Astron, Knoxville, TN 37996 USA.
   [Erler, Jochen; Kortelainen, Markus; Nazarewicz, Witold; Olsen, Erik; Stoitsov, Mario] Oak Ridge Natl Lab, Div Phys, Oak Ridge, TN 37831 USA.
   [Kortelainen, Markus] Univ Jyvaskyla, Dept Phys, FI-40014 Jyvaskyla, Finland.
   [Nazarewicz, Witold] Univ Warsaw, Inst Theoret Phys, PL-00681 Warsaw, Poland.
C3 University of Tennessee System; University of Tennessee Knoxville; United States Department of Energy (DOE); Oak Ridge National Laboratory; University of Jyvaskyla; University of Warsaw
RP Nazarewicz, W (corresponding author), Univ Tennessee, Dept Phys & Astron, Knoxville, TN 37996 USA.
EM witek@utk.edu
FU Office of Nuclear Physics, US Department of Energy; Academy of Finland
NR 30
TC 412
Z9 485
U1 2
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 28
PY 2012
VL 486
IS 7404
BP 509
EP 512
DI 10.1038/nature11188
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 965IJ
UT WOS:000305760600038
PM 22739315
DA 2026-03-09
ER

PT J
AU Logothetis, NK
   Eschenko, O
   Murayama, Y
   Augath, M
   Steudel, T
   Evrard, HC
   Besserve, M
   Oeltermann, A
AF Logothetis, N. K.
   Eschenko, O.
   Murayama, Y.
   Augath, M.
   Steudel, T.
   Evrard, H. C.
   Besserve, M.
   Oeltermann, A.
TI Hippocampal-cortical interaction during periods of subcortical silence
SO NATURE
LA English
DT Article
ID slow-wave sleep; training reversible inactivation; memory-systems; declarative memory; sharp waves; ripples; oscillation; consolidation; reactivation; state
AB Hippocampal ripples, episodic high-frequency field-potential oscillations primarily occurring during sleep and calmness, have been described in mice, rats, rabbits, monkeys and humans, and so far they have been associated with retention of previously acquired awake experience. Although hippocampal ripples have been studied in detail using neurophysiological methods, the global effects of ripples on the entire brain remain elusive, primarily owing to a lack of methodologies permitting concurrent hippocampal recordings and whole-brain activity mapping. By combining electrophysiological recordings in hippocampus with ripple-triggered functional magnetic resonance imaging, here we show that most of the cerebral cortex is selectively activated during the ripples, whereas most diencephalic, midbrain and brainstem regions are strongly and consistently inhibited. Analysis of regional temporal response patterns indicates that thalamic activity suppression precedes the hippocampal population burst, which itself is temporally bounded by massive activations of association and primary cortical areas. These findings suggest that during off-line memory consolidation, synergistic thalamocortical activity may be orchestrating a privileged interaction state between hippocampus and cortex by silencing the output of subcortical centres involved in sensory processing or potentially mediating procedural learning. Such a mechanism would cause minimal interference, enabling consolidation of hippocampus-dependent memory.
C1 [Logothetis, N. K.; Eschenko, O.; Murayama, Y.; Augath, M.; Steudel, T.; Evrard, H. C.; Besserve, M.; Oeltermann, A.] Max Planck Inst Biol Cybernet, D-72076 Tubingen, Germany.
   [Logothetis, N. K.] Univ Manchester, Biomed Imaging Inst, Ctr Imaging Sci, Manchester M13 9PT, Lancs, England.
   [Besserve, M.] Max Planck Inst Intelligent Syst, D-72076 Tubingen, Germany.
C3 Max Planck Society; University of Manchester; Max Planck Society
RP Logothetis, NK (corresponding author), Max Planck Inst Biol Cybernet, Spemannstr 38, D-72076 Tubingen, Germany.
EM Nikos.Logothetis@tuebingen.mpg.de
FU Max Planck Society
NR 50
TC 323
Z9 393
U1 0
U2 66
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD NOV 22
PY 2012
VL 491
IS 7425
BP 547
EP 553
DI 10.1038/nature11618
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 040RE
UT WOS:000311339800042
PM 23172213
DA 2026-03-09
ER

PT J
AU Papadopoulos, F
   Kitsak, M
   Serrano, MA
   Boguñá, M
   Krioukov, D
AF Papadopoulos, Fragkiskos
   Kitsak, Maksim
   Angeles Serrano, M.
   Boguna, Marian
   Krioukov, Dmitri
TI Popularity versus similarity in growing networks
SO NATURE
LA English
DT Article
ID preferential attachment; emergence; evolution; paper
AB The principle(1) that 'popularity is attractive' underlies preferential attachment(2), which is a common explanation for the emergence of scaling in growing networks. If new connections are made preferentially to more popular nodes, then the resulting distribution of the number of connections possessed by nodes follows power laws(3,4), as observed in many real networks(5,6). Preferential attachment has been directly validated for some real networks (including the Internet(7,8)), and can be a consequence of different underlying processes based on node fitness, ranking, optimization, random walks or duplication(9-16). Here we show that popularity is just one dimension of attractiveness; another dimension is similarity(17-24). We develop a framework in which new connections optimize certain trade-offs between popularity and similarity, instead of simply preferring popular nodes. The framework has a geometric interpretation in which popularity preference emerges from local optimization. As opposed to preferential attachment, our optimization framework accurately describes the large-scale evolution of technological (the Internet), social (trust relationships between people) and biological (Escherichia coli metabolic) networks, predicting the probability of new links with high precision. The framework that we have developed can thus be used for predicting new links in evolving networks, and provides a different perspective on preferential attachment as an emergent phenomenon.
C1 [Papadopoulos, Fragkiskos] Cyprus Univ Technol, Dept Elect Engn Comp Engn & Informat, CY-3036 Limassol, Cyprus.
   [Kitsak, Maksim; Krioukov, Dmitri] Univ Calif San Diego, CAIDA, La Jolla, CA 92093 USA.
   [Angeles Serrano, M.; Boguna, Marian] Univ Barcelona, Dept Fis Fonamental, E-08028 Barcelona, Spain.
C3 Cyprus University of Technology; University of California System; University of California San Diego; University of Barcelona
RP Papadopoulos, F (corresponding author), Cyprus Univ Technol, Dept Elect Engn Comp Engn & Informat, 33 Saripolou St, CY-3036 Limassol, Cyprus.
EM f.papadopoulos@cut.ac.cy; dima@ucsd.edu
FU Marie Curie International Reintegration Grant within the 7th European Community Framework Programme; MICINN [FIS2010-21781-C02-02, BFU2010-21847-C02-02]; Generalitat de Catalunya [2009SGR838]; Ramon y Cajal programme of the Spanish Ministry of Science; ICREA Academia; Generalitat de Catalunya; NSF [CNS-0964236, CNS-1039646, CNS-0722070]; DHS [N66001-08-C-2029]; DARPA [HR0011-12-1-0012]; Cisco Systems; Division Of Computer and Network Systems; Direct For Computer & Info Scie & Enginr [1039646, 0964236] Funding Source: National Science Foundation
NR 30
TC 479
Z9 552
U1 3
U2 171
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 27
PY 2012
VL 489
IS 7417
BP 537
EP 540
DI 10.1038/nature11459
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 011LT
UT WOS:000309167100044
PM 22972194
DA 2026-03-09
ER

PT J
AU Hughes, AL
   Gottschling, DE
AF Hughes, Adam L.
   Gottschling, Daniel E.
TI An early age increase in vacuolar pH limits mitochondrial function and lifespan in yeast
SO NATURE
LA English
DT Article
ID saccharomyces-cerevisiae; calorie restriction; h+-atpase; proteins; mechanisms; membrane; inheritance; morphology; exchanger; insights
AB Mitochondria have a central role in ageing. They are considered to be both a target of the ageing process and a contributor to it(1). Alterations in mitochondrial structure and function are evident during ageing in most eukaryotes(2), but how this occurs is poorly understood. Here we identify a functional link between the lysosome-like vacuole and mitochondria in Saccharomyces cerevisiae, and show that mitochondrial dysfunction in replicatively aged yeast arises from altered vacuolar pH. We found that vacuolar acidity declines during the early asymmetric divisions of a mother cell, and that preventing this decline suppresses mitochondrial dysfunction and extends lifespan. Surprisingly, changes in vacuolar pH do not limit mitochondrial function by disrupting vacuolar protein degradation, but rather by reducing pH-dependent amino acid storage in the vacuolar lumen. We also found that calorie restriction promotes lifespan extension at least in part by increasing vacuolar acidity via conserved nutrient-sensing pathways(3). Interestingly, although vacuolar acidity is reduced in aged mother cells, acidic vacuoles are regenerated in newborn daughters, coinciding with daughter cells having a renewed lifespan potential(4). Overall, our results identify vacuolar pH as a critical regulator of ageing and mitochondrial function, and outline a potentially conserved mechanism by which calorie restriction delays the ageing process. Because the functions of the vacuole are highly conserved throughout evolution(5), we propose that lysosomal pH may modulate mitochondrial function and lifespan in other eukaryotic cells.
C1 [Hughes, Adam L.; Gottschling, Daniel E.] Fred Hutchinson Canc Res Ctr, Div Basic Sci, Seattle, WA 98109 USA.
C3 Fred Hutchinson Cancer Center
RP Gottschling, DE (corresponding author), Fred Hutchinson Canc Res Ctr, Div Basic Sci, Seattle, WA 98109 USA.
EM dgottsch@fhcrc.org
FU National Institutes of Health [AG037512, AG023779]; Glenn Award for Research in Biological Mechanisms of Aging; Helen Hay Whitney Foundation; Genetic Approaches to Aging Training Grant [T32 AG000057]; National Cancer Institute [P30CA015704] Funding Source: NIH RePORTER
NR 41
TC 430
Z9 525
U1 2
U2 99
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 13
PY 2012
VL 492
IS 7428
BP 261
EP +
DI 10.1038/nature11654
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 053GM
UT WOS:000312259300044
PM 23172144
DA 2026-03-09
ER

PT J
AU Groenen, MAM
   Archibald, AL
   Uenishi, H
   Tuggle, CK
   Takeuchi, Y
   Rothschild, MF
   Rogel-Gaillard, C
   Park, C
   Milan, D
   Megens, HJ
   Li, ST
   Larkin, DM
   Kim, H
   Frantz, LAF
   Caccamo, M
   Ahn, H
   Aken, BL
   Anselmo, A
   Anthon, C
   Auvil, L
   Badaoui, B
   Beattie, CW
   Bendixen, C
   Berman, D
   Blecha, F
   Blomberg, J
   Bolund, L
   Bosse, M
   Botti, S
   Zhan, BJ
   Bystrom, M
   Capitanu, B
   Carvalho-Silva, D
   Chardon, P
   Chen, C
   Cheng, R
   Choi, SH
   Chow, W
   Clark, RC
   Clee, C
   Crooijmans, RPMA
   Dawson, HD
   Dehais, P
   De Sapio, F
   Dibbits, B
   Drou, N
   Du, ZQ
   Eversole, K
   Fadista, J
   Fairley, S
   Faraut, T
   Faulkner, GJ
   Fowler, KE
   Fredholm, M
   Fritz, E
   Gilbert, JGR
   Giuffra, E
   Gorodkin, J
   Griffin, DK
   Harrow, JL
   Hayward, A
   Howe, K
   Hu, ZL
   Humphray, SJ
   Hunt, T
   Hornshoj, H
   Jeon, JT
   Jern, P
   Jones, M
   Jurka, J
   Kanamori, H
   Kapetanovic, R
   Kim, J
   Kim, JH
   Kim, KW
   Kim, TH
   Larson, G
   Lee, K
   Lee, KT
   Leggett, R
   Lewin, HA
   Li, YR
   Liu, WS
   Loveland, JE
   Lu, Y
   Lunney, JK
   Ma, J
   Madsen, O
   Mann, K
   Matthews, L
   McLaren, S
   Morozumi, T
   Murtaugh, MP
   Narayan, J
   Nguyen, DT
   Ni, PX
   Oh, SJ
   Onteru, S
   Panitz, F
   Park, EW
   Park, HS
   Pascal, G
   Paudel, Y
   Perez-Enciso, M
   Ramirez-Gonzalez, R
   Reecy, JM
   Rodriguez-Zas, S
   Rohrer, GA
   Rund, L
   Sang, YM
   Schachtschneider, K
   Schraiber, JG
   Schwartz, J
   Scobie, L
   Scott, C
   Searle, S
   Servin, B
   Southey, BR
   Sperber, G
   Stadler, P
   Sweedler, JV
   Tafer, H
   Thomsen, B
   Wali, R
   Wang, J
   Wang, J
   White, S
   Xu, X
   Yerle, M
   Zhang, GJ
   Zhang, JG
   Zhang, J
   Zhao, SH
   Rogers, J
   Churcher, C
   Schook, LB
AF Groenen, Martien A. M.
   Archibald, Alan L.
   Uenishi, Hirohide
   Tuggle, Christopher K.
   Takeuchi, Yasuhiro
   Rothschild, Max F.
   Rogel-Gaillard, Claire
   Park, Chankyu
   Milan, Denis
   Megens, Hendrik-Jan
   Li, Shengting
   Larkin, Denis M.
   Kim, Heebal
   Frantz, Laurent A. F.
   Caccamo, Mario
   Ahn, Hyeonju
   Aken, Bronwen L.
   Anselmo, Anna
   Anthon, Christian
   Auvil, Loretta
   Badaoui, Bouabid
   Beattie, Craig W.
   Bendixen, Christian
   Berman, Daniel
   Blecha, Frank
   Blomberg, Jonas
   Bolund, Lars
   Bosse, Mirte
   Botti, Sara
   Zhan Bujie
   Bystrom, Megan
   Capitanu, Boris
   Carvalho-Silva, Denise
   Chardon, Patrick
   Chen, Celine
   Cheng, Ryan
   Choi, Sang-Haeng
   Chow, William
   Clark, Richard C.
   Clee, Christopher
   Crooijmans, Richard P. M. A.
   Dawson, Harry D.
   Dehais, Patrice
   De Sapio, Fioravante
   Dibbits, Bert
   Drou, Nizar
   Du, Zhi-Qiang
   Eversole, Kellye
   Fadista, Joao
   Fairley, Susan
   Faraut, Thomas
   Faulkner, Geoffrey J.
   Fowler, Katie E.
   Fredholm, Merete
   Fritz, Eric
   Gilbert, James G. R.
   Giuffra, Elisabetta
   Gorodkin, Jan
   Griffin, Darren K.
   Harrow, Jennifer L.
   Hayward, Alexander
   Howe, Kerstin
   Hu, Zhi-Liang
   Humphray, Sean J.
   Hunt, Toby
   Hornshoj, Henrik
   Jeon, Jin-Tae
   Jern, Patric
   Jones, Matthew
   Jurka, Jerzy
   Kanamori, Hiroyuki
   Kapetanovic, Ronan
   Kim, Jaebum
   Kim, Jae-Hwan
   Kim, Kyu-Won
   Kim, Tae-Hun
   Larson, Greger
   Lee, Kyooyeol
   Lee, Kyung-Tai
   Leggett, Richard
   Lewin, Harris A.
   Li, Yingrui
   Liu, Wansheng
   Loveland, Jane E.
   Lu, Yao
   Lunney, Joan K.
   Ma, Jian
   Madsen, Ole
   Mann, Katherine
   Matthews, Lucy
   McLaren, Stuart
   Morozumi, Takeya
   Murtaugh, Michael P.
   Narayan, Jitendra
   Dinh Truong Nguyen
   Ni, Peixiang
   Oh, Song-Jung
   Onteru, Suneel
   Panitz, Frank
   Park, Eung-Woo
   Park, Hong-Seog
   Pascal, Geraldine
   Paudel, Yogesh
   Perez-Enciso, Miguel
   Ramirez-Gonzalez, Ricardo
   Reecy, James M.
   Rodriguez-Zas, Sandra
   Rohrer, Gary A.
   Rund, Lauretta
   Sang, Yongming
   Schachtschneider, Kyle
   Schraiber, Joshua G.
   Schwartz, John
   Scobie, Linda
   Scott, Carol
   Searle, Stephen
   Servin, Bertrand
   Southey, Bruce R.
   Sperber, Goran
   Stadler, Peter
   Sweedler, Jonathan V.
   Tafer, Hakim
   Thomsen, Bo
   Wali, Rashmi
   Wang, Jian
   Wang, Jun
   White, Simon
   Xu, Xun
   Yerle, Martine
   Zhang, Guojie
   Zhang, Jianguo
   Zhang, Jie
   Zhao, Shuhong
   Rogers, Jane
   Churcher, Carol
   Schook, Lawrence B.
TI Analyses of pig genomes provide insight into porcine demography and evolution
SO NATURE
LA English
DT Article
ID sequence; gene; receptor; taste
AB For 10,000 years pigs and humans have shared a close and complex relationship. From domestication to modern breeding practices, humans have shaped the genomes of domestic pigs. Here we present the assembly and analysis of the genome sequence of a female domestic Duroc pig (Sus scrofa) and a comparison with the genomes of wild and domestic pigs from Europe and Asia. Wild pigs emerged in South East Asia and subsequently spread across Eurasia. Our results reveal a deep phylogenetic split between European and Asian wild boars similar to 1 million years ago, and a selective sweep analysis indicates selection on genes involved in RNA processing and regulation. Genes associated with immune response and olfaction exhibit fast evolution. Pigs have the largest repertoire of functional olfactory receptor genes, reflecting the importance of smell in this scavenging animal. The pig genome sequence provides an important resource for further improvements of this important livestock species, and our identification of many putative disease-causing variants extends the potential of the pig as a biomedical model.
C1 [Groenen, Martien A. M.; Megens, Hendrik-Jan; Frantz, Laurent A. F.; Bosse, Mirte; Crooijmans, Richard P. M. A.; Dibbits, Bert; Madsen, Ole; Paudel, Yogesh] Wageningen Univ, Anim Breeding & Genom Ctr, NL-6708 WD Wageningen, Netherlands.
   [Archibald, Alan L.; De Sapio, Fioravante; Faulkner, Geoffrey J.; Kapetanovic, Ronan] Univ Edinburgh, Roslin Inst, Easter Bush EH25 9RG, Midlothian, Scotland.
   [Archibald, Alan L.; De Sapio, Fioravante; Faulkner, Geoffrey J.; Kapetanovic, Ronan] Univ Edinburgh, R D SVS, Easter Bush EH25 9RG, Midlothian, Scotland.
   [Uenishi, Hirohide; Kanamori, Hiroyuki] Natl Inst Agrobiol Sci, Tsukuba, Ibaraki 3058602, Japan.
   [Tuggle, Christopher K.; Rothschild, Max F.; Bystrom, Megan; Cheng, Ryan; Du, Zhi-Qiang; Fritz, Eric; Hu, Zhi-Liang; Onteru, Suneel; Reecy, James M.] Iowa State Univ, Dept Anim Sci, Ames, IA 50011 USA.
   [Tuggle, Christopher K.; Rothschild, Max F.; Bystrom, Megan; Cheng, Ryan; Du, Zhi-Qiang; Fritz, Eric; Hu, Zhi-Liang; Onteru, Suneel; Reecy, James M.] Iowa State Univ, Ctr Integrated Anim Genom, Ames, IA 50011 USA.
   [Takeuchi, Yasuhiro] UCL, Div Infect & Immun, MRC, UCL Ctr Med Mol Virol, London WC1E 6BT, England.
   [Takeuchi, Yasuhiro] UCL, Div Infect & Immun, Wohl Vir Ctr, London WC1E 6BT, England.
   [Rogel-Gaillard, Claire; Chardon, Patrick; Giuffra, Elisabetta] INRA, Lab Anim Genet & Integrat Biol, Lab Radiobiol & Etud Genome, AgroParisTech,CEA,DSV,IRCM, F-78350 Jouy En Josas, France.
   [Park, Chankyu; Kim, Jaebum; Lee, Kyooyeol; Dinh Truong Nguyen] Konkuk Univ, Dept Anim Biotechnol, Seoul 143701, South Korea.
   [Milan, Denis; Dehais, Patrice; Faraut, Thomas; Servin, Bertrand; Yerle, Martine] INRA, Lab Genet Cellulaire, F-31320 Castanet Tolosan, France.
   [Li, Shengting; Bolund, Lars; Li, Yingrui; Lu, Yao; Ni, Peixiang; Wang, Jian; Wang, Jun; Xu, Xun; Zhang, Guojie; Zhang, Jianguo] BGI Shenzhen, Shenzhen 518083, Peoples R China.
   [Li, Shengting; Bolund, Lars] Aarhus Univ, Dept Biomed, DK-8000 Aarhus C, Denmark.
   [Larkin, Denis M.; Narayan, Jitendra] Aberystwyth Univ, Inst Biol Environm & Rural Sci, Aberystwyth SY23 3DA, Ceredigion, Wales.
   [Kim, Heebal; Ahn, Hyeonju] Seoul Natl Univ, Dept Agr Biotechnol & C&K Genom, Seoul 151742, South Korea.
   [Caccamo, Mario; Drou, Nizar; Leggett, Richard; Ramirez-Gonzalez, Ricardo; Rogers, Jane] Genome Anal Ctr, Norwich NR4 7UH, Norfolk, England.
   [Aken, Bronwen L.; Chow, William; Clark, Richard C.; Clee, Christopher; Fairley, Susan; Gilbert, James G. R.; Harrow, Jennifer L.; Howe, Kerstin; Humphray, Sean J.; Hunt, Toby; Jones, Matthew; Loveland, Jane E.; Matthews, Lucy; McLaren, Stuart; Scott, Carol; Searle, Stephen; White, Simon; Churcher, Carol] Wellcome Trust Sanger Inst, Hinxton CB10 1SA, Cambs, England.
   [Anselmo, Anna; Badaoui, Bouabid; Botti, Sara; Giuffra, Elisabetta] Parco Tecnol Padano, I-26900 Lodi, Italy.
   [Anthon, Christian; Fredholm, Merete; Gorodkin, Jan] IBHV Univ Copenhagen, Ctr Noncoding RNA Technol & Hlth, Frederiksberg, Denmark.
   [Auvil, Loretta; Capitanu, Boris] Univ Illinois, Illinois Informat Inst, Urbana, IL 61801 USA.
   [Beattie, Craig W.] Univ Illinois, Dept Surg, Chicago, IL 60612 USA.
   [Bendixen, Christian; Zhan Bujie; Fadista, Joao; Hornshoj, Henrik; Panitz, Frank; Thomsen, Bo] Aarhus Univ, Dept Mol Biol & Genet, DK-8830 Tjele, Denmark.
   [Berman, Daniel; Lunney, Joan K.; Mann, Katherine] USDA ARS, BARC Anim Parasit Dis Lab, Beltsville, MD 20705 USA.
   [Blecha, Frank; Sang, Yongming] Kansas State Univ, Coll Vet Med, Dept Anat & Physiol, Manhattan, KS 66506 USA.
   [Blomberg, Jonas] Uppsala Univ, Dept Med Sci, Acad Hosp, S-75185 Uppsala, Sweden.
   [Carvalho-Silva, Denise] European Bioinformat Inst, Hinxton CB10 1SD, Cambs, England.
   [Chen, Celine; Dawson, Harry D.] USDA, Immunol Lab, Beltsville Human Nutr Res Ctr, BARC E, Beltsville, MD 20705 USA.
   [Choi, Sang-Haeng; Park, Hong-Seog] Korean Res Inst Biosci & Biotechnol, Taejon 305806, South Korea.
   [Eversole, Kellye] Eversole Associates, Bethesda, MD 20816 USA.
   [Eversole, Kellye] Alliance Anim Genome Res, Bethesda, MD 20816 USA.
   [Fowler, Katie E.; Griffin, Darren K.] Univ Kent, Sch Biosci, Canterbury CT2 7NJ, Kent, England.
   [Hayward, Alexander; Jern, Patric] Uppsala Univ, Dept Med Biochem & Microbiol, Sci Life Lab, BMC, SE-75123 Uppsala, Sweden.
   [Jeon, Jin-Tae] Gyeongsang Natl Univ, Coll Agr & Life Sci, Dept Anim Sci, Jinju 660701, South Korea.
   [Jurka, Jerzy] Genet Informat Res Inst, Mountain View, CA 94043 USA.
   [Kanamori, Hiroyuki; Morozumi, Takeya] Inst Japan Assoc Technoinnovat Agr Forestry & Fis, Tsukuba, Ibaraki 3050854, Japan.
   [Kim, Jaebum] Univ Illinois, Inst Genom Biol, Urbana, IL 61801 USA.
   [Kim, Jae-Hwan] Natl Inst Anim Sci, Anim Genet Resources Stn, RDA, Namwon 590832, South Korea.
   [Kim, Kyu-Won] C&K Genom, Seoul 151742, South Korea.
   [Kim, Tae-Hun; Lee, Kyung-Tai; Park, Eung-Woo] Natl Inst Anim Sci, Anim Genom & Bioinformat Div, RDA, Suwon 441706, South Korea.
   [Larson, Greger] Univ Durham, Dept Archaeol, Durham DH1 3LE, England.
   [Lewin, Harris A.] Univ Calif Davis, UC Davis Genome Ctr, Dept Ecol & Evolut, Davis, CA 95618 USA.
   [Liu, Wansheng] Penn State Univ, Coll Agr Sci, CRBH, Dept Dairy & Anim Sci, University Pk, PA 16802 USA.
   [Ma, Jian] Univ Illinois, Dept Bioengn, Urbana, IL 61801 USA.
   [Ma, Jian] Univ Illinois, Inst Genom Biol, Urbana, IL 61801 USA.
   [Murtaugh, Michael P.; Schwartz, John] Univ Minnesota, Dept Vet & Biomed Sci, St Paul, MN 55108 USA.
   [Oh, Song-Jung] Jeju Natl Univ, Cheju 690756, South Korea.
   [Pascal, Geraldine] INRA, CNRS, UMR85, IFCE,Physiol Reprod & Comportements UMR7247, F-37380 Nouzilly, France.
   [Pascal, Geraldine] Univ Tours, F-37041 Tours, France.
   [Perez-Enciso, Miguel] CRAG, ICREA, E-08193 Bellaterra, Spain.
   [Perez-Enciso, Miguel] UAB, Fac Vet, E-08193 Bellaterra, Spain.
   [Rodriguez-Zas, Sandra; Rund, Lauretta; Schachtschneider, Kyle; Southey, Bruce R.] Univ Illinois, Dept Anim Sci, Urbana, IL 61801 USA.
   [Rohrer, Gary A.] ARS, USDA, US Meat Anim Res Ctr, Clay Ctr, NE 68933 USA.
   [Schraiber, Joshua G.] Univ Calif Berkeley, Dept Integrat Biol, Berkeley, CA 94720 USA.
   [Scobie, Linda; Wali, Rashmi] Glasgow Caledonian Univ, Dept Life Sci, Glasgow G4 0BA, Lanark, Scotland.
   [Sperber, Goran] Uppsala Univ, Biomed Ctr, Dept Neurosci, S-75124 Uppsala, Sweden.
   [Stadler, Peter; Tafer, Hakim] Univ Leipzig, Dept Comp Sci, Interdisciplinary Ctr Bioinformat, Bioinformat Grp, Leipzig, Germany.
   [Sweedler, Jonathan V.] Univ Illinois, Dept Chem, Urbana, IL 61801 USA.
   [Wang, Jun] Univ Copenhagen, Novo Nordisk Fdn Ctr Basic Metab Res, DK-2200 Copenhagen, Denmark.
   [Wang, Jun] Univ Copenhagen, Dept Biol, DK-2200 Copenhagen, Denmark.
   [Zhang, Guojie] BGI Europe, DK-2200 Copenhagen N, Denmark.
   [Zhang, Jie; Zhao, Shuhong] Huazhong Agr Univ, Minist Educ, Key Lab Anim Genet Breeding & Reprod, Wuhan 430070, Peoples R China.
   [Schook, Lawrence B.] Univ Illinois, Dept Anim Sci, Urbana, IL 61801 USA.
   [Schook, Lawrence B.] Univ Illinois, Inst Genom Biol, Urbana, IL 61801 USA.
C3 Wageningen University & Research; University of Edinburgh; UK Research & Innovation (UKRI); Biotechnology and Biological Sciences Research Council (BBSRC); Roslin Institute; University of Edinburgh; National Institute of Agrobiological Sciences - Japan; Iowa State University; Iowa State University; University of London; University College London; University of London; University College London; Institut National de la Sante et de la Recherche Medicale (Inserm); Universite Paris Saclay; AgroParisTech; CEA; INRAE; Konkuk University; INRAE; Beijing Genomics Institute (BGI); Aarhus University; UK Research & Innovation (UKRI); Biotechnology and Biological Sciences Research Council (BBSRC); Institute of Biological, Environmental, Rural & Sciences (IBERS); Aberystwyth University; Seoul National University (SNU); UK Research & Innovation (UKRI); Biotechnology and Biological Sciences Research Council (BBSRC); Earlham Institute; Wellcome Trust Sanger Institute; University of Illinois System; University of Illinois Urbana-Champaign; University of Illinois System; University of Illinois Chicago; University of Illinois Chicago Hospital; Aarhus University; United States Department of Agriculture (USDA); Kansas State University; Uppsala University; European Molecular Biology Laboratory (EMBL); European Bioinformatics Institute; United States Department of Agriculture (USDA); Korea Research Institute of Bioscience & Biotechnology (KRIBB); University of Kent; Uppsala University; Gyeongsang National University; University of Illinois System; University of Illinois Urbana-Champaign; National Institute of Animal Science, Republic of Korea; Rural Development Administration (RDA), Republic of Korea; National Institute of Animal Science, Republic of Korea; Rural Development Administration (RDA), Republic of Korea; Durham University; University of California System; University of California Davis; Pennsylvania Commonwealth System of Higher Education (PCSHE); Pennsylvania State University; Pennsylvania State University - University Park; University of Illinois System; University of Illinois Urbana-Champaign; University of Illinois System; University of Illinois Urbana-Champaign; University of Minnesota System; University of Minnesota Twin Cities; Jeju National University; INRAE; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB); Universite de Tours; ICREA; Consejo Superior de Investigaciones Cientificas (CSIC); Centre de Recerca en Agrigenomica (CRAG); Autonomous University of Barcelona; University of Illinois System; University of Illinois Urbana-Champaign; United States Department of Agriculture (USDA); University of California System; University of California Berkeley; Glasgow Caledonian University; Uppsala University; Leipzig University; University of Illinois System; University of Illinois Urbana-Champaign; University of Copenhagen; Novo Nordisk Foundation; University of Copenhagen; Huazhong Agricultural University; University of Illinois System; University of Illinois Urbana-Champaign; University of Illinois System; University of Illinois Urbana-Champaign
RP Groenen, MAM (corresponding author), Wageningen Univ, Anim Breeding & Genom Ctr, Elst 1, NL-6708 WD Wageningen, Netherlands.
EM martien.groenen@wur.nl; alan.archibald@roslin.ed.ac.uk
FU USDA CSREES/NIFA Swine Genome Coordination Program; College of Agricultural, Consumer and Environmental Sciences, University of Illinois; College of Agriculture and Life Sciences, Iowa State University; North Carolina Agricultural Research Service; USA National Pork Board; Iowa Pork Producers Association; North Carolina Pork Council; Danish government; TOPIGS Research Center IPG The Netherlands; INRA Genescope, France; Wellcome Trust Sanger Institute and BGI.; BBSRC [BB/E010520/1, BB/E010520/2, BB/I025328/1, BB/H005935/1, BB/G004013/1]; EC FP6 'Cutting edge genomics for sustainable animal breeding (SABRE)'; EC FP7 'Quantomics'; Australian NHMRC [575585]; Next-Generation BioGreen 21 Program [PJ009019, PJ0081162012, PJ0080892011]; RDA, Republic of Korea; Ministry of Research (Spain); NIH [R13 RR020283A, NIH R13 RR032267A, ILLU 535-314, ILLU 538-379, ILLU-538-312, ILLU-538-34, 5 P41LM006252, P20-RR017686, 5 P41 LM006252]; CSREES; NIFA; MAFF [IRPPIAUGT-AG 1101/1201]; USDA-NRSP8 Bioinformatics Coordination and Pig Genome Coordination funds; US-UK Fulbright Commission; USDA-ARS Project Plan [1235-51000-055-00D, 1265-32000-098-00D]; USDA AFRI NIFA/DHS [2010-39559-21860]; USDA ARS; USDA-NRSP8 Bioinformatics; NSFC [31025026]; Swedish Research Council FORMAS; Swedish Wenner-Gren Foundations; European Commission [LSHB-CT-2006-037377]; BioGreen21; RDA [PJ00622901, PJ00622902, PJ00622903, 20040301034467]; European Research Council under the European Community [249894]; NIH NIDA [P30 DA018310, R21 DA027548]; ANR [ANR07-GANI-001]; FTP/DFF [09-066598]; DSF/Strategic Growth Technologies [09-067036]; Lundbeck foundation [374/06]; DCSC (Scientific Computing); Funds for International Cooperation from the Ministry of Science and Technology of China [2002AA229061]; PL-Grid project: [POIG.02.03.00-00-007/08-00]; USDA-NIFA-CREES [AG 2006-35216-16668, AG 2002-34480-11828, AG 2003-34480-13172, AG 2004-34480-14417, AG 2005-34480-15939, AG 2006-34480-17150, AG 2008-34480-19328, AG 2009-34480-19875, AG 2002-35205-12712, AG 2008-35205-18769, AG 2009-65205-05642, AG 2004-3881-02193];  [USDA-NRI-2009-35205-05192];  [USDA-NRI-2006-35204-17337]; ICREA Funding Source: Custom; BBSRC [BBS/E/T/000PR5885, BB/I025506/1, BB/E010520/2, BBS/E/D/20211550, BB/E010768/1, BB/G004013/1, BB/I025360/1, BB/E011640/1, BB/E010520/1, BB/I025328/1, BBS/E/D/05191130, BB/H005935/1] Funding Source: UKRI; MRC [G0900950] Funding Source: UKRI; NERC [NE/H005269/1, NE/H005552/1, NE/F003382/2, NE/F003382/1] Funding Source: UKRI; National Health and Medical Research Council (NHMRC) [575585] Funding Source: National Health and Medical Research Council (NHMRC); National Institute of Allergy and Infectious Diseases [T32AI083196] Funding Source: NIH RePORTER; National Institute on Drug Abuse [P30DA018310] Funding Source: NIH RePORTER; Biotechnology and Biological Sciences Research Council [BB/E010768/1, BB/I025328/1, BBS/E/T/000PR5885, BB/I025360/1, BB/E010520/2, BB/G004013/1, BBS/E/D/05191130, BB/E011640/1, BB/I025506/1, BB/E010520/1, BB/H005935/1, BBS/E/D/20211550] Funding Source: researchfish; Chief Scientist Office [ETM/32] Funding Source: researchfish; Medical Research Council [G0900950, G0900950B] Funding Source: researchfish; Natural Environment Research Council [NE/H005269/1, NE/H005552/1, NE/F003382/2, NE/F003382/1] Funding Source: researchfish
NR 45
TC 1124
Z9 1268
U1 3
U2 474
PU NATURE PUBLISHING 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 15
PY 2012
VL 491
IS 7424
BP 393
EP 398
DI 10.1038/nature11622
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 036MY
UT WOS:000311031600036
PM 23151582
DA 2026-03-09
ER

PT J
AU Wu, X
   Northcott, PA
   Dubuc, A
   Dupuy, AJ
   Shih, DJH
   Witt, H
   Croul, S
   Bouffet, E
   Fults, DW
   Eberhart, CG
   Garzia, L
   Van Meter, T
   Zagzag, D
   Jabado, N
   Schwartzentruber, J
   Majewski, J
   Scheetz, TE
   Pfister, SM
   Korshunov, A
   Li, XN
   Scherer, SW
   Cho, YJ
   Akagi, K
   MacDonald, TJ
   Koster, J
   McCabe, MG
   Sarver, AL
   Collins, VP
   Weiss, WA
   Largaespada, DA
   Collier, LS
   Taylor, MD
AF Wu, Xiaochong
   Northcott, Paul A.
   Dubuc, Adrian
   Dupuy, Adam J.
   Shih, David J. H.
   Witt, Hendrik
   Croul, Sidney
   Bouffet, Eric
   Fults, Daniel W.
   Eberhart, Charles G.
   Garzia, Livia
   Van Meter, Timothy
   Zagzag, David
   Jabado, Nada
   Schwartzentruber, Jeremy
   Majewski, Jacek
   Scheetz, Todd E.
   Pfister, Stefan M.
   Korshunov, Andrey
   Li, Xiao-Nan
   Scherer, Stephen W.
   Cho, Yoon-Jae
   Akagi, Keiko
   MacDonald, Tobey J.
   Koster, Jan
   McCabe, Martin G.
   Sarver, Aaron L.
   Collins, V. Peter
   Weiss, William A.
   Largaespada, David A.
   Collier, Lara S.
   Taylor, Michael D.
TI Clonal selection drives genetic divergence of metastatic medulloblastoma
SO NATURE
LA English
DT Article
ID cancer; aberrations; mutagenesis; expression; cells; mycn
AB Medulloblastoma, the most common malignant paediatric brain tumour, arises in the cerebellum and disseminates through the cerebrospinal fluid in the leptomeningeal space to coat the brain and spinal cord(1). Dissemination, a marker of poor prognosis, is found in up to 40% of children at diagnosis and inmost children at the time of recurrence. Affected children therefore are treated with radiation to the entire developing brain and spinal cord, followed by high-dose chemotherapy, with the ensuing deleterious effects on the developing nervous system(2). The mechanisms of dissemination through the cerebrospinal fluid are poorly studied, and medulloblastoma metastases have been assumed to be biologically similar to the primary tumour(3,4). Here we show that in both mouse and human medulloblastoma, the metastases from an individual are extremely similar to each other but are divergent from the matched primary tumour. Clonal genetic events in the metastases can be demonstrated in a restricted subclone of the primary tumour, suggesting that only rare cells within the primary tumour have the ability to metastasize. Failure to account for the bicompartmental nature of metastatic medulloblastoma could be a major barrier to the development of effective targeted therapies.
C1 [Taylor, Michael D.] Univ Toronto, Hosp Sick Children, Arthur & Sonia Labatt Brain Tumour Res Ctr, Div Neurosurg, Toronto, ON M5G 1X8, Canada.
   [Taylor, Michael D.] Univ Toronto, Hosp Sick Children, Program Dev & Stem Cell Biol, Toronto, ON M5G 1X8, Canada.
   [Wu, Xiaochong; Northcott, Paul A.; Dubuc, Adrian; Shih, David J. H.; Garzia, Livia] Hosp Sick Children, Arthur & Sonia Labatt Brain Tumour Res Ctr, Toronto, ON M5G 1X8, Canada.
   [Wu, Xiaochong; Northcott, Paul A.; Dubuc, Adrian; Shih, David J. H.; Garzia, Livia] Hosp Sick Children, Program Dev & Stem Cell Biol, Toronto, ON M5G 1X8, Canada.
   [Dupuy, Adam J.; Scheetz, Todd E.] Univ Iowa, Mol & Cellular Biol Program, Iowa City, IA 52242 USA.
   [Witt, Hendrik; Pfister, Stefan M.] Univ Heidelberg Hosp, German Canc Res Ctr DKFZ, D-69120 Heidelberg, Germany.
   [Witt, Hendrik; Pfister, Stefan M.] Univ Heidelberg Hosp, Dept Pediat Oncol Hematol & Immunol, D-69120 Heidelberg, Germany.
   [Croul, Sidney] Univ Toronto, Dept Lab Med & Pathobiol, Arthur & Sonia Labatt Brain Tumour Res Ctr, Univ Hlth Network Pathol, Toronto, ON M5S 1A1, Canada.
   [Bouffet, Eric] Hosp Sick Children, Brain Tumour Program, Toronto, ON M5G 1X8, Canada.
   [Fults, Daniel W.] Univ Utah, Sch Med, Dept Neurosurg, Salt Lake City, UT 84132 USA.
   [Eberhart, Charles G.] Johns Hopkins Univ, Baltimore, MD 21210 USA.
   [Van Meter, Timothy] Virginia Commonwealth Univ, Richmond, VA 23284 USA.
   [Zagzag, David] NYU, Sch Med, Div Neuropathol, Dept Pathol & Neurosurg, New York, NY 10016 USA.
   [Jabado, Nada; Majewski, Jacek] McGill Univ, Dept Human Genet, Montreal, PQ H3Z 2Z3, Canada.
   [Jabado, Nada; Majewski, Jacek] McGill Univ, Dept Expt Med, Montreal, PQ H3Z 2Z3, Canada.
   [Schwartzentruber, Jeremy] McGill Univ, Montreal, PQ H3A 0G1, Canada.
   [Schwartzentruber, Jeremy] Genome Quebec Innovat Ctr, Montreal, PQ H3A 0G1, Canada.
   [Korshunov, Andrey] Heidelberg Univ, German Canc Res Inst DKFZ, D-69120 Heidelberg, Germany.
   [Korshunov, Andrey] Heidelberg Univ, Dept Neuropathol, D-69120 Heidelberg, Germany.
   [Li, Xiao-Nan] Texas Childrens Canc Ctr, Brain Tumor Program, Houston, TX 77030 USA.
   [Li, Xiao-Nan] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA.
   [Scherer, Stephen W.] Hosp Sick Children, Program Genet & Genom Biol, Toronto, ON M5S 1A1, Canada.
   [Scherer, Stephen W.] Hosp Sick Children, Ctr Appl Genom, Toronto, ON M5S 1A1, Canada.
   [Scherer, Stephen W.] Univ Toronto, McLaughlin Ctr, Toronto, ON M5S 1A1, Canada.
   [Scherer, Stephen W.] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A1, Canada.
   [Cho, Yoon-Jae] Stanford Univ, Sch Med, Dept Neurol, Stanford, CA 94305 USA.
   [Cho, Yoon-Jae] Stanford Univ, Sch Med, Dept Neurosurg, Stanford, CA 94305 USA.
   [Akagi, Keiko] Ohio State Univ, Ctr Comprehens Canc, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43210 USA.
   [MacDonald, Tobey J.] Emory Univ, Sch Med, Pediat Neurooncol Program, Atlanta, GA 30307 USA.
   [Koster, Jan] Univ Amsterdam, Acad Med Ctr, Dept Human Genet, NL-1100 DE Amsterdam, Netherlands.
   [McCabe, Martin G.] Univ Manchester, Sch Canc & Enabling Sci, Manchester M20 4BX, Lancs, England.
   [Sarver, Aaron L.; Largaespada, David A.] Univ Minnesota, Masonic Canc Ctr, Minneapolis, MN 55455 USA.
   [Collins, V. Peter] Univ Cambridge, Dept Pathol, Cambridge CB2 1QP, England.
   [Weiss, William A.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA.
   [Weiss, William A.] Univ Calif San Francisco, Dept Pediat & Neurol Surg, San Francisco, CA 94143 USA.
   [Collier, Lara S.] Univ Wisconsin, Sch Pharmacol, Madison, WI 53715 USA.
C3 University of Toronto; Hospital for Sick Children (SickKids); University of Toronto; Hospital for Sick Children (SickKids); University of Toronto; Hospital for Sick Children (SickKids); University of Toronto; Hospital for Sick Children (SickKids); University of Iowa; Ruprecht Karls University Heidelberg; Helmholtz Association; German Cancer Research Center (DKFZ); Ruprecht Karls University Heidelberg; University of Toronto; University Health Network Toronto; University of Toronto; Hospital for Sick Children (SickKids); Utah System of Higher Education; University of Utah; Johns Hopkins University; Virginia Commonwealth University; New York University; McGill University; McGill University; McGill University; Ruprecht Karls University Heidelberg; Helmholtz Association; German Cancer Research Center (DKFZ); Ruprecht Karls University Heidelberg; Texas Children's Cancer Center; Baylor College of Medicine; University of Toronto; Hospital for Sick Children (SickKids); University of Toronto; Hospital for Sick Children (SickKids); University of Toronto; University of Toronto; Stanford University; Stanford University; James Cancer Hospital & Solove Research Institute; University System of Ohio; Ohio State University; Emory University; University of Amsterdam; Academic Medical Center Amsterdam; University of Manchester; University of Minnesota System; University of Minnesota Twin Cities; University of Cambridge; University of California System; University of California San Francisco; University of California System; University of California San Francisco; University of Wisconsin System; University of Wisconsin Madison
RP Taylor, MD (corresponding author), Univ Toronto, Hosp Sick Children, Arthur & Sonia Labatt Brain Tumour Res Ctr, Div Neurosurg, Toronto, ON M5G 1X8, Canada.
EM mdtaylor@sickkids.ca
FU National Institutes of Health [R01CA148699, NS055089]; Pediatric Brain Tumor Foundation; Canadian Cancer Society; Brainchild; American Brain Tumor Association; Canadian Institutes of Health Research; Kimmel Foundation;  [K01CA122183]; The Brain Tumour Charity [10/106] Funding Source: researchfish
NR 28
TC 339
Z9 415
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 FEB 23
PY 2012
VL 482
IS 7386
BP 529
EP U254
DI 10.1038/nature10825
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 898VM
UT WOS:000300770500051
PM 22343890
DA 2026-03-09
ER

PT J
AU Su, CY
   Menuz, K
   Reisert, J
   Carlson, JR
AF Su, Chih-Ying
   Menuz, Karen
   Reisert, Johannes
   Carlson, John R.
TI Non-synaptic inhibition between grouped neurons in an olfactory circuit
SO NATURE
LA English
DT Article
ID receptor neurons; drosophila-melanogaster; chemosensory receptors; behavioral-responses; molecular-basis; pheromone; sensilla; organization; moth; perception
AB Diverse sensory organs, including mammalian taste buds and insect chemosensory sensilla, show a marked compartmentalization of receptor cells; however, the functional impact of this organization remains unclear. Here we show that compartmentalized Drosophila olfactory receptor neurons (ORNs) communicate with each other directly. The sustained response of one ORN is inhibited by the transient activation of a neighbouring ORN. Mechanistically, such lateral inhibition does not depend on synapses and is probably mediated by ephaptic coupling. Moreover, lateral inhibition in the periphery can modulate olfactory behaviour. Together, the results show that integration of olfactory information can occur via lateral interactions between ORNs. Inhibition of a sustained response by a transient response may provide a means of encoding salience. Finally, a CO2-sensitive ORN in the malaria mosquito Anopheles can also be inhibited by excitation of an adjacent ORN, suggesting a broad occurrence of lateral inhibition in insects and possible applications in insect control.
C1 [Su, Chih-Ying; Menuz, Karen; Carlson, John R.] Yale Univ, Dept Mol Cellular & Dev Biol, New Haven, CT 06520 USA.
   [Reisert, Johannes] Monell Chem Senses Ctr, Philadelphia, PA 19104 USA.
C3 Yale University; Monell Chemical Senses Center
RP Carlson, JR (corresponding author), Yale Univ, Dept Mol Cellular & Dev Biol, New Haven, CT 06520 USA.
EM john.carlson@yale.edu
FU National Institutes of Health (NIH) [NIH DC009613]; Foundation for the NIH through the Grand Challenges in Global Health Initiative (GCGH) [121]; NRSA [NIH F32DC011242]; National Institute on Deafness and Other Communication Disorders [R01DC004729, R01DC011697] Funding Source: NIH RePORTER
NR 50
TC 179
Z9 229
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 DEC 6
PY 2012
VL 492
IS 7427
BP 66
EP +
DI 10.1038/nature11712
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 048EQ
UT WOS:000311893400046
PM 23172146
DA 2026-03-09
ER

PT J
AU Cingöz, A
   Yost, DC
   Allison, TK
   Ruehl, A
   Fermann, ME
   Hartl, I
   Ye, J
AF Cingoez, Arman
   Yost, Dylan C.
   Allison, Thomas K.
   Ruehl, Axel
   Fermann, Martin E.
   Hartl, Ingmar
   Ye, Jun
TI Direct frequency comb spectroscopy in the extreme ultraviolet
SO NATURE
LA English
DT Article
ID high-harmonic-generation; spectrum; pulses; power
AB The development of the optical frequency comb(a spectrum consisting of a series of evenly spaced lines) has revolutionized metrology and precision spectroscopy owing to its ability to provide a precise and direct link between microwave and optical frequencies(1,2). A further advance in frequency comb technology is the generation of frequency combs in the extreme-ultraviolet spectral range by means of high-harmonic generation in a femtosecond enhancement cavity(3,4). Until now, combs produced by this method have lacked sufficient power for applications, a drawback that has also hampered efforts to observe phase coherence of the high-repetition-rate pulse train produced by high-harmonic generation, which is an extremely nonlinear process. Here we report the generation of extreme-ultraviolet frequency combs, reaching wavelengths of 40 nanometres, by coupling a high-power near-infrared frequency comb(5) to a robust femtosecond enhancement cavity. These combs are powerful enough for us to observe single-photon spectroscopy signals for both an argon transition at 82 nanometres and a neon transition at 63 nanometres, thus confirming the combs' coherence in the extreme ultraviolet. The absolute frequency of the argon transition has been determined by direct frequency comb spectroscopy. The resolved ten-megahertz linewidth of the transition, which is limited by the temperature of the argon atoms, is unprecedented in this spectral region and places a stringent upper limit on the linewidth of individual comb teeth. Owing to the lack of continuous-wave lasers, extreme-ultraviolet frequency combs are at present the only promising route to extending ultrahigh-precision spectroscopy to the spectral region below 100 nanometres. At such wavelengths there is a wide range of applications, including the spectroscopy of electronic transitions in molecules(6), experimental tests of bound-state and many-body quantum electrodynamics in singly ionized helium and neutral helium(7-9), the development of next-generation 'nuclear' clocks(10-12) and searches for variation of fundamental constants(13) using the enhanced sensitivity of highly charged ions(14).
C1 [Cingoez, Arman; Yost, Dylan C.; Allison, Thomas K.; Ye, Jun] Natl Inst Stand & Technol, Joint Inst Lab Astrophys, Boulder, CO 80309 USA.
   [Cingoez, Arman; Yost, Dylan C.; Allison, Thomas K.; Ye, Jun] Univ Colorado, Dept Phys, Boulder, CO 80309 USA.
   [Ruehl, Axel; Fermann, Martin E.; Hartl, Ingmar] IMRA Amer Inc, Ann Arbor, MI 48105 USA.
C3 National Institute of Standards & Technology (NIST) - USA; University of Colorado System; University of Colorado Boulder; IMRA America, Inc.
RP Cingöz, A (corresponding author), Natl Inst Stand & Technol, Joint Inst Lab Astrophys, Boulder, CO 80309 USA.
EM acingoz@jila.colorado.edu; junye@jila.colorado.edu
FU DARPA; AFOSR; NIST; NSF; Alexander von Humboldt Foundation (Germany); Direct For Mathematical & Physical Scien; Division Of Physics [1125844] Funding Source: National Science Foundation
NR 30
TC 397
Z9 449
U1 5
U2 225
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 2
PY 2012
VL 482
IS 7383
BP 68
EP 71
DI 10.1038/nature10711
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 884RN
UT WOS:000299726000036
PM 22297971
DA 2026-03-09
ER

PT J
AU Vakarelski, IU
   Patankar, NA
   Marston, JO
   Chan, DYC
   Thoroddsen, ST
AF Vakarelski, Ivan U.
   Patankar, Neelesh A.
   Marston, Jeremy O.
   Chan, Derek Y. C.
   Thoroddsen, Sigurdur T.
TI Stabilization of Leidenfrost vapour layer by textured superhydrophobic surfaces
SO NATURE
LA English
DT Article
ID heat-transfer; wettability; spheres; water; drag
AB In 1756, Leidenfrost(1) observed that water drops skittered on a sufficiently hot skillet, owing to levitation by an evaporative vapour film. Such films are stable only when the hot surface is above a critical temperature, and are a central phenomenon in boiling(2). In this so-called Leidenfrost regime, the low thermal conductivity of the vapour layer inhibits heat transfer between the hot surface and the liquid. When the temperature of the cooling surface drops below the critical temperature, the vapour film collapses and the system enters a nucleate-boiling regime, which can result in vapour explosions that are particularly detrimental in certain contexts, such as in nuclear power plants(3). The presence of these vapour films can also reduce liquid-solid drag(4-6). Here we show how vapour film collapse can be completely suppressed at textured superhydrophobic surfaces. At a smooth hydrophobic surface, the vapour film still collapses on cooling, albeit at a reduced critical temperature, and the system switches explosively to nucleate boiling. In contrast, at textured, superhydrophobic surfaces, the vapour layer gradually relaxes until the surface is completely cooled, without exhibiting a nucleate-boiling phase. This result demonstrates that topological texture on superhydrophobic materials is critical in stabilizing the vapour layer and thus in controlling-by heat transfer-the liquid-gas phase transition at hot surfaces. This concept can potentially be applied to control other phase transitions, such as ice or frost formation(7-9), and to the design of low-drag surfaces at which the vapour phase is stabilized in the grooves of textures without heating(10).
C1 [Vakarelski, Ivan U.; Marston, Jeremy O.; Thoroddsen, Sigurdur T.] King Abdullah Univ Sci & Technol KAUST, Div Phys Sci & Engn, Thuwal 239556900, Saudi Arabia.
   [Vakarelski, Ivan U.; Thoroddsen, Sigurdur T.] King Abdullah Univ Sci & Technol KAUST, Clean Combust Res Ctr, Thuwal 239556900, Saudi Arabia.
   [Patankar, Neelesh A.] Northwestern Univ, Dept Mech Engn, Evanston, IL 60208 USA.
   [Chan, Derek Y. C.] Univ Melbourne, Dept Math & Stat, Parkville, Vic 3010, Australia.
   [Chan, Derek Y. C.] Swinburne Univ Technol, Fac Life & Social Sci, Hawthorn, Vic 3122, Australia.
C3 King Abdullah University of Science & Technology; King Abdullah University of Science & Technology; Northwestern University; University of Melbourne; Swinburne University of Technology
RP Vakarelski, IU (corresponding author), King Abdullah Univ Sci & Technol KAUST, Div Phys Sci & Engn, Thuwal 239556900, Saudi Arabia.
EM ivanuriev.vakarelski@kaust.edu.sa; n-patankar@northwestern.edu
NR 32
TC 510
Z9 579
U1 18
U2 777
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 13
PY 2012
VL 489
IS 7415
BP 274
EP 277
DI 10.1038/nature11418
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 003UC
UT WOS:000308635900037
PM 22972299
DA 2026-03-09
ER

PT J
AU Bridges, NT
   Ayoub, F
   Avouac, JP
   Leprince, S
   Lucas, A
   Mattson, S
AF Bridges, N. T.
   Ayoub, F.
   Avouac, J-P.
   Leprince, S.
   Lucas, A.
   Mattson, S.
TI Earth-like sand fluxes on Mars
SO NATURE
LA English
DT Article
ID dune movement; model; california; abrasion; ripples; erosion; valley
AB Strong and sustained winds on Mars have been considered rare, on the basis of surface meteorology measurements and global circulation models(1,2), raising the question of whether the abundant dunes and evidence for wind erosion seen on the planet are a current process. Recent studies(3-6) showed sand activity, but could not determine whether entire dunes were moving-implying large sand fluxes-or whether more localized and surficial changes had occurred. Here we present measurements of the migration rate of sand ripples and dune lee fronts at the Nili Patera dune field. We show that the dunes are near steady state, with their entire volumes composed of mobile sand. The dunes have unexpectedly high sand fluxes, similar, for example, to those in Victoria Valley, Antarctica, implying that rates of landscape modification on Mars and Earth are similar.
C1 [Bridges, N. T.] Johns Hopkins Univ, Appl Phys Lab, Dept Space, Laurel, MD 20723 USA.
   [Ayoub, F.; Avouac, J-P.; Leprince, S.; Lucas, A.] CALTECH, Div Geol & Planetary Sci, Pasadena, CA 91125 USA.
   [Mattson, S.] Univ Arizona, Lunar & Planetary Lab, Tucson, AZ 85721 USA.
C3 Johns Hopkins University; Johns Hopkins University Applied Physics Laboratory; California Institute of Technology; University of Arizona
RP Bridges, NT (corresponding author), Johns Hopkins Univ, Appl Phys Lab, Dept Space, Johns Hopkins Rd, Laurel, MD 20723 USA.
EM nathan.bridges@jhuapl.edu
FU NASA; Keck Institute for Space Studies; Jet Propulsion Laboratory
NR 30
TC 232
Z9 250
U1 2
U2 77
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD MAY 17
PY 2012
VL 485
IS 7398
BP 339
EP 342
DI 10.1038/nature11022
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 943CW
UT WOS:000304099100035
PM 22596156
DA 2026-03-09
ER

PT J
AU Hao, HX
   Xie, Y
   Zhang, Y
   Charlat, O
   Oster, E
   Avello, M
   Lei, H
   Mickanin, C
   Liu, D
   Ruffner, H
   Mao, XH
   Ma, QC
   Zamponi, R
   Bouwmeester, T
   Finan, PM
   Kirschner, MW
   Porter, JA
   Serluca, FC
   Cong, F
AF Hao, Huai-Xiang
   Xie, Yang
   Zhang, Yue
   Charlat, Olga
   Oster, Emma
   Avello, Monika
   Lei, Hong
   Mickanin, Craig
   Liu, Dong
   Ruffner, Heinz
   Mao, Xiaohong
   Ma, Qicheng
   Zamponi, Raffaella
   Bouwmeester, Tewis
   Finan, Peter M.
   Kirschner, Marc W.
   Porter, Jeffery A.
   Serluca, Fabrizio C.
   Cong, Feng
TI ZNRF3 promotes Wnt receptor turnover in an R-spondin-sensitive manner
SO NATURE
LA English
DT Article
ID beta-catenin function; wnt/beta-catenin; lens morphogenesis; r-spondin1; pathway; lrp6; lgr5; phosphorylation; inhibition; disruption
AB R-spondin proteins strongly potentiate Wnt signalling and function as stem-cell growth factors. Despite the biological and therapeutic significance, the molecular mechanism of R-spondin action remains unclear. Here we show that the cell-surface transmembrane E3 ubiquitin ligase zinc and ring finger 3 (ZNRF3) and its homologue ring finger 43 (RNF43) are negative feedback regulators of Wnt signalling. ZNRF3 is associated with the Wnt receptor complex, and inhibits Wnt signalling by promoting the turnover of frizzled and LRP6. Inhibition of ZNRF3 enhances Wnt/beta-catenin signalling and disrupts Wnt/ planar cell polarity signalling in vivo. Notably, R-spondin mimics ZNRF3 inhibition by increasing the membrane level of Wnt receptors. Mechanistically, R-spondin interacts with the extracellular domain of ZNRF3 and induces the association between ZNRF3 and LGR4, which results in membrane clearance of ZNRF3. These data suggest that R-spondin enhances Wnt signalling by inhibiting ZNRF3. Our study provides new mechanistic insights into the regulation of Wnt receptor turnover, and reveals ZNRF3 as a tractable target for therapeutic exploration.
C1 [Hao, Huai-Xiang; Xie, Yang; Zhang, Yue; Charlat, Olga; Oster, Emma; Avello, Monika; Lei, Hong; Mickanin, Craig; Liu, Dong; Mao, Xiaohong; Ma, Qicheng; Zamponi, Raffaella; Finan, Peter M.; Porter, Jeffery A.; Serluca, Fabrizio C.; Cong, Feng] Novartis Inst Biomed Res, Cambridge, MA 02139 USA.
   [Ruffner, Heinz; Bouwmeester, Tewis] Novartis Pharma AG, Novartis Inst Biomed Res, CH-4002 Basel, Switzerland.
   [Kirschner, Marc W.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA.
C3 Novartis; Novartis USA; Novartis; Harvard University; Harvard Medical School
RP Cong, F (corresponding author), Novartis Inst Biomed Res, 250 Massachusetts Ave, Cambridge, MA 02139 USA.
EM feng.cong@novartis.com
CR Unknown -, 1995, THE ZEBRAFISH BOOK. A GUIDE FOR THE LABORATORY USE OF ZEBRAFISH (DANIO RERIO), V0, P0
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NR 37
TC 778
Z9 945
U1 1
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 MAY 10
PY 2012
VL 485
IS 7397
BP 195
EP U76
DI 10.1038/nature11019
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 939HJ
UT WOS:000303799800032
PM 22575959
DA 2026-03-09
ER

PT J
AU Lalonde, K
   Mucci, A
   Ouellet, A
   Gélinas, Y
AF Lalonde, Karine
   Mucci, Alfonso
   Ouellet, Alexandre
   Gelinas, Yves
TI Preservation of organic matter in sediments promoted by iron
SO NATURE
LA English
DT Article
ID marine-sediments; mineral surfaces; sorption; metal; soil
AB The biogeochemical cycles of iron and organic carbon are strongly interlinked. In oceanic waters, organic ligands have been shown to control the concentration of dissolved iron(1). In soils, solid iron phases shelter and preserve organic carbon(2), but the role of iron in the preservation of organic matter in sediments has not been clearly established. Here we use an iron reduction method previously applied to soils(3) to determine the amount of organic carbon associated with reactive iron phases in sediments of various mineralogies collected from a wide range of depositional environments. Our findings suggest that 21.5 +/- 8.6 per cent of the organic carbon in sediments is directly bound to reactive iron phases. We further estimate that a global mass of (19-45) x 10(15) grams of organic carbon is preserved in surface marine sediments as a result of its association with iron(4). We propose that these associations between organic carbon and iron, which are formed primarily through co-precipitation and/or direct chelation, promote the preservation of organic carbon in sediments. Because reactive iron phases are metastable over geological timescales, we suggest that they serve as an efficient 'rusty sink' for organic carbon, acting as a key factor in the long-term storage of organic carbon and thus contributing to the global cycles of carbon, oxygen and sulphur(5).
C1 [Lalonde, Karine; Ouellet, Alexandre; Gelinas, Yves] Concordia Univ, GEOTOP, Montreal, PQ H4B 1R6, Canada.
   [Lalonde, Karine; Ouellet, Alexandre; Gelinas, Yves] Concordia Univ, Dept Chem & Biochem, Montreal, PQ H4B 1R6, Canada.
   [Mucci, Alfonso] McGill Univ, GEOTOP, Montreal, PQ H3A 2A7, Canada.
C3 Concordia University - Canada; Concordia University - Canada; McGill University
RP Gélinas, Y (corresponding author), Concordia Univ, GEOTOP, 7141 Sherbrooke St W, Montreal, PQ H4B 1R6, Canada.
EM ygelinas@alcor.concordia.ca
FU NSERC; CFI; FQRNT
NR 28
TC 1188
Z9 1418
U1 96
U2 1970
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 8
PY 2012
VL 483
IS 7388
BP 198
EP 200
DI 10.1038/nature10855
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 904DT
UT WOS:000301174900035
PM 22398559
DA 2026-03-09
ER

PT J
AU Koralek, AC
   Jin, X
   Ii, JDL
   Costa, RM
   Carmena, JM
AF Koralek, Aaron C.
   Jin, Xin
   Ii, John D. Long
   Costa, Rui M.
   Carmena, Jose M.
TI Corticostriatal plasticity is necessary for learning intentional neuroprosthetic skills
SO NATURE
LA English
DT Article
ID prefrontal cortex; striatal neurons; acquisition; consolidation; performance; contingency; activation; networks; circuits
AB The ability to learn new skills and perfect them with practice applies not only to physical skills but also to abstract skills(1), like motor planning or neuroprosthetic actions. Although plasticity in corticostriatal circuits has been implicated in learning physical skills(2-4), it remains unclear if similar circuits or processes are required for abstract skill learning. Here we use a novel behavioural task in rodents to investigate the role of corticostriatal plasticity in abstract skill learning. Rodents learned to control the pitch of an auditory cursor to reach one of two targets by modulating activity in primary motor cortex irrespective of physical movement. Degradation of the relation between action and outcome, as well as sensory-specific devaluation and omission tests, demonstrate that these learned neuroprosthetic actions are intentional and goal-directed, rather than habitual. Striatal neurons change their activity with learning, with more neurons modulating their activity in relation to target-reaching as learning progresses. Concomitantly, strong relations between the activity of neurons in motor cortex and the striatum emerge. Specific deletion of striatal NMDA receptors impairs the development of this corticostriatal plasticity, and disrupts the ability to learn neuroprosthetic skills. These results suggest that corticostriatal plasticity is necessary for abstract skill learning, and that neuroprosthetic movements capitalize on the neural circuitry involved in natural motor learning.
C1 [Jin, Xin; Costa, Rui M.] NIAAA, Lab Integrat Neurosci, NIH, Bethesda, MD 20892 USA.
   [Koralek, Aaron C.; Ii, John D. Long; Carmena, Jose M.] Univ Calif Berkeley, Helen Wills Neurosci Inst, Berkeley, CA 94720 USA.
   [Carmena, Jose M.] Univ Calif Berkeley, Dept Elect Engn & Comp Sci, Berkeley, CA 94720 USA.
   [Carmena, Jose M.] Univ Calif Berkeley, Program Cognit Sci, Berkeley, CA 94720 USA.
   [Carmena, Jose M.] Univ Calif Berkeley, UC Berkeley & UC San Francisco Joint Grad Grp Bio, Berkeley, CA 94720 USA.
   [Costa, Rui M.] Champalimaud Ctr Unknown, Champalimaud Neurosci Programme, P-1400038 Lisbon, Portugal.
C3 National Institutes of Health (NIH) - USA; NIH National Institute on Alcohol Abuse & Alcoholism (NIAAA); University of California System; University of California Berkeley; University of California System; University of California Berkeley; University of California System; University of California Berkeley; University of California System; University of California Berkeley; Fundacao Champalimaud
RP Costa, RM (corresponding author), NIAAA, Lab Integrat Neurosci, NIH, 5625 Fishers Lane, Bethesda, MD 20892 USA.
EM ruicosta@fchampalimaud.org; carmena@eecs.berkeley.edu
FU National Science Foundation [0954243]; Multiscale Systems Research Center; Defense Advanced Research Projects Agency [N66001-10-C-2008]; Division of Intramural Clinical and Basic Research of the National Institute on Alcohol Abuse and Alcoholism [239527]; European Research Council [STG 243393]; Directorate For Engineering [0954243] Funding Source: National Science Foundation; Div Of Chem, Bioeng, Env, & Transp Sys [0954243] Funding Source: National Science Foundation; National Institute on Alcohol Abuse and Alcoholism [ZIAAA000416] Funding Source: NIH RePORTER
NR 30
TC 276
Z9 348
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 MAR 15
PY 2012
VL 483
IS 7389
BP 331
EP 335
DI 10.1038/nature10845
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 908HP
UT WOS:000301481800049
PM 22388818
DA 2026-03-09
ER

PT J
AU M'Gonigle, LK
   Mazzucco, R
   Otto, SP
   Dieckmann, U
AF M'Gonigle, Leithen K.
   Mazzucco, Rupert
   Otto, Sarah P.
   Dieckmann, Ulf
TI Sexual selection enables long-term coexistence despite ecological equivalence
SO NATURE
LA English
DT Article
ID sympatric speciation; incipient speciation; female choice; hybrid zones; evolution; preference; diversity; models; space
AB Empirical data indicate that sexual preferences are critical for maintaining species boundaries(1-4), yet theoretical work has suggested that, on their own, they can have only a minimal role in maintaining biodiversity(5-9). This is because long-term coexistence within overlapping ranges is thought to be unlikely in the absence of ecological differentiation(9). Here we challenge this widely held view by generalizing a standard model of sexual selection to include two ubiquitous features of populations with sexual selection: spatial variation in local carrying capacity, and mate-search costs in females. We show that, when these two features are combined, sexual preferences can single-handedly maintain coexistence, even when spatial variation in local carrying capacity is so slight that it might go unnoticed empirically. This theoretical study demonstrates that sexual selection alone can promote the long-term coexistence of ecologically equivalent species with overlapping ranges, and it thus provides a novel explanation for the maintenance of species diversity.
C1 [M'Gonigle, Leithen K.; Otto, Sarah P.] Univ British Columbia, Dept Zool, Vancouver, BC V6T 1Z4, Canada.
   [Mazzucco, Rupert; Dieckmann, Ulf] Int Inst Appl Syst Anal, Evolut & Ecol Program, A-2361 Laxenburg, Austria.
C3 University of British Columbia; International Institute for Applied Systems Analysis (IIASA)
RP M'Gonigle, LK (corresponding author), Univ Calif Berkeley, Dept Environm Sci, 130 Mulford Hall, Berkeley, CA 94720 USA.
EM mgonigle@zoology.ubc.ca
FU Natural Sciences and Engineering Research Council (Canada); European Science Foundation; WWTF; European Commission; Austrian Science Fund; Austrian Ministry of Science and Research; Austrian Science Fund (FWF) [I 106] Funding Source: researchfish
NR 26
TC 80
Z9 86
U1 2
U2 86
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD APR 26
PY 2012
VL 484
IS 7395
BP 506
EP 509
DI 10.1038/nature10971
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 931FF
UT WOS:000303200400049
PM 22466286
DA 2026-03-09
ER

PT J
AU DeConto, RM
   Galeotti, S
   Pagani, M
   Tracy, D
   Schaefer, K
   Zhang, TJ
   Pollard, D
   Beerling, DJ
AF DeConto, Robert M.
   Galeotti, Simone
   Pagani, Mark
   Tracy, David
   Schaefer, Kevin
   Zhang, Tingjun
   Pollard, David
   Beerling, David J.
TI Past extreme warming events linked to massive carbon release from thawing permafrost
SO NATURE
LA English
DT Article
ID eocene thermal maximum; atmospheric co2; late paleocene; climate-change; global carbon; methane; model; ocean; hyperthermals; sensitivity
AB Between about 55.5 and 52 million years ago, Earth experienced a series of sudden and extreme global warming events (hyperthermals) superimposed on a long-term warming trend(1). The first and largest of these events, the Palaeocene-Eocene Thermal Maximum (PETM), is characterized by a massive input of carbon, ocean acidification(2) and an increase in global temperature of about 5 degrees C within a few thousand years(3). Although various explanations for the PETM have been proposed(4-6), a satisfactory model that accounts for the source, magnitude and timing of carbon release at the PETM and successive hyperthermals remains elusive. Here we use a new astronomically calibrated cyclostratigraphic record from central Italy(7) to show that the Early Eocene hyperthermals occurred during orbits with a combination of high eccentricity and high obliquity. Corresponding climate-ecosystem-soil simulations accounting for rising concentrations of background greenhouse gases(8) and orbital forcing show that the magnitude and timing of the PETM and subsequent hyperthermals can be explained by the orbitally triggered decomposition of soil organic carbon in circum-Arctic and Antarctic terrestrial permafrost. This massive carbon reservoir had the potential to repeatedly release thousands of petagrams (10(15) grams) of carbon to the atmosphere-ocean system, once a long-term warming threshold had been reached just before the PETM. Replenishment of permafrost soil carbon stocks following peak warming probably contributed to the rapid recovery from each event(9), while providing a sensitive carbon reservoir for the next hyperthermal(10). As background temperatures continued to rise following the PETM, the areal extent of permafrost steadily declined, resulting in an incrementally smaller available carbon pool and smaller hyperthermals at each successive orbital forcing maximum. A mechanism linking Earth's orbital properties with release of soil carbon from permafrost provides a unifying model accounting for the salient features of the hyperthermals.
C1 [DeConto, Robert M.; Tracy, David] Univ Massachusetts, Dept Geosci, Amherst, MA 01002 USA.
   [Galeotti, Simone] Univ Urbino, Earth Life & Environm Sci Dept, I-61029 Urbino, Italy.
   [Pagani, Mark] Yale Univ, Dept Geol & Geophys, New Haven, CT 06520 USA.
   [Schaefer, Kevin; Zhang, Tingjun] Univ Colorado, Cooperat Inst Res Environm Sci, Natl Snow & Ice Data Ctr, Boulder, CO 80309 USA.
   [Pollard, David] Penn State Univ, Earth & Environm Syst Inst, University Pk, PA 16802 USA.
   [Beerling, David J.] Univ Sheffield, Dept Anim & Plant Sci, Sheffield S10 2TN, S Yorkshire, England.
   [Zhang, Tingjun] Lanzhou Univ, Minist Educ, Key Lab W Chinas Environm Syst, Lanzhou 730000, Gansu, Peoples R China.
C3 University of Massachusetts System; University of Massachusetts Amherst; University of Urbino; Yale University; University of Colorado System; University of Colorado Boulder; Pennsylvania Commonwealth System of Higher Education (PCSHE); Pennsylvania State University; Pennsylvania State University - University Park; University of Sheffield; Lanzhou University
RP DeConto, RM (corresponding author), Univ Massachusetts, Dept Geosci, Amherst, MA 01002 USA.
EM deconto@geo.umass.edu
FU US National Science Foundation [ATM-0513402/0513421, EAR-0628358]; Royal Society; Directorate For Geosciences; Division Of Polar Programs [0901962] Funding Source: National Science Foundation
NR 46
TC 275
Z9 329
U1 6
U2 495
PU NATURE PUBLISHING 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 5
PY 2012
VL 484
IS 7392
BP 87
EP +
DI 10.1038/nature10929
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 919QN
UT WOS:000302343400039
PM 22481362
DA 2026-03-09
ER

PT J
AU Vonk, JE
   Sánchez-García, L
   van Dongen, BE
   Alling, V
   Kosmach, D
   Charkin, A
   Semiletov, IP
   Dudarev, OV
   Shakhova, N
   Roos, P
   Eglinton, TI
   Andersson, A
   Gustafsson, Ö
AF Vonk, J. E.
   Sanchez-Garcia, L.
   van Dongen, B. E.
   Alling, V.
   Kosmach, D.
   Charkin, A.
   Semiletov, I. P.
   Dudarev, O. V.
   Shakhova, N.
   Roos, P.
   Eglinton, T. I.
   Andersson, A.
   Gustafsson, O.
TI Activation of old carbon by erosion of coastal and subsea permafrost in Arctic Siberia
SO NATURE
LA English
DT Article
ID offshore permafrost; shelf; degradation; release; matter; laptev; cycle
AB The future trajectory of greenhouse gas concentrations depends on interactions between climate and the biogeosphere(1,2). Thawing of Arctic permafrost could release significant amounts of carbon into the atmosphere in this century(3). Ancient Ice Complex deposits outcropping along the similar to 7,000-kilometre-long coastline of the East Siberian Arctic Shelf (ESAS)(4,5), and associated shallow subsea permafrost(6,7), are two large pools of permafrost carbon(8), yet their vulnerabilities towards thawing and decomposition are largely unknown(9-11). Recent Arctic warming is stronger than has been predicted by several degrees, and is particularly pronounced over the coastal ESAS region(12,13). There is thus a pressing need to improve our understanding of the links between permafrost carbon and climate in this relatively inaccessible region. Here we show that extensive release of carbon from these Ice Complex deposits dominates (57 +/- 2 per cent) the sedimentary carbon budget of the ESAS, the world's largest continental shelf, overwhelming the marine and topsoil terrestrial components. Inverse modelling of the dual-carbon isotope composition of organic carbon accumulating in ESAS surface sediments, using Monte Carlo simulations to account for uncertainties, suggests that 44 +/- 10 teragrams of old carbon is activated annually from Ice Complex permafrost, an order of magnitude more than has been suggested by previous studies(14). We estimate that about two-thirds (66 +/- 16 per cent) of this old carbon escapes to the atmosphere as carbon dioxide, with the remainder being re-buried in shelf sediments. Thermal collapse and erosion of these carbon-rich Pleistocene coastline and seafloor deposits may accelerate with Arctic amplification of climate warming(2,13).
C1 [Vonk, J. E.; Sanchez-Garcia, L.; van Dongen, B. E.; Alling, V.; Andersson, A.; Gustafsson, O.] Stockholm Univ, Dept Appl Environm Sci ITM, SE-11418 Stockholm, Sweden.
   [Vonk, J. E.; Sanchez-Garcia, L.; van Dongen, B. E.; Alling, V.; Andersson, A.; Gustafsson, O.] Stockholm Univ, Bert Bolin Ctr Climate Res, SE-11418 Stockholm, Sweden.
   [Kosmach, D.; Charkin, A.; Semiletov, I. P.; Dudarev, O. V.; Shakhova, N.] Russian Acad Sci, Pacific Oceanol Inst, Vladivostok 690041, Russia.
   [Semiletov, I. P.; Shakhova, N.] Univ Alaska, Int Arctic Res Ctr, Fairbanks, AK 99775 USA.
   [Roos, P.] Riso Natl Lab Sustainable Energy, DK-4000 Roskilde, Denmark.
   [Eglinton, T. I.] Swiss Fed Inst Technol, Inst Geol, CH-8092 Zurich, Switzerland.
C3 Stockholm University; Stockholm University; Ilichev Pacific Oceanological Institute; Russian Academy of Sciences; University of Alaska System; University of Alaska Fairbanks; Technical University of Denmark; Swiss Federal Institutes of Technology Domain; ETH Zurich
RP Gustafsson, Ö (corresponding author), Stockholm Univ, Dept Appl Environm Sci ITM, Svante Arrhenius Vag 8, SE-11418 Stockholm, Sweden.
EM orjan.gustafsson@itm.su.se
FU Knut and Alice Wallenberg Foundation; Far Eastern Branch of the Russian Academy of Sciences; Swedish Research Council; US National Oceanic and Atmospheric Administration; Russian Foundation of Basic Research; Swedish Polar Research Secretariat; Nordic Council of Ministers; Swedish Royal Academy of Sciences; EU Marie Curie grant; US National Science Foundation; NOAA OAR Climate Program Office; NERC [NE/I024798/1] Funding Source: UKRI; Natural Environment Research Council [NE/I024798/1] Funding Source: researchfish
NR 30
TC 327
Z9 366
U1 5
U2 342
PU NATURE PUBLISHING 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 6
PY 2012
VL 489
IS 7414
BP 137
EP 140
DI 10.1038/nature11392
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 999WW
UT WOS:000308347000050
PM 22932271
DA 2026-03-09
ER

PT J
AU Ellegren, H
   Smeds, L
   Burri, R
   Olason, PI
   Backström, N
   Kawakami, T
   Künstner, A
   Mäkinen, H
   Nadachowska-Brzyska, K
   Qvarnström, A
   Uebbing, S
   Wolf, JBW
AF Ellegren, Hans
   Smeds, Linnea
   Burri, Reto
   Olason, Pall I.
   Backstrom, Niclas
   Kawakami, Takeshi
   Kunstner, Axel
   Makinen, Hannu
   Nadachowska-Brzyska, Krystyna
   Qvarnstrom, Anna
   Uebbing, Severin
   Wolf, Jochen B. W.
TI The genomic landscape of species divergence in Ficedula flycatchers
SO NATURE
LA English
DT Article
ID wild bird population; female meiotic drive; reproductive isolation; ecological speciation; hybrid sterility; evolution; consequences; hitchhiking; chicken
AB Unravelling the genomic landscape of divergence between lineages is key to understanding speciation(1). The naturally hybridizing collared flycatcher and pied flycatcher are important avian speciation models(2-7) that show pre- as well as postzygotic isolation(8,9). We sequenced and assembled the 1.1-Gb flycatcher genome, physically mapped the assembly to chromosomes using a low-density linkage map(10) and re-sequenced population samples of each species. Here we show that the genomic landscape of species differentiation is highly heterogeneous with approximately 50 'divergence islands' showing up to 50-fold higher sequence divergence than the genomic background. These non-randomly distributed islands, with between one and three regions of elevated divergence per chromosome irrespective of chromosome size, are characterized by reduced levels of nucleotide diversity, skewed allele-frequency spectra, elevated levels of linkage disequilibrium and reduced proportions of shared polymorphisms in both species, indicative of parallel episodes of selection. Proximity of divergence peaks to genomic regions resistant to sequence assembly, potentially including centromeres and telomeres, indicate that complex repeat structures may drive species divergence. A much higher background level of species divergence of the Z chromosome, and a lower proportion of shared polymorphisms, indicate that sex chromosomes and autosomes are at different stages of speciation. This study provides a roadmap to the emerging field of speciation genomics.
C1 [Ellegren, Hans; Smeds, Linnea; Burri, Reto; Olason, Pall I.; Backstrom, Niclas; Kawakami, Takeshi; Kunstner, Axel; Makinen, Hannu; Nadachowska-Brzyska, Krystyna; Uebbing, Severin; Wolf, Jochen B. W.] Uppsala Univ, Dept Evolutionary Biol, Evolutionary Biol Ctr, SE-75236 Uppsala, Sweden.
   [Qvarnstrom, Anna] Uppsala Univ, Dept Anim Ecol, Evolutionary Biol Ctr, SE-75263 Uppsala, Sweden.
C3 Uppsala University; Uppsala University
RP Ellegren, H (corresponding author), Uppsala Univ, Dept Evolutionary Biol, Evolutionary Biol Ctr, Norbyvagen 18D, SE-75236 Uppsala, Sweden.
EM Hans.Ellegren@ebc.uu.se
FU European Research Council; Knut and Alice Wallenberg Scholar Grant; Swedish Research Council; Swiss National Science Foundation [PBLAB3-134299, PBLAB1-140171]; Knut and Alice Wallenberg Foundation; Swedish National Infrastructure for Computing (SNIC)
NR 30
TC 500
Z9 593
U1 1
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 NOV 29
PY 2012
VL 491
IS 7426
BP 756
EP 760
DI 10.1038/nature11584
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 044FY
UT WOS:000311606000045
PM 23103876
DA 2026-03-09
ER

PT J
AU Lyons, JA
   Aragao, D
   Slattery, O
   Pisliakov, AV
   Soulimane, T
   Caffrey, M
AF Lyons, Joseph A.
   Aragao, David
   Slattery, Orla
   Pisliakov, Andrei V.
   Soulimane, Tewfik
   Caffrey, Martin
TI Structural insights into electron transfer in caa3-type cytochrome oxidase
SO NATURE
LA English
DT Article
ID crystallizing membrane-proteins; c-oxidase; thermus-thermophilus; paracoccus-denitrificans; nucleotide-sequence; molecular-dynamics; force-field; subunit; complex; site
AB Cytochrome c oxidase is a member of the haem copper oxidase superfamily (HCO)(1). HCOs function as the terminal enzymes in the respiratory chain of mitochondria and aerobic prokaryotes, coupling molecular oxygen reduction to transmembrane proton pumping. Integral to the enzyme's function is the transfer of electrons from cytochrome c to the oxidase via a transient association of the two proteins. Electron entry and exit are proposed to occur from the same site on cytochrome c(2-4). Here we report the crystal structure of the caa(3)-type cytochrome oxidase from Thermus thermophilus, which has a covalently tethered cytochrome c domain. Crystals were grown in a bicontinuous mesophase using a synthetic short-chain monoacylglycerol as the hosting lipid. From the electron density map, at 2.36 angstrom resolution, a novel integral membrane subunit and a native glycoglycerophospholipid embedded in the complex were identified. Contrary to previous electron transfer mechanisms observed for soluble cytochrome c, the structure reveals the architecture of the electron transfer complex for the fused cupredoxin/cytochrome c domain, which implicates different sites on cytochrome c for electron entry and exit. Support for an alternative to the classical proton gate characteristic of this HCO class is presented.
C1 [Lyons, Joseph A.; Slattery, Orla; Soulimane, Tewfik] Univ Limerick, Dept Chem & Environm Sci, Limerick, Ireland.
   [Lyons, Joseph A.; Aragao, David; Caffrey, Martin] Trinity Coll Dublin, Sch Biochem & Immunol, Dublin, Ireland.
   [Aragao, David] Australian Synchrotron, Clayton, Vic 3168, Australia.
   [Pisliakov, Andrei V.] RIKEN Adv Sci Inst, Theoret Biochem Lab, Wako, Saitama 3510198, Japan.
   [Soulimane, Tewfik] Univ Limerick, Mat & Surface Sci Inst, Limerick, Ireland.
   [Caffrey, Martin] Trinity Coll Dublin, Sch Med, Dublin, Ireland.
C3 University of Limerick; Trinity College Dublin; Australian Synchrotron; RIKEN; University of Limerick; Trinity College Dublin
RP Soulimane, T (corresponding author), Univ Limerick, Dept Chem & Environm Sci, Limerick, Ireland.
EM tewfik.soulimane@ul.ie; martin.caffrey@tcd.ie
FU Science Foundation Ireland [07/IN.1/B1836, BICF685]; National Institutes of Health [GM75915, P50GM073210, U54GM094599]; FP7 COST [CM0902]; Marie Curie Actions [PIEF-GA-2009-235612]; Grants-in-Aid for Scientific Research [22770163] Funding Source: KAKEN
NR 58
TC 111
Z9 125
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 JUL 26
PY 2012
VL 487
IS 7408
BP 514
EP 518
DI 10.1038/nature11182
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 979KD
UT WOS:000306815300045
PM 22763450
DA 2026-03-09
ER

PT J
AU Marinari, E
   Mehonic, A
   Curran, S
   Gale, J
   Duke, T
   Baum, B
AF Marinari, Eliana
   Mehonic, Aida
   Curran, Scott
   Gale, Jonathan
   Duke, Thomas
   Baum, Buzz
TI Live-cell delamination counterbalances epithelial growth to limit tissue overcrowding
SO NATURE
LA English
DT Article
ID drosophila; morphogenesis; mechanism
AB The development and maintenance of an epithelium requires finely balanced rates of growth and cell death. However, the mechanical and biochemical mechanisms that ensure proper feedback control of tissue growth(1-4), which when deregulated contribute to tumorigenesis, are poorly understood. Here we use the fly notum as a model system(5) to identify a novel process of crowding-induced cell delamination that balances growth to ensure the development of well-ordered cell packing. In crowded regions of the tissue, a proportion of cells undergo a serial loss of cell-cell junctions and a progressive loss of apical area, before being squeezed out by their neighbours. This path of delamination is recapitulated by a simple computational model of epithelial mechanics, in which stochastic cell loss relieves overcrowding as the system tends towards equilibrium. We show that this process of delamination is mechanistically distinct from apoptosis-mediated cell extrusion(6-8) and precedes the first signs of cell death. Overall, this analysis reveals a simple mechanism that buffers epithelia against variations in growth. Because live-cell delamination constitutes a mechanistic link between epithelial hyperplasia and cell invasion, this is likely to have important implications for our understanding of the early stages of cancer development.
C1 [Marinari, Eliana; Curran, Scott; Baum, Buzz] UCL, MRC, Mol Cell Biol Lab, London WC1E 6BT, England.
   [Mehonic, Aida; Duke, Thomas] UCL, London Ctr Nanotechnol, London WC1E 6BT, England.
   [Mehonic, Aida; Duke, Thomas] UCL, Dept Phys & Astron, London WC1E 6BT, England.
   [Gale, Jonathan] UCL, UCL Ear Inst, London WC1X 8EE, England.
C3 University of London; University College London; University of London; University College London; University of London; University College London; University of London; University College London
RP Baum, B (corresponding author), UCL, MRC, Mol Cell Biol Lab, Gower St, London WC1E 6BT, England.
EM b.baum@ucl.ac.uk
FU Cancer Research UK; University College London, Wellcome and the Royal Society; Medical Research Council [MC_CF12266] Funding Source: researchfish
NR 19
TC 340
Z9 387
U1 0
U2 66
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD APR 26
PY 2012
VL 484
IS 7395
BP 542
EP U177
DI 10.1038/nature10984
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 931FF
UT WOS:000303200400057
PM 22504180
DA 2026-03-09
ER

PT J
AU Brelidze, TI
   Carlson, AE
   Sankaran, B
   Zagotta, WN
AF Brelidze, Tinatin I.
   Carlson, Anne E.
   Sankaran, Banumathi
   Zagotta, William N.
TI Structure of the carboxy-terminal region of a KCNH channel
SO NATURE
LA English
DT Article
ID long-qt syndrome; functional-property; potassium channels; herg; activation; domain; validation
AB The KCNH family of ion channels, comprising ether-a-go-go (EAG), EAG-related gene (ERG), and EAG-like (ELK) K+-channel subfamilies, is crucial for repolarization of the cardiac action potential(1), regulation of neuronal excitability(2) and proliferation of tumour cells(3). The carboxy-terminal region of KCNH channels contains a cyclic-nucleotide-binding homology domain (CNBHD) and C-linker that couples the CNBHD to the pore(4). The C-linker/CNBHD is essential for proper function and trafficking of ion channels in the KCNH family(5-9). However, despite the importance of the C-linker/CNBHD for the function of KCNH channels, the structural basis of ion-channel regulation by the C-linker/CNBHD is unknown. Here we report the crystal structure of the C-linker/CNBHD of zebrafish ELK channels at 2.2-angstrom resolution. Although the overall structure of the C-linker/CNBHD of ELK channels is similar to the cyclic-nucleotide-binding domain (CNBD) structure of the related hyperpolarization-activated cyclic-nucleotide-modulated (HCN) channels(10), there are marked differences. Unlike the CNBD of HCN, the CNBHD of ELK displays a negatively charged electrostatic profile that explains the lack of binding and regulation of KCNH channels by cyclic nucleotides(4,11). Instead of cyclic nucleotide, the binding pocket is occupied by a short beta-strand. Mutations of the beta-strand shift the voltage dependence of activation to more depolarized voltages, implicating the beta-strand as an intrinsic ligand for the CNBHD of ELK channels. In both ELK and HCN channels the C-linker is the site of virtually all of the intersubunit interactions in the C-terminal region. However, in the zebrafish ELK structure there is a reorientation in the C-linker so that the subunits form dimers instead of tetramers, as observed in HCN channels. These results provide a structural framework for understanding the regulation of ion channels in the KCNH family by the C-linker/CNBHD and may guide the design of specific drugs.
C1 [Brelidze, Tinatin I.; Carlson, Anne E.; Zagotta, William N.] Univ Washington, Dept Physiol & Biophys, Sch Med, Seattle, WA 98195 USA.
   [Sankaran, Banumathi] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Berkeley Ctr Struct Biol, Berkeley, CA 94720 USA.
C3 University of Washington; University of Washington Seattle; United States Department of Energy (DOE); Lawrence Berkeley National Laboratory; University of California System; University of California Berkeley
RP Zagotta, WN (corresponding author), Univ Washington, Dept Physiol & Biophys, Sch Med, Box 357290, Seattle, WA 98195 USA.
EM zagotta@u.washington.edu
FU Howard Hughes Medical Institute; National Institutes of Health (NIH) [R01 EY010329, F32 HL095241]; NIH, National Institute of General Medical Sciences; Office of Science, Office of Basic Energy Sciences, of the US Department of Energy [DE-AC02-05CH11231]; National Eye Institute [R01EY010329] Funding Source: NIH RePORTER
NR 38
TC 105
Z9 116
U1 0
U2 21
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 26
PY 2012
VL 481
IS 7382
BP 530
EP U147
DI 10.1038/nature10735
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 881GY
UT WOS:000299471800045
PM 22230959
DA 2026-03-09
ER

PT J
AU Wilken, T
   Lo Curto, G
   Probst, RA
   Steinmetz, T
   Manescau, A
   Pasquini, L
   Hernández, JIG
   Rebolo, R
   Hänsch, TW
   Udem, T
   Holzwarth, R
AF Wilken, Tobias
   Lo Curto, Gaspare
   Probst, Rafael A.
   Steinmetz, Tilo
   Manescau, Antonio
   Pasquini, Luca
   Gonzalez Hernandez, Jonay I.
   Rebolo, Rafael
   Haensch, Theodor W.
   Udem, Thomas
   Holzwarth, Ronald
TI A spectrograph for exoplanet observations calibrated at the centimetre-per-second level
SO NATURE
LA English
DT Article
ID extra-solar planets; radial-velocity measurements; laser frequency combs; astronomical spectrographs; harps search; astro-comb; precision; deceleration; metrology
AB The best spectrographs are limited in stability by their calibration light source(1). Laser frequency combs are the ideal calibrators for astronomical spectrographs(2). They emit a spectrum of lines that are equally spaced in frequency(3) and that are as accurate and stable as the atomic clock relative to which the comb is stabilized. Absolute calibration(4) provides the radial velocity of an astronomical object relative to the observer (on Earth). For the detection of Earth-mass exoplanets(5,6) in Earth-like orbits around solar-type stars, or of cosmic acceleration(7-9), the observable is a tiny velocity change of less than 10 cm s(-1), where the repeatability of the calibration-the variation in stability across observations-is important. Hitherto, only laboratory systems(10-12) or spectrograph calibrations of limited performance(4,13,14) have been demonstrated. Here we report the calibration of an astronomical spectrograph with a short-term Doppler shift repeatability of 2.5 cm s(-1), and use it to monitor the star HD75289 and recompute the orbit of its planet. This repeatability should make it possible to detect Earth-like planets in the habitable zone of star or even to measure the cosmic acceleration directly.
C1 [Wilken, Tobias; Probst, Rafael A.; Steinmetz, Tilo; Haensch, Theodor W.; Udem, Thomas; Holzwarth, Ronald] Max Planck Inst Quantum Opt, D-85748 Garching, Germany.
   [Wilken, Tobias; Steinmetz, Tilo; Holzwarth, Ronald] Menlo Syst GmbH, D-82152 Martinsried, Germany.
   [Lo Curto, Gaspare; Manescau, Antonio; Pasquini, Luca] European So Observ, D-85748 Garching, Germany.
   [Gonzalez Hernandez, Jonay I.; Rebolo, Rafael] Inst Astrofis Canarias, E-38205 San Cristobal la Laguna, Spain.
   [Gonzalez Hernandez, Jonay I.; Rebolo, Rafael] Univ La Laguna, Dept Astrofis, E-38206 San Cristobal la Laguna, Spain.
   [Rebolo, Rafael] CSIC, E-28006 Madrid, Spain.
C3 Max Planck Society; Menlo Systems GmbH; European Southern Observatory; Instituto de Astrofisica de Canarias; Universidad de la Laguna; Consejo Superior de Investigaciones Cientificas (CSIC)
RP Wilken, T (corresponding author), Max Planck Inst Quantum Opt, Hans Kopfermann Str 1, D-85748 Garching, Germany.
EM tobias.wilken@mpq.mpg.de; rlh@mpq.mpg.de
FU Max Planck Foundation
NR 24
TC 221
Z9 256
U1 1
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 MAY 31
PY 2012
VL 485
IS 7400
BP 611
EP 614
DI 10.1038/nature11092
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 949WP
UT WOS:000304608000041
PM 22660320
DA 2026-03-09
ER

PT J
AU Kinoshita, M
   Matsui, R
   Kato, S
   Hasegawa, T
   Kasahara, H
   Isa, K
   Watakabe, A
   Yamamori, T
   Nishimura, Y
   Alstermark, B
   Watanabe, D
   Kobayashi, K
   Isa, T
AF Kinoshita, Masaharu
   Matsui, Ryosuke
   Kato, Shigeki
   Hasegawa, Taku
   Kasahara, Hironori
   Isa, Kaoru
   Watakabe, Akiya
   Yamamori, Tetsuo
   Nishimura, Yukio
   Alstermark, Bror
   Watanabe, Dai
   Kobayashi, Kazuto
   Isa, Tadashi
TI Genetic dissection of the circuit for hand dexterity in primates
SO NATURE
LA English
DT Article
ID disynaptic pyramidal excitation; spinal-cord-injury; propriospinal neurons; forelimb motoneurons; macaque monkey; motor system; expression; pathways; integration; cat
AB It is generally accepted that the direct connection from the motor cortex to spinal motor neurons is responsible for dexterous hand movements in primates(1-3). However, the role of the 'phylogenetically older' indirect pathways from the motor cortex to motor neurons, mediated by spinal interneurons, remains elusive. Here we used a novel double-infection technique to interrupt the transmission through the propriospinal neurons (PNs)(4-6), which act as a relay of the indirect pathway in macaque monkeys (Macaca fuscata and Macaca mulatta). The PNs were double infected by injection of a highly efficient retrograde gene-transfer vector into their target area and subsequent injection of adeno-associated viral vector at the location of cell somata. This method enabled reversible expression of green fluorescent protein (GFP)-tagged tetanus neurotoxin, thereby permitting the selective and temporal blockade of the motor cortex-PN-motor neuron pathway. This treatment impaired reach and grasp movements, revealing a critical role for the PN-mediated pathway in the control of hand dexterity. Anti-GFP immunohistochemistry visualized the cell bodies and axonal trajectories of the blocked PNs, which confirmed their anatomical connection to motor neurons. This pathway-selective and reversible technique for blocking neural transmission does not depend on cell-specific promoters or transgenic techniques, and is a new and powerful tool for functional dissection in system-level neuroscience studies.
C1 [Kinoshita, Masaharu; Isa, Kaoru; Nishimura, Yukio; Isa, Tadashi] Natl Inst Physiol Sci, Dept Dev Physiol, Okazaki, Aichi 4448585, Japan.
   [Matsui, Ryosuke; Hasegawa, Taku; Kasahara, Hironori; Watanabe, Dai] Kyoto Univ, Grad Sch Biostudies, Dept Mol & Syst Biol, Sakyo Ku, Kyoto 6068501, Japan.
   [Kato, Shigeki; Kobayashi, Kazuto] Fukushima Med Univ Sch Med, Inst Biomed Sci, Dept Mol Genet, Fukushima 9601295, Japan.
   [Watakabe, Akiya; Yamamori, Tetsuo] Natl Inst Basic Biol, Div Brain Biol, Okazaki, Aichi 4448585, Japan.
   [Watakabe, Akiya; Yamamori, Tetsuo; Nishimura, Yukio; Isa, Tadashi] Grad Univ Adv Studies Sokendai, Kanagawa 2400193, Japan.
   [Nishimura, Yukio] Japan Sci & Technol Agcy JST, Precursory Res Embryon Sci & Technol PRESTO, Tokyo 1020076, Japan.
   [Alstermark, Bror] Umea Univ, Physiol Sect, Dept Integrat Med Biol, S-90187 Umea, Sweden.
C3 National Institutes of Natural Sciences (NINS) - Japan; National Institute for Physiological Sciences (NIPS); Kyoto University; Fukushima Medical University; National Institutes of Natural Sciences (NINS) - Japan; National Institute for Basic Biology (NIBB); Graduate University for Advanced Studies - Japan; Japan Science & Technology Agency (JST); Umea University
RP Isa, T (corresponding author), Natl Inst Physiol Sci, Dept Dev Physiol, Okazaki, Aichi 4448585, Japan.
EM tisa@nips.ac.jp
FU Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan; Swedish Research Council; Grants-in-Aid for Scientific Research [20240030, 24120513, 22123009] Funding Source: KAKEN
NR 32
TC 198
Z9 224
U1 0
U2 41
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUL 12
PY 2012
VL 487
IS 7406
BP 235
EP U1510
DI 10.1038/nature11206
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 972LP
UT WOS:000306278900040
PM 22722837
DA 2026-03-09
ER

PT J
AU van Beijnum, F
   Rétif, C
   Smiet, CB
   Liu, HT
   Lalanne, P
   van Exter, MP
AF van Beijnum, Frerik
   Retif, Chris
   Smiet, Chris B.
   Liu, Haitao
   Lalanne, Philippe
   van Exter, Martin P.
TI Quasi-cylindrical wave contribution in experiments on extraordinary optical transmission
SO NATURE
LA English
DT Article
ID subwavelength hole arrays; plasmons
AB A metal film perforated by a regular array of subwavelength holes shows unexpectedly large transmission at particular wavelengths, a phenomenon known as the extraordinary optical transmission (EOT) of metal hole arrays(1). EOT was first attributed to surface plasmon polaritons, stimulating a renewed interest in plasmonics(2-4) and metallic surfaces with subwavelength features(5-7). Experiments soon revealed that the field diffracted at a hole or slit is not a surface plasmon polariton mode alone8. Further theoretical analysis(9) predicted that the extra contribution, from quasi-cylindrical waves(10-13), also affects EOT. Here we report the experimental demonstration of the relative importance of surface plasmon polaritons and quasi-cylindrical waves in EOT by considering hole arrays of different hole densities. From the measured transmission spectra, we determine microscopic scattering parameters which allow us to show that quasi-cylindrical waves affect EOT only for high densities, when the hole spacing is roughly one wavelength. Apart from providing a deeper understanding of EOT, the determination of microscopic scattering parameters from the measurement of macroscopic optical properties paves the way to novel design strategies.
C1 [van Beijnum, Frerik; Smiet, Chris B.; van Exter, Martin P.] Leiden Univ, Huygens Lab, NL-2300 RA Leiden, Netherlands.
   [Retif, Chris] FOM Inst Atom & Mol Phys, NL-1098 XG Amsterdam, Netherlands.
   [Liu, Haitao] Nankai Univ, Inst Modern Opt, Minist Educ, Key Lab Opt Informat Sci & Technol, Tianjin 300071, Peoples R China.
   [Lalanne, Philippe] Univ Bordeaux 1, CNRS, Inst Opt, Lab Photon Numer & Nanosci LP2N, F-33405 Talence, France.
C3 Leiden University - Excl LUMC; Leiden University; AMOLF; Nankai University; Universite de Bordeaux; Centre National de la Recherche Scientifique (CNRS); Universite Paris Saclay
RP van Beijnum, F (corresponding author), Leiden Univ, Huygens Lab, POB 9504, NL-2300 RA Leiden, Netherlands.
EM beijnum@physics.leidenuniv.nl
FU CNRS; 973 Program [2013CB328701]
NR 25
TC 99
Z9 109
U1 2
U2 187
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD DEC 20
PY 2012
VL 492
IS 7429
BP 411
EP 414
DI 10.1038/nature11669
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 056KQ
UT WOS:000312488200052
PM 23257884
DA 2026-03-09
ER

PT J
AU Zhu, GZ
   Radtke, G
   Botton, GA
AF Zhu, Guo-zhen
   Radtke, Guillaume
   Botton, Gianluigi A.
TI Bonding and structure of a reconstructed (001) surface of SrTiO3 from TEM
SO NATURE
LA English
DT Article
ID electron; microscopy
AB The determination of the atomic structure and the retrieval of information about reconstruction and bonding of metal oxide surfaces is challenging owing to the highly defective structure and insulating properties of these surfaces. Transmission electron microscopy (TEM) offers extremely high spatial resolution (less than one angstrom) and the ability to provide systematic information from both real and reciprocal space. However, very few TEM studies(1-3) have been carried out on surfaces because the information from the bulk dominates the very weak signals originating from surfaces. Here we report an experimental approach to extract surface information effectively from a thickness series of electron energy-loss spectra containing different weights of surface signals, using a wedge-shaped sample. Using the (001) surface of the technologically important compound strontium titanate, SrTiO3 (refs 4-6), as a model system for validation, our method shows that surface spectra are sensitive to the atomic reconstruction and indicate bonding and crystal-field changes surrounding the surface Ti cations. Very good agreement can be achieved between the experimental surface spectra and crystal-field multiplet calculations based on the proposed atomic surface structure optimized by density functional calculations(3). The distorted TiO6-x units indicated by the proposed model can be viewed directly in our high-resolution scanning TEM images. We suggest that this approach be used as a general method to extract valuable spectroscopic information from surface atoms in parallel with high-resolution images in TEM.
C1 [Zhu, Guo-zhen; Botton, Gianluigi A.] McMaster Univ, Canadian Ctr Electron Microscopy, Hamilton, ON L8S 4M1, Canada.
   [Zhu, Guo-zhen; Botton, Gianluigi A.] McMaster Univ, Dept Mat Sci & Engn, Hamilton, ON L8S 4M1, Canada.
   [Radtke, Guillaume] Aix Marseille Univ, Fac Sci St Jerome, CNRS, IM2NP,UMR 7334,Case 262, F-13397 Marseille 20, France.
C3 McMaster University; McMaster University; Aix-Marseille Universite; Centre National de la Recherche Scientifique (CNRS)
RP Botton, GA (corresponding author), McMaster Univ, Canadian Ctr Electron Microscopy, 1280 Main St W, Hamilton, ON L8S 4M1, Canada.
EM gbotton@mcmaster.ca
FU NSERC; McMaster University
NR 21
TC 98
Z9 109
U1 1
U2 294
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 18
PY 2012
VL 490
IS 7420
BP 384
EP 387
DI 10.1038/nature11563
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 021XI
UT WOS:000309918500042
PM 23051749
DA 2026-03-09
ER

PT J
AU Rest, A
   Prieto, JL
   Walborn, NR
   Smith, N
   Bianco, FB
   Chornock, R
   Welch, DL
   Howell, DA
   Huber, ME
   Foley, RJ
   Fong, W
   Sinnott, B
   Bond, HE
   Smith, RC
   Toledo, I
   Minniti, D
   Mandel, K
AF Rest, A.
   Prieto, J. L.
   Walborn, N. R.
   Smith, N.
   Bianco, F. B.
   Chornock, R.
   Welch, D. L.
   Howell, D. A.
   Huber, M. E.
   Foley, R. J.
   Fong, W.
   Sinnott, B.
   Bond, H. E.
   Smith, R. C.
   Toledo, I.
   Minniti, D.
   Mandel, K.
TI Light echoes reveal an unexpectedly cool η Carinae during its nineteenth-century Great Eruption
SO NATURE
LA English
DT Article
ID luminous blue variables; homunculus; spectra; progenitors; transients; supernovae; diversity; nebula; analog; mass
AB eta Carinae is one of the most massive binary stars in the Milky Way(1,2). It became the second-brightest star in our sky during its mid-nineteenth-century 'Great Eruption', but then faded from view (with only naked-eye estimates of brightness(3,4)). Its eruption is unique in that it exceeded the Eddington luminosity limit for ten years. Because it is only 2.3 kiloparsecs away, spatially resolved studies of the nebula have constrained the ejected mass and velocity, indicating that during its nineteenth-century eruption, eta Car ejected more than ten solar masses in an event that released ten per cent of the energy of a typical core-collapse supernova(5,6), without destroying the star. Here we report observations of light echoes of eta Carinae from the 1838-1858 Great Eruption. Spectra of these light echoes show only absorption lines, which are blueshifted by -210 km s(-1), in good agreement with predicted expansion speeds(6). The light-echo spectra correlate best with those of G2-to-G5 supergiants, which have effective temperatures of around 5,000 kelvin. In contrast to the class of extragalactic outbursts assumed to be analogues of the Great Eruption of eta Carinae(7-12), the effective temperature of its outburst is significantly lower than that allowed by standard opaque wind models(13). This indicates that other physical mechanisms such as an energetic blast wave may have triggered and influenced the eruption.
C1 [Rest, A.; Walborn, N. R.; Bond, H. E.] Space Telescope Sci Inst, Baltimore, MD 21218 USA.
   [Prieto, J. L.] Carnegie Observ, Pasadena, CA 91101 USA.
   [Prieto, J. L.] Princeton Univ, Dept Astrophys Sci, Princeton, NJ 08544 USA.
   [Smith, N.] Univ Arizona, Steward Observ, Tucson, AZ 85721 USA.
   [Bianco, F. B.; Howell, D. A.] Las Cumbres Observ Global Telescope Network, Goleta, CA 93117 USA.
   [Bianco, F. B.; Howell, D. A.] Univ Calif Santa Barbara, Dept Phys, Santa Barbara, CA 93106 USA.
   [Chornock, R.; Foley, R. J.; Fong, W.; Mandel, K.] Harvard Smithsonian Ctr Astrophys, Cambridge, MA 02138 USA.
   [Welch, D. L.; Sinnott, B.] McMaster Univ, Dept Phys & Astron, Hamilton, ON L8S 4M1, Canada.
   [Huber, M. E.] Johns Hopkins Univ, Dept Phys & Astron, Baltimore, MD 21218 USA.
   [Smith, R. C.] Cerro Tololo Interamer Observ, Natl Opt Astron Observ, La Serena, Chile.
   [Toledo, I.] ALMA, San Pedro De Atacama, Ii Region, Chile.
   [Minniti, D.] Pontificia Univ Catolica Chile, Dept Astron & Astrophys, Santiago 22, Chile.
   [Mandel, K.] Univ London Imperial Coll Sci Technol & Med, Blackett Lab, London SW7 2AZ, England.
C3 Space Telescope Science Institute; Carnegie Institution for Science; Princeton University; University of Arizona; University of California System; University of California Santa Barbara; Harvard University; Smithsonian Institution; Smithsonian Astrophysical Observatory; McMaster University; Johns Hopkins University; National Optical Astronomy Observatory; Cerro Tololo Inter-American Observatory; Pontificia Universidad Catolica de Chile; Imperial College London
RP Rest, A (corresponding author), Space Telescope Sci Inst, 3700 San Martin Dr, Baltimore, MD 21218 USA.
EM arest@stsci.edu
FU National Science Foundation; LCOGT
CR [Bagnulo SESO Paranal Science Operations Team ESO Paranal Science Operations Team], 2003, THE MESSENGER, V114, P10
   Cenarro AJ, 2001, MON NOT R ASTRON SOC, V326, P959, DOI 10.1046/j.1365-8711.2001.04688.x
   Damineli A, 1996, ASTROPHYS J, V460, PL49, DOI 10.1086/309961
   DAVIDSON K, 1987, ASTROPHYS J, V317, P760, DOI 10.1086/165324
   Davidson K, 1997, ANNU REV ASTRON ASTR, V35, P1, DOI 10.1146/annurev.astro.35.1.1
   Foley RJ, 2011, ASTROPHYS J, V732, P0, DOI 10.1088/0004-637X/732/1/32
   Frew DJ, 2004, J ASTRONOMICAL DATA, V10, P6
   GOODRICH RW, 1989, ASTROPHYS J, V342, P908, DOI 10.1086/167646
   Humphreys RM, 2008, ASTRON J, V135, P1249
   Humphreys RM, 1999, PUBL ASTRON SOC PAC, V111, P1124, DOI 10.1086/316420
   HUMPHREYS RM, 1994, PUBL ASTRON SOC PAC, V106, P1025, DOI 10.1086/133478
   Kashi A, 2010, ASTROPHYS J LETT, V709, PL11, DOI 10.1088/2041-8205/709/1/L11
   Le Sueur A, 1870, P R SOC LONDON, V19, P18
   Rest A, 2008, ASTROPHYS J LETT, V681, PL81, DOI 10.1086/590427
   Rest A, 2005, NATURE, V438, P1132, DOI 10.1038/nature04365
   Rest A, 2011, ASTROPHYS J, V732, P0, DOI 10.1088/0004-637X/732/1/2
   Smith N, 2005, MON NOT R ASTRON SOC, V357, P1330, DOI 10.1111/j.1365-2966.2005.08750.x
   Smith N, 2004, ASTROPHYS J, V615, P475, DOI 10.1086/424030
   Smith N, 2003, ASTRON J, V125, P1458, DOI 10.1086/346278
   Smith N, 2008, NATURE, V455, P201, DOI 10.1038/nature07269
   Smith N, 2006, ASTROPHYS J, V644, P1151, DOI 10.1086/503766
   Smith N, 2011, MON NOT R ASTRON SOC, V415, P2009, DOI 10.1111/j.1365-2966.2011.18993.x
   Smith N, 2011, MON NOT R ASTRON SOC, V415, P773, DOI 10.1111/j.1365-2966.2011.18763.x
   Smith N, 2010, ASTRON J, V139, P1451, DOI 10.1088/0004-6256/139/4/1451
   Van Dyk SD, 2000, PUBL ASTRON SOC PAC, V112, P1532, DOI 10.1086/317727
   Vink JS, 2009, ETA CARINAE LUMINOUS, V0, P0
   Walborn NR, 1977, ASTROPHYS J, V211, P181
NR 28
TC 64
Z9 75
U1 0
U2 5
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD FEB 16
PY 2012
VL 482
IS 7385
BP 375
EP 378
DI 10.1038/nature10775
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 892LG
UT WOS:000300287100040
PM 22337057
DA 2026-03-09
ER

PT J
AU Mueller, ND
   Gerber, JS
   Johnston, M
   Ray, DK
   Ramankutty, N
   Foley, JA
AF Mueller, Nathaniel D.
   Gerber, James S.
   Johnston, Matt
   Ray, Deepak K.
   Ramankutty, Navin
   Foley, Jonathan A.
TI Closing yield gaps through nutrient and water management
SO NATURE
LA English
DT Article
ID intensification; climate; imbalances; challenge; demand
AB In the coming decades, a crucial challenge for humanity will be meeting future food demands without undermining further the integrity of the Earth's environmental systems(1-6). Agricultural systems are already major forces of global environmental degradation(4,7), but population growth and increasing consumption of calorie- and meat-intensive diets are expected to roughly double human food demand by 2050 (ref. 3). Responding to these pressures, there is increasing focus on 'sustainable intensification' as a means to increase yields on underperforming landscapes while simultaneously decreasing the environmental impacts of agricultural systems(2-4,8-11). However, it is unclear what such efforts might entail for the future of global agricultural landscapes. Here we present a global-scale assessment of intensification prospects from closing 'yield gaps' (differences between observed yields and those attainable in a given region), the spatial patterns of agricultural management practices and yield limitation, and the management changes that may be necessary to achieve increased yields. We find that global yield variability is heavily controlled by fertilizer use, irrigation and climate. Large production increases (45% to 70% for most crops) are possible from closing yield gaps to 100% of attainable yields, and the changes to management practices that are needed to close yield gaps vary considerably by region and current intensity. Furthermore, we find that there are large opportunities to reduce the environmental impact of agriculture by eliminating nutrient overuse, while still allowing an approximately 30% increase in production of major cereals (maize, wheat and rice). Meeting the food security and sustainability challenges of the coming decades is possible, but will require considerable changes in nutrient and water management.
C1 [Mueller, Nathaniel D.; Gerber, James S.; Johnston, Matt; Ray, Deepak K.; Foley, Jonathan A.] Univ Minnesota, Inst Environm IonE, St Paul, MN 55108 USA.
   [Ramankutty, Navin] McGill Univ, Dept Geog, Montreal, PQ H3A 2K6, Canada.
   [Ramankutty, Navin] McGill Univ, Global Environm & Climate Change Ctr, Montreal, PQ H3A 2K6, Canada.
C3 University of Minnesota System; University of Minnesota Twin Cities; McGill University; McGill University
RP Mueller, ND (corresponding author), Univ Minnesota, Inst Environm IonE, St Paul, MN 55108 USA.
EM muell512@umn.edu
FU National Science Foundation Graduate Research Fellowship; University of Minnesota College of Food, Agricultural and Natural Resource Sciences Fellowship; Natural Sciences and Engineering Research Council (NSERC) of Canada Discovery Grant; Gordon and Betty Moore Foundation; University of Minnesota Institute on the Environment
NR 29
TC 2140
Z9 2514
U1 39
U2 2453
PU NATURE PUBLISHING 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 11
PY 2012
VL 490
IS 7419
BP 254
EP 257
DI 10.1038/nature11420
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 019IY
UT WOS:000309733300048
PM 22932270
DA 2026-03-09
ER

PT J
AU Pugh, TJ
   Weeraratne, SD
   Archer, TC
   Krummel, DAP
   Auclair, D
   Bochicchio, J
   Carneiro, MO
   Carter, SL
   Cibulskis, K
   Erlich, RL
   Greulich, H
   Lawrence, MS
   Lennon, NJ
   McKenna, A
   Meldrim, J
   Ramos, AH
   Ross, MG
   Russ, C
   Shefler, E
   Sivachenko, A
   Sogoloff, B
   Stojanov, P
   Tamayo, P
   Mesirov, JP
   Amani, V
   Teider, N
   Sengupta, S
   Francois, JP
   Northcott, PA
   Taylor, MD
   Yu, FR
   Crabtree, GR
   Kautzman, AG
   Gabriel, SB
   Getz, G
   Jäger, N
   Jones, DTW
   Lichter, P
   Pfister, SM
   Roberts, TM
   Meyerson, M
   Pomeroy, SL
   Cho, YJ
AF Pugh, Trevor J.
   Weeraratne, Shyamal Dilhan
   Archer, Tenley C.
   Krummel, Daniel A. Pomeranz
   Auclair, Daniel
   Bochicchio, James
   Carneiro, Mauricio O.
   Carter, Scott L.
   Cibulskis, Kristian
   Erlich, Rachel L.
   Greulich, Heidi
   Lawrence, Michael S.
   Lennon, Niall J.
   McKenna, Aaron
   Meldrim, James
   Ramos, Alex H.
   Ross, Michael G.
   Russ, Carsten
   Shefler, Erica
   Sivachenko, Andrey
   Sogoloff, Brian
   Stojanov, Petar
   Tamayo, Pablo
   Mesirov, Jill P.
   Amani, Vladimir
   Teider, Natalia
   Sengupta, Soma
   Francois, Jessica Pierre
   Northcott, Paul A.
   Taylor, Michael D.
   Yu, Furong
   Crabtree, Gerald R.
   Kautzman, Amanda G.
   Gabriel, Stacey B.
   Getz, Gad
   Jaeger, Natalie
   Jones, David T. W.
   Lichter, Peter
   Pfister, Stefan M.
   Roberts, Thomas M.
   Meyerson, Matthew
   Pomeroy, Scott L.
   Cho, Yoon-Jae
TI Medulloblastoma exome sequencing uncovers subtype-specific somatic mutations
SO NATURE
LA English
DT Article
ID structural basis; childhood; landscape; complex; genes
AB Medulloblastomas are themost commonmalignant brain tumours in children(1). Identifying and understanding the genetic events that drive these tumours is critical for the development of more effective diagnostic, prognostic and therapeutic strategies. Recently, our group and others described distinct molecular subtypes ofmedulloblastoma on the basis of transcriptional and copy number profiles(2-5). Here we use whole-exome hybrid capture and deep sequencing to identify somatic mutations across the coding regions of 92 primary medulloblastoma/normal pairs. Overall, medulloblastomas have low mutation rates consistent with other paediatric tumours, with a median of 0.35 non-silent mutations per megabase. We identified twelve genes mutated at statistically significant frequencies, including previously known mutated genes in medulloblastoma such as CTNNB1, PTCH1, MLL2, SMARCA4 andTP53. Recurrent somatic mutations were newly identified in an RNA helicase gene, DDX3X, often concurrent with CTNNB1 mutations, and in the nuclear co-repressor (N-CoR) complex genes GPS2, BCOR and LDB1. We show that mutant DDX3X potentiates transactivation of a TCF promoter and enhances cell viability in combination with mutant, but not wild-type, beta-catenin. Together, our study reveals the alteration ofWNT, hedgehog, histone methyltransferase and now N-CoR pathways across medulloblastomas and within specific subtypes of this disease, and nominates theRNA helicase DDX3X as a component of pathogenic b-catenin signalling in medulloblastoma.
C1 [Pugh, Trevor J.; Auclair, Daniel; Bochicchio, James; Carneiro, Mauricio O.; Carter, Scott L.; Cibulskis, Kristian; Erlich, Rachel L.; Greulich, Heidi; Lawrence, Michael S.; Lennon, Niall J.; McKenna, Aaron; Meldrim, James; Ramos, Alex H.; Ross, Michael G.; Russ, Carsten; Shefler, Erica; Sivachenko, Andrey; Sogoloff, Brian; Stojanov, Petar; Tamayo, Pablo; Mesirov, Jill P.; Gabriel, Stacey B.; Getz, Gad; Meyerson, Matthew; Pomeroy, Scott L.; Cho, Yoon-Jae] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.
   [Pugh, Trevor J.; Greulich, Heidi; Ramos, Alex H.; Roberts, Thomas M.; Meyerson, Matthew] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
   [Pugh, Trevor J.; Greulich, Heidi; Ramos, Alex H.; Roberts, Thomas M.; Meyerson, Matthew] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Dept Med Oncol, Boston, MA 02115 USA.
   [Pugh, Trevor J.; Weeraratne, Shyamal Dilhan; Archer, Tenley C.; Greulich, Heidi; Ramos, Alex H.; Amani, Vladimir; Teider, Natalia; Sengupta, Soma; Francois, Jessica Pierre; Roberts, Thomas M.; Meyerson, Matthew; Pomeroy, Scott L.; Cho, Yoon-Jae] Harvard Univ, Sch Med, Boston, MA 02115 USA.
   [Weeraratne, Shyamal Dilhan; Archer, Tenley C.; Amani, Vladimir; Teider, Natalia; Sengupta, Soma; Francois, Jessica Pierre; Pomeroy, Scott L.; Cho, Yoon-Jae] Childrens Hosp, Dept Neurol, Boston, MA 02115 USA.
   [Krummel, Daniel A. Pomeranz] Brandeis Univ, Waltham, MA 02453 USA.
   [Northcott, Paul A.; Taylor, Michael D.] Hosp Sick Children, Toronto, ON M5G 1X8, Canada.
   [Yu, Furong; Crabtree, Gerald R.; Kautzman, Amanda G.; Cho, Yoon-Jae] Stanford Univ, Sch Med, Dept Neurol, Stanford, CA 94305 USA.
   [Yu, Furong; Crabtree, Gerald R.; Kautzman, Amanda G.; Cho, Yoon-Jae] Stanford Univ, Sch Med, Dept Neurosurg, Stanford, CA 94305 USA.
   [Crabtree, Gerald R.] Stanford Univ, Howard Hughes Med Inst, Stanford, CA 94305 USA.
   [Jaeger, Natalie; Jones, David T. W.; Lichter, Peter; Pfister, Stefan M.] German Canc Res Ctr, D-69120 Heidelberg, Germany.
   [Meyerson, Matthew] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 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; Dana-Farber Cancer Institute; Harvard University; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Brandeis University; University of Toronto; Hospital for Sick Children (SickKids); Stanford University; Stanford University; Stanford University; Howard Hughes Medical Institute; Helmholtz Association; German Cancer Research Center (DKFZ); Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital
RP Cho, YJ (corresponding author), Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.
EM matthew_meyerson@dfci.harvard.edu; scott.pomeroy@childrens.harvard.edu; yjcho1@stanford.edu
FU NIH [NHGRI U54HG003067, R01CA109467, R01CA105607, P30 HD18655, R01 CA030002, CA050661, R01 NS046789, R01 CA154480, R25NS070682, R01CA148699]; St. Baldrick's Foundation Scholar Award; Beirne Faculty Scholar endowment and Center for Children's Brain Tumors at Stanford University; German Cancer Aid [109252]; BMBF ICGC-PedBrain project; HHMI; Pediatric Brain Tumor Foundation; Canadian Institutes of Health Research Fellowship; Hospital for Sick Children; Mullarkey Research Fund; National Institute of Neurological Disorders and Stroke [R25NS070682] Funding Source: NIH RePORTER
NR 29
TC 627
Z9 752
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 AUG 2
PY 2012
VL 488
IS 7409
BP 106
EP 110
DI 10.1038/nature11329
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 981ZE
UT WOS:000307010700042
PM 22820256
DA 2026-03-09
ER

PT J
AU Nishimasu, H
   Ishizu, H
   Saito, K
   Fukuhara, S
   Kamatani, MK
   Bonnefond, L
   Matsumoto, N
   Nishizawa, T
   Nakanaga, K
   Aoki, J
   Ishitani, R
   Siomi, H
   Siomi, MC
   Nureki, O
AF Nishimasu, Hiroshi
   Ishizu, Hirotsugu
   Saito, Kuniaki
   Fukuhara, Satoshi
   Kamatani, Miharu K.
   Bonnefond, Luc
   Matsumoto, Naoki
   Nishizawa, Tomohiro
   Nakanaga, Keita
   Aoki, Junken
   Ishitani, Ryuichiro
   Siomi, Haruhiko
   Siomi, Mikiko C.
   Nureki, Osamu
TI Structure and function of Zucchini endoribonuclease in piRNA biogenesis
SO NATURE
LA English
DT Article
ID phospholipase-d family; crystal-structure; nuage formation; small rnas; drosophila; germline; genome; piwi; replacement; mechanism
AB PIWI-interacting RNAs (piRNAs) silence transposons to maintain genome integrity in animal germ lines(1-4). piRNAs are classified as primary and secondary piRNAs, depending on their biogenesis machinery(5-10). Primary piRNAs are processed from long non-coding RNA precursors transcribed from piRNA clusters in the genome through the primary processing pathway(5,8-10). Although the existence of a ribonuclease participating in this pathway has been predicted, its molecular identity remained unknown. Here we show that Zucchini (Zuc), a mitochondrial phospholipase D (PLD) superfamily member(11), is an endoribonuclease essential for primary piRNA biogenesis. We solved the crystal structure of Drosophila melanogaster Zuc (DmZuc) at 1.75 angstrom resolution. The structure revealed that DmZuc has a positively charged, narrow catalytic groove at the dimer interface, which could accommodate a single-stranded, but not a double-stranded, RNA. DmZuc and the mouse homologue MmZuc (also known as Pld6 and MitoPLD)(12-14) showed endoribonuclease activity for single-stranded RNAs in vitro. The RNA cleavage products bear a 5'-monophosphate group, a hallmark of mature piRNAs. Mutational analyses revealed that the conserved active-site residues of DmZuc are critical for the ribonuclease activity in vitro, and for piRNA maturation and transposon silencing in vivo. We propose a model for piRNA biogenesis in animal germ lines, in which the Zuc endoribonuclease has a key role in primary piRNA maturation.
C1 [Nishimasu, Hiroshi; Ishizu, Hirotsugu; Fukuhara, Satoshi; Bonnefond, Luc; Matsumoto, Naoki; Nishizawa, Tomohiro; Ishitani, Ryuichiro; Siomi, Mikiko C.; Nureki, Osamu] Univ Tokyo, Grad Sch Sci, Dept Biophys & Biochem, Tokyo 1130032, Japan.
   [Ishizu, Hirotsugu; Saito, Kuniaki; Kamatani, Miharu K.; Siomi, Haruhiko; Siomi, Mikiko C.] Keio Univ, Sch Med, Dept Mol Biol, Tokyo 1608582, Japan.
   [Nakanaga, Keita; Aoki, Junken] Tohoku Univ, Grad Sch Pharmaceut Sci, Sendai, Miyagi 9808578, Japan.
   [Siomi, Mikiko C.; Nureki, Osamu] Japan Sci & Technol Agcy JST, Core Res Evolut Sci & Technol CREST, Saitama 3320012, Japan.
C3 University of Tokyo; Keio University; Tohoku University; Japan Science & Technology Agency (JST)
RP Nureki, O (corresponding author), Univ Tokyo, Grad Sch Sci, Dept Biophys & Biochem, Tokyo 1130032, Japan.
EM siomim@biochem.s.u-tokyo.ac.jp; nureki@biochem.s.u-tokyo.ac.jp
FU Japan Society for the Promotion of Science (JSPS); Core Research for Evolutional Science and Technology (CREST) program 'The Creation of Basic Medical Technologies to Clarify and Control the Mechanisms Underlying Chronic Inflammation' of the Japan Science and Technology Agency (JST); Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan; Grants-in-Aid for Scientific Research [20221008, 22687007, 23687014, 22117007, 10J56562, 11J05211] Funding Source: KAKEN
NR 33
TC 273
Z9 328
U1 0
U2 44
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD NOV 8
PY 2012
VL 491
IS 7423
BP 284
EP U157
DI 10.1038/nature11509
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 033DP
UT WOS:000310774300050
PM 23064230
DA 2026-03-09
ER

PT J
AU Grebenev, SA
   Lutovinov, AA
   Tsygankov, SS
   Winkler, C
AF Grebenev, S. A.
   Lutovinov, A. A.
   Tsygankov, S. S.
   Winkler, C.
TI Hard-X-ray emission lines from the decay of 44Ti in the remnant of supernova 1987A
SO NATURE
LA English
DT Article
ID sn 1987a; galactic supernova; sn-1987a; spectrum; cassiopeia; ejecta; co-57
AB It is assumed(1-3) that the radioactive decay of Ti-44 powers the infrared, optical and ultraviolet emission of supernova remnants after the complete decay of Co-56 and Co-57 (the isotopes that dominated the energy balance during the first three to four years after the explosion) until the beginning of active interaction of the ejecta with the surrounding matter. Simulations(4,5) show that the initial mass of Ti-44 synthesized in core-collapse supernovae is (0.02-2.5) x 10(-4) solar masses (M-circle dot). Hard X-rays and gamma-rays from the decay of this Ti-44 have been unambiguously observed from Cassiopeia A only(6-8), leading to the suggestion that values of the initial mass of Ti-44 near the upper bound of the predictions occur only in exceptional cases(9). For the remnant of supernova 1987A(10,11), an upper limit to the initial mass of Ti-44 of <10(-3)M(circle dot) has been obtained from direct X-ray observations(12), and an estimate of (1-2) x 10(-4)M(circle dot) has been made from infrared light curves and ultraviolet spectra by complex and model-dependent computations(13-15). Here we report observations of hard X-rays from the remnant of supernova 1987A in the narrow band containing two direct-escape lines of Ti-44 at 67.9 and 78.4 keV. The measured line fluxes imply that this decay provided sufficient energy to power the remnant at late times. We estimate that the initial mass of Ti-44 was (3.1 +/- 0.8) x 10(-4)M(circle dot), which is near the upper bound of theoretical predictions.
C1 [Grebenev, S. A.; Lutovinov, A. A.; Tsygankov, S. S.] RAS, Space Res Inst, Moscow 117997, Russia.
   [Tsygankov, S. S.] Max Planck Inst Astrophys, D-85741 Garching, Germany.
   [Tsygankov, S. S.] Univ Turku, FINCA, FI-21500 Piikkio, Finland.
   [Tsygankov, S. S.] Univ Oulu, Astron Div, Dept Phys, FI-90014 Oulu, Finland.
   [Winkler, C.] European Space Agcy, Estec, NL-2200 AG Noordwijk, Netherlands.
C3 Russian Academy of Sciences; Space Research Institute of the Russian Academy of Sciences; Max Planck Society; University of Turku; University of Oulu; European Space Agency; European Space Research & Technology Centre
RP Grebenev, SA (corresponding author), RAS, Space Res Inst, Profsoyuznaya 84-32, Moscow 117997, Russia.
EM sergei@hea.iki.rssi.ru
FU [RFBR-11-02-12285ofi-m-2011];  [RAS-P20]
NR 29
TC 100
Z9 105
U1 0
U2 8
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD OCT 18
PY 2012
VL 490
IS 7420
BP 373
EP 375
DI 10.1038/nature11473
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 021XI
UT WOS:000309918500039
PM 23075986
DA 2026-03-09
ER

PT J
AU Savage, KJ
   Hawkeye, MM
   Esteban, R
   Borisov, AG
   Aizpurua, J
   Baumberg, JJ
AF Savage, Kevin J.
   Hawkeye, Matthew M.
   Esteban, Ruben
   Borisov, Andrei G.
   Aizpurua, Javier
   Baumberg, Jeremy J.
TI Revealing the quantum regime in tunnelling plasmonics
SO NATURE
LA English
DT Article
ID metallic nanoparticles; optical rectification; field enhancement; light-emission; microscope; dimers; model; pairs
AB When two metal nanostructures are placed nanometres apart, their optically driven free electrons couple electrically across the gap. The resulting plasmons have enhanced optical fields of a specific colour tightly confined inside the gap. Many emerging nanophotonic technologies depend on the careful control of this plasmonic coupling, including optical nanoantennas for high-sensitivity chemical and biological sensors(1), nanoscale control of active devices(2-4), and improved photovoltaic devices(5). But for subnanometre gaps, coherent quantum tunnelling becomes possible and the system enters a regime of extreme non-locality in which previous classical treatments(6-14) fail. Electron correlations across the gap that are driven by quantum tunnelling require a new description of non-local transport, which is crucial in nanoscale optoelectronics and single-molecule electronics. Here, by simultaneously measuring both the electrical and optical properties of two gold nanostructures with controllable subnanometre separation, we reveal the quantum regime of tunnelling plasmonics in unprecedented detail. All observed phenomena are in good agreement with recent quantum-based models of plasmonic systems(15), which eliminate the singularities predicted by classical theories. These findings imply that tunnelling establishes a quantum limit for plasmonic field confinement of about 10(-8) lambda(3) for visible light (of wavelength lambda). Our work thus prompts new theoretical and experimental investigations into quantum-domain plasmonic systems, and will affect the future of nanoplasmonic device engineering and nanoscale photochemistry.
C1 [Savage, Kevin J.; Hawkeye, Matthew M.; Baumberg, Jeremy J.] Univ Cambridge, Cavendish Lab, Nanophoton Ctr, Cambridge CB3 0HE, England.
   [Esteban, Ruben; Borisov, Andrei G.; Aizpurua, Javier] Mat Phys Ctr CSIC UPV EHU, Donostia San Sebastian 20018, Spain.
   [Esteban, Ruben; Borisov, Andrei G.; Aizpurua, Javier] Donostia Int Phys Ctr DIPC, Donostia San Sebastian 20018, Spain.
   [Borisov, Andrei G.] Univ Paris 11, CNRS, UMR 8214, Inst Sci Mol Orsay, F-91405 Orsay, France.
C3 University of Cambridge; University of Basque Country; Consejo Superior de Investigaciones Cientificas (CSIC); Universite Paris Saclay; Centre National de la Recherche Scientifique (CNRS); CNRS - Institute of Physics (INP)
RP Baumberg, JJ (corresponding author), Univ Cambridge, Cavendish Lab, Nanophoton Ctr, Cambridge CB3 0HE, England.
EM jjb12@cam.ac.uk
FU EPSRC [EP/G060649/1, EP/H007024/1]; EU grant CUBi-HOLE; Spanish Ministry of Science and Innovation [FIS2010-19609-C02-01, EUI200803816]; Ikerbasque Foundation; Jesus College Cambridge; University of Cambridge; Canadian NSERC post-doctoral fellowship; EPSRC [EP/H007024/1, EP/G060649/1] Funding Source: UKRI; Engineering and Physical Sciences Research Council [EP/H007024/1, EP/G060649/1] Funding Source: researchfish
NR 30
TC 902
Z9 995
U1 4
U2 721
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD NOV 22
PY 2012
VL 491
IS 7425
BP 574
EP 577
DI 10.1038/nature11653
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 040RE
UT WOS:000311339800047
PM 23135399
DA 2026-03-09
ER

PT J
AU Shen, K
   Arslan, S
   Akopian, D
   Ha, T
   Shan, SO
AF Shen, Kuang
   Arslan, Sinan
   Akopian, David
   Ha, Taekjip
   Shan, Shu-ou
TI Activated GTPase movement on an RNA scaffold drives co-translational protein targeting
SO NATURE
LA English
DT Article
ID signal recognition particle; single-molecule fret; srp rna; crystal-structure; receptor; ribosome; complex; mechanism; translocation; components
AB Approximately one-third of the proteome is initially destined for the eukaryotic endoplasmic reticulum or the bacterial plasma membrane(1). The proper localization of these proteins is mediated by a universally conserved protein-targeting machinery, the signal recognition particle (SRP), which recognizes ribosomes carrying signal sequences(2-4) and, through interactions with the SRP receptor(5,6), delivers them to the protein-translocation machinery on the target membrane(7). The SRP is an ancient ribonucleoprotein particle containing an essential, elongated SRP RNA for which precise functions have remained elusive. Here we used single-molecule fluorescence microscopy to show that the Escherichia coli SRP-SRP receptor GTPase complex, after initial assembly at the tetra-loop end of SRP RNA, travels over 100 angstrom to the distal end of this RNA, where rapid GTP hydrolysis occurs. This movement is negatively regulated by the translating ribosome and, at a later stage, positively regulated by the SecYEG translocon, providing an attractive mechanism for ensuring the productive exchange of the targeting and translocation machineries at the ribosome exit site with high spatial and temporal accuracy. Our results show that large RNAs can act as molecular scaffolds that enable the easy exchange of distinct factors and precise timing of molecular events in a complex cellular process; this concept may be extended to similar phenomena in other ribonucleoprotein complexes.
C1 [Shen, Kuang; Akopian, David; Shan, Shu-ou] CALTECH, Div Chem & Chem Engn, Pasadena, CA 91125 USA.
   [Arslan, Sinan; Ha, Taekjip] Univ Illinois, Dept Phys, Ctr Phys Living Cells, Urbana, IL 61801 USA.
   [Ha, Taekjip] Howard Hughes Med Inst, Urbana, IL 61801 USA.
C3 California Institute of Technology; University of Illinois System; University of Illinois Urbana-Champaign; Howard Hughes Medical Institute
RP Shan, SO (corresponding author), CALTECH, Div Chem & Chem Engn, Pasadena, CA 91125 USA.
EM sshan@caltech.edu
FU National Institutes of Health (NIH) [GM078024, GM45162, GM065367]; Caltech [350270]; Beckman Young Investigator award; David and Lucile Packard Fellowship in Science and Engineering; Henry Dreyfus Teacher-Scholar award; National Science Foundation Physics Frontiers Centers program [08222613]
NR 38
TC 67
Z9 83
U1 1
U2 62
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD DEC 13
PY 2012
VL 492
IS 7428
BP 271
EP +
DI 10.1038/nature11726
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 053GM
UT WOS:000312259300046
PM 23235881
DA 2026-03-09
ER

PT J
AU Regensburger, A
   Bersch, C
   Miri, MA
   Onishchukov, G
   Christodoulides, DN
   Peschel, U
AF Regensburger, Alois
   Bersch, Christoph
   Miri, Mohammad-Ali
   Onishchukov, Georgy
   Christodoulides, Demetrios N.
   Peschel, Ulf
TI Parity-time synthetic photonic lattices
SO NATURE
LA English
DT Article
ID optical bloch oscillations; non-hermitian hamiltonians; symmetry; light; real; propagation; amplifiers; spectra
AB The development of new artificial structures and materials is today one of the major research challenges in optics. In most studies so far, the design of such structures has been based on the judicious manipulation of their refractive index properties. Recently, the prospect of simultaneously using gain and loss was suggested as a new way of achieving optical behaviour that is at present unattainable with standard arrangements. What facilitated these quests is the recently developed notion of 'parity-time symmetry' in optical systems, which allows a controlled interplay between gain and loss. Here we report the experimental observation of light transport in large-scale temporal lattices that are parity-time symmetric. In addition, we demonstrate that periodic structures respecting this symmetry can act as unidirectional invisible media when operated near their exceptional points. Our experimental results represent a step in the application of concepts from parity-time symmetry to a new generation of multifunctional optical devices and networks.
C1 [Regensburger, Alois; Bersch, Christoph; Peschel, Ulf] Univ Erlangen Nurnberg, Inst Opt Informat & Photon, D-91058 Erlangen, Germany.
   [Regensburger, Alois; Bersch, Christoph; Onishchukov, Georgy] Max Planck Inst Sci Light, D-91058 Erlangen, Germany.
   [Miri, Mohammad-Ali; Christodoulides, Demetrios N.] Univ Cent Florida, Coll Opt & Photon, CREOL, Orlando, FL 32816 USA.
C3 University of Erlangen Nuremberg; Max Planck Society; State University System of Florida; University of Central Florida
RP Peschel, U (corresponding author), Univ Erlangen Nurnberg, Inst Opt Informat & Photon, Staudtstr 7-B2, D-91058 Erlangen, Germany.
EM demetri@creol.ucf.edu; ulf.peschel@physik.uni-erlangen.de
FU DFG [Forschergruppe 760]; Cluster of Excellence Engineering of Advanced Materials, SAOT; German-Israeli Foundation; NSF [ECCS-1128520]; AFOSR [FA95501210148]
NR 45
TC 1775
Z9 1916
U1 9
U2 429
PU NATURE PUBLISHING 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 9
PY 2012
VL 488
IS 7410
BP 167
EP 171
DI 10.1038/nature11298
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 985LE
UT WOS:000307267000024
PM 22874962
DA 2026-03-09
ER

PT J
AU Jäger, S
   Cimermancic, P
   Gulbahce, N
   Johnson, JR
   McGovern, KE
   Clarke, SC
   Shales, M
   Mercenne, G
   Pache, L
   Li, K
   Hernandez, H
   Jang, GM
   Roth, SL
   Akiva, E
   Marlett, J
   Stephens, M
   D'Orso, I
   Fernandes, J
   Fahey, M
   Mahon, C
   O'Donoghue, AJ
   Todorovic, A
   Morris, JH
   Maltby, DA
   Alber, T
   Cagney, G
   Bushman, FD
   Young, JA
   Chanda, SK
   Sundquist, WI
   Kortemme, T
   Hernandez, RD
   Craik, CS
   Burlingame, A
   Sali, A
   Frankel, AD
   Krogan, NJ
AF Jaeger, Stefanie
   Cimermancic, Peter
   Gulbahce, Natali
   Johnson, Jeffrey R.
   McGovern, Kathryn E.
   Clarke, Starlynn C.
   Shales, Michael
   Mercenne, Gaelle
   Pache, Lars
   Li, Kathy
   Hernandez, Hilda
   Jang, Gwendolyn M.
   Roth, Shoshannah L.
   Akiva, Eyal
   Marlett, John
   Stephens, Melanie
   D'Orso, Ivan
   Fernandes, Jason
   Fahey, Marie
   Mahon, Cathal
   O'Donoghue, Anthony J.
   Todorovic, Aleksandar
   Morris, John H.
   Maltby, David A.
   Alber, Tom
   Cagney, Gerard
   Bushman, Frederic D.
   Young, John A.
   Chanda, Sumit K.
   Sundquist, Wesley I.
   Kortemme, Tanja
   Hernandez, Ryan D.
   Craik, Charles S.
   Burlingame, Alma
   Sali, Andrej
   Frankel, Alan D.
   Krogan, Nevan J.
TI Global landscape of HIV-human protein complexes
SO NATURE
LA English
DT Article
ID saccharomyces-cerevisiae; interaction map; replication; interactome; purification; infection; resource; cleavage; database; network
AB Human immunodeficiency virus (HIV) has a small genome and therefore relies heavily on the host cellular machinery to replicate. Identifying which host proteins and complexes come into physical contact with the viral proteins is crucial for a comprehensive understanding of how HIV rewires the host's cellular machinery during the course of infection. Here we report the use of affinity tagging and purification mass spectrometry(1-3) to determine systematically the physical interactions of all 18 HIV-1 proteins and polyproteins with host proteins in two different human cell lines (HEK293 and Jurkat). Using a quantitative scoring system that we call MiST, we identified with high confidence 497 HIV-human protein-protein interactions involving 435 individual human proteins, with similar to 40% of the interactions being identified in both cell types. We found that the host proteins hijacked by HIV, especially those found interacting in both cell types, are highly conserved across primates. We uncovered a number of host complexes targeted by viral proteins, including the finding that HIV protease cleaves eIF3d, a subunit of eukaryotic translation initiation factor 3. This host protein is one of eleven identified in this analysis that act to inhibit HIV replication. This data set facilitates a more comprehensive and detailed understanding of how the host machinery is manipulated during the course of HIV infection.
C1 [Jaeger, Stefanie; Gulbahce, Natali; Johnson, Jeffrey R.; McGovern, Kathryn E.; Shales, Michael; Li, Kathy; Hernandez, Hilda; Jang, Gwendolyn M.; Fahey, Marie; Mahon, Cathal; Krogan, Nevan J.] Univ Calif San Francisco, Dept Cellular & Mol Pharmacol, San Francisco, CA 94158 USA.
   [Jaeger, Stefanie; Cimermancic, Peter; Gulbahce, Natali; Johnson, Jeffrey R.; McGovern, Kathryn E.; Shales, Michael; Li, Kathy; Hernandez, Hilda; Jang, Gwendolyn M.; Akiva, Eyal; Fahey, Marie; Mahon, Cathal; Kortemme, Tanja; Hernandez, Ryan D.; Craik, Charles S.; Burlingame, Alma; Sali, Andrej; Frankel, Alan D.; Krogan, Nevan J.] QB3, Calif Inst Quantitat Biosci, San Francisco, CA 94158 USA.
   [Cimermancic, Peter; Akiva, Eyal; Kortemme, Tanja; Hernandez, Ryan D.] Univ Calif San Francisco, Dept Bioengn & Therapeut Sci, San Francisco, CA 94158 USA.
   [Johnson, Jeffrey R.; Krogan, Nevan J.] J David Gladstone Inst, San Francisco, CA 94158 USA.
   [Clarke, Starlynn C.; Li, Kathy; Hernandez, Hilda; Mahon, Cathal; O'Donoghue, Anthony J.; Morris, John H.; Maltby, David A.; Craik, Charles S.; Burlingame, Alma; Sali, Andrej] Univ Calif San Francisco, Dept Pharmaceut Chem, San Francisco, CA 94158 USA.
   [Mercenne, Gaelle; Sundquist, Wesley I.] Univ Utah, Dept Biochem, Salt Lake City, UT 84112 USA.
   [Pache, Lars; Chanda, Sumit K.] Sanford Burnham Med Res Inst, La Jolla, CA 92037 USA.
   [Jang, Gwendolyn M.; D'Orso, Ivan; Fernandes, Jason; Bushman, Frederic D.] Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94158 USA.
   [Roth, Shoshannah L.; Stephens, Melanie; Bushman, Frederic D.] Univ Penn, Dept Microbiol, Philadelphia, PA 19104 USA.
   [Marlett, John; Young, John A.] Salk Inst Biol Studies, La Jolla, CA 92037 USA.
   [Todorovic, Aleksandar] Univ Calif Berkeley, Dept Chem, Berkeley, CA 94720 USA.
   [Alber, Tom] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA.
   [Cagney, Gerard] Univ Coll Dublin, Conway Inst, Dublin 4, Ireland.
   [Kortemme, Tanja; Hernandez, Ryan D.; Sali, Andrej; Frankel, Alan D.; Krogan, Nevan J.] Univ Calif San Francisco, Host Pathogen Circuitry Grp, San Francisco, CA 94158 USA.
C3 University of California System; University of California San Francisco; University of California System; University of California San Francisco; University of California System; University of California San Francisco; The J David Gladstone Institutes; University of California System; University of California San Francisco; Utah System of Higher Education; University of Utah; Sanford Burnham Prebys Medical Discovery Institute; University of California System; University of California San Francisco; University of Pennsylvania; Salk Institute; University of California System; University of California Berkeley; University of California System; University of California Berkeley; University College Dublin; University of California System; University of California San Francisco
RP Krogan, NJ (corresponding author), Univ Calif San Francisco, Dept Cellular & Mol Pharmacol, San Francisco, CA 94158 USA.
EM krogan@cmp.ucsf.edu
FU QB3@UCSF; National Institutes of Health [P50 GM082250, P01 AI090935, P50 GM081879, P50 GM082545, P41RR001614, U54 RR022220, P01 GM073732-05, CHRP-ID08-TBI-063, P41 RR001081]; Nomis Foundation
NR 28
TC 573
Z9 700
U1 0
U2 110
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JAN 19
PY 2012
VL 481
IS 7381
BP 365
EP 370
DI 10.1038/nature10719
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 877VK
UT WOS:000299210600043
PM 22190034
DA 2026-03-09
ER

PT J
AU Lee, EJ
   Groisman, EA
AF Lee, Eun-Jin
   Groisman, Eduardo A.
TI Control of a Salmonella virulence locus by an ATP-sensing leader messenger RNA
SO NATURE
LA English
DT Article
ID phop-regulated genes; escherichia-coli; mycobacterium-tuberculosis; intramacrophage survival; sensor kinase; typhimurium; expression; enterica; mgtc; transcription
AB The facultative intracellular pathogen Salmonella enterica resides within a membrane-bound compartment inside macrophages(1). This compartment must be acidified for Salmonella to survive within macrophages(2), possibly because acidic pH promotes expression of Salmonella virulence proteins(3,4). We reasoned that Salmonella might sense its surroundings have turned acidic not only upon protonation of the extracytoplasmic domain of a protein sensor(5) but also by an increase in cytosolic ATP levels, because conditions that enhance the proton gradient across the bacterial inner membrane stimulate ATP synthesis(6,7). Here we report that an increase in cytosolic ATP promotes transcription of the coding region for the virulence gene mgtC, which is the most highly induced horizontally acquired gene when Salmonella is inside macrophages(8). This transcript is induced both upon media acidification and by physiological conditions that increase ATP levels independently of acidification. ATP is sensed by the coupling/uncoupling of transcription of the unusually long mgtC leader messenger RNA and translation of a short open reading frame located in this region. A mutation in the mgtC leader messenger RNA that eliminates the response to ATP hinders mgtC expression inside macrophages and attenuates Salmonella virulence in mice. Our results define a singular example of an ATP-sensing leader messenger RNA. Moreover, they indicate that pathogens can interpret extracellular cues by the impact they have on cellular metabolites.
C1 [Lee, Eun-Jin; Groisman, Eduardo A.] Yale Univ, Howard Hughes Med Inst, Sch Med, Sect Microbial Pathogenesis,Boyer Ctr Mol Med, New Haven, CT 06536 USA.
   [Lee, Eun-Jin; Groisman, Eduardo A.] Yale Microbial Divers Inst, West Haven, CT 06516 USA.
C3 Yale University; Howard Hughes Medical Institute
RP Groisman, EA (corresponding author), Yale Univ, Howard Hughes Med Inst, Sch Med, Sect Microbial Pathogenesis,Boyer Ctr Mol Med, 295 Congress Ave, New Haven, CT 06536 USA.
EM eduardo.groisman@yale.edu
FU National Institutes of Health [AI49561]; National Institute of Allergy and Infectious Diseases [R01AI049561] Funding Source: NIH RePORTER
NR 39
TC 75
Z9 83
U1 0
U2 34
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 14
PY 2012
VL 486
IS 7402
BP 271
EP +
DI 10.1038/nature11090
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 957UH
UT WOS:000305189000038
PM 22699622
DA 2026-03-09
ER

PT J
AU Jacob, T
   Wahr, J
   Pfeffer, WT
   Swenson, S
AF Jacob, Thomas
   Wahr, John
   Pfeffer, W. Tad
   Swenson, Sean
TI Recent contributions of glaciers and ice caps to sea level rise
SO NATURE
LA English
DT Article
ID mass changes; grace; gravity
AB Glaciers and ice caps (GICs) are important contributors to present-day global mean sea level rise(1-4). Most previous global mass balance estimates for GICs rely on extrapolation of sparse mass balance measurements(1,2,4) representing only a small fraction of the GIC area, leaving their overall contribution to sea level rise unclear. Here we show that GICs, excluding the Greenland and Antarctic peripheral GICs, lost mass at a rate of 148 +/- 30 Gt yr(-1) from January 2003 to December 2010, contributing 0.41 +/- 0.08 mm yr(-1) to sea level rise. Our results are based on a global, simultaneous inversion of monthly GRACE-derived satellite gravity fields, from which we calculate the mass change over all ice-covered regions greater in area than 100 km(2). The GIC rate for 2003-2010 is about 30 per cent smaller than the previous mass balance estimate that most closely matches our study period(2). The high mountains of Asia, in particular, show a mass loss of only 4 +/- 20 Gt yr(-1) for 2003-2010, compared with 47-55 Gt yr(-1) in previously published estimates(2,5). For completeness, we also estimate that the Greenland and Antarctic ice sheets, including their peripheral GICs, contributed 1.06 +/- 0.19 mm yr(-1) to sea level rise over the same time period. The total contribution to sea level rise from all ice-covered regions is thus 1.48 +/- 0.26 mm yr(-1), which agrees well with independent estimates of sea level rise originating from land ice loss and other terrestrial sources(6).
C1 [Jacob, Thomas; Wahr, John] Univ Colorado, Dept Phys, Boulder, CO 80309 USA.
   [Jacob, Thomas; Wahr, John] Univ Colorado, Cooperat Inst Environm Studies, Boulder, CO 80309 USA.
   [Pfeffer, W. Tad] Univ Colorado, Inst Arctic & Alpine Res, Boulder, CO 80309 USA.
   [Pfeffer, W. Tad] Univ Colorado, Dept Civil Environm & Architectural Engn, Boulder, CO 80309 USA.
   [Swenson, Sean] Natl Ctr Atmospher Res, Boulder, CO 80305 USA.
C3 University of Colorado System; University of Colorado Boulder; University of Colorado System; University of Colorado Boulder; University of Colorado System; University of Colorado Boulder; University of Colorado System; University of Colorado Boulder; National Center Atmospheric Research (NCAR) - USA
RP Wahr, J (corresponding author), Univ Colorado, Dept Phys, Boulder, CO 80309 USA.
EM john.wahr@gmail.com
FU NASA [NNX08AF02G, NNXI0AR66G]; NASA [NNX08AF02G, 102864] Funding Source: Federal RePORTER
NR 29
TC 834
Z9 990
U1 1
U2 430
PU NATURE PUBLISHING 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 23
PY 2012
VL 482
IS 7386
BP 514
EP 518
DI 10.1038/nature10847
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 898VM
UT WOS:000300770500048
PM 22318519
DA 2026-03-09
ER

PT J
AU Quint, M
   Drost, HG
   Gabel, A
   Ullrich, KK
   Bönn, M
   Grosse, I
AF Quint, Marcel
   Drost, Hajk-Georg
   Gabel, Alexander
   Ullrich, Kristian Karsten
   Boenn, Markus
   Grosse, Ivo
TI A transcriptomic hourglass in plant embryogenesis
SO NATURE
LA English
DT Article
ID gene-expression; arabidopsis; beginnings; evolution
AB Animal and plant development starts with a constituting phase called embryogenesis, which evolved independently in both lineages(1). Comparative anatomy of vertebrate development-based on the Meckel-Serres law(2) and von Baer's laws of embryology(3) from the early nineteenth century-shows that embryos from various taxa appear different in early stages, converge to a similar form during mid-embryogenesis, and again diverge in later stages. This morphogenetic series is known as the embryonic 'hourglass'(4,5), and its bottleneck of high conservation in mid-embryogenesis is referred to as the phylotypic stage(6). Recent analyses in zebrafish and Drosophila embryos provided convincing molecular support for the hourglass model, because during the phylotypic stage the transcriptome was dominated by ancient genes(7) and global gene expression profiles were reported to be most conserved(8). Although extensively explored in animals, an embryonic hourglass has not been reported in plants, which represent the second major kingdom in the tree of life that evolved embryogenesis. Here we provide phylotranscriptomic evidence for a molecular embryonic hourglass in Arabidopsis thaliana, using two complementary approaches. This is particularly significant because the possible absence of an hourglass based on morphological features in plants suggests that morphological and molecular patterns might be uncoupled. Together with the reported developmental hourglass patterns in animals, these findings indicate convergent evolution of the molecular hourglass and a conserved logic of embryogenesis across kingdoms.
C1 [Quint, Marcel; Ullrich, Kristian Karsten] Leibniz Inst Plant Biochem, Independent Jr Res Grp, Dept Mol Signal Proc, D-06120 Halle, Saale, Germany.
   [Drost, Hajk-Georg; Gabel, Alexander; Boenn, Markus; Grosse, Ivo] Univ Halle Wittenberg, Inst Comp Sci, D-06120 Halle, Saale, Germany.
   [Boenn, Markus] UFZ Helmholtz Ctr Environm Res, Dept Soil Ecol, D-06120 Halle, Saale, Germany.
C3 Leibniz Institut fur Pflanzenbiochemie; Martin Luther University Halle Wittenberg; Helmholtz Association; Helmholtz Center for Environmental Research (UFZ)
RP Quint, M (corresponding author), Leibniz Inst Plant Biochem, Independent Jr Res Grp, Dept Mol Signal Proc, Weinberg 3, D-06120 Halle, Saale, Germany.
EM mquint@ipb-halle.de
FU 'Exzellenznetzwerk fur Biowissenschaften' of the Federal State of Sachsen-Anhalt, Germany
NR 31
TC 154
Z9 172
U1 0
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 OCT 4
PY 2012
VL 490
IS 7418
BP 98
EP +
DI 10.1038/nature11394
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 015LG
UT WOS:000309446800040
PM 22951968
DA 2026-03-09
ER

PT J
AU Kim, C
   Schmidt, T
   Cho, EG
   Ye, F
   Ulmer, TS
   Ginsberg, MH
AF Kim, Chungho
   Schmidt, Thomas
   Cho, Eun-Gyung
   Ye, Feng
   Ulmer, Tobias S.
   Ginsberg, Mark H.
TI Basic amino-acid side chains regulate transmembrane integrin signalling
SO NATURE
LA English
DT Article
ID membrane-proteins; activation; complex; alpha-iib-beta-3; residues; segment; domains
AB Side chains of Lys/Arg near transmembrane domain (TMD)(1-3) membrane-water interfaces can 'snorkel', placing their positive charge near negatively charged phospholipid head groups(4-6); however, snorkelling's functional effects are obscure. Integrin beta TMDs have such conserved basic amino acids. Here we use NMR spectroscopy(7,8) to show that integrin beta(3)(Lys 716) helps determine beta(3) TMD topography. The alpha(IIb)beta(3) TMD structure indicates that precise beta(3) TMD crossing angles enable the assembly of outer and inner membrane 'clasps' that hold the ab TMD together to limit transmembrane signalling(9). Mutation of beta(3)(Lys 716) caused dissociation of alpha(IIb)beta(3) TMDs and integrin activation. To confirm that altered topography of beta(3)(Lys 716) mutants activated alpha(IIb)beta(3), we used directed evolution of beta(3)(K716A) to identify substitutions restoring default state. Introduction of Pro(711) at the midpoint of beta(3) TMD (A711P) increased alpha(IIb)beta(3) TMD association and inactivated integrin alpha(IIb)beta(3)(A711P, K716A). beta(3)(Pro 711) introduced a TMD kink of 30 +/- 1 degrees precisely at the border of the outer and inner membrane clasps, thereby decoupling the tilt between these segments. Thus, widely occurring snorkelling residues in TMDs can help maintain TMD topography and membrane-embedding, thereby regulating transmembrane signalling.
C1 [Kim, Chungho; Ye, Feng; Ginsberg, Mark H.] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA.
   [Schmidt, Thomas; Ulmer, Tobias S.] Univ So Calif, Keck Sch Med, Dept Biochem & Mol Biol, Zilkha Neurogenet Inst, Los Angeles, CA 90033 USA.
   [Cho, Eun-Gyung] Sanford Burnham Med Res Inst, Ctr Neurosci Aging & Stem Cell Res, La Jolla, CA 92037 USA.
C3 University of California System; University of California San Diego; University of Southern California; Sanford Burnham Prebys Medical Discovery Institute
RP Ginsberg, MH (corresponding author), Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA.
EM tulmer@usc.edu; mhginsberg@ucsd.edu
FU National Institutes of Health of the USA; National Institutes of Health [HL089726]; American Institute for Cancer Research;  [HL078784];  [HL57900];  [AR27214]
NR 25
TC 102
Z9 118
U1 0
U2 43
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JAN 12
PY 2012
VL 481
IS 7380
BP 209
EP +
DI 10.1038/nature10697
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 874TO
UT WOS:000298981200041
PM 22178926
DA 2026-03-09
ER

PT J
AU Thompson, DWJ
   Seidel, DJ
   Randel, WJ
   Zou, CZ
   Butler, AH
   Mears, C
   Osso, A
   Long, C
   Lin, R
AF Thompson, David W. J.
   Seidel, Dian J.
   Randel, William J.
   Zou, Cheng-Zhi
   Butler, Amy H.
   Mears, Carl
   Osso, Albert
   Long, Craig
   Lin, Roger
TI The mystery of recent stratospheric temperature trends
SO NATURE
LA English
DT Article
ID brewer-dobson circulation; sounding unit; climate; msu; construction; extension; records
AB A new data set of middle- and upper-stratospheric temperatures based on reprocessing of satellite radiances provides a view of stratospheric climate change during the period 1979-2005 that is strikingly different from that provided by earlier data sets. The new data call into question our understanding of observed stratospheric temperature trends and our ability to test simulations of the stratospheric response to emissions of greenhouse gases and ozone-depleting substances. Here we highlight the important issues raised by the new data and suggest how the climate science community can resolve them.
C1 [Thompson, David W. J.] Colorado State Univ, Dept Atmospher Sci, Ft Collins, CO 80523 USA.
   [Seidel, Dian J.] NOAA Air Resources Lab, College Pk, MD 20740 USA.
   [Randel, William J.] NCAR, Atmospher Chem Div, Boulder, CO 80307 USA.
   [Zou, Cheng-Zhi] NOAA NESDIS Ctr Satellite Applicat & Res, College Pk, MD 20740 USA.
   [Butler, Amy H.; Long, Craig; Lin, Roger] NOAA NWS NCEP Climate Predict Ctr, College Pk, MD 20740 USA.
   [Mears, Carl] Remote Sensing Syst, Santa Rosa, CA 95401 USA.
   [Osso, Albert] Univ Barcelona, Dept Astron & Meteorol, E-08028 Barcelona, Spain.
C3 Colorado State University System; Colorado State University Fort Collins; National Oceanic Atmospheric Admin (NOAA) - USA; National Center Atmospheric Research (NCAR) - USA; National Oceanic Atmospheric Admin (NOAA) - USA; National Oceanic Atmospheric Admin (NOAA) - USA; University of Barcelona
RP Thompson, DWJ (corresponding author), Colorado State Univ, Dept Atmospher Sci, Ft Collins, CO 80523 USA.
EM davet@atmos.colostate.edu
FU National Science Foundation Climate Dynamics Program [AGS-0936255]; Directorate For Geosciences; Div Atmospheric & Geospace Sciences [0936255] Funding Source: National Science Foundation
NR 33
TC 99
Z9 111
U1 3
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 NOV 29
PY 2012
VL 491
IS 7426
BP 692
EP 697
DI 10.1038/nature11579
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 044FY
UT WOS:000311606000032
PM 23192146
DA 2026-03-09
ER

PT J
AU Lemos, JC
   Wanat, MJ
   Smith, JS
   Reyes, BAS
   Hollon, NG
   Van Bockstaele, EJ
   Chavkin, C
   Phillips, PEM
AF Lemos, Julia C.
   Wanat, Matthew J.
   Smith, Jeffrey S.
   Reyes, Beverly A. S.
   Hollon, Nick G.
   Van Bockstaele, Elisabeth J.
   Chavkin, Charles
   Phillips, Paul E. M.
TI Severe stress switches CRF action in the nucleus accumbens from appetitive to aversive
SO NATURE
LA English
DT Article
ID corticotropin-releasing-factor; dopaminergic-neurons; factor receptors; behavior; anxiety; activation; depression; mouse
AB Stressors motivate an array of adaptive responses ranging from 'fight or flight' to an internal urgency signal facilitating long-term goals(1). However, traumatic or chronic uncontrollable stress promotes the onset of major depressive disorder, in which acute stressors lose their motivational properties and are perceived as insurmountable impediments(2). Consequently, stress-induced depression is a debilitating human condition characterized by an affective shift from engagement of the environment to withdrawal(3). An emerging neurobiological substrate of depression and associated pathology is the nucleus accumbens, a region with the capacity to mediate a diverse range of stress responses by interfacing limbic, cognitive and motor circuitry(4). Here we report that corticotropin-releasing factor (CRF), a neuropeptide released in response to acute stressors(5) and other arousing environmental stimuli(6), acts in the nucleus accumbens of naive mice to increase dopamine release through coactivation of the receptors CRFR1 and CRFR2. Remarkably, severe-stress exposure completely abolished this effect without recovery for at least 90 days. This loss of CRF's capacity to regulate dopamine release in the nucleus accumbens is accompanied by a switch in the reaction to CRF from appetitive to aversive, indicating a diametric change in the emotional response to acute stressors. Thus, the current findings offer a biological substrate for the switch in affect which is central to stress-induced depressive disorders.
C1 [Lemos, Julia C.; Wanat, Matthew J.; Hollon, Nick G.; Phillips, Paul E. M.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA.
   [Lemos, Julia C.; Wanat, Matthew J.; Smith, Jeffrey S.; Hollon, Nick G.; Chavkin, Charles; Phillips, Paul E. M.] Univ Washington, Dept Pharmacol, Seattle, WA 98195 USA.
   [Lemos, Julia C.; Hollon, Nick G.; Chavkin, Charles; Phillips, Paul E. M.] Univ Washington, Program Neurobiol & Behav, Seattle, WA 98195 USA.
   [Reyes, Beverly A. S.; Van Bockstaele, Elisabeth J.] Thomas Jefferson Univ, Farber Inst Neurosci, Dept Neurosci, Philadelphia, PA 19107 USA.
C3 University of Washington; University of Washington Seattle; University of Washington; University of Washington Seattle; University of Washington; University of Washington Seattle; Thomas Jefferson University
RP Phillips, PEM (corresponding author), Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA.
EM pemp@uw.edu
FU National Institutes of Health [F31-MH086269, F32-DA026273, R01-DA009082, R01-DA030074, R01-MH079292, R01-DA016782]; National Science Foundation; NARSAD
NR 35
TC 241
Z9 301
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 OCT 18
PY 2012
VL 490
IS 7420
BP 402
EP +
DI 10.1038/nature11436
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 021XI
UT WOS:000309918500046
PM 22992525
DA 2026-03-09
ER

PT J
AU Decker, RB
   Krimigis, SM
   Roelof, EC
   Hill, ME
AF Decker, Robert B.
   Krimigis, Stamatios M.
   Roelof, Edmond C.
   Hill, Matthew E.
TI No meridional plasma flow in the heliosheath transition region
SO NATURE
LA English
DT Article
AB Over a two-year period, Voyager 1 observed a gradual slowing-down of radial plasma flow in the heliosheath to near-zero velocity(1) after April 2010 at a distance of 113.5 astronomical units from the Sun (1 astronomical unit equals 1.5x10(8) kilometres). Voyager 1 was then about 20 astronomical units beyond the shock that terminates the free expansion of the solar wind and was immersed in the heated non-thermal plasma region called the heliosheath. The expectation from contemporary simulations(2,3) was that the heliosheath plasma would be deflected from radial flow to meridional flow (in solar heliospheric coordinates), which at Voyager 1 would lie mainly on the (locally spherical) surface called the heliopause. This surface is supposed to separate the heliosheath plasma, which is of solar origin, from the interstellar plasma, which is of local Galactic origin. In 2011, the Voyager project began occasional temporary re-orientations of the spacecraft (totalling about 10-25 hours every 2 months) to re-align the Low-Energy Charged Particle instrument on board Voyager 1 so that it could measure meridional flow. Here we report that, contrary to expectations, these observations yielded a meridional flow velocity of +3 +/- 11 km s(-1), that is, one consistent with zero within statistical uncertainties. [GRAPHICS] .
C1 [Decker, Robert B.; Krimigis, Stamatios M.; Roelof, Edmond C.; Hill, Matthew E.] Johns Hopkins Univ, Appl Phys Lab, Laurel, MD 20707 USA.
   [Krimigis, Stamatios M.] Acad Athens, Athens 11527, Greece.
C3 Johns Hopkins University; Johns Hopkins University Applied Physics Laboratory; Academy of Athens
RP Decker, RB (corresponding author), Johns Hopkins Univ, Appl Phys Lab, Johns Hopkins Rd, Laurel, MD 20707 USA.
EM robert.decker@jhuapl.edu
FU Johns Hopkins University Applied Physics Laboratory by NASA [NNN06AA01C]
NR 5
TC 70
Z9 73
U1 0
U2 19
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD SEP 6
PY 2012
VL 489
IS 7414
BP 124
EP 127
DI 10.1038/nature11441
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 999WW
UT WOS:000308347000047
PM 22955623
DA 2026-03-09
ER

PT J
AU Becker, T
   Franckenberg, S
   Wickles, S
   Shoemaker, CJ
   Anger, AM
   Armache, JP
   Sieber, H
   Ungewickell, C
   Berninghausen, O
   Daberkow, I
   Karcher, A
   Thomm, M
   Hopfner, KP
   Green, R
   Beckmann, R
AF Becker, Thomas
   Franckenberg, Sibylle
   Wickles, Stephan
   Shoemaker, Christopher J.
   Anger, Andreas M.
   Armache, Jean-Paul
   Sieber, Heidemarie
   Ungewickell, Charlotte
   Berninghausen, Otto
   Daberkow, Ingo
   Karcher, Annette
   Thomm, Michael
   Hopfner, Karl-Peter
   Green, Rachel
   Beckmann, Roland
TI Structural basis of highly conserved ribosome recycling in eukaryotes and archaea
SO NATURE
LA English
DT Article
ID messenger-rna decay; no-go decay; free protein-synthesis; x-ray-structure; atp-binding; translation termination; electron-microscopy; crystal-structure; 80s ribosome; thermococcus-kodakaraensis
AB Ribosome-driven protein biosynthesis is comprised of four phases: initiation, elongation, termination and recycling. In bacteria, ribosome recycling requires ribosome recycling factor and elongation factor G, and several structures of bacterial recycling complexes have been determined. In the eukaryotic and archaeal kingdoms, however, recycling involves the ABC-type ATPase ABCE1 and little is known about its structural basis. Here we present cryo-electron microscopy reconstructions of eukaryotic and archaeal ribosome recycling complexes containing ABCE1 and the termination factor paralogue Pelota. These structures reveal the overall binding mode of ABCE1 to be similar to canonical translation factors. Moreover, the iron-sulphur cluster domain of ABCE1 interacts with and stabilizes Pelota in a conformation that reaches towards the peptidyl transferase centre, thus explaining how ABCE1 may stimulate peptide-release activity of canonical termination factors. Using the mechanochemical properties of ABCE1, a conserved mechanism in archaea and eukaryotes is suggested that couples translation termination to recycling, and eventually to re-initiation.
C1 [Becker, Thomas; Franckenberg, Sibylle; Wickles, Stephan; Anger, Andreas M.; Armache, Jean-Paul; Sieber, Heidemarie; Ungewickell, Charlotte; Berninghausen, Otto; Karcher, Annette; Hopfner, Karl-Peter; Beckmann, Roland] Univ Munich, Dept Biochem, Gene Ctr, D-81377 Munich, Germany.
   [Becker, Thomas; Franckenberg, Sibylle; Wickles, Stephan; Anger, Andreas M.; Armache, Jean-Paul; Sieber, Heidemarie; Ungewickell, Charlotte; Berninghausen, Otto; Karcher, Annette; Hopfner, Karl-Peter; Beckmann, Roland] Univ Munich, Dept Biochem, Ctr Integrated Prot Sci Munich CiPSM, D-81377 Munich, Germany.
   [Shoemaker, Christopher J.; Green, Rachel] Johns Hopkins Univ, Sch Med, Dept Mol Biol & Genet, Howard Hughes Med Inst, Baltimore, MD 21205 USA.
   [Karcher, Annette] Tietz Video & Image Proc Syst GmbH, D-82131 Gauting, Germany.
   [Thomm, Michael] Univ Icking, D-82057 Icking, Germany.
   [Thomm, Michael] Univ Regensburg, Dept Microbiol, NWF Biol & Preclin Med 3, D-93053 Regensburg, Germany.
C3 University of Munich; University of Munich; Johns Hopkins University; Howard Hughes Medical Institute; University of Regensburg
RP Beckmann, R (corresponding author), Univ Munich, Dept Biochem, Gene Ctr, Feodor Lynen Str 25, D-81377 Munich, Germany.
EM becker@lmb.uni-muenchen.de; beckmann@lmb.uni-muenchen.de
FU Deutsche Forschungsgemeinschaft [SFB594, SFB646]; National Institutes of Health [U19 AI083025]; Fonds der chemischen Industrie
NR 56
TC 198
Z9 229
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 FEB 23
PY 2012
VL 482
IS 7386
BP 501
EP U221
DI 10.1038/nature10829
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 898VM
UT WOS:000300770500045
PM 22358840
DA 2026-03-09
ER

PT J
AU Stein, WE
   Berry, CM
   Hernick, LV
   Mannolini, F
AF Stein, William E.
   Berry, Christopher M.
   Hernick, Linda VanAller
   Mannolini, Frank
TI Surprisingly complex community discovered in the mid-Devonian fossil forest at Gilboa
SO NATURE
LA English
DT Article
ID new-york-state; evolution; pennsylvania; venezuela; wetlands; usa
AB The origin of trees by the mid-Devonian epoch (398-385 million years ago) signals a major change in terrestrial ecosystems with potential long-term consequences including increased weathering, drop in atmospheric CO2, modified climate, changes in sedimentation patterns and mass extinction(1-3). However, little is known about the ecology of early forests or how changes in early terrestrial ecosystems influenced global processes. One of the most famous palaeontological records for this time is the 'oldest fossil forest' at Riverside Quarry, Gilboa, New York, USA, discovered in the 1920s(4,5). Hundreds of large Eospermatopteris sandstone casts, now thought to represent the bases of standing cladoxylopsid trees(6), were recovered from a horizon that was originally interpreted as a muddy swamp. After quarry operations ceased, relatively minor outcrops of similar fossils at nearby localities have provided limited opportunities to evaluate this pervasive view using modern methods(7,8). In 2010, removal of the quarry backfill enabled reappraisal of the palaeoecology of this important site. Here we describe a 1,200 m(2) map showing numerous Eospermatopteris root systems in life position within a mixed-age stand of trees. Unexpectedly, large woody rhizomes with adventitious roots and aerial branch systems identified as aneurophytalean progymnosperms run between, and probably climb into, Eospermatopteris trees. We describe the overall habit for these surprisingly large aneurophytaleans, the earliest fossil group having wood produced by a bifacial vascular cambium. The site also provides evidence for arborescence within lycopsids, extending the North American range for trees in this ecologically critical group. The rooting horizon is a dark grey sandy mudstone showing limited root penetration. Although clearly belonging to a wetland coastal plain environment(9), the forest was probably limited in duration and subject to periodic disturbance. These observations provide fundamental clarification of the palaeoecology of this mixed-group early forest, with important implications for interpreting coeval assemblage data worldwide.
C1 [Stein, William E.] SUNY Binghamton, Dept Biol Sci, Binghamton, NY 13902 USA.
   [Berry, Christopher M.] Cardiff Univ, Sch Earth & Ocean Sci, Cardiff CF10 3YE, S Glam, Wales.
   [Hernick, Linda VanAller; Mannolini, Frank] New York State Museum & Sci Serv, Albany, NY 12230 USA.
C3 State University of New York (SUNY) System; Binghamton University, SUNY; Cardiff University
RP Stein, WE (corresponding author), SUNY Binghamton, Dept Biol Sci, Binghamton, NY 13902 USA.
EM stein@binghamton.edu
FU New York State Museum; UK Natural Environment Research Council (NERC) [NE/F010699/1]; Natural Environment Research Council [NE/F010699/1] Funding Source: researchfish; NERC [NE/F010699/1] Funding Source: UKRI
NR 28
TC 157
Z9 191
U1 3
U2 119
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD MAR 1
PY 2012
VL 483
IS 7387
BP 78
EP 81
DI 10.1038/nature10819
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 900HP
UT WOS:000300877900048
PM 22382983
DA 2026-03-09
ER

PT J
AU Gontan, C
   Achame, EM
   Demmers, J
   Barakat, TS
   Rentmeester, E
   van IJcken, W
   Grootegoed, JA
   Gribnau, J
AF Gontan, Cristina
   Achame, Eskeatnaf Mulugeta
   Demmers, Jeroen
   Barakat, Tahsin Stefan
   Rentmeester, Eveline
   van IJcken, Wilfred
   Grootegoed, J. Anton
   Gribnau, Joost
TI RNF12 initiates X-chromosome inactivation by targeting REX1 for degradation
SO NATURE
LA English
DT Article
ID cells; gene; pluripotency; rex1/zfp42; activator; motifs; yy1
AB Evolution of the mammalian sex chromosomes has resulted in a heterologous X and Y pair, where the Y chromosome has lost most of its genes. Hence, there is a need for X-linked gene dosage compensation between XY males and XX females. In placental mammals, this is achieved by random inactivation of one X chromosome in all female somatic cells(1). Upregulation of Xist transcription on the future inactive X chromosome acts against Tsix antisense transcription, and spreading of Xist RNA in cis triggers epigenetic changes leading to X-chromosome inactivation. Previously, we have shown that the X-encoded E3 ubiquitin ligase RNF12 is upregulated in differentiating mouse embryonic stem cells and activates Xist transcription and X-chromosome inactivation(2). Here we identify the pluripotency factor REX1 as a key target of RNF12 in the mechanism of X-chromosome inactivation. RNF12 causes ubiquitination and proteasomal degradation of REX1, and Rnf12 knockout embryonic stem cells show an increased level of REX1. Using chromatin immunoprecipitation sequencing, REX1 binding sites were detected in Xist and Tsix regulatory regions. Overexpression of REX1 in female embryonic stem cells was found to inhibit Xist transcription and X-chromosome inactivation, whereas male Rex1(+/-) embryonic stem cells showed ectopic X-chromosome inactivation. From this, we propose that RNF12 causes REX1 breakdown through dose-dependent catalysis, thereby representing an important pathway to initiate X-chromosome inactivation. Rex1 and Xist are present only in placental mammals, which points to co-evolution of these two genes and X-chromosome inactivation.
C1 [Gontan, Cristina; Achame, Eskeatnaf Mulugeta; Barakat, Tahsin Stefan; Rentmeester, Eveline; Grootegoed, J. Anton; Gribnau, Joost] Univ Med Ctr, Erasmus MC, Dept Reprod & Dev, NL-3015 GE Rotterdam, Netherlands.
   [Demmers, Jeroen] Univ Med Ctr, Erasmus MC, Prote Ctr, NL-3015 GE Rotterdam, Netherlands.
   [van IJcken, Wilfred] Univ Med Ctr, Erasmus MC, Bi Dept, NL-3015 GE Rotterdam, Netherlands.
C3 Erasmus University Rotterdam; Erasmus MC; Erasmus University Rotterdam; Erasmus MC; Erasmus University Rotterdam; Erasmus MC
RP Gribnau, J (corresponding author), Univ Med Ctr, Erasmus MC, Dept Reprod & Dev, Dr Molewaterplein 50, NL-3015 GE Rotterdam, Netherlands.
EM j.gribnau@erasmusmc.nl
FU Netherlands Organisation for Scientific Research (NWO-TOP); Netherlands Organisation for Scientific Research (NWO-VICI); European Research Council
NR 17
TC 169
Z9 193
U1 1
U2 48
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD MAY 17
PY 2012
VL 485
IS 7398
BP 386
EP U138
DI 10.1038/nature11070
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 943CW
UT WOS:000304099100046
PM 22596162
DA 2026-03-09
ER

PT J
AU Gill, RJ
   Ramos-Rodriguez, O
   Raine, NE
AF Gill, Richard J.
   Ramos-Rodriguez, Oscar
   Raine, Nigel E.
TI Combined pesticide exposure severely affects individual- and colony-level traits in bees
SO NATURE
LA English
DT Article
ID honey-bees; risk-assessment; systemic insecticides; hymenoptera apidae; bombus-terrestris; foraging success; apis-mellifera; pollinators; miticides; toxicity
AB Reported widespread declines of wild and managed insect pollinators have serious consequences for global ecosystem services and agricultural production(1-3). Bees contribute approximately 80% of insect pollination, so it is important to understand and mitigate the causes of current declines in bee populations(4-6). Recent studies have implicated the role of pesticides in these declines, as exposure to these chemicals has been associated with changes in bee behaviour(7-11) and reductions in colony queen production(12). However, the key link between changes in individual behaviour and the consequent impact at the colony level has not been shown. Social bee colonies depend on the collective performance of many individual workers. Thus, although field-level pesticide concentrations can have subtle or sublethal effects at the individual level(8), it is not known whether bee societies can buffer such effects or whether it results in a severe cumulative effect at the colony level. Furthermore, widespread agricultural intensification means that bees are exposed to numerous pesticides when foraging(13-15), yet the possible combinatorial effects of pesticide exposure have rarely been investigated(16,17). Here we show that chronic exposure of bumblebees to two pesticides (neonicotinoid and pyrethroid) at concentrations that could approximate field-level exposure impairs natural foraging behaviour and increases worker mortality leading to significant reductions in brood development and colony success. We found that worker foraging performance, particularly pollen collecting efficiency, was significantly reduced with observed knock-on effects for forager recruitment, worker losses and overall worker productivity. Moreover, we provide evidence that combinatorial exposure to pesticides increases the propensity of colonies to fail.
C1 [Gill, Richard J.; Ramos-Rodriguez, Oscar; Raine, Nigel E.] Univ London, Sch Biol Sci, Egham TW20 0EX, Surrey, England.
C3 University of London; Royal Holloway University London
RP Gill, RJ (corresponding author), Univ London, Sch Biol Sci, Egham TW20 0EX, Surrey, England.
EM richard.gill@rhul.ac.uk; nigel.raine@rhul.ac.uk
FU Insect Pollinator Initiative; Living with Environmental Change programme, Biotechnology and Biological Sciences Research Council (BBSRC); Wellcome Trust; Scottish Government; Department for Environment, Food and Rural Affairs (DEFRA); Natural Environment Research Council (NERC) [BB/I000178/1]; BBSRC [BB/I000178/1] Funding Source: UKRI; Biotechnology and Biological Sciences Research Council [BB/I000178/1] Funding Source: researchfish
NR 40
TC 753
Z9 902
U1 14
U2 1313
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD NOV 1
PY 2012
VL 491
IS 7422
BP 105
EP U119
DI 10.1038/nature11585
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 028PM
UT WOS:000310434500039
PM 23086150
DA 2026-03-09
ER

PT J
AU Baranova, E
   Fronzes, R
   Garcia-Pino, A
   Van Gerven, N
   Papapostolou, D
   Péhau-Arnaudet, G
   Pardon, E
   Steyaert, J
   Howorka, S
   Remaut, H
AF Baranova, Ekaterina
   Fronzes, Remi
   Garcia-Pino, Abel
   Van Gerven, Nani
   Papapostolou, David
   Pehau-Arnaudet, Gerard
   Pardon, Els
   Steyaert, Jan
   Howorka, Stefan
   Remaut, Han
TI SbsB structure and lattice reconstruction unveil Ca2+ triggered S-layer assembly
SO NATURE
LA English
DT Article
ID protein sbsb; domains; binding; system; organization; scattering; anthracis; residues; adhesion; model
AB S-layers are regular two-dimensional semipermeable protein layers that constitute a major cell-wall component in archaea and many bacteria(1-3). The nanoscale repeat structure of the S-layer lattices and their self-assembly from S-layer proteins (SLPs) have sparked interest in their use as patterning and display scaffolds for a range of nano-biotechnological applications(4-7). Despite their biological abundance and the technological interest in them, structural information about SLPs is limited to truncated and assembly-negative proteins(8-10). Here we report the X-ray structure of the SbsB SLP of Geobacillus stearothermophilus PV72/p2 by the use of nanobody-aided crystallization. SbsB consists of a seven-domain protein, formed by an amino-terminal cell-wall attachment domain and six consecutive immunoglobulin-like domains, that organize into a phi-shaped disk-like monomeric crystallization unit stabilized by interdomain Ca2+ ion coordination. A Ca2+-dependent switch to the condensed SbsB quaternary structure pre-positions intermolecular contact zones and renders the protein competent for S-layer assembly. On the basis of crystal packing, chemical crosslinking data and cryo-electron microscopy projections, we present a model for the molecular organization of this SLP into a porous protein sheet inside the S-layer. The SbsB lattice represents a previously undescribed structural model for protein assemblies and may advance our understanding of SLP physiology and self-assembly, as well as the rational design of engineered higher-order structures for biotechnology(4-7).
C1 [Baranova, Ekaterina; Van Gerven, Nani; Remaut, Han] VIB, VIB Dept Struct Biol, B-1050 Brussels, Belgium.
   [Baranova, Ekaterina; Garcia-Pino, Abel; Van Gerven, Nani; Pardon, Els; Steyaert, Jan; Remaut, Han] Vrije Univ Brussel, B-1050 Brussels, Belgium.
   [Fronzes, Remi] Inst Pasteur, Unite G5, F-75015 Paris, France.
   [Fronzes, Remi; Pehau-Arnaudet, Gerard] Inst Pasteur, CNRS, Unite Rech Mixte 3538, F-75015 Paris, France.
   [Papapostolou, David; 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; Centre National de la Recherche Scientifique (CNRS); Pasteur Network; Universite Paris Cite; Institut Pasteur Paris; University of London; Birkbeck University London; University College London
RP Remaut, H (corresponding author), VIB, VIB Dept Struct Biol, Pl Laan 2, B-1050 Brussels, Belgium.
EM han.remaut@vib-vub.be
FU VIB (Vlaams Institute voor Biotechnologie) [PRJ9]; Fonds Wetenschappelijk Onderzoek-Vlaanderen through an Odysseus grant; Centre National de la Recherche Scientifique (CNRS); Institut Pasteur; Interuniversity Attraction Poles grant [P6/19]; Biotechnology and Biological Sciences Research Council [BB/E010466/1]; University College London;  [FWO551]; Biotechnology and Biological Sciences Research Council [BB/E010466/1] Funding Source: researchfish; BBSRC [BB/E010466/1] Funding Source: UKRI
NR 47
TC 125
Z9 144
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 JUL 5
PY 2012
VL 487
IS 7405
BP 119
EP +
DI 10.1038/nature11155
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 968LM
UT WOS:000305982900062
PM 22722836
DA 2026-03-09
ER

PT J
AU Degner, JF
   Pai, AA
   Pique-Regi, R
   Veyrieras, JB
   Gaffney, DJ
   Pickrell, JK
   De Leon, S
   Michelini, K
   Lewellen, N
   Crawford, GE
   Stephens, M
   Gilad, Y
   Pritchard, JK
AF Degner, Jacob F.
   Pai, Athma A.
   Pique-Regi, Roger
   Veyrieras, Jean-Baptiste
   Gaffney, Daniel J.
   Pickrell, Joseph K.
   De Leon, Sherryl
   Michelini, Katelyn
   Lewellen, Noah
   Crawford, Gregory E.
   Stephens, Matthew
   Gilad, Yoav
   Pritchard, Jonathan K.
TI DNase I sensitivity QTLs are a major determinant of human expression variation
SO NATURE
LA English
DT Article
ID human gene-expression; transcription factor-binding; genome-wide association; open chromatin; map; yeast
AB The mapping of expression quantitative trait loci (eQTLs) has emerged as an important tool for linking genetic variation to changes in gene regulation(1-5). However, it remains difficult to identify the causal variants underlying eQTLs, and little is known about the regulatory mechanisms by which they act. Here we show that genetic variants that modify chromatin accessibility and transcription factor binding are a major mechanism through which genetic variation leads to gene expression differences among humans. We used DNase I sequencing to measure chromatin accessibility in 70 Yoruba lymphoblastoid cell lines, for which genome-wide genotypes and estimates of gene expression levels are also available(6-8). We obtained a total of 2.7 billion uniquely mapped DNase I-sequencing (DNase-seq) reads, which allowed us to produce genome-widemaps of chromatin accessibility for each individual. We identified 8,902 locations at which the DNase-seq read depth correlated significantly with genotype at a nearby single nucleotide polymorphism or insertion/deletion (false discovery rate = 10%). We call such variants 'DNase I sensitivity quantitative trait loci' (dsQTLs). We found that dsQTLs are strongly enriched within inferred transcription factor binding sites and are frequently associated with allele-specific changes in transcription factor binding. A substantial fraction (16%) of dsQTLs are also associated with variation in the expression levels of nearby genes (that is, these loci are also classified as eQTLs). Conversely, we estimate that as many as 55% of eQTL single nucleotide polymorphisms are also dsQTLs. Our observations indicate that dsQTLs are highly abundant in the human genome and are likely to be important contributors to phenotypic variation.
C1 [Degner, Jacob F.; Pai, Athma A.; Pique-Regi, Roger; Veyrieras, Jean-Baptiste; Gaffney, Daniel J.; Pickrell, Joseph K.; Stephens, Matthew; Gilad, Yoav; Pritchard, Jonathan K.] Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA.
   [Degner, Jacob F.] Univ Chicago, Comm Genet Genom & Syst Biol, Chicago, IL 60637 USA.
   [Veyrieras, Jean-Baptiste] BioMiningLabs, F-69001 Lyon, France.
   [Gaffney, Daniel J.; De Leon, Sherryl; Michelini, Katelyn; Lewellen, Noah; Pritchard, Jonathan K.] Univ Chicago, Howard Hughes Med Inst, Chicago, IL 60637 USA.
   [Crawford, Gregory E.] Duke Univ, Inst Genome Sci & Policy, Durham, NC 27708 USA.
   [Crawford, Gregory E.] Duke Univ, Div Med Genet, Dept Pediat, Sch Med, Durham, NC 27708 USA.
   [Stephens, Matthew] Univ Chicago, Dept Stat, Chicago, IL 60637 USA.
C3 University of Chicago; University of Chicago; University of Chicago; Howard Hughes Medical Institute; Duke University; Duke University; University of Chicago
RP Pritchard, JK (corresponding author), Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA.
EM gilad@uchicago.edu; pritch@uchicago.edu
FU National Institutes of Health [HG006123, MH084703, MH090951]; Howard Hughes Medical Institute; Chicago Fellows Program; American Heart Association
NR 30
TC 481
Z9 643
U1 0
U2 66
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD FEB 16
PY 2012
VL 482
IS 7385
BP 390
EP 394
DI 10.1038/nature10808
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 892LG
UT WOS:000300287100044
PM 22307276
DA 2026-03-09
ER

PT J
AU Biswas, K
   He, JQ
   Blum, ID
   Wu, CI
   Hogan, TP
   Seidman, DN
   Dravid, VP
   Kanatzidis, MG
AF Biswas, Kanishka
   He, Jiaqing
   Blum, Ivan D.
   Wu, Chun-I
   Hogan, Timothy P.
   Seidman, David N.
   Dravid, Vinayak P.
   Kanatzidis, Mercouri G.
TI High-performance bulk thermoelectrics with all-scale hierarchical architectures
SO NATURE
LA English
DT Article
ID figure; pbte; merit
AB With about two-thirds of all used energy being lost as waste heat, there is a compelling need for high-performance thermoelectric materials that can directly and reversibly convert heat to electrical energy. However, the practical realization of thermoelectric materials is limited by their hitherto low figure of merit, ZT, which governs the Carnot efficiency according to the second law of thermodynamics. The recent successful strategy of nanostructuring to reduce thermal conductivity has achieved record-high ZT values in the range 1.5-1.8 at 750-900 kelvin(1-3), but still falls short of the generally desired threshold value of 2. Nanostructures in bulk thermoelectrics allow effective phonon scattering of a significant portion of the phonon spectrum, but phonons with long mean free paths remain largely unaffected. Here we show that heat-carrying phonons with long mean free paths can be scattered by controlling and fine-tuning the mesoscale architecture of nanostructured thermoelectric materials. Thus, by considering sources of scattering on all relevant length scales in a hierarchical fashion-from atomic-scale lattice disorder and nanoscale endotaxial precipitates to mesoscale grain boundaries-we achieve the maximum reduction in lattice thermal conductivity and a large enhancement in the thermoelectric performance of PbTe. By taking such a panoscopic approach to the scattering of heat-carrying phonons across integrated length scales, we go beyond nanostructuring and demonstrate a ZT value of similar to 2.2 at 915 kelvin in p-type PbTe endotaxially nanostructured with SrTe at a concentration of 4 mole per cent and mesostructured with powder processing and spark plasma sintering. This increase in ZT beyond the threshold of 2 highlights the role of, and need for, multiscale hierarchical architecture in controlling phonon scattering in bulk thermoelectrics, and offers a realistic prospect of the recovery of a significant portion of waste heat.
C1 [Biswas, Kanishka; He, Jiaqing; Kanatzidis, Mercouri G.] Northwestern Univ, Dept Chem, Evanston, IL 60208 USA.
   [Wu, Chun-I; Hogan, Timothy P.] Michigan State Univ, Dept Elect & Comp Engn, E Lansing, MI 48824 USA.
   [Kanatzidis, Mercouri G.] Argonne Natl Lab, Mat Sci Div, Argonne, IL 60439 USA.
C3 Northwestern University; Michigan State University; United States Department of Energy (DOE); Argonne National Laboratory
RP Kanatzidis, MG (corresponding author), Northwestern Univ, Dept Chem, 2145 Sheridan Rd, Evanston, IL 60208 USA.
EM m-kanatzidis@northwestern.edu
FU Energy Frontier Research Center for Revolutionary Materials for Solid State Energy Conversion; US Department of Energy, Office of Science, Basic Energy Sciences [DE-SC0001054]; ONR DURIP [N00014-0400798, N00014-0610539, N00014-0910781]; NSF-MRI [DMR-0420532]; MRSEC [DMR-1121262]; ISEN at Northwestern University
NR 31
TC 4179
Z9 4535
U1 41
U2 2696
PU NATURE PUBLISHING 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 20
PY 2012
VL 489
IS 7416
BP 414
EP 418
DI 10.1038/nature11439
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 007AK
UT WOS:000308860900041
PM 22996556
DA 2026-03-09
ER

PT J
AU Breen, MS
   Kemena, C
   Vlasov, PK
   Notredame, C
   Kondrashov, FA
AF Breen, Michael S.
   Kemena, Carsten
   Vlasov, Peter K.
   Notredame, Cedric
   Kondrashov, Fyodor A.
TI Epistasis as the primary factor in molecular evolution
SO NATURE
LA English
DT Article
ID multiple sequence alignment; compensatory evolution; adaptive evolution; protein evolution; natural-selection; genetic-variation; perspective; drosophila; mutations; landscape
AB The main forces directing long-term molecular evolution remain obscure. A sizable fraction of amino-acid substitutions seem to be fixed by positive selection(1-4), but it is unclear to what degree long-term protein evolution is constrained by epistasis, that is, instances when substitutions that are accepted in one genotype are deleterious in another. Here we obtain a quantitative estimate of the prevalence of epistasis in long-term protein evolution by relating data on amino-acid usage in 14 organelle proteins and 2 nuclear-encoded proteins to their rates of short-term evolution. We studied multiple alignments of at least 1,000 orthologues for each of these 16 proteins from species from a diverse phylogenetic background and found that an average site contained approximately eight different amino acids. Thus, without epistasis an average site should accept two-fifths of all possible amino acids, and the average rate of amino-acid substitutions should therefore be about three-fifths lower than the rate of neutral evolution. However, we found that the measured rate of amino-acid substitution in recent evolution is 20 times lower than the rate of neutral evolution and an order of magnitude lower than that expected in the absence of epistasis. These data indicate that epistasis is pervasive throughout protein evolution: about 90 per cent of all amino-acid substitutions have a neutral or beneficial impact only in the genetic backgrounds in which they occur, and must therefore be deleterious in a different background of other species. Our findings show that most amino-acid substitutions have different fitness effects in different species and that epistasis provides the primary conceptual framework to describe the tempo and mode of long-term protein evolution.
C1 [Breen, Michael S.; Kemena, Carsten; Vlasov, Peter K.; Notredame, Cedric; Kondrashov, Fyodor A.] Ctr Genom Regulat, Bioinformat & Genom Programme, Barcelona 08003, Spain.
   [Breen, Michael S.; Kemena, Carsten; Vlasov, Peter K.; Notredame, Cedric; Kondrashov, Fyodor A.] Univ Pompeu Fabra, Barcelona 08003, Spain.
   [Kondrashov, Fyodor A.] 23 Passeig Lluis Co, ICREA, Barcelona 08010, Spain.
C3 Barcelona Institute of Science & Technology; Pompeu Fabra University; Centre de Regulacio Genomica (CRG); Pompeu Fabra University; ICREA
RP Kondrashov, FA (corresponding author), Ctr Genom Regulat, Bioinformat & Genom Programme, 88 Dr Aiguader, Barcelona 08003, Spain.
EM fyodor.kondrashov@crg.es
FU Spanish Ministry of Science and Innovation; European Union [KBBE2A222664]; ICREA Funding Source: Custom
NR 38
TC 281
Z9 349
U1 0
U2 99
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 25
PY 2012
VL 490
IS 7421
BP 535
EP +
DI 10.1038/nature11510
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 025NK
UT WOS:000310196200041
PM 23064225
DA 2026-03-09
ER

PT J
AU McNally, BA
   Somasundaram, A
   Yamashita, M
   Prakriya, M
AF McNally, Beth A.
   Somasundaram, Agila
   Yamashita, Megumi
   Prakriya, Murali
TI Gated regulation of CRAC channel ion selectivity by STIM1
SO NATURE
LA English
DT Article
ID ca2+-dependent inactivation; orai1; pore; permeation; subunit
AB Two defining functional features of ion channels are ion selectivity and channel gating. Ion selectivity is generally considered an immutable property of the open channel structure, whereas gating involves transitions between open and closed channel states, typically without changes in ion selectivity(1). In store-operated Ca2+ release-activated Ca2+ (CRAC) channels, the molecular mechanism of channel gating by the CRAC channel activator, stromal interaction molecule 1 (STIM1), remains unknown. CRAC channels are distinguished by a very high Ca2+ selectivity and are instrumental in generating sustained intracellular calcium concentration elevations that are necessary for gene expression and effector function in many eukaryotic cells(2). Here we probe the central features of the STIM1 gating mechanism in the human CRAC channel protein, ORAI1, and identify V102, a residue located in the extracellular region of the pore, as a candidate for the channel gate. Mutations at V102 produce constitutively active CRAC channels that are open even in the absence of STIM1. Unexpectedly, although STIM1-free V102 mutant channels are not Ca2+-selective, their Ca2+ selectivity is dose-dependently boosted by interactions with STIM1. Similar enhancement of Ca2+ selectivity is also seen in wild-type ORAI1 channels by increasing the number of STIM1 activation domains that are directly tethered to ORAI1 channels, or by increasing the relative expression of full-length STIM1. Thus, exquisite Ca2+ selectivity is not an intrinsic property of CRAC channels but rather a tuneable feature that is bestowed on otherwise non-selective ORAI1 channels by STIM1. Our results demonstrate that STIM1-mediated gating of CRAC channels occurs through an unusual mechanism in which permeation and gating are closely coupled.
C1 [McNally, Beth A.; Somasundaram, Agila; Yamashita, Megumi; Prakriya, Murali] Northwestern Univ, Dept Mol Pharmacol & Biol Chem, Sch Med, Chicago, IL 60611 USA.
C3 Northwestern University
RP Prakriya, M (corresponding author), Northwestern Univ, Dept Mol Pharmacol & Biol Chem, Sch Med, 303 E Chicago Ave,Ward 8-296, Chicago, IL 60611 USA.
EM m-prakriya@northwestern.edu
FU NIH [NS057499]; American Heart Association; Austrian Science Fund (FWF) [P 22565, P 22747] Funding Source: researchfish; National Institute of Neurological Disorders and Stroke [R01NS057499] Funding Source: NIH RePORTER
NR 30
TC 189
Z9 213
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 FEB 9
PY 2012
VL 482
IS 7384
BP 241
EP U136
DI 10.1038/nature10752
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 888HI
UT WOS:000299994100043
PM 22278058
DA 2026-03-09
ER

PT J
AU Su, D
   Hu, Q
   Li, Q
   Thompson, JR
   Cui, GF
   Fazly, A
   Davies, BA
   Botuyan, MV
   Zhang, ZG
   Mer, G
AF Su, Dan
   Hu, Qi
   Li, Qing
   Thompson, James R.
   Cui, Gaofeng
   Fazly, Ahmed
   Davies, Brian A.
   Botuyan, Maria Victoria
   Zhang, Zhiguo
   Mer, Georges
TI Structural basis for recognition of H3K56-acetylated histone H3-H4 by the chaperone Rtt106
SO NATURE
LA English
DT Article
ID nucleosome core particle; macromolecular structures; lysine 56; acetylation; dna; chromatin; h3; model; spectroscopy; refinement
AB Dynamic variations in the structure of chromatin influence virtually all DNA-related processes in eukaryotes and are controlled in part by post-translational modifications of histones(1-3). One such modification, the acetylation of lysine 56 (H3K56ac) in the amino-terminal alpha-helix (alpha N) of histone H3, has been implicated in the regulation of nucleosome assembly during DNA replication and repair, and nucleosome disassembly during gene transcription(4-10). In Saccharomyces cerevisiae, the histone chaperone Rtt106 contributes to the deposition of newly synthesized H3K56ac-carrying H3-H4 complex on replicating DNA(5), but it is unclear how Rtt106 binds H3-H4 and specifically recognizes H3K56ac as there is no apparent acetylated lysine reader domain in Rtt106. Here, we show that two domains of Rtt106 are involved in a combinatorial recognition of H3-H4. An N-terminal domain homodimerizes and interacts with H3-H4 independently of acetylation while a double pleckstrin-homology (PH) domain binds the K56-containing region of H3. Affinity is markedly enhanced upon acetylation of K56, an effect that is probably due to increased conformational entropy of the aN helix of H3. Our data support a mode of interaction where the N-terminal homodimeric domain of Rtt106 intercalates between the two H3-H4 components of the (H3-H4)(2) tetramer while two double PH domains in the Rtt106 dimer interact with each of the two H3K56ac sites in (H3-H4)(2). We show that the Rtt106-(H3-H4)(2) interaction is important for gene silencing and the DNA damage response.
C1 [Su, Dan; Hu, Qi; Li, Qing; Cui, Gaofeng; Fazly, Ahmed; Davies, Brian A.; Botuyan, Maria Victoria; Zhang, Zhiguo; Mer, Georges] Mayo Clin, Dept Biochem & Mol Biol, Rochester, MN 55905 USA.
   [Thompson, James R.] Mayo Clin, Dept Physiol & Biomed Engn, Rochester, MN 55905 USA.
C3 Mayo Clinic; Mayo Clinic
RP Zhang, ZG (corresponding author), Mayo Clin, Dept Biochem & Mol Biol, Rochester, MN 55905 USA.
EM zhang.zhiguo@mayo.edu; mer.georges@mayo.edu
FU US Department of Energy, Basic Energy Sciences, Office of Science [W-31-109-ENG-38]; National Institutes of Health
NR 38
TC 93
Z9 121
U1 0
U2 43
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD MAR 1
PY 2012
VL 483
IS 7387
BP 104
EP U152
DI 10.1038/nature10861
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 900HP
UT WOS:000300877900054
PM 22307274
DA 2026-03-09
ER

PT J
AU Murooka, TT
   Deruaz, M
   Marangoni, F
   Vrbanac, VD
   Seung, E
   von Andrian, UH
   Tager, AM
   Luster, AD
   Mempel, TR
AF Murooka, Thomas T.
   Deruaz, Maud
   Marangoni, Francesco
   Vrbanac, Vladimir D.
   Seung, Edward
   von Andrian, Ulrich H.
   Tager, Andrew M.
   Luster, Andrew D.
   Mempel, Thorsten R.
TI HIV-infected T cells are migratory vehicles for viral dissemination
SO NATURE
LA English
DT Article
ID human-immunodeficiency-virus; sexual transmission; immune-responses; down-modulation; envelope; receptor; cd4(+); type-1; env; motility
AB After host entry through mucosal surfaces, human immunodeficiency virus-1 (HIV-1) disseminates to lymphoid tissues to establish a generalized infection of the immune system. The mechanisms by which this virus spreads among permissive target cells locally during the early stages of transmission and systemically during subsequent dissemination are not known(1). In vitro studies suggest that the formation of virological synapses during stable contacts between infected and uninfected T cells greatly increases the efficiency of viral transfer(2). It is unclear, however, whether T-cell contacts are sufficiently stable in vivo to allow for functional synapse formation under the conditions of perpetual cell motility in epithelial(3) and lymphoid tissues(4). Here, using multiphoton intravital microscopy, we examine the dynamic behaviour of HIV-infected T cells in the lymph nodes of humanized mice. We find that most productively infected T cells migrate robustly, resulting in their even distribution throughout the lymph node cortex. A subset of infected cells formed multinucleated syncytia through HIV envelope-dependent cell fusion. Both uncoordinated motility of syncytia and adhesion to CD4(+) lymph node cells led to the formation of long membrane tethers, increasing cell lengths to up to ten times that of migrating uninfected T cells. Blocking the egress of migratory T cells from the lymph nodes into efferent lymph vessels, and thus interrupting T-cell recirculation, limited HIV dissemination and strongly reduced plasma viraemia. Thus, we have found that HIV-infected T cells are motile, form syncytia and establish tethering interactions that may facilitate cell-to-cell transmission through virological synapses. Migration of T cells in lymph nodes therefore spreads infection locally, whereas their recirculation through tissues is important for efficient systemic viral spread, suggesting new molecular targets to antagonize HIV infection.
C1 [Murooka, Thomas T.; Deruaz, Maud; Marangoni, Francesco; Vrbanac, Vladimir D.; Seung, Edward; Tager, Andrew M.; Luster, Andrew D.; Mempel, Thorsten R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA.
   [von Andrian, Ulrich H.] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA.
   [von Andrian, Ulrich H.] Harvard Univ, Sch Med, Dept Microbiol & Immunol, Boston, MA 02115 USA.
C3 Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Boston Children's Hospital; Program in Cellular & Molecular Medicine (PCMM); Harvard University; Harvard Medical School
RP Mempel, TR (corresponding author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA.
EM tmempel@mgh.harvard.edu
FU National Institutes of Health (NIH) [P01 AI0178897, R56 AI097052, R01 CA150975, P30 AI060354]; Ragon Institute of Massachusetts General Hospital (MGH); Massachusetts Institute of Technology (MIT); Harvard; MGH ECOR Tosteson Postdoctoral Fellowship Award; NIH [T32 AI007387]; Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Institute of Diabetes and Digestive and Kidney Diseases; National Institute of Allergy and Infectious Diseases; National Institute of Dental and Craniofacial Research; National Heart Lung and Blood Institute; National Cancer Institute; National Institute on Minority Health and Health Disparities; National Institute of Nursing Research; National Institute on Aging; National Institute on Drug Abuse [P30AI060354] Funding Source: NIH RePORTER; National Institute of Allergy and Infectious Diseases [T32AI007387] Funding Source: NIH RePORTER; National Institute of Diabetes and Digestive and Kidney Diseases [P30DK043351] Funding Source: NIH RePORTER
NR 38
TC 267
Z9 303
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 OCT 11
PY 2012
VL 490
IS 7419
BP 283
EP +
DI 10.1038/nature11398
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 019IY
UT WOS:000309733300054
PM 22854780
DA 2026-03-09
ER

PT J
AU Smith, DJ
   Whitehouse, I
AF Smith, Duncan J.
   Whitehouse, Iestyn
TI Intrinsic coupling of lagging-strand synthesis to chromatin assembly
SO NATURE
LA English
DT Article
ID dna-polymerase-delta; okazaki fragment maturation; saccharomyces-cerevisiae; replication fork; simian virus-40; flap endonuclease-1; in-vivo; nucleosome; yeast; transcription
AB Fifty per cent of the genome is discontinuously replicated on the lagging strand as Okazaki fragments. Eukaryotic Okazaki fragments remain poorly characterized and, because nucleosomes are rapidly deposited on nascent DNA, Okazaki fragment processing and nucleosome assembly potentially affect one another. Here we show that ligation-competent Okazaki fragments in Saccharomyces cerevisiae are sized according to the nucleosome repeat. Using deep sequencing, we demonstrate that ligation junctions preferentially occur near nucleosome midpoints rather than in internucleosomal linker regions. Disrupting chromatin assembly or lagging-strand polymerase processivity affects both the size and the distribution of Okazaki fragments, suggesting a role for nascent chromatin, assembled immediately after the passage of the replication fork, in the termination of Okazaki fragment synthesis. Our studies represent the first high-resolution analysis-to our knowledge-of eukaryotic Okazaki fragments in vivo, and reveal the interconnection between lagging-strand synthesis and chromatin assembly.
C1 [Smith, Duncan J.; Whitehouse, Iestyn] Mem Sloan Kettering Canc Ctr, Program Mol Biol, New York, NY 10065 USA.
C3 Memorial Sloan Kettering Cancer Center
RP Whitehouse, I (corresponding author), Mem Sloan Kettering Canc Ctr, Program Mol Biol, 1275 York Ave, New York, NY 10065 USA.
EM whitehoi@mskcc.org
FU Louis V. Gerstner Jr Young Investigator Award; Alfred Bressler Scholars Endowment Award; National Cancer Institute [P30CA008748] Funding Source: NIH RePORTER
NR 42
TC 226
Z9 277
U1 0
U2 36
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 22
PY 2012
VL 483
IS 7390
BP 434
EP U80
DI 10.1038/nature10895
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 912CC
UT WOS:000301771200036
PM 22419157
DA 2026-03-09
ER

PT J
AU Vincent, R
   Klyatskaya, S
   Ruben, M
   Wernsdorfer, W
   Balestro, F
AF Vincent, Romain
   Klyatskaya, Svetlana
   Ruben, Mario
   Wernsdorfer, Wolfgang
   Balestro, Franck
TI Electronic read-out of a single nuclear spin using a molecular spin transistor
SO NATURE
LA English
DT Article
ID magnetic-anisotropy; quantum; bis(phthalocyaninato)terbium; spintronics
AB Quantum control of individual spins in condensed-matter devices is an emerging field with a wide range of applications, from nanospintronics(1,2) to quantum computing(3). The electron, possessing spin and orbital degrees of freedom, is conventionally used as the carrier of quantum information in proposed devices(4,5,6,7,8,9). However, electrons couple strongly to the environment, and so have very short relaxation and coherence times. It is therefore extremely difficult to achieve quantum coherence and stable entanglement of electron spins. Alternative concepts propose nuclear spins as the building blocks for quantum computing(10), because such spins are extremely well isolated from the environment and less prone to decoherence. However, weak coupling comes at a price: it remains challenging to address and manipulate individual nuclear spins(11,12,13,14). Here we show that the nuclear spin of an individual metal atom embedded in a single-molecule magnet can be read out electronically. The observed long lifetimes ( tens of seconds) and relaxation characteristics of nuclear spin at the single-atom scale open the way to a completely new world of devices in which quantum logic may be implemented.
C1 [Vincent, Romain; Wernsdorfer, Wolfgang; Balestro, Franck] CNRS, Inst Neel, F-38042 Grenoble 9, France.
   [Vincent, Romain; Wernsdorfer, Wolfgang; Balestro, Franck] Univ Grenoble 1, F-38042 Grenoble 9, France.
   [Klyatskaya, Svetlana; Ruben, Mario] Karlsruhe Inst Technol, Inst Nanotechnol, D-76344 Eggenstein Leopoldshafen, Germany.
   [Ruben, Mario] Univ Strasbourg, CNRS, Inst Phys & Chim Mat Strasbourg, F-67034 Strasbourg, France.
C3 Communaute Universite Grenoble Alpes; Universite Grenoble Alpes (UGA); Centre National de la Recherche Scientifique (CNRS); Communaute Universite Grenoble Alpes; Universite Grenoble Alpes (UGA); Helmholtz Association; Karlsruhe Institute of Technology; Universites de Strasbourg Etablissements Associes; Universite de Strasbourg; Centre National de la Recherche Scientifique (CNRS)
RP Balestro, F (corresponding author), CNRS, Inst Neel, BP 166, F-38042 Grenoble 9, France.
EM mario.ruben@kit.edu; franck.balestro@grenoble.cnrs.fr
FU French National Research Agency National Programme in Nanosciences and Nanotechnologies (ANR-PNANO) project MolNanoSpin [ANR-08-NANO-002]; European Research Council Advanced Grant MolNanoSpin [226558]; Future Emerging Technologies Open, Quantum Information Processing Specific Targeted Research Project [ICT-2007.8.0, 211284 MolSpinQIP]; German Research Foundation programme TRR 88 '3Met'; Cible; Nanosciences Foundation of Grenoble
NR 31
TC 752
Z9 818
U1 3
U2 438
PU NATURE PUBLISHING 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 16
PY 2012
VL 488
IS 7411
BP 357
EP 360
DI 10.1038/nature11341
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 988OS
UT WOS:000307501000037
PM 22895342
DA 2026-03-09
ER

PT J
AU Zhang, WY
   Du, J
   Evans, SL
   Yu, YK
   Yu, XF
AF Zhang, Wenyan
   Du, Juan
   Evans, Sean L.
   Yu, Yunkai
   Yu, Xiao-Fang
TI T-cell differentiation factor CBF-β regulates HIV-1 Vif-mediated evasion of host restriction
SO NATURE
LA English
DT Article
ID virus type-1 vif; e3 ubiquitin ligase; antiviral activity; enzyme apobec3g; runt domain; socs-box; degradation; complex; binding; protein
AB The human APOBEC3 cytidine deaminases are potent inhibitors of diverse retroviruses, including human immunodeficiency virus-1 (HIV-1)(1-6). HIV-1 Vif forms an E3 ubiquitin ligase complex with cullin 5 (CUL5), elongin B and elongin C (7-9), which promotes the polyubiquitination and degradation of APOBEC3 substrates(7,10-14). Here we demonstrate in human T cells that core binding factor beta (CBF-beta) is a key regulator of the evasion of HIV-1 from the host defence mediated by APOBEC3. CBF-beta, the non-DNA-binding subunit of a heterodimeric transcription factor, regulates the folding and DNA-binding activity of partner RUNX family proteins, which have important roles in the development and differentiation of diverse cell types, including T lymphocytes(15,16). In our study, knockdown of endogenous CBF-beta blocked Vif-induced APOBEC3G polyubiquitination and degradation. CBF-beta was not required for the interaction between Vif and APOBEC3G, yet was essential for the assembly of the Vif-CUL5 E3-ubiquitin-ligase complex. CBF-beta proved to be a unique regulator of primate lentiviral Vif and not a general component of the CUL5 E3 ubiquitin ligase. We show that Vif and CBF-beta physically interact, and that the amino-terminal region of Vif is required for this interaction. Furthermore, interactions with Vif required regions in CBF-beta that are not involved in RUNX protein binding(17-19). Considering the importance of the interaction between Vif and CBF-beta, disrupting this interaction represents an attractive pharmacological intervention against HIV-1.
C1 [Zhang, Wenyan; Du, Juan; Yu, Xiao-Fang] Jilin Univ, Hosp 1, Inst Virol & AIDS Res, Changchun 130021, Jilin Province, Peoples R China.
   [Du, Juan; Evans, Sean L.; Yu, Yunkai; Yu, Xiao-Fang] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD 21205 USA.
C3 Jilin University; Johns Hopkins University; Johns Hopkins Bloomberg School of Public Health
RP Yu, XF (corresponding author), Jilin Univ, Hosp 1, Inst Virol & AIDS Res, Changchun 130021, Jilin Province, Peoples R China.
EM xfyu@jhsph.edu
FU Chinese Ministry of Science and Technology [2012CB911100]; Chinese Ministry of Education [IRT1016]; Key Laboratory of Molecular Virology, Jilin Province, China [20102209]; NIAID [2R56AI62644-6]
NR 30
TC 227
Z9 243
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 JAN 19
PY 2012
VL 481
IS 7381
BP 376
EP 379
DI 10.1038/nature10718
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 877VK
UT WOS:000299210600045
PM 22190036
DA 2026-03-09
ER

PT J
AU Pierce, SE
   Clack, JA
   Hutchinson, JR
AF Pierce, Stephanie E.
   Clack, Jennifer A.
   Hutchinson, John R.
TI Three-dimensional limb joint mobility in the early tetrapod Ichthyostega
SO NATURE
LA English
DT Article
ID devonian tetrapod; pectoral fin; hindlimb kinematics; terrestrial; locomotion; evolution; walking; trackways; anatomy; origin
AB The origin of tetrapods and the transition from swimming to walking was a pivotal step in the evolution and diversification of terrestrial vertebrates. During this time, modifications of the limbs-particularly the specialization of joints and the structures that guide their motions-fundamentally changed the ways in which early tetrapods could move(1-4). Nonetheless, little is known about the functional consequences of limb anatomy in early tetrapods and how that anatomy influenced locomotion capabilities at this very critical stage in vertebrate evolution. Here we present a three-dimensional reconstruction of the iconic Devonian tetrapod Ichthyostega and a quantitative and comparative analysis of limb mobility in this early tetrapod. We show that Ichthyostega could not have employed typical tetrapod locomotory behaviours, such as lateral sequence walking. In particular, it lacked the necessary rotary motions in its limbs to push the body off the ground and move the limbs in an alternating sequence. Given that long-axis rotation was present in the fins of tetrapodomorph fishes(5-7), it seems that either early tetrapods evolved through an initial stage of restricted shoulder(8,9) and hip joint mobility or that Ichthyostega was unique in this respect. We conclude that early tetrapods with the skeletal morphology and limb mobility of Ichthyostega were unlikely to have made some of the recently described Middle Devonian trackways(10).
C1 [Pierce, Stephanie E.; Hutchinson, John R.] Royal Vet Coll, Dept Vet Basic Sci & Struct & Motion Lab, Hatfield AL9 7TA, Herts, England.
   [Pierce, Stephanie E.; Clack, Jennifer A.] Univ Cambridge, Dept Zool, Univ Museum Zool, Cambridge CB2 3EJ, England.
C3 University of London; University of London Royal Veterinary College; University of Cambridge
RP Pierce, SE (corresponding author), Royal Vet Coll, Dept Vet Basic Sci & Struct & Motion Lab, Hawkshead Lane, Hatfield AL9 7TA, Herts, England.
EM spierce@rvc.ac.uk
FU National Science Foundation [IIS-9874781, IIS-0208675]; Natural Environment Research Council [NE/G005877/1, NE/G00711X/1]; NERC [NE/G00711X/1, NE/G005877/1] Funding Source: UKRI; Natural Environment Research Council [NE/G005877/1, NE/G00711X/1] Funding Source: researchfish; Division Of Earth Sciences; Directorate For Geosciences [0948842] Funding Source: National Science Foundation
NR 30
TC 170
Z9 196
U1 2
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 JUN 28
PY 2012
VL 486
IS 7404
BP 523
EP U123
DI 10.1038/nature11124
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 965IJ
UT WOS:000305760600041
PM 22722854
DA 2026-03-09
ER

PT J
AU Hochberg, LR
   Bacher, D
   Jarosiewicz, B
   Masse, NY
   Simeral, JD
   Vogel, J
   Haddadin, S
   Liu, J
   Cash, SS
   van der Smagt, P
   Donoghue, JP
AF Hochberg, Leigh R.
   Bacher, Daniel
   Jarosiewicz, Beata
   Masse, Nicolas Y.
   Simeral, John D.
   Vogel, Joern
   Haddadin, Sami
   Liu, Jie
   Cash, Sydney S.
   van der Smagt, Patrick
   Donoghue, John P.
TI Reach and grasp by people with tetraplegia using a neurally controlled robotic arm
SO NATURE
LA English
DT Article
ID local-field potentials; primary motor; cortical control; spiking activity; prosthetic arm; brain; restoration; movements; signals; humans
AB Paralysis following spinal cord injury, brainstem stroke, amyotrophic lateral sclerosis and other disorders can disconnect the brain from the body, eliminating the ability to perform volitional movements. A neural interface system(1-5) could restore mobility and independence for people with paralysis by translating neuronal activity directly into control signals for assistive devices. We have previously shown that people with long-standing tetraplegia can use a neural interface system to move and click a computer cursor and to control physical devices(6-8). Able-bodied monkeys have used a neural interface system to control a robotic arm(9), but it is unknown whether people with profound upper extremity paralysis or limb loss could use cortical neuronal ensemble signals to direct useful arm actions. Here we demonstrate the ability of two people with long-standing tetraplegia to use neural interface system-based control of a robotic arm to perform three-dimensional reach and grasp movements. Participants controlled the arm and hand over a broad space without explicit training, using signals decoded from a small, local population of motor cortex (MI) neurons recorded from a 96-channel microelectrode array. One of the study participants, implanted with the sensor 5 years earlier, also used a robotic arm to drink coffee from a bottle. Although robotic reach and grasp actions were not as fast or accurate as those of an able-bodied person, our results demonstrate the feasibility for people with tetraplegia, years after injury to the central nervous system, to recreate useful multidimensional control of complex devices directly from a small sample of neural signals.
C1 [Hochberg, Leigh R.; Jarosiewicz, Beata; Simeral, John D.; Liu, Jie; Donoghue, John P.] Rehabil Res & Dev Serv, Dept Vet Affairs, Providence, RI 02908 USA.
   [Hochberg, Leigh R.; Bacher, Daniel; Simeral, John D.; Liu, Jie; Donoghue, John P.] Brown Univ, Sch Engn, Providence, RI 02912 USA.
   [Hochberg, Leigh R.; Bacher, Daniel; Jarosiewicz, Beata; Masse, Nicolas Y.; Simeral, John D.; Liu, Jie; Donoghue, John P.] Brown Univ, Inst Brain Sci, Providence, RI 02912 USA.
   [Hochberg, Leigh R.; Simeral, John D.; Cash, Sydney S.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
   [Hochberg, Leigh R.; Cash, Sydney S.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
   [Jarosiewicz, Beata; Masse, Nicolas Y.; Donoghue, John P.] Brown Univ, Dept Neurosci, Providence, RI 02912 USA.
   [Vogel, Joern; Haddadin, Sami; van der Smagt, Patrick] German Aerosp Ctr, Inst Robot & Mechatron DLR Oberpfaffenhofen, D-82230 Oberpfaffenhofen, Germany.
C3 Brown University; Brown University; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard Medical School; Brown University; Helmholtz Association; German Aerospace Centre (DLR)
RP Donoghue, JP (corresponding author), Rehabil Res & Dev Serv, Dept Vet Affairs, Providence, RI 02908 USA.
EM leigh@brown.edu; john_donoghue@brown.edu
FU Rehabilitation Research and Development Service, Office of Research and Development, Department of Veterans Affairs [B6453R, A6779I, B6310N]; National Institutes of Health: NINDS/NICHD [RC1HD063931]; NIDCD [R01DC009899]; NICHD-NCMRR [N01HD53403, N01HD10018]; NIBIB [R01EB007401]; NINDS-Javits [NS25074]; Defense Advanced Research Projects Agency (DARPA); Department of Veterans Affairs; Doris Duke Charitable Foundation; MGH-Deane Institute for Integrated Research on Atrial Fibrillation and Stroke; Katie Samson Foundation; Craig H. Neilsen Foundation; European Commission [248587]; Cyberkinetics Neurotechnology Systems (CKI)
NR 38
TC 1886
Z9 2328
U1 36
U2 1183
PU NATURE PUBLISHING 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 17
PY 2012
VL 485
IS 7398
BP 372
EP U121
DI 10.1038/nature11076
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 943CW
UT WOS:000304099100043
PM 22596161
DA 2026-03-09
ER

PT J
AU Lai, CSW
   Franke, TF
   Gan, WB
AF Lai, Cora Sau Wan
   Franke, Thomas F.
   Gan, Wen-Biao
TI Opposite effects of fear conditioning and extinction on dendritic spine remodelling
SO NATURE
LA English
DT Article
ID prefrontal cortex; memory; amygdala; neurons; rat; consolidation; mechanisms; circuits; context
AB It is generally believed that fear extinction is a form of new learning that inhibits rather than erases previously acquired fear memories(1-3). Although this view has gained much support from behavioural and electrophysiological studies(1-10), the hypothesis that extinction causes the partial erasure of fear memories remains viable. Using transcranial two-photon microscopy(11,12), we investigated how neural circuits are modified by fear learning and extinction by examining the formation and elimination of postsynaptic dendritic spines of layer-V pyramidal neurons in the mouse frontal association cortex. Here we show that fear conditioning by pairing an auditory cue with a footshock increases the rate of spine elimination. By contrast, fear extinction by repeated presentation of the same auditory cue without a footshock increases the rate of spine formation. The degrees of spine remodelling induced by fear conditioning and extinction strongly correlate with the expression and extinction of conditioned fear responses, respectively. Notably, spine elimination and formation induced by fear conditioning and extinction occur on the same dendritic branches in a cue-and location-specific manner: cue-specific extinction causes formation of dendritic spines within a distance of two micrometres from spines that were eliminated after fear conditioning. Furthermore, reconditioning preferentially induces elimination of dendritic spines that were formed after extinction. Thus, within vastly complex neuronal networks, fear conditioning, extinction and reconditioning lead to opposing changes at the level of individual synapses. These findings also suggest that fear memory traces are partially erased after extinction.
C1 [Lai, Cora Sau Wan; Gan, Wen-Biao] NYU, Sch Med, Skirball Inst, Mol Neurobiol Program,Dept Physiol & Neurosci, New York, NY 10016 USA.
   [Franke, Thomas F.] NYU, Sch Med, Dept Psychiat, New York, NY 10016 USA.
   [Franke, Thomas F.] NYU, Sch Med, Dept Pharmacol, New York, NY 10016 USA.
C3 New York University; New York University; New York University
RP Gan, WB (corresponding author), NYU, Sch Med, Skirball Inst, Mol Neurobiol Program,Dept Physiol & Neurosci, 540 1st Ave, New York, NY 10016 USA.
EM gan@saturn.med.nyu.edu
FU National Institutes of Health [NS047325]; Alzheimer's Association; National Science Foundation [IOS-0757780]; NARSAD; G. Harold & Leila Y. Mathers Foundation
NR 24
TC 317
Z9 382
U1 0
U2 76
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD MAR 1
PY 2012
VL 483
IS 7387
BP 87
EP U130
DI 10.1038/nature10792
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 900HP
UT WOS:000300877900050
PM 22343895
DA 2026-03-09
ER

PT J
AU Godfrin, H
   Meschke, M
   Lauter, HJ
   Sultan, A
   Böhm, HM
   Krotscheck, E
   Panholzer, M
AF Godfrin, Henri
   Meschke, Matthias
   Lauter, Hans-Jochen
   Sultan, Ahmad
   Boehm, Helga M.
   Krotscheck, Eckhard
   Panholzer, Martin
TI Observation of a roton collective mode in a two-dimensional Fermi liquid
SO NATURE
LA English
DT Article
ID effective-mass; elementary excitations; spin fluctuations; zero sound; he-3; plasmons; dynamics
AB Understanding the dynamics of correlated many-body quantum systems is a challenge for modern physics. Owing to the simplicity of theirHamiltonians, He-4 (bosons) and He-3 (fermions) have served as model systems for strongly interacting quantum fluids, with substantial efforts devoted to their understanding. An important milestone was the direct observation of the collective phonon-roton mode in liquid He-4 by neutron scattering, verifying Landau's prediction(1) and his fruitful concept of elementary excitations. In a Fermi system, collective density fluctuations (known as 'zero-sound' in He-3, and 'plasmons' in charged systems) and incoherent particle-hole excitations are observed. At small wavevectors and energies, both types of excitation are described by Landau's theory of Fermi liquids(2,3). At higher wavevectors, the collectivemode enters the particle-hole band, where it is strongly damped. The dynamics of Fermi liquids at high wavevectors was thus believed to be essentially incoherent. Here we report inelastic neutron scattering measurements of a monolayer of liquid He-3, observing a roton-like excitation. We find that the collective density mode reappears as a well defined excitation atmomentum transfers larger than twice the Fermi momentum. We thus observe unexpected collective behaviour of a Fermi many-body system in the regime beyond the scope of Landau's theory. A satisfactory interpretation of the measured spectra is obtained using a dynamic many-body theory(4).
C1 [Godfrin, Henri; Meschke, Matthias; Sultan, Ahmad] CNRS, Inst Neel, F-38042 Grenoble 9, France.
   [Godfrin, Henri; Meschke, Matthias; Sultan, Ahmad] Univ Grenoble 1, F-38042 Grenoble 9, France.
   [Meschke, Matthias] Aalto Univ, Low Temp Lab, Aalto 00076, Finland.
   [Lauter, Hans-Jochen] Inst Laue Langevin, F-38042 Grenoble 9, France.
   [Lauter, Hans-Jochen] Oak Ridge Natl Lab, Oak Ridge, TN 37831 USA.
   [Boehm, Helga M.; Krotscheck, Eckhard; Panholzer, Martin] Johannes Kepler Univ Linz, Inst Theoret Phys, A-4040 Linz, Austria.
   [Krotscheck, Eckhard] SUNY Buffalo, Dept Phys, Buffalo, NY 14260 USA.
C3 Centre National de la Recherche Scientifique (CNRS); Communaute Universite Grenoble Alpes; Universite Grenoble Alpes (UGA); Communaute Universite Grenoble Alpes; Universite Grenoble Alpes (UGA); Aalto University; Institut Laue-Langevin (ILL); United States Department of Energy (DOE); Oak Ridge National Laboratory; Johannes Kepler University Linz; State University of New York (SUNY) System; University at Buffalo, SUNY
RP Godfrin, H (corresponding author), CNRS, Inst Neel, BP 166, F-38042 Grenoble 9, France.
EM henri.godfrin@grenoble.cnrs.fr
FU Austrian Fonds zur Forderung der wissenschaftlichen Forschung (FWF) [P21264]; French Agence Nationale de la Recherche [ANR-2010-INTB-403-01]; EU [228464]; Austrian Science Fund (FWF) [P21264] Funding Source: Austrian Science Fund (FWF)
NR 31
TC 69
Z9 71
U1 0
U2 50
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 29
PY 2012
VL 483
IS 7391
BP 576
EP 579
DI 10.1038/nature10919
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 915EF
UT WOS:000302006100034
PM 22460903
DA 2026-03-09
ER

PT J
AU Mukhopadhyay, S
AF Mukhopadhyay, Sujoy
TI Early differentiation and volatile accretion recorded in deep-mantle neon and xenon
SO NATURE
LA English
DT Article
ID rare-gas systematics; earths mantle; noble-gases; helium; evolution; isotopes; atmosphere; origin; heterogeneity; convection
AB The isotopes Xe-129, produced from the radioactive decay of extinct I-129, and Xe-136, produced from extinct Pu-244 and extant U-238, have provided important constraints on early mantle outgassing and volatile loss from Earth(1,2). The low ratios of radiogenic to non-radiogenic xenon (Xe-129/Xe-130) in ocean island basalts (OIBs) compared with mid-ocean-ridge basalts (MORBs) have been used as evidence for the existence of a relatively undegassed primitive deep-mantle reservoir(1). However, the low Xe-129/Xe-130 ratios in OIBs have also been attributed to mixing between subducted atmospheric Xe and MORB Xe, which obviates the need for a less degassed deep-mantle reservoir(3,4). Here I present new noble gas (He, Ne, Ar, Xe) measurements from an Icelandic OIB that reveal differences in elemental abundances and Ne-20/Ne-22 ratios between the Iceland mantle plume and the MORB source. These observations show that the lower Xe-129/Xe-130 ratios in OIBs are due to a lower I/Xe ratio in the OIB mantle source and cannot be explained solely by mixing atmospheric Xe with MORB-type Xe. Because I-129 became extinct about 100 million years after the formation of the Solar System, OIB and MORB mantle sources must have differentiated by 4.45 billion years ago and subsequent mixing must have been limited. The Iceland plume source also has a higher proportion of Pu- to U-derived fission Xe, requiring the plume source to be less degassed than MORBs, a conclusion that is independent of noble gas concentrations and the partitioning behaviour of the noble gases with respect to their radiogenic parents. Overall, these results show that Earth's mantle accreted volatiles from at least two separate sources and that neither the Moon-forming impact nor 4.45 billion years of mantle convection has erased the signature of Earth's heterogeneous accretion and early differentiation.
C1 Harvard Univ, Dept Earth & Planetary Sci, Cambridge, MA 02138 USA.
C3 Harvard University
RP Mukhopadhyay, S (corresponding author), Harvard Univ, Dept Earth & Planetary Sci, 20 Oxford St, Cambridge, MA 02138 USA.
EM sujoy@eps.harvard.edu
FU NSF [EAR 0911363]; Division Of Earth Sciences; Directorate For Geosciences [0911363] Funding Source: National Science Foundation
NR 30
TC 304
Z9 342
U1 2
U2 147
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUN 7
PY 2012
VL 486
IS 7401
BP 101
EP U124
DI 10.1038/nature11141
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 953GD
UT WOS:000304854000035
PM 22678288
DA 2026-03-09
ER

PT J
AU Nour-Eldin, HH
   Andersen, TG
   Burow, M
   Madsen, SR
   Jorgensen, ME
   Olsen, CE
   Dreyer, I
   Hedrich, R
   Geiger, D
   Halkier, BA
AF Nour-Eldin, Hussam Hassan
   Andersen, Tonni Grube
   Burow, Meike
   Madsen, Svend Roesen
   Jorgensen, Morten Egevang
   Olsen, Carl Erik
   Dreyer, Ingo
   Hedrich, Rainer
   Geiger, Dietmar
   Halkier, Barbara Ann
TI NRT/PTR transporters are essential for translocation of glucosinolate defence compounds to seeds
SO NATURE
LA English
DT Article
ID arabidopsis-thaliana; phloem; accumulation; products; pathway; nitrate; cloning; growth; fiber; food
AB In plants, transport processes are important for the reallocation of defence compounds to protect tissues of high value(1), as demonstrated in the plant model Arabidopsis, in which the major defence compounds, glucosinolates(2), are translocated to seeds on maturation(3). The molecular basis for long-distance transport of glucosinolates and other defence compounds, however, remains unknown. Here we identify and characterize two members of the nitrate/peptide transporter family, GTR1 and GTR2, as high-affinity, proton-dependent glucosinolate-specific transporters. The gtr1 gtr2 double mutant did not accumulate glucosinolates in seeds and had more than tenfold over-accumulation in source tissues such as leaves and silique walls, indicating that both plasma membrane-localized transporters are essential for long-distance transport of glucosinolates. We propose that GTR1 and GTR2 control the loading of glucosinolates from the apoplasm into the phloem. Identification of the glucosinolate transporters has agricultural potential as a means to control allocation of defence compounds in a tissue-specific manner.
C1 [Nour-Eldin, Hussam Hassan; Andersen, Tonni Grube; Burow, Meike; Madsen, Svend Roesen; Jorgensen, Morten Egevang; Olsen, Carl Erik; Halkier, Barbara Ann] Univ Copenhagen, Fac Sci, Dept Plant & Environm Sci, VKR Res Ctr Proact Plants, DK-1871 Frederiksberg C, Denmark.
   [Nour-Eldin, Hussam Hassan; Andersen, Tonni Grube; Burow, Meike; Madsen, Svend Roesen; Jorgensen, Morten Egevang; Olsen, Carl Erik; Halkier, Barbara Ann] Univ Copenhagen, Fac Sci, Dept Plant & Environm Sci, DynaMo Ctr Excellence, DK-1871 Frederiksberg C, Denmark.
   [Dreyer, Ingo] Univ Politecn Madrid, Ctr Plant Biotechnol & Genom, E-28223 Pozuelo De Alarcon, Madrid, Spain.
   [Hedrich, Rainer; Geiger, Dietmar] Univ Wurzburg, Julius von Sachs Inst, D-97082 Wurzburg, Germany.
C3 University of Copenhagen; University of Copenhagen; Universidad Politecnica de Madrid; Centro de Investigacion en Biotecnologia Genomica de Plantas (CBGP); University of Wurzburg
RP Halkier, BA (corresponding author), Univ Copenhagen, Fac Sci, Dept Plant & Environm Sci, VKR Res Ctr Proact Plants, Thorvaldsensvej 40, DK-1871 Frederiksberg C, Denmark.
EM bah@life.ku.dk
FU Danish Research Council for Technology and Production (FTP) [09-065827/274-08-0354]; Marie Curie fellowship [PIEF-GA-2008-221236]; European Union [303674]; Deutsche Forschungsgemeinschaft [GE2195/1-1, FOR 1061]; Villum Kann Rasmussen Foundation; Danish National Research Foundation
NR 30
TC 402
Z9 461
U1 1
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 AUG 23
PY 2012
VL 488
IS 7412
BP 531
EP 534
DI 10.1038/nature11285
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 992FS
UT WOS:000307761600041
PM 22864417
DA 2026-03-09
ER

PT J
AU Eisenbarth, SC
   Williams, A
   Colegio, OR
   Meng, HL
   Strowig, T
   Rongvaux, A
   Henao-Mejia, J
   Thaiss, CA
   Joly, S
   Gonzalez, DG
   Xu, L
   Zenewicz, LA
   Haberman, AM
   Elinav, E
   Kleinstein, SH
   Sutterwala, FS
   Flavell, RA
AF Eisenbarth, Stephanie C.
   Williams, Adam
   Colegio, Oscar R.
   Meng, Hailong
   Strowig, Till
   Rongvaux, Anthony
   Henao-Mejia, Jorge
   Thaiss, Christoph A.
   Joly, Sophie
   Gonzalez, David G.
   Xu, Lan
   Zenewicz, Lauren A.
   Haberman, Ann M.
   Elinav, Eran
   Kleinstein, Steven H.
   Sutterwala, Fayyaz S.
   Flavell, Richard A.
TI NLRP10 is a NOD-like receptor essential to initiate adaptive immunity by dendritic cells
SO NATURE
LA English
DT Article
ID cutting edge; autoimmune encephalomyelitis; lymph-nodes; dc subsets; migration; antigen; inflammasome; expression; chemokine; sphingosine-1-phosphate
AB NLRs (nucleotide-binding domain leucine-rich-repeat-containing receptors; NOD-like receptors) are a class of pattern recognition receptor (PRR) that respond to host perturbation from either infectious agents or cellular stress(1,2). The function of most NLR family members has not been characterized and their role in instructing adaptive immune responses remains unclear(2,3). NLRP10 (also known as PYNOD, NALP10, PAN5 and NOD8) is the only NLR lacking the putative ligand-binding leucine-rich-repeat domain, and has been postulated to be a negative regulator of other NLR members, including NLRP3 (refs 4-6). We did not find evidence that NLRP10 functions through an inflammasome to regulate caspase-1 activity nor that it regulates other inflammasomes. Instead, Nlrp10(-/-) mice had a profound defect in helper T-cell-driven immune responses to a diverse array of adjuvants, including lipopolysaccharide, aluminium hydroxide and complete Freund's adjuvant. Adaptive immunity was impaired in the absence of NLRP10 because of a dendritic cell (DC) intrinsic defect in emigration from inflamed tissues, whereas upregulation of DC costimulatory molecules and chemotaxis to CCR7-dependent and -independent ligands remained intact. The loss of antigen transport to the draining lymph nodes by a subset of migratory DCs resulted in an almost absolute loss in naive CD4(+) T-cell priming, highlighting the critical link between diverse innate immune stimulation, NLRP10 activity and the immune function of mature DCs.
C1 [Eisenbarth, Stephanie C.; Gonzalez, David G.; Xu, Lan; Haberman, Ann M.] Yale Univ, Sch Med, Dept Lab Med, New Haven, CT 06520 USA.
   [Williams, Adam; Strowig, Till; Rongvaux, Anthony; Henao-Mejia, Jorge; Thaiss, Christoph A.; Zenewicz, Lauren A.; Elinav, Eran; Flavell, Richard A.] Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT 06520 USA.
   [Colegio, Oscar R.; Xu, Lan] Yale Univ, Sch Med, Dept Dermatol, New Haven, CT 06520 USA.
   [Meng, Hailong; Kleinstein, Steven H.] Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06520 USA.
   [Joly, Sophie; Sutterwala, Fayyaz S.] Univ Iowa, Dept Internal Med, Inflammat Program, Iowa City, IA 52242 USA.
   [Kleinstein, Steven H.] Yale Univ, Sch Med, Interdep Program Computat Biol & Bioinformat, New Haven, CT 06520 USA.
   [Flavell, Richard A.] Yale Univ, Sch Med, Howard Hughes Med Inst, New Haven, CT 06520 USA.
   [Sutterwala, Fayyaz S.] Vet Affairs Med Ctr, Iowa City, IA 52241 USA.
C3 Yale University; Yale University; Yale University; Yale University; University of Iowa; Yale University; Howard Hughes Medical Institute; Yale University; US Department of Veterans Affairs; Veterans Health Administration (VHA); Iowa City VA Health Care System
RP Eisenbarth, SC (corresponding author), Yale Univ, Sch Med, Dept Lab Med, 333 Cedar St, New Haven, CT 06520 USA.
EM stephanie.eisenbarth@yale.edu; richard.flavell@yale.edu
FU Yale CTSA [UL1 RR024139, 5KL2RR024138]; Damon Runyon Cancer Research Foundation [DRG 108-09]; Yale SPORE in Skin Cancer [1 P50 CA121974]; Dermatology Foundation; Cancer Research Institute; American Physicians for Medicine in Israel Foundation; United States-Israel binational Foundation; Yale Rheumatologic Disease Research Core Center [P30AR053495]; Edward Mallinckrodt, Jr. Foundation;  [T32HL007974];  [K08AI085038];  [R01AI087630]; National Cancer Institute [P50CA121974] Funding Source: NIH RePORTER; National Heart Lung and Blood Institute [T32HL007974] Funding Source: NIH RePORTER
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NR 36
TC 113
Z9 140
U1 1
U2 44
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 26
PY 2012
VL 484
IS 7395
BP 510
EP U133
DI 10.1038/nature11012
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 931FF
UT WOS:000303200400050
PM 22538615
DA 2026-03-09
ER

PT J
AU Sanchis-Ojeda, R
   Fabrycky, DC
   Winn, JN
   Barclay, T
   Clarke, BD
   Ford, EB
   Fortney, JJ
   Geary, JC
   Holman, MJ
   Howard, AW
   Jenkins, JM
   Koch, D
   Lissauer, JJ
   Marcy, GW
   Mullally, F
   Ragozzine, D
   Seader, SE
   Still, M
   Thompson, SE
AF Sanchis-Ojeda, Roberto
   Fabrycky, Daniel C.
   Winn, Joshua N.
   Barclay, Thomas
   Clarke, Bruce D.
   Ford, Eric B.
   Fortney, Jonathan J.
   Geary, John C.
   Holman, Matthew J.
   Howard, Andrew W.
   Jenkins, Jon M.
   Koch, David
   Lissauer, Jack J.
   Marcy, Geoffrey W.
   Mullally, Fergal
   Ragozzine, Darin
   Seader, Shawn E.
   Still, Martin
   Thompson, Susan E.
TI Alignment of the stellar spin with the orbits of a three-planet system
SO NATURE
LA English
DT Article
ID extrasolar planets; star; starspots; transits; mass
AB The Sun's equator and the planets' orbital planes are nearly aligned, which is presumably a consequence of their formation from a single spinning gaseous disk. For exoplanetary systems this well-aligned configuration is not guaranteed: dynamical interactions may tilt planetary orbits, or stars may be misaligned with the protoplanetary disk through chaotic accretion(1), magnetic interactions(2) or torques from neighbouring stars. Indeed, isolated 'hot Jupiters' are often misaligned and even orbiting retrograde(3,4). Here we report an analysis of transits of planets over starspots(5-7) on the Sun-like star Kepler-30 (ref. 8), and show that the orbits of its three planets are aligned with the stellar equator. Furthermore, the orbits are aligned with one another to within a few degrees. This configuration is similar to that of our Solar System, and contrasts with the isolated hot Jupiters. The orderly alignment seen in the Kepler-30 system suggests that high obliquities are confined to systems that experienced disruptive dynamical interactions. Should this be corroborated by observations of other coplanar multi-planet systems, then star-disk misalignments would be ruled out as the explanation for the high obliquities of hot Jupiters, and dynamical interactions would be implicated as the origin of hot Jupiters.
C1 [Sanchis-Ojeda, Roberto; Winn, Joshua N.] MIT, Dept Phys, Cambridge, MA 02139 USA.
   [Fabrycky, Daniel C.; Fortney, Jonathan J.] Univ Calif Santa Cruz, Dept Astron & Astrophys, Santa Cruz, CA 95064 USA.
   [Barclay, Thomas; Still, Martin] Bay Area Environm Res Inst, Sonoma, CA 95476 USA.
   [Barclay, Thomas; Clarke, Bruce D.; Jenkins, Jon M.; Koch, David; Lissauer, Jack J.; Mullally, Fergal; Seader, Shawn E.; Still, Martin; Thompson, Susan E.] NASA, Ames Res Ctr, Moffett Field, CA 94035 USA.
   [Clarke, Bruce D.; Jenkins, Jon M.; Mullally, Fergal; Seader, Shawn E.; Thompson, Susan E.] SETI Inst, Mountain View, CA USA.
   [Ford, Eric B.] Univ Florida, Bryant Space Sci Ctr 211, Gainesville, FL 32611 USA.
   [Geary, John C.; Holman, Matthew J.; Ragozzine, Darin] Harvard Smithsonian Ctr Astrophys, Cambridge, MA 02138 USA.
   [Howard, Andrew W.; Marcy, Geoffrey W.] Univ Calif Berkeley, Dept Astron, Berkeley, CA 94720 USA.
C3 Massachusetts Institute of Technology (MIT); University of California System; University of California Santa Cruz; National Aeronautics & Space Administration (NASA); NASA Ames Research Center; SETI Institute; State University System of Florida; University of Florida; Smithsonian Institution; Harvard University; Smithsonian Astrophysical Observatory; University of California System; University of California Berkeley
RP Sanchis-Ojeda, R (corresponding author), MIT, Dept Phys, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
EM rsanchis86@gmail.com; daniel.fabrycky@gmail.com
FU NASA's Science Mission Directorate; NASA [NAS5-26555]; NASA Office of Space Science [NNX09AF08G]; NASA through Hubble Fellowship [HF-51272.01-A]; STScI; NASA through the Kepler Participating Scientist programme
NR 20
TC 161
Z9 178
U1 0
U2 13
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUL 26
PY 2012
VL 487
IS 7408
BP 449
EP 453
DI 10.1038/nature11301
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 979KD
UT WOS:000306815300031
PM 22836999
DA 2026-03-09
ER

PT J
AU Onder, TT
   Kara, N
   Cherry, A
   Sinha, AU
   Zhu, N
   Bernt, KM
   Cahan, P
   Mancarci, BO
   Unternaehrer, J
   Gupta, PB
   Lander, ES
   Armstrong, SA
   Daley, GQ
AF Onder, Tamer T.
   Kara, Nergis
   Cherry, Anne
   Sinha, Amit U.
   Zhu, Nan
   Bernt, Kathrin M.
   Cahan, Patrick
   Mancarci, B. Ogan
   Unternaehrer, Juli
   Gupta, Piyush B.
   Lander, Eric S.
   Armstrong, Scott A.
   Daley, George Q.
TI Chromatin-modifying enzymes as modulators of reprogramming
SO NATURE
LA English
DT Article
ID histone methylation; pluripotent; cells; leukemia; prc2
AB Generation of induced pluripotent stem cells (iPSCs) by somatic cell reprogramming involves global epigenetic remodelling(1). Whereas several proteins are known to regulate chromatin marks associated with the distinct epigenetic states of cells before and after reprogramming(2,3), the role of specific chromatin-modifying enzymes in reprogramming remains to be determined. To address how chromatin-modifying proteins influence reprogramming, we used short hairpin RNAs (shRNAs) to target genes in DNA and histone methylation pathways, and identified positive and negative modulators of iPSC generation. Whereas inhibition of the core components of the polycomb repressive complex 1 and 2, including the histone 3 lysine 27 methyltransferase EZH2, reduced reprogramming efficiency, suppression of SUV39H1, YY1 and DOT1L enhanced reprogramming. Specifically, inhibition of the H3K79 histone methyltransferase DOT1L by shRNA or a small molecule accelerated reprogramming, significantly increased the yield of iPSC colonies, and substituted for KLF4 and c-Myc (also known as MYC). Inhibition of DOT1L early in the reprogramming process is associated with a marked increase in two alternative factors, NANOG and LIN28, which play essential functional roles in the enhancement of reprogramming. Genome-wide analysis of H3K79me2 distribution revealed that fibroblast-specific genes associated with the epithelial to mesenchymal transition lose H3K79me2 in the initial phases of reprogramming. DOT1L inhibition facilitates the loss of this mark from genes that are fated to be repressed in the pluripotent state. These findings implicate specific chromatin-modifying enzymes as barriers to or facilitators of reprogramming, and demonstrate how modulation of chromatinmodifying enzymes can be exploited to more efficiently generate iPSCs with fewer exogenous transcription factors.
C1 [Onder, Tamer T.; Cherry, Anne; Cahan, Patrick; Unternaehrer, Juli; Daley, George Q.] Childrens Hosp Boston, Manton Ctr Orphan Dis Res, Div Pediat Hematol & Oncol, Stem Cell Transplantat Program, Boston, MA 02115 USA.
   [Onder, Tamer T.; Cherry, Anne; Cahan, Patrick; Unternaehrer, Juli; Daley, George Q.] Dana Farber Canc Inst, Boston, MA 02115 USA.
   [Onder, Tamer T.; Cherry, Anne; Cahan, Patrick; Unternaehrer, Juli; Daley, George Q.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
   [Onder, Tamer T.; Cherry, Anne; Zhu, Nan; Bernt, Kathrin M.; Cahan, Patrick; Unternaehrer, Juli; Armstrong, Scott A.; Daley, George Q.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA.
   [Onder, Tamer T.; Cherry, Anne; Cahan, Patrick; Unternaehrer, Juli; Daley, George Q.] Childrens Hosp Boston, Stem Cell Program, Boston, MA 02115 USA.
   [Kara, Nergis] German Canc Res Ctr, D-69120 Heidelberg, Germany.
   [Sinha, Amit U.; Zhu, Nan; Bernt, Kathrin M.; Armstrong, Scott A.; Daley, George Q.] Harvard Univ, Sch Med, Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA.
   [Sinha, Amit U.; Zhu, Nan; Bernt, Kathrin M.; Armstrong, Scott A.] Harvard Univ, Sch Med, Dept Pediat Oncol, Boston, MA 02115 USA.
   [Mancarci, B. Ogan] Bilkent Univ, Dept Mol Biol & Genet, TR-06800 Ankara, Turkey.
   [Gupta, Piyush B.; Lander, Eric S.] MIT, Dept Biol, Cambridge, MA 02142 USA.
   [Gupta, Piyush B.] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA.
   [Lander, Eric S.] Broad Inst Harvard & Massachusetts Inst Technol, Cambridge, MA 02142 USA.
   [Lander, Eric S.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA.
   [Daley, George Q.] Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA.
   [Daley, George Q.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA.
C3 Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard Medical School; Harvard University; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Helmholtz Association; German Cancer Research Center (DKFZ); Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Harvard Medical School; Harvard University; Harvard Medical School; Ihsan Dogramaci Bilkent University; Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); Whitehead Institute; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Harvard University; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Howard Hughes Medical Institute
RP Daley, GQ (corresponding author), Childrens Hosp Boston, Manton Ctr Orphan Dis Res, Div Pediat Hematol & Oncol, Stem Cell Transplantat Program, Boston, MA 02115 USA.
EM George.Daley@childrens.harvard.edu
FU US National Institutes of Health (NIH) [CA140575]; CHB Stem Cell Program
NR 30
TC 532
Z9 648
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 MAR 29
PY 2012
VL 483
IS 7391
BP 598
EP U119
DI 10.1038/nature10953
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 915EF
UT WOS:000302006100039
PM 22388813
DA 2026-03-09
ER

PT J
AU Alon, A
   Grossman, I
   Gat, Y
   Kodali, VK
   DiMaio, F
   Mehlman, T
   Haran, G
   Baker, D
   Thorpe, C
   Fass, D
AF Alon, Assaf
   Grossman, Iris
   Gat, Yair
   Kodali, Vamsi K.
   DiMaio, Frank
   Mehlman, Tevie
   Haran, Gilad
   Baker, David
   Thorpe, Colin
   Fass, Deborah
TI The dynamic disulphide relay of quiescin sulphydryl oxidase
SO NATURE
LA English
DT Article
ID k epoxide reductase; protein-structure; family; qsox; er
AB Protein stability, assembly, localization and regulation often depend on the formation of disulphide crosslinks between cysteine side chains. Enzymes known as sulphydryl oxidases catalysede novo disulphide formation and initiate intra-and intermolecular dithiol/disulphide relays to deliver the disulphides to substrate proteins(1,2). Quiescin sulphydryl oxidase (QSOX) is a unique, multi-domain disulphide catalyst that is localized primarily to the Golgi apparatus and secreted fluids(3) and has attracted attention owing to its overproduction in tumours(4,5). In addition to its physiological importance, QSOX is a mechanistically intriguing enzyme, encompassing functions typically carried out by a series of proteins in other disulphide-formation pathways. How disulphides are relayed through the multiple redox-active sites of QSOX and whether there is a functional benefit to concatenating these sites on a single polypeptide are open questions. Here we present the first crystal structure of an intact QSOX enzyme, derived from a trypanosome parasite. Notably, sequential sites in the disulphide relay were found more than 40 angstrom apart in this structure, too far for direct disulphide transfer. To resolve this puzzle, we trapped and crystallized an intermediate in the disulphide hand-off, which showed a 165 degrees domain rotation relative to the original structure, bringing the two active sites within disulphide-bonding distance. The comparable structure of a mammalian QSOX enzyme, also presented here, shows further biochemical features that facilitate disulphide transfer in metazoan orthologues. Finally, we quantified the contribution of concatenation to QSOX activity, providing general lessons for the understanding of multi-domain enzymes and the design of new catalytic relays.
C1 [Alon, Assaf; Grossman, Iris; Gat, Yair; Fass, Deborah] Weizmann Inst Sci, Dept Biol Struct, IL-76100 Rehovot, Israel.
   [Kodali, Vamsi K.; Thorpe, Colin] Univ Delaware, Dept Chem & Biochem, Newark, DE 19716 USA.
   [DiMaio, Frank; Baker, David] Univ Washington, Dept Biochem, Seattle, WA 98195 USA.
   [Mehlman, Tevie] Weizmann Inst Sci, Dept Biol Res Support, IL-76100 Rehovot, Israel.
   [Haran, Gilad] Weizmann Inst Sci, Dept Chem Phys, IL-76100 Rehovot, Israel.
C3 Weizmann Institute of Science; University of Delaware; University of Washington; University of Washington Seattle; Weizmann Institute of Science; Weizmann Institute of Science
RP Fass, D (corresponding author), Weizmann Inst Sci, Dept Biol Struct, IL-76100 Rehovot, Israel.
EM deborah.fass@weizmann.ac.il
FU Israel Science Foundation; Kimmelman Center for Macromolecular Assemblies; National Institutes of Health (NIH) [GM26643]; NIH [P41 RR001081]
NR 34
TC 67
Z9 93
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 AUG 16
PY 2012
VL 488
IS 7411
BP 414
EP +
DI 10.1038/nature11267
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 988OS
UT WOS:000307501000049
PM 22801504
DA 2026-03-09
ER

PT J
AU Allen, NJ
   Bennett, ML
   Foo, LC
   Wang, GX
   Chakraborty, C
   Smith, SJ
   Barres, B
AF Allen, Nicola J.
   Bennett, Mariko L.
   Foo, Lynette C.
   Wang, Gordon X.
   Chakraborty, Chandrani
   Smith, Stephen J.
   Barres, Ben A.
TI Astrocyte glypicans 4 and 6 promote formation of excitatory synapses via GluA1 AMPA receptors
SO NATURE
LA English
DT Article
ID synaptic plasticity; cns synaptogenesis; secreted proteins; neurons; brain; strength; roles; lar
AB In the developing central nervous system (CNS), the control of synapse number and function is critical to the formation of neural circuits. We previously demonstrated that astrocyte-secreted factors powerfully induce the formation of functional excitatory synapses between CNS neurons(1). Astrocyte-secreted thrombospondins induce the formation of structural synapses, but these synapses are postsynaptically silent(2). Here we use biochemical fractionation of astrocyte-conditioned medium to identify glypican 4 (Gpc4) and glypican 6 (Gpc6) as astrocyte-secreted signals sufficient to induce functional synapses between purified retinal ganglion cell neurons, and show that depletion of these molecules from astrocyte-conditioned medium significantly reduces its ability to induce postsynaptic activity. Application of Gpc4 to purified neurons is sufficient to increase the frequency and amplitude of glutamatergic synaptic events. This is achieved by increasing the surface level and clustering, but not overall cellular protein level, of the GluA1 subunit of the AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) glutamate receptor (AMPAR). Gpc4 and Gpc6 are expressed by astrocytes in vivo in the developing CNS, with Gpc4 expression enriched in the hippocampus and Gpc6 enriched in the cerebellum. Finally, we demonstrate that Gpc4-deficient mice have defective synapse formation, with decreased amplitude of excitatory synaptic currents in the developing hippocampus and reduced recruitment of AMPARs to synapses. These data identify glypicans as a family of novel astrocyte-derived molecules that are necessary and sufficient to promote glutamate receptor clustering and receptivity and to induce the formation of postsynaptically functioning CNS synapses.
C1 [Allen, Nicola J.; Bennett, Mariko L.; Foo, Lynette C.; Chakraborty, Chandrani; Barres, Ben A.] Stanford Univ, Sch Med, Dept Neurobiol, Stanford, CA 94305 USA.
   [Wang, Gordon X.; Smith, Stephen J.] Stanford Univ, Sch Med, Dept Mol & Cellular Physiol, Stanford, CA 94305 USA.
C3 Stanford University; Stanford University
RP Allen, NJ (corresponding author), Salk Inst Biol Studies, Mol Neurobiol Lab, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA.
EM nallen@salk.edu
FU NIDA [R01DA015043]; Human Frontiers Long Term Fellowship; NIH/NINDS [R01NS0725252, R01NS077601]
NR 32
TC 583
Z9 732
U1 2
U2 90
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUN 21
PY 2012
VL 486
IS 7403
BP 410
EP +
DI 10.1038/nature11059
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 961LV
UT WOS:000305466800045
PM 22722203
DA 2026-03-09
ER

PT J
AU Morison, J
   Kwok, R
   Peralta-Ferriz, C
   Alkire, M
   Rigor, I
   Andersen, R
   Steele, M
AF Morison, James
   Kwok, Ron
   Peralta-Ferriz, Cecilia
   Alkire, Matt
   Rigor, Ignatius
   Andersen, Roger
   Steele, Mike
TI Changing Arctic Ocean freshwater pathways
SO NATURE
LA English
DT Article
ID beaufort gyre; ice; temperature; variability; runoff; model
AB Freshening in the Canada basin of the Arctic Ocean began in the 1990s(1,2) and continued(3) to at least the end of 2008. By then, the Arctic Ocean might have gained four times as much fresh water as comprised the Great Salinity Anomaly(4,5) of the 1970s, raising the spectre of slowing global ocean circulation(6). Freshening has been attributed to increased sea ice melting(1) and contributions from runoff(7), but a leading explanation has been a strengthening of the Beaufort High-a characteristic peak in sea level atmospheric pressure(2,8)-which tends to accelerate an anticyclonic (clockwise) wind pattern causing convergence of fresh surface water. Limited observations have made this explanation difficult to verify, and observations of increasing freshwater content under a weakened Beaufort High suggest that other factors(2) must be affecting freshwater content. Here we use observations to show that during a time of record reductions in ice extent from 2005 to 2008, the dominant freshwater content changes were an increase in the Canada basin balanced by a decrease in the Eurasian basin. Observations are drawn from satellite data (sea surface height and ocean-bottom pressure) and in situ data. The freshwater changes were due to a cyclonic (anticlockwise) shift in the ocean pathway of Eurasian runoff forced by strengthening of the west-to-east Northern Hemisphere atmospheric circulation characterized by an increased Arctic Oscillation(9) index. Our results confirm that runoff is an important influence on the Arctic Ocean and establish that the spatial and temporal manifestations of the runoff pathways are modulated by the Arctic Oscillation, rather than the strength of the wind-driven Beaufort Gyre circulation.
C1 [Morison, James; Peralta-Ferriz, Cecilia; Alkire, Matt; Rigor, Ignatius; Andersen, Roger; Steele, Mike] Univ Washington, Appl Phys Lab, Polar Sci Ctr, Seattle, WA 98105 USA.
   [Kwok, Ron] CALTECH, Jet Prop Lab, Pasadena, CA 91109 USA.
C3 University of Washington; University of Washington Seattle; National Aeronautics & Space Administration (NASA); NASA Jet Propulsion Laboratory (JPL); California Institute of Technology
RP Morison, J (corresponding author), Univ Washington, Appl Phys Lab, Polar Sci Ctr, 1013 NE 40th St, Seattle, WA 98105 USA.
EM morison@apl.washington.edu
FU NSF [OPP 0352754]; NASA [NNX08AH62G]; Jet Propulsion Laboratory, California Institute of Technology; NASA MEASURES;  [ARC-0634226];  [ARC-0856330]; Directorate For Geosciences; Office of Polar Programs (OPP) [0856177, 1022710] Funding Source: National Science Foundation; Office of Polar Programs (OPP); Directorate For Geosciences [1022475, 1203506, 0856330] Funding Source: National Science Foundation; NASA [NNX08AH62G, 100903] Funding Source: Federal RePORTER
NR 31
TC 356
Z9 406
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 JAN 5
PY 2012
VL 481
IS 7379
BP 66
EP 70
DI 10.1038/nature10705
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 872VD
UT WOS:000298836900030
PM 22222749
DA 2026-03-09
ER

PT J
AU Wagner, CE
   Harmon, LJ
   Seehausen, O
AF Wagner, Catherine E.
   Harmon, Luke J.
   Seehausen, Ole
TI Ecological opportunity and sexual selection together predict adaptive radiation
SO NATURE
LA English
DT Article
ID logistic-regression; mixed models; speciation; evolution; diversity; determinism; gradient; fishes; scale
AB A fundamental challenge to our understanding of biodiversity is to explain why some groups of species undergo adaptive radiations, diversifying extensively into many and varied species, whereas others do not(1,2). Both extrinsic environmental factors (for example, resource availability, climate) and intrinsic lineage-specific traits (for example, behavioural or morphological traits, genetic architecture) influence diversification, but few studies have addressed how such factors interact. Radiations of cichlid fishes in the African Great Lakes provide some of the most dramatic cases of species diversification. However, most cichlid lineages in African lakes have not undergone adaptive radiations. Here we compile data on cichlid colonization and diversification in 46 African lakes, along with lake environmental features and information about the traits of colonizing cichlid lineages, to investigate why adaptive radiation does and does not occur. We find that extrinsic environmental factors related to ecological opportunity and intrinsic lineage-specific traits related to sexual selection both strongly influence whether cichlids radiate. Cichlids are more likely to radiate in deep lakes, in regions with more incident solar radiation and in lakes where there has been more time for diversification. Weak or negative associations between diversification and lake surface area indicate that cichlid speciation is not constrained by area, in contrast to diversification in many terrestrial taxa(3). Among the suite of intrinsic traits that we investigate, sexual dichromatism, a surrogate for the intensity of sexual selection, is consistently positively associated with diversification. Thus, for cichlids, it is the coincidence between ecological opportunity and sexual selection that best predicts whether adaptive radiation will occur. These findings suggest that adaptive radiation is predictable, but only when species traits and environmental factors are jointly considered.
C1 [Wagner, Catherine E.; Seehausen, Ole] EAWAG Ctr Ecol Evolut & Biogeochem, Dept Fish Ecol & Evolut, CH-6047 Kastanienbaum, Switzerland.
   [Wagner, Catherine E.; Seehausen, Ole] Univ Bern, Inst Ecol & Evolut, Dept Aquat Ecol, CH-3012 Bern, Switzerland.
   [Wagner, Catherine E.] Cornell Univ, Dept Ecol & Evolutionary Biol, Ithaca, NY 14853 USA.
   [Wagner, Catherine E.] Cornell Univ, Ornithol Lab, Fuller Evolutionary Biol Program, Ithaca, NY 14850 USA.
   [Harmon, Luke J.] Univ Idaho, Dept Biol Sci, Moscow, ID 83844 USA.
C3 Swiss Federal Institutes of Technology Domain; Swiss Federal Institute of Aquatic Science & Technology (EAWAG); University of Bern; Cornell University; Cornell University; University of Idaho
RP Wagner, CE (corresponding author), EAWAG Ctr Ecol Evolut & Biogeochem, Dept Fish Ecol & Evolut, CH-6047 Kastanienbaum, Switzerland.
EM catherine.wagner@eawag.ch; ole.seehausen@eawag.ch
FU National Center for Research Resources [5P20RR016448-10]; National Institute of General Medical Sciences from the National Institutes of Health [8 P20 GM103397-10]; Swiss National Science Foundation [31003A-118293]; US National Science Foundation [DEB 0919499]; Direct For Biological Sciences; Division Of Environmental Biology [0919499] Funding Source: National Science Foundation; Swiss National Science Foundation (SNF) [31003A-118293] Funding Source: Swiss National Science Foundation (SNF)
NR 33
TC 394
Z9 450
U1 1
U2 390
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUL 19
PY 2012
VL 487
IS 7407
BP 366
EP U124
DI 10.1038/nature11144
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 975JB
UT WOS:000306506500043
PM 22722840
DA 2026-03-09
ER

PT J
AU Davis, SP
   Finarelli, JA
   Coates, MI
AF Davis, Samuel P.
   Finarelli, John A.
   Coates, Michael I.
TI Acanthodes and shark-like conditions in the last common ancestor of modern gnathostomes
SO NATURE
LA English
DT Article
ID braincase; chondrichthyan
AB Acanthodians, an exclusively Palaeozoic group of fish, are central to a renewed debate on the origin of modern gnathostomes: jawed vertebrates comprising Chondrichthyes (sharks, rays and ratfish) and Osteichthyes (bony fishes and tetrapods)(1-6). Acanthodian internal anatomy is primarily understood from Acanthodes bronni(2,7-10) because it remains the only example preserved in substantial detail, central to which is an ostensibly osteichthyan braincase(1,2,7). For this reason, Acanthodes has become an indispensible component in early gnathostome phylogenies(1,11-17). Here we present a new description of the Acanthodes braincase, yielding new details of external and internal morphology, notably the regions surrounding and within the ear capsule and neurocranial roof. These data contribute to a new reconstruction that, unexpectedly, resembles early chondrichthyan crania. Principal coordinates analysis of a character-taxon matrix including these new data confirms this impression: Acanthodes is quantifiably closer to chondrichthyans than to osteichthyans. However, phylogenetic analysis places Acanthodes on the osteichthyan stem, as part of a well-resolved tree that also recovers acanthodians as stem chondrichthyans and stem gnathostomes. As such, perceived chondrichthyan features of the Acanthodes cranium represent shared primitive conditions for crown group gnathostomes. Moreover, this increasingly detailed picture of early gnathostome evolution highlights ongoing and profound anatomical reorganization of vertebrate crania after the origin of jaws but before the divergence of living clades.
C1 [Coates, Michael I.] Univ Chicago, Dept Organismal Biol & Anat, Chicago, IL 60637 USA.
   [Finarelli, John A.] Univ Coll Dublin, UCD Sch Biol & Environm Sci, UCD Sci Educ & Res Ctr, Dublin 4, Ireland.
C3 University of Chicago; University College Dublin
RP Coates, MI (corresponding author), Univ Chicago, Dept Organismal Biol & Anat, 1025 E 57Th St, Chicago, IL 60637 USA.
EM mcoates@uchicago.edu
FU Natural Environment Research Council (UK) [GT4/97/183ES]; National Science Foundation (USA) [DEB-0917922]; Division Of Environmental Biology; Direct For Biological Sciences [0917922] Funding Source: National Science Foundation
NR 37
TC 147
Z9 173
U1 1
U2 113
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 14
PY 2012
VL 486
IS 7402
BP 247
EP +
DI 10.1038/nature11080
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 957UH
UT WOS:000305189000033
PM 22699617
DA 2026-03-09
ER

PT J
AU Ekiert, DC
   Kashyap, AK
   Steel, J
   Rubrum, A
   Bhabha, G
   Khayat, R
   Lee, JH
   Dillon, MA
   O'Neil, RE
   Faynboym, AM
   Horowitz, M
   Horowitz, L
   Ward, AB
   Palese, P
   Webby, R
   Lerner, RA
   Bhatt, RR
   Wilson, IA
AF Ekiert, Damian C.
   Kashyap, Arun K.
   Steel, John
   Rubrum, Adam
   Bhabha, Gira
   Khayat, Reza
   Lee, Jeong Hyun
   Dillon, Michael A.
   O'Neil, Ryann E.
   Faynboym, Aleksandr M.
   Horowitz, Michael
   Horowitz, Lawrence
   Ward, Andrew B.
   Palese, Peter
   Webby, Richard
   Lerner, Richard A.
   Bhatt, Ramesh R.
   Wilson, Ian A.
TI Cross-neutralization of influenza A viruses mediated by a single antibody loop
SO NATURE
LA English
DT Article
ID potent neutralization; crystal-structure; structural basis; hemagglutinin; epitope; system; broad; recognition; insertions; deletions
AB Immune recognition of protein antigens relies on the combined interaction of multiple antibody loops, which provide a fairly large footprint and constrain the size and shape of protein surfaces that can be targeted. Single protein loops can mediate extremely high-affinity binding, but it is unclear whether such a mechanism is available to antibodies. Here we report the isolation and characterization of an antibody called C05, which neutralizes strains from multiple subtypes of influenza A virus, including H1, H2 and H3. X-ray and electron microscopy structures show that C05 recognizes conserved elements of the receptor-binding site on the haemagglutinin surface glycoprotein. Recognition of the haemagglutinin receptor-binding site is dominated by a single heavy-chain complementarity-determining region 3 loop, with minor contacts from heavy-chain complementarity-determining region 1, and is sufficient to achieve nanomolar binding with a minimal footprint. Thus, binding predominantly with a single loop can allow antibodies to target small, conserved functional sites on otherwise hypervariable antigens.
C1 [Ekiert, Damian C.; Bhabha, Gira; Khayat, Reza; Lee, Jeong Hyun; Ward, Andrew B.; Wilson, Ian A.] Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA.
   [Kashyap, Arun K.; Dillon, Michael A.; O'Neil, Ryann E.; Faynboym, Aleksandr M.; Horowitz, Michael; Horowitz, Lawrence; Bhatt, Ramesh R.] Sea Lane Biotechnol, Mountain View, CA 94043 USA.
   [Steel, John; Palese, Peter] Mt Sinai Sch Med, Dept Microbiol, New York, NY 10029 USA.
   [Rubrum, Adam; Webby, Richard] St Jude Childrens Res Hosp, Dept Infect Dis, Memphis, TN 38105 USA.
   [Lerner, Richard A.] Scripps Res Inst, Dept Chem, La Jolla, CA 92037 USA.
   [Wilson, Ian A.] Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA.
C3 Scripps Research Institute; Icahn School of Medicine at Mount Sinai; St Jude Children's Research Hospital; Scripps Research Institute; Scripps Research Institute
RP Wilson, IA (corresponding author), Scripps Res Inst, Dept Mol Biol, 10550 N Torrey Pines Rd, La Jolla, CA 92037 USA.
EM ramesh.bhatt@sealanebio.com; wilson@scripps.edu
FU National Institutes of Health (NIH) [P01AI058113]; Achievement Rewards for College Scientists Foundation [GM080209]; NIH Molecular Evolution Training Program; Skaggs Institute; Northeast Biodefense Center [U54-AI057158-Lipkin]; National Institute of Allergy and Infectious Diseases (NIAID) [U01AI070373]; Center for Research on Influenza Pathogenesis NIAID [HHSN266200700010C]; DOE Office of Biological and Environmental Research; NIH, National Center for Research Resources, Biomedical Technology Program; National Institute of General Medical Sciences (NIGMS); National Cancer Institute [Y1-CO-1020]; NIGMS [Y1-GM-1104]; US Department of Energy, Basic Energy Sciences, Office of Science [DE-AC02-06CH11357]; NIH though the P41 program at the National Center for Research Resources [RR017573]; NIH [U54 GM094586]
NR 50
TC 421
Z9 516
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 SEP 27
PY 2012
VL 489
IS 7417
BP 526
EP +
DI 10.1038/nature11414
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 011LT
UT WOS:000309167100042
PM 22982990
DA 2026-03-09
ER

PT J
AU Levendorf, MP
   Kim, CJ
   Brown, L
   Huang, PY
   Havener, RW
   Muller, DA
   Park, J
AF Levendorf, Mark P.
   Kim, Cheol-Joo
   Brown, Lola
   Huang, Pinshane Y.
   Havener, Robin W.
   Muller, David A.
   Park, Jiwoong
TI Graphene and boron nitride lateral heterostructures for atomically thin circuitry
SO NATURE
LA English
DT Article
ID grain-boundary; high-quality; growth
AB Precise spatial control over the electrical properties of thin films is the key capability enabling the production of modern integrated circuitry. Although recent advances in chemical vapour deposition methods have enabled the large-scale production of both intrinsic and doped graphene(1-6), as well as hexagonal boron nitride (h-BN)(7-10), controlled fabrication of lateral heterostructures in these truly atomically thin systems has not been achieved. Graphene/h-BN interfaces are of particular interest, because it is known that areas of different atomic compositions may coexist within continuous atomically thin films(5,10) and that, with proper control, the bandgap and magnetic properties can be precisely engineered(11-13). However, previously reported approaches for controlling these interfaces have fundamental limitations and cannot be easily integrated with conventional lithography(14-16). Here we report a versatile and scalable process, which we call 'patterned regrowth', that allows for the spatially controlled synthesis of lateral junctions between electrically conductive graphene and insulating h-BN, as well as between intrinsic and substitutionally doped graphene. We demonstrate that the resulting films form mechanically continuous sheets across these heterojunctions. Conductance measurements confirm laterally insulating behaviour for h-BN regions, while the electrical behaviour of both doped and undoped graphene sheets maintain excellent properties, with low sheet resistances and high carrier mobilities. Our results represent an important step towards developing atomically thin integrated circuitry and enable the fabrication of electrically isolated active and passive elements embedded in continuous, one-atom-thick sheets, which could be manipulated and stacked to form complex devices at the ultimate thickness limit.
C1 [Levendorf, Mark P.; Kim, Cheol-Joo; Brown, Lola; Park, Jiwoong] Cornell Univ, Dept Chem & Chem Biol, Ithaca, NY 14853 USA.
   [Huang, Pinshane Y.; Havener, Robin W.; Muller, David A.] Cornell Univ, Sch Appl & Engn Phys, Ithaca, NY 14853 USA.
   [Muller, David A.; Park, Jiwoong] Cornell Nanoscale Sci, Kavli Inst, Ithaca, NY 14853 USA.
C3 Cornell University; Cornell University
RP Park, J (corresponding author), Cornell Univ, Dept Chem & Chem Biol, Ithaca, NY 14853 USA.
EM jpark@cornell.edu
FU AFOSR [FA9550-09-1-0691, FA9550-10-1-0410]; NSF through the Cornell Centers for Materials Research [NSF DMR-1120296]; Alfred P. Sloan Foundation; Fullbright scholarship; NSF Graduate Research Fellowship; National Science Foundation [ECS-0335765]
NR 31
TC 765
Z9 871
U1 4
U2 943
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 30
PY 2012
VL 488
IS 7413
BP 627
EP 632
DI 10.1038/nature11408
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 996NC
UT WOS:000308095100050
PM 22932386
DA 2026-03-09
ER

PT J
AU Leow, D
   Li, G
   Mei, TS
   Yu, JQ
AF Leow, Dasheng
   Li, Gang
   Mei, Tian-Sheng
   Yu, Jin-Quan
TI Activation of remote meta-C-H bonds assisted by an end-on template
SO NATURE
LA English
DT Article
ID carbon-hydrogen bonds; room-temperature; arylation; olefination; catalyst; arenes; functionalization; selectivity; reactivity; complexes
AB Functionalization of unactivated carbon-hydrogen (C-H) single bonds is an efficient strategy for rapid generation of complex molecules from simpler ones. However, it is difficult to achieve selectivity when multiple inequivalent C-H bonds are present in the target molecule. The usual approach is to use sigma-chelating directing groups, which lead to ortho-selectivity through the formation of a conformationally rigid six- or seven-membered cyclic pre-transition state(1-14). Despite the broad utility of this approach, proximity-driven reactivity prevents the activation of remote C-H bonds. Here we report a class of easily removable nitrile-containing templates that direct the activation of distal meta-C-H bonds (more than ten bonds away) of a tethered arene. We attribute this new mode of C-H activation to a weak 'end-on' interaction(15) between the linear nitrile group and the metal centre. The 'end-on' coordination geometry relieves the strain of the cyclophane-like pre-transition state of the meta-C-H activation event. In addition, this template overrides the intrinsic electronic and steric biases as well as ortho-directing effects with two broadly useful classes of arene substrates (toluene derivatives and hydrocinnamic acids).
C1 [Leow, Dasheng; Li, Gang; Mei, Tian-Sheng; Yu, Jin-Quan] Scripps Res Inst, Dept Chem, La Jolla, CA 92037 USA.
C3 Scripps Research Institute
RP Yu, JQ (corresponding author), Scripps Res Inst, Dept Chem, 10550 N Torrey Pines Rd, La Jolla, CA 92037 USA.
EM yu200@scripps.edu
FU Scripps Research Institute; NIH (NIGMS) [1 R01 GM084019-03]; Agency for Science, Technology and Research (A*STAR) in Singapore; National Institute of General Medical Sciences [R01GM084019] Funding Source: NIH RePORTER
NR 30
TC 793
Z9 869
U1 8
U2 483
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUN 28
PY 2012
VL 486
IS 7404
BP 518
EP 522
DI 10.1038/nature11158
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 965IJ
UT WOS:000305760600040
PM 22739317
DA 2026-03-09
ER

PT J
AU Gassmann, R
   Rechtsteiner, A
   Yuen, KW
   Muroyama, A
   Egelhofer, T
   Gaydos, L
   Barron, F
   Maddox, P
   Essex, A
   Monen, J
   Ercan, S
   Lieb, JD
   Oegema, K
   Strome, S
   Desai, A
AF Gassmann, Reto
   Rechtsteiner, Andreas
   Yuen, Karen W.
   Muroyama, Andrew
   Egelhofer, Thea
   Gaydos, Laura
   Barron, Francie
   Maddox, Paul
   Essex, Anthony
   Monen, Joost
   Ercan, Sevinc
   Lieb, Jason D.
   Oegema, Karen
   Strome, Susan
   Desai, Arshad
TI An inverse relationship to germline transcription defines centromeric chromatin in C. elegans
SO NATURE
LA English
DT Article
ID caenorhabditis-elegans; chromosome segregation; cenp-a; kinetochore; dynamics; requires; embryos; mitosis
AB Centromeres are chromosomal loci that direct segregation of the genome during cell division. The histone H3 variant CENP-A (also known as CenH3) defines centromeres in monocentric organisms, which confine centromere activity to a discrete chromosomal region, and holocentric organisms, which distribute centromere activity along the chromosome length(1-3). Because the highly repetitive DNA found at most centromeres is neither necessary nor sufficient for centromere function, stable inheritance of CENP-A nucleosomal chromatin is postulated to propagate centromere identity epigenetically(4). Here, we show that in the holocentric nematode Caenorhabditis elegans pre-existing CENP-A nucleosomes are not necessary to guide recruitment of new CENP-A nucleosomes. This is indicated by lack of CENP-A transmission by sperm during fertilization and by removal and subsequent reloading of CENP-A during oogenic meiotic prophase. Genome-wide mapping of CENP-A location in embryos and quantification of CENP-A molecules in nuclei revealed that CENP-A is incorporated at low density in domains that cumulatively encompass half the genome. Embryonic CENP-A domains are established in a pattern inverse to regions that are transcribed in the germline and early embryo, and ectopic transcription of genes in a mutant germline altered the pattern of CENP-A incorporation in embryos. Furthermore, regions transcribed in the germline but not embryos fail to incorporate CENP-A throughout embryogenesis. We propose that germline transcription defines genomic regions that exclude CENP-A incorporation in progeny, and that zygotic transcription during early embryogenesis remodels and reinforces this basal pattern. These findings link centromere identity to transcription and shed light on the evolutionary plasticity of centromeres.
C1 [Gassmann, Reto; Yuen, Karen W.; Muroyama, Andrew; Barron, Francie; Maddox, Paul; Essex, Anthony; Monen, Joost; Oegema, Karen; Desai, Arshad] Univ Calif San Diego, Ludwig Inst Canc Res, La Jolla, CA 92037 USA.
   [Gassmann, Reto; Yuen, Karen W.; Muroyama, Andrew; Barron, Francie; Maddox, Paul; Essex, Anthony; Monen, Joost; Oegema, Karen; Desai, Arshad] Univ Calif San Diego, Dept Cellular & Mol Med, La Jolla, CA 92037 USA.
   [Rechtsteiner, Andreas; Egelhofer, Thea; Gaydos, Laura; Strome, Susan] Univ Calif Santa Cruz, Dept Mol Cell & Dev Biol, Santa Cruz, CA 95064 USA.
   [Ercan, Sevinc; Lieb, Jason D.] Univ N Carolina, Dept Biol, Carolina Ctr Genome Sci, Chapel Hill, NC 27599 USA.
   [Ercan, Sevinc; Lieb, Jason D.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA.
C3 Ludwig Institute for Cancer Research; 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 Santa Cruz; University of North Carolina; University of North Carolina Chapel Hill; University of North Carolina; University of North Carolina Chapel Hill
RP Desai, A (corresponding author), Univ Calif San Diego, Ludwig Inst Canc Res, La Jolla, CA 92037 USA.
EM sstrome@ucsc.edu; abdesai@ucsd.edu
FU modENCODE [U01 HG004270]; NIH [GM074215, GM34059, T32 GM008646]; National Science Foundation of Switzerland; Ludwig Institute for Cancer Research; National Institute of General Medical Sciences [R01GM074215] Funding Source: NIH RePORTER
NR 34
TC 137
Z9 153
U1 0
U2 34
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD APR 26
PY 2012
VL 484
IS 7395
BP 534
EP U166
DI 10.1038/nature10973
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 931FF
UT WOS:000303200400055
PM 22495302
DA 2026-03-09
ER

PT J
AU Li, PL
   Banjade, S
   Cheng, HC
   Kim, S
   Chen, B
   Guo, L
   Llaguno, M
   Hollingsworth, JV
   King, DS
   Banani, SF
   Russo, PS
   Jiang, QX
   Nixon, BT
   Rosen, MK
AF Li, Pilong
   Banjade, Sudeep
   Cheng, Hui-Chun
   Kim, Soyeon
   Chen, Baoyu
   Guo, Liang
   Llaguno, Marc
   Hollingsworth, Javoris V.
   King, David S.
   Banani, Salman F.
   Russo, Paul S.
   Jiang, Qiu-Xing
   Nixon, B. Tracy
   Rosen, Michael K.
TI Phase transitions in the assembly of multivalent signalling proteins
SO NATURE
LA English
DT Article
ID nuclear-body; nck; mechanisms; rna; polymerization; translation; polymers; granules; domains; motifs
AB Cells are organized on length scales ranging from angstrom to micrometres. However, the mechanisms by which angstrom-scale molecular properties are translated to micrometre-scale macroscopic properties are not well understood. Here we show that interactions between diverse synthetic, multivalent macromolecules (including multi-domain proteins and RNA) produce sharp liquid-liquid demixing phase separations, generating micrometre-sized liquid droplets in aqueous solution. This macroscopic transition corresponds to a molecular transition between small complexes and large, dynamic supramolecular polymers. The concentrations needed for phase transition are directly related to the valency of the interacting species. In the case of the actin-regulatory protein called neural Wiskott-Aldrich syndrome protein (N-WASP) interacting with its established biological partners NCK and phosphorylated nephrin(1), the phase transition corresponds to a sharp increase in activity towards an actin nucleation factor, the Arp2/3 complex. The transition is governed by the degree of phosphorylation of nephrin, explaining how this property of the system can be controlled to regulatory effect by kinases. The widespread occurrence of multivalent systems suggests that phase transitions may be used to spatially organize and biochemically regulate information throughout biology.
C1 [Li, Pilong; Banjade, Sudeep; Cheng, Hui-Chun; Kim, Soyeon; Chen, Baoyu; Banani, Salman F.; Rosen, Michael K.] Univ Texas SW Med Ctr Dallas, Dept Biochem, Dallas, TX 75390 USA.
   [Li, Pilong; Banjade, Sudeep; Cheng, Hui-Chun; Kim, Soyeon; Chen, Baoyu; Banani, Salman F.; Rosen, Michael K.] Univ Texas SW Med Ctr Dallas, Howard Hughes Med Inst, Dallas, TX 75390 USA.
   [Guo, Liang] Argonne Natl Lab, BioCAT IIT Adv Photon Source, Argonne, IL 60439 USA.
   [Llaguno, Marc; Jiang, Qiu-Xing] Univ Texas SW Med Ctr Dallas, Dept Cell Biol, Dallas, TX 75390 USA.
   [Hollingsworth, Javoris V.; Russo, Paul S.] Louisiana State Univ, Dept Chem, Baton Rouge, LA 70803 USA.
   [Hollingsworth, Javoris V.; Russo, Paul S.] Louisiana State Univ, Macromol Studies Grp, Baton Rouge, LA 70803 USA.
   [King, David S.] Univ Calif Berkeley, Howard Hughes Med Inst, Mass Spectrometry Lab, Berkeley, CA 94720 USA.
   [King, David S.] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA.
   [Nixon, B. Tracy] Penn State Univ, Dept Biochem & Mol Biol, University Pk, PA 16802 USA.
C3 University of Texas System; University of Texas Southwestern Medical Center; University of Texas System; University of Texas Southwestern Medical Center; Howard Hughes Medical Institute; United States Department of Energy (DOE); Argonne National Laboratory; University of Texas System; University of Texas Southwestern Medical Center; Louisiana State University System; Louisiana State University; Louisiana State University System; Louisiana State University; University of California System; University of California Berkeley; Howard Hughes Medical Institute; University of California System; University of California Berkeley; Pennsylvania Commonwealth System of Higher Education (PCSHE); Pennsylvania State University; Pennsylvania State University - University Park
RP Rosen, MK (corresponding author), Univ Texas SW Med Ctr Dallas, Dept Biochem, Dallas, TX 75390 USA.
EM Michael.Rosen@utsouthwestern.edu
FU Howard Hughes Medical Institute; National Institutes of Health (NIH) [R01-GM56322, RR-08630]; Welch Foundation [I-1544]; Chilton Foundation; NIH EUREKA [R01-GM088745]; National Science Foundation [DMR-1005707]; Gates Millennium Fund; US Department of Energy, Basic Energy Sciences, Office of Science [W-31-109-ENG-38]; National Cancer Institute [P30CA142543] Funding Source: NIH RePORTER; Division Of Materials Research; Direct For Mathematical & Physical Scien [1005707] Funding Source: National Science Foundation
NR 34
TC 1971
Z9 2380
U1 21
U2 705
PU NATURE PUBLISHING 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 15
PY 2012
VL 483
IS 7389
BP 336
EP U129
DI 10.1038/nature10879
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 908HP
UT WOS:000301481800050
PM 22398450
DA 2026-03-09
ER

PT J
AU Sanada, T
   Kim, M
   Mimuro, H
   Suzuki, M
   Ogawa, M
   Oyama, A
   Ashida, H
   Kobayashi, T
   Koyama, T
   Nagai, S
   Shibata, Y
   Gohda, J
   Inoue, J
   Mizushima, T
   Sasakawa, C
AF Sanada, Takahito
   Kim, Minsoo
   Mimuro, Hitomi
   Suzuki, Masato
   Ogawa, Michinaga
   Oyama, Akiho
   Ashida, Hiroshi
   Kobayashi, Taira
   Koyama, Tomohiro
   Nagai, Shinya
   Shibata, Yuri
   Gohda, Jin
   Inoue, Jun-ichiro
   Mizushima, Tsunehiro
   Sasakawa, Chihiro
TI The Shigella flexneri effector OspI deamidates UBC13 to dampen the inflammatory response
SO NATURE
LA English
DT Article
ID nf-kappa-b; crystal-structures; protein; kinase; activation; host; traf6; invasion; bacteria; domain
AB Many bacterial pathogens can enter various host cells and then survive intracellularly, transiently evade humoral immunity, and further disseminate to other cells and tissues. When bacteria enter host cells and replicate intracellularly, the host cells sense the invading bacteria as damage-associated molecular patterns (DAMPs) and pathogen-associated molecular patterns (PAMPs) by way of various pattern recognition receptors. As a result, the host cells induce alarm signals that activate the innate immune system(1). Therefore, bacteria must modulate host inflammatory signalling and dampen these alarm signals(2-4.) How pathogens do this after invading epithelial cells remainsunclear, however. Herewe showthat OspI, a Shigella flexneri effector encoded by ORF169b on the large plasmid and delivered by the type III secretion system, dampens acute inflammatory responses during bacterial invasion by suppressing the tumour-necrosis factor (TNF)-receptor-associated factor 6 (TRAF6)-mediated signalling pathway. OspI is a glutamine deamidase that selectively deamidates the glutamine residue at position 100 in UBC13 to a glutamic acid residue. Consequently, the E2 ubiquitin-conjugating activity required for TRAF6 activation is inhibited, allowing S. flexneri OspI to modulate the diacylglycerolCBM (CARD-BCL10-MALT1) complex-TRAF6-nuclear-factorkB signalling pathway. We determined the 2.0 angstrom crystal structure of OspI, which contains a putative cysteine-histidine-aspartic acid catalytic triad. A mutational analysis showed this catalytic triad to be essential for the deamidation of UBC13. Our results suggest that S. flexneri inhibits acute inflammatory responses in the initial stage of infection by targeting the UBC13-TRAF6 complex.
C1 [Sanada, Takahito; Kim, Minsoo; Sasakawa, Chihiro] Univ Tokyo, Dept Infect Dis Control, Int Res Ctr Infect Dis, Minato Ku, Tokyo 1088639, Japan.
   [Mimuro, Hitomi] Univ Tokyo, Int Res Ctr Infect Dis, Dept Infect Dis Control, Div Bacteriol,Minato Ku, Tokyo 1088639, Japan.
   [Suzuki, Masato; Ogawa, Michinaga; Oyama, Akiho; Ashida, Hiroshi; Kobayashi, Taira; Sasakawa, Chihiro] Univ Tokyo, Inst Med Sci, Dept Microbiol & Immunol, Div Bacterial Infect,Minato Ku, Tokyo 1088639, Japan.
   [Koyama, Tomohiro; Nagai, Shinya; Sasakawa, Chihiro] Nippon Inst Biol Sci, Tokyo 1980024, Japan.
   [Shibata, Yuri; Gohda, Jin; Inoue, Jun-ichiro] Univ Tokyo, Inst Med Sci, Dept Canc Biol, Div Cellular & Mol Biol,Minato Ku, Tokyo 1088639, Japan.
   [Mizushima, Tsunehiro] Univ Hyogo, Grad Sch Life Sci, Dept Life Sci, Picobiol Inst, Akoh, Hyogo 6781297, Japan.
C3 University of Tokyo; University of Tokyo; University of Tokyo; University of Tokyo; University of Hyogo
RP Sasakawa, C (corresponding author), Univ Tokyo, Dept Infect Dis Control, Int Res Ctr Infect Dis, Minato Ku, Tokyo 1088639, Japan.
EM mizushi@sci.u-hyogo.ac.jp; sasakawa@ims.u-tokyo.ac.jp
FU Japan Initiative for Global Research Network on Infectious Diseases; Naito Foundation; Waksman Foundation of Japan; Yakult Bio-Science Foundation; Yakult Central Institute; Hayashi Memorial Foundation for Female Natural Scientists;  [23121525];  [23000012];  [23689027];  [23790471];  [23790472];  [22790403];  [23390102];  [23659220];  [18073003]; Grants-in-Aid for Scientific Research [22790403, 23770203, 23790471, 23689027, 23390102, 23121525, 22117002, 22117001, 23000012] Funding Source: KAKEN
NR 45
TC 144
Z9 171
U1 1
U2 26
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 29
PY 2012
VL 483
IS 7391
BP 623
EP U149
DI 10.1038/nature10894
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 915EF
UT WOS:000302006100044
PM 22407319
DA 2026-03-09
ER

PT J
AU Barber, MF
   Michishita-Kioi, E
   Xi, YX
   Tasselli, L
   Kioi, M
   Moqtaderi, Z
   Tennen, RI
   Paredes, S
   Young, NL
   Chen, KF
   Struhl, K
   Garcia, BA
   Gozani, O
   Li, W
   Chua, KF
AF Barber, Matthew F.
   Michishita-Kioi, Eriko
   Xi, Yuanxin
   Tasselli, Luisa
   Kioi, Mitomu
   Moqtaderi, Zarmik
   Tennen, Ruth I.
   Paredes, Silvana
   Young, Nicolas L.
   Chen, Kaifu
   Struhl, Kevin
   Garcia, Benjamin A.
   Gozani, Or
   Li, Wei
   Chua, Katrin F.
TI SIRT7 links H3K18 deacetylation to maintenance of oncogenic transformation
SO NATURE
LA English
DT Article
ID life-span; histone modification; predict prognosis; binding profiles; transcription; gene; chromatin; expression; patterns; cancer
AB Sirtuin proteins regulate diverse cellular pathways that influence genomic stability, metabolism and ageing(1,2). SIRT7 is a mammalian sirtuin whose biochemical activity, molecular targets and physiological functions have been unclear. Here we show that SIRT7 is an NAD(+)-dependent H3K18Ac (acetylated lysine 18 of histone H3) deacetylase that stabilizes the transformed state of cancer cells. Genome-wide binding studies reveal that SIRT7 binds to promoters of a specific set of gene targets, where it deacetylates H3K18Ac and promotes transcriptional repression. The spectrum of SIRT7 target genes is defined in part by its interaction with the cancer-associated E26 transformed specific (ETS) transcription factor ELK4, and comprises numerous genes with links to tumour suppression. Notably, selective hypoacetylation of H3K18Ac has been linked to oncogenic transformation, and in patients is associated with aggressive tumour phenotypes and poor prognosis(3-6). We find that deacetylation of H3K18Ac by SIRT7 is necessary for maintaining essential features of human cancer cells, including anchorage-independent growth and escape from contact inhibition. Moreover, SIRT7 is necessary for a global hypoacetylation of H3K18Ac associated with cellular transformation by the viral oncoprotein E1A. Finally, SIRT7 depletion markedly reduces the tumorigenicity of human cancer cell xenografts in mice. Together, our work establishes SIRT7 as a highly selective H3K18Ac deacetylase and demonstrates a pivotal role for SIRT7 in chromatin regulation, cellular transformation programs and tumour formation in vivo.
C1 [Barber, Matthew F.; Michishita-Kioi, Eriko; Tasselli, Luisa; Tennen, Ruth I.; Paredes, Silvana; Chua, Katrin F.] Stanford Univ, Dept Med, Div Endocrinol Gerontol & Metab, Stanford, CA 94305 USA.
   [Barber, Matthew F.; Gozani, Or] Stanford Univ, Dept Biol, Stanford, CA 94305 USA.
   [Michishita-Kioi, Eriko; Tasselli, Luisa; Paredes, Silvana; Chua, Katrin F.] VA Palo Alto Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Palo Alto, CA 94304 USA.
   [Xi, Yuanxin; Chen, Kaifu; Li, Wei] Baylor Coll Med, Dept Mol & Cellular Biol, Dan L Duncan Canc Ctr, Div Biostat, Houston, TX 77030 USA.
   [Kioi, Mitomu] Stanford Univ, Dept Radiat Oncol, Stanford, CA 94305 USA.
   [Moqtaderi, Zarmik; Struhl, Kevin] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
   [Tennen, Ruth I.; Chua, Katrin F.] Stanford Univ, Canc Biol Program, Stanford, CA 94305 USA.
   [Young, Nicolas L.; Garcia, Benjamin A.] Princeton Univ, Dept Mol Biol, Princeton, NJ 08544 USA.
C3 Stanford University; Stanford University; US Department of Veterans Affairs; Veterans Health Administration (VHA); VA Palo Alto Health Care System; Geriatric Research Education & Clinical Center; Baylor College of Medicine; Stanford University; Harvard University; Harvard Medical School; Stanford University; Princeton University
RP Chua, KF (corresponding author), Stanford Univ, Dept Med, Div Endocrinol Gerontol & Metab, Stanford, CA 94305 USA.
EM WL1@bcm.edu; kfchua@stanford.edu
FU National Institutes of Health (NIH) [K08 AG028961, R01 AG028867, U01DA025956, R01 GM079641, GM 30186, HG 4558, DP2OD007447, 1018438-142 PABCA, 3T32DK007217-36S1]; National Science Foundation [CBET-0941143]; Department of Defense [PC094421]; Cancer Prevention and Research Institute of Texas (CPRIT) [RP110471-C3]; Department of Veterans Affairs; ARCS Scholarship; American Italian Cancer Foundation Post-doctoral Research Fellowship; Duncan Scholar Award; Mason Case Graduate Fellowship; National Cancer Institute [T32CA009302] Funding Source: NIH RePORTER; National Institute of Diabetes and Digestive and Kidney Diseases [T32DK007217] Funding Source: NIH RePORTER
NR 42
TC 522
Z9 603
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 JUL 5
PY 2012
VL 487
IS 7405
BP 114
EP +
DI 10.1038/nature11043
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 968LM
UT WOS:000305982900061
PM 22722849
DA 2026-03-09
ER

PT J
AU Fridman, M
   Farsi, A
   Okawachi, Y
   Gaeta, AL
AF Fridman, Moti
   Farsi, Alessandro
   Okawachi, Yoshitomo
   Gaeta, Alexander L.
TI Demonstration of temporal cloaking
SO NATURE
LA English
DT Article
ID silicon-chip; time lens; frequency; principles
AB Recent research has uncovered a remarkable ability to manipulate and control electromagnetic fields to produce effects such as perfect imaging and spatial cloaking(1,2). To achieve spatial cloaking, the index of refraction is manipulated to flow light from a probe around an object in such a way that a 'hole' in space is created, and the object remains hidden(3-14). Alternatively, it may be desirable to cloak the occurrence of an event over a finite time period, and the idea of temporal cloaking has been proposed in which the dispersion of the material is manipulated in time, producing a 'time hole' in the probe beam to hide the occurrence of the event from the observer(15). This approach is based on accelerating the front part of a probe light beam and slowing down its rear part to create a well controlled temporal gap-inside which an event occurs-such that the probe beam is not modified in any way by the event. The probe beam is then restored to its original form by the reverse manipulation of the dispersion. Here we present an experimental demonstration of temporal cloaking in an optical fibre-based system by applying concepts from the space-time duality between diffraction and dispersive broadening(16). We characterize the performance of our temporal cloak by detecting the spectral modification of a probe beam due to an optical interaction and show that the amplitude of the event (at the picosecond timescale) is reduced by more than an order of magnitude when the cloak is turned on. These results are a significant step towards the development of full spatio-temporal cloaking.
C1 [Fridman, Moti; Farsi, Alessandro; Okawachi, Yoshitomo; Gaeta, Alexander L.] Cornell Univ, Sch Appl & Engn Phys, Ithaca, NY 14853 USA.
C3 Cornell University
RP Gaeta, AL (corresponding author), Cornell Univ, Sch Appl & Engn Phys, Ithaca, NY 14853 USA.
EM alg3@cornell.edu
FU Defence Advanced Research Project Agency; Center for Nanoscale Systems; National Science Foundation for Science, Technology, and Innovation (NYSTAR)
NR 23
TC 181
Z9 203
U1 1
U2 78
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JAN 5
PY 2012
VL 481
IS 7379
BP 62
EP 65
DI 10.1038/nature10695
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 872VD
UT WOS:000298836900029
PM 22222748
DA 2026-03-09
ER

PT J
AU Gupta, V
   Poss, KD
AF Gupta, Vikas
   Poss, Kenneth D.
TI Clonally dominant cardiomyocytes direct heart morphogenesis
SO NATURE
LA English
DT Article
ID zebrafish heart; mouse heart; stem-cells; regeneration; progenitors; field; differentiation; population; myocardium; phases
AB As vertebrate embryos develop to adulthood, their organs undergo marked changes in size and tissue architecture. The heart acquires muscle mass and matures structurally to fulfil increasing circulatory needs, a process that is incompletely understood. Here we used multicolour clonal analysis to define the contributions of individual cardiomyocytes as the zebrafish heart undergoes morphogenesis from a primitive embryonic structure into its complex adult form. We find that the single-cardiomyocyte-thick wall of the juvenile ventricle forms by lateral expansion of several dozen cardiomyocytes into muscle patches of variable sizes and shapes. As juvenile zebrafish mature into adults, this structure becomes fully enveloped by a new lineage of cortical muscle. Adult cortical muscle originates from a small number of cardiomyocytes-an average of approximately eight per animal-that display clonal dominance reminiscent of stem cell populations. Cortical cardiomyocytes initially emerge from internal myofibres that in rare events breach the juvenile ventricular wall, and then expand over the surface. Our results illuminate the dynamic proliferative behaviours that generate adult cardiac structure, revealing clonal dominance as a key mechanism that shapes a vertebrate organ.
C1 [Gupta, Vikas; Poss, Kenneth D.] Duke Univ, Med Ctr, Dept Cell Biol, Durham, NC 27710 USA.
   [Gupta, Vikas; Poss, Kenneth D.] Duke Univ, Med Ctr, Howard Hughes Med Inst, Durham, NC 27710 USA.
C3 Duke University; Howard Hughes Medical Institute; Duke University
RP Poss, KD (corresponding author), Duke Univ, Med Ctr, Dept Cell Biol, Durham, NC 27710 USA.
EM kenneth.poss@duke.edu
FU National Heart, Lung, and Blood Institute (NHLBI) [HL081674]; American Heart Association
NR 27
TC 204
Z9 251
U1 0
U2 36
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD APR 26
PY 2012
VL 484
IS 7395
BP 479
EP U102
DI 10.1038/nature11045
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 931FF
UT WOS:000303200400043
PM 22538609
DA 2026-03-09
ER

PT J
AU Zhang, GF
   Fang, XD
   Guo, XM
   Li, L
   Luo, RB
   Xu, F
   Yang, PC
   Zhang, LL
   Wang, XT
   Qi, HG
   Xiong, ZQ
   Que, HY
   Xie, YL
   Holland, PWH
   Paps, J
   Zhu, YB
   Wu, FC
   Chen, YX
   Wang, JF
   Peng, CF
   Meng, J
   Yang, L
   Liu, J
   Wen, B
   Zhang, N
   Huang, ZY
   Zhu, QH
   Feng, Y
   Mount, A
   Hedgecock, D
   Xu, Z
   Liu, YJ
   Domazet-Loso, T
   Du, YS
   Sun, XQ
   Zhang, SD
   Liu, BH
   Cheng, PZ
   Jiang, XT
   Li, J
   Fan, DD
   Wang, W
   Fu, WJ
   Wang, T
   Wang, B
   Zhang, JB
   Peng, ZY
   Li, YX
   Li, N
   Wang, JP
   Chen, MS
   He, Y
   Tan, FJ
   Song, XR
   Zheng, QM
   Huang, RL
   Yang, HL
   Du, XD
   Chen, L
   Yang, M
   Gaffney, PM
   Wang, S
   Luo, LH
   She, ZC
   Ming, Y
   Huang, W
   Zhang, S
   Huang, BY
   Zhang, Y
   Qu, T
   Ni, PX
   Miao, GY
   Wang, JY
   Wang, Q
   Steinberg, CEW
   Wang, HY
   Li, N
   Qian, LM
   Zhang, GJ
   Li, YR
   Yang, HM
   Liu, X
   Wang, J
   Yin, Y
   Wang, J
AF Zhang, Guofan
   Fang, Xiaodong
   Guo, Ximing
   Li, Li
   Luo, Ruibang
   Xu, Fei
   Yang, Pengcheng
   Zhang, Linlin
   Wang, Xiaotong
   Qi, Haigang
   Xiong, Zhiqiang
   Que, Huayong
   Xie, Yinlong
   Holland, Peter W. H.
   Paps, Jordi
   Zhu, Yabing
   Wu, Fucun
   Chen, Yuanxin
   Wang, Jiafeng
   Peng, Chunfang
   Meng, Jie
   Yang, Lan
   Liu, Jun
   Wen, Bo
   Zhang, Na
   Huang, Zhiyong
   Zhu, Qihui
   Feng, Yue
   Mount, Andrew
   Hedgecock, Dennis
   Xu, Zhe
   Liu, Yunjie
   Domazet-Loso, Tomislav
   Du, Yishuai
   Sun, Xiaoqing
   Zhang, Shoudu
   Liu, Binghang
   Cheng, Peizhou
   Jiang, Xuanting
   Li, Juan
   Fan, Dingding
   Wang, Wei
   Fu, Wenjing
   Wang, Tong
   Wang, Bo
   Zhang, Jibiao
   Peng, Zhiyu
   Li, Yingxiang
   Li, Na
   Wang, Jinpeng
   Chen, Maoshan
   He, Yan
   Tan, Fengji
   Song, Xiaorui
   Zheng, Qiumei
   Huang, Ronglian
   Yang, Hailong
   Du, Xuedi
   Chen, Li
   Yang, Mei
   Gaffney, Patrick M.
   Wang, Shan
   Luo, Longhai
   She, Zhicai
   Ming, Yao
   Huang, Wen
   Zhang, Shu
   Huang, Baoyu
   Zhang, Yong
   Qu, Tao
   Ni, Peixiang
   Miao, Guoying
   Wang, Junyi
   Wang, Qiang
   Steinberg, Christian E. W.
   Wang, Haiyan
   Li, Ning
   Qian, Lumin
   Zhang, Guojie
   Li, Yingrui
   Yang, Huanming
   Liu, Xiao
   Wang, Jian
   Yin, Ye
   Wang, Jun
TI The oyster genome reveals stress adaptation and complexity of shell formation
SO NATURE
LA English
DT Article
ID transposable elements; crassostrea-gigas; bivalve mollusks; parahox genes; proteins; sequence; evolution; discovery; apoptosis; pathway
AB The Pacific oyster Crassostrea gigas belongs to one of the most species-rich but genomically poorly explored phyla, the Mollusca. Here we report the sequencing and assembly of the oyster genome using short reads and a fosmid-pooling strategy, along with transcriptomes of development and stress response and the proteome of the shell. The oyster genome is highly polymorphic and rich in repetitive sequences, with some transposable elements still actively shaping variation. Transcriptome studies reveal an extensive set of genes responding to environmental stress. The expansion of genes coding for heat shock protein 70 and inhibitors of apoptosis is probably central to the oyster's adaptation to sessile life in the highly stressful intertidal zone. Our analyses also show that shell formation in molluscs is more complex than currently understood and involves extensive participation of cells and their exosomes. The oyster genome sequence fills a void in our understanding of the Lophotrochozoa.
C1 [Fang, Xiaodong; Luo, Ruibang; Yang, Pengcheng; Xiong, Zhiqiang; Xie, Yinlong; Zhu, Yabing; Chen, Yuanxin; Peng, Chunfang; Yang, Lan; Wen, Bo; Huang, Zhiyong; Feng, Yue; Liu, Yunjie; Sun, Xiaoqing; Liu, Binghang; Jiang, Xuanting; Fan, Dingding; Fu, Wenjing; Wang, Bo; Peng, Zhiyu; Li, Na; Chen, Maoshan; Tan, Fengji; Zheng, Qiumei; Yang, Hailong; Chen, Li; Luo, Longhai; Ming, Yao; Zhang, Shu; Zhang, Yong; Ni, Peixiang; Wang, Junyi; Li, Ning; Zhang, Guojie; Li, Yingrui; Yang, Huanming; Wang, Jian; Yin, Ye; Wang, Jun] BGI Shenzhen, Shenzhen 518083, Peoples R China.
   [Zhang, Guofan; Li, Li; Xu, Fei; Zhang, Linlin; Wang, Xiaotong; Qi, Haigang; Que, Huayong; Wu, Fucun; Wang, Jiafeng; Meng, Jie; Liu, Jun; Zhang, Na; Zhu, Qihui; Du, Yishuai; Zhang, Shoudu; Cheng, Peizhou; Li, Juan; Wang, Wei; Wang, Tong; Zhang, Jibiao; Li, Yingxiang; Wang, Jinpeng; Song, Xiaorui; Huang, Ronglian; Du, Xuedi; Yang, Mei; She, Zhicai; Huang, Wen; Huang, Baoyu; Qu, Tao; Miao, Guoying; Wang, Qiang; Wang, Haiyan; Liu, Xiao] Chinese Acad Sci, Inst Oceanol, Qingdao 266071, Peoples R China.
   [Guo, Ximing; He, Yan; Wang, Shan; Qian, Lumin] Rutgers State Univ, Inst Marine & Coastal Sci, Haskin Shellfish Res Lab, Port Norris, NJ 08349 USA.
   [Luo, Ruibang; Xie, Yinlong; Liu, Binghang] HKU BGI Bioinformat Algorithms & Core Technol Res, Hong Kong, Hong Kong, Peoples R China.
   [Holland, Peter W. H.; Paps, Jordi] Univ Oxford, Dept Zool, Oxford OX1 3PS, England.
   [Mount, Andrew] Clemson Univ, Dept Biol Sci, Clemson, SC 29634 USA.
   [Hedgecock, Dennis] Univ So Calif, Dept Biol Sci, Los Angeles, CA 90089 USA.
   [Xu, Zhe] Atlantic Cape Community Coll, Mays Landing, NJ 08330 USA.
   [Domazet-Loso, Tomislav] Rudjer Boskovic Inst, Lab Evolutionary Genet, HR-10002 Zagreb, Croatia.
   [Gaffney, Patrick M.] Univ Delaware, Sch Marine Sci & Policy, Lewes, DE 19958 USA.
   [Steinberg, Christian E. W.] Humboldt Univ Berlin Arboretum, Inst Biol, D-12437 Berlin, Germany.
   [Wang, Jun] Univ Copenhagen, Dept Biol, DK-2200 Copenhagen, Denmark.
   [Wang, Jun] Univ Copenhagen, Novo Nordisk Fdn Ctr Basic Metab Res, DK-2200 Copenhagen, Denmark.
C3 Beijing Genomics Institute (BGI); Chinese Academy of Sciences; Institute of Oceanology, CAS; Rutgers University System; Rutgers University New Brunswick; University of Hong Kong; University of Oxford; Clemson University; University of Southern California; Rudjer Boskovic Institute; University of Delaware; University of Copenhagen; Novo Nordisk Foundation; University of Copenhagen
RP Wang, J (corresponding author), BGI Shenzhen, Shenzhen 518083, Peoples R China.
EM gzhang@qdio.ac.cn; xguo@hsrl.rutgers.edu; yinye@genomics.org.cn; wangj@genomics.org.cn
FU National High-Technology Research and Development Program of China (863 program) [2010AA10A110]; National Basic Research Program of China (973 Program) [2010CB126401, 2010CB126402]; 863 program [2012AA10A405]; Basic Research Program by Shenzhen City [JC2010526019]; Shenzhen Key Laboratory of Transomics Biotechnologies [CXB201108250096A]; Mollusc Research and Development Center; CARS; Shenzhen Key Laboratory of Gene Bank for National Life Science; Taishan Scholar and Scholar Climbing Programs of Shandong; US Department of Agriculture [2009-35205-05052, NJ32108]; Chinese Academy of Science Marine Functional Genomics Oversea Team; Taishan Scholar Fund; European Research Council (EU FP7 ERC) [[268513]11]; Beatriu de Pinos of the Generalitat de Catalunya [2009 BP-DGR]; Dalian Zhangzidao Fishery Group Co. Ltd; NIFA [2009-35205-05052, 582554] Funding Source: Federal RePORTER
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NR 47
TC 1875
Z9 2096
U1 19
U2 870
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD OCT 4
PY 2012
VL 490
IS 7418
BP 49
EP 54
DI 10.1038/nature11413
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 015LG
UT WOS:000309446800030
PM 22992520
DA 2026-03-09
ER

PT J
AU Nam, KH
   Park, IH
   Ko, SH
AF Nam, Koo Hyun
   Park, Il H.
   Ko, Seung Hwan
TI Patterning by controlled cracking
SO NATURE
LA English
DT Article
ID quenched glass plates; materials science; fracture; instability; trimaterial; interface; ceramics; break
AB Crack formation drives material failure and is often regarded as a process to be avoided(1-3). However, closer examination of cracking phenomena has revealed exquisitely intricate patterns such as spirals(4), oscillating(5,6,7) and branched(7) fracture paths and fractal geometries(8). Here we demonstrate the controlled initiation, propagation and termination of a variety of channelled crack patterns in a film/substrate system(9-11) comprising a silicon nitride thin film deposited on a silicon substrate using low-pressure chemical vapour deposition. Micro-notches etched into the silicon substrate concentrated stress for crack initiation, which occurred spontaneously during deposition of the silicon nitride layer. We reproducibly created three distinct crack morphologies-straight, oscillatory and orderly bifurcated (stitchlike)-through careful selection of processing conditions and parameters. We induced direction changes by changing the system parameters, and we terminated propagation at preformed multi-step crack stops. We believe that our patterning technique presents new opportunities in nanofabrication and offers a starting point for atomic-scale pattern formation(12), which would be difficult even with current state-of-the-art nanofabrication methodologies.
C1 [Nam, Koo Hyun; Park, Il H.] Ewha Womans Univ, Dept Phys, Res Ctr MEMS Space Telescope, Seoul 120750, South Korea.
   [Ko, Seung Hwan] Korea Adv Inst Sci & Technol, Dept Mech Engn, Appl Nano Technol & Sci Lab, Taejon 305701, South Korea.
C3 Ewha Womans University; Korea Advanced Institute of Science & Technology (KAIST)
RP Nam, KH (corresponding author), Ewha Womans Univ, Dept Phys, Res Ctr MEMS Space Telescope, Daehyun Dong 11-1, Seoul 120750, South Korea.
EM koonam@namk.org; maxko@kaist.ac.kr
FU Creative Research Initiatives (Research Center of MEMS Space Telescope) of MEST/NRF
NR 30
TC 239
Z9 271
U1 7
U2 314
PU NATURE PUBLISHING 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 10
PY 2012
VL 485
IS 7397
BP 221
EP 224
DI 10.1038/nature11002
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 939HJ
UT WOS:000303799800037
PM 22575963
DA 2026-03-09
ER

PT J
AU Contreras, FX
   Ernst, AM
   Haberkant, P
   Björkholm, P
   Lindahl, E
   Gönen, B
   Tischer, C
   Elofsson, A
   von Heijne, G
   Thiele, C
   Pepperkok, R
   Wieland, F
   Brügger, B
AF Contreras, F. -Xabier
   Ernst, Andreas M.
   Haberkant, Per
   Bjoerkholm, Patrik
   Lindahl, Erik
   Goenen, Basak
   Tischer, Christian
   Elofsson, Arne
   von Heijne, Gunnar
   Thiele, Christoph
   Pepperkok, Rainer
   Wieland, Felix
   Bruegger, Britta
TI Molecular recognition of a single sphingolipid species by a protein's transmembrane domain
SO NATURE
LA English
DT Article
ID to-golgi transport; gxxxg motif; sphingomyelin; cholesterol; reveals; system
AB Functioning and processing of membrane proteins critically depend on the way their transmembrane segments are embedded in the membrane(1). Sphingolipids are structural components of membranes and can also act as intracellular second messengers. Not much is known of sphingolipids binding to transmembrane domains (TMDs) of proteins within the hydrophobic bilayer, and how this could affect protein function. Here we show a direct and highly specific interaction of exclusively one sphingomyelin species, SM 18, with the TMD of the COPI machinery protein p24 (ref. 2). Strikingly, the interaction depends on both the head-group and the backbone of the sphingolipid, and on a signature sequence (VXXTLXXIY) within the TMD. Molecular dynamics simulations show a close interaction of SM 18 with the TMD. We suggest a role of SM 18 in regulating the equilibrium between an inactive monomeric and an active oligomeric state of the p24 protein(3,4), which in turn regulates COPI-dependent transport. Bioinformatic analyses predict that the signature sequence represents a conserved sphingolipid-binding cavity in a variety of mammalian membrane proteins. Thus, in addition to a function as second messengers, sphingolipids can act as cofactors to regulate the function of transmembrane proteins. Our discovery of an unprecedented specificity of interaction of a TMD with an individual sphingolipid species adds to our understanding of why biological membranes are assembled from such a large variety of different lipids.
C1 [Contreras, F. -Xabier; Ernst, Andreas M.; Haberkant, Per; Goenen, Basak; Wieland, Felix; Bruegger, Britta] Heidelberg Univ, Biochem Ctr, D-69120 Heidelberg, Germany.
   [Bjoerkholm, Patrik; Lindahl, Erik; Elofsson, Arne; von Heijne, Gunnar] Stockholm Univ, Ctr Biomembrane Res, Dept Biochem & Biophys, SE-10691 Stockholm, Sweden.
   [Bjoerkholm, Patrik; Elofsson, Arne; von Heijne, Gunnar] Stockholm Univ, Stockholm Bioinformat Ctr, Sci Life Lab, SE-17121 Solna, Sweden.
   [Lindahl, Erik] AlbaNova Univ Ctr, Royal Inst Technol, SE-10691 Stockholm, Sweden.
   [Tischer, Christian; Pepperkok, Rainer] EMBL, ALMF, D-69117 Heidelberg, Germany.
   [Thiele, Christoph] LIMES Life & Med Sci Inst, D-53115 Bonn, Germany.
C3 Ruprecht Karls University Heidelberg; Stockholm University; Stockholm University; Royal Institute of Technology; European Molecular Biology Laboratory (EMBL); University of Bonn
RP Brügger, B (corresponding author), Heidelberg Univ, Biochem Ctr, Neuenheimer Feld 328, D-69120 Heidelberg, Germany.
EM britta.bruegger@bzh.uni-heidelberg.de
FU German research foundation (DFG) [TRR83]; ERC [209825, AdG232648]; FEBS; Peter and Traudl Engelhorn foundation; European Research Council (ERC) [209825] Funding Source: European Research Council (ERC)
NR 23
TC 311
Z9 340
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 JAN 26
PY 2012
VL 481
IS 7382
BP 525
EP 529
DI 10.1038/nature10742
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 881GY
UT WOS:000299471800044
PM 22230960
DA 2026-03-09
ER

PT J
AU Oka, T
   Hikoso, S
   Yamaguchi, O
   Taneike, M
   Takeda, T
   Tamai, T
   Oyabu, J
   Murakawa, T
   Nakayama, H
   Nishida, K
   Akira, S
   Yamamoto, A
   Komuro, I
   Otsu, K
AF Oka, Takafumi
   Hikoso, Shungo
   Yamaguchi, Osamu
   Taneike, Manabu
   Takeda, Toshihiro
   Tamai, Takahito
   Oyabu, Jota
   Murakawa, Tomokazu
   Nakayama, Hiroyuki
   Nishida, Kazuhiko
   Akira, Shizuo
   Yamamoto, Akitsugu
   Komuro, Issei
   Otsu, Kinya
TI Mitochondrial DNA that escapes from autophagy causes inflammation and heart failure
SO NATURE
LA English
DT Article
ID pattern; damps
AB Heart failure is a leading cause of morbidity and mortality in industrialized countries. Although infection with microorganisms is not involved in the development of heart failure in most cases, inflammation has been implicated in the pathogenesis of heart failure(1). However, the mechanisms responsible for initiating and integrating inflammatory responses within the heart remain poorly defined. Mitochondria are evolutionary endosymbionts derived from bacteria and contain DNA similar to bacterial DNA(2-4). Mitochondria damaged by external haemodynamic stress are degraded by the autophagy/lysosome systemin cardiomyocytes(5). Here we show that mitochondrial DNA that escapes from autophagy cell-autonomously leads to Toll-like receptor (TLR) 9-mediated inflammatory responses in cardiomyocytes and is capable of inducing myocarditis and dilated cardiomyopathy. Cardiac-specific deletion of lysosomal deoxyribonuclease (DNase) II showed no cardiac phenotypes under baseline conditions, but increased mortality and caused severe myocarditis and dilated cardiomyopathy 10 days after treatment with pressure overload. Early in the pathogenesis, DNase II-deficient hearts showed infiltration of inflammatory cells and increased messenger RNA expression of inflammatory cytokines, with accumulation of mitochondrial DNA deposits in autolysosomes in the myocardium. Administration of inhibitory oligodeoxynucleotides against TLR9, which is known to be activated by bacterial DNA(6), or ablation of Tlr9 attenuated the development of cardiomyopathy in DNase II-deficient mice. Furthermore, Tlr9 ablation improved pressure overload-induced cardiac dysfunction and inflammation even in mice with wild-type Dnase2a alleles. These data provide new perspectives on the mechanism of genesis of chronic inflammation in failing hearts.
C1 [Oka, Takafumi; Hikoso, Shungo; Yamaguchi, Osamu; Taneike, Manabu; Takeda, Toshihiro; Tamai, Takahito; Oyabu, Jota; Murakawa, Tomokazu; Nishida, Kazuhiko; Komuro, Issei; Otsu, Kinya] Osaka Univ, Grad Sch Med, Dept Cardiovasc Med, Suita, Osaka 5650871, Japan.
   [Taneike, Manabu; Nishida, Kazuhiko; Otsu, Kinya] Kings Coll London, Div Cardiovasc, London SE5 9NU, England.
   [Nakayama, Hiroyuki] Osaka Univ, Grad Sch Pharmaceut Sci, Dept Clin Pharmacol & Pharmacogen, Suita, Osaka 5650871, Japan.
   [Akira, Shizuo] Osaka Univ, WPI Immunol Frontier Res Ctr, Host Def Lab, Suita, Osaka 5650871, Japan.
   [Akira, Shizuo] Osaka Univ, Microbial Dis Res Inst, Dept Host Def, Suita, Osaka 5650871, Japan.
   [Yamamoto, Akitsugu] Nagahama Inst Biosci & Technol, Fac Biosci, Nagahama, Shiga 5260829, Japan.
C3 University of Osaka; University of London; King's College London; University of Osaka; University of Osaka; University of Osaka; Nagahama Institute of Bio-Science & Technology
RP Otsu, K (corresponding author), Osaka Univ, Grad Sch Med, Dept Cardiovasc Med, 2-2 Yamadaoka, Suita, Osaka 5650871, Japan.
EM kinya.otsu@kcl.ac.uk
FU Ministry of Education, Culture, Sports, Science and Technology in Japan; Mitsubishi Pharma Research Foundation; British Heart Foundation [CH/11/3/29051, RG/11/12/29052]; British Heart Foundation [RG/11/12/29052] Funding Source: researchfish; Grants-in-Aid for Scientific Research [21390240, 21229010] Funding Source: KAKEN
NR 26
TC 994
Z9 1125
U1 9
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 MAY 10
PY 2012
VL 485
IS 7397
BP 251
EP U142
DI 10.1038/nature10992
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 939HJ
UT WOS:000303799800044
PM 22535248
DA 2026-03-09
ER

PT J
AU DeVore, NM
   Scott, EE
AF DeVore, Natasha M.
   Scott, Emily E.
TI Structures of cytochrome P450 17A1 with prostate cancer drugs abiraterone and TOK-001
SO NATURE
LA English
DT Article
ID crystal-structures; binding domain; human p450c17; cyp17; inhibitors; purification; expression; physiology; mutation
AB Cytochrome P450 17A1 (also known as CYP17A1 and cytochrome P450c17) catalyses the biosynthesis of androgens in humans(1). As prostate cancer cells proliferate in response to androgen steroids(2,3), CYP17A1 inhibition is a new strategy to prevent androgen synthesis and treat lethal metastatic castration-resistant prostate cancer(4), but drug development has been hampered by lack of information regarding the structure of CYP17A1. Here we report X-ray crystal structures of CYP17A1, which were obtained in the presence of either abiraterone, a first-in-class steroidal inhibitor recently approved by the US Food and Drug Administration for late-stage prostate cancer(5), or TOK-001, an inhibitor that is currently undergoing clinical trials(4,6). Both of these inhibitors bind the haem iron, forming a 60 degrees angle above the haem plane and packing against the central I helix with the 3 beta-OH interacting with aspargine 202 in the F helix. Notably, this binding mode differs substantially from those that are predicted by homology models and from steroids in other cytochrome P450 enzymes with known structures, and some features of this binding mode are more similar to steroid receptors. Whereas the overall structure of CYP17A1 provides a rationale for understanding many mutations that are found in patients with steroidogenic diseases, the active site reveals multiple steric and hydrogen bonding features that will facilitate a better understanding of the enzyme's dual hydroxylase and lyase catalytic capabilities and assist in rational drug design. Specifically, structure-based design is expected to aid development of inhibitors that bind only CYP17A1 and solely inhibit its androgen-generating lyase activity to improve treatment of prostate and other hormone-responsive cancers.
C1 [DeVore, Natasha M.; Scott, Emily E.] Univ Kansas, Dept Med Chem, Lawrence, KS 66045 USA.
C3 University of Kansas
RP Scott, EE (corresponding author), Univ Kansas, Dept Med Chem, 1251 Wescoe Hall Dr, Lawrence, KS 66045 USA.
EM eescott@ku.edu
FU US Department of Energy Office of Biological and Environmental Research; US National Institutes of Health (NIH), National Center for Research Resources; National Institute of General Medical Sciences; NIH through the KU COBRE Center for Protein Structure and Function [NIH RR17708];  [GM076343]; National Institute of General Medical Sciences [R37GM076343] Funding Source: NIH RePORTER
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   Mast N, 2008, P NATL ACAD SCI USA, V105, P9546, DOI 10.1073/pnas.0803717105
   Mast N, 2011, J BIOL CHEM, V286, P5607, DOI 10.1074/jbc.M110.188433
   Miller WL, 2011, ENDOCR REV, V32, P81, DOI 10.1210/er.2010-0013
   Molina A, 2011, J UROLOGY, V185, P787, DOI 10.1016/j.juro.2010.10.042
   Murshudov GN, 1997, ACTA CRYSTALLOGR D, V53, P240, DOI 10.1107/S0907444996012255
   Pechurskaya TA, 2008, BIOCHEMISTRY-MOSCOW+, V73, P806, DOI 10.1134/S0006297908070092
   Rosa S, 2010, HORM RES PAEDIAT, V73, P198, DOI 10.1159/000284362
   Sahakitrungruang T, 2009, J CLIN ENDOCR METAB, V94, P3089, DOI 10.1210/jc.2009-0645
   SHEN AL, 1989, J BIOL CHEM, V264, P7584
   Swart AC, 2010, J STEROID BIOCHEM, V119, P112, DOI 10.1016/j.jsbmb.2009.12.014
   Tiosano D, 2008, EUR J ENDOCRINOL, V158, P385, DOI 10.1530/EJE-07-0712
   Vasaitis T, 2008, MOL CANCER THER, V7, P2348, DOI 10.1158/1535-7163.MCT-08-0230
   Vasaitis TS, 2011, J STEROID BIOCHEM, V125, P23, DOI 10.1016/j.jsbmb.2010.11.005
   Yap TA, 2008, CURR OPIN PHARMACOL, V8, P449, DOI 10.1016/j.coph.2008.06.004
NR 43
TC 293
Z9 341
U1 0
U2 86
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 2
PY 2012
VL 482
IS 7383
BP 116
EP U149
DI 10.1038/nature10743
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 884RN
UT WOS:000299726000047
PM 22266943
DA 2026-03-09
ER

PT J
AU Strader, J
   Chomiuk, L
   Maccarone, TJ
   Miller-Jones, JCA
   Seth, AC
AF Strader, Jay
   Chomiuk, Laura
   Maccarone, Thomas J.
   Miller-Jones, James C. A.
   Seth, Anil C.
TI Two stellar-mass black holes in the globular cluster M22
SO NATURE
LA English
DT Article
ID x-ray binary; star-clusters; quiescence; emission; catalog; jets
AB Hundreds of stellar-mass black holes probably form in a typical globular star cluster, with all but one predicted to be ejected through dynamical interactions(1-3). Some observational support for this idea is provided by the lack of X-ray-emitting binary stars comprising one black hole and one other star ('black-hole/X-ray binaries') in Milky Way globular clusters, even though many neutron-star/X-ray binaries are known(4). Although a few black holes have been seen in globular clusters around other galaxies(5,6), the masses of these cannot be determined, and some may be intermediate-mass black holes that form through exotic mechanisms(7). Here we report the presence of two flat-spectrum radio sources in the Milky Way globular cluster M22, and we argue that these objects are black holes of stellar mass (each similar to 10-20 times more massive than the Sun) that are accreting matter. We find a high ratio of radio-to-X-ray flux for these black holes, consistent with the larger predicted masses of black holes in globular clusters compared to those outside(8). The identification of two black holes in one cluster shows that ejection of black holes is not as efficient as predicted by most models(1,2,4), and we argue that M22 may contain a total population of similar to 5-100 black holes. The large core radius of M22 could arise from heating produced by the black holes(9).
C1 [Strader, Jay; Chomiuk, Laura] Michigan State Univ, Dept Phys & Astron, E Lansing, MI 48824 USA.
   [Strader, Jay; Chomiuk, Laura] Harvard Smithsonian Ctr Astrophys, Cambridge, MA 02138 USA.
   [Chomiuk, Laura] Natl Radio Astron Observ, Socorro, NM 87801 USA.
   [Maccarone, Thomas J.] Univ Southampton, Sch Phys & Astron, Southampton SO17 1BJ, Hants, England.
   [Miller-Jones, James C. A.] Curtin Univ Technol, Int Ctr Radio Astron Res, Perth, WA 6845, Australia.
   [Seth, Anil C.] Univ Utah, Dept Phys & Astron, Salt Lake City, UT 84112 USA.
C3 Michigan State University; Harvard University; Smithsonian Institution; Smithsonian Astrophysical Observatory; National Radio Astronomy Observatory (NRAO); University of Southampton; Curtin University; University of Western Australia; Utah System of Higher Education; University of Utah
RP Strader, J (corresponding author), Michigan State Univ, Dept Phys & Astron, E Lansing, MI 48824 USA.
EM strader@pa.msu.edu
NR 29
TC 217
Z9 239
U1 0
U2 8
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD OCT 4
PY 2012
VL 490
IS 7418
BP 71
EP 73
DI 10.1038/nature11490
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 015LG
UT WOS:000309446800033
PM 23038466
DA 2026-03-09
ER

PT J
AU Kosa, T
   Sukhomlinova, L
   Su, LL
   Taheri, B
   White, TJ
   Bunning, TJ
AF Kosa, Tamas
   Sukhomlinova, Ludmila
   Su, Linli
   Taheri, Bahman
   White, Timothy J.
   Bunning, Timothy J.
TI Light-induced liquid crystallinity
SO NATURE
LA English
DT Article
ID phase; naphthopyran
AB Liquid crystals are traditionally classified as thermotropic, lyotropic or polymeric, based on the stimulus that governs the organization and order of the molecular system(1). The most widely known and applied class of liquid crystals are a subset of thermotropic liquid crystals known as calamitic, in which adding heat can result in phase transitions from or into the nematic, cholesteric and smectic mesophases. Photoresponsive liquid-crystal materials and mixtures can undergo isothermal phase transitions if light affects the order parameter of the system within a mesophase sufficiently. In nearly all previous examinations, light exposure of photoresponsive liquid-crystal materials and mixtures resulted in order-decreasing photo-induced isothermal phase transitions(2). Under specialized conditions, an increase in order with light exposure has been reported, despite the tendency of the photoresponsive liquid-crystal system to reduce order in the exposed state(3-7). A direct, photoinduced transition from the isotropic to the nematic phase has been observed in a mixture of spiropyran molecules and a nematic liquid crystal(8). Here we report a class of naphthopyran-based materials that exhibit photo-induced conformational changes in molecular structure capable of yielding order-increasing phase transitions. Appropriate functionalization of the naphthopyran molecules leads to an exceedingly large order parameter in the open form, which results in a clear to strongly absorbing dichroic state. The increase in order with light exposure has profound implications in optics, photonics, lasing and displays and will merit further consideration for applications in solar energy harvesting. The large, photoinduced dichroism exhibited by the material system has been long sought in ophthalmic applications such as photochromic and polarized variable transmission sunglasses.
C1 [Kosa, Tamas; Sukhomlinova, Ludmila; Su, Linli; Taheri, Bahman] Alpha Micron Inc, Kent, OH 44240 USA.
   [White, Timothy J.; Bunning, Timothy J.] Mat & Mfg Directorate, AF Res Lab, Wright Patterson AFB, OH 45433 USA.
C3 United States Department of Defense; United States Air Force; US Air Force Research Laboratory
RP Kosa, T (corresponding author), Alpha Micron Inc, Kent, OH 44240 USA.
EM tamas@alphamicron.com; timothy.white2@wpafb.af.mil
FU US Air Force Office of Scientific Research; Materials and Manufacturing Directorate of the US Air Force Office of Scientific Research; US Air Force [FA8650-05-D-5807]
NR 11
TC 154
Z9 168
U1 4
U2 284
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD MAY 17
PY 2012
VL 485
IS 7398
BP 347
EP 349
DI 10.1038/nature11122
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 943CW
UT WOS:000304099100037
PM 22596158
DA 2026-03-09
ER

PT J
AU Southwell, DG
   Paredes, MF
   Galvao, RP
   Jones, DL
   Froemke, RC
   Sebe, JY
   Alfaro-Cervello, C
   Tang, YS
   Garcia-Verdugo, JM
   Rubenstein, JL
   Baraban, SC
   Alvarez-Buylla, A
AF Southwell, Derek G.
   Paredes, Mercedes F.
   Galvao, Rui P.
   Jones, Daniel L.
   Froemke, Robert C.
   Sebe, Joy Y.
   Alfaro-Cervello, Clara
   Tang, Yunshuo
   Garcia-Verdugo, Jose M.
   Rubenstein, John L.
   Baraban, Scott C.
   Alvarez-Buylla, Arturo
TI Intrinsically determined cell death of developing cortical interneurons
SO NATURE
LA English
DT Article
ID fluorescent protein expression; gabaergic neurons; nervous-system; es cells; mice; adult; brain; trkc; neurogenesis; receptors
AB Cortical inhibitory circuits are formed by gamma-aminobutyric acid (GABA)-secreting interneurons, a cell population that originates far from the cerebral cortex in the embryonic ventral forebrain. Given their distant developmental origins, it is intriguing how the number of cortical interneurons is ultimately determined. One possibility, suggested by the neurotrophic hypothesis(1-5), is that cortical interneurons are overproduced, and then after their migration into cortex the excess interneurons are eliminated through a competition for extrinsically derived trophic signals. Here we characterize the developmental cell death of mouse cortical interneurons in vivo, in vitro and after transplantation. We found that 40% of developing cortical interneurons were eliminated through Bax (Bcl-2-associated X)-dependent apoptosis during postnatal life. When cultured in vitro or transplanted into the cortex, interneuron precursors died at a cellular age similar to that at which endogenous interneurons died during normal development. Over transplant sizes that varied 200-fold, a constant fraction of the transplanted population underwent cell death. The death of transplanted neurons was not affected by the cell-autonomous disruption of TrkB (tropomyosin kinase receptor B), the main neurotrophin receptor expressed by neurons of the central nervous system(6-8). Transplantation expanded the cortical interneuron population by up to 35%, but the frequency of inhibitory synaptic events did not scale with the number of transplanted interneurons. Taken together, our findings indicate that interneuron cell death is determined intrinsically, either cell-autonomously or through a population-autonomous competition for survival signals derived from other interneurons.
C1 [Southwell, Derek G.; Jones, Daniel L.; Baraban, Scott C.; Alvarez-Buylla, Arturo] Univ Calif San Francisco, Grad Program Neurosci, San Francisco, CA 94143 USA.
   [Southwell, Derek G.; Paredes, Mercedes F.; Galvao, Rui P.; Jones, Daniel L.; Sebe, Joy Y.; Tang, Yunshuo; Baraban, Scott C.; Alvarez-Buylla, Arturo] Univ Calif San Francisco, Dept Neurosci, San Francisco, CA 94143 USA.
   [Southwell, Derek G.; Paredes, Mercedes F.; Galvao, Rui P.; Jones, Daniel L.; Sebe, Joy Y.; Tang, Yunshuo; Baraban, Scott C.; Alvarez-Buylla, Arturo] Univ Calif San Francisco, Dept Neurosurg, San Francisco, CA 94143 USA.
   [Southwell, Derek G.; Paredes, Mercedes F.; Galvao, Rui P.; Jones, Daniel L.; Sebe, Joy Y.; Tang, Yunshuo; Rubenstein, John L.; Baraban, Scott C.; Alvarez-Buylla, Arturo] Univ Calif San Francisco, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, San Francisco, CA 94143 USA.
   [Southwell, Derek G.; Tang, Yunshuo] Univ Calif San Francisco, Med Scientist Training Program, San Francisco, CA 94143 USA.
   [Paredes, Mercedes F.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA.
   [Froemke, Robert C.] Univ Calif San Francisco, Coleman Mem Lab, Dept Otolaryngol, San Francisco, CA 94143 USA.
   [Froemke, Robert C.] Univ Calif San Francisco, WM Keck Fdn Ctr Integrat Neurosci, San Francisco, CA 94143 USA.
   [Alfaro-Cervello, Clara; Garcia-Verdugo, Jose M.] Univ Valencia, CIBERNED, Inst Cavanilles, Valencia 46071, Spain.
   [Tang, Yunshuo] Univ Calif San Francisco, Biomed Sci Grad Program, San Francisco, CA 94143 USA.
   [Rubenstein, John L.] Univ Calif San Francisco, Dept Psychiat, 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 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 Valencia; CIBERNED; University of California System; University of California San Francisco; University of California System; University of California San Francisco
RP Southwell, DG (corresponding author), Stanford Univ, Sch Med, Dept Neurosurg, Stanford, CA 94305 USA.
EM dereksouthwell@gmail.com; abuylla@stemcell.ucsf.edu
FU California Institute for Regenerative Medicine [TR2-01749]; National Institute of Neurologic Disorders and Stroke [F32NS061497]; John G. Bowes Research Fund; Spanish Ministry of Science and Innovation [SAF-2008-01274]; National Institutes of Health [R01 NS071785, R01 NS048528]; National Institute of Neurological Disorders and Stroke [R01NS071785] Funding Source: NIH RePORTER
NR 24
TC 271
Z9 350
U1 0
U2 32
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD NOV 1
PY 2012
VL 491
IS 7422
BP 109
EP U172
DI 10.1038/nature11523
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 028PM
UT WOS:000310434500040
PM 23041929
DA 2026-03-09
ER

PT J
AU Wu, CH
   Fallini, C
   Ticozzi, N
   Keagle, PJ
   Sapp, PC
   Piotrowska, K
   Lowe, P
   Koppers, M
   McKenna-Yasek, D
   Baron, DM
   Kost, JE
   Gonzalez-Perez, P
   Fox, AD
   Adams, J
   Taroni, F
   Tiloca, C
   Leclerc, AL
   Chafe, SC
   Mangroo, D
   Moore, MJ
   Zitzewitz, JA
   Xu, ZS
   van den Berg, LH
   Glass, JD
   Siciliano, G
   Cirulli, ET
   Goldstein, DB
   Salachas, F
   Meininger, V
   Rossoll, W
   Ratti, A
   Gellera, C
   Bosco, DA
   Bassell, GJ
   Silani, V
   Drory, VE
   Brown, RH
   Landers, JE
AF Wu, Chi-Hong
   Fallini, Claudia
   Ticozzi, Nicola
   Keagle, Pamela J.
   Sapp, Peter C.
   Piotrowska, Katarzyna
   Lowe, Patrick
   Koppers, Max
   McKenna-Yasek, Diane
   Baron, Desiree M.
   Kost, Jason E.
   Gonzalez-Perez, Paloma
   Fox, Andrew D.
   Adams, Jenni
   Taroni, Franco
   Tiloca, Cinzia
   Leclerc, Ashley Lyn
   Chafe, Shawn C.
   Mangroo, Dev
   Moore, Melissa J.
   Zitzewitz, Jill A.
   Xu, Zuo-Shang
   van den Berg, Leonard H.
   Glass, Jonathan D.
   Siciliano, Gabriele
   Cirulli, Elizabeth T.
   Goldstein, David B.
   Salachas, Francois
   Meininger, Vincent
   Rossoll, Wilfried
   Ratti, Antonia
   Gellera, Cinzia
   Bosco, Daryl A.
   Bassell, Gary J.
   Silani, Vincenzo
   Drory, Vivian E.
   Brown, Robert H., Jr.
   Landers, John E.
TI Mutations in the profilin 1 gene cause familial amyotrophic lateral sclerosis
SO NATURE
LA English
DT Article
ID hexanucleotide repeat; spastic paraplegia; neurite outgrowth; mutant sod1; protein; actin; als; c9orf72; expansion; increase
AB Amyotrophic lateral sclerosis (ALS) is a late-onset neurodegenerative disorder resulting from motor neuron death. Approximately 10% of cases are familial (FALS), typically with a dominant inheritance mode. Despite numerous advances in recent years(1-9), nearly 50% of FALS cases have unknown genetic aetiology. Here we show that mutations within the profilin 1 (PFN1) gene can cause FALS. PFN1 is crucial for the conversion of monomeric (G)-actin to filamentous (F)-actin. Exome sequencing of two large ALS families showed different mutations within the PFN1 gene. Further sequence analysis identified 4 mutations in 7 out of 274 FALS cases. Cells expressing PFN1 mutants contain ubiquitinated, insoluble aggregates that in many cases contain the ALS-associated protein TDP-43. PFN1 mutants also display decreased bound actin levels and can inhibit axon outgrowth. Furthermore, primary motor neurons expressing mutant PFN1 display smaller growth cones with a reduced F/G-actin ratio. These observations further document that cytoskeletal pathway alterations contribute to ALS pathogenesis.
C1 [Wu, Chi-Hong; Keagle, Pamela J.; Sapp, Peter C.; Piotrowska, Katarzyna; Lowe, Patrick; McKenna-Yasek, Diane; Baron, Desiree M.; Kost, Jason E.; Gonzalez-Perez, Paloma; Fox, Andrew D.; Adams, Jenni; Leclerc, Ashley Lyn; Bosco, Daryl A.; Brown, Robert H., Jr.; Landers, John E.] Univ Massachusetts, Sch Med, Dept Neurol, Worcester, MA 01605 USA.
   [Fallini, Claudia; Rossoll, Wilfried; Bassell, Gary J.] Emory Univ, Sch Med, Dept Cell Biol, Atlanta, GA 30322 USA.
   [Ticozzi, Nicola; Tiloca, Cinzia; Ratti, Antonia; Silani, Vincenzo] IRCCS Ist Auxol Italiano, Dept Neurol, I-20149 Milan, Italy.
   [Ticozzi, Nicola; Tiloca, Cinzia; Ratti, Antonia; Silani, Vincenzo] IRCCS Ist Auxol Italiano, Neurosci Lab, I-20149 Milan, Italy.
   [Sapp, Peter C.] MIT, Dept Biol, Howard Hughes Med Inst, Cambridge, MA 02139 USA.
   [Koppers, Max; van den Berg, Leonard H.] Univ Med Ctr Utrecht, Rudolf Magnus Inst Neurosci, Dept Neurol, NL-3584 CX Utrecht, Netherlands.
   [Taroni, Franco; Gellera, Cinzia] Fdn IRCCS Ist Neurol Carlo Besta, Unit Genet Neurodegenerat & Metab Dis, I-20133 Milan, Italy.
   [Tiloca, Cinzia] Univ Milan, Dept Sci & Biomed Technol, Doctoral Sch Mol Med, I-20122 Milan, Italy.
   [Chafe, Shawn C.; Mangroo, Dev] Univ Guelph, Dept Mol & Cellular Biol, Guelph, ON N1G 2W1, Canada.
   [Moore, Melissa J.] Univ Massachusetts, Sch Med, Howard Hughes Med Inst, Dept Biochem & Mol Pharmacol, Worcester, MA 01605 USA.
   [Zitzewitz, Jill A.; Xu, Zuo-Shang] Univ Massachusetts, Sch Med, Dept Mol Pharmacol & Biochem, Worcester, MA 01605 USA.
   [Glass, Jonathan D.; Bassell, Gary J.] Emory Univ, Sch Med, Ctr Neurodegenerat Dis, Dept Neurol, Atlanta, GA 30322 USA.
   [Siciliano, Gabriele] Univ Pisa, Dept Neurosci, I-56126 Pisa, Italy.
   [Cirulli, Elizabeth T.; Goldstein, David B.] Duke Univ, Sch Med, Ctr Human Genome Variat, Durham, NC 27708 USA.
   [Salachas, Francois; Meininger, Vincent] UPMC, Hop La Pitie Salpetriere, APHP, Ctr Referent Malad Rares, F-75013 Paris, France.
   [Ratti, Antonia; Silani, Vincenzo] Univ Milan, Dino Ferrari Ctr, Dipartimento Fisiopatol Medicochirurg & Trapianti, I-20122 Milan, Italy.
   [Drory, Vivian E.] Tel Aviv Sourasky Med Ctr, Dept Neurol, IL-64239 Tel Aviv, Israel.
C3 University of Massachusetts System; University of Massachusetts Worcester; Emory University; IRCCS Istituto Auxologico Italiano; IRCCS Istituto Auxologico Italiano; Massachusetts Institute of Technology (MIT); Howard Hughes Medical Institute; Utrecht University; Utrecht University Medical Center; Fondazione IRCCS Istituto Neurologico Carlo Besta; University of Milan; University of Guelph; University of Massachusetts System; University of Massachusetts Worcester; Howard Hughes Medical Institute; University of Massachusetts System; University of Massachusetts Worcester; Emory University; University of Pisa; Duke University; Assistance Publique Hopitaux Paris (APHP); Universite Paris Cite; Hopital Universitaire Hotel-Dieu - APHP; Sorbonne Universite; Hopital Universitaire Pitie-Salpetriere - APHP; Hopital Universitaire Ambroise-Pare - APHP; University of Milan; Tel Aviv University; Sackler Faculty of Medicine; Tel Aviv Sourasky Medical Center
RP Landers, JE (corresponding author), Univ Massachusetts, Sch Med, Dept Neurol, Worcester, MA 01605 USA.
EM john.landers@umassmed.edu
FU ALS Therapy Alliance; Project ALS; P2ALS; Angel Fund; Pierre L. de Bourgknecht ALS Research Foundation; Al-Athel ALS Research Foundation; ALS Family Charitable Foundation; National Institutes of Health (NIH)/National Institute of Neurological Disorders and Stroke (NINDS) [1R01NS065847, 1R01NS050557, RC2-NS070-342]; Muscular Dystrophy Association [MDA173851]; Ministry of Health; SMA Europe fellowship; Massachusetts Institute of Technology
NR 39
TC 478
Z9 568
U1 0
U2 83
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD AUG 23
PY 2012
VL 488
IS 7412
BP 499
EP +
DI 10.1038/nature11280
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 992FS
UT WOS:000307761600034
PM 22801503
DA 2026-03-09
ER

PT J
AU Lammel, S
   Lim, BK
   Ran, C
   Huang, KW
   Betley, MJ
   Tye, KM
   Deisseroth, K
   Malenka, RC
AF Lammel, Stephan
   Lim, Byung Kook
   Ran, Chen
   Huang, Kee Wui
   Betley, Michael J.
   Tye, Kay M.
   Deisseroth, Karl
   Malenka, Robert C.
TI Input-specific control of reward and aversion in the ventral tegmental area
SO NATURE
LA English
DT Article
ID midbrain dopamine neurons; lateral habenula; gaba neurons; prefrontal cortex; nucleus-accumbens; substantia-nigra; rabies virus; rat; activation; stimulation
AB Ventral tegmental area (VTA) dopamine neurons have important roles in adaptive and pathological brain functions related to reward and motivation. However, it is unknown whether subpopulations of VTA dopamine neurons participate in distinct circuits that encode different motivational signatures, and whether inputs to the VTA differentially modulate such circuits. Here we show that, because of differences in synaptic connectivity, activation of inputs to the VTA from the laterodorsal tegmentum and the lateral habenula elicit reward and aversion in mice, respectively. Laterodorsal tegmentum neurons preferentially synapse on dopamine neurons projecting to the nucleus accumbens lateral shell, whereas lateral habenula neurons synapse primarily on dopamine neurons projecting to the medial prefrontal cortex as well as on GABAergic (gamma-aminobutyric-acid-containing) neurons in the rostromedial tegmental nucleus. These results establish that distinct VTA circuits generate reward and aversion, and thereby provide a new framework for understanding the circuit basis of adaptive and pathological motivated behaviours.
C1 [Lammel, Stephan; Lim, Byung Kook; Ran, Chen; Huang, Kee Wui; Betley, Michael J.; Malenka, Robert C.] Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Nancy Pritzker Lab, Stanford, CA 94305 USA.
   [Tye, Kay M.] MIT, Dept Brain & Cognit Sci, Picower Inst Learning & Memory, Cambridge, MA 02139 USA.
   [Deisseroth, Karl] Stanford Univ, Dept Bioengn, Stanford, CA 94305 USA.
   [Deisseroth, Karl] Stanford Univ, Dept Psychiat, Stanford, CA 94305 USA.
C3 Stanford University; Massachusetts Institute of Technology (MIT); Stanford University; Stanford University
RP Malenka, RC (corresponding author), Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Nancy Pritzker Lab, 265 Campus Dr, Stanford, CA 94305 USA.
EM malenka@stanford.edu
FU National Institutes of Health [NIH NS069375]; Simons Foundation; DARPA REPAIR program; Wiegers Family Fund; German Academy of Sciences Leopoldina; Davis Foundation Postdoctoral Fellowship in Eating Disorders Research; JPB Foundation; NIMH
NR 42
TC 1032
Z9 1307
U1 2
U2 187
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD NOV 8
PY 2012
VL 491
IS 7423
BP 212
EP +
DI 10.1038/nature11527
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 033DP
UT WOS:000310774300035
PM 23064228
DA 2026-03-09
ER

PT J
AU Sneddon, JB
   Borowiak, M
   Melton, DA
AF Sneddon, Julie B.
   Borowiak, Malgorzata
   Melton, Douglas A.
TI Self-renewal of embryonic-stem-cell-derived progenitors by organ-matched mesenchyme
SO NATURE
LA English
DT Article
ID differentiation; mouse; expression; derivation; endoderm
AB One goal of regenerative medicine, to use stem cells to replace cells lost by injury or disease, depends on producing an excess of the relevant cell for study or transplantation. To this end, the stepwise differentiation of stem cells into specialized derivatives has been successful for some cell types(1-3), but a major problem remains the inefficient conversion of cells from one stage of differentiation to the next. If specialized cells are to be produced in large numbers it will be necessary to expand progenitor cells, without differentiation, at some steps of the process. Using the pancreatic lineage as a model for embryonic-stem-cell differentiation, we demonstrate that this is a solvable problem. Co-culture with organ-matched mesenchyme permits proliferation and self-renewal of progenitors, without differentiation, and enables an expansion of more than a million-fold for human endodermal cells with full retention of their developmental potential. This effect is specific both to the mesenchymal cell and to the progenitor being amplified. Progenitors that have been serially expanded on mesenchyme give rise to glucose-sensing, insulin-secreting cells when transplanted in vivo. Theoretically, the identification of stage-specific renewal signals can be incorporated into any scheme for the efficient production of large numbers of differentiated cells from stem cells and may therefore have wide application in regenerative biology.
C1 [Sneddon, Julie B.; Borowiak, Malgorzata; Melton, Douglas A.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Harvard Stem Cell Inst, Cambridge, MA 02138 USA.
C3 Harvard University
RP Melton, DA (corresponding author), Harvard Univ, Dept Stem Cell & Regenerat Biol, Harvard Stem Cell Inst, 7 Divin Ave, Cambridge, MA 02138 USA.
EM dmelton@harvard.edu
FU National Institutes of Health [5 U42 RR006042-20, K08 DK084206]; Howard Hughes Medical Institute; Leona M. and Harry B. Helmsley Charitable Trust
NR 25
TC 107
Z9 178
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 NOV 29
PY 2012
VL 491
IS 7426
BP 765
EP +
DI 10.1038/nature11463
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 044FY
UT WOS:000311606000047
PM 23041930
DA 2026-03-09
ER

PT J
AU Zielinski, CE
   Mele, F
   Aschenbrenner, D
   Jarrossay, D
   Ronchi, F
   Gattorno, M
   Monticelli, S
   Lanzavecchia, A
   Sallusto, F
AF Zielinski, Christina E.
   Mele, Federico
   Aschenbrenner, Dominik
   Jarrossay, David
   Ronchi, Francesca
   Gattorno, Marco
   Monticelli, Silvia
   Lanzavecchia, Antonio
   Sallusto, Federica
TI Pathogen-induced human TH17 cells produce IFN-γ or IL-10 and are regulated by IL-1β
SO NATURE
LA English
DT Article
ID growth-factor-beta; hyper-ige syndrome; cd4(+) t-cells; th17 cells; tgf-beta; helper-cells; differentiation; memory; interleukin-1-beta; prostaglandin-e2
AB IL-17-producing CD4(+) T helper cells (T(H)17) have been extensively investigated in mouse models of autoimmunity(1). However, the requirements for differentiation and the properties of pathogen-induced human T(H)17 cells remain poorly defined. Using an approach that combines the in vitro priming of naive T cells with the ex vivo analysis of memory T cells, we describe here two types of human T(H)17 cells with distinct effector function and differentiation requirements. Candida albicans-specific T(H)17 cells produced IL-17 and IFN-gamma, but no IL-10, whereas Staphylococcus aureus-specific T(H)17 cells produced IL-17 and could produce IL-10 upon restimulation. IL-6, IL-23 and IL-1 beta contributed to T(H)17 differentiation induced by both pathogens, but IL-1 beta was essential in C. albicans-induced T(H)17 differentiation to counteract the inhibitory activity of IL-12 and to prime IL-17/IFN-gamma double-producing cells. In addition, IL-1 beta inhibited IL-10 production in differentiating and in memory T(H)17 cells, whereas blockade of IL-1 beta in vivo led to increased IL-10 production by memory T(H)17 cells. We also show that, after restimulation, T(H)17 cells transiently downregulated IL-17 production through a mechanism that involved IL-2-induced activation of STAT5 and decreased expression of ROR-gamma t. Taken together these findings demonstrate that by eliciting different cytokines C. albicans and S. aureus prime T(H)17 cells that produce either IFN-gamma or IL-10, and identify IL-1 beta and IL-2 as pro-and anti-inflammatory regulators of T(H)17 cells both at priming and in the effector phase.
C1 [Zielinski, Christina E.; Mele, Federico; Aschenbrenner, Dominik; Jarrossay, David; Ronchi, Francesca; Monticelli, Silvia; Lanzavecchia, Antonio; Sallusto, Federica] Inst Res Biomed, CH-6500 Bellinzona, Switzerland.
   [Gattorno, Marco] G Gaslini Sci Inst, I-16147 Genoa, Italy.
   [Lanzavecchia, Antonio] ETH, Inst Microbiol, CH-8093 Zurich, Switzerland.
C3 Universita della Svizzera Italiana; University of Genoa; IRCCS Istituto Giannina Gaslini; Swiss Federal Institutes of Technology Domain; ETH Zurich
RP Sallusto, F (corresponding author), Inst Res Biomed, Via Vincenzo Vela 6, CH-6500 Bellinzona, Switzerland.
EM christina.zielinski@charite.de; federica.sallusto@irb.usi.ch
FU German Research Foundation (DFG) [Zi 1262/1-1]; Swiss National Science Foundation [131092, 126027]; Institute of Arthritis Research (IAR); Helmut Horten Foundation
NR 30
TC 788
Z9 898
U1 1
U2 100
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD APR 26
PY 2012
VL 484
IS 7395
BP 514
EP U139
DI 10.1038/nature10957
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 931FF
UT WOS:000303200400051
PM 22466287
DA 2026-03-09
ER

PT J
AU Balazs, AB
   Chen, J
   Hong, CM
   Rao, DS
   Yang, LL
   Baltimore, D
AF Balazs, Alejandro B.
   Chen, Joyce
   Hong, Christin M.
   Rao, Dinesh S.
   Yang, Lili
   Baltimore, David
TI Antibody-based protection against HIV infection by vectored immunoprophylaxis
SO NATURE
LA English
DT Article
ID immunodeficiency-virus type-1; mediated gene-transfer; neutralizing antibody; monoclonal-antibody; adenoassociated virus; therapeutic levels; factor-ix; broad; expression; design
AB Despite tremendous efforts, development of an effective vaccine against human immunodeficiency virus (HIV) has proved an elusive goal. Recently, however, numerous antibodies have been identified that are capable of neutralizing most circulating HIV strains(1-5). These antibodies all exhibit an unusually high level of somatic mutation(6), presumably owing to extensive affinity maturation over the course of continuous exposure to an evolving antigen(7). Although substantial effort has focused on the design of immunogens capable of eliciting antibodies de novo that would target similar epitopes(8-10), it remains uncertain whether a conventional vaccine will be able to elicit analogues of the existing broadly neutralizing antibodies. As an alternative to immunization, vector-mediated gene transfer could be used to engineer secretion of the existing broadly neutralizing antibodies into the circulation. Here we describe a practical implementation of this approach, which we call vectored immunoprophylaxis (VIP), which in mice induces lifelong expression of these monoclonal antibodies at high concentrations from a single intramuscular injection. This is achieved using a specialized adeno-associated virus vector optimized for the production of full-length antibody from muscle tissue. We show that humanized mice receiving VIP appear to be fully protected from HIV infection, even when challenged intravenously with very high doses of replication-competent virus. Our results suggest that successful translation of this approach to humans may produce effective prophylaxis against HIV.
C1 [Balazs, Alejandro B.; Chen, Joyce; Hong, Christin M.; Yang, Lili; Baltimore, David] CALTECH, Div Biol, Pasadena, CA 91125 USA.
   [Rao, Dinesh S.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA.
C3 California Institute of Technology; University of California System; University of California Los Angeles; University of California Los Angeles Medical Center; David Geffen School of Medicine at UCLA
RP Baltimore, D (corresponding author), CALTECH, Div Biol, 1200 E Calif Blvd, Pasadena, CA 91125 USA.
EM baltimo@caltech.edu
FU Bill and Melinda Gates Foundation through Grand Challenges in Global Health Initiative [37866]; National Institutes of Health through the National Institute of Allergy and Infectious Disease (NIAID) [HHSN266200500035C]; Joint Center for Translational Medicine; amfAR [107756-47-RFVA]; National Institutes of Health [1K08CA133521]; National Heart Lung and Blood Institute; National Institute on Minority Health and Health Disparities; 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; National Institute on Aging; National Institute of Diabetes and Digestive and Kidney Diseases; National Institute of Dental and Craniofacial Research; National Cancer Institute; National Institute of Allergy and Infectious Diseases [P30AI027763] Funding Source: NIH RePORTER
NR 38
TC 454
Z9 597
U1 0
U2 97
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JAN 5
PY 2012
VL 481
IS 7379
BP 81
EP U88
DI 10.1038/nature10660
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 872VD
UT WOS:000298836900033
PM 22139420
DA 2026-03-09
ER

PT J
AU Cooray, A
   Smidt, J
   De Bernardis, F
   Gong, Y
   Stern, D
   Ashby, MLN
   Eisenhardt, PR
   Frazer, CC
   Gonzalez, AH
   Kochanek, CS
   Kozlowski, S
   Wright, EL
AF Cooray, Asantha
   Smidt, Joseph
   De Bernardis, Francesco
   Gong, Yan
   Stern, Daniel
   Ashby, Matthew L. N.
   Eisenhardt, Peter R.
   Frazer, Christopher C.
   Gonzalez, Anthony H.
   Kochanek, Christopher S.
   Kozlowski, Szymon
   Wright, Edward L.
TI Near-infrared background anisotropies from diffuse intrahalo light of galaxies
SO NATURE
LA English
DT Article
ID brightest cluster galaxy; wide-field survey; intracluster light; population-iii; stellar halos; fluctuations; stars; deep; reionization; calibration
AB Unresolved anisotropies of the cosmic near-infrared background radiation are expected to have contributions from the earliest galaxies during the epoch of reionization(1-5) and from faint, dwarf galaxies at intermediate redshifts(6,7). Previous measurements(8-12) were unable to pinpoint conclusively the dominant origin because they did not sample spatial scales that were sufficiently large to distinguish between these two possibilities. Here we report a measurement of the anisotropy power spectrum from subarcminute to one-degree angular scales, and find the clustering amplitude to be larger than predicted by the models based on the two existing explanations. As the shot-noise level of the power spectrum is consistent with that expected from faint galaxies, a new source population on the sky is not necessary to explain the observations. However, a physical mechanism that increases the clustering amplitude is needed. Motivated by recent results related to the extended stellar light profile in dark-matter haloes(13-15), we consider the possibility that the fluctuations originate from intrahalo stars of all galaxies. We find that the measured power spectrum can be explained by an intrahalo light fraction of 0.07 to 0.2 per cent relative to the total luminosity in dark-matter haloes of 10(9) to 10(12) solar masses at redshifts of about 1 to 4.
C1 [Cooray, Asantha; Smidt, Joseph; De Bernardis, Francesco; Gong, Yan; Frazer, Christopher C.] Univ Calif Irvine, Dept Phys & Astron, Irvine, CA 92697 USA.
   [Stern, Daniel; Eisenhardt, Peter R.] CALTECH, Jet Prop Lab, Pasadena, CA 91109 USA.
   [Ashby, Matthew L. N.] Harvard Smithsonian Ctr Astrophys, Cambridge, MA 02138 USA.
   [Gonzalez, Anthony H.] Univ Florida, Dept Astron, Gainesville, FL 32611 USA.
   [Kochanek, Christopher S.; Kozlowski, Szymon] Ohio State Univ, Dept Astron, Columbus, OH 43210 USA.
   [Kozlowski, Szymon] Univ Warsaw Observ, PL-00478 Warsaw, Poland.
   [Wright, Edward L.] Univ Calif Los Angeles, Dept Phys & Astron, Los Angeles, CA 90095 USA.
C3 University of California System; University of California Irvine; National Aeronautics & Space Administration (NASA); NASA Jet Propulsion Laboratory (JPL); California Institute of Technology; Smithsonian Institution; Harvard University; Smithsonian Astrophysical Observatory; State University System of Florida; University of Florida; University System of Ohio; Ohio State University; University of Warsaw; Warsaw University Observatory; University of California System; University of California Los Angeles
RP Cooray, A (corresponding author), Univ Calif Irvine, Dept Phys & Astron, Irvine, CA 92697 USA.
EM acooray@uci.edu
FU NSF CAREER; NASA ADAP; JPL/Caltech
NR 30
TC 100
Z9 113
U1 1
U2 11
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 25
PY 2012
VL 490
IS 7421
BP 514
EP 516
DI 10.1038/nature11474
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 025NK
UT WOS:000310196200036
PM 23099405
DA 2026-03-09
ER

PT J
AU Pälike, H
   Lyle, MW
   Nishi, H
   Raffi, I
   Ridgwell, A
   Gamage, K
   Klaus, A
   Acton, G
   Anderson, L
   Backman, J
   Baldauf, J
   Beltran, C
   Bohaty, SM
   Bown, P
   Busch, W
   Channell, JET
   Chun, COJ
   Delaney, M
   Dewangan, P
   Dunkley Jones, T
   Edgar, KM
   Evans, H
   Fitch, P
   Foster, GL
   Gussone, N
   Hasegawa, H
   Hathorne, EC
   Hayashi, H
   Herrle, JO
   Holbourn, A
   Hovan, S
   Hyeong, K
   Iijima, K
   Ito, T
   Kamikuri, S
   Kimoto, K
   Kuroda, J
   Leon-Rodriguez, L
   Malinverno, A
   Moore, TC
   Murphy, BH
   Murphy, DP
   Nakamura, H
   Ogane, K
   Ohneiser, C
   Richter, C
   Robinson, R
   Rohling, EJ
   Romero, O
   Sawada, K
   Scher, H
   Schneider, L
   Sluijs, A
   Takata, H
   Tian, J
   Tsujimoto, A
   Wade, BS
   Westerhold, T
   Wilkens, R
   Williams, T
   Wilson, PA
   Yamamoto, Y
   Yamamoto, S
   Yamazaki, T
   Zeebe, RE
AF Paelike, Heiko
   Lyle, Mitchell W.
   Nishi, Hiroshi
   Raffi, Isabella
   Ridgwell, Andy
   Gamage, Kusali
   Klaus, Adam
   Acton, Gary
   Anderson, Louise
   Backman, Jan
   Baldauf, Jack
   Beltran, Catherine
   Bohaty, Steven M.
   Bown, Paul
   Busch, William
   Channell, Jim E. T.
   Chun, Cecily O. J.
   Delaney, Margaret
   Dewangan, Pawan
   Dunkley Jones, Tom
   Edgar, Kirsty M.
   Evans, Helen
   Fitch, Peter
   Foster, Gavin L.
   Gussone, Nikolaus
   Hasegawa, Hitoshi
   Hathorne, Ed C.
   Hayashi, Hiroki
   Herrle, Jens O.
   Holbourn, Ann
   Hovan, Steve
   Hyeong, Kiseong
   Iijima, Koichi
   Ito, Takashi
   Kamikuri, Shin-ichi
   Kimoto, Katsunori
   Kuroda, Junichiro
   Leon-Rodriguez, Lizette
   Malinverno, Alberto
   Moore, Ted C., Jr.
   Murphy, Brandon H.
   Murphy, Daniel P.
   Nakamura, Hideto
   Ogane, Kaoru
   Ohneiser, Christian
   Richter, Carl
   Robinson, Rebecca
   Rohling, Eelco J.
   Romero, Oscar
   Sawada, Ken
   Scher, Howie
   Schneider, Leah
   Sluijs, Appy
   Takata, Hiroyuki
   Tian, Jun
   Tsujimoto, Akira
   Wade, Bridget S.
   Westerhold, Thomas
   Wilkens, Roy
   Williams, Trevor
   Wilson, Paul A.
   Yamamoto, Yuhji
   Yamamoto, Shinya
   Yamazaki, Toshitsugu
   Zeebe, Richard E.
TI A Cenozoic record of the equatorial Pacific carbonate compensation depth
SO NATURE
LA English
DT Article
ID antarctic glaciation; calcite compensation; organic-carbon; model; ocean; cycle; dioxide; history; sr/ca; onset
AB Atmospheric carbon dioxide concentrations and climate are regulated on geological timescales by the balance between carbon input from volcanic and metamorphic outgassing and its removal by weathering feedbacks; these feedbacks involve the erosion of silicate rocks and organic-carbon-bearing rocks. The integrated effect of these processes is reflected in the calcium carbonate compensation depth, which is the oceanic depth at which calcium carbonate is dissolved. Here we present a carbonate accumulation record that covers the past 53 million years from a depth transect in the equatorial Pacific Ocean. The carbonate compensation depth tracks long-term ocean cooling, deepening from 3.0-3.5 kilometres during the early Cenozoic (approximately 55 million years ago) to 4.6 kilometres at present, consistent with an overall Cenozoic increase in weathering. We find large superimposed fluctuations in carbonate compensation depth during the middle and late Eocene. Using Earth system models, we identify changes in weathering and the mode of organic-carbon delivery as two key processes to explain these large-scale Eocene fluctuations of the carbonate compensation depth.
C1 [Paelike, Heiko; Bohaty, Steven M.; Chun, Cecily O. J.; Edgar, Kirsty M.; Foster, Gavin L.; Murphy, Daniel P.; Rohling, Eelco J.; Wilson, Paul A.] Univ Southampton, Natl Oceanog Ctr Southampton, Southampton SO14 3ZH, Hants, England.
   [Lyle, Mitchell W.; Baldauf, Jack; Murphy, Daniel P.] Texas A&M Univ, Dept Oceanog, College Stn, TX 77840 USA.
   [Nishi, Hiroshi] Tohoku Univ, Tohoku Univ Museum, Ctr Acad Resources & Arch, Aoba Ku, Sendai, Miyagi 9808578, Japan.
   [Raffi, Isabella] Univ G DAnnunzio, DiGAT CeRS Geo, Dipartimento Geotecnol Ambiente & Terr, Chieti, Italy.
   [Ridgwell, Andy] Univ Bristol, Sch Geog Sci, Bristol BS8 1SS, Avon, England.
   [Gamage, Kusali; Klaus, Adam] Texas A&M Univ, Integrated Ocean Drilling Program, College Stn, TX 77845 USA.
   [Acton, Gary] Univ Calif Davis, Dept Geol, Davis, CA 95616 USA.
   [Anderson, Louise] Univ Leicester, Dept Geol, Leicester LE1 7RH, Leics, England.
   [Backman, Jan] Stockholm Univ, Dept Geol Sci, SE-10691 Stockholm, Sweden.
   [Beltran, Catherine] Univ Paris 06, ISTeP, UMR 7193, F-75252 Paris 05, France.
   [Bown, Paul] UCL, London WC1E 6BT, England.
   [Busch, William] Univ New Orleans, New Orleans, LA 70148 USA.
   [Channell, Jim E. T.] Univ Florida, Dept Geol Sci, Gainesville, FL 32611 USA.
   [Chun, Cecily O. J.; Herrle, Jens O.] Goethe Univ Frankfurt, Inst Geosci, D-60438 Frankfurt, Germany.
   [Chun, Cecily O. J.; Herrle, Jens O.] Biodivers & Climate Res Ctr BIK F, D-60325 Frankfurt, Germany.
   [Chun, Cecily O. J.; Herrle, Jens O.] Senckenberg Gesell Nat Forsch, D-60325 Frankfurt, Germany.
   [Delaney, Margaret; Murphy, Brandon H.] Univ Calif Santa Cruz, Santa Cruz, CA 95064 USA.
   [Dewangan, Pawan] Natl Inst Oceanog, Panaji 403004, Goa, India.
   [Dunkley Jones, Tom; Fitch, Peter] Univ London Imperial Coll Sci Technol & Med, Dept Earth Sci & Engn, London SW7 2AZ, England.
   [Dunkley Jones, Tom] Univ Birmingham, Sch Geog Earth & Environm Sci, Birmingham B15 2TT, W Midlands, England.
   [Edgar, Kirsty M.] Cardiff Univ, Sch Earth & Ocean Sci, Cardiff CF10 3AT, S Glam, Wales.
   [Evans, Helen; Malinverno, Alberto; Williams, Trevor] Columbia Univ, Lamont Doherty Earth Observ, Palisades, NY 10964 USA.
   [Gussone, Nikolaus] Univ Munster, Inst Mineral, D-48149 Munster, Germany.
   [Hasegawa, Hitoshi] Hokkaido Univ, Grad Sch Sci, Dept Nat Hist Sci, Kita Ku, Sapporo, Hokkaido 0600810, Japan.
   [Hathorne, Ed C.] Helmholtz Ctr Ocean Res Kiel, GEOMAR, D-24148 Kiel, Germany.
   [Hayashi, Hiroki] Shimane Univ, Interdisciplinary Fac Sci & Engn, Matsue, Shimane 6908504, Japan.
   [Holbourn, Ann] Univ Kiel, Inst Geowissensch, D-24098 Kiel, Germany.
   [Hovan, Steve] Indiana Univ Penn, Dept Geosci, Indiana, PA 15705 USA.
   [Hyeong, Kiseong] Korea Ocean Res & Dev Inst, Deep Sea Resources Res Ctr, Seoul 425600, South Korea.
   [Iijima, Koichi] Japan Agcy Marine Earth Sci & Technol, Inst Biogeosci, Yokosuka, Kanagawa 2370061, Japan.
   [Ito, Takashi] Ibaraki Univ, Fac Educ, Mito, Ibaraki 3108512, Japan.
   [Kamikuri, Shin-ichi; Nakamura, Hideto; Sawada, Ken] Hokkaido Univ, Div Nat Hist Sci, Fac Sci, Kita Ku, Sapporo, Hokkaido 0600810, Japan.
   [Kamikuri, Shin-ichi; Yamamoto, Yuhji] Kochi Univ, Ctr Adv Marine Core Res, Kochi 7838502, Japan.
   [Kimoto, Katsunori] JAMSTEC, RIGC, Yokosuka, Kanagawa 2370061, Japan.
   [Kuroda, Junichiro] JAMSTEC, IFREE, Yokosuka, Kanagawa 2370061, Japan.
   [Leon-Rodriguez, Lizette] Rice Univ, Dept Earth Sci, Houston, TX 77005 USA.
   [Moore, Ted C., Jr.] Univ Michigan, Dept Geol Sci, Ann Arbor, MI 48109 USA.
   [Ogane, Kaoru] Tohoku Univ, Inst Geol & Paleontol, Aoba Ku, Sendai, Miyagi 9808578, Japan.
   [Ohneiser, Christian] Univ Otago, Dept Geol, Dunedin, New Zealand.
   [Richter, Carl] Univ Louisiana, Sch Geosci, Lafayette, LA 70504 USA.
   [Robinson, Rebecca] Univ Rhode Isl, Grad Sch Oceanog, Narragansett, RI 02882 USA.
   [Romero, Oscar] Univ Granada, Inst Andaluz Ciencias Tierra, Granada 18002, Spain.
   [Scher, Howie] Univ S Carolina, Dept Earth & Ocean Sci, Columbia, SC 29208 USA.
   [Schneider, Leah] Penn State Univ, Dept Geosci, University Pk, PA 16802 USA.
   [Sluijs, Appy] Univ Utrecht, Palaeobot & Palynol Lab, Fac Geosci, Dept Earth Sci, NL-3584 CD Utrecht, Netherlands.
   [Takata, Hiroyuki] Pusan Natl Univ, Div Earth Environm Syst, Coastal Environm Syst Sch BK21, Pusan 609735, South Korea.
   [Tian, Jun] Tongji Univ, State Key Lab Marine Geol, Shanghai 200092, Peoples R China.
   [Tsujimoto, Akira] Shimane Univ, Fac Educ, Matsue, Shimane 6908504, Japan.
   [Wade, Bridget S.] Texas A&M Univ, Dept Geol & Geophys, College Stn, TX 77843 USA.
   [Wade, Bridget S.] Univ Leeds, Sch Earth & Environm, Leeds LS2 9JT, W Yorkshire, England.
   [Westerhold, Thomas] Univ Bremen, Ctr Marine Environm Sci MARUM, D-28359 Bremen, Germany.
   [Wilkens, Roy] Univ Hawaii Manoa, Hawaii Inst Geophys & Planetol, Honolulu, HI 96822 USA.
   [Yamamoto, Shinya] Yamanashi Inst Environm Sci, Fujiyoshida, Yamanashi 4030005, Japan.
   [Yamazaki, Toshitsugu] AIST, Geol Survey Japan, Tsukuba, Ibaraki 3058567, Japan.
   [Zeebe, Richard E.] Univ Hawaii Manoa, Dept Oceanog, Sch Ocean & Earth Sci & Technol, Honolulu, HI 96822 USA.
C3 University of Southampton; NERC National Oceanography Centre; Texas A&M University System; Texas A&M University College Station; Tohoku University; G d'Annunzio University of Chieti-Pescara; University of Bristol; Texas A&M University System; Texas A&M University College Station; University of California System; University of California Davis; University of Leicester; Stockholm University; Sorbonne Universite; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Earth Sciences & Astronomy (INSU); University of London; University College London; University of Louisiana System; University of New Orleans; State University System of Florida; University of Florida; Goethe University Frankfurt; Leibniz Association; Senckenberg Gesellschaft fur Naturforschung (SGN); Senckenberg Biodiversitat & Klima- Forschungszentrum (BiK-F); Leibniz Association; Senckenberg Gesellschaft fur Naturforschung (SGN); University of California System; University of California Santa Cruz; Council of Scientific & Industrial Research (CSIR) - India; CSIR - National Institute of Oceanography (NIO); Imperial College London; University of Birmingham; Cardiff University; Columbia University; University of Munster; Hokkaido University; Helmholtz Association; GEOMAR Helmholtz Center for Ocean Research Kiel; Shimane University; University of Kiel; Pennsylvania State System of Higher Education (PASSHE); Indiana University of Pennsylvania; Korea Institute of Ocean Science & Technology (KIOST); Japan Agency for Marine-Earth Science & Technology (JAMSTEC); Ibaraki University; Hokkaido University; Kochi University; Japan Agency for Marine-Earth Science & Technology (JAMSTEC); Japan Agency for Marine-Earth Science & Technology (JAMSTEC); Rice University; University of Michigan System; University of Michigan; Tohoku University; University of Otago; University of Louisiana Lafayette; University of Rhode Island; Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Instituto Andaluz de Ciencias de la Tierra (IACT); University of Granada; University of South Carolina System; University of South Carolina Columbia; Pennsylvania Commonwealth System of Higher Education (PCSHE); Pennsylvania State University; Pennsylvania State University - University Park; Utrecht University; Pusan National University; Tongji University; Shimane University; Texas A&M University System; Texas A&M University College Station; University of Leeds; University of Bremen; University of Hawaii System; University of Hawaii Manoa; National Institute of Advanced Industrial Science & Technology (AIST); University of Hawaii System; University of Hawaii Manoa
RP Pälike, H (corresponding author), Univ Southampton, Natl Oceanog Ctr Southampton, Waterfront Campus,European Way, Southampton SO14 3ZH, Hants, England.
EM hpaelike@marum.de
FU Philip Leverhulme Prize; BIK-F; NERC [NE/H000089/1, NE/H020136/1, NE/G003270/1, NE/F003641/1, NE/H022554/1, NE/I006168/1]; Grants-in-Aid for Scientific Research [23740387, 22403015, 23740377, 23540542] Funding Source: KAKEN; Division Of Ocean Sciences; Directorate For Geosciences [0961412, 0962184] Funding Source: National Science Foundation; Division Of Ocean Sciences; Directorate For Geosciences [0960999] Funding Source: National Science Foundation; Natural Environment Research Council [NE/H023852/1, NE/I000011/1, NE/I006168/1, NE/H020136/1, NE/H022554/1, NE/H000089/1, NE/F003641/1, NE/G003270/1, NE/G014817/1, NE/I005595/1, NE/H001298/1] Funding Source: researchfish; Science and Technology Facilities Council [PP/D002176/1] Funding Source: researchfish; NERC [NE/H020136/1, NE/I006168/1, NE/G003270/1, NE/I005595/1, NE/H000089/1, NE/G014817/1, NE/H023852/1, NE/H016457/1, NE/F003641/1, NE/I000011/1, NE/H001298/1, NE/H022554/1] Funding Source: UKRI; STFC [PP/D002176/1] Funding Source: UKRI
NR 40
TC 310
Z9 354
U1 3
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 AUG 30
PY 2012
VL 488
IS 7413
BP 609
EP +
DI 10.1038/nature11360
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 996NC
UT WOS:000308095100047
PM 22932385
DA 2026-03-09
ER

PT J
AU Oxborrow, M
   Breeze, JD
   Alford, NM
AF Oxborrow, Mark
   Breeze, Jonathan D.
   Alford, Neil M.
TI Room-temperature solid-state maser
SO NATURE
LA English
DT Article
ID photo-excited triplet; p-terphenyl; amplifiers; pentacene; polarization; crystals; epr
AB The invention of the laser has resulted in many innovations, and the device has become ubiquitous. However, the maser, which amplifies microwave radiation rather than visible light, has not had as large an impact, despite being instrumental in the laser's birth(1,2). The maser's relative obscurity has mainly been due to the inconvenience of the operating conditions needed for its various realizations: atomic(3) and free-electron(4) masers require vacuum chambers and pumping; and solid-state masers(5), although they excel as low-noise amplifiers(6) and are occasionally incorporated in ultrastable oscillators(7,8), typically require cryogenic refrigeration. Most realizations of masers also require strong magnets, magnetic shielding or both. Overcoming these various obstacles would pave the way for improvements such as more-sensitive chemical assays, more-precise determinations of biomolecular structure and function, and more-accurate medical diagnostics (including tomography) based on enhanced magnetic resonance spectrometers(9) incorporating maser amplifiers and oscillators. Here we report the experimental demonstration of a solid-state maser operating at room temperature in pulsed mode. It works on a laboratory bench, in air, in the terrestrial magnetic field and amplifies at around 1.45 gigahertz. In contrast to the cryogenic ruby maser(6), in our maser the gain medium is an organic mixed molecular crystal, p-terphenyl doped with pentacene, the latter being photo-excited by yellow light. The maser's pumping mechanism exploits spin-selective molecular intersystem crossing(10) into pentacene's triplet ground state(11,12). When configured as an oscillator, the solid-state maser's measured output power of around -10 decibel milliwatts is approximately 100 million times greater than that of an atomic hydrogen maser(3), which oscillates at a similar frequency (about 1.42 gigahertz). By exploiting the high levels of spin polarization readily generated by intersystem crossing in photo-excited pentacene and other aromatic molecules, this new type of maser seems to be capable of amplifying with a residual noise temperature far below room temperature.
C1 [Oxborrow, Mark] Natl Phys Lab, Teddington TW11 0LW, Middx, England.
   [Breeze, Jonathan D.; Alford, Neil M.] Imperial Coll London, Dept Mat, London SW7 2AZ, England.
C3 National Physical Laboratory - UK; Imperial College London
RP Oxborrow, M (corresponding author), Natl Phys Lab, Hampton Rd, Teddington TW11 0LW, Middx, England.
EM mo@npl.co.uk; n.alford@imperial.ac.uk
FU NMS Pathfinder Metrology Programme; Engineering and Physical Sciences Research Council
NR 30
TC 120
Z9 139
U1 4
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 AUG 16
PY 2012
VL 488
IS 7411
BP 353
EP +
DI 10.1038/nature11339
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 988OS
UT WOS:000307501000036
PM 22895341
DA 2026-03-09
ER

PT J
AU Andersen, CBF
   Torvund-Jensen, M
   Nielsen, MJ
   de Oliveira, CLP
   Hersleth, HP
   Andersen, NH
   Pedersen, JS
   Andersen, GR
   Moestrup, SK
AF Andersen, Christian Brix Folsted
   Torvund-Jensen, Morten
   Nielsen, Marianne Jensby
   Pinto de Oliveira, Cristiano Luis
   Hersleth, Hans-Petter
   Andersen, Niels Hojmark
   Pedersen, Jan Skov
   Andersen, Gregers Rom
   Moestrup, Soren Kragh
TI Structure of the haptoglobin-haemoglobin complex
SO NATURE
LA English
DT Article
ID serine-protease; biological macromolecules; subunit dissociation; solution scattering; crystal-structure; catalytic domain; binding; resolution; cd163; equilibrium
AB Red cell haemoglobin is the fundamental oxygen-transporting molecule in blood, but also a potentially tissue-damaging compound owing to its highly reactive haem groups. During intravascular haemolysis, such as in malaria and haemoglobinopathies(1), haemoglobin is released into the plasma, where it is captured by the protective acute-phase protein haptoglobin. This leads to formation of the haptoglobin-haemoglobin complex, which represents a virtually irreversible non-covalent protein-protein interaction(2). Here we present the crystal structure of the dimeric porcine haptoglobin-haemoglobin complex determined at 2.9 angstrom resolution. This structure reveals that haptoglobin molecules dimerize through an unexpected beta-strand swap between two complement control protein (CCP) domains, defining a new fusion CCP domain structure. The haptoglobin serine protease domain forms extensive interactions with both the alpha- and beta-subunits of haemoglobin, explaining the tight binding between haptoglobin and haemoglobin. The haemoglobin-interacting region in the alpha beta dimer is highly overlapping with the interface between the two alpha beta dimers that constitute the native haemoglobin tetramer. Several haemoglobin residues prone to oxidative modification after exposure to haem-induced reactive oxygen species are buried in the haptoglobin-haemoglobin interface, thus showing a direct protective role of haptoglobin. The haptoglobin loop previously shown to be essential for binding of haptoglobin-haemoglobin to the macrophage scavenger receptor CD163 (ref. 3) protrudes from the surface of the distal end of the complex, adjacent to the associated haemoglobin alpha-subunit. Small-angle X-ray scattering measurements of human haptoglobin-haemoglobin bound to the ligand-binding fragment of CD163 confirm receptor binding in this area, and show that the rigid dimeric complex can bind two receptors. Such receptor cross-linkage may facilitate scavenging and explain the increased functional affinity of multimeric haptoglobin-haemoglobin for CD163 (ref. 4).
C1 [Andersen, Christian Brix Folsted; Torvund-Jensen, Morten; Nielsen, Marianne Jensby; Moestrup, Soren Kragh] Aarhus Univ, Dept Biomed, DK-8000 Aarhus C, Denmark.
   [Pinto de Oliveira, Cristiano Luis] Univ Sao Paulo, Inst Phys, BR-0531497 Sao Paulo, Brazil.
   [Pinto de Oliveira, Cristiano Luis; Pedersen, Jan Skov] Aarhus Univ, Dept Chem, DK-8000 Aarhus C, Denmark.
   [Pinto de Oliveira, Cristiano Luis; Pedersen, Jan Skov] Aarhus Univ, INANO Interdisciplinary Nanosci Ctr, DK-8000 Aarhus C, Denmark.
   [Hersleth, Hans-Petter] Univ Oslo, Dept Mol Biosci, NO-0316 Oslo, Norway.
   [Andersen, Niels Hojmark] Univ Oslo, Dept Chem, NO-0315 Oslo, Norway.
   [Andersen, Gregers Rom] Aarhus Univ, Dept Mol Biol & Genet, DK-8000 Aarhus C, Denmark.
C3 Aarhus University; Universidade de Sao Paulo; Aarhus University; Aarhus University; University of Oslo; University of Oslo; Aarhus University
RP Andersen, CBF (corresponding author), Aarhus Univ, Dept Biomed, DK-8000 Aarhus C, Denmark.
EM cbfa@biokemi.au.dk; skm@biokemi.au.dk
FU Lundbeck Foundation; Novo Nordisk Foundation; Research Council of Norway; European Research Council; Danish Council for Independent Research; Lundbeck Foundation [R54-2010-5637] Funding Source: researchfish
NR 47
TC 201
Z9 233
U1 3
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 SEP 20
PY 2012
VL 489
IS 7416
BP 456
EP U150
DI 10.1038/nature11369
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 007AK
UT WOS:000308860900051
PM 22922649
DA 2026-03-09
ER

PT J
AU Driessens, G
   Beck, B
   Caauwe, A
   Simons, BD
   Blanpain, C
AF Driessens, Gregory
   Beck, Benjamin
   Caauwe, Amelie
   Simons, Benjamin D.
   Blanpain, Cedric
TI Defining the mode of tumour growth by clonal analysis
SO NATURE
LA English
DT Article
ID cancer stem-cells; mouse skin; adult tissue; evolution; epidermis; replacement; units; fate; beta
AB Recent studies using the isolation of a subpopulation of tumour cells followed by their transplantation into immunodeficient mice provide evidence that certain tumours(1,2), including squamous skin tumours(3-5), contain cells with high clonogenic potential that have been referred to as cancer stem cells (CSCs). Until now, CSC properties have only been investigated by transplantation assays, and their existence in unperturbed tumour growth is unproven. Here we make use of clonal analysis of squamous skin tumours using genetic lineage tracing to unravel the mode of tumour growth in vivo in its native environment. To this end, we used a genetic labelling strategy that allows individual tumour cells to be marked and traced over time at different stages of tumour progression. Surprisingly, we found that the majority of labelled tumour cells in benign papilloma have only limited proliferative potential, whereas a fraction has the capacity to persist long term, giving rise to progeny that occupy a significant part of the tumour. As well as confirming the presence of two distinct proliferative cell compartments within the papilloma, mirroring the composition, hierarchy and fate behaviour of normal tissue, quantitative analysis of clonal fate data indicates that the more persistent population has stem-cell-like characteristics and cycles twice per day, whereas the second represents a slower cycling transient population that gives rise to terminally differentiated tumour cells. Such behaviour is shown to be consistent with double-labelling experiments and detailed clonal fate characteristics. By contrast, measurements of clone size and proliferative potential in invasive squamous cell carcinoma show a different pattern of behaviour, consistent with geometric expansion of a single CSC population with limited potential for terminal differentiation. This study presents the first experimental evidence for the existence of CSCs during unperturbed solid tumour growth.
C1 [Simons, Benjamin D.] Univ Cambridge, Cavendish Lab, Dept Phys, Cambridge CB3 0HE, England.
   [Driessens, Gregory; Beck, Benjamin; Caauwe, Amelie; Blanpain, Cedric] Univ Libre Brussels, IRIBHM, B-1070 Brussels, Belgium.
   [Simons, Benjamin D.] Univ Cambridge, Wellcome Trust Canc Res UK Gurdon Inst, Cambridge CB2 1QN, England.
   [Blanpain, Cedric] WELBIO, B-1070 Brussels, Belgium.
C3 University of Cambridge; Universite Libre de Bruxelles; University of Cambridge; WELBIO
RP Simons, BD (corresponding author), Univ Cambridge, Cavendish Lab, Dept Phys, JJ Thomson Ave, Cambridge CB3 0HE, England.
EM bds10@cam.ac.uk; Cedric.Blanpain@ulb.ac.be
FU Brussels Region; FNRS; program d'excellence CIBLES of the Wallonia Region; Fondation Contre le Cancer; ULB foundation; fond Gaston Ithier; European Research Council (ERC); EMBO; Engineering and Physical Sciences Research Council [EP/F032773/1] Funding Source: researchfish; EPSRC [EP/F032773/1] Funding Source: UKRI
NR 26
TC 576
Z9 680
U1 0
U2 157
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD AUG 23
PY 2012
VL 488
IS 7412
BP 527
EP +
DI 10.1038/nature11344
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 992FS
UT WOS:000307761600040
PM 22854777
DA 2026-03-09
ER

PT J
AU Waitukaitis, SR
   Jaeger, HM
AF Waitukaitis, Scott R.
   Jaeger, Heinrich M.
TI Impact-activated solidification of dense suspensions via dynamic jamming fronts
SO NATURE
LA English
DT Article
ID supercooled liquids; colloidal dispersions; shear; dilatancy; spheres
AB Although liquids typically flow around intruding objects, a counterintuitive phenomenon occurs in dense suspensions of micrometre-sized particles: they become liquid-like when perturbed lightly, but harden when driven strongly(1-5). Rheological experiments have investigated how such thickening arises under shear, and linked it to hydrodynamic interactions(1,3) or granular dilation(2,4). However, neither of these mechanisms alone can explain the ability of suspensions to generate very large, positive normal stresses under impact. To illustrate the phenomenon, such stresses can be large enough to allow a person to run across a suspension without sinking, and far exceed the upper limit observed under shear or extension(2,4,6,7). Here we show that these stresses originate from an impact-generated solidification front that transforms an initially compressible particle matrix into a rapidly growing jammed region, ultimately leading to extraordinary amounts of momentum absorption. Using high-speed videography, embedded force sensing and X-ray imaging, we capture the detailed dynamics of this process as it decelerates a metal rod hitting a suspension of cornflour (cornstarch) in water. We develop a model for the dynamic solidification and its effect on the surrounding suspension that reproduces the observed behaviour quantitatively. Our findings suggest that prior interpretations of the impact resistance as dominated by shear thickening need to be revisited.
C1 [Waitukaitis, Scott R.; Jaeger, Heinrich M.] Univ Chicago, James Franck Inst, Chicago, IL 60637 USA.
   [Waitukaitis, Scott R.; Jaeger, Heinrich M.] Univ Chicago, Dept Phys, Chicago, IL 60637 USA.
C3 University of Chicago; University of Chicago
RP Waitukaitis, SR (corresponding author), Univ Chicago, James Franck Inst, 5640 S Ellis Ave, Chicago, IL 60637 USA.
EM swaitukaitis@uchicago.edu
FU NSF through MRSEC programme [DMR-0820054]; US Army Research Office [W911NF-12-1-0182]; Millikan fellowship; Division Of Materials Research; Direct For Mathematical & Physical Scien [0820054] Funding Source: National Science Foundation
NR 30
TC 263
Z9 305
U1 5
U2 243
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUL 12
PY 2012
VL 487
IS 7406
BP 205
EP 209
DI 10.1038/nature11187
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 972LP
UT WOS:000306278900033
PM 22785316
DA 2026-03-09
ER

PT J
AU Aynajian, P
   Neto, EHD
   Gyenis, A
   Baumbach, RE
   Thompson, JD
   Fisk, Z
   Bauer, ED
   Yazdani, A
AF Aynajian, Pegor
   da Silva Neto, Eduardo H.
   Gyenis, Andras
   Baumbach, Ryan E.
   Thompson, J. D.
   Fisk, Zachary
   Bauer, Eric D.
   Yazdani, Ali
TI Visualizing heavy fermions emerging in a quantum critical Kondo lattice
SO NATURE
LA English
DT Article
ID hidden order; transitions; cerhin5; cecoin5
AB In solids containing elements with f orbitals, the interaction between f-electron spins and those of itinerant electrons leads to the development of low-energy fermionic excitations with a heavy effective mass. These excitations are fundamental to the appearance of unconventional superconductivity and non-Fermi-liquid behaviour observed in actinide- and lanthanide-based compounds. Here we use spectroscopic mapping with the scanning tunnelling microscope to detect the emergence of heavy excitations with lowering of temperature in a prototypical family of cerium-based heavy-fermion compounds. Wedemonstrate the sensitivity of the tunnelling process to the compositenature of these heavy quasiparticles, which arises from quantum entanglement of itinerant conduction and f electrons. Scattering and interference of the composite quasiparticles is used to resolve their energy-momentum structure and to extract their mass enhancement, which develops with decreasing temperature. The lifetime of the emergent heavy quasiparticles reveals signatures of enhanced scattering and their spectral lineshape shows evidence of energy-temperature scaling. These findings demonstrate that proximity to a quantum critical point results in critical damping of the emergent heavy excitation of our Kondo lattice system.
C1 [Aynajian, Pegor; da Silva Neto, Eduardo H.; Gyenis, Andras; Yazdani, Ali] Princeton Univ, Joseph Henry Labs, Princeton, NJ 08544 USA.
   [Aynajian, Pegor; da Silva Neto, Eduardo H.; Gyenis, Andras; Yazdani, Ali] Princeton Univ, Dept Phys, Princeton, NJ 08544 USA.
   [Baumbach, Ryan E.; Thompson, J. D.; Bauer, Eric D.] Los Alamos Natl Lab, Los Alamos, NM 87545 USA.
   [Fisk, Zachary] Univ Calif Irvine, Dept Phys & Astron, Irvine, CA 92697 USA.
C3 Princeton University; Princeton University; United States Department of Energy (DOE); Los Alamos National Laboratory; University of California System; University of California Irvine
RP Yazdani, A (corresponding author), Princeton Univ, Joseph Henry Labs, Princeton, NJ 08544 USA.
EM yazdani@princeton.edu
FU DOE Office of Basic Energy Sciences [DE-FG02-07ER46419]; Princeton Center for Complex Materials [NSF-DMR1104612, NSF-MRSEC, DMR-0819860]; W.M. Keck foundation; Eric and Linda Schmidt Transformative fund at Princeton; Princeton Center for Complex Materials; NSF-MRSEC; US Department of Energy, Office of Basic Energy Sciences, Division of Materials Science and Engineering;  [NSF-DMR-0801253]; Direct For Mathematical & Physical Scien; Division Of Materials Research [1104612, 0801253] Funding Source: National Science Foundation
NR 50
TC 183
Z9 218
U1 4
U2 194
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 14
PY 2012
VL 486
IS 7402
BP 201
EP 206
DI 10.1038/nature11204
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 957UH
UT WOS:000305189000024
PM 22699608
DA 2026-03-09
ER

PT J
AU Higgins, SI
   Scheiter, S
AF Higgins, Steven I.
   Scheiter, Simon
TI Atmospheric CO2 forces abrupt vegetation shifts locally, but not globally
SO NATURE
LA English
DT Article
ID african savanna; climate-change; forest; variability; resilience; grasslands; mechanism; dieback; trees; cycle
AB It is possible that anthropogenic climate change will drive the Earth system into a qualitatively different state(1). Although different types of uncertainty limit our capacity to assess this risk(2), Earth system scientists are particularly concerned about tipping elements, large-scale components of the Earth system that can be switched into qualitatively different states by small perturbations. Despite growing evidence that tipping elements exist in the climate system(1,3), whether large-scale vegetation systems can tip into alternative states is poorly understood(4). Here we show that tropical grassland, savanna and forest ecosystems, areas large enough to have powerful impacts on the Earth system, are likely to shift to alternative states. Specifically, we show that increasing atmospheric CO2 concentration will force transitions to vegetation states characterized by higher biomass and/or woody-plant dominance. The timing of these critical transitions varies as a result of between-site variance in the rate of temperature increase, as well as a dependence on stochastic variation in fire severity and rainfall. We further show that the locations of bistable vegetation zones (zones where alternative vegetation states can exist) will shift as climate changes. We conclude that even though large-scale directional regime shifts in terrestrial ecosystems are likely, asynchrony in the timing of these shifts may serve to dampen, but not nullify, the shock that these changes may represent to the Earth system.
C1 [Higgins, Steven I.] Goethe Univ Frankfurt, Inst Phys Geog, Altenhoferallee 1, D-60438 Frankfurt, Germany.
   [Scheiter, Simon] Senckenberg Gesell Nat Forsch, Biodivers & Climate Res Ctr BiK F, D-60325 Frankfurt, Germany.
C3 Goethe University Frankfurt; Senckenberg Biodiversitat & Klima- Forschungszentrum (BiK-F); Leibniz Association; Senckenberg Gesellschaft fur Naturforschung (SGN)
RP Higgins, SI (corresponding author), Goethe Univ Frankfurt, Inst Phys Geog, Altenhoferallee 1, D-60438 Frankfurt, Germany.
EM higgins@em.uni-frankfurt.de
FU Deutsche Forschungsgemeinschaft; Hesse's Landes-Offensive zur Entwicklung Wissenschaftlich-okonomischer Exzellenz (LOEWE) programme
NR 30
TC 304
Z9 340
U1 2
U2 228
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 9
PY 2012
VL 488
IS 7410
BP 209
EP 212
DI 10.1038/nature11238
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 985LE
UT WOS:000307267000033
PM 22763447
DA 2026-03-09
ER

PT J
AU Morens, DM
   Subbarao, K
   Taubenberger, JK
AF Morens, David M.
   Subbarao, Kanta
   Taubenberger, Jeffery K.
TI Engineering H5N1 avian influenza viruses to study human adaptation
SO NATURE
LA English
DT Article
ID a virus; receptor specificity; mouse model; virulence determinants; swine influenza; cleavage site; transmission; hemagglutinin; ferrets; replication
AB Two studies of H5N1 avian influenza viruses that had been genetically engineered to render them transmissible between ferrets have proved highly controversial. Divergent opinions exist about the importance of these studies of influenza transmission and about potential 'dual use' research implications. No consensus has developed yet about how to balance these concerns. After not recommending immediate full publication of earlier, less complete versions of the studies, the United States National Science Advisory Board for Biosecurity subsequently recommended full publication of more complete manuscripts; however, controversy about this and similar research remains.
C1 [Morens, David M.; Subbarao, Kanta; Taubenberger, Jeffery K.] NIAID, NIH, Bethesda, MD 20892 USA.
C3 National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID)
RP Morens, DM (corresponding author), NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM dm270q@nih.gov
FU National Institutes of Health; National Institute of Allergy and Infectious Diseases; National Institute of Allergy and Infectious Diseases [ZIAAI000986] Funding Source: NIH RePORTER
NR 101
TC 46
Z9 52
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 JUN 21
PY 2012
VL 486
IS 7403
BP 335
EP 340
DI 10.1038/nature11170
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 961LV
UT WOS:000305466800031
PM 22722191
DA 2026-03-09
ER

PT J
AU Benedito, R
   Rocha, SF
   Woeste, M
   Zamykal, M
   Radtke, F
   Casanovas, O
   Duarte, A
   Pytowski, B
   Adams, RH
AF Benedito, Rui
   Rocha, Susana F.
   Woeste, Marina
   Zamykal, Martin
   Radtke, Freddy
   Casanovas, Oriol
   Duarte, Antonio
   Pytowski, Bronislaw
   Adams, Ralf H.
TI Notch-dependent VEGFR3 upregulation allows angiogenesis without VEGF-VEGFR2 signalling
SO NATURE
LA English
DT Article
ID tip cell-formation; dll4; activation; growth; bevacizumab; pathways; inhibit; ligand; mouse; d114
AB Developing tissues and growing tumours produce vascular endothelial growth factors (VEGFs), leading to the activation of the corresponding receptors in endothelial cells. The resultant angiogenic expansion of the local vasculature can promote physiological and pathological growth processes(1). Previous work has uncovered that the VEGF and Notch pathways are tightly linked. Signalling triggered by VEGF-A (also known as VEGF) has been shown to induce expression of the Notch ligand DLL4 in angiogenic vessels and, most prominently, in the tip of endothelial sprouts(2,3). DLL4 activates Notch in adjacent cells, which suppresses the expression of VEGF receptors and thereby restrains endothelial sprouting and proliferation(2,4-6). Here we show, by using inducible loss-of-function genetics in combination with inhibitors in vivo, that DLL4 protein expression in retinal tip cells is only weakly modulated by VEGFR2 signalling. Surprisingly, Notch inhibition also had no significant impact on VEGFR2 expression and induced deregulated endothelial sprouting and proliferation even in the absence of VEGFR2, which is the most important VEGF-A receptor and is considered to be indispensable for these processes. By contrast, VEGFR3, the main receptor for VEGF-C, was strongly modulated by Notch. VEGFR3 kinase-activity inhibitors but not ligand-blocking antibodies suppressed the sprouting of endothelial cells that had low Notch signalling activity. Our results establish that VEGFR2 and VEGFR3 are regulated in a highly differential manner by Notch. We propose that successful anti-angiogenic targeting of these receptors and their ligands will strongly depend on the status of endothelial Notch signalling.
C1 [Benedito, Rui; Rocha, Susana F.; Woeste, Marina; Zamykal, Martin; Adams, Ralf H.] Max Planck Inst Mol Biomed, Dept Tissue Morphogenesis, D-48149 Munster, Germany.
   [Benedito, Rui; Rocha, Susana F.; Woeste, Marina; Zamykal, Martin; Adams, Ralf H.] Univ Munster, Fac Med, D-48149 Munster, Germany.
   [Radtke, Freddy] Ecole Polytech Fed Lausanne, Swiss Inst Expt Canc Res ISREC, CH-1015 Lausanne, Switzerland.
   [Casanovas, Oriol] IDIBELL, Catalan Inst Oncol, Translat Res Lab, Lhospitalet De Llobregat 08907, Spain.
   [Duarte, Antonio] Univ Tecn Lisboa, Fac Vet Med, Interdisciplinary Ctr Res Anim Hlth CIISA, P-1300474 Lisbon, Portugal.
   [Pytowski, Bronislaw] ImClone Syst, New York, NY 10014 USA.
C3 Max Planck Society; University of Munster; Swiss Institute Experimental Cancer Research; Swiss Federal Institutes of Technology Domain; Ecole Polytechnique Federale de Lausanne; Institut d'Investigacio Biomedica de Bellvitge (IDIBELL); Institut Catala d'Oncologia; Universidade de Lisboa; Eli Lilly; Imclone Systems Inc
RP Adams, RH (corresponding author), Max Planck Inst Mol Biomed, Dept Tissue Morphogenesis, D-48149 Munster, Germany.
EM rui.benedito@mpi-muenster.mpg.de; ralf.adams@mpi-muenster.mpg.de
FU Max Planck Society; University of Munster; German Research Foundation [SFB 629, SPP 1190]
NR 36
TC 294
Z9 353
U1 0
U2 97
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 5
PY 2012
VL 484
IS 7392
BP 110
EP +
DI 10.1038/nature10908
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 919QN
UT WOS:000302343400044
PM 22426001
DA 2026-03-09
ER

PT J
AU Thurman, RE
   Rynes, E
   Humbert, R
   Vierstra, J
   Maurano, MT
   Haugen, E
   Sheffield, NC
   Stergachis, AB
   Wang, H
   Vernot, B
   Garg, K
   John, S
   Sandstrom, R
   Bates, D
   Boatman, L
   Canfield, TK
   Diegel, M
   Dunn, D
   Ebersol, AK
   Frum, T
   Giste, E
   Johnson, AK
   Johnson, EM
   Kutyavin, T
   Lajoie, B
   Lee, BK
   Lee, K
   London, D
   Lotakis, D
   Neph, S
   Neri, F
   Nguyen, ED
   Qu, HZ
   Reynolds, AP
   Roach, V
   Safi, A
   Sanchez, ME
   Sanyal, A
   Shafer, A
   Simon, JM
   Song, LY
   Vong, S
   Weaver, M
   Yan, YQ
   Zhang, ZC
   Zhang, ZZ
   Lenhard, B
   Tewari, M
   Dorschner, MO
   Hansen, RS
   Navas, PA
   Stamatoyannopoulos, G
   Iyer, VR
   Lieb, JD
   Sunyaev, SR
   Akey, JM
   Sabo, PJ
   Kaul, R
   Furey, TS
   Dekker, J
   Crawford, GE
   Stamatoyannopoulos, JA
AF Thurman, Robert E.
   Rynes, Eric
   Humbert, Richard
   Vierstra, Jeff
   Maurano, Matthew T.
   Haugen, Eric
   Sheffield, Nathan C.
   Stergachis, Andrew B.
   Wang, Hao
   Vernot, Benjamin
   Garg, Kavita
   John, Sam
   Sandstrom, Richard
   Bates, Daniel
   Boatman, Lisa
   Canfield, Theresa K.
   Diegel, Morgan
   Dunn, Douglas
   Ebersol, Abigail K.
   Frum, Tristan
   Giste, Erika
   Johnson, Audra K.
   Johnson, Ericka M.
   Kutyavin, Tanya
   Lajoie, Bryan
   Lee, Bum-Kyu
   Lee, Kristen
   London, Darin
   Lotakis, Dimitra
   Neph, Shane
   Neri, Fidencio
   Nguyen, Eric D.
   Qu, Hongzhu
   Reynolds, Alex P.
   Roach, Vaughn
   Safi, Alexias
   Sanchez, Minerva E.
   Sanyal, Amartya
   Shafer, Anthony
   Simon, Jeremy M.
   Song, Lingyun
   Vong, Shinny
   Weaver, Molly
   Yan, Yongqi
   Zhang, Zhancheng
   Zhang, Zhuzhu
   Lenhard, Boris
   Tewari, Muneesh
   Dorschner, Michael O.
   Hansen, R. Scott
   Navas, Patrick A.
   Stamatoyannopoulos, George
   Iyer, Vishwanath R.
   Lieb, Jason D.
   Sunyaev, Shamil R.
   Akey, Joshua M.
   Sabo, Peter J.
   Kaul, Rajinder
   Furey, Terrence S.
   Dekker, Job
   Crawford, Gregory E.
   Stamatoyannopoulos, John A.
TI The accessible chromatin landscape of the human genome
SO NATURE
LA English
DT Article
ID locus-control region; beta-globin locus; transcription; binding; distinct; protein; nf-e2
AB DNase I hypersensitive sites (DHSs) are markers of regulatory DNA and have underpinned the discovery of all classes of cis-regulatory elements including enhancers, promoters, insulators, silencers and locus control regions. Here we present the first extensive map of human DHSs identified through genome-wide profiling in 125 diverse cell and tissue types. We identify similar to 2.9 million DHSs that encompass virtually all known experimentally validated cis-regulatory sequences and expose a vast trove of novel elements, most with highly cell-selective regulation. Annotating these elements using ENCODE data reveals novel relationships between chromatin accessibility, transcription, DNA methylation and regulatory factor occupancy patterns. We connect similar to 580,000 distal DHSs with their target promoters, revealing systematic pairing of different classes of distal DHSs and specific promoter types. Patterning of chromatin accessibility at many regulatory regions is organized with dozens to hundreds of co-activated elements, and the transcellular DNase I sensitivity pattern at a given region can predict cell-type-specific functional behaviours. The DHS landscape shows signatures of recent functional evolutionary constraint. However, the DHS compartment in pluripotent and immortalized cells exhibits higher mutation rates than that in highly differentiated cells, exposing an unexpected link between chromatin accessibility, proliferative potential and patterns of human variation.
C1 [Thurman, Robert E.; Rynes, Eric; Humbert, Richard; Vierstra, Jeff; Maurano, Matthew T.; Haugen, Eric; Stergachis, Andrew B.; Wang, Hao; Vernot, Benjamin; John, Sam; Sandstrom, Richard; Bates, Daniel; Canfield, Theresa K.; Diegel, Morgan; Dunn, Douglas; Giste, Erika; Johnson, Audra K.; Kutyavin, Tanya; Lee, Kristen; Neph, Shane; Neri, Fidencio; Qu, Hongzhu; Reynolds, Alex P.; Roach, Vaughn; Shafer, Anthony; Vong, Shinny; Weaver, Molly; Akey, Joshua M.; Sabo, Peter J.; Stamatoyannopoulos, John A.] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA.
   [Sheffield, Nathan C.; London, Darin; Safi, Alexias; Song, Lingyun; Crawford, Gregory E.] Duke Univ, Inst Genome Sci & Policy, Durham, NC 27708 USA.
   [Garg, Kavita; Tewari, Muneesh] Fred Hutchinson Canc Res Ctr, Div Human Biol, Seattle, WA 98109 USA.
   [Boatman, Lisa; Ebersol, Abigail K.; Frum, Tristan; Johnson, Ericka M.; Lotakis, Dimitra; Nguyen, Eric D.; Sanchez, Minerva E.; Yan, Yongqi; Hansen, R. Scott; Navas, Patrick A.; Stamatoyannopoulos, George; Kaul, Rajinder] Univ Washington, Dept Med, Div Med Genet, Seattle, WA 98195 USA.
   [Lajoie, Bryan; Sanyal, Amartya; Dekker, Job] Univ Massachusetts, Program Syst Biol, Sch Med, Worcester, MA 01605 USA.
   [Lee, Bum-Kyu; Iyer, Vishwanath R.] Univ Texas Austin, Inst Cellular & Mol Biol, Austin, TX 78712 USA.
   [Qu, Hongzhu] Chinese Acad Sci, Lab Dis Genom & Individualized Med, Beijing Inst Genom, Beijing 100029, Peoples R China.
   [Simon, Jeremy M.; Zhang, Zhancheng; Zhang, Zhuzhu; Lieb, Jason D.; Furey, Terrence S.] Univ N Carolina, Dept Biol, Chapel Hill, NC 27599 USA.
   [Lenhard, Boris] Univ Bergen, Dept Biol, N-5008 Bergen, Norway.
   [Lenhard, Boris] Univ Bergen, Bergen Ctr Computat Sci, N-5008 Bergen, Norway.
   [Dorschner, Michael O.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA.
   [Sunyaev, Shamil R.] Brigham & Womens Hosp, Dept Med, Div Genet, Boston, MA 02115 USA.
   [Sunyaev, Shamil R.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
   [Stamatoyannopoulos, John A.] Univ Washington, Dept Med, Div Oncol, Seattle, WA 98195 USA.
C3 University of Washington; University of Washington Seattle; Duke University; Fred Hutchinson Cancer Center; University of Washington; University of Washington Seattle; University of Massachusetts System; University of Massachusetts Worcester; University of Texas System; University of Texas Austin; Chinese Academy of Sciences; Beijing Institute of Genomics, CAS; University of North Carolina; University of North Carolina Chapel Hill; University of Bergen; University of Bergen; University of Washington; University of Washington Seattle; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard University; Harvard Medical School; University of Washington; University of Washington Seattle
RP Stamatoyannopoulos, JA (corresponding author), Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA.
EM jstam@uw.edu
FU National Institutes of Health [HG004592, HG004563, GM076036, R01MH084676]; National Science Foundation Graduate Research Fellowship [DGE-0718124]; National Science Foundation; Research Council of Norway; caBIG In Silico Center of Excellence, NCI/NIH [HHSN261200800001E]; National Cancer Institute [P30CA016086] Funding Source: NIH RePORTER; National Human Genome Research Institute [R01HG003143] Funding Source: NIH RePORTER; Medical Research Council [MC_UP_1102/1] Funding Source: researchfish; MRC [MC_UP_1102/1] Funding Source: UKRI
NR 32
TC 1999
Z9 2532
U1 0
U2 235
PU NATURE PUBLISHING 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 6
PY 2012
VL 489
IS 7414
BP 75
EP 82
DI 10.1038/nature11232
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 999WW
UT WOS:000308347000040
PM 22955617
DA 2026-03-09
ER

PT J
AU Zhang, L
   Ding, XJ
   Cui, J
   Xu, H
   Chen, J
   Gong, YN
   Hu, LY
   Zhou, Y
   Ge, JN
   Lu, QH
   Liu, LP
   Chen, S
   Shao, F
AF Zhang, Li
   Ding, Xiaojun
   Cui, Jixin
   Xu, Hao
   Chen, Jing
   Gong, Yi-Nan
   Hu, Liyan
   Zhou, Yan
   Ge, Jianning
   Lu, Qiuhe
   Liu, Liping
   Chen, She
   Shao, Feng
TI Cysteine methylation disrupts ubiquitin-chain sensing in NF-κB activation
SO NATURE
LA English
DT Article
ID escherichia-coli ada; polyubiquitin chains; effector family; binding; protein; tab3; pathway; complex; domain; zinc
AB NF-kappa B is crucial for innate immune defence against microbial infection(1,2). Inhibition of NF-kappa B signalling has been observed with various bacterial infections(3,4). The NF-kappa B pathway critically requires multiple ubiquitin-chain signals of different natures(5,6). The question of whether ubiquitin-chain signalling and its specificity in NF-kappa B activation are regulated during infection, and how this regulation takes place, has not been explored. Here we show that human TAB2 and TAB3, ubiquitin-chain sensory proteins involved in NF-kappa B signalling, are directly inactivated by enteropathogenic Escherichia coli NleE, a conserved bacterial type-III-secreted effector responsible for blocking host NF-kappa B signalling. NleE harboured an unprecedented S-adenosyl-L-methionine-dependent methyltransferase activity that specifically modified a zinc-coordinating cysteine in the Npl4 zinc finger ( NZF) domains in TAB2 and TAB3. Cysteine-methylated TAB2-NZF and TAB3-NZF ( truncated proteins only comprising the NZF domain) lost the zinc ion as well as the ubiquitin-chain binding activity. Ectopically expressed or type-III-secretion-system-delivered NleE methylated TAB2 and TAB3 in host cells and diminished their ubiquitin-chain binding activity. Replacement of the NZF domain of TAB3 with the NleE methylation-insensitive Npl4 NZF domain resulted in NleE-resistant NF-kappa B activation. Given the prevalence of zinc-finger motifs and activation of cysteine thiol by zinc binding, methylation of zinc-finger cysteine might regulate other eukaryotic pathways in addition to NF-kappa B signalling.
C1 [Zhang, Li; Ding, Xiaojun; Cui, Jixin; Xu, Hao; Chen, Jing; Gong, Yi-Nan; Hu, Liyan; Zhou, Yan; Ge, Jianning; Lu, Qiuhe; Liu, Liping; Chen, She; Shao, Feng] Natl Inst Biol Sci, Beijing 102206, Peoples R China.
   [Zhang, Li] Chinese Acad Med Sci, Grad Program, Beijing 100730, Peoples R China.
   [Zhang, Li] Peking Union Med Coll, Beijing 100730, Peoples R China.
C3 National Institute of Biological Sciences, Beijing; Chinese Academy of Medical Sciences - Peking Union Medical College; Chinese Academy of Medical Sciences - Peking Union Medical College; Peking Union Medical College
RP Shao, F (corresponding author), Natl Inst Biol Sci, Beijing 102206, Peoples R China.
EM shaofeng@nibs.ac.cn
FU National Basic Research Program of China (973 Programs) [2010CB835400, 2012CB518700]
NR 35
TC 167
Z9 202
U1 0
U2 63
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JAN 12
PY 2012
VL 481
IS 7380
BP 204
EP +
DI 10.1038/nature10690
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 874TO
UT WOS:000298981200040
PM 22158122
DA 2026-03-09
ER

PT J
AU Devkota, S
   Wang, YW
   Musch, MW
   Leone, V
   Fehlner-Peach, H
   Nadimpalli, A
   Antonopoulos, DA
   Jabri, B
   Chang, EB
AF Devkota, Suzanne
   Wang, Yunwei
   Musch, Mark W.
   Leone, Vanessa
   Fehlner-Peach, Hannah
   Nadimpalli, Anuradha
   Antonopoulos, Dionysios A.
   Jabri, Bana
   Chang, Eugene B.
TI Dietary-fat-induced taurocholic acid promotes pathobiont expansion and colitis in Il10-/- mice
SO NATURE
LA English
DT Article
ID sulfate-reducing bacteria; conjugated bile-acids; bilophila-wadsworthia; hydrogen-sulfide; healthy; microbiota; specimens; diseases; culture; liver
AB The composite human microbiome of Western populations has probably changed over the past century, brought on by new environmental triggers that often have a negative impact on human health(1). Here we show that consumption of a diet high in saturated (milk-derived) fat, but not polyunsaturated (safflower oil) fat, changes the conditions for microbial assemblage and promotes the expansion of a low-abundance, sulphite-reducing pathobiont, Bilophila wadsworthia(2). This was associated with a pro-inflammatory T helper type 1 (T(H)1) immune response and increased incidence of colitis in genetically susceptible Il10(-/-), but not wild-type mice. These effects are mediated by milk-derived-fat-promoted taurine conjugation of hepatic bile acids, which increases the availability of organic sulphur used by sulphite-reducing microorganisms like B. wadsworthia. When mice were fed a low-fat diet supplemented with taurocholic acid, but not with glycocholic acid, for example, a bloom of B. wadsworthia and development of colitis were observed in Il10(-/-) mice. Together these data show that dietary fats, by promoting changes in host bile acid composition, can markedly alter conditions for gut microbial assemblage, resulting in dysbiosis that can perturb immune homeostasis. The data provide a plausible mechanistic basis by which Western-type diets high in certain saturated fats might increase the prevalence of complex immune-mediated diseases like inflammatory bowel disease in genetically susceptible hosts.
C1 [Devkota, Suzanne; Wang, Yunwei; Musch, Mark W.; Leone, Vanessa; Fehlner-Peach, Hannah; Nadimpalli, Anuradha; Jabri, Bana; Chang, Eugene B.] Univ Chicago, Dept Med, Knapp Ctr Biomed Discovery, Gastroenterol Sect, Chicago, IL 60637 USA.
   [Antonopoulos, Dionysios A.] Argonne Natl Lab, Inst Genom & Syst Biol, Argonne, IL 60439 USA.
C3 University of Chicago; United States Department of Energy (DOE); Argonne National Laboratory
RP Chang, EB (corresponding author), Univ Chicago, Dept Med, Knapp Ctr Biomed Discovery, Gastroenterol Sect, 900 E 57th St, Chicago, IL 60637 USA.
EM echang@medicine.bsd.uchicago.edu
FU National Center for Research Resources; NIDDK of the National Institutes of Health; NIGMS of the National Institutes of Health; NCCAM of the National Institutes of Health [DK-42086, DK47722, UH3DK083993, F31AT006073]; Gastrointestinal Research Foundation; Crohns and Colitis Foundation of America; Peter and Carol Goldman Family Research Fund; Harry and Leona Helmsley Trust Foundation (SHARE); National Institute of Diabetes and Digestive and Kidney Diseases [T32DK007074, P30DK042086] Funding Source: NIH RePORTER
NR 26
TC 1499
Z9 1734
U1 9
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 JUL 5
PY 2012
VL 487
IS 7405
BP 104
EP +
DI 10.1038/nature11225
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 968LM
UT WOS:000305982900059
PM 22722865
DA 2026-03-09
ER

PT J
AU Reipurth, B
   Mikkola, S
AF Reipurth, Bo
   Mikkola, Seppo
TI Formation of the widest binary stars from dynamical unfolding of triple systems
SO NATURE
LA English
DT Article
ID proper motion; tertiary companions; hipparcos stars; evolution; catalog; cluster; disk
AB The formation of very wide binary systems(1-3), such as the a Centauri system with Proxima (also known as a Centauri C) separated from a Centauri (which itself is a close binaryA/B) by 15,000 astronomical units(4) (1 AU is the distance from Earth to the Sun), challenges current theories of star formation, because their separation can exceed the typical size of a collapsing cloud core. Various hypotheses have been proposed to overcome this problem, including the suggestion that ultrawide binaries result from the dissolution of a star cluster-when a cluster star gravitationally captures another, distant, cluster star(5-7). Recent observations have shown that very wide binaries are frequently members of triple systems(8,9) and that close binaries often have a distant third companion(10-12). Here we report N-body simulations of the dynamical evolution of newborn triple systems still embedded in their nascent cloud cores that match observations of very wide systems(13-15). We find that although the triple systems are born very compact-and therefore initially are more protected against disruption by passing stars(16,17)-they can develop extreme hierarchical architectures on timescales of millions of years as one component is dynamically scattered into a very distant orbit. The energy of ejection comes from shrinking the orbits of the other two stars, often making them look from a distance like a single star. Such loosely bound triple systems will therefore appear to be very wide binaries.
C1 [Reipurth, Bo] Univ Hawaii Manoa, Inst Astron, Hilo, HI 96720 USA.
   [Mikkola, Seppo] Univ Turku, Tuorla Observ, FI-21500 Piikkio, Finland.
C3 University of Hawaii System; University of Hawaii Manoa; University of Turku
RP Reipurth, B (corresponding author), Univ Hawaii Manoa, Inst Astron, 640 N Aohoku Pl, Hilo, HI 96720 USA.
EM reipurth@ifa.hawaii.edu
FU National Aeronautics and Space Administration through the NASA Astrobiology Institute through the Office of Space Science [NNA09DA77A]
NR 30
TC 167
Z9 183
U1 0
U2 9
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 13
PY 2012
VL 492
IS 7428
BP 221
EP 224
DI 10.1038/nature11662
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 053GM
UT WOS:000312259300035
PM 23222523
DA 2026-03-09
ER

PT J
AU Ortiz, JL
   Sicardy, B
   Braga-Ribas, F
   Alvarez-Candal, A
   Lellouch, E
   Duffard, R
   Pinilla-Alonso, N
   Ivanov, VD
   Littlefair, SP
   Camargo, JIB
   Assafin, M
   Unda-Sanzana, E
   Jehin, E
   Morales, N
   Tancredi, G
   Gil-Hutton, R
   De la Cueva, I
   Colque, JP
   Neto, DND
   Manfroid, J
   Thirouin, A
   Gutierrez, PJ
   Lecacheux, J
   Gillon, M
   Maury, A
   Colas, F
   Licandro, J
   Mueller, T
   Jacques, C
   Weaver, D
   Milone, A
   Salvo, R
   Bruzzone, S
   Organero, F
   Behrend, R
   Roland, S
   Vieira-Martins, R
   Widemann, T
   Roques, F
   Santos-Sanz, P
   Hestroffer, D
   Dhillon, VS
   Marsh, TR
   Harlingten, C
   Bagatin, AC
   Alonso, ML
   Ortiz, M
   Colazo, C
   Lima, HJF
   Oliveira, AS
   Kerber, LO
   Smiljanic, R
   Pimentel, E
   Giacchini, B
   Cacella, P
   Emilio, M
AF Ortiz, J. L.
   Sicardy, B.
   Braga-Ribas, F.
   Alvarez-Candal, A.
   Lellouch, E.
   Duffard, R.
   Pinilla-Alonso, N.
   Ivanov, V. D.
   Littlefair, S. P.
   Camargo, J. I. B.
   Assafin, M.
   Unda-Sanzana, E.
   Jehin, E.
   Morales, N.
   Tancredi, G.
   Gil-Hutton, R.
   De la Cueva, I.
   Colque, J. P.
   Da Silva Neto, D. N.
   Manfroid, J.
   Thirouin, A.
   Gutierrez, P. J.
   Lecacheux, J.
   Gillon, M.
   Maury, A.
   Colas, F.
   Licandro, J.
   Mueller, T.
   Jacques, C.
   Weaver, D.
   Milone, A.
   Salvo, R.
   Bruzzone, S.
   Organero, F.
   Behrend, R.
   Roland, S.
   Vieira-Martins, R.
   Widemann, T.
   Roques, F.
   Santos-Sanz, P.
   Hestroffer, D.
   Dhillon, V. S.
   Marsh, T. R.
   Harlingten, C.
   Campo Bagatin, A.
   Alonso, M. L.
   Ortiz, M.
   Colazo, C.
   Lima, H. J. F.
   Oliveira, A. S.
   Kerber, L. O.
   Smiljanic, R.
   Pimentel, E.
   Giacchini, B.
   Cacella, P.
   Emilio, M.
TI Albedo and atmospheric constraints of dwarf planet Makemake from a stellar occultation
SO NATURE
LA English
DT Article
ID trans-neptunian objects; photometric-observations; pluto; size; ice; variability; surface; eris
AB Pluto and Eris are icy dwarf planets with nearly identical sizes, comparable densities and similar surface compositions as revealed by spectroscopic studies(1,2). Pluto possesses an atmosphere whereas Eris does not; the difference probably arises from their differing distances from the Sun, and explains their different albedos(3). Makemake is another icy dwarf planet with a spectrum similar to Eris and Pluto(4), and is currently at a distance to the Sun intermediate between the two. Although Makemake's size (1,420 +/- 60 km) and albedo are roughly known(5,6), there has been no constraint on its density and there were expectations that it could have a Pluto-like atmosphere(4,7,8). Here we report the results from a stellar occultation by Makemake on 2011 April 23. Our preferred solution that fits the occultation chords corresponds to a body with projected axes of 1,430 +/- 9 km (1 sigma) and 1,502 +/- 45 km, implying a V-band geometric albedo p(V) = 0.77 +/- 0.03. This albedo is larger than that of Pluto, but smaller than that of Eris. The disappearances and reappearances of the star were abrupt, showing that Makemake has no global Pluto-like atmosphere at an upper limit of 4-12 nano-bar (1 sigma) for the surface pressure, although a localized atmosphere is possible. A density of 1.7 +/- 0.3 g cm(-3) is inferred from the data.
C1 [Ortiz, J. L.; Alvarez-Candal, A.; Duffard, R.; Pinilla-Alonso, N.; Morales, N.; Thirouin, A.; Gutierrez, P. J.; Santos-Sanz, P.] CSIC, Inst Astrofis Andalucia, E-18080 Granada, Spain.
   [Sicardy, B.; Braga-Ribas, F.; Lellouch, E.; Lecacheux, J.; Widemann, T.; Roques, F.; Santos-Sanz, P.] Univ Paris Diderot, Univ Paris 06, CNRS, Observ Paris,LESIA, F-92195 Meudon, France.
   [Sicardy, B.] Univ Paris 06, F-75252 Paris 5, France.
   [Sicardy, B.] Inst Univ France, F-75005 Paris, France.
   [Braga-Ribas, F.; Camargo, J. I. B.; Da Silva Neto, D. N.; Vieira-Martins, R.] Observ Nacl MCTI, BR-20921400 Rio De Janeiro, Brazil.
   [Alvarez-Candal, A.; Ivanov, V. D.] European So Observ, Santiago 19, Chile.
   [Pinilla-Alonso, N.] SETI Inst, Mountain View, CA 94043 USA.
   [Littlefair, S. P.; Dhillon, V. S.] Univ Sheffield, Dept Phys & Astron, Sheffield S3 7RH, S Yorkshire, England.
   [Assafin, M.; Vieira-Martins, R.] Univ Fed Rio de Janeiro, Observ Valongo, BR-20080090 Rio De Janeiro, Brazil.
   [Unda-Sanzana, E.; Colque, J. P.] Univ Antofagasta, Fac Ciencias Basicas, Unidad Astron, Antofagasta, Chile.
   [Jehin, E.; Manfroid, J.; Gillon, M.] Univ Liege, Inst Astrophys, B-4000 Liege, Belgium.
   [Tancredi, G.; Salvo, R.; Bruzzone, S.; Roland, S.] Observ Astron Los Molinos DICYT MEC, Montevideo 12400, Uruguay.
   [Gil-Hutton, R.] Complejo Astron El Leoncito CASLEO, San Juan, Argentina.
   [Gil-Hutton, R.] San Juan Natl Univ, San Juan, Argentina.
   [De la Cueva, I.] Astroimagen, Ibiza 07800, Spain.
   [Maury, A.] San Pedro Atacama Celestial Explorat, San Pedro De Atacama, Chile.
   [Colas, F.; Vieira-Martins, R.; Hestroffer, D.] Univ Lille 1, UPMC, Observ Paris, CNRS,IMCCE, F-75014 Paris, France.
   [Licandro, J.] Inst Astrofis Canarias, Tenerife 38250, Spain.
   [Mueller, T.] Max Planck Inst Extraterr Phys, D-85748 Garching, Germany.
   [Jacques, C.; Pimentel, E.; Giacchini, B.] Observ CEAMIG REA, BR-31545120 Belo Horizonte, MG, Brazil.
   [Weaver, D.] Univ Fortaleza, Observ Astron Christus, Fortaleza, Ceara, Brazil.
   [Milone, A.] Inst Nacl Pesquisas Espaciais MCTI, Div Astrofis, BR-12227010 Sao Jose Dos Campos, SP, Brazil.
   [Organero, F.] Observ Astron La Hita, Toledo 45840, Spain.
   [Behrend, R.] Observ Geneva, CH-1290 Sauverny, Switzerland.
   [Marsh, T. R.] Univ Warwick, Dept Phys, Coventry CV4 7AL, W Midlands, England.
   [Harlingten, C.] Caisey Harlingten Observ, Erpingham NR11 7QX, Norfolk, England.
   [Campo Bagatin, A.] Univ Alcala de Henares, Dept Fis Ingn Sistemas & Teoria Senal, Alicante 03080, Spain.
   [Campo Bagatin, A.] Univ Alcala de Henares, Inst Fis Aplicada Ciencias & Tecnol, Alicante 03080, Spain.
   [Alonso, M. L.] Katholieke Univ Leuven, Inst Sterrenkunde, B-3001 Heverlee, Belgium.
   [Ortiz, M.] Pontificia Univ Catolica Chile, Santiago 7820436, Chile.
   [Colazo, C.] Observ Astron Gato Gris, Cordoba, Argentina.
   [Lima, H. J. F.; Oliveira, A. S.] Univ Vale Paraiba, IP&D, BR-12244000 Sao Jose Dos Campos, Brazil.
   [Kerber, L. O.] Univ Estadual Santa Cruz, Dept Ciencias Exatas & Tecnol, Lab Astrofis Teor & Observ, Santa Cruz, RJ, Brazil.
   [Smiljanic, R.] European So Observ, D-85748 Garching, Germany.
   [Cacella, P.] Rede Astron Observ, BR-71745501 Brasilia, DF, Brazil.
   [Emilio, M.] Univ Estadual Ponta Grossa, OA DEGEO, BR-84030900 Ponta Grossa, Brazil.
C3 Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Instituto de Astrofisica de Andalucia (IAA); Sorbonne Universite; Centre National de la Recherche Scientifique (CNRS); Universite Paris Cite; Universite PSL; Observatoire de Paris; Sorbonne Universite; Institut Universitaire de France; European Southern Observatory; SETI Institute; University of Sheffield; Universidade Federal do Rio de Janeiro; Universidad de Antofagasta; University of Liege; Universidad Nacional de San Juan; Centre National de la Recherche Scientifique (CNRS); Universite de Lille; Universite PSL; Observatoire de Paris; Sorbonne Universite; Instituto de Astrofisica de Canarias; Max Planck Society; Universidade Fortaleza; University of Geneva; University of Warwick; Universidad de Alcala; Universidad de Alcala; KU Leuven; Pontificia Universidad Catolica de Chile; Universidade do Vale do Paraiba; Universidade Estadual de Santa Cruz; European Southern Observatory; Universidade Estadual de Ponta Grossa
RP Ortiz, JL (corresponding author), CSIC, Inst Astrofis Andalucia, Apartado 3004, E-18080 Granada, Spain.
EM ortiz@iaa.es
FU European Southern Observatory Telescopes at the La Silla and Paranal Observatories under programme [287C-5013]; European Regional Development Fund (FEDER); French National Research Agency (ANR); Institut Universitaire de France; Chilean National Commission for Scientific and Technical Research (Gemini-CONICYT funds); North Catholic University of Chile Vicerectorate of Research and Technology Development (UCN-VRIDT); Belgian Fund for Scientific Research (FRS-FNRS); Brazilian National Council for the Development of Science and Technology (CNPq); Foundation for Research Support of the State of Rio de Janeiro (FAPERJ); Centre National de la Recherche Scientifique (CNRS); Argentinian National Scientific and Technical Research Council (CONICET); French-Brazilian Doctoral College Coordination of Improvement of Graduated Personnel programme (CDFB/CAPES); Marie Curie Actions of the European Commission (FP7-COFUND); ULTRACAM from the UK Science and Technology Facilities Council; Spanish Ministry of Economics and Competitiveness; Science and Technology Facilities Council [ST/K002783/1, ST/G003092/1, ST/H008500/1, ST/I001719/1, ST/J001589/1] Funding Source: researchfish; STFC [ST/H008500/1, ST/J001589/1, ST/K002783/1, ST/G003092/1, ST/I001719/1] Funding Source: UKRI
NR 27
TC 98
Z9 103
U1 0
U2 36
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 22
PY 2012
VL 491
IS 7425
BP 566
EP 569
DI 10.1038/nature11597
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 040RE
UT WOS:000311339800045
PM 23172214
DA 2026-03-09
ER

PT J
AU Yu, YC
   He, SJ
   Chen, S
   Fu, YH
   Brown, KN
   Yao, XH
   Ma, J
   Gao, KP
   Sosinsky, GE
   Huang, K
   Shi, SH
AF Yu, Yong-Chun
   He, Shuijin
   Chen, She
   Fu, Yinghui
   Brown, Keith N.
   Yao, Xing-Hua
   Ma, Jian
   Gao, Kate P.
   Sosinsky, Gina E.
   Huang, Kun
   Shi, Song-Hai
TI Preferential electrical coupling regulates neocortical lineage-dependent microcircuit assembly
SO NATURE
LA English
DT Article
ID inhibitory neurons; circuit formation; mammalian brain; synapses; junction; cells; connexin; mouse; mechanisms; networks
AB Radial glial cells are the primary neural progenitor cells in the developing neocortex(1). Consecutive asymmetric divisions of individual radial glial progenitor cells produce a number of sister excitatory neurons that migrate along the elongated radial glial fibre, resulting in the formation of ontogenetic columns(2-4). Moreover, sister excitatory neurons in ontogenetic columns preferentially develop specific chemical synapses with each other rather than with nearby non-siblings(5). Although these findings provide crucial insight into the emergence of functional columns in the neocortex, little is known about the basis of this lineage-dependent assembly of excitatory neuron microcircuits at single-cell resolution. Here we show that transient electrical coupling between radially aligned sister excitatory neurons regulates the subsequent formation of specific chemical synapses in the neocortex. Multiple-electrode whole-cell recordings showed that sister excitatory neurons preferentially form strong electrical coupling with each other rather than with adjacent non-sister excitatory neurons during early postnatal stages. This preferential coupling allows selective electrical communication between sister excitatory neurons, promoting their action potential generation and synchronous firing. Interestingly, although this electrical communication largely disappears before the appearance of chemical synapses, blockade of the electrical communication impairs the subsequent formation of specific chemical synapses between sister excitatory neurons in ontogenetic columns. These results suggest a strong link between lineage-dependent transient electrical coupling and the assembly of precise excitatory neuron microcircuits in the neocortex.
C1 [Yu, Yong-Chun; Fu, Yinghui; Yao, Xing-Hua; Ma, Jian] Fudan Univ, Inst Brain Sci, Inst Neurobiol, Shanghai 200032, Peoples R China.
   [Yu, Yong-Chun; Fu, Yinghui; Yao, Xing-Hua; Ma, Jian] Fudan Univ, State Key Lab Med Neurobiol, Shanghai 200032, Peoples R China.
   [He, Shuijin; Chen, She; Brown, Keith N.; Gao, Kate P.; Shi, Song-Hai] Mem Sloan Kettering Canc Ctr, Dev Biol Program, New York, NY 10065 USA.
   [Brown, Keith N.; Gao, Kate P.; Shi, Song-Hai] Weill Cornell Med Coll, Grad Program Neurosci, New York, NY 10065 USA.
   [Sosinsky, Gina E.] Univ Calif San Diego, Natl Ctr Microscopy & Imaging Res, La Jolla, CA 92093 USA.
   [Sosinsky, Gina E.] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA.
   [Huang, Kun] Ohio State Univ, Comprehens Canc Ctr Biomed Informat Shared Resour, Dept Biomed Informat, Columbus, OH 43210 USA.
C3 Fudan University; Fudan University; Memorial Sloan Kettering Cancer Center; Cornell University; Weill Cornell Medicine; University of California System; University of California San Diego; University of California System; University of California San Diego; University System of Ohio; Ohio State University
RP Yu, YC (corresponding author), Fudan Univ, Inst Brain Sci, Inst Neurobiol, 138 Yixueyuan Rd, Shanghai 200032, Peoples R China.
EM ycyu@fudan.edu.cn; hes@mskcc.org; shis@mskcc.org
FU Ministry of Science and Technology of China [2012CB966300]; Natural Science Foundation of China [31121061, 31070947]; Shanghai Science and Technology Committee [10PJ1400700]; Foundation of the Ministry of Education of China [20100071120061]; National Institutes of Health [R01DA024681, R21NS072483, R21MH083624, R01GM065947]; McKnight Foundation; March of Dimes Foundation
NR 33
TC 184
Z9 216
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 JUN 7
PY 2012
VL 486
IS 7401
BP 113
EP U139
DI 10.1038/nature10958
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 953GD
UT WOS:000304854000038
PM 22678291
DA 2026-03-09
ER

PT J
AU Garaycoechea, JI
   Crossan, GP
   Langevin, F
   Daly, M
   Arends, MJ
   Patel, KJ
AF Garaycoechea, Juan I.
   Crossan, Gerry P.
   Langevin, Frederic
   Daly, Maria
   Arends, Mark J.
   Patel, Ketan J.
TI Genotoxic consequences of endogenous aldehydes on mouse haematopoietic stem cell function
SO NATURE
LA English
DT Article
ID fanconi-anemia; dehydrogenase-activity; progenitor cells; dna-repair; marrow-cells; mice; transplantation; suppression; pathway; assays
AB Haematopoietic stem cells (HSCs) regenerate blood cells throughout the lifespan of an organism. With age, the functional quality of HSCs declines, partly owing to the accumulation of damaged DNA(1-3). However, the factors that damage DNA and the protective mechanisms that operate in these cells are poorly understood. We have recently shown that the Fanconi anaemia DNA-repair pathway counteracts the genotoxic effects of reactive aldehydes(4,5). Mice with combined inactivation of aldehyde catabolism (through Aldh2 knockout) and the Fanconi anaemia DNA-repair pathway (Fancd2 knockout) display developmental defects, a predisposition to leukaemia, and are susceptible to the toxic effects of ethanol-an exogenous source of acetaldehyde(4). Here we report that aged Aldh2(-/-) Fancd2(-/-) mutant mice that do not develop leukaemia spontaneously develop aplastic anaemia, with the concomitant accumulation of damaged DNA within the haematopoietic stem and progenitor cell (HSPC) pool. Unexpectedly, we find that only HSPCs, and not more mature blood precursors, require Aldh2 for protection against acetaldehyde toxicity. Additionally, the aldehyde-oxidizing activity of HSPCs, as measured by Aldefluor stain, is due to Aldh2 and correlates with this protection. Finally, there is more than a 600-fold reduction in the HSC pool of mice deficient in both Fanconi anaemia pathway-mediated DNA repair and acetaldehyde detoxification. Therefore, the emergence of bone marrow failure in Fanconi anaemia is probably due to aldehyde-mediated genotoxicity restricted to the HSPC pool. These findings identify a new link between endogenous reactive metabolites and DNA damage in HSCs, and define the protective mechanisms that counteract this threat.
C1 [Garaycoechea, Juan I.; Crossan, Gerry P.; Langevin, Frederic; Daly, Maria; Patel, Ketan J.] MRC, Mol Biol Lab, Cambridge CB2 0QH, England.
   [Arends, Mark J.] Univ Cambridge, Addenbrookes Hosp, Dept Pathol, Cambridge CB2 2QQ, England.
   [Patel, Ketan J.] Univ Cambridge, Addenbrookes Hosp, Dept Med, Cambridge CB2 0QQ, England.
C3 MRC Laboratory Molecular Biology; Cambridge University Hospitals NHS Foundation Trust; Addenbrooke's Hospital; University of Cambridge; Cambridge University Hospitals NHS Foundation Trust; Addenbrooke's Hospital; University of Cambridge
RP Patel, KJ (corresponding author), MRC, Mol Biol Lab, Hills Rd, Cambridge CB2 0QH, England.
EM kjp@mrc-lmb.cam.ac.uk
FU CRUK; Homerton College, Cambridge; Milstein Fund; Darwin Trust of Edinburgh; March of Dimes Foundation; Cancer Research UK [13647] Funding Source: researchfish; Medical Research Council [MC_U105178811] Funding Source: researchfish; MRC [MC_U105178811] Funding Source: UKRI
NR 34
TC 313
Z9 367
U1 0
U2 75
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD SEP 27
PY 2012
VL 489
IS 7417
BP 571
EP +
DI 10.1038/nature11368
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 046RG
UT WOS:000311781500005
PM 22922648
DA 2026-03-09
ER

PT J
AU Duprat, C
   Protière, S
   Beebe, AY
   Stone, HA
AF Duprat, C.
   Protiere, S.
   Beebe, A. Y.
   Stone, H. A.
TI Wetting of flexible fibre arrays
SO NATURE
LA English
DT Article
AB Fibrous media are functional and versatile materials, as demonstrated by their ubiquity both in natural systems such as feathers(1-4) and adhesive pads(5) and in engineered systems from nanotextured surfaces(6) to textile products(7), where they offer benefits in filtration, insulation, wetting and colouring. The elasticity and high aspect ratios of the fibres allow deformation under capillary forces, which cause mechanical damage(8), matting(5,9) self-assembly(10,11) or colour changes(12), with many industrial and ecological consequences. Attempts to understand these systems have mostly focused on the wetting of rigid fibres(13-17) or on elastocapillary effects in planar geometries(18) and on a fibre brush withdrawn from an infinite bath(19). Here we consider the frequently encountered case of a liquid drop deposited on a flexible fibre array and show that flexibility, fibre geometry and drop volume are the crucial parameters that are necessary to understand the various observations referred to above. We identify the conditions required for a drop to remain compact with minimal spreading or to cause a pair of elastic fibres to coalesce. We find that there is a critical volume of liquid, and, hence, a critical drop size, above which this coalescence does not occur. We also identify a drop size that maximizes liquid capture. For both wetting and deformation of the substrates, we present rules that are deduced from the geometric and material properties of the fibres and the volume of the drop. These ideas are applicable to a wide range of fibrous materials, as we illustrate with examples for feathers, beetle tarsi, sprays and microfabricated systems.
C1 [Duprat, C.; Beebe, A. Y.; Stone, H. A.] Princeton Univ, Dept Mech & Aerosp Engn, Princeton, NJ 08544 USA.
   [Protiere, S.] CNRS, UMR 7190, Inst Jean le Rond dAlembert, F-75005 Paris, France.
   [Protiere, S.] Univ Paris 06, UMR 7190, Inst Jean le Rond dAlembert, F-75005 Paris, France.
C3 Princeton University; Centre National de la Recherche Scientifique (CNRS); CNRS - Institute for Engineering & Systems Sciences (INSIS); Sorbonne Universite; Centre National de la Recherche Scientifique (CNRS); CNRS - Institute for Engineering & Systems Sciences (INSIS); Sorbonne Universite
RP Stone, HA (corresponding author), Princeton Univ, Dept Mech & Aerosp Engn, Princeton, NJ 08544 USA.
EM hastone@princeton.edu
FU Unilever; NFS; Emergence(s) Program of the City of Paris; CNRS; Div Of Chem, Bioeng, Env, & Transp Sys; Directorate For Engineering [1132835] Funding Source: National Science Foundation
NR 23
TC 262
Z9 285
U1 3
U2 387
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 23
PY 2012
VL 482
IS 7386
BP 510
EP 513
DI 10.1038/nature10779
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 898VM
UT WOS:000300770500047
PM 22358841
DA 2026-03-09
ER

PT J
AU Ohsawa, S
   Sato, Y
   Enomoto, M
   Nakamura, M
   Betsumiya, A
   Igaki, T
AF Ohsawa, Shizue
   Sato, Yoshitaka
   Enomoto, Masato
   Nakamura, Mai
   Betsumiya, Aya
   Igaki, Tatsushi
TI Mitochondrial defect drives non-autonomous tumour progression through Hippo signalling in Drosophila
SO NATURE
LA English
DT Article
ID stem-cell proliferation; tissue overgrowth; oxidative stress; pathway; cancer; regeneration; growth; cooperation; invasion; midgut
AB Mitochondrial respiratory function is frequently impaired in human cancers(1-4). However, the mechanisms by which mitochondrial dysfunction contributes to tumour progression remain elusive. Here we show in Drosophila imaginal epithelium that defects in mitochondrial function potently induce tumour progression of surrounding tissue in conjunction with oncogenic Ras. Our data show that Ras activation and mitochondrial dysfunction cooperatively stimulate production of reactive oxygen species, which causes activation of c-Jun amino (N)-terminal kinase (JNK) signalling. JNK cooperates with oncogenic Ras to inactivate the Hippo pathway, leading to upregulation of its targets Unpaired (an interleukin-6 homologue) and Wingless (a Wnt homologue). Mitochondrial dysfunction in Ras-activated cells further cooperates with Ras signalling in neighbouring cells with normal mitochondrial function, causing benign tumours to exhibit metastatic behaviour. Our findings provide a mechanistic basis for interclonal tumour progression driven by mitochondrial dysfunction and oncogenic Ras.
C1 [Ohsawa, Shizue; Sato, Yoshitaka; Enomoto, Masato; Nakamura, Mai; Betsumiya, Aya; Igaki, Tatsushi] Kobe Univ, Grad Sch Med, Div Genet, Chuo Ku, Kobe, Hyogo 6500017, Japan.
   [Igaki, Tatsushi] Japan Sci & Technol Agcy JST, PRESTO, Kawaguchi, Saitama 3320012, Japan.
C3 Kobe University; Japan Science & Technology Agency (JST)
RP Igaki, T (corresponding author), Kobe Univ, Grad Sch Med, Div Genet, Chuo Ku, 7-5-1 Kusunoki Cho, Kobe, Hyogo 6500017, Japan.
EM igaki@med.kobe-u.ac.jp
FU Ministry of Education, Culture, Sports, Science and Technology (MEXT); MEXT; Japan Society for the Promotion of Science for Young Scientists; Japan Science and Technology Agency; G-COE program for Global Center for Education and Research in Integrative Membrane Biology; Fumi Yamamura Memorial Foundation for Female Natural Scientists; Tomizawa Jun-ichi & Keiko Fund of the Molecular Biology Society of Japan for Young Scientists; Takeda Science Foundation; Astellas Foundation for Research on Metabolic Disorders; Kanae Foundation for the Promotion of Medical Science; Senri Life Science Foundation; Human Frontier Science Program Career Development Award; Grants-in-Aid for Scientific Research [23650596] Funding Source: KAKEN
NR 29
TC 167
Z9 181
U1 1
U2 62
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD OCT 25
PY 2012
VL 490
IS 7421
BP 547
EP +
DI 10.1038/nature11452
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 025NK
UT WOS:000310196200044
PM 23023132
DA 2026-03-09
ER

PT J
AU Chalifoux, WA
   Reznik, SK
   Leighton, JL
AF Chalifoux, Wesley A.
   Reznik, Samuel K.
   Leighton, James L.
TI Direct and highly regioselective and enantioselective allylation of β-diketones
SO NATURE
LA English
DT Article
ID asymmetric allylboration; aldehyde crotylation; ketones; rearrangements; acetophenones; conformations; macrolide; silicon
AB The enantioselective allylation of ketones is a problem of fundamental importance in asymmetric reaction design, especially given that only a very small number of methods can generate tertiary carbinols. Despite the vast amount of attention that synthetic chemists have given to this problem(1-8), success has generally been limited to just a few simple ketone types. A method for the selective allylation of functionally complex ketones would greatly increase the utility of ketone allylation methods in the chemical synthesis of important targets. Here we describe the operationally simple, direct, regioselective and enantioselective allylation of beta-diketones. The strong tendency of beta-diketones to act as nucleophilic species was overcome by using their enol form to provide the necessary Bronsted-acid activation. This reaction significantly expands the pool of enantiomerically enriched and functionally complex tertiary carbinols that may be easily accessed. It also overturns more than a century of received wisdom regarding the reactivity of beta-diketones.
C1 [Chalifoux, Wesley A.; Reznik, Samuel K.; Leighton, James L.] Columbia Univ, Dept Chem, New York, NY 10027 USA.
C3 Columbia University
RP Leighton, JL (corresponding author), Columbia Univ, Dept Chem, New York, NY 10027 USA.
EM leighton@chem.columbia.edu
FU National Institute of General Medical Sciences [GM58133]; Natural Sciences and Engineering Research Council of Canada
NR 30
TC 37
Z9 48
U1 0
U2 59
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUL 5
PY 2012
VL 487
IS 7405
BP 86
EP 89
DI 10.1038/nature11189
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 968LM
UT WOS:000305982900055
PM 22763452
DA 2026-03-09
ER

PT J
AU Gregoire, LJ
   Payne, AJ
   Valdes, PJ
AF Gregoire, Lauren J.
   Payne, Antony J.
   Valdes, Paul J.
TI Deglacial rapid sea level rises caused by ice-sheet saddle collapses
SO NATURE
LA English
DT Article
ID meltwater pulse 1a; climate-change; lake agassiz; cold event; model; reconstructions; drainage; trigger; ages
AB The last deglaciation (21 to 7 thousand years ago) was punctuated by several abrupt meltwater pulses, which sometimes caused noticeable climate change(1,2). Around 14 thousand years ago, meltwater pulse 1A (MWP-1A), the largest of these events, produced a sea level rise of 14-18 metres over 350 years(3). Although this enormous surge of water certainly originated from retreating ice sheets, there is no consensus on the geographical source or underlying physical mechanisms governing the rapid sea level rise(4-6). Here we present an ice-sheet modelling simulation in which the separation of the Laurentide and Cordilleran ice sheets in North America produces a meltwater pulse corresponding to MWP-1A. Another meltwater pulse is produced when the Labrador and Baffin ice domes around Hudson Bay separate, which could be associated with the '8,200-year' event, the most pronounced abrupt climate event of the past nine thousand years(7). For both modelled pulses, the saddle between the two ice domes becomes subject to surface melting because of a general surface lowering caused by climate warming. The melting then rapidly accelerates as the saddle between the two domes gets lower, producing nine metres of sea level rise over 500 years. This mechanism of an ice 'saddle collapse' probably explains MWP-1A and the 8,200-year event and sheds light on the consequences of these events on climate.
C1 [Gregoire, Lauren J.; Payne, Antony J.; Valdes, Paul J.] Univ Bristol, Sch Geog Sci, Bristol BS8 1SS, Avon, England.
C3 University of Bristol
RP Gregoire, LJ (corresponding author), Univ Bristol, Sch Geog Sci, Univ Rd, Bristol BS8 1SS, Avon, England.
EM lauren.gregoire@bristol.ac.uk
FU Marie Curie Research Training Network NICE [MRTN-CT-2006-036127]; NERC QUEST [NE/D001846/1]; ORMEN [NE/C509558/1]; NERC [NE/D001846/1] Funding Source: UKRI; Natural Environment Research Council [NE/D001846/1] Funding Source: researchfish; Directorate For Geosciences; Division Of Earth Sciences [1023724] Funding Source: National Science Foundation
NR 43
TC 183
Z9 209
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 JUL 12
PY 2012
VL 487
IS 7406
BP 219
EP U1506
DI 10.1038/nature11257
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 972LP
UT WOS:000306278900036
PM 22785319
DA 2026-03-09
ER

PT J
AU Mansour, AA
   Gafni, O
   Weinberger, L
   Zviran, A
   Ayyash, M
   Rais, Y
   Krupalnik, V
   Zerbib, M
   Amann-Zalcenstein, D
   Maza, I
   Geula, S
   Viukov, S
   Holtzman, L
   Pribluda, A
   Canaani, E
   Horn-Saban, S
   Amit, I
   Novershtern, N
   Hanna, JH
AF Mansour, Abed AlFatah
   Gafni, Ohad
   Weinberger, Leehee
   Zviran, Asaf
   Ayyash, Muneef
   Rais, Yoach
   Krupalnik, Vladislav
   Zerbib, Mirie
   Amann-Zalcenstein, Daniela
   Maza, Itay
   Geula, Shay
   Viukov, Sergey
   Holtzman, Liad
   Pribluda, Ariel
   Canaani, Eli
   Horn-Saban, Shirley
   Amit, Ido
   Novershtern, Noa
   Hanna, Jacob H.
TI The H3K27 demethylase Utx regulates somatic and germ cell epigenetic reprogramming
SO NATURE
LA English
DT Article
ID embryonic stem-cells; pluripotent ground-state; mouse; genome; jmjd3; dynamics; network; nanog; model
AB Induced pluripotent stem cells (iPSCs) can be derived from somatic cells by ectopic expression of different transcription factors, classically Oct4 (also known as Pou5f1), Sox2, Klf4 and Myc (abbreviated as OSKM)(1). This process is accompanied by genome-wide epigenetic changes(2-5), but how these chromatin modifications are biochemically determined requires further investigation. Here we show in mice and humans that the histone H3 methylated Lys 27(H3K27) demethylase Utx(6-9) (also known as Kdm6a) regulates the efficient induction, rather than maintenance, of pluripotency. Murine embryonic stem cells lacking Utx can execute lineage commitment and contribute to adult chimaeric animals; however, somatic cells lacking Utx fail to robustly reprogram back to the ground state of pluripotency. Utx directly partners with OSK reprogramming factors and uses its histone demethylase catalytic activity to facilitate iPSC formation. Genomic analysis indicates that Utx depletion results in aberrant dynamics of H3K27me3 repressive chromatin demethylation in somatic cells undergoing reprogramming. The latter directly hampers the derepression of potent pluripotency promoting gene modules (including Sall1, Sall4 and Utf1), which can cooperatively substitute for exogenous OSK supplementation in iPSC formation. Remarkably, Utx safeguards the timely execution of H3K27me3 demethylation observed in embryonic day 10.5-11 primordial germcells (PGCs)(10), and Utx-deficientPGCs show cell-autonomous aberrant epigenetic reprogramming dynamics during their embryonic maturation in vivo. Subsequently, this disrupts PGC development by embryonic day 12.5, and leads to diminished germline transmission in mouse chimaeras generated from Utx-knockout pluripotent cells. Thus, we identify Utx as a novel mediator with distinct functions during the re-establishment of pluripotency and germ cell development. Furthermore, our findings highlight the principle that molecular regulators mediating loss of repressive chromatin during in vivo germ cell reprogramming can be co-opted during in vitro reprogramming towards ground state pluripotency.
C1 [Mansour, Abed AlFatah; Gafni, Ohad; Weinberger, Leehee; Zviran, Asaf; Rais, Yoach; Krupalnik, Vladislav; Zerbib, Mirie; Maza, Itay; Geula, Shay; Viukov, Sergey; Holtzman, Liad; Pribluda, Ariel; Novershtern, Noa; Hanna, Jacob H.] Weizmann Inst Sci, Dept Mol Genet, IL-76100 Rehovot, Israel.
   [Ayyash, Muneef] Weizmann Inst Sci, Dept Biol Chem, IL-76100 Rehovot, Israel.
   [Amann-Zalcenstein, Daniela; Amit, Ido] Weizmann Inst Sci, Dept Immunol, IL-76100 Rehovot, Israel.
   [Amann-Zalcenstein, Daniela; Horn-Saban, Shirley] Weizmann Inst Sci, Dept Biol Serv, Genom Unit, IL-76100 Rehovot, Israel.
   [Canaani, Eli] Weizmann Inst Sci, Dept Mol Cell Biol, 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 Hanna, JH (corresponding author), Weizmann Inst Sci, Dept Mol Genet, IL-76100 Rehovot, Israel.
EM noa.novershtern@weizmann.ac.il; jacob.hanna@weizmann.ac.il
FU ERC starting investigator grant [StG-2011-281906]; Israel Science Foundation Regular and Bikura research grants; ICRF Foundation; Fritz Thyssen Stiftung; Alon Foundation; E. A. and R. Drake, and the Leona M. and Harry B. Helmsley Charitable Trust; Weizmann Dean fellowship awards
NR 35
TC 295
Z9 345
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 AUG 16
PY 2012
VL 488
IS 7411
BP 409
EP +
DI 10.1038/nature11272
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 988OS
UT WOS:000307501000048
PM 22801502
DA 2026-03-09
ER

PT J
AU Fressin, F
   Torres, G
   Rowe, JF
   Charbonneau, D
   Rogers, LA
   Ballard, S
   Batalha, NM
   Borucki, WJ
   Bryson, ST
   Buchhave, LA
   Ciardi, DR
   Désert, JM
   Dressing, CD
   Fabrycky, DC
   Ford, EB
   Gautier, TN
   Henze, CE
   Holman, MJ
   Howard, A
   Howell, SB
   Jenkins, JM
   Koch, DG
   Latham, DW
   Lissauer, JJ
   Marcy, GW
   Quinn, SN
   Ragozzine, D
   Sasselov, DD
   Seager, S
   Barclay, T
   Mullally, F
   Seader, SE
   Still, M
   Twicken, JD
   Thompson, SE
   Uddin, K
AF Fressin, Francois
   Torres, Guillermo
   Rowe, Jason F.
   Charbonneau, David
   Rogers, Leslie A.
   Ballard, Sarah
   Batalha, Natalie M.
   Borucki, William J.
   Bryson, Stephen T.
   Buchhave, Lars A.
   Ciardi, David R.
   Desert, Jean-Michel
   Dressing, Courtney D.
   Fabrycky, Daniel C.
   Ford, Eric B.
   Gautier, Thomas N., III
   Henze, Christopher E.
   Holman, Matthew J.
   Howard, Andrew
   Howell, Steve B.
   Jenkins, Jon M.
   Koch, David G.
   Latham, David W.
   Lissauer, Jack J.
   Marcy, Geoffrey W.
   Quinn, Samuel N.
   Ragozzine, Darin
   Sasselov, Dimitar D.
   Seager, Sara
   Barclay, Thomas
   Mullally, Fergal
   Seader, Shawn E.
   Still, Martin
   Twicken, Joseph D.
   Thompson, Susan E.
   Uddin, Kamal
TI Two Earth-sized planets orbiting Kepler-20
SO NATURE
LA English
DT Article
ID transiting planet; blend scenarios; multiple system; giant impacts; candidates; validation; exoplanets; companion
AB Since the discovery of the first extrasolar giant planets around Sun-like stars(1,2), evolving observational capabilities have brought us closer to the detection of true Earth analogues. The size of an exoplanet can be determined when it periodically passes in front of (transits) its parent star, causing a decrease in starlight proportional to its radius. The smallest exoplanet hitherto discovered(3) has a radius 1.42 times that of the Earth's radius (R-circle plus), and hence has 2.9 times its volume. Here we report the discovery of two planets, one Earth-sized (1.03 R-circle plus) and the other smaller than the Earth (0.87 R-circle plus), orbiting the star Kepler-20, which is already known to host three other, larger, transiting planets(4). The gravitational pull of the new planets on the parent star is too small to measure with current instrumentation. We apply a statistical method to show that the likelihood of the planetary interpretation of the transit signals is more than three orders of magnitude larger than that of the alternative hypothesis that the signals result from an eclipsing binary star. Theoretical considerations imply that these planets are rocky, with a composition of iron and silicate. The outer planet could have developed a thick water vapour atmosphere.
C1 [Fressin, Francois; Torres, Guillermo; Charbonneau, David; Ballard, Sarah; Desert, Jean-Michel; Dressing, Courtney D.; Holman, Matthew J.; Latham, David W.; Quinn, Samuel N.; Ragozzine, Darin; Sasselov, Dimitar D.] Harvard Smithsonian Ctr Astrophys, Cambridge, MA 02138 USA.
   [Rowe, Jason F.; Borucki, William J.; Bryson, Stephen T.; Henze, Christopher E.; Howell, Steve B.; Koch, David G.; Lissauer, Jack J.; Barclay, Thomas; Still, Martin] NASA, Ames Res Ctr, Moffett Field, CA 94035 USA.
   [Rogers, Leslie A.; Seager, Sara] MIT, Dept Phys, Cambridge, MA 02139 USA.
   [Batalha, Natalie M.] San Jose State Univ, Dept Phys & Astron, San Jose, CA 95192 USA.
   [Buchhave, Lars A.] Univ Copenhagen, Niels Bohr Inst, DK-2100 Copenhagen, Denmark.
   [Buchhave, Lars A.] Univ Copenhagen, Ctr Star & Planet Format, DK-1350 Copenhagen, Denmark.
   [Ciardi, David R.] CALTECH, NASA Exoplanet Sci Inst, Pasadena, CA 91125 USA.
   [Fabrycky, Daniel C.] Univ Calif Santa Cruz, Dept Astron & Astrophys, Santa Cruz, CA 95064 USA.
   [Ford, Eric B.] Univ Florida, Dept Astron, Gainesville, FL 32111 USA.
   [Gautier, Thomas N., III] CALTECH, Jet Prop Lab, Pasadena, CA 91109 USA.
   [Howard, Andrew; Marcy, Geoffrey W.] Univ Calif Berkeley, Dept Astron, Berkeley, CA 94720 USA.
   [Jenkins, Jon M.; Mullally, Fergal; Seader, Shawn E.; Twicken, Joseph D.; Thompson, Susan E.] NASA, Ames Res Ctr, SETI Inst, Moffett Field, CA 94035 USA.
   [Uddin, Kamal] NASA, Ames Res Ctr, Orbital Sci Corp, Moffett Field, CA 94035 USA.
C3 Smithsonian Astrophysical Observatory; Harvard University; Smithsonian Institution; National Aeronautics & Space Administration (NASA); NASA Ames Research Center; Massachusetts Institute of Technology (MIT); California State University System; San Jose State University; University of Copenhagen; Niels Bohr Institute; University of Copenhagen; California Institute of Technology; National Aeronautics & Space Administration (NASA); University of California System; University of California Santa Cruz; State University System of Florida; University of Florida; California Institute of Technology; National Aeronautics & Space Administration (NASA); NASA Jet Propulsion Laboratory (JPL); University of California System; University of California Berkeley; SETI Institute; National Aeronautics & Space Administration (NASA); NASA Ames Research Center; Orbital Sciences Corporation; National Aeronautics & Space Administration (NASA); NASA Ames Research Center
RP Fressin, F (corresponding author), Harvard Smithsonian Ctr Astrophys, 60 Garden St, Cambridge, MA 02138 USA.
EM ffressin@cfa.harvard.edu
FU NASA's Science Mission Directorate
NR 28
TC 126
Z9 143
U1 0
U2 78
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD FEB 9
PY 2012
VL 482
IS 7384
BP 195
EP 198
DI 10.1038/nature10780
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 888HI
UT WOS:000299994100033
PM 22186831
DA 2026-03-09
ER

PT J
AU Johnson, ZL
   Cheong, CG
   Lee, SY
AF Johnson, Zachary Lee
   Cheong, Cheom-Gil
   Lee, Seok-Yong
TI Crystal structure of a concentrative nucleoside transporter from Vibrio cholerae at 2.4 Å
SO NATURE
LA English
DT Article
ID conserved glutamate residues; cnt family; drugs; identification; cotransport; pyrimidine; resistance; homolog; reveals; protein
AB Nucleosides are required for DNA and RNA synthesis, and the nucleoside adenosine has a function in a variety of signalling processes(1,2). Transport of nucleosides across cell membranes provides the major source of nucleosides in many cell types and is also responsible for the termination of adenosine signalling. As a result of their hydrophilic nature, nucleosides require a specialized class of integral membrane proteins, known as nucleoside transporters (NTs), for specific transport across cell membranes. In addition to nucleosides, NTs are important determinants for the transport of nucleoside-derived drugs across cell membranes(3-5). A wide range of nucleoside-derived drugs, including anticancer drugs (such as Ara-C and gemcitabine) and antiviral drugs (such as zidovudine and ribavirin), have been shown to depend, at least in part, on NTs for transport across cell membranes(4,6-13). Concentrative nucleoside transporters, members of the solute carrier transporter superfamily SLC28, use an ion gradient in the active transport of both nucleosides and nucleoside-derived drugs against their chemical gradients. The structural basis for selective ion-coupled nucleoside transport by concentrative nucleoside transporters is unknown. Here we present the crystal structure of a concentrative nucleoside transporter from Vibrio cholerae in complex with uridine at 2.4 angstrom. Our functional data show that, like its human orthologues, the transporter uses a sodium-ion gradient for nucleoside transport. The structure reveals the overall architecture of this class of transporter, unravels the molecular determinants for nucleoside and sodium binding, and provides a framework for understanding the mechanism of nucleoside and nucleoside drug transport across cell membranes.
C1 [Johnson, Zachary Lee; Cheong, Cheom-Gil; Lee, Seok-Yong] Duke Univ, Med Ctr, Dept Biochem, Durham, NC 27710 USA.
   [Johnson, Zachary Lee; Cheong, Cheom-Gil; Lee, Seok-Yong] Duke Univ, Med Ctr, Ion Channel Res Unit, Durham, NC 27710 USA.
C3 Duke University; Duke University
RP Lee, SY (corresponding author), Duke Univ, Med Ctr, Dept Biochem, 2 Genome Court, Durham, NC 27710 USA.
EM sylee@biochem.duke.edu
FU Duke University Medical Center; McKnight Endowment Fund for Neuroscience; Alfred P. Sloan Foundation; Klingenstein Fund; Mallinckrodt foundation; March of Dimes Foundation [5-FY10-473]; National Institutes of Health [1 DP2 OD008380-01]
NR 39
TC 100
Z9 117
U1 0
U2 44
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 22
PY 2012
VL 483
IS 7390
BP 489
EP U150
DI 10.1038/nature10882
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 912CC
UT WOS:000301771200048
PM 22407322
DA 2026-03-09
ER

PT J
AU Sotomayor, M
   Weihofen, WA
   Gaudet, R
   Corey, DP
AF Sotomayor, Marcos
   Weihofen, Wilhelm A.
   Gaudet, Rachelle
   Corey, David P.
TI Structure of a force-conveying cadherin bond essential for inner-ear mechanotransduction
SO NATURE
LA English
DT Article
ID usher-syndrome; hair-cells; molecular-dynamics; sensory transduction; hearing-loss; adhesion; mutations; pcdh15; cdh23; stereocilia
AB Hearing and balance use hair cells in the inner ear to transform mechanical stimuli into electrical signals(1). Mechanical force from sound waves or head movements is conveyed to hair-cell transduction channels by tip links(2,3), fine filaments formed by two atypical cadherins known as protocadherin 15 and cadherin 23 (refs 4, 5). These two proteins are involved in inherited deafness(6-10) and feature long extracellular domains that interact tip-to-tip(5,11) in a Ca2+-dependent manner. However, the molecular architecture of this complex is unknown. Here we combine crystallography, molecular dynamics simulations and binding experiments to characterize the protocadherin 15-cadherin 23 bond. We find a unique cadherin interaction mechanism, in which the two most amino-terminal cadherin repeats (extracellular cadherin repeats 1 and 2) of each protein interact to form an overlapped, antiparallel heterodimer. Simulations predict that this tip-link bond is mechanically strong enough to resist forces in hair cells. In addition, the complex is shown to become unstable in response to Ca2+ removal owing to increased flexure of Ca2+-free cadherin repeats. Finally, we use structures and biochemical measurements to study the molecular mechanisms by which deafness mutations disrupt tip-link function. Overall, our results shed light on the molecular mechanics of hair-cell sensory transduction and on new interaction mechanisms for cadherins, a large protein family implicated in tissue and organ morphogenesis(12,13), neural connectivity(14) and cancer(15).
C1 [Sotomayor, Marcos; Corey, David P.] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA.
   [Sotomayor, Marcos; Corey, David P.] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA.
   [Weihofen, Wilhelm A.; Gaudet, Rachelle] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA.
C3 Harvard University; Harvard Medical School; Howard Hughes Medical Institute; Harvard University; Harvard Medical School; Harvard University
RP Corey, DP (corresponding author), Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA.
EM gaudet@mcb.harvard.edu; dcorey@hms.harvard.edu
FU NIH [R01 DC02281, RC2GM093307, RR-15301]; National Science Foundation through TeraGrid/XSEDE [TRAC MCB080015]; Department of Energy (DOE) [DE-AC02-06CH11357]; DOE [DE-AC02-05CH11231]
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NR 46
TC 128
Z9 164
U1 1
U2 70
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 6
PY 2012
VL 492
IS 7427
BP 128
EP +
DI 10.1038/nature11590
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 048EQ
UT WOS:000311893400059
PM 23135401
DA 2026-03-09
ER

PT J
AU Han, TH
   Helton, JS
   Chu, SY
   Nocera, DG
   Rodriguez-Rivera, JA
   Broholm, C
   Lee, YS
AF Han, Tian-Heng
   Helton, Joel S.
   Chu, Shaoyan
   Nocera, Daniel G.
   Rodriguez-Rivera, Jose A.
   Broholm, Collin
   Lee, Young S.
TI Fractionalized excitations in the spin-liquid state of a kagome-lattice antiferromagnet
SO NATURE
LA English
DT Article
ID valence-bond state
AB The experimental realization of quantum spin liquids is a long-sought goal in physics, as they represent new states of matter. Quantum spin liquids cannot be described by the broken symmetries associated with conventional ground states. In fact, the interacting magnetic moments in these systems do not order, but are highly entangled with one another over long ranges(1). Spin liquids have a prominent role in theories describing high-transition-temperature superconductors(2,3), and the topological properties of these states may have applications in quantum information(4). A key feature of spin liquids is that they support exotic spin excitations carrying fractional quantum numbers. However, detailed measurements of these 'fractionalized excitations' have been lacking. Here we report neutron scattering measurements on single-crystal samples of the spin-1/2 kagome-lattice antiferromagnet ZnCu3(OD)(6)Cl-2 (also called herbertsmithite), which provide striking evidence for this characteristic feature of spin liquids. At low temperatures, we find that the spin excitations form a continuum, in contrast to the conventional spin waves expected in ordered antiferromagnets. The observation of such a continuum is noteworthy because, so far, this signature of fractional spin excitations has been observed only in one-dimensional systems. The results also serve as a hallmark of the quantum spin-liquid state in herbertsmithite.
C1 [Han, Tian-Heng; Lee, Young S.] MIT, Dept Phys, Cambridge, MA 02139 USA.
   [Helton, Joel S.; Rodriguez-Rivera, Jose A.; Broholm, Collin] NIST, NIST Ctr Neutron Res, Gaithersburg, MD 20899 USA.
   [Chu, Shaoyan] MIT, Ctr Mat Sci & Engn, Cambridge, MA 02139 USA.
   [Nocera, Daniel G.] MIT, Dept Chem, Cambridge, MA 02139 USA.
   [Rodriguez-Rivera, Jose A.] Univ Maryland, Dept Mat Sci & Engn, College Pk, MD 20742 USA.
   [Broholm, Collin] Johns Hopkins Univ, Dept Phys & Astron, Baltimore, MD 21218 USA.
   [Broholm, Collin] Johns Hopkins Univ, Inst Quantum Matter, Baltimore, MD 21218 USA.
C3 Massachusetts Institute of Technology (MIT); National Institute of Standards & Technology (NIST) - USA; Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); University System of Maryland; University of Maryland College Park; Johns Hopkins University; Johns Hopkins University
RP Lee, YS (corresponding author), MIT, Dept Phys, Cambridge, MA 02139 USA.
EM tianheng@alum.mit.edu; younglee@mit.edu
FU US Department of Energy (DOE), Office of Science, Office of Basic Energy Sciences [DE-FG02-07ER46134]; US National Science Foundation [DMR-0944772]; DOE, Office of Basic Energy Sciences, Division of Material Sciences and Engineering [DE-FG02-08ER46544]
NR 30
TC 1044
Z9 1154
U1 5
U2 533
PU NATURE PUBLISHING 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 20
PY 2012
VL 492
IS 7429
BP 406
EP 410
DI 10.1038/nature11659
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 056KQ
UT WOS:000312488200051
PM 23257883
DA 2026-03-09
ER

PT J
AU Pieters, CM
   Ammannito, E
   Blewett, DT
   Denevi, BW
   De Sanctis, MC
   Gaffey, MJ
   Le Corre, L
   Li, JY
   Marchi, S
   McCord, TB
   McFadden, LA
   Mittlefehldt, DW
   Nathues, A
   Palmer, E
   Reddy, V
   Raymond, CA
   Russell, CT
AF Pieters, C. M.
   Ammannito, E.
   Blewett, D. T.
   Denevi, B. W.
   De Sanctis, M. C.
   Gaffey, M. J.
   Le Corre, L.
   Li, J. -Y.
   Marchi, S.
   McCord, T. B.
   McFadden, L. A.
   Mittlefehldt, D. W.
   Nathues, A.
   Palmer, E.
   Reddy, V.
   Raymond, C. A.
   Russell, C. T.
TI Distinctive space weathering on Vesta from regolith mixing processes
SO NATURE
LA English
DT Article
ID itokawa dust particles; asteroid 4 vesta; ordinary chondrites; irradiation; morphology; mineralogy; surface; albedo; belt; dawn
AB The surface of the asteroid Vesta has prominent near-infrared absorption bands characteristic of a range of pyroxenes, confirming a direct link to the basaltic howardite-eucrite-diogenite class of meteorites(1,2,3). Processes active in the space environment produce 'space weathering' products that substantially weaken or mask such diagnostic absorption on airless bodies observed elsewhere(4,5), and it has long been a mystery why Vesta's absorption bands are so strong. Analyses of soil samples from both the Moon(6) and the asteroid Itokawa(7) determined that nanophase metallic particles (commonly nanophase iron) accumulate on the rims of regolith grains with time, accounting for an observed optical degradation. These nanophase particles, believed to be related to solar wind and micrometeoroid bombardment processes, leave unique spectroscopic signatures that can be measured remotely(8-10) but require sufficient spatial resolution to discern the geologic context and history of the surface, which has not been achieved for Vesta until now. Here we report that Vesta shows its own form of space weathering, which is quite different from that of other airless bodies visited. No evidence is detected on Vesta for accumulation of lunar-like nanophase iron on regolith particles, even though distinct material exposed at several fresh craters becomes gradually masked and fades into the background as the craters age. Instead, spectroscopic data reveal that on Vesta a locally homogenized upper regolith is generated with time through small-scale mixing of diverse surface components.
C1 [Pieters, C. M.] Brown Univ, Dept Geol Sci, Providence, RI 02912 USA.
   [Ammannito, E.; De Sanctis, M. C.] ARTOV, INAF, Ist Astrofis & Planetol Spaziali, I-00133 Rome, Italy.
   [Blewett, D. T.; Denevi, B. W.] Johns Hopkins Univ, Appl Phys Lab, Laurel, MD 20723 USA.
   [Gaffey, M. J.] Univ N Dakota, Dept Space Studies, Grand Forks, ND 58202 USA.
   [Le Corre, L.; Nathues, A.; Reddy, V.] Max Planck Inst Solar Syst Res, D-37191 Katlenburg Lindau, Germany.
   [Li, J. -Y.] Univ Maryland, Dept Astron, College Pk, MD 20742 USA.
   [Marchi, S.] NASA, Lunar Sci Inst, Boulder, CO 80302 USA.
   [McCord, T. B.] Bear Fight Inst, Winthrop, WA 98862 USA.
   [McFadden, L. A.] NASA, Goddard Space Flight Ctr, Greenbelt, MD 20771 USA.
   [Mittlefehldt, D. W.] NASA, Lyndon B Johnson Space Ctr, Houston, TX 77058 USA.
   [Palmer, E.] Planetary Sci Inst, Tucson, AZ 85719 USA.
   [Raymond, C. A.] CALTECH, Jet Prop Lab, Pasadena, CA 91109 USA.
   [Russell, C. T.] Univ Calif Los Angeles, Los Angeles, CA 90095 USA.
C3 Brown University; Istituto Nazionale Astrofisica (INAF); Johns Hopkins University; Johns Hopkins University Applied Physics Laboratory; University of North Dakota Grand Forks; Max Planck Society; University System of Maryland; University of Maryland College Park; National Aeronautics & Space Administration (NASA); National Aeronautics & Space Administration (NASA); NASA Goddard Space Flight Center; National Aeronautics & Space Administration (NASA); NASA Johnson Space Center; California Institute of Technology; National Aeronautics & Space Administration (NASA); NASA Jet Propulsion Laboratory (JPL); University of California System; University of California Los Angeles
RP Pieters, CM (corresponding author), Brown Univ, Dept Geol Sci, Providence, RI 02912 USA.
EM carle_pieters@brown.edu
FU NASA [NNM05AA86C]; NASA Dawn participating scientist programme
NR 31
TC 127
Z9 143
U1 4
U2 48
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD NOV 1
PY 2012
VL 491
IS 7422
BP 79
EP 82
DI 10.1038/nature11534
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 028PM
UT WOS:000310434500033
PM 23128227
DA 2026-03-09
ER

PT J
AU Petreanu, L
   Gutnisky, DA
   Huber, D
   Xu, NL
   O'Connor, DH
   Tian, L
   Looger, L
   Svoboda, K
AF Petreanu, Leopoldo
   Gutnisky, Diego A.
   Huber, Daniel
   Xu, Ning-long
   O'Connor, Dan H.
   Tian, Lin
   Looger, Loren
   Svoboda, Karel
TI Activity in motor-sensory projections reveals distributed coding in somatosensation
SO NATURE
LA English
DT Article
ID object localization; action-potentials; neural activity; layer-i; cortex; rat; organization; plasticity; circuits; dynamics
AB Cortical-feedback projections to primary sensory areas terminate most heavily in layer 1 (L1) of the neocortex(1,2), where they make synapses with tuft dendrites of pyramidal neurons. L1 input is thought to provide 'contextual' information(3), but the signals transmitted by L1 feedback remain uncharacterized. In the rodent somatosensory system, the spatially diffuse(4) feedback projection from vibrissal motor cortex (vM1) to vibrissal somatosensory cortex (vS1, also known as the barrel cortex) may allow whisker touch to be interpreted in the context of whisker position to compute object location(5,6). When mice palpate objects with their whiskers to localize object features(7,8), whisker touch excites vS1(9) and later vM1 in a somatotopic manner(10-13). Here we use axonal calcium imaging to track activity in vM1 -> vS1 afferents in L1 of the barrel cortex while mice performed whisker-dependent object localization. Spatially intermingled individual axons represent whisker movements, touch and other behavioural features. In a subpopulation of axons, activity depends on object location and persists for seconds after touch. Neurons in the barrel cortex thus have information to integrate movements and touches of multiple whiskers over time, key components of object identification and navigation by active touch.
C1 [Petreanu, Leopoldo; Gutnisky, Diego A.; Huber, Daniel; Xu, Ning-long; O'Connor, Dan H.; Tian, Lin; Looger, Loren; Svoboda, Karel] Howard Hughes Med Inst, Ashburn, VA 20147 USA.
C3 Howard Hughes Medical Institute
RP Svoboda, K (corresponding author), Howard Hughes Med Inst, Janelia Farm Res Campus, Ashburn, VA 20147 USA.
EM svobodak@janelia.hhmi.org
FU Howard Hughes Medical Institute Funding Source: Medline
NR 41
TC 250
Z9 295
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 SEP 13
PY 2012
VL 489
IS 7415
BP 299
EP +
DI 10.1038/nature11321
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 003UC
UT WOS:000308635900043
PM 22922646
DA 2026-03-09
ER

PT J
AU Broz, P
   Ruby, T
   Belhocine, K
   Bouley, DM
   Kayagaki, N
   Dixit, VM
   Monack, DM
AF Broz, Petr
   Ruby, Thomas
   Belhocine, Kamila
   Bouley, Donna M.
   Kayagaki, Nobuhiko
   Dixit, Vishva M.
   Monack, Denise M.
TI Caspase-11 increases susceptibility to Salmonella infection in the absence of caspase-1
SO NATURE
LA English
DT Article
ID inflammasome receptors; host-defense; interleukin-1-beta; activation; typhimurium; flagellin; neutrophils; secretion; adapters; family
AB Inflammasomes are cytosolic multiprotein complexes assembled by intracellular nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) and they initiate innate immune responses to invading pathogens and danger signals by activating caspase-1 (ref. 1). Caspase-1 activation leads to the maturation and release of the pro-inflammatory cytokines interleukin (IL)-1 beta and IL-18, as well as lytic inflammatory cell death known as pyroptosis(2). Recently, a new non-canonical inflammasome was described that activates caspase-11, a pro-inflammatory caspase required for lipopolysaccharide-induced lethality(3). This study also highlighted that previously generated caspase-1 knockout mice lack a functional allele of Casp11 (also known as Casp4), making them functionally Casp1 Casp11 double knockouts(3-6). Previous studies have shown that these mice are more susceptible to infections with microbial pathogens(1), including the bacterial pathogen Salmonella enterica serovar Typhimurium (S. typhimurium)(7,8), but the individual contributions of caspase-1 and caspase-11 to this phenotype are not known. Here we show that non-canonical caspase-11 activation contributes to macrophage death during S. typhimurium infection. Toll-like receptor 4 (TLR4)-dependent and TIR-domaincontaining adaptor-inducing interferon-beta (TRIF)-dependent interferon-beta production is crucial for caspase-11 activation in macrophages, but is only partially required for pro-caspase-11 expression, consistent with the existence of an interferon-inducible activator of caspase-11. Furthermore, Casp1(-/-) mice were significantly more susceptible to infection with S. typhimurium than mice lacking both pro-inflammatory caspases (Casp1(-/-) Casp11(-/-)). This phenotype was accompanied by higher bacterial counts, the formation of extracellular bacterial microcolonies in the infected tissue and a defect in neutrophil-mediated clearance. These results indicate that caspase-11-dependent cell death is detrimental to the host in the absence of caspase-1-mediated innate immunity, resulting in extracellular replication of a facultative intracellular bacterial pathogen.
C1 [Broz, Petr; Ruby, Thomas; Belhocine, Kamila; Monack, Denise M.] Stanford Univ, Dept Microbiol & Immunol, Stanford Sch Med, Stanford, CA 94305 USA.
   [Bouley, Donna M.] Stanford Univ, Dept Comparat Med, Stanford Sch Med, Stanford, CA 94305 USA.
   [Kayagaki, Nobuhiko; Dixit, Vishva M.] Genentech Inc, San Francisco, CA 94080 USA.
C3 Stanford University; Stanford University; Roche Holding; Genentech; Roche Holding USA
RP Monack, DM (corresponding author), Stanford Univ, Dept Microbiol & Immunol, Stanford Sch Med, Stanford, CA 94305 USA.
EM dmonack@stanford.edu
FU National Institute of Allergy and Infectious Diseases (NIAID) [AI095396, AI08972]; Stanford Digestive Disease Center (DDC) pilot grant; Human Frontiers in Science Program (HFSP) [LT000636/2009-L]
NR 23
TC 449
Z9 523
U1 1
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 OCT 11
PY 2012
VL 490
IS 7419
BP 288
EP +
DI 10.1038/nature11419
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 019IY
UT WOS:000309733300055
PM 22895188
DA 2026-03-09
ER

PT J
AU Vinko, SM
   Ciricosta, O
   Cho, BI
   Engelhorn, K
   Chung, HK
   Brown, CRD
   Burian, T
   Chalupsky, J
   Falcone, RW
   Graves, C
   Hájková, V
   Higginbotham, A
   Juha, L
   Krzywinski, J
   Lee, HJ
   Messerschmidt, M
   Murphy, CD
   Ping, Y
   Scherz, A
   Schlotter, W
   Toleikis, S
   Turner, JJ
   Vysin, L
   Wang, T
   Wu, B
   Zastrau, U
   Zhu, D
   Lee, RW
   Heimann, PA
   Nagler, B
   Wark, JS
AF Vinko, S. M.
   Ciricosta, O.
   Cho, B. I.
   Engelhorn, K.
   Chung, H-K
   Brown, C. R. D.
   Burian, T.
   Chalupsky, J.
   Falcone, R. W.
   Graves, C.
   Hajkova, V.
   Higginbotham, A.
   Juha, L.
   Krzywinski, J.
   Lee, H. J.
   Messerschmidt, M.
   Murphy, C. D.
   Ping, Y.
   Scherz, A.
   Schlotter, W.
   Toleikis, S.
   Turner, J. J.
   Vysin, L.
   Wang, T.
   Wu, B.
   Zastrau, U.
   Zhu, D.
   Lee, R. W.
   Heimann, P. A.
   Nagler, B.
   Wark, J. S.
TI Creation and diagnosis of a solid-density plasma with an X-ray free-electron laser
SO NATURE
LA English
DT Article
ID fluorescence yields; target; aluminum; pulses; auger; gain
AB Matter with a high energy density (>10(5) joules per cm(3)) is prevalent throughout the Universe, being present in all types of stars(1) and towards the centre of the giant planets(2,3); it is also relevant for inertial confinement fusion(4). Its thermodynamic and transport properties are challenging to measure, requiring the creation of sufficiently long-lived samples at homogeneous temperatures and densities(5,6). With the advent of the Linac Coherent Light Source (LCLS) X-ray laser(7), high-intensity radiation (>10(17) watts per cm(2), previously the domain of optical lasers) can be produced at X-ray wavelengths. The interaction of single atoms with such intense X-rays has recently been investigated(8). An understanding of the contrasting case of intense X-ray interaction with dense systems is important from a fundamental viewpoint and for applications. Here we report the experimental creation of a solid-density plasma at temperatures in excess of 10(6) kelvin on inertial-confinement time-scales using an X-ray free-electron laser. We discuss the pertinent physics of the intense X-ray-matter interactions, and illustrate the importance of electron-ion collisions. Detailed simulations of the interaction process conducted with a radiative-collisional code show good qualitative agreement with the experimental results. We obtain insights into the evolution of the charge state distribution of the system, the electron density and temperature, and the time-scales of collisional processes. Our results should inform future high-intensity X-ray experiments involving dense samples, such as X-ray diffractive imaging of biological systems, material science investigations, and the study of matter in extreme conditions.
C1 [Vinko, S. M.; Ciricosta, O.; Higginbotham, A.; Murphy, C. D.; Wark, J. S.] Univ Oxford, Dept Phys, Clarendon Lab, Oxford OX1 3PU, England.
   [Cho, B. I.; Engelhorn, K.; Falcone, R. W.; Heimann, P. A.] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Berkeley, CA 94720 USA.
   [Chung, H-K] IAEA, Nucl Data Sect, Atom & Mol Data Unit, A-1400 Vienna, Austria.
   [Brown, C. R. D.] AWE Aldermaston, Dept Plasma Phys, Reading RG7 4PR, Berks, England.
   [Burian, T.; Chalupsky, J.; Hajkova, V.; Juha, L.; Vysin, L.] Inst Phys ASCR, Prague 18221 8, Czech Republic.
   [Falcone, R. W.] Univ Calif Berkeley, Dept Phys, Berkeley, CA 94720 USA.
   [Graves, C.; Krzywinski, J.; Lee, H. J.; Messerschmidt, M.; Scherz, A.; Schlotter, W.; Turner, J. J.; Wang, T.; Wu, B.; Zhu, D.; Lee, R. W.; Nagler, B.] SLAC Natl Accelerator Lab, Menlo Pk, CA 94025 USA.
   [Ping, Y.] Lawrence Livermore Natl Lab, Livermore, CA 94550 USA.
   [Toleikis, S.] Deutsch Elektronensynchrotron DESY, D-22603 Hamburg, Germany.
   [Zastrau, U.] Univ Jena, IOQ, D-07743 Jena, Germany.
C3 University of Oxford; United States Department of Energy (DOE); Lawrence Berkeley National Laboratory; University of California System; University of California Berkeley; International Atomic Energy Agency; Czech Academy of Sciences; Institute of Physics of the Czech Academy of Sciences; University of California System; University of California Berkeley; Stanford University; United States Department of Energy (DOE); SLAC National Accelerator Laboratory; United States Department of Energy (DOE); Lawrence Livermore National Laboratory; Helmholtz Association; Deutsches Elektronen-Synchrotron (DESY); Friedrich Schiller University of Jena
RP Vinko, SM (corresponding author), Univ Oxford, Dept Phys, Clarendon Lab, Parks Rd, Oxford OX1 3PU, England.
EM sam.vinko@physics.ox.ac.uk
FU LCLS; Stanford University through the Stanford Institute for Materials Energy Sciences (SIMES); Lawrence Berkeley National Laboratory (LBNL); University of Hamburg through the BMBF [FSP 301]; Center for Free Electron Laser Science (CFEL); UK EPSRC [EP/F020449/1, EP/H035877/1, EP/G007187/1]; US DOE Basic Energy Science [DE-AC03-76SF00098]; SSAA [DE-FG52-06NA26212]; German Ministry for Education and Research (BMBF) [FSP 301];  [LC510];  [LC528];  [LA08024];  [ME10046];  [P108/11/1312];  [P205/11/0571];  [IAAX00100903];  [KAN300100702]; Engineering and Physical Sciences Research Council [EP/H035877/1, EP/G007187/1, EP/F020449/1] Funding Source: researchfish; EPSRC [EP/H035877/1, EP/F020449/1, EP/G007187/1] Funding Source: UKRI
NR 26
TC 428
Z9 461
U1 1
U2 188
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD FEB 2
PY 2012
VL 482
IS 7383
BP 59
EP U75
DI 10.1038/nature10746
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 884RN
UT WOS:000299726000034
PM 22278059
DA 2026-03-09
ER

PT J
AU Adesnik, H
   Bruns, W
   Taniguchi, H
   Huang, ZJ
   Scanziani, M
AF Adesnik, Hillel
   Bruns, William
   Taniguchi, Hiroki
   Huang, Z. Josh
   Scanziani, Massimo
TI A neural circuit for spatial summation in visual cortex
SO NATURE
LA English
DT Article
ID classical receptive-field; neurons; inhibition; contrast; v1; connections; generation; responses; dynamics; sparse
AB The response of cortical neurons to a sensory stimulus is modulated by the context. In the visual cortex, for example, stimulation of a pyramidal cell's receptive-field surround can attenuate the cell's response to a stimulus in the centre of its receptive field, a phenomenon called surround suppression. Whether cortical circuits contribute to surround suppression or whether the phenomenon is entirely relayed from earlier stages of visual processing is debated. Here we show that, in contrast to pyramidal cells, the response of somatostatin-expressing inhibitory neurons (SOMs) in the superficial layers of the mouse visual cortex increases with stimulation of the receptive-field surround. This difference results from the preferential excitation of SOMs by horizontal cortical axons. By perturbing the activity of SOMs, we show that these neurons contribute to pyramidal cells' surround suppression. These results establish a cortical circuit for surround suppression and attribute a particular function to a genetically defined type of inhibitory neuron.
C1 [Adesnik, Hillel; Bruns, William; Scanziani, Massimo] Univ Calif San Diego, Howard Hughes Med Inst, Ctr Neural Circuits & Behav, Neurobiol Sect, La Jolla, CA 92093 USA.
   [Adesnik, Hillel; Bruns, William; Scanziani, Massimo] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA.
   [Taniguchi, Hiroki; Huang, Z. Josh] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA.
C3 Howard Hughes Medical Institute; University of California System; University of California San Diego; University of California System; University of California San Diego; Cold Spring Harbor Laboratory
RP Scanziani, M (corresponding author), Univ Calif San Diego, Howard Hughes Med Inst, Ctr Neural Circuits & Behav, Neurobiol Sect, La Jolla, CA 92093 USA.
EM massimo@ucsd.edu
FU Helen Hay Whitney Foundation; Howard Hughes Medical Institute (HHMI); Gatsby charitable foundation; US National Institute of Health [NS069010]
NR 40
TC 499
Z9 627
U1 1
U2 101
PU NATURE PUBLISHING 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 11
PY 2012
VL 490
IS 7419
BP 226
EP 231
DI 10.1038/nature11526
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 019IY
UT WOS:000309733300042
PM 23060193
DA 2026-03-09
ER

PT J
AU Bond, RM
   Fariss, CJ
   Jones, JJ
   Kramer, AI
   Marlow, C
   Settle, JE
   Fowler, JH
AF Bond, Robert M.
   Fariss, Christopher J.
   Jones, Jason J.
   Kramer, Adamd. I.
   Marlow, Cameron
   Settle, Jaime E.
   Fowler, James H.
TI A 61-million-person experiment in social influence and political mobilization
SO NATURE
LA English
DT Article
ID voter turnout; network; spread; cooperation; dynamics; behavior; adoption
AB Human behaviour is thought to spread through face-to-face social networks, but it is difficult to identify social influence effects in observational studies(9-13), and it is unknown whether online social networks operate in the same way(14-19). Here we report results from a randomized controlled trial of political mobilization messages delivered to 61 million Facebook users during the 2010 US congressional elections. The results show that the messages directly influenced political self-expression, information seeking and real-world voting behaviour of millions of people. Furthermore, the messages not only influenced the users who received them but also the users' friends, and friends of friends. The effect of social transmission on real-world voting was greater than the direct effect of the messages themselves, and nearly all the transmission occurred between 'close friends' who were more likely to have a face-to-face relationship. These results suggest that strong ties are instrumental for spreading both online and real-world behaviour in human social networks.
C1 [Bond, Robert M.; Fariss, Christopher J.; Settle, Jaime E.; Fowler, James H.] Univ Calif San Diego, Dept Polit Sci, La Jolla, CA 92093 USA.
   [Jones, Jason J.] Univ Calif San Diego, Dept Psychol, La Jolla, CA 92093 USA.
   [Kramer, Adamd. I.; Marlow, Cameron] Facebook Inc, Data Sci, Menlo Pk, CA 94025 USA.
   [Fowler, James H.] Univ Calif San Diego, Div Med Genet, La Jolla, CA 92093 USA.
C3 University of California System; University of California San Diego; University of California System; University of California San Diego; Facebook Inc; University of California System; University of California San Diego
RP Fowler, JH (corresponding author), Univ Calif San Diego, Dept Polit Sci, La Jolla, CA 92093 USA.
EM jhfowler@ucsd.edu
FU James S. McDonnell Foundation; University of Notre Dame; John Templeton Foundation; National Institute of General Medical Sciences [P41GM103504] Funding Source: NIH RePORTER
NR 30
TC 1533
Z9 2032
U1 11
U2 609
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 13
PY 2012
VL 489
IS 7415
BP 295
EP 298
DI 10.1038/nature11421
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 003UC
UT WOS:000308635900042
PM 22972300
DA 2026-03-09
ER

PT J
AU Vaidya, N
   Manapat, ML
   Chen, IA
   Xulvi-Brunet, R
   Hayden, EJ
   Lehman, N
AF Vaidya, Nilesh
   Manapat, Michael L.
   Chen, Irene A.
   Xulvi-Brunet, Ramon
   Hayden, Eric J.
   Lehman, Niles
TI Spontaneous network formation among cooperative RNA replicators
SO NATURE
LA English
DT Article
ID natural self-organization; evolution; ribozyme; origin; hypercycle; principle; life; emergence; selection; systems
AB The origins of life on Earth required the establishment of self-replicating chemical systems capable of maintaining and evolving biological information. In an RNA world, single self-replicating RNAs would have faced the extreme challenge of possessing a mutation rate low enough both to sustain their own information and to compete successfully against molecular parasites with limited evolvability. Thus theoretical analyses suggest that networks of interacting molecules were more likely to develop and sustain life-like behaviour. Here we show that mixtures of RNA fragments that self-assemble into self-replicating ribozymes spontaneously form cooperative catalytic cycles and networks. We find that a specific three-membered network has highly cooperative growth dynamics. When such cooperative networks are competed directly against selfish autocatalytic cycles, the former grow faster, indicating an intrinsic ability of RNA populations to evolve greater complexity through cooperation. We can observe the evolvability of networks through in vitro selection. Our experiments highlight the advantages of cooperative behaviour even at the molecular stages of nascent life.
C1 [Vaidya, Nilesh; Lehman, Niles] Portland State Univ, Dept Chem, Portland, OR 97207 USA.
   [Manapat, Michael L.] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA.
   [Manapat, Michael L.] Harvard Univ, Program Evolutionary Dynam, Cambridge, MA 02138 USA.
   [Chen, Irene A.; Xulvi-Brunet, Ramon] Harvard Univ, FAS Ctr Syst Biol, Cambridge, MA 02138 USA.
   [Hayden, Eric J.] Stanford Univ, Dept Bioengn, Stanford, CA 94305 USA.
C3 Portland State University; Harvard University; Harvard University; Harvard University; Stanford University
RP Lehman, N (corresponding author), Portland State Univ, Dept Chem, POB 751, Portland, OR 97207 USA.
EM niles@pdx.edu
FU NASA [NNX10AR15G]; Center for Life in Extreme Environments at Portland State University; Human Frontier Science Program Organization; Div Of Biological Infrastructure; Direct For Biological Sciences [0963548] Funding Source: National Science Foundation; NASA [125200, NNX10AR15G] Funding Source: Federal RePORTER
NR 32
TC 276
Z9 303
U1 1
U2 137
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD NOV 1
PY 2012
VL 491
IS 7422
BP 72
EP 77
DI 10.1038/nature11549
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 028PM
UT WOS:000310434500032
PM 23075853
DA 2026-03-09
ER

PT J
AU Deary, IJ
   Yang, J
   Davies, G
   Harris, SE
   Tenesa, A
   Liewald, D
   Luciano, M
   Lopez, LM
   Gow, AJ
   Corley, J
   Redmond, P
   Fox, HC
   Rowe, SJ
   Haggarty, P
   McNeill, G
   Goddard, ME
   Porteous, DJ
   Whalley, LJ
   Starr, JM
   Visscher, PM
AF Deary, Ian J.
   Yang, Jian
   Davies, Gail
   Harris, Sarah E.
   Tenesa, Albert
   Liewald, David
   Luciano, Michelle
   Lopez, Lorna M.
   Gow, Alan J.
   Corley, Janie
   Redmond, Paul
   Fox, Helen C.
   Rowe, Suzanne J.
   Haggarty, Paul
   McNeill, Geraldine
   Goddard, Michael E.
   Porteous, David J.
   Whalley, Lawrence J.
   Starr, John M.
   Visscher, Peter M.
TI Genetic contributions to stability and change in intelligence from childhood to old age
SO NATURE
LA English
DT Article
ID common snps explain; later life; cognitive decline; large proportion; human height; heritability; ability; variance; models
AB Understanding the determinants of healthy mental ageing is a priority for society today(1,2). So far, we know that intelligence differences show high stability from childhood to old age(3,4) and there are estimates of the genetic contribution to intelligence at different ages(5,6). However, attempts to discover whether genetic causes contribute to differences in cognitive ageing have been relatively uninformative(7-10). Here we provide an estimate of the genetic and environmental contributions to stability and change in intelligence across most of the human lifetime. We used genome-wide single nucleotide polymorphism (SNP) data from 1,940 unrelated individuals whose intelligence was measured in childhood (age 11 years) and again in old age (age 65, 70 or 79 years)(11,12). We use a statistical method that allows genetic (co)variance to be estimated from SNP data on unrelated individuals(13-17). We estimate that causal genetic variants in linkage disequilibrium with common SNPs account for 0.24 of the variation in cognitive ability change from childhood to old age. Using bivariate analysis, we estimate a genetic correlation between intelligence at age 11 years and in old age of 0.62. These estimates, derived from rarely available data on lifetime cognitive measures, warrant the search for genetic causes of cognitive stability and change.
C1 [Deary, Ian J.; Davies, Gail; Liewald, David; Luciano, Michelle; Lopez, Lorna M.; Gow, Alan J.; Corley, Janie; Redmond, Paul] Univ Edinburgh, Dept Psychol, Edinburgh EH8 9JZ, Midlothian, Scotland.
   [Deary, Ian J.; Davies, Gail; Harris, Sarah E.; Liewald, David; Luciano, Michelle; Lopez, Lorna M.; Gow, Alan J.; Porteous, David J.; Starr, John M.; Visscher, Peter M.] Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh EH8 9JZ, Midlothian, Scotland.
   [Yang, Jian; Visscher, Peter M.] Queensland Inst Med Res, Brisbane, Qld 4006, Australia.
   [Harris, Sarah E.; Tenesa, Albert; Porteous, David J.] Western Gen Hosp, Inst Genet & Mol Med, Med Genet Sect, Mol Med Ctr, Edinburgh EH4 2XU, Midlothian, Scotland.
   [Tenesa, Albert; Rowe, Suzanne J.] Univ Edinburgh, Sch Vet Studies, Roslin Inst, Edinburgh EH25 9RG, Midlothian, Scotland.
   [McNeill, Geraldine; Whalley, Lawrence J.] Inst Appl Hlth Sci, Aberdeen AB25 2ZD, Scotland.
   [Redmond, Paul] Univ Aberdeen, Rowett Inst Nutr & Hlth, Nutr & Epigenet Grp, Aberdeen AB21 9SB, Scotland.
   [Goddard, Michael E.] Australia & Victorian Dept Primary Ind, Bundoora, Vic 3083, Australia.
   [Goddard, Michael E.] Univ Melbourne, Dept Food & Agr Syst, Parkville, Vic 3011, Australia.
   [Starr, John M.] Univ Edinburgh, Alzheimer Scotland Dementia Res Ctr, Edinburgh EH8 9JZ, Midlothian, Scotland.
   [Visscher, Peter M.] Univ Queensland, Diamantina Inst, Princess Alexandra Hosp, Brisbane, Qld 4102, Australia.
   [Visscher, Peter M.] Univ Queensland, Queensland Brain Inst, Brisbane, Qld 4072, Australia.
C3 University of Edinburgh; University of Edinburgh; QIMR Berghofer Medical Research Institute; University of Edinburgh; UK Research & Innovation (UKRI); Biotechnology and Biological Sciences Research Council (BBSRC); Roslin Institute; University of Edinburgh; University of Aberdeen; University of Aberdeen; University of Melbourne; University of Edinburgh; University of Queensland; Princess Alexandra Hospital; University of Queensland
RP Deary, IJ (corresponding author), Univ Edinburgh, Dept Psychol, 7 George Sq, Edinburgh EH8 9JZ, Midlothian, Scotland.
EM i.deary@ed.ac.uk; peter.visscher@uq.edu.au
FU Australian Research Council; National Health and Medical Research Council; BBSRC; EPSRC; ESRC; MRC; Biotechnology and Biological Sciences Research Council [BB/F019394/1] Funding Source: researchfish; Chief Scientist Office [ETM/55, CZB/4/505] Funding Source: researchfish; Medical Research Council [G0701120, G0700704B, G0700704] Funding Source: researchfish; BBSRC [BB/F019394/1] Funding Source: UKRI; MRC [G0700704] Funding Source: UKRI
NR 27
TC 200
Z9 214
U1 1
U2 113
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD FEB 9
PY 2012
VL 482
IS 7384
BP 212
EP 215
DI 10.1038/nature10781
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 888HI
UT WOS:000299994100037
PM 22258510
DA 2026-03-09
ER

PT J
AU Yamaguchi, S
   Hong, K
   Liu, R
   Shen, L
   Inoue, A
   Diep, D
   Zhang, K
   Zhang, Y
AF Yamaguchi, Shinpei
   Hong, Kwonho
   Liu, Rui
   Shen, Li
   Inoue, Azusa
   Diep, Dinh
   Zhang, Kun
   Zhang, Yi
TI Tet1 controls meiosis by regulating meiotic gene expression
SO NATURE
LA English
DT Article
ID primordial germ-cells; dna methylation; epigenetic events; mammalian dna; mouse; mice; 5-carboxylcytosine; 5-methylcytosine; specification; pluripotency
AB Meiosis is a germ-cell-specific cell division process through which haploid gametes are produced for sexual reproduction(1). Before the initiation of meiosis, mouse primordial germ cells undergo a series of epigenetic reprogramming steps(2,3), including the global erasure of DNA methylation at the 5-position of cytosine (5mC) in CpG-rich DNA(4,5). Although several epigenetic regulators, such as Dnmt3l and the histone methyltransferases G9a and Prdm9, have been reported to be crucial for meiosis(6), little is known about how the expression of meiotic genes is regulated and how their expression contributes to normal meiosis. Using a loss-of-function approach in mice, here we show that the 5mC-specific dioxygenase Tet1 has an important role in regulating meiosis in mouse oocytes. Tet1 deficiency significantly reduces female germ-cell numbers and fertility. Univalent chromosomes and unresolved DNA double-strand breaks are also observed in Tet1-deficient oocytes. Tet1 deficiency does not greatly affect the genome-wide demethylation that takes place in primordial germ cells, but leads to defective DNA demethylation and decreased expression of a subset of meiotic genes. Our study thus establishes a function for Tet1 in meiosis and meiotic gene activation in female germ cells.
C1 [Liu, Rui; Diep, Dinh; Zhang, Kun] Univ Calif San Diego, Dept Bioengn, La Jolla, CA 92093 USA.
   [Yamaguchi, Shinpei; Hong, Kwonho; Shen, Li; Inoue, Azusa; Zhang, Yi] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA.
   [Yamaguchi, Shinpei; Hong, Kwonho; Shen, Li; Inoue, Azusa; Zhang, Yi] Harvard Univ, Sch Med, Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA.
   [Yamaguchi, Shinpei; Hong, Kwonho; Shen, Li; Inoue, Azusa; Zhang, Yi] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
   [Zhang, Yi] Harvard Univ, Sch Med, Harvard Stem Cell Inst, Boston, MA 02115 USA.
C3 University of California System; University of California San Diego; Harvard University; Harvard Medical School; Howard Hughes Medical Institute; Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Boston Children's Hospital; Program in Cellular & Molecular Medicine (PCMM); Harvard University; Harvard Medical School; Harvard University; Harvard Medical School
RP Zhang, K (corresponding author), Univ Calif San Diego, Dept Bioengn, La Jolla, CA 92093 USA.
EM kzhang@bioeng.ucsd.edu; yzhang@genetics.med.harvard.edu
FU National Institutes of Health [U01DK089565]; CIRM [BRB3-05083];  [R01GM097253]
NR 29
TC 254
Z9 313
U1 0
U2 84
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD DEC 20
PY 2012
VL 492
IS 7429
BP 443
EP +
DI 10.1038/nature11709
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 056KQ
UT WOS:000312488200059
PM 23151479
DA 2026-03-09
ER

PT J
AU Schaefer, BE
   Pagnotta, A
AF Schaefer, Bradley E.
   Pagnotta, Ashley
TI An absence of ex-companion stars in the type Ia supernova remnant SNR 05092-67.5
SO NATURE
LA English
DT Article
ID large-magellanic-cloud; x-ray phase; light echoes; white-dwarfs; progenitors; binary; identification; galaxy; impact
AB A type Ia supernova is thought to begin with the explosion of a white dwarf star(1). The explosion could be triggered by the merger of two white dwarfs(2,3) (a 'double-degenerate' origin), or by mass transfer from a companion star(4,5) (the 'single-degenerate' path). The identity of the progenitor is still controversial; for example, a recent argument against the single-degenerate origin(6) has been widely rejected(7-11). One way to distinguish between the double-and single-degenerate progenitors is to look at the centre of a known type Ia supernova remnant to see whether any former companion star is present(12,13). A likely ex-companion star for the progenitor of the supernova observed by Tycho Brahe has been identified(14), but that claim is still controversial(15-18). Here we report that the central region of the supernova remnant SNR 0509-67.5 (the site of a type Ia supernova 400650 years ago, based on its light echo(19,20)) in the Large Magellanic Cloud contains no ex-companion star to a visualmagnitude limit of 26.9 (an absolute magnitude of M-V = +8.4) within a region of radius 1.43 arcseconds. (This corresponds to the 3 sigma maximum distance to which a companion could have been 'kicked' by the explosion.) This lack of any ex-companion star to deep limits rules out all published single-degenerate models for this supernova. The only remaining possibility is that the progenitor of this particular type Ia supernova was a double-degenerate system.
C1 [Schaefer, Bradley E.; Pagnotta, Ashley] Louisiana State Univ, Dept Phys & Astron, Baton Rouge, LA 70803 USA.
C3 Louisiana State University System; Louisiana State University
RP Schaefer, BE (corresponding author), Louisiana State Univ, Dept Phys & Astron, Baton Rouge, LA 70803 USA.
EM schaefer@lsu.edu
FU National Science Foundation; Direct For Mathematical & Physical Scien; Division Of Astronomical Sciences [1109420] Funding Source: National Science Foundation
NR 28
TC 231
Z9 267
U1 0
U2 7
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JAN 12
PY 2012
VL 481
IS 7380
BP 164
EP 166
DI 10.1038/nature10692
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 874TO
UT WOS:000298981200030
PM 22237107
DA 2026-03-09
ER

PT J
AU Biankin, AV
   Waddell, N
   Kassahn, KS
   Gingras, MC
   Muthuswamy, LB
   Johns, AL
   Miller, DK
   Wilson, PJ
   Patch, AM
   Wu, JM
   Chang, DK
   Cowley, MJ
   Gardiner, BB
   Song, S
   Harliwong, I
   Idrisoglu, S
   Nourse, C
   Nourbakhsh, E
   Manning, S
   Wani, S
   Gongora, M
   Pajic, M
   Scarlett, CJ
   Gill, AJ
   Pinho, AV
   Rooman, I
   Anderson, M
   Holmes, O
   Leonard, C
   Taylor, D
   Wood, S
   Xu, QY
   Nones, K
   Fink, JL
   Christ, A
   Bruxner, T
   Cloonan, N
   Kolle, G
   Newell, F
   Pinese, M
   Mead, RS
   Humphris, JL
   Kaplan, W
   Jones, MD
   Colvin, EK
   Nagrial, AM
   Humphrey, ES
   Chou, A
   Chin, VT
   Chantrill, LA
   Mawson, A
   Samra, JS
   Kench, JG
   Lovell, JA
   Daly, RJ
   Merrett, ND
   Toon, C
   Epari, K
   Nguyen, NQ
   Barbour, A
   Zeps, N
   Kakkar, N
   Zhao, FM
   Wu, YQ
   Wang, M
   Muzny, DM
   Fisher, WE
   Brunicardi, FC
   Hodges, SE
   Reid, JG
   Drummond, J
   Chang, K
   Han, Y
   Lewis, LR
   Dinh, H
   Buhay, CJ
   Beck, T
   Timms, L
   Sam, M
   Begley, K
   Brown, A
   Pai, D
   Panchal, A
   Buchner, N
   De Borja, R
   Denroche, RE
   Yung, CK
   Serra, S
   Onetto, N
   Mukhopadhyay, D
   Tsao, MS
   Shaw, PA
   Petersen, GM
   Gallinger, S
   Hruban, RH
   Maitra, A
   Iacobuzio-Donahue, CA
   Schulick, RD
   Wolfgang, CL
   Morgan, RA
   Lawlor, RT
   Capelli, P
   Corbo, V
   Scardoni, M
   Tortora, G
   Tempero, MA
   Mann, KM
   Jenkins, NA
   Perez-Mancera, PA
   Adams, DJ
   Largaespada, DA
   Wessels, LFA
   Rust, AG
   Stein, LD
   Tuveson, DA
   Copeland, NG
   Musgrove, EA
   Scarpa, A
   Eshleman, JR
   Hudson, TJ
   Sutherland, RL
   Wheeler, DA
   Pearson, JV
   McPherson, JD
   Gibbs, RA
   Grimmond, SM
AF Biankin, Andrew V.
   Waddell, Nicola
   Kassahn, Karin S.
   Gingras, Marie-Claude
   Muthuswamy, Lakshmi B.
   Johns, Amber L.
   Miller, David K.
   Wilson, Peter J.
   Patch, Ann-Marie
   Wu, Jianmin
   Chang, David K.
   Cowley, Mark J.
   Gardiner, Brooke B.
   Song, Sarah
   Harliwong, Ivon
   Idrisoglu, Senel
   Nourse, Craig
   Nourbakhsh, Ehsan
   Manning, Suzanne
   Wani, Shivangi
   Gongora, Milena
   Pajic, Marina
   Scarlett, Christopher J.
   Gill, Anthony J.
   Pinho, Andreia V.
   Rooman, Ilse
   Anderson, Matthew
   Holmes, Oliver
   Leonard, Conrad
   Taylor, Darrin
   Wood, Scott
   Xu, Qinying
   Nones, Katia
   Fink, J. Lynn
   Christ, Angelika
   Bruxner, Tim
   Cloonan, Nicole
   Kolle, Gabriel
   Newell, Felicity
   Pinese, Mark
   Mead, R. Scott
   Humphris, Jeremy L.
   Kaplan, Warren
   Jones, Marc D.
   Colvin, Emily K.
   Nagrial, Adnan M.
   Humphrey, Emily S.
   Chou, Angela
   Chin, Venessa T.
   Chantrill, Lorraine A.
   Mawson, Amanda
   Samra, Jaswinder S.
   Kench, James G.
   Lovell, Jessica A.
   Daly, Roger J.
   Merrett, Neil D.
   Toon, Christopher
   Epari, Krishna
   Nguyen, Nam Q.
   Barbour, Andrew
   Zeps, Nikolajs
   Kakkar, Nipun
   Zhao, Fengmei
   Wu, Yuan Qing
   Wang, Min
   Muzny, Donna M.
   Fisher, William E.
   Brunicardi, F. Charles
   Hodges, Sally E.
   Reid, Jeffrey G.
   Drummond, Jennifer
   Chang, Kyle
   Han, Yi
   Lewis, Lora R.
   Dinh, Huyen
   Buhay, Christian J.
   Beck, Timothy
   Timms, Lee
   Sam, Michelle
   Begley, Kimberly
   Brown, Andrew
   Pai, Deepa
   Panchal, Ami
   Buchner, Nicholas
   De Borja, Richard
   Denroche, Robert E.
   Yung, Christina K.
   Serra, Stefano
   Onetto, Nicole
   Mukhopadhyay, Debabrata
   Tsao, Ming-Sound
   Shaw, Patricia A.
   Petersen, Gloria M.
   Gallinger, Steven
   Hruban, Ralph H.
   Maitra, Anirban
   Iacobuzio-Donahue, Christine A.
   Schulick, Richard D.
   Wolfgang, Christopher L.
   Morgan, Richard A.
   Lawlor, Rita T.
   Capelli, Paola
   Corbo, Vincenzo
   Scardoni, Maria
   Tortora, Giampaolo
   Tempero, Margaret A.
   Mann, Karen M.
   Jenkins, Nancy A.
   Perez-Mancera, Pedro A.
   Adams, David J.
   Largaespada, David A.
   Wessels, Lodewyk F. A.
   Rust, Alistair G.
   Stein, Lincoln D.
   Tuveson, David A.
   Copeland, Neal G.
   Musgrove, Elizabeth A.
   Scarpa, Aldo
   Eshleman, James R.
   Hudson, Thomas J.
   Sutherland, Robert L.
   Wheeler, David A.
   Pearson, John V.
   McPherson, John D.
   Gibbs, Richard A.
   Grimmond, Sean M.
TI Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes
SO NATURE
LA English
DT Article
ID somatic mutations; tumor; instability; expression; resection; roles
AB Pancreatic cancer is a highly lethal malignancy with few effective therapies. We performed exome sequencing and copy number analysis to define genomic aberrations in a prospectively accrued clinical cohort (n=142) of early (stage I and II) sporadic pancreatic ductal adenocarcinoma. Detailed analysis of 99 informative tumours identified substantial heterogeneity with 2,016 non-silent mutations and 1,628 copy-number variations. We define 16 significantly mutated genes, reaffirming known mutations (KRAS, TP53, CDKN2A, SMAD4, MLL3, TGFBR2, ARID1A and SF3B1), and uncover novel mutated genes including additional genes involved in chromatin modification (EPC1 and ARID2), DNA damage repair (ATM) and other mechanisms (ZIM2, MAP2K4, NALCN, SLC16A4 and MAGEA6). Integrative analysis with in vitro functional data and animal models provided supportive evidence for potential roles for these genetic aberrations in carcinogenesis. Pathway-based analysis of recurrently mutated genes recapitulated clustering in core signalling pathways in pancreatic ductal adenocarcinoma, and identified new mutated genes in each pathway. We also identified frequent and diverse somatic aberrations in genes described traditionally as embryonic regulators of axon guidance, particularly SLIT/ROBO signalling, which was also evident in murine Sleeping Beauty transposon-mediated somatic mutagenesis models of pancreatic cancer, providing further supportive evidence for the potential involvement of axon guidance genes in pancreatic carcinogenesis.
C1 [Waddell, Nicola; Kassahn, Karin S.; Miller, David K.; Wilson, Peter J.; Patch, Ann-Marie; Gardiner, Brooke B.; Song, Sarah; Harliwong, Ivon; Idrisoglu, Senel; Nourse, Craig; Nourbakhsh, Ehsan; Manning, Suzanne; Wani, Shivangi; Gongora, Milena; Anderson, Matthew; Holmes, Oliver; Leonard, Conrad; Taylor, Darrin; Wood, Scott; Xu, Qinying; Nones, Katia; Fink, J. Lynn; Christ, Angelika; Bruxner, Tim; Cloonan, Nicole; Newell, Felicity; Pearson, John V.; Grimmond, Sean M.] Univ Queensland, Inst Mol Biosci, Queensland Ctr Med Genom, Brisbane, Qld 4072, Australia.
   [Biankin, Andrew V.; Johns, Amber L.; Wu, Jianmin; Chang, David K.; Cowley, Mark J.; Pajic, Marina; Scarlett, Christopher J.; Gill, Anthony J.; Pinho, Andreia V.; Rooman, Ilse; Pinese, Mark; Mead, R. Scott; Humphris, Jeremy L.; Kaplan, Warren; Jones, Marc D.; Colvin, Emily K.; Nagrial, Adnan M.; Humphrey, Emily S.; Chou, Angela; Chin, Venessa T.; Chantrill, Lorraine A.; Mawson, Amanda; Kench, James G.; Lovell, Jessica A.; Daly, Roger J.; Toon, Christopher; Musgrove, Elizabeth A.; Sutherland, Robert L.] Kinghorn Canc Ctr, Darlinghurst, NSW, Australia.
   [Biankin, Andrew V.; Johns, Amber L.; Wu, Jianmin; Chang, David K.; Cowley, Mark J.; Pajic, Marina; Scarlett, Christopher J.; Gill, Anthony J.; Pinho, Andreia V.; Rooman, Ilse; Pinese, Mark; Mead, R. Scott; Humphris, Jeremy L.; Kaplan, Warren; Jones, Marc D.; Colvin, Emily K.; Nagrial, Adnan M.; Humphrey, Emily S.; Chou, Angela; Chin, Venessa T.; Chantrill, Lorraine A.; Mawson, Amanda; Kench, James G.; Lovell, Jessica A.; Daly, Roger J.; Toon, Christopher; Musgrove, Elizabeth A.; Sutherland, Robert L.] Garvan Inst Med Res, Canc Res Program, Sydney, NSW 2010, Australia.
   [Biankin, Andrew V.; Chang, David K.; Merrett, Neil D.] Bankstown Hosp, Dept Surg, Sydney, NSW 2200, Australia.
   [Biankin, Andrew V.; Chang, David K.] Univ New S Wales, Fac Med, S Western Sydney Clin Sch, Liverpool, NSW 2170, Australia.
   [Gingras, Marie-Claude; Kakkar, Nipun; Zhao, Fengmei; Wu, Yuan Qing; Wang, Min; Muzny, Donna M.; Reid, Jeffrey G.; Drummond, Jennifer; Chang, Kyle; Han, Yi; Lewis, Lora R.; Dinh, Huyen; Buhay, Christian J.; Wheeler, David A.; Gibbs, Richard A.] Baylor Coll Med, Human Genome Sequencing Ctr, Dept Mol & Human Genet, Houston, TX 77030 USA.
   [Gingras, Marie-Claude; Fisher, William E.; Hodges, Sally E.] Baylor Coll Med, Michael E DeBakey Dept Surg, Houston, TX 77030 USA.
   [Muthuswamy, Lakshmi B.; Beck, Timothy; Timms, Lee; Sam, Michelle; Begley, Kimberly; Brown, Andrew; Pai, Deepa; Panchal, Ami; Buchner, Nicholas; De Borja, Richard; Denroche, Robert E.; Yung, Christina K.; Onetto, Nicole; Stein, Lincoln D.; Hudson, Thomas J.; McPherson, John D.] Ontario Inst Canc Res, Toronto, ON M5G 0A3, Canada.
   [Scarlett, Christopher J.] Univ Newcastle, Sch Environm & Life Sci, Ourimbah, NSW 2258, Australia.
   [Gill, Anthony J.; Samra, Jaswinder S.] Royal N Shore Hosp, Dept Anat Pathol, Sydney, NSW 2065, Australia.
   [Gill, Anthony J.; Kench, James G.] Univ Sydney, Sydney, NSW 2006, Australia.
   [Kolle, Gabriel] Life Technol, Brisbane, Qld 4000, Australia.
   [Mead, R. Scott; Chou, Angela] St Vincents Hosp, Dept Anat Pathol, Sydney, NSW 2010, Australia.
   [Samra, Jaswinder S.] Royal N Shore Hosp, Dept Surg, Sydney, NSW 2065, Australia.
   [Kench, James G.] Royal Prince Alfred Hosp, Camperdown, NSW 2050, Australia.
   [Merrett, Neil D.] Univ Western Sydney, Sch Med, Penrith, NSW 2175, Australia.
   [Epari, Krishna] Fremantle Hosp, Dept Surg, Fremantle, WA 6160, Australia.
   [Nguyen, Nam Q.] Royal Adelaide Hosp, Dept Gastroenterol, Adelaide, SA 5000, Australia.
   [Barbour, Andrew] Univ Queensland, Princess Alexandra Hosp, Dept Surg, Woollongabba, Qld 4102, Australia.
   [Zeps, Nikolajs] Univ Western Australia, Sch Surg M507, Nedlands, WA 6009, Australia.
   [Zeps, Nikolajs] St John God Pathol, Subiaco, WA 6008, Australia.
   [Fisher, William E.; Hodges, Sally E.] Baylor Coll Med, Elkins Pancreas Ctr, Houston, TX 77030 USA.
   [Brunicardi, F. Charles] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90024 USA.
   [Serra, Stefano; Tsao, Ming-Sound; Shaw, Patricia A.; Gallinger, Steven] Univ Hlth Network, Toronto, ON M5G 2C4, Canada.
   [Mukhopadhyay, Debabrata; Petersen, Gloria M.] Mayo Clin, Rochester, MN 55905 USA.
   [Gallinger, Steven] Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada.
   [Hruban, Ralph H.; Maitra, Anirban; Iacobuzio-Donahue, Christine A.; Morgan, Richard A.; Eshleman, James R.] Johns Hopkins Univ, Sch Med, Sol Goldman Pancreat Canc Res Ctr, Dept Pathol, Baltimore, MD 21231 USA.
   [Schulick, Richard D.; Wolfgang, Christopher L.] Johns Hopkins Univ, Sch Med, Sol Goldman Pancreat Canc Res Ctr, Dept Surg, Baltimore, MD 21231 USA.
   [Lawlor, Rita T.; Corbo, Vincenzo; Scarpa, Aldo] Univ & Hosp Trust Verona, ARC NET Ctr Appl Res Canc, I-37134 Verona, Italy.
   [Capelli, Paola; Scardoni, Maria; Scarpa, Aldo] Univ Verona, Dept Pathol & Diagnost, I-37134 Verona, Italy.
   [Tortora, Giampaolo] Univ & Hosp Trust Verona, Dept Surg & Oncol, I-37134 Verona, Italy.
   [Tempero, Margaret A.] Univ Calif San Francisco, Div Hematol & Oncol, San Francisco, CA 94115 USA.
   [Mann, Karen M.; Jenkins, Nancy A.; Copeland, Neal G.] Methodist Hosp, Res Inst, Canc Res Program, Houston, TX 77030 USA.
   [Perez-Mancera, Pedro A.; Tuveson, David A.] Canc Res UK, Cambridge Res Inst, Li Ka Shing Ctr, Cambridge CB2 0RE, England.
   [Perez-Mancera, Pedro A.; Tuveson, David A.] Dept Oncol, Cambridge CB2 0RE, England.
   [Adams, David J.; Rust, Alistair G.] Wellcome Trust Sanger Inst, Hinxton CB10 1HH, England.
   [Largaespada, David A.] Univ Minnesota, Masonic Canc Ctr, Minneapolis, MN 55455 USA.
   [Wessels, Lodewyk F. A.] Netherlands Canc Inst, NL-1066 CX Amsterdam, Netherlands.
   [Musgrove, Elizabeth A.; Sutherland, Robert L.] Univ New S Wales, Fac Med, St Vincents Clin Sch, Sydney, NSW 2010, Australia.
C3 University of Queensland; The Kinghorn Cancer Centre; Garvan Institute of Medical Research; NSW Health; Bankstown Lidcombe Hospital; University of New South Wales Sydney; Baylor College of Medicine; Baylor College of Medicine; University of Toronto; Ontario Institute for Cancer Research; University of Newcastle; University of Sydney; Royal North Shore Hospital; University of Sydney; Thermo Fisher Scientific; NSW Health; St Vincents Hospital Sydney; Royal North Shore Hospital; University of Sydney; NSW Health; Royal Prince Alfred Hospital; University of Sydney; Western Sydney University; University of Western Australia; South Metropolitan Health Service; Fiona Stanley Fremantle Hospitals Group; Fremantle Hospital; Royal Adelaide Hospital; University of Queensland; Princess Alexandra Hospital; University of Western Australia; St John of God Health Care; Baylor College 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 Toronto; University Health Network Toronto; Mayo Clinic; University of Toronto; Sinai Health System Toronto; Johns Hopkins University; Johns Hopkins University; University of Verona; Azienda Ospedaliera Universitaria Integrata Verona; University of Verona; University of Verona; Azienda Ospedaliera Universitaria Integrata Verona; University of California System; University of California San Francisco; Houston Methodist; University of Cambridge; Cancer Research UK; CRUK Cambridge Institute; Wellcome Trust Sanger Institute; University of Minnesota System; University of Minnesota Twin Cities; Netherlands Cancer Institute; University of New South Wales Sydney
RP Grimmond, SM (corresponding author), Univ Queensland, Inst Mol Biosci, Queensland Ctr Med Genom, Brisbane, Qld 4072, Australia.
EM s.grimmond@imb.uq.edu.au
FU National Health and Medical Research Council of Australia (NHMRC) [631701, 535903, 427601, 535914]; Australian Government: Department of Innovation, Industry, Science, Research and Tertiary Education (DIISRTE); Australian Cancer Research Foundation (ACRF); Queensland Government (NIRAP); University of Queensland; Cancer Council NSW [SRP06-01, ICGC09-01, SRP11-01]; Cancer Institute NSW [06/ECF/1-24, 09/CDF/2-40, 07/CDF/1-03, 10/CRF/1-01, 08/RSA/1-15, 07/CDF/1-28, 10/CDF/2-26, 10/FRL/2-03, 06/RSA/1-05, 09/RIG/1-02, 10/TPG/1-04, 11/REG/1-10, 11/CDF/3-26]; Garvan Institute of Medical Research; Avner Nahmani Pancreatic Cancer Research Foundation; R.T. Hall Trust; Petre Foundation; Jane Hemstritch in memory of Philip Hemstritch; Gastroenterological Society of Australia (GESA); American Association for Cancer Research (AACR) Landon Foundation-INNOVATOR Award; Royal Australasian College of Surgeons (RACS); Royal Australasian College of Physicians (RACP); Royal College of Pathologists of Australasia (RCPA); HGSC-BCM: NHGRI [U54 HG003273]; CPRIT [RP101353-P7]; Ontario Institute for Cancer Research; Ontario Ministry of Economic Development and Innovation; Canada Foundation for Innovation; Pancreatic Cancer Genetic Epidemiology Consortium, NIH [R01 CA97075]; Agency for Science, Technology, and Research (Singapore); University of Verona; Italian Ministry of University, Rome, Italy [FIRB RBAP10AHJB]; Cancer Research UK; Wellcome Trust; CPRIT (Cancer Prevention Research Institute of Texas); NIH [P50CA062924, P01CA134292]; Sol Goldman Pancreatic Cancer Research Center; NCI [R01 CA97075, P50 CA102701]; NIH SPORE grant [2P50CA101955]; AIRC (Associazione Italiana Ricerca sul Cancro), Italy [12182]; Cancer Research UK [13031] Funding Source: researchfish; National Cancer Institute [P50CA062924] Funding Source: NIH RePORTER; National Health and Medical Research Council (NHMRC) [535914, 427601] Funding Source: National Health and Medical Research Council (NHMRC)
NR 38
TC 1697
Z9 1940
U1 3
U2 295
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 15
PY 2012
VL 491
IS 7424
BP 399
EP 405
DI 10.1038/nature11547
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 036MY
UT WOS:000311031600037
PM 23103869
DA 2026-03-09
ER

PT J
AU Sanders, SJ
   Murtha, MT
   Gupta, AR
   Murdoch, JD
   Raubeson, MJ
   Willsey, AJ
   Ercan-Sencicek, AG
   DiLullo, NM
   Parikshak, NN
   Stein, JL
   Walker, MF
   Ober, GT
   Teran, NA
   Song, Y
   El-Fishawy, P
   Murtha, RC
   Choi, M
   Overton, JD
   Bjornson, RD
   Carriero, NJ
   Meyer, KA
   Bilguvar, K
   Mane, SM
   Sestan, N
   Lifton, RP
   Günel, M
   Roeder, K
   Geschwind, DH
   Devlin, B
   State, MW
AF Sanders, Stephan J.
   Murtha, Michael T.
   Gupta, Abha R.
   Murdoch, John D.
   Raubeson, Melanie J.
   Willsey, A. Jeremy
   Ercan-Sencicek, A. Gulhan
   DiLullo, Nicholas M.
   Parikshak, Neelroop N.
   Stein, Jason L.
   Walker, Michael F.
   Ober, Gordon T.
   Teran, Nicole A.
   Song, Youeun
   El-Fishawy, Paul
   Murtha, Ryan C.
   Choi, Murim
   Overton, John D.
   Bjornson, Robert D.
   Carriero, Nicholas J.
   Meyer, Kyle A.
   Bilguvar, Kaya
   Mane, Shrikant M.
   Sestan, Nenad
   Lifton, Richard P.
   Guenel, Murat
   Roeder, Kathryn
   Geschwind, Daniel H.
   Devlin, Bernie
   State, Matthew W.
TI De novo mutations revealed by whole-exome sequencing are strongly associated with autism
SO NATURE
LA English
DT Article
ID spectrum disorders; gene scn2a; schizophrenia; components; constraint; evolution; proteome; epilepsy
AB Multiple studies have confirmed the contribution of rare de novo copy number variations to the risk for autism spectrum disorders(1-3). But whereas de novo single nucleotide variants have been identified in affected individuals(4), their contribution to risk has yet to be clarified. Specifically, the frequency and distribution of these mutations have not been well characterized in matched unaffected controls, and such data are vital to the interpretation of de novo coding mutations observed in probands. Here we show, using whole-exome sequencing of 928 individuals, including 200 phenotypically discordant sibling pairs, that highly disruptive (nonsense and splice-site) de novo mutations in brain-expressed genes are associated with autism spectrum disorders and carry large effects. On the basis of mutation rates in unaffected individuals, we demonstrate that multiple independent de novo single nucleotide variants in the same gene among unrelated probands reliably identifies risk alleles, providing a clear path forward for gene discovery. Among a total of 279 identified de novo coding mutations, there is a single instance in probands, and none in siblings, in which two independent nonsense variants disrupt the same gene, SCN2A (sodium channel, voltage-gated, type II, alpha subunit), a result that is highly unlikely by chance.
C1 [Sanders, Stephan J.; Murtha, Michael T.; Murdoch, John D.; Raubeson, Melanie J.; Willsey, A. Jeremy; Ercan-Sencicek, A. Gulhan; DiLullo, Nicholas M.; Walker, Michael F.; Ober, Gordon T.; Teran, Nicole A.; Song, Youeun; El-Fishawy, Paul; Murtha, Ryan C.; State, Matthew W.] Yale Univ, Sch Med, Dept Genet, Ctr Child Study,Dept Psychiat,Program Neurogenet, New Haven, CT 06520 USA.
   [Gupta, Abha R.] Yale Univ, Sch Med, Dept Pediat, Ctr Child Study, New Haven, CT 06520 USA.
   [Parikshak, Neelroop N.; Stein, Jason L.; Geschwind, Daniel H.] Univ Calif Los Angeles, Neurogenet Program, Los Angeles, CA 90095 USA.
   [Choi, Murim; Overton, John D.; Lifton, Richard P.] Yale Univ, Sch Med, Howard Hughes Med Inst, Dept Genet, New Haven, CT 06510 USA.
   [Bjornson, Robert D.; Carriero, Nicholas J.] Yale Univ, Dept Comp Sci, Yale Ctr Genome Anal, New Haven, CT 06511 USA.
   [Meyer, Kyle A.; Sestan, Nenad] Yale Univ, Sch Med, Kavli Inst Neurosci, Dept Neurobiol, New Haven, CT 06520 USA.
   [Bilguvar, Kaya; Guenel, Murat] Yale Univ, Sch Med, Program Neurogenet, Ctr Human Genet & Genom,Dept Neurosurg, New Haven, CT 06520 USA.
   [Mane, Shrikant M.] Yale Ctr Genome Anal, West Haven, CT 06516 USA.
   [Roeder, Kathryn] Carnegie Mellon Univ, Dept Stat, Pittsburgh, PA 15213 USA.
   [Devlin, Bernie] Univ Pittsburgh, Sch Med, Dept Psychiat & Human Genet, Pittsburgh, PA 15213 USA.
C3 Yale University; Yale University; University of California System; University of California Los Angeles; Howard Hughes Medical Institute; Yale University; Yale University; Yale University; Yale University; Carnegie Mellon University; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh
RP State, MW (corresponding author), Yale Univ, Sch Med, Dept Genet, Ctr Child Study,Dept Psychiat,Program Neurogenet, 230 S Frontage Rd, New Haven, CT 06520 USA.
EM dhg@mednet.ucla.edu; devlinbj@upmc.edu; matthew.state@yale.edu
FU Simons Foundation; National Institute of General Medical Sciences [T32GM008042] Funding Source: NIH RePORTER; National Institute of Mental Health [R25MH077823] Funding Source: NIH RePORTER
NR 23
TC 1569
Z9 1913
U1 1
U2 260
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD MAY 10
PY 2012
VL 485
IS 7397
BP 237
EP U124
DI 10.1038/nature10945
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 939HJ
UT WOS:000303799800041
PM 22495306
DA 2026-03-09
ER

PT J
AU Koga, N
   Tatsumi-Koga, R
   Liu, GH
   Xiao, R
   Acton, TB
   Montelione, GT
   Baker, D
AF Koga, Nobuyasu
   Tatsumi-Koga, Rie
   Liu, Gaohua
   Xiao, Rong
   Acton, Thomas B.
   Montelione, Gaetano T.
   Baker, David
TI Principles for designing ideal protein structures
SO NATURE
LA English
DT Article
ID de-novo design; torsion angle dynamics; computational design; structure prediction; negative design; nmr structure; local-structure; folding funnel; redesign; refinement
AB Unlike random heteropolymers, natural proteins fold into unique ordered structures. Understanding how these are encoded in amino-acid sequences is complicated by energetically unfavourable non-ideal features-for example kinked alpha-helices, bulged beta-strands, strained loops and buried polar groups-that arise in proteins from evolutionary selection for biological function or from neutral drift. Here we describe an approach to designing ideal protein structures stabilized by completely consistent local and non-local interactions. The approach is based on a set of rules relating secondary structure patterns to protein tertiary motifs, which make possible the design of funnel-shaped protein folding energy landscapes leading into the target folded state. Guided by these rules, we designed sequences predicted to fold into ideal protein structures consisting of alpha-helices, beta-strands and minimal loops. Designs for five different topologies were found to be monomeric and very stable and to adopt structures in solution nearly identical to the computational models. These results illuminate how the folding funnels of natural proteins arise and provide the foundation for engineering a new generation of functional proteins free from natural evolution.
C1 [Koga, Nobuyasu; Tatsumi-Koga, Rie; Baker, David] Univ Washington, Dept Biochem, Seattle, WA 98195 USA.
   [Koga, Nobuyasu; Tatsumi-Koga, Rie; Baker, David] Univ Washington, Howard Hughes Med Inst, Seattle, WA 98195 USA.
   [Liu, Gaohua; Xiao, Rong; Acton, Thomas B.; Montelione, Gaetano T.] Rutgers State Univ, Ctr Adv Biotechnol & Med, Dept Mol Biol & Biochem, NE Struct Genom Consortium, Piscataway, NJ 08854 USA.
   [Liu, Gaohua; Xiao, Rong; Acton, Thomas B.; Montelione, Gaetano T.] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Biochem & Mol Biol, Piscataway, NJ 08854 USA.
C3 University of Washington; University of Washington Seattle; Howard Hughes Medical Institute; University of Washington; University of Washington Seattle; Rutgers University System; Rutgers University New Brunswick; Rutgers University System; Rutgers University New Brunswick; Rutgers University Biomedical & Health Sciences
RP Baker, D (corresponding author), Univ Washington, Dept Biochem, Seattle, WA 98195 USA.
EM guy@cabm.rutgers.edu; dabaker@u.washington.edu
FU HHMI; DOE; DARPA; DTRA; National Institutes of General Medical Science Protein Structure Initiative (PSI: Biology) programme [U54 GM094597]; Japan Society for the Promotion of Science (JSPS) Postdoctoral Fellowships for Research Abroad
NR 71
TC 447
Z9 580
U1 2
U2 429
PU NATURE PUBLISHING 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 8
PY 2012
VL 491
IS 7423
BP 222
EP 227
DI 10.1038/nature11600
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 033DP
UT WOS:000310774300037
PM 23135467
DA 2026-03-09
ER

PT J
AU Peyronel, T
   Firstenberg, O
   Liang, QY
   Hofferberth, S
   Gorshkov, AV
   Pohl, T
   Lukin, MD
   Vuletic, V
AF Peyronel, Thibault
   Firstenberg, Ofer
   Liang, Qi-Yu
   Hofferberth, Sebastian
   Gorshkov, Alexey V.
   Pohl, Thomas
   Lukin, Mikhail D.
   Vuletic, Vladan
TI Quantum nonlinear optics with single photons enabled by strongly interacting atoms
SO NATURE
LA English
DT Article
ID electromagnetically induced transparency; rydberg blockade; gas
AB The realization of strong nonlinear interactions between individual light quanta (photons) is a long-standing goal in optical science and engineering(1,2), being of both fundamental and technological significance. In conventional optical materials, the nonlinearity at light powers corresponding to single photons is negligibly weak. Here we demonstrate a medium that is nonlinear at the level of individual quanta, exhibiting strong absorption of photon pairs while remaining transparent to single photons. The quantum nonlinearity is obtained by coherently coupling slowly propagating photons(3-5) to strongly interacting atomic Rydberg states(6-12) in a cold, dense atomic gas(13,14). Our approach paves the way for quantum-byquantum control of light fields, including single-photon switching(15), all-optical deterministic quantum logic(16) and the realization of strongly correlated many-body states of light(17).
C1 [Firstenberg, Ofer; Hofferberth, Sebastian; Lukin, Mikhail D.] Harvard Univ, Dept Phys, Cambridge, MA 02138 USA.
   [Peyronel, Thibault; Firstenberg, Ofer; Liang, Qi-Yu; Hofferberth, Sebastian; Vuletic, Vladan] MIT, Dept Phys, Cambridge, MA 02139 USA.
   [Peyronel, Thibault; Firstenberg, Ofer; Liang, Qi-Yu; Hofferberth, Sebastian; Vuletic, Vladan] MIT, Elect Res Lab, Cambridge, MA 02139 USA.
   [Gorshkov, Alexey V.] CALTECH, Inst Quantum Informat & Matter, Pasadena, CA 91125 USA.
   [Pohl, Thomas] Max Planck Inst Phys Komplexer Syst, D-01187 Dresden, Germany.
C3 Harvard University; Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); California Institute of Technology; Max Planck Society
RP Lukin, MD (corresponding author), Harvard Univ, Dept Phys, Cambridge, MA 02138 USA.
EM lukin@fas.harvard.edu; vuletic@mit.edu
FU NSF; CUA; AFOSR Quantum Memories MURI; Lee A. DuBridge Foundation; IQIM; NSF Physics Frontiers Center; Gordon and Betty Moore Foundation; Division Of Physics; Direct For Mathematical & Physical Scien [0969816, 0803371] Funding Source: National Science Foundation
NR 31
TC 686
Z9 765
U1 5
U2 281
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD AUG 2
PY 2012
VL 488
IS 7409
BP 57
EP 60
DI 10.1038/nature11361
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 981ZE
UT WOS:000307010700031
PM 22832584
DA 2026-03-09
ER

PT J
AU Bottke, WF
   Vokrouhlicky, D
   Minton, D
   Nesvorny, D
   Morbidelli, A
   Brasser, R
   Simonson, B
   Levison, HF
AF Bottke, William F.
   Vokrouhlicky, David
   Minton, David
   Nesvorny, David
   Morbidelli, Alessandro
   Brasser, Ramon
   Simonson, Bruce
   Levison, Harold F.
TI An Archaean heavy bombardment from a destabilized extension of the asteroid belt
SO NATURE
LA English
DT Article
ID inner solar-system; origin; impact; shergottite; evolution; planets; ejecta; period; layers; ages
AB The barrage of comets and asteroids that produced many young lunar basins (craters over 300 kilometres in diameter) has frequently been called the Late Heavy Bombardment(1) (LHB). Many assume the LHB ended about 3.7 to 3.8 billion years (Gyr) ago with the formation of Orientale basin(2,3). Evidence for LHB-sized blasts on Earth, however, extend into the Archaean and early Proterozoic eons, in the form of impact spherule beds: globally distributed ejecta layers created by Chicxulub-sized or larger cratering events(4). At least seven spherule beds have been found that formed between 3.23 and 3.47 Gyr ago, four between 2.49 and 2.63 Gyr ago, and one between 1.7 and 2.1 Gyr ago(5-9). Here we report that the LHB lasted much longer than previously thought, with most late impactors coming from the E belt, an extended and now largely extinct portion of the asteroid belt between 1.7 and 2.1 astronomical units from Earth. This region was destabilized by late giant planet migration(10-13). E-belt survivors now make up the high-inclination Hungaria asteroids(14,15). Scaling from the observed Hungaria asteroids, we find that E-belt projectiles made about ten lunar basins between 3.7 and 4.1 Gyr ago. They also produced about 15 terrestrial basins between 2.5 and 3.7 Gyr ago, as well as around 70 and four Chicxulub-sized or larger craters on the Earth and Moon, respectively, between 1.7 and 3.7 Gyr ago. These rates reproduce impact spherule bed and lunar crater constraints.
C1 [Bottke, William F.; Vokrouhlicky, David; Minton, David; Nesvorny, David; Morbidelli, Alessandro; Brasser, Ramon; Levison, Harold F.] SW Res Inst, Boulder, CO 80302 USA.
   [Bottke, William F.; Vokrouhlicky, David; Minton, David; Nesvorny, David; Morbidelli, Alessandro; Brasser, Ramon; Levison, Harold F.] NASA, Lunar Sci Inst, Boulder, CO 80302 USA.
   [Vokrouhlicky, David] Charles Univ Prague, Inst Astron, CR-18000 Prague 8, Czech Republic.
   [Minton, David] Purdue Univ, Dept Earth & Atmospher Sci, W Lafayette, IN 47907 USA.
   [Morbidelli, Alessandro; Brasser, Ramon] Univ Nice Sophia Antipolis, CNRS, Observ Cote Azur, Lab Cassiopee, F-06304 Nice 4, France.
   [Brasser, Ramon] Acad Sinica, Inst Astron & Astrophys, Taipei 106, Taiwan.
   [Simonson, Bruce] Oberlin Coll, Dept Geol, Oberlin, OH 44074 USA.
C3 National Aeronautics & Space Administration (NASA); Charles University Prague; Purdue University System; Purdue University; Universite Cote d'Azur; Observatoire de la Cote d'Azur; Centre National de la Recherche Scientifique (CNRS); Academia Sinica - Taiwan; University System of Ohio; Oberlin College
RP Bottke, WF (corresponding author), SW Res Inst, 1050 Walnut St,Suite 300, Boulder, CO 80302 USA.
EM bottke@boulder.swri.edu
FU University of Hawaii; NASA's Lunar Science Institute (Center for Lunar Origin and Evolution) [NNA09DB32A]; Grant Agency of the Czech Republic; Germany's Helmholtz Alliance; NASA [NNX08AI29G]; NASA through the NASA Advanced Supercomputing (NAS) Division at Ames Research Center; NASA [118138, 100278, NNA09DB32A, NNX08AI29G] Funding Source: Federal RePORTER
NR 30
TC 281
Z9 311
U1 3
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 MAY 3
PY 2012
VL 485
IS 7396
BP 78
EP 81
DI 10.1038/nature10967
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 934NV
UT WOS:000303451900037
PM 22535245
DA 2026-03-09
ER

PT J
AU He, CC
   Bassik, MC
   Moresi, V
   Sun, K
   Wei, YJ
   Zou, ZJ
   An, ZY
   Loh, J
   Fisher, J
   Sun, QH
   Korsmeyer, S
   Packer, M
   May, HI
   Hill, JA
   Virgin, HW
   Gilpin, C
   Xiao, GH
   Bassel-Duby, R
   Scherer, PE
   Levine, B
AF He, Congcong
   Bassik, Michael C.
   Moresi, Viviana
   Sun, Kai
   Wei, Yongjie
   Zou, Zhongju
   An, Zhenyi
   Loh, Joy
   Fisher, Jill
   Sun, Qihua
   Korsmeyer, Stanley
   Packer, Milton
   May, Herman I.
   Hill, Joseph A.
   Virgin, Herbert W.
   Gilpin, Christopher
   Xiao, Guanghua
   Bassel-Duby, Rhonda
   Scherer, Philipp E.
   Levine, Beth
TI Exercise-induced BCL2-regulated autophagy is required for muscle glucose homeostasis
SO NATURE
LA English
DT Article
ID causes insulin-resistance; mice; beclin-1; mouse; gene; diet; phosphorylation; tumorigenesis; sensitivity; disruption
AB Exercise has beneficial effects on human health, including protection against metabolic disorders such as diabetes(1). However, the cellular mechanisms underlying these effects are incompletely understood. The lysosomal degradation pathway, autophagy, is an intracellular recycling system that functions during basal conditions in organelle and protein quality control(2). During stress, increased levels of autophagy permit cells to adapt to changing nutritional and energy demands through protein catabolism(3). Moreover, in animal models, autophagy protects against diseases such as cancer, neurodegenerative disorders, infections, inflammatory diseases, ageing and insulin resistance(4-6). Here we show that acute exercise induces autophagy in skeletal and cardiac muscle of fed mice. To investigate the role of exercise-mediated autophagy in vivo, we generated mutant mice that show normal levels of basal autophagy but are deficient in stimulus (exercise- or starvation)-induced autophagy. These mice (termed BCL2 AAA mice) contain knock-in mutations in BCL2 phosphorylation sites (Thr69Ala, Ser70Ala and Ser84Ala) that prevent stimulus-induced disruption of the BCL2-beclin-1 complex and autophagy activation. BCL2 AAA mice show decreased endurance and altered glucose metabolism during acute exercise, as well as impaired chronic exercise-mediated protection against high-fat-diet-induced glucose intolerance. Thus, exercise induces autophagy, BCL2 is a crucial regulator of exercise- (and starvation)-induced autophagy in vivo, and autophagy induction may contribute to the beneficial metabolic effects of exercise.
C1 [He, Congcong; Wei, Yongjie; Zou, Zhongju; An, Zhenyi; Sun, Qihua; Levine, Beth] Univ Texas SW Med Ctr Dallas, Ctr Autophagy Res, Dallas, TX 75390 USA.
   [He, Congcong; Sun, Kai; Wei, Yongjie; Zou, Zhongju; An, Zhenyi; Sun, Qihua; May, Herman I.; Hill, Joseph A.; Scherer, Philipp E.; Levine, Beth] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Dallas, TX 75390 USA.
   [He, Congcong; Wei, Yongjie; Zou, Zhongju; Levine, Beth] Univ Texas SW Med Ctr Dallas, Howard Hughes Med Inst, Dallas, TX 75390 USA.
   [Bassik, Michael C.; Fisher, Jill; Korsmeyer, Stanley] Dana Farber Canc Inst, Boston, MA 02115 USA.
   [Moresi, Viviana; Bassel-Duby, Rhonda] Univ Texas SW Med Ctr Dallas, Dept Mol Biol, Dallas, TX 75390 USA.
   [Sun, Kai; Scherer, Philipp E.] Univ Texas SW Med Ctr Dallas, Touchstone Diabet Ctr, Dallas, TX 75390 USA.
   [Loh, Joy; Virgin, Herbert W.] Washington Univ, Dept Pathol & Immunol, Sch Med, St Louis, MO USA.
   [Packer, Milton; Xiao, Guanghua] Univ Texas SW Med Ctr Dallas, Dept Clin Sci, Dallas, TX 75390 USA.
   [Gilpin, Christopher] Univ Texas SW Med Ctr Dallas, Dept Cell Biol, Dallas, TX 75390 USA.
   [Levine, Beth] Univ Texas SW Med Ctr Dallas, Dept Microbiol, Dallas, TX 75390 USA.
C3 University of Texas System; University of Texas Southwestern Medical Center; University of Texas System; University of Texas Southwestern Medical Center; University of Texas System; University of Texas Southwestern Medical Center; Howard Hughes Medical Institute; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; University of Texas System; University of Texas Southwestern Medical Center; University of Texas System; University of Texas Southwestern Medical Center; Washington University (WUSTL); University of Texas System; University of Texas Southwestern Medical Center; University of Texas System; University of Texas Southwestern Medical Center; University of Texas System; University of Texas Southwestern Medical Center
RP Levine, B (corresponding author), Univ Texas SW Med Ctr Dallas, Ctr Autophagy Res, 5323 Harry Hines Blvd, Dallas, TX 75390 USA.
EM beth.levine@utsouthwestern.edu
FU National Institutes of Health [RO1 CA109618, ROI HL080244, ROI HL090842, ROI AI084887, RCI DK086629, RO1 CA112023, 1PO1 DK0887761]; National Cancer Institute [P30CA142543] Funding Source: NIH RePORTER; National Institute of Diabetes and Digestive and Kidney Diseases [R01DK055758] Funding Source: NIH RePORTER
NR 32
TC 931
Z9 1078
U1 1
U2 249
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JAN 26
PY 2012
VL 481
IS 7382
BP 511
EP U126
DI 10.1038/nature10758
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 881GY
UT WOS:000299471800041
PM 22258505
DA 2026-03-09
ER

PT J
AU Demeshkina, N
   Jenner, L
   Westhof, E
   Yusupov, M
   Yusupova, G
AF Demeshkina, Natalia
   Jenner, Lasse
   Westhof, Eric
   Yusupov, Marat
   Yusupova, Gulnara
TI A new understanding of the decoding principle on the ribosome
SO NATURE
LA English
DT Article
ID aminoacyl-transfer-rna; ef-tu; messenger-rna; selection; recognition; fidelity; activation; mechanism
AB During protein synthesis, the ribosome accurately selects transfer RNAs (tRNAs) in accordance with the messenger RNA (mRNA) triplet in the decoding centre. tRNA selection is initiated by elongation factor Tu, which delivers tRNA to the aminoacyl tRNA-binding site (A site) and hydrolyses GTP upon establishing codon-anticodon interactions in the decoding centre(1-9). At the following proofreading step the ribosome re-examines the tRNA and rejects it if it does not match the A codon(2,3,10-14). It was suggested that universally conserved G530, A1492 and A1493 of 16S ribosomal RNA, critical for tRNA binding in the Asite(15-17), actively monitor cognate tRNA(18), and that recognition of the correct codon-anticodon duplex induces an overall ribosome conformational change (domain closure)(19). Here we propose an integrated mechanism for decoding based on six X-ray structures of the 70S ribosome determined at 3.1-3.4A resolution, modelling cognate or near-cognate states of the decoding centre at the proofreading step. We show that the 30S subunit undergoes an identical domain closure upon binding of either cognate or near-cognate tRNA. This conformational change of the 30S subunit forms a decoding centre that constrains the mRNA in such a way that the first two nucleotides of the A codon are limited to form Watson-Crick base pairs. When U center dot G and G center dot U mismatches, generally considered to form wobble base pairs, are at the first or second codon-anticodon position, the decoding centre forces this pair to adopt the geometry close to that of a canonical C center dot G pair. This by itself, or with distortions in the codon-anticodon mini-helix and the anticodon loop, causes the near-cognate tRNA to dissociate from the ribosome.
C1 [Demeshkina, Natalia; Jenner, Lasse; Yusupov, Marat; Yusupova, Gulnara] Inst Genet & Biol Mol & Cellulaire, Dept Biol & Genom Struct, F-67400 Illkirch Graffenstaden, France.
   [Demeshkina, Natalia; Jenner, Lasse; Yusupov, Marat; Yusupova, Gulnara] CNRS, UMR7104, F-67400 Illkirch Graffenstaden, France.
   [Demeshkina, Natalia; Jenner, Lasse; Yusupov, Marat; Yusupova, Gulnara] INSERM, U964, F-67400 Illkirch Graffenstaden, France.
   [Demeshkina, Natalia; Jenner, Lasse; Yusupov, Marat; Yusupova, Gulnara] Univ Strasbourg, F-67000 Strasbourg, France.
   [Westhof, Eric] Univ Strasbourg, CNRS, Inst Biol Mol & Cellulaire, Architecture & Reactivite ARN, F-67084 Strasbourg, France.
C3 Universites de Strasbourg Etablissements Associes; Universite de Strasbourg; Institut National de la Sante et de la Recherche Medicale (Inserm); Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB); Institut National de la Sante et de la Recherche Medicale (Inserm); Universites de Strasbourg Etablissements Associes; Universite de Strasbourg; 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)
RP Yusupov, M (corresponding author), Inst Genet & Biol Mol & Cellulaire, Dept Biol & Genom Struct, F-67400 Illkirch Graffenstaden, France.
EM marat@igbmc.fr; gula@igbmc.fr
FU ANR [BLAN07-3_190451, ANR-07-PCVI-0015-01]; Fondation pour la Recherche Medicale en France; European Commission SPINE2; Agence Nationale de la Recherche (ANR) [ANR-07-PCVI-0015] Funding Source: Agence Nationale de la Recherche (ANR)
NR 31
TC 282
Z9 347
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 APR 12
PY 2012
VL 484
IS 7393
BP 256
EP U146
DI 10.1038/nature10913
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 930OV
UT WOS:000303149900038
PM 22437501
DA 2026-03-09
ER

PT J
AU Dethoff, EA
   Petzold, K
   Chugh, J
   Casiano-Negroni, A
   Al-Hashimi, HM
AF Dethoff, Elizabeth A.
   Petzold, Katja
   Chugh, Jeetender
   Casiano-Negroni, Anette
   Al-Hashimi, Hashim M.
TI Visualizing transient low-populated structures of RNA
SO NATURE
LA English
DT Article
ID immunodeficiency-virus type-1; hiv-1 tar rna; relaxation dispersion nmr; lead-dependent ribozyme; 16s ribosomal-rna; nucleocapsid protein; molecular-dynamics; spin relaxation; initiation site; loop sequence
AB The visualization of RNA conformational changes has provided fundamental insights into how regulatory RNAs carry out their biological functions. The RNA structural transitions that have been characterized so far involve long-lived species that can be captured by structure characterization techniques. Here we report the nuclear magnetic resonance visualization of RNA transitions towards 'invisible' excited states (ESs), which exist in too little abundance (2-13%) and for too short a duration (45-250 ms) to allow structural characterization by conventional techniques. Transitions towards ESs result in localized rearrangements in base-pairing that alter building block elements of RNA architecture, including helix-junction-helix motifs and apical loops. The ES can inhibit function by sequestering residues involved in recognition and signalling or promote ATP-independent strand exchange. Thus, RNAs do not adopt a single conformation, but rather exist in rapid equilibrium with alternative ESs, which can be stabilized by cellular cues to affect functional outcomes.
C1 [Dethoff, Elizabeth A.; Petzold, Katja; Chugh, Jeetender; Casiano-Negroni, Anette; Al-Hashimi, Hashim M.] Univ Michigan, Dept Chem & Biophys, Ann Arbor, MI 48109 USA.
C3 University of Michigan System; University of Michigan
RP Al-Hashimi, HM (corresponding author), Univ Michigan, Dept Chem & Biophys, 930 N Univ Ave, Ann Arbor, MI 48109 USA.
EM hashimi@umich.edu
FU Michigan Economic Development Cooperation; Michigan Technology Tri-Corridor; Swedish Research Council [VR-K2011-78PK-21662-0-12]; US National Institutes of Health [R01 Al066975]; University of Michigan
NR 53
TC 168
Z9 212
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 NOV 29
PY 2012
VL 491
IS 7426
BP 724
EP +
DI 10.1038/nature11498
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 044FY
UT WOS:000311606000037
PM 23041928
DA 2026-03-09
ER

PT J
AU Clark, MK
AF Clark, Marin Kristen
TI Continental collision slowing due to viscous mantle lithosphere rather than topography
SO NATURE
LA English
DT Article
ID northeastern tibetan plateau; altyn-tagh fault; tectonic evolution; india; deformation; history; system; growth; region; margin
AB Because the inertia of tectonic plates is negligible, plate velocities result from the balance of forces acting at plate margins and along their base(1). Observations of past plate motion derived from marine magnetic anomalies provide evidence of how continental deformation may contribute to plate driving forces(2-8). A decrease in convergence rate at the inception of continental collision is expected because of the greater buoyancy of continental than oceanic lithosphere(2,3), but post-collisional rates are less well understood. Slowing of convergence has generally been attributed to the development of high topography that further resists convergent motion(7-10); however, the role of deforming continental mantle lithosphere on plate motions has not previously been considered. Here I show that the rate of India's penetration into Eurasia has decreased exponentially since their collision. The exponential decrease in convergence rate suggests that contractional strain across Tibet has been constant throughout the collision at a rate of 7.03 x 10(-16) s(-1), which matches the current rate. A constant bulk strain rate of the orogen suggests that convergent motion is resisted by constant average stress (constant force) applied to a relatively uniform layer or interface at depth. This finding follows new evidence that the mantle lithosphere beneath Tibet is intact(11), which supports the interpretation that the long-term strain history of Tibet reflects deformation of the mantle lithosphere. Under conditions of constant stress and strength, the deforming continental lithosphere creates a type of viscous resistance that affects plate motion irrespective of how topography evolved.
C1 Univ Michigan, Dept Earth & Environm Sci, Ann Arbor, MI 48109 USA.
C3 University of Michigan System; University of Michigan
RP Clark, MK (corresponding author), Univ Michigan, Dept Earth & Environm Sci, Ann Arbor, MI 48109 USA.
EM marinkc@umich.edu
FU National Science Foundation [EAR-0549748, EAR-0908711]; Directorate For Geosciences [0908711] Funding Source: National Science Foundation; Directorate For Geosciences; Division Of Earth Sciences [1211434] Funding Source: National Science Foundation; Division Of Earth Sciences [0908711] Funding Source: National Science Foundation
NR 39
TC 133
Z9 152
U1 3
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 MAR 1
PY 2012
VL 483
IS 7387
BP 74
EP U1502
DI 10.1038/nature10848
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 900HP
UT WOS:000300877900047
PM 22382982
DA 2026-03-09
ER

PT J
AU Charlesworth, JD
   Warren, TL
   Brainard, MS
AF Charlesworth, Jonathan D.
   Warren, Timothy L.
   Brainard, Michael S.
TI Covert skill learning in a cortical-basal ganglia circuit
SO NATURE
LA English
DT Article
ID forebrain circuit; birdsong; model; variability; performance; mechanisms; reward; signal; song
AB We learn complex skills such as speech and dance through a gradual process of trial and error. Cortical-basal ganglia circuits have an important yet unresolved function in this trial-and-error skill learning(1); influential 'actor-critic' models propose that basal ganglia circuits generate a variety of behaviours during training and learn to implement the successful behaviours in their repertoire(2,3). Here we show that the anterior forebrain pathway (AFP), a cortical-basal ganglia circuit(4), contributes to skill learning even when it does not contribute to such 'exploratory' variation in behavioural performance during training. Blocking the output of the AFP while training Bengalese finches to modify their songs prevented the gradual improvement that normally occurs in this complex skill during training. However, unblocking the output of the AFP after training caused an immediate transition from naive performance to excellent performance, indicating that the AFP covertly gained the ability to implement learned skill performance without contributing to skill practice. In contrast, inactivating the output nucleus of the AFP during training completely prevented learning, indicating that learning requires activity within the AFP during training. Our results suggest a revised model of skill learning: basal ganglia circuits can monitor the consequences of behavioural variation produced by other brain regions and then direct those brain regions to implement more successful behaviours. The ability of the AFP to identify successful performances generated by other brain regions indicates that basal ganglia circuits receive a detailed efference copy of premotor activity in those regions. The capacity of the AFP to implement successful performances that were initially produced by other brain regions indicates precise functional connections between basal ganglia circuits and the motor regions that directly control performance.
C1 [Charlesworth, Jonathan D.; Warren, Timothy L.; Brainard, Michael S.] Univ Calif San Francisco, WM Keck Ctr Integrat Neurosci, Dept Physiol, San Francisco, CA 94143 USA.
   [Charlesworth, Jonathan D.; Warren, Timothy L.; Brainard, Michael S.] Univ Calif San Francisco, Neurosci Grad Program, 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 Charlesworth, JD (corresponding author), Univ Calif San Francisco, WM Keck Ctr Integrat Neurosci, Dept Physiol, San Francisco, CA 94143 USA.
EM jcharles@phy.ucsf.edu
FU National Institutes of Health [NIDCD R01]; National Institute of Mental Health [P50]; National Science Foundation
NR 28
TC 81
Z9 95
U1 0
U2 34
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 14
PY 2012
VL 486
IS 7402
BP 251
EP +
DI 10.1038/nature11078
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 957UH
UT WOS:000305189000034
PM 22699618
DA 2026-03-09
ER

PT J
AU Bérut, A
   Arakelyan, A
   Petrosyan, A
   Ciliberto, S
   Dillenschneider, R
   Lutz, E
AF Berut, Antoine
   Arakelyan, Artak
   Petrosyan, Artyom
   Ciliberto, Sergio
   Dillenschneider, Raoul
   Lutz, Eric
TI Experimental verification of Landauer's principle linking information and thermodynamics
SO NATURE
LA English
DT Article
ID maxwells demon; logical reversibility; heat-generation; physical limits; computation; dissipation; energy; erasure
AB In 1961, Rolf Landauer argued that the erasure of information is a dissipative process(1). A minimal quantity of heat, proportional to the thermal energy and called the Landauer bound, is necessarily produced when a classical bit of information is deleted. A direct consequence of this logically irreversible transformation is that the entropy of the environment increases by a finite amount. Despite its fundamental importance for information theory and computer science(2-5), the erasure principle has not been verified experimentally so far, the main obstacle being the difficulty of doing single-particle experiments in the low-dissipation regime. Here we experimentally show the existence of the Landauer bound in a generic model of a one-bit memory. Using a system of a single colloidal particle trapped in a modulated double-well potential, we establish that the mean dissipated heat saturates at the Landauer bound in the limit of long erasure cycles. This result demonstrates the intimate link between information theory and thermodynamics. It further highlights the ultimate physical limit of irreversible computation.
C1 [Berut, Antoine; Arakelyan, Artak; Petrosyan, Artyom; Ciliberto, Sergio] Ecole Normale Super Lyon, Phys Lab, CNRS, UMR5672, F-69364 Lyon, France.
   [Dillenschneider, Raoul] Univ Kaiserslautern, Dept Phys, D-67663 Kaiserslautern, Germany.
   [Dillenschneider, Raoul] Univ Kaiserslautern, Res Ctr OPTIMAS, D-67663 Kaiserslautern, Germany.
   [Lutz, Eric] Univ Augsburg, Dept Phys, D-86135 Augsburg, Germany.
C3 Ecole Normale Superieure de Lyon (ENS de LYON); Centre National de la Recherche Scientifique (CNRS); CNRS - Institute of Physics (INP); RPTU University Kaiserslautern; RPTU University Kaiserslautern; University of Augsburg
RP Lutz, E (corresponding author), Free Univ Berlin, Dahlem Ctr Complex Quantum Syst, D-14195 Berlin, Germany.
EM eric.lutz@fu-berlin.de
FU DFG [LU1382/1-1]; Cluster of Excellence Nanosystems Initiative Munich (NIM), DAAD; Research Center of the DFG [Transregio 49]
NR 30
TC 874
Z9 945
U1 4
U2 194
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD MAR 8
PY 2012
VL 483
IS 7388
BP 187
EP U1500
DI 10.1038/nature10872
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 904DT
UT WOS:000301174900032
PM 22398556
DA 2026-03-09
ER

PT J
AU Barretina, J
   Caponigro, G
   Stransky, N
   Venkatesan, K
   Margolin, AA
   Kim, S
   Wilson, CJ
   Lehár, J
   Kryukov, GV
   Sonkin, D
   Reddy, A
   Liu, MW
   Murray, L
   Berger, MF
   Monahan, JE
   Morais, P
   Meltzer, J
   Korejwa, A
   Jané-Valbuena, J
   Mapa, FA
   Thibault, J
   Bric-Furlong, E
   Raman, P
   Shipway, A
   Engels, IH
   Cheng, J
   Yu, GYK
   Yu, JJ
   Aspesi, P
   de Silva, M
   Jagtap, K
   Jones, MD
   Wang, L
   Hatton, C
   Palescandolo, E
   Gupta, S
   Mahan, S
   Sougnez, C
   Onofrio, RC
   Liefeld, T
   MacConaill, L
   Winckler, W
   Reich, M
   Li, NX
   Mesirov, JP
   Gabriel, SB
   Getz, G
   Ardlie, K
   Chan, V
   Myer, VE
   Weber, BL
   Porter, J
   Warmuth, M
   Finan, P
   Harris, JL
   Meyerson, M
   Golub, TR
   Morrissey, MP
   Sellers, WR
   Schlegel, R
   Garraway, LA
AF Barretina, Jordi
   Caponigro, Giordano
   Stransky, Nicolas
   Venkatesan, Kavitha
   Margolin, Adam A.
   Kim, Sungjoon
   Wilson, Christopher J.
   Lehar, Joseph
   Kryukov, Gregory V.
   Sonkin, Dmitriy
   Reddy, Anupama
   Liu, Manway
   Murray, Lauren
   Berger, Michael F.
   Monahan, John E.
   Morais, Paula
   Meltzer, Jodi
   Korejwa, Adam
   Jane-Valbuena, Judit
   Mapa, Felipa A.
   Thibault, Joseph
   Bric-Furlong, Eva
   Raman, Pichai
   Shipway, Aaron
   Engels, Ingo H.
   Cheng, Jill
   Yu, Guoying K.
   Yu, Jianjun
   Aspesi, Peter, Jr.
   de Silva, Melanie
   Jagtap, Kalpana
   Jones, Michael D.
   Wang, Li
   Hatton, Charles
   Palescandolo, Emanuele
   Gupta, Supriya
   Mahan, Scott
   Sougnez, Carrie
   Onofrio, Robert C.
   Liefeld, Ted
   MacConaill, Laura
   Winckler, Wendy
   Reich, Michael
   Li, Nanxin
   Mesirov, Jill P.
   Gabriel, Stacey B.
   Getz, Gad
   Ardlie, Kristin
   Chan, Vivien
   Myer, Vic E.
   Weber, Barbara L.
   Porter, Jeff
   Warmuth, Markus
   Finan, Peter
   Harris, Jennifer L.
   Meyerson, Matthew
   Golub, Todd R.
   Morrissey, Michael P.
   Sellers, William R.
   Schlegel, Robert
   Garraway, Levi A.
TI The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity
SO NATURE
LA English
DT Article
ID malignant-melanoma; inhibitor; kinase; receptor; antagonist; expression
AB The systematic translation of cancer genomic data into knowledge of tumour biology and therapeutic possibilities remains challenging. Such efforts should be greatly aided by robust preclinical model systems that reflect the genomic diversity of human cancers and for which detailed genetic and pharmacological annotation is available(1). Here we describe the Cancer Cell Line Encyclopedia (CCLE): a compilation of gene expression, chromosomal copy number and massively parallel sequencing data from947 human cancer cell lines. When coupled with pharmacological profiles for 24 anticancer drugs across 479 of the cell lines, this collection allowed identification of genetic, lineage, and gene-expression-based predictors of drug sensitivity. In addition to known predictors, we found that plasma cell lineage correlated with sensitivity to IGF1 receptor inhibitors; AHR expression was associated with MEK inhibitor efficacy in NRAS-mutant lines; and SLFN11 expression predicted sensitivity to topoisomerase inhibitors. Together, our results indicate that large, annotated cell-line collections may help to enable preclinical stratification schemata for anticancer agents. The generation of genetic predictions of drug response in the preclinical setting and their incorporation into cancer clinical trial design could speed the emergence of 'personalized' therapeutic regimens(2).
C1 [Barretina, Jordi; Stransky, Nicolas; Margolin, Adam A.; Kryukov, Gregory V.; Murray, Lauren; Berger, Michael F.; Morais, Paula; Korejwa, Adam; Jane-Valbuena, Judit; Gupta, Supriya; Mahan, Scott; Sougnez, Carrie; Onofrio, Robert C.; Liefeld, Ted; Winckler, Wendy; Reich, Michael; Mesirov, Jill P.; Gabriel, Stacey B.; Getz, Gad; Ardlie, Kristin; Meyerson, Matthew; Golub, Todd R.; Garraway, Levi A.] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA.
   [Barretina, Jordi; Jane-Valbuena, Judit; Meyerson, Matthew; Garraway, Levi A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
   [Barretina, Jordi; Hatton, Charles; Palescandolo, Emanuele; MacConaill, Laura; Meyerson, Matthew; Golub, Todd R.; Garraway, Levi A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA.
   [Caponigro, Giordano; Venkatesan, Kavitha; Wilson, Christopher J.; Lehar, Joseph; Sonkin, Dmitriy; Reddy, Anupama; Liu, Manway; Monahan, John E.; Meltzer, Jodi; Mapa, Felipa A.; Bric-Furlong, Eva; Raman, Pichai; Aspesi, Peter, Jr.; de Silva, Melanie; Jagtap, Kalpana; Jones, Michael D.; Wang, Li; Myer, Vic E.; Weber, Barbara L.; Porter, Jeff; Warmuth, Markus; Finan, Peter; Morrissey, Michael P.; Sellers, William R.; Schlegel, Robert] Novartis Inst Biomed Res, Cambridge, MA 02139 USA.
   [Kim, Sungjoon; Thibault, Joseph; Shipway, Aaron; Engels, Ingo H.; Li, Nanxin; Harris, Jennifer L.] Novartis Res Fdn, Genom Inst, San Diego, CA 92121 USA.
   [Cheng, Jill; Yu, Guoying K.; Yu, Jianjun; Chan, Vivien] Novartis Inst Biomed Res, Emeryville, CA 94608 USA.
   [Golub, Todd R.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
   [Golub, Todd R.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA.
C3 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; Dana-Farber Cancer Institute; Novartis; Novartis USA; Novartis; Novartis USA; Novartis; Novartis USA; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Howard Hughes Medical Institute
RP Garraway, LA (corresponding author), Broad Inst Harvard & MIT, Cambridge, MA 02142 USA.
EM robert.schlegel@novartis.com; Levi_Garraway@dfci.harvard.edu
FU Novartis Institutes for Biomedical Research; National Cancer Institute; Starr Cancer Consortium; NIH
NR 26
TC 6111
Z9 7140
U1 7
U2 631
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD MAR 29
PY 2012
VL 483
IS 7391
BP 603
EP 607
DI 10.1038/nature11003
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 915EF
UT WOS:000302006100040
PM 22460905
DA 2026-03-09
ER

PT J
AU Baconguis, I
   Gouaux, E
AF Baconguis, Isabelle
   Gouaux, Eric
TI Structural plasticity and dynamic selectivity of acid-sensing ion channel-spider toxin complexes
SO NATURE
LA English
DT Article
ID epithelial sodium-channel; gated cation channel; functional expression; extracellular domain; tarantula peptide; asic1a channels; nervous-system; p2x receptors; na+ channel; pore
AB Acid-sensing ion channels (ASICs) are voltage-independent, amiloride-sensitive channels involved in diverse physiological processes ranging from nociception to taste. Despite the importance of ASICs in physiology, we know little about the mechanism of channel activation. Here we show that psalmotoxin activates non-selective and Na+-selective currents in chicken ASIC1a at pH 7.25 and 5.5, respectively. Crystal structures of ASIC1a-psalmotoxin complexes map the toxin binding site to the extracellular domain and show how toxin binding triggers an expansion of the extracellular vestibule and stabilization of the open channel pore. At pH 7.25 the pore is approximately 10 angstrom in diameter, whereas at pH 5.5 the pore is largely hydrophobic and elliptical in cross-section with dimensions of approximately 5 by 7 angstrom, consistent with a barrier mechanism for ion selectivity. These studies define mechanisms for activation of ASICs, illuminate the basis for dynamic ion selectivity and provide the blueprints for new therapeutic agents.
C1 [Baconguis, Isabelle; Gouaux, Eric] Oregon Hlth & Sci Univ, Vollum Inst, Portland, OR 97239 USA.
   [Gouaux, Eric] Oregon Hlth & Sci Univ, Howard Hughes Med Inst, Portland, OR 97239 USA.
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 National Institute of Neurological Disorders and Stroke; NIH
NR 58
TC 233
Z9 260
U1 2
U2 49
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD SEP 20
PY 2012
VL 489
IS 7416
BP 400
EP U86
DI 10.1038/nature11375
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 007AK
UT WOS:000308860900038
PM 22842900
DA 2026-03-09
ER

PT J
AU Klein, F
   Halper-Stromberg, A
   Horwitz, JA
   Gruell, H
   Scheid, JF
   Bournazos, S
   Mouquet, H
   Spatz, LA
   Diskin, R
   Abadir, A
   Zang, T
   Dorner, M
   Billerbeck, E
   Labitt, RN
   Gaebler, C
   Marcovecchio, PM
   Incesu, RB
   Eisenreich, TR
   Bieniasz, PD
   Seaman, MS
   Bjorkman, PJ
   Ravetch, JV
   Ploss, A
   Nussenzweig, MC
AF Klein, Florian
   Halper-Stromberg, Ariel
   Horwitz, Joshua A.
   Gruell, Henning
   Scheid, Johannes F.
   Bournazos, Stylianos
   Mouquet, Hugo
   Spatz, Linda A.
   Diskin, Ron
   Abadir, Alexander
   Zang, Trinity
   Dorner, Marcus
   Billerbeck, Eva
   Labitt, Rachael N.
   Gaebler, Christian
   Marcovecchio, Paola M.
   Incesu, Reha-Baris
   Eisenreich, Thomas R.
   Bieniasz, Paul D.
   Seaman, Michael S.
   Bjorkman, Pamela J.
   Ravetch, Jeffrey V.
   Ploss, Alexander
   Nussenzweig, Michel C.
TI HIV therapy by a combination of broadly neutralizing antibodies in humanized mice
SO NATURE
LA English
DT Article
ID monoclonal-antibody; passive transfer; b-cells; infection; protection; generation; viremia; gene; pcr
AB Human antibodies to human immunodeficiency virus-1 (HIV-1) can neutralize a broad range of viral isolates in vitro and protect non-human primates against infection(1,2). Previous work showed that antibodies exert selective pressure on the virus but escape variants emerge within a short period of time(3,4). However, these experiments were performed before the recent discovery of more potent anti-HIV-1 antibodies and their improvement by structure-based design(5-9). Here we re-examine passive antibody transfer as a therapeutic modality in HIV-1-infected humanized mice. Although HIV-1 can escape from antibody monotherapy, combinations of broadly neutralizing antibodies can effectively control HIV-1 infection and suppress viral load to levels below detection. Moreover, in contrast to antiretroviral therapy(10-12), the longer half-life of antibodies led to control of viraemia for an average of 60 days after cessation of therapy. Thus, combinations of potent monoclonal antibodies can effectively control HIV-1 replication in humanized mice, and should be re-examined as a therapeutic modality in HIV-1-infected individuals.
C1 [Klein, Florian; Halper-Stromberg, Ariel; Horwitz, Joshua A.; Gruell, Henning; Scheid, Johannes F.; Mouquet, Hugo; Spatz, Linda A.; Abadir, Alexander; Gaebler, Christian; Incesu, Reha-Baris; Eisenreich, Thomas R.; Nussenzweig, Michel C.] Rockefeller Univ, Lab Mol Immunol, New York, NY 10065 USA.
   [Gruell, Henning] Univ Munster, Fak Med, D-48149 Munster, Germany.
   [Scheid, Johannes F.] Charite, D-10117 Berlin, Germany.
   [Bournazos, Stylianos; Ravetch, Jeffrey V.] Rockefeller Univ, Lab Mol Genet & Immunol, New York, NY 10065 USA.
   [Spatz, Linda A.] CUNY City Coll, Sophie Davis Sch Biomed Educ, Dept Microbiol & Immunol, New York, NY 10031 USA.
   [Diskin, Ron; Marcovecchio, Paola M.; Bjorkman, Pamela J.] CALTECH, Div Biol, Pasadena, CA 91125 USA.
   [Zang, Trinity; Bieniasz, Paul D.] Rockefeller Univ, Lab Retrovirol, Aaron Diamond AIDS Res Ctr, New York, NY 10065 USA.
   [Dorner, Marcus; Billerbeck, Eva; Labitt, Rachael N.; Ploss, Alexander] Rockefeller Univ, Lab Virol & Infect Dis, New York, NY 10065 USA.
   [Gaebler, Christian] Tech Univ Dresden, Fac Med Carl Gustav Carus, D-01307 Dresden, Germany.
   [Bieniasz, Paul D.; Nussenzweig, Michel C.] Rockefeller Univ, Howard Hughes Med Inst, New York, NY 10065 USA.
   [Seaman, Michael S.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
   [Bjorkman, Pamela J.] CALTECH, Howard Hughes Med Inst, Pasadena, CA 91125 USA.
C3 Rockefeller University; University of Munster; Free University of Berlin; Humboldt University of Berlin; Charite Universitatsmedizin Berlin; Rockefeller University; City University of New York (CUNY) System; Sophie Davis School of Biomedical Education; City College of New York (CUNY); California Institute of Technology; Rockefeller University; Rockefeller University; Technische Universitat Dresden; Howard Hughes Medical Institute; Rockefeller University; Harvard University; Harvard University Medical Affiliates; Beth Israel Deaconess Medical Center; Howard Hughes Medical Institute; California Institute of Technology
RP Nussenzweig, MC (corresponding author), Rockefeller Univ, Lab Mol Immunol, New York, NY 10065 USA.
EM nussen@rockefeller.edu
FU German Research Foundation (DFG) [KL 2389/1-1, DO 1450/1-1, BI 1422/1-1]; German National Academic Foundation; Bill and Melinda Gates Foundation's Comprehensive Antibody Vaccine Immune Monitoring Consortium [1032144]; American Liver Foundation; CAVD from the Bill and Melinda Gates Foundation [OPP1033115]; NIAID [1UM1AI100663]; NIH [AI081677]; National Institute of General Medical Sciences [T32GM007739] Funding Source: NIH RePORTER
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NR 36
TC 431
Z9 562
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 6
PY 2012
VL 492
IS 7427
BP 118
EP +
DI 10.1038/nature11604
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 048EQ
UT WOS:000311893400057
PM 23103874
DA 2026-03-09
ER

PT J
AU Misale, S
   Yaeger, R
   Hobor, S
   Scala, E
   Janakiraman, M
   Liska, D
   Valtorta, E
   Schiavo, R
   Buscarino, M
   Siravegna, G
   Bencardino, K
   Cercek, A
   Chen, CT
   Veronese, S
   Zanon, C
   Sartore-Bianchi, A
   Gambacorta, M
   Gallicchio, M
   Vakiani, E
   Boscaro, V
   Medico, E
   Weiser, M
   Siena, S
   Di Nicolantonio, F
   Solit, D
   Bardelli, A
AF Misale, Sandra
   Yaeger, Rona
   Hobor, Sebastijan
   Scala, Elisa
   Janakiraman, Manickam
   Liska, David
   Valtorta, Emanuele
   Schiavo, Roberta
   Buscarino, Michela
   Siravegna, Giulia
   Bencardino, Katia
   Cercek, Andrea
   Chen, Chin-Tung
   Veronese, Silvio
   Zanon, Carlo
   Sartore-Bianchi, Andrea
   Gambacorta, Marcello
   Gallicchio, Margherita
   Vakiani, Efsevia
   Boscaro, Valentina
   Medico, Enzo
   Weiser, Martin
   Siena, Salvatore
   Di Nicolantonio, Federica
   Solit, David
   Bardelli, Alberto
TI Emergence of KRAS mutations and acquired resistance to anti-EGFR therapy in colorectal cancer
SO NATURE
LA English
DT Article
ID k-ras mutations; cetuximab; panitumumab; mechanisms; tumors; cells
AB A main limitation of therapies that selectively target kinase signalling pathways is the emergence of secondary drug resistance. Cetuximab, a monoclonal antibody that binds the extracellular domain of epidermal growth factor receptor (EGFR), is effective in a subset of KRAS wild-type metastatic colorectal cancers(1). After an initial response, secondary resistance invariably ensues, thereby limiting the clinical benefit of this drug(2). The molecular bases of secondary resistance to cetuximab in colorectal cancer are poorly understood(3-8). Here we show that molecular alterations (in most instances point mutations) of KRAS are causally associated with the onset of acquired resistance to anti-EGFR treatment in colorectal cancers. Expression of mutant KRAS under the control of its endogenous gene promoter was sufficient to confer cetuximab resistance, but resistant cells remained sensitive to combinatorial inhibition of EGFR and mitogen-activated protein-kinase kinase (MEK). Analysis of metastases from patients who developed resistance to cetuximab or panitumumab showed the emergence of KRAS amplification in one sample and acquisition of secondary KRAS mutations in 60% (6 out of 10) of the cases. KRAS mutant alleles were detectable in the blood of cetuximab-treated patients as early as 10 months before radiographic documentation of disease progression. In summary, the results identify KRAS mutations as frequent drivers of acquired resistance to cetuximab in colorectal cancers, indicate that the emergence of KRAS mutant clones can be detected non-invasively months before radiographic progression and suggest early initiation of a MEK inhibitor as a rational strategy for delaying or reversing drug resistance.
C1 [Yaeger, Rona; Cercek, Andrea; Solit, David] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10065 USA.
   [Misale, Sandra; Hobor, Sebastijan; Scala, Elisa; Buscarino, Michela; Siravegna, Giulia; Zanon, Carlo; Di Nicolantonio, Federica; Bardelli, Alberto] Inst Canc Res & Treatment IRCC, Mol Genet Lab, I-10060 Turin, Italy.
   [Misale, Sandra; Scala, Elisa; Buscarino, Michela; Medico, Enzo; Bardelli, Alberto] Univ Torino, Sch Med, Dept Oncol Sci, I-10060 Turin, Italy.
   [Janakiraman, Manickam; Solit, David] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10065 USA.
   [Liska, David; Chen, Chin-Tung; Weiser, Martin] Mem Sloan Kettering Canc Ctr, Dept Surg, New York, NY 10065 USA.
   [Valtorta, Emanuele; Veronese, Silvio; Gambacorta, Marcello] Osped Niguarda Ca Granda, Dept Pathol, I-20162 Milan, Italy.
   [Schiavo, Roberta; Bencardino, Katia; Sartore-Bianchi, Andrea; Siena, Salvatore] Osped Niguarda Ca Granda, Falck Div Med Oncol, I-20162 Milan, Italy.
   [Gallicchio, Margherita; Boscaro, Valentina] Univ Turin, Dipartimento Sci & Tecnol Farmaco, I-10125 Turin, Italy.
   [Vakiani, Efsevia] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10065 USA.
   [Medico, Enzo] Inst Canc Res & Treatment IRCC, Lab Funct Genom, I-10060 Turin, Italy.
   [Di Nicolantonio, Federica; Bardelli, Alberto] FIRC Inst Mol Oncol IFOM, I-20139 Milan, Italy.
C3 Memorial Sloan Kettering Cancer Center; IRCCS Fondazione del Piemonte per l'Oncologia; Consiglio Nazionale delle Ricerche (CNR); Istituto di Genetica Molecolare (IGM-CNR); University of Turin; Memorial Sloan Kettering Cancer Center; Memorial Sloan Kettering Cancer Center; IRCCS Ca Granda Ospedale Maggiore Policlinico; Ospedale Niguarda Ca' Granda; Ospedale Niguarda Ca' Granda; IRCCS Ca Granda Ospedale Maggiore Policlinico; University of Turin; Memorial Sloan Kettering Cancer Center; IRCCS Fondazione del Piemonte per l'Oncologia; IFOM - FIRC Institute of Molecular Oncology
RP Solit, D (corresponding author), Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10065 USA.
EM solitd@mskcc.org; alberto.bardelli@ircc.it
FU European Union [259015 COLTHERES]; Associazione Italiana per la Ricerca sul Cancro (AIRC) [9970]; Regione Piemonte; Fondazione Piemontese per la Ricerca sul Cancro (FPRC) Intramural Grant, 5xmille 2008, ONLUS; AIRC MFAG [11349]; Oncologia Ca' Granda ONLUS (OCGO); Commonwealth Foundation for Cancer Research; Experimental Therapeutics Center of Memorial Sloan-Kettering Cancer Center; Society of MSKCC; National Institutes of Health; Beene Foundation; Regione Lombardia; Ministerio Salute grant 'Gene Mutation Monitoring in mCRC'; National Cancer Institute [P30CA008748, T32CA009207] Funding Source: NIH RePORTER
NR 21
TC 1538
Z9 1781
U1 6
U2 253
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUN 28
PY 2012
VL 486
IS 7404
BP 532
EP U131
DI 10.1038/nature11156
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 965IJ
UT WOS:000305760600043
PM 22722830
DA 2026-03-09
ER

PT J
AU Garnett, MJ
   Edelman, EJ
   Heidorn, SJ
   Greenman, CD
   Dastur, A
   Lau, KW
   Greninger, P
   Thompson, IR
   Luo, X
   Soares, J
   Liu, QS
   Iorio, F
   Surdez, D
   Chen, L
   Milano, RJ
   Bignell, GR
   Tam, AT
   Davies, H
   Stevenson, JA
   Barthorpe, S
   Lutz, SR
   Kogera, F
   Lawrence, K
   McLaren-Douglas, A
   Mitropoulos, X
   Mironenko, T
   Thi, H
   Richardson, L
   Zhou, WJ
   Jewitt, F
   Zhang, TH
   O'Brien, P
   Boisvert, JL
   Price, S
   Hur, W
   Yang, WJ
   Deng, XM
   Butler, A
   Choi, HG
   Chang, J
   Baselga, J
   Stamenkovic, I
   Engelman, JA
   Sharma, SV
   Delattre, O
   Saez-Rodriguez, J
   Gray, NS
   Settleman, J
   Futreal, PA
   Haber, DA
   Stratton, MR
   Ramaswamy, S
   McDermott, U
   Benes, CH
AF Garnett, Mathew J.
   Edelman, Elena J.
   Heidorn, Sonja J.
   Greenman, Chris D.
   Dastur, Anahita
   Lau, King Wai
   Greninger, Patricia
   Thompson, I. Richard
   Luo, Xi
   Soares, Jorge
   Liu, Qingsong
   Iorio, Francesco
   Surdez, Didier
   Chen, Li
   Milano, Randy J.
   Bignell, Graham R.
   Tam, Ah T.
   Davies, Helen
   Stevenson, Jesse A.
   Barthorpe, Syd
   Lutz, Stephen R.
   Kogera, Fiona
   Lawrence, Karl
   McLaren-Douglas, Anne
   Mitropoulos, Xeni
   Mironenko, Tatiana
   Thi, Helen
   Richardson, Laura
   Zhou, Wenjun
   Jewitt, Frances
   Zhang, Tinghu
   O'Brien, Patrick
   Boisvert, Jessica L.
   Price, Stacey
   Hur, Wooyoung
   Yang, Wanjuan
   Deng, Xianming
   Butler, Adam
   Choi, Hwan Geun
   Chang, JaeWon
   Baselga, Jose
   Stamenkovic, Ivan
   Engelman, Jeffrey A.
   Sharma, Sreenath V.
   Delattre, Olivier
   Saez-Rodriguez, Julio
   Gray, Nathanael S.
   Settleman, Jeffrey
   Futreal, P. Andrew
   Haber, Daniel A.
   Stratton, Michael R.
   Ramaswamy, Sridhar
   McDermott, Ultan
   Benes, Cyril H.
TI Systematic identification of genomic markers of drug sensitivity in cancer cells
SO NATURE
LA English
DT Article
ID mesenchymal progenitor cells; kinase inhibitor; in-vivo; poly(adp-ribose) polymerase; ewings-sarcoma; lung-cancer; p53 pathway; growth; expression; melanoma
AB Clinical responses to anticancer therapies are often restricted to a subset of patients. In some cases, mutated cancer genes are potent biomarkers for responses to targeted agents. Here, to uncover new biomarkers of sensitivity and resistance to cancer therapeutics, we screened a panel of several hundred cancer cell lines-which represent much of the tissue-type and genetic diversity of human cancers-with 130 drugs under clinical and preclinical investigation. In aggregate, we found that mutated cancer genes were associated with cellular response to most currently available cancer drugs. Classic oncogene addiction paradigms were modified by additional tissue-specific or expression biomarkers, and some frequently mutated genes were associated with sensitivity to a broad range of therapeutic agents. Unexpected relationships were revealed, including the marked sensitivity of Ewing's sarcoma cells harbouring the EWS (also known as EWSR1)-FLI1 gene translocation to poly(ADP-ribose) polymerase (PARP) inhibitors. By linking drug activity to the functional complexity of cancer genomes, systematic pharmacogenomic profiling in cancer cell lines provides a powerful biomarker discovery platform to guide rational cancer therapeutic strategies.
C1 [Garnett, Mathew J.; Heidorn, Sonja J.; Greenman, Chris D.; Lau, King Wai; Thompson, I. Richard; Soares, Jorge; Iorio, Francesco; Bignell, Graham R.; Davies, Helen; Barthorpe, Syd; Kogera, Fiona; Lawrence, Karl; McLaren-Douglas, Anne; Mironenko, Tatiana; Richardson, Laura; Jewitt, Frances; O'Brien, Patrick; Price, Stacey; Yang, Wanjuan; Butler, Adam; Futreal, P. Andrew; Stratton, Michael R.; McDermott, Ultan] Wellcome Trust Sanger Inst, Canc Genome Project, Hinxton CB10 1SA, England.
   [Edelman, Elena J.; Dastur, Anahita; Greninger, Patricia; Luo, Xi; Chen, Li; Milano, Randy J.; Stevenson, Jesse A.; Lutz, Stephen R.; Mitropoulos, Xeni; Thi, Helen; Boisvert, Jessica L.; Baselga, Jose; Engelman, Jeffrey A.; Sharma, Sreenath V.; Settleman, Jeffrey; Haber, Daniel A.; Ramaswamy, Sridhar; Benes, Cyril H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Charlestown, MA 02129 USA.
   [Liu, Qingsong; Zhou, Wenjun; Zhang, Tinghu; Hur, Wooyoung; Deng, Xianming; Choi, Hwan Geun; Chang, JaeWon; Gray, Nathanael S.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
   [Liu, Qingsong; Zhou, Wenjun; Zhang, Tinghu; Hur, Wooyoung; Deng, Xianming; Choi, Hwan Geun; Chang, JaeWon; Gray, Nathanael S.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
   [Iorio, Francesco; Saez-Rodriguez, Julio] EMBL EBI, Cambridge CB10 1SD, England.
   [Surdez, Didier; Delattre, Olivier] Inst Curie, Lab Genet & Biol Canc, F-75248 Paris 05, France.
   [Stamenkovic, Ivan] CHU Vaudois, Inst Pathol, Div Expt Pathol, CH-1005 Lausanne, Switzerland.
   [Haber, Daniel A.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA.
C3 Wellcome Trust Sanger Institute; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard Medical School; European Molecular Biology Laboratory (EMBL); European Bioinformatics Institute; UNICANCER; Universite PSL; Institut Curie; University of Lausanne; Centre Hospitalier Universitaire Vaudois (CHUV); Howard Hughes Medical Institute
RP McDermott, U (corresponding author), Wellcome Trust Sanger Inst, Canc Genome Project, Hinxton CB10 1SA, England.
EM um1@sanger.ac.uk; cbenes@partners.org
FU Wellcome Trust [086357]; National Institutes of Health [P41GM079575-02, 1U54HG006097-01]; Howard Hughes Medical Institute; Cancer Research UK Clinician Scientist Fellowship; Div Of Chem, Bioeng, Env, & Transp Sys; Directorate For Engineering [0744413] Funding Source: National Science Foundation
NR 37
TC 1924
Z9 2188
U1 3
U2 396
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD MAR 29
PY 2012
VL 483
IS 7391
BP 570
EP U87
DI 10.1038/nature11005
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 915EF
UT WOS:000302006100033
PM 22460902
DA 2026-03-09
ER

PT J
AU Sun, LF
   Zeng, X
   Yan, CY
   Sun, XY
   Gong, XQ
   Rao, Y
   Yan, NE
AF Sun, Linfeng
   Zeng, Xin
   Yan, Chuangye
   Sun, Xiuyun
   Gong, Xinqi
   Rao, Yu
   Yan, Nieng
TI Crystal structure of a bacterial homologue of glucose transporters GLUT1-4
SO NATURE
LA English
DT Article
ID deficiency syndrome glut1ds; molecular-basis; classification database; substrate recognition; lactose permease; binding-site; mechanism; proteins; gene; sequence
AB Glucose transporters are essential for metabolism of glucose in cells of diverse organisms from microbes to humans, exemplified by the disease-related human proteins GLUT1, 2, 3 and 4. Despite rigorous efforts, the structural information for GLUT1-4 or their homologues remains largely unknown. Here we report three related crystal structures of XylE, an Escherichia coli homologue of GLUT1-4, in complex with D-xylose, D-glucose and 6-bromo-6-deoxy-D-glucose, at resolutions of 2.8, 2.9 and 2.6 angstrom, respectively. The structure consists of a typical major facilitator superfamily fold of 12 transmembrane segments and a unique intracellular four-helix domain. XylE was captured in an outward-facing, partly occluded conformation. Most of the important amino acids responsible for recognition of D-xylose or D-glucose are invariant in GLUT1-4, suggesting functional and mechanistic conservations. Structure-based modelling of GLUT1-4 allows mapping and interpretation of disease-related mutations. The structural and biochemical information reported here constitutes an important framework for mechanistic understanding of glucose transporters and sugar porters in general.
C1 [Sun, Linfeng; Zeng, Xin; Yan, Chuangye; Gong, Xinqi; Yan, Nieng] Tsinghua Univ, Struct Biol Ctr, State Key Lab Biomembrane & Membrane Biotechnol, Beijing 100084, Peoples R China.
   [Sun, Linfeng; Zeng, Xin; Yan, Chuangye; Sun, Xiuyun; Gong, Xinqi; Rao, Yu; Yan, Nieng] Tsinghua Univ, Sch Life Sci, Beijing 100084, Peoples R China.
   [Sun, Linfeng; Zeng, Xin; Yan, Chuangye; Sun, Xiuyun; Gong, Xinqi; Rao, Yu; Yan, Nieng] Tsinghua Univ, Sch Med, Beijing 100084, Peoples R China.
   [Sun, Linfeng; Zeng, Xin; Yan, Chuangye; Gong, Xinqi; 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, NE (corresponding author), Tsinghua Univ, Struct Biol Ctr, State Key Lab Biomembrane & Membrane Biotechnol, Beijing 100084, Peoples R China.
EM nyan@tsinghua.edu.cn
FU Ministry of Science and Technology [2009CB918802, 2011CB910501]; National Natural Science Foundation of China [31125009, 91017011]; Tsinghua University
NR 62
TC 388
Z9 454
U1 6
U2 473
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 18
PY 2012
VL 490
IS 7420
BP 361
EP +
DI 10.1038/nature11524
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 021XI
UT WOS:000309918500037
PM 23075985
DA 2026-03-09
ER

PT J
AU Huttenhower, C
   Gevers, D
   Knight, R
   Abubucker, S
   Badger, JH
   Chinwalla, AT
   Creasy, HH
   Earl, AM
   FitzGerald, MG
   Fulton, RS
   Giglio, MG
   Hallsworth-Pepin, K
   Lobos, EA
   Madupu, R
   Magrini, V
   Martin, JC
   Mitreva, M
   Muzny, DM
   Sodergren, EJ
   Versalovic, J
   Wollam, AM
   Worley, KC
   Wortman, JR
   Young, SK
   Zeng, QD
   Aagaard, KM
   Abolude, OO
   Allen-Vercoe, E
   Alm, EJ
   Alvarado, L
   Andersen, GL
   Anderson, S
   Appelbaum, E
   Arachchi, HM
   Armitage, G
   Arze, CA
   Ayvaz, T
   Baker, CC
   Begg, L
   Belachew, T
   Bhonagiri, V
   Bihan, M
   Blaser, MJ
   Bloom, T
   Bonazzi, V
   Brooks, JP
   Buck, GA
   Buhay, CJ
   Busam, DA
   Campbell, JL
   Canon, SR
   Cantarel, BL
   Chain, PSG
   Chen, IMA
   Chen, L
   Chhibba, S
   Chu, K
   Ciulla, DM
   Clemente, JC
   Clifton, SW
   Conlan, S
   Crabtree, J
   Cutting, MA
   Davidovics, NJ
   Davis, CC
   DeSantis, TZ
   Deal, C
   Delehaunty, KD
   Dewhirst, FE
   Deych, E
   Ding, Y
   Dooling, DJ
   Dugan, SP
   Dunne, WM
   Durkin, AS
   Edgar, RC
   Erlich, RL
   Farmer, CN
   Farrell, RM
   Faust, K
   Feldgarden, M
   Felix, VM
   Fisher, S
   Fodor, AA
   Forney, LJ
   Foster, L
   Di Francesco, V
   Friedman, J
   Friedrich, DC
   Fronick, CC
   Fulton, LL
   Gao, HY
   Garcia, N
   Giannoukos, G
   Giblin, C
   Giovanni, MY
   Goldberg, JM
   Goll, J
   Gonzalez, A
   Griggs, A
   Gujja, S
   Haake, SK
   Haas, BJ
   Hamilton, HA
   Harris, EL
   Hepburn, TA
   Herter, B
   Hoffmann, DE
   Holder, ME
   Howarth, C
   Huang, KH
   Huse, SM
   Izard, J
   Jansson, JK
   Jiang, HY
   Jordan, C
   Joshi, V
   Katancik, JA
   Keitel, WA
   Kelley, ST
   Kells, C
   King, NB
   Knights, D
   Kong, HDH
   Koren, O
   Koren, S
   Kota, KC
   Kovar, CL
   Kyrpides, NC
   La Rosa, PS
   Lee, SL
   Lemon, KP
   Lennon, N
   Lewis, CM
   Lewis, L
   Ley, RE
   Li, K
   Liolios, K
   Liu, B
   Liu, Y
   Lo, CC
   Lozupone, CA
   Lunsford, RD
   Madden, T
   Mahurkar, AA
   Mannon, PJ
   Mardis, ER
   Markowitz, VM
   Mavromatis, K
   McCorrison, JM
   McDonald, D
   McEwen, J
   McGuire, AL
   McInnes, P
   Mehta, T
   Mihindukulasuriya, KA
   Miller, JR
   Minx, PJ
   Newsham, I
   Nusbaum, C
   O'Laughlin, M
   Orvis, J
   Pagani, I
   Palaniappan, K
   Patel, SM
   Pearson, M
   Peterson, J
   Podar, M
   Pohl, C
   Pollard, KS
   Pop, M
   Priest, ME
   Proctor, LM
   Qin, X
   Raes, J
   Ravel, J
   Reid, JG
   Rho, M
   Rhodes, R
   Riehle, KP
   Rivera, MC
   Rodriguez-Mueller, B
   Rogers, YH
   Ross, MC
   Russ, C
   Sanka, RK
   Sankar, P
   Sathirapongsasuti, JF
   Schloss, JA
   Schloss, PD
   Schmidt, TM
   Scholz, M
   Schriml, L
   Schubert, AM
   Segata, N
   Segre, JA
   Shannon, WD
   Sharp, RR
   Sharpton, TJ
   Shenoy, N
   Sheth, NU
   Simone, GA
   Singh, I
   Smillie, CS
   Sobel, JD
   Sommer, DD
   Spicer, P
   Sutton, GG
   Sykes, SM
   Tabbaa, DG
   Thiagarajan, M
   Tomlinson, CM
   Torralba, M
   Treangen, TJ
   Truty, RM
   Vishnivetskaya, TA
   Walker, J
   Wang, L
   Wang, ZY
   Ward, DV
   Warren, W
   Watson, MA
   Wellington, C
   Wetterstrand, KA
   White, JR
   Wilczek-Boney, K
   Wu, YQ
   Wylie, KM
   Wylie, T
   Yandava, C
   Ye, L
   Ye, YZ
   Yooseph, S
   Youmans, BP
   Zhang, L
   Zhou, YJ
   Zhu, YM
   Zoloth, L
   Zucker, JD
   Birren, BW
   Gibbs, RA
   Highlander, SK
   Methé, BA
   Nelson, KE
   Petrosino, JF
   Weinstock, GM
   Wilson, RK
   White, O
AF Huttenhower, Curtis
   Gevers, Dirk
   Knight, Rob
   Abubucker, Sahar
   Badger, Jonathan H.
   Chinwalla, Asif T.
   Creasy, Heather H.
   Earl, Ashlee M.
   FitzGerald, Michael G.
   Fulton, Robert S.
   Giglio, Michelle G.
   Hallsworth-Pepin, Kymberlie
   Lobos, Elizabeth A.
   Madupu, Ramana
   Magrini, Vincent
   Martin, John C.
   Mitreva, Makedonka
   Muzny, Donna M.
   Sodergren, Erica J.
   Versalovic, James
   Wollam, Aye M.
   Worley, Kim C.
   Wortman, Jennifer R.
   Young, Sarah K.
   Zeng, Qiandong
   Aagaard, Kjersti M.
   Abolude, Olukemi O.
   Allen-Vercoe, Emma
   Alm, Eric J.
   Alvarado, Lucia
   Andersen, Gary L.
   Anderson, Scott
   Appelbaum, Elizabeth
   Arachchi, Harindra M.
   Armitage, Gary
   Arze, Cesar A.
   Ayvaz, Tulin
   Baker, Carl C.
   Begg, Lisa
   Belachew, Tsegahiwot
   Bhonagiri, Veena
   Bihan, Monika
   Blaser, Martin J.
   Bloom, Toby
   Bonazzi, Vivien
   Brooks, J. Paul
   Buck, Gregory A.
   Buhay, Christian J.
   Busam, Dana A.
   Campbell, Joseph L.
   Canon, Shane R.
   Cantarel, Brandi L.
   Chain, Patrick S. G.
   Chen, I-Min A.
   Chen, Lei
   Chhibba, Shaila
   Chu, Ken
   Ciulla, Dawn M.
   Clemente, Jose C.
   Clifton, Sandra W.
   Conlan, Sean
   Crabtree, Jonathan
   Cutting, Mary A.
   Davidovics, Noam J.
   Davis, Catherine C.
   DeSantis, Todd Z.
   Deal, Carolyn
   Delehaunty, Kimberley D.
   Dewhirst, Floyd E.
   Deych, Elena
   Ding, Yan
   Dooling, David J.
   Dugan, Shannon P.
   Dunne, Wm Michael
   Durkin, A. Scott
   Edgar, Robert C.
   Erlich, Rachel L.
   Farmer, Candace N.
   Farrell, Ruth M.
   Faust, Karoline
   Feldgarden, Michael
   Felix, Victor M.
   Fisher, Sheila
   Fodor, Anthony A.
   Forney, Larry J.
   Foster, Leslie
   Di Francesco, Valentina
   Friedman, Jonathan
   Friedrich, Dennis C.
   Fronick, Catrina C.
   Fulton, Lucinda L.
   Gao, Hongyu
   Garcia, Nathalia
   Giannoukos, Georgia
   Giblin, Christina
   Giovanni, Maria Y.
   Goldberg, Jonathan M.
   Goll, Johannes
   Gonzalez, Antonio
   Griggs, Allison
   Gujja, Sharvari
   Haake, Susan Kinder
   Haas, Brian J.
   Hamilton, Holli A.
   Harris, Emily L.
   Hepburn, Theresa A.
   Herter, Brandi
   Hoffmann, Diane E.
   Holder, Michael E.
   Howarth, Clinton
   Huang, Katherine H.
   Huse, Susan M.
   Izard, Jacques
   Jansson, Janet K.
   Jiang, Huaiyang
   Jordan, Catherine
   Joshi, Vandita
   Katancik, James A.
   Keitel, Wendy A.
   Kelley, Scott T.
   Kells, Cristyn
   King, Nicholas B.
   Knights, Dan
   Kong, Heidi H.
   Koren, Omry
   Koren, Sergey
   Kota, Karthik C.
   Kovar, Christie L.
   Kyrpides, Nikos C.
   La Rosa, Patricio S.
   Lee, Sandra L.
   Lemon, Katherine P.
   Lennon, Niall
   Lewis, Cecil M.
   Lewis, Lora
   Ley, Ruth E.
   Li, Kelvin
   Liolios, Konstantinos
   Liu, Bo
   Liu, Yue
   Lo, Chien-Chi
   Lozupone, Catherine A.
   Lunsford, R. Dwayne
   Madden, Tessa
   Mahurkar, Anup A.
   Mannon, Peter J.
   Mardis, Elaine R.
   Markowitz, Victor M.
   Mavromatis, Konstantinos
   McCorrison, Jamison M.
   McDonald, Daniel
   McEwen, Jean
   McGuire, Amy L.
   McInnes, Pamela
   Mehta, Teena
   Mihindukulasuriya, Kathie A.
   Miller, Jason R.
   Minx, Patrick J.
   Newsham, Irene
   Nusbaum, Chad
   O'Laughlin, Michelle
   Orvis, Joshua
   Pagani, Ioanna
   Palaniappan, Krishna
   Patel, Shital M.
   Pearson, Matthew
   Peterson, Jane
   Podar, Mircea
   Pohl, Craig
   Pollard, Katherine S.
   Pop, Mihai
   Priest, Margaret E.
   Proctor, Lita M.
   Qin, Xiang
   Raes, Jeroen
   Ravel, Jacques
   Reid, Jeffrey G.
   Rho, Mina
   Rhodes, Rosamond
   Riehle, Kevin P.
   Rivera, Maria C.
   Rodriguez-Mueller, Beltran
   Rogers, Yu-Hui
   Ross, Matthew C.
   Russ, Carsten
   Sanka, Ravi K.
   Sankar, Pamela
   Sathirapongsasuti, J. Fah
   Schloss, Jeffery A.
   Schloss, Patrick D.
   Schmidt, Thomas M.
   Scholz, Matthew
   Schriml, Lynn
   Schubert, Alyxandria M.
   Segata, Nicola
   Segre, Julia A.
   Shannon, William D.
   Sharp, Richard R.
   Sharpton, Thomas J.
   Shenoy, Narmada
   Sheth, Nihar U.
   Simone, Gina A.
   Singh, Indresh
   Smillie, Christopher S.
   Sobel, Jack D.
   Sommer, Daniel D.
   Spicer, Paul
   Sutton, Granger G.
   Sykes, Sean M.
   Tabbaa, Diana G.
   Thiagarajan, Mathangi
   Tomlinson, Chad M.
   Torralba, Manolito
   Treangen, Todd J.
   Truty, Rebecca M.
   Vishnivetskaya, Tatiana A.
   Walker, Jason
   Wang, Lu
   Wang, Zhengyuan
   Ward, Doyle V.
   Warren, Wesley
   Watson, Mark A.
   Wellington, Christopher
   Wetterstrand, Kris A.
   White, James R.
   Wilczek-Boney, Katarzyna
   Wu, YuanQing
   Wylie, Kristine M.
   Wylie, Todd
   Yandava, Chandri
   Ye, Liang
   Ye, Yuzhen
   Yooseph, Shibu
   Youmans, Bonnie P.
   Zhang, Lan
   Zhou, Yanjiao
   Zhu, Yiming
   Zoloth, Laurie
   Zucker, Jeremy D.
   Birren, Bruce W.
   Gibbs, Richard A.
   Highlander, Sarah K.
   Methe, Barbara A.
   Nelson, Karen E.
   Petrosino, Joseph F.
   Weinstock, George M.
   Wilson, Richard K.
   White, Owen
TI Structure, function and diversity of the healthy human microbiome
SO NATURE
LA English
DT Article
ID identification; bacteria
AB Studies of the human microbiome have revealed that even healthy individuals differ remarkably in the microbes that occupy habitats such as the gut, skin and vagina. Much of this diversity remains unexplained, although diet, environment, host genetics and early microbial exposure have all been implicated. Accordingly, to characterize the ecology of human-associated microbial communities, the Human Microbiome Project has analysed the largest cohort and set of distinct, clinically relevant body habitats so far. We found the diversity and abundance of each habitat's signature microbes to vary widely even among healthy subjects, with strong niche specialization both within and among individuals. The project encountered an estimated 81-99% of the genera, enzyme families and community configurations occupied by the healthy Western microbiome. Metagenomic carriage of metabolic pathways was stable among individuals despite variation in community structure, and ethnic/racial background proved to be one of the strongest associations of both pathways and microbes with clinical metadata. These results thus delineate the range of structural and functional configurations normal in the microbial communities of a healthy population, enabling future characterization of the epidemiology, ecology and translational applications of the human microbiome.
C1 [Huttenhower, Curtis; Sathirapongsasuti, J. Fah; Segata, Nicola] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
   [Huttenhower, Curtis; Gevers, Dirk; Earl, Ashlee M.; FitzGerald, Michael G.; Young, Sarah K.; Zeng, Qiandong; Alm, Eric J.; Alvarado, Lucia; Anderson, Scott; Arachchi, Harindra M.; Bloom, Toby; Ciulla, Dawn M.; Erlich, Rachel L.; Feldgarden, Michael; Fisher, Sheila; Friedrich, Dennis C.; Giannoukos, Georgia; Goldberg, Jonathan M.; Griggs, Allison; Gujja, Sharvari; Haas, Brian J.; Hepburn, Theresa A.; Howarth, Clinton; Huang, Katherine H.; Kells, Cristyn; Lennon, Niall; Mehta, Teena; Nusbaum, Chad; Pearson, Matthew; Priest, Margaret E.; Russ, Carsten; Shenoy, Narmada; Sykes, Sean M.; Tabbaa, Diana G.; Ward, Doyle V.; Yandava, Chandri; Zucker, Jeremy D.; Birren, Bruce W.] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.
   [Knight, Rob; Clemente, Jose C.; Lozupone, Catherine A.; McDonald, Daniel] Univ Colorado, Dept Chem & Biochem, Boulder, CO 80309 USA.
   [Knight, Rob] Howard Hughes Med Inst, Boulder, CO 80309 USA.
   [Abubucker, Sahar; Chinwalla, Asif T.; Fulton, Robert S.; Hallsworth-Pepin, Kymberlie; Lobos, Elizabeth A.; Magrini, Vincent; Martin, John C.; Mitreva, Makedonka; Sodergren, Erica J.; Wollam, Aye M.; Appelbaum, Elizabeth; Bhonagiri, Veena; Chen, Lei; Clifton, Sandra W.; Delehaunty, Kimberley D.; Dooling, David J.; Farmer, Candace N.; Fronick, Catrina C.; Fulton, Lucinda L.; Gao, Hongyu; Herter, Brandi; Kota, Karthik C.; Mardis, Elaine R.; Mihindukulasuriya, Kathie A.; Minx, Patrick J.; O'Laughlin, Michelle; Pohl, Craig; Tomlinson, Chad M.; Walker, Jason; Wang, Zhengyuan; Warren, Wesley; Wylie, Kristine M.; Wylie, Todd; Ye, Liang; Zhou, Yanjiao; Weinstock, George M.; Wilson, Richard K.] Washington Univ, Sch Med, Genome Inst, St Louis, MO 63108 USA.
   [Badger, Jonathan H.; Madupu, Ramana; Bihan, Monika; Busam, Dana A.; Durkin, A. Scott; Foster, Leslie; Goll, Johannes; Li, Kelvin; McCorrison, Jamison M.; Miller, Jason R.; Rogers, Yu-Hui; Sanka, Ravi K.; Singh, Indresh; Sutton, Granger G.; Thiagarajan, Mathangi; Torralba, Manolito; Methe, Barbara A.; Nelson, Karen E.] J Craig Venter Inst, Rockville, MD 20850 USA.
   [Creasy, Heather H.; Giglio, Michelle G.; Wortman, Jennifer R.; Abolude, Olukemi O.; Arze, Cesar A.; Cantarel, Brandi L.; Crabtree, Jonathan; Davidovics, Noam J.; Felix, Victor M.; Jordan, Catherine; Mahurkar, Anup A.; Orvis, Joshua; Ravel, Jacques; Schriml, Lynn; White, James R.; White, Owen] Univ Maryland, Sch Med, Inst Genome Sci, Baltimore, MD 21201 USA.
   [Muzny, Donna M.; Worley, Kim C.; Buhay, Christian J.; Ding, Yan; Dugan, Shannon P.; Holder, Michael E.; Jiang, Huaiyang; Joshi, Vandita; Kovar, Christie L.; Lee, Sandra L.; Lewis, Lora; Liu, Yue; Newsham, Irene; Qin, Xiang; Reid, Jeffrey G.; Wilczek-Boney, Katarzyna; Wu, YuanQing; Zhang, Lan; Zhu, Yiming; Gibbs, Richard A.; Highlander, Sarah K.; Petrosino, Joseph F.] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA.
   [Versalovic, James] Baylor Coll Med, Dept Pathol & Immunol, Houston, TX 77030 USA.
   [Versalovic, James] Texas Childrens Hosp, Dept Pathol, Houston, TX 77030 USA.
   [Aagaard, Kjersti M.] Baylor Coll Med, Dept Obstet & Gynecol, Div Maternal Fetal Med, Houston, TX 77030 USA.
   [Allen-Vercoe, Emma] Univ Guelph, Guelph, ON N1G 2W1, Canada.
   [Alm, Eric J.] MIT, Dept Civil & Environm Engn, Cambridge, MA 02139 USA.
   [Andersen, Gary L.] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Ctr Environm Biotechnol, Berkeley, CA 94720 USA.
   [Armitage, Gary] Univ Calif San Francisco, Sch Dent, San Francisco, CA 94143 USA.
   [Baker, Carl C.] Natl Inst Arthrit & Musculoskeletal & Skin, NIH, Bethesda, MD 20892 USA.
   [Begg, Lisa] Off Res Womens Hlth, NIH, Bethesda, MD 20892 USA.
   [Belachew, Tsegahiwot; Campbell, Joseph L.; Deal, Carolyn; Di Francesco, Valentina; Giblin, Christina; Giovanni, Maria Y.] NIAID, NIH, Bethesda, MD 20892 USA.
   [Blaser, Martin J.] NYU, Langone Med Ctr, Dept Med, New York, NY 10016 USA.
   [Bonazzi, Vivien; Campbell, Joseph L.; Chhibba, Shaila; McEwen, Jean; Peterson, Jane; Proctor, Lita M.; Schloss, Jeffery A.; Wang, Lu; Wellington, Christopher; Wetterstrand, Kris A.] NHGRI, NIH, Bethesda, MD 20892 USA.
   [Brooks, J. Paul] Virginia Commonwealth Univ, Dept Stat Sci & Operat Res, Richmond, VA 23284 USA.
   [Brooks, J. Paul; Buck, Gregory A.; Rivera, Maria C.; Sheth, Nihar U.] Virginia Commonwealth Univ, Ctr Study Biol Complex, Richmond, VA 23284 USA.
   [Buck, Gregory A.; Rivera, Maria C.] Virginia Commonwealth Univ, Dept Biol, Richmond, VA 23284 USA.
   [Canon, Shane R.] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Natl Energy Res Sci Comp Ctr, Technol Integrat Grp, Berkeley, CA 94720 USA.
   [Chain, Patrick S. G.; Lo, Chien-Chi; Scholz, Matthew] Los Alamos Natl Lab, Biosci Div, Genome Sci Grp, Los Alamos, NM 87545 USA.
   [Chain, Patrick S. G.; Kyrpides, Nikos C.; Liolios, Konstantinos; Markowitz, Victor M.; Mavromatis, Konstantinos; Pagani, Ioanna] Joint Genome Inst, Walnut Creek, CA 94598 USA.
   [Chen, I-Min A.; Chu, Ken; Markowitz, Victor M.; Palaniappan, Krishna] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Computat Res Div, Biol Data Management & Technol Ctr, Berkeley, CA 94720 USA.
   [Cutting, Mary A.; Hamilton, Holli A.; Harris, Emily L.; Lunsford, R. Dwayne; McInnes, Pamela] NIDCR, NIH, Bethesda, MD 20892 USA.
   [Davis, Catherine C.] Procter & Gamble Co, FemCare Prod Safety & Regulatory Affairs, Cincinnati, OH 45224 USA.
   [DeSantis, Todd Z.] Second Genome Inc, Bioinformat Dept, San Bruno, CA 94066 USA.
   [Dewhirst, Floyd E.; Izard, Jacques; Lemon, Katherine P.] Forsyth Inst, Dept Mol Genet, Cambridge, MA 02142 USA.
   [Dewhirst, Floyd E.; Izard, Jacques] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA.
   [Deych, Elena; La Rosa, Patricio S.; Shannon, William D.] Washington Univ, Sch Med, Dept Med, Div Gen Med Sci, St Louis, MO 63110 USA.
   [Dunne, Wm Michael; Watson, Mark A.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA.
   [Dunne, Wm Michael] bioMerieux Inc, Durham, SC 27712 USA.
   [Edgar, Robert C.] Drive5 Com, Tiburon, CA 94920 USA.
   [Farrell, Ruth M.; Sharp, Richard R.] Cleveland Clin, Ctr Eth Humanities & Spiritual Care, Cleveland, OH 44195 USA.
   [Faust, Karoline; Raes, Jeroen] VIB, Dept Biol Struct, B-1050 Ixelles, Belgium.
   [Faust, Karoline; Raes, Jeroen] Vrije Univ Brussel, Dept Appl Biol Sci DBIT, B-1050 Ixelles, Belgium.
   [Fodor, Anthony A.] Univ N Carolina, Dept Bioinformat & Genom, Charlotte, NC 28223 USA.
   [Forney, Larry J.] Univ Idaho, Dept Biol Sci, Moscow, ID 83844 USA.
   [Garcia, Nathalia] St Louis Univ, Ctr Adv Dent Educ, St Louis, MO 63104 USA.
   [Gonzalez, Antonio; Knights, Dan] Univ Colorado, Dept Comp Sci, Boulder, CO 80309 USA.
   [Haake, Susan Kinder] Univ Calif Los Angeles, Sch Dent, Div Associated Clin Specialties, Los Angeles, CA 90095 USA.
   [Haake, Susan Kinder] Univ Calif Los Angeles, Sch Dent, Dent Res Inst, Los Angeles, CA 90095 USA.
   [Hoffmann, Diane E.] Univ Maryland, Francis King Carey Sch Law, Baltimore, MD 21201 USA.
   [Huse, Susan M.] Marine Biol Lab, Josephine Bay Paul Ctr, Woods Hole, MA 02543 USA.
   [Jansson, Janet K.] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Div Earth Sci, Dept Ecol, Berkeley, CA 94720 USA.
   [Katancik, James A.] Univ Texas Hlth Sci Ctr, Sch Dent, Dept Periodont, Houston, TX 77030 USA.
   [Kelley, Scott T.; Rodriguez-Mueller, Beltran] San Diego State Univ, Dept Biol, San Diego, CA 92182 USA.
   [King, Nicholas B.; Podar, Mircea] McGill Univ, Fac Med, Montreal, PQ H3A 1X1, Canada.
   [Kong, Heidi H.] NCI, Dermatol Branch, CCR, Bethesda, MD 20892 USA.
   [Koren, Omry; Ley, Ruth E.] Cornell Univ, Dept Microbiol, Ithaca, NY 14853 USA.
   [Koren, Sergey; Liu, Bo; Pop, Mihai; Sommer, Daniel D.] Univ Maryland, Ctr Bioinformat & Computat Biol, College Pk, MD 20742 USA.
   [Lemon, Katherine P.] Harvard Univ, Sch Med, Childrens Hosp Boston, Div Infect Dis, Boston, MA 02115 USA.
   [Lewis, Cecil M.; Spicer, Paul] Univ Oklahoma, Dept Anthropol, Norman, OK 73019 USA.
   [Madden, Tessa] Washington Univ, Sch Med, Dept Obstet & Gynecol, St Louis, MO 63110 USA.
   [Mannon, Peter J.] Univ Alabama Birmingham, Div Gastroenterol & Hepatol, Birmingham, AL 35294 USA.
   [McGuire, Amy L.] Baylor Coll Med, Ctr Med Eth & Hlth Policy, Houston, TX 77030 USA.
   [Vishnivetskaya, Tatiana A.] Oak Ridge Natl Lab, Biosci Div, Oak Ridge, TN 37831 USA.
   [Pollard, Katherine S.; Sharpton, Thomas J.; Truty, Rebecca M.] Univ Calif San Francisco, Gladstone Inst, San Francisco, CA 94158 USA.
   [Pollard, Katherine S.] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94158 USA.
   [Pollard, Katherine S.] Univ Calif San Francisco, Div Biostat, San Francisco, CA 94158 USA.
   [Pop, Mihai] Univ Maryland, Dept Comp Sci, College Pk, MD 20742 USA.
   [Rho, Mina; Ye, Yuzhen] Indiana Univ, Sch Informat & Comp, Bloomington, IN 47405 USA.
   [Rhodes, Rosamond] Mt Sinai Sch Med, New York, NY 10029 USA.
   [Sankar, Pamela] Univ Penn, Ctr Bioeth, Philadelphia, PA 19104 USA.
   [Sankar, Pamela] Univ Penn, Dept Med Eth, Philadelphia, PA 19104 USA.
   [Schloss, Patrick D.; Schubert, Alyxandria M.] Univ Michigan, Dept Microbiol & Immunol, Ann Arbor, MI 48109 USA.
   [Schmidt, Thomas M.] Michigan State Univ, Dept Microbiol & Mol Genet, E Lansing, MI 48824 USA.
   [Simone, Gina A.] EMMES Corp, Rockville, MD 20850 USA.
   [Sobel, Jack D.] Wayne State Univ, Sch Med, Harper Univ Hosp, Detroit, MI 48201 USA.
   [Treangen, Todd J.] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD 21205 USA.
   [Yooseph, Shibu] J Craig Venter Inst, San Diego, CA 92121 USA.
   [Zoloth, Laurie] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA.
   [Petrosino, Joseph F.] Baylor Coll Med, Alkek Ctr Metagenom & Microbiome Res, Houston, TX 77030 USA.
   [Conlan, Sean; Segre, Julia A.] NHGRI, Genet & Mol Biol Branch, Bethesda, MD 20892 USA.
C3 Harvard University; Harvard T.H. Chan School of Public Health; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; University of Colorado System; University of Colorado Boulder; Howard Hughes Medical Institute; Washington University (WUSTL); J. Craig Venter Institute; University System of Maryland; University of Maryland Baltimore; Baylor College of Medicine; Baylor College of Medicine; Baylor College of Medicine; Baylor College Medical Hospital; Baylor College of Medicine; University of Guelph; Massachusetts Institute of Technology (MIT); 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; National Institutes of Health (NIH) - USA; NIH National Institute of Arthritis & Musculoskeletal & Skin Diseases (NIAMS); National Institutes of Health (NIH) - USA; NIH Office of Research on Women's Health (ORWH); National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID); NYU Langone Medical Center; New York University; National Institutes of Health (NIH) - USA; NIH National Human Genome Research Institute (NHGRI); Virginia Commonwealth University; Virginia Commonwealth University; Virginia Commonwealth University; United States Department of Energy (DOE); Lawrence Berkeley National Laboratory; University of California System; University of California Berkeley; United States Department of Energy (DOE); Los Alamos National Laboratory; United States Department of Energy (DOE); Joint Genome Institute - JGI; Joint BioEnergy Institute - JBEI; United States Department of Energy (DOE); Lawrence Berkeley National Laboratory; University of California System; University of California Berkeley; National Institutes of Health (NIH) - USA; NIH National Institute of Dental & Craniofacial Research (NIDCR); Procter & Gamble; Harvard University; Harvard University Medical Affiliates; Forsyth Institute; Harvard University; Washington University (WUSTL); Washington University (WUSTL); Cleveland Clinic Foundation; Flanders Institute for Biotechnology (VIB); Vrije Universiteit Brussel; University of North Carolina; University of North Carolina Charlotte; University of Idaho; Saint Louis University; University of Colorado System; University of Colorado Boulder; University of California System; University of California Los Angeles; University of California System; University of California Los Angeles; University System of Maryland; University of Maryland Baltimore; Marine Biological Laboratory - Woods Hole; University of California System; University of California Berkeley; United States Department of Energy (DOE); Lawrence Berkeley National Laboratory; University of Texas System; University of Texas Health Science Center Houston; California State University System; San Diego State University; McGill University; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); Cornell University; University System of Maryland; University of Maryland College Park; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Harvard Medical School; University of Oklahoma System; University of Oklahoma - Norman; Washington University (WUSTL); University of Alabama System; University of Alabama Birmingham; Baylor College of Medicine; United States Department of Energy (DOE); Oak Ridge National Laboratory; 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 System of Maryland; University of Maryland College Park; Indiana University System; Indiana University Bloomington; Icahn School of Medicine at Mount Sinai; University of Pennsylvania; University of Pennsylvania; University of Michigan System; University of Michigan; Michigan State University; Emmes Corporation; Wayne State University; Johns Hopkins University; J. Craig Venter Institute; Northwestern University; Feinberg School of Medicine; Baylor College of Medicine; National Institutes of Health (NIH) - USA; NIH National Human Genome Research Institute (NHGRI)
RP Huttenhower, C (corresponding author), Harvard Univ, Sch Publ Hlth, 665 Huntington Ave, Boston, MA 02115 USA.
EM chuttenh@hsph.harvard.edu
FU National Institutes of Health [U54HG004969, U54HG003273, U54HG004973, U54HG003067, U54AI084844, N01AI30071, U54HG004968, U01HG004866, U54HG003079, R01HG005969, R01HG004872, R01HG004885, R01HG005975, R01HG004908, R01HG004900, R01HG005171, R01HG004853]; Army Research Office [W911NF-11-1-0473]; National Science Foundation [NSF DBI-1053486, NSF IIS-0812111]; Office of Science of the US Department of Energy [DE-AC02-05CH11231]; LANL Laboratory-Directed Research and Development [20100034DR]; US Defense Threat Reduction Agency [B104153I, B084531I]; Research Foundation - Flanders (FWO); Gordon & Betty Moore Foundation; J. David Gladstone Institutes; Rackham Graduate School; Colitis Foundation of Canada; IBM;  [UH2AR057506];  [UH2AI083263];  [UH3AI083263];  [UH3DK083993];  [UH2DK083990];  [UH2AR057504];  [UH3AR057504];  [DP2OD001500];  [N01HG62088];  [U01DE016937];  [RC1DE0202098];  [R01DE021574];  [R21CA139193];  [P30DE020751]; Div Of Biological Infrastructure; Direct For Biological Sciences [1053486] Funding Source: National Science Foundation
NR 26
TC 6143
Z9 7195
U1 53
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 14
PY 2012
VL 486
IS 7402
BP 207
EP 214
DI 10.1038/nature11234
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 957UH
UT WOS:000305189000025
PM 22699609
DA 2026-03-09
ER

PT J
AU Kon, T
   Oyama, T
   Shimo-Kon, R
   Imamula, K
   Shima, T
   Sutoh, K
   Kurisu, G
AF Kon, Takahide
   Oyama, Takuji
   Shimo-Kon, Rieko
   Imamula, Kenji
   Shima, Tomohiro
   Sutoh, Kazuo
   Kurisu, Genji
TI The 2.8 Å crystal structure of the dynein motor domain
SO NATURE
LA English
DT Article
ID microtubule-binding domain; cytoplasmic dynein; coiled-coil; atp hydrolysis; aaa; mechanism; program; crystallography; expression; transport
AB Dyneins are microtubule-based AAA(+) motor complexes that power ciliary beating, cell division, cell migration and intracellular transport. Here we report the most complete structure obtained so far, to our knowledge, of the 380-kDa motor domain of Dictyostelium discoideum cytoplasmic dynein at 2.8 angstrom resolution; the data are reliable enough to discuss the structure and mechanism at the level of individual amino acid residues. Features that can be clearly visualized at this resolution include the coordination of ADP in each of four distinct nucleotide-binding sites in the ring-shaped AAA(+) ATPase unit, a newly identified interaction interface between the ring and mechanical linker, and junctional structures between the ring and microtubule-binding stalk, all of which should be critical for the mechanism of dynein motility. We also identify a long-range allosteric communication pathway between the primary ATPase and the microtubule-binding sites. Our work provides a framework for understanding the mechanism of dynein-based motility.
C1 [Kon, Takahide; Oyama, Takuji; Shimo-Kon, Rieko; Kurisu, Genji] Osaka Univ, Inst Prot Res, Suita, Osaka 5650871, Japan.
   [Kon, Takahide; Kurisu, Genji] Osaka Univ, Dept Macromol Sci, Sch Sci, Osaka 5600043, Japan.
   [Imamula, Kenji] Univ Tokyo, Dept Life Sci, Sch Arts & Sci, Tokyo 1538902, Japan.
   [Shima, Tomohiro] Univ Tokyo, Dept Phys, Grad Sch Sci, Bunkyou Ku, Tokyo 1130033, Japan.
   [Sutoh, Kazuo] Waseda Univ, Res Inst Sci & Engn, Toshima Ku, Tokyo 1710033, Japan.
C3 University of Osaka; University of Osaka; University of Tokyo; University of Tokyo; Waseda University
RP Kon, T (corresponding author), Osaka Univ, Inst Prot Res, 3-2 Yamadaoka, Suita, Osaka 5650871, Japan.
EM takahide.kon@protein.osaka-u.ac.jp
FU Ministry of Education, Culture Sports, Science, and Technology of Japan [17770126, 20687011, 23370073, 16083205, 17107003, 17053006, 18054008, 20051006]; Human Frontier Science Program; Grants-in-Aid for Scientific Research [20051006, 17770126, 20687011, 18054008, 09J10824, 23370075, 17053006, 16083205, 23370073, 17107003] Funding Source: KAKEN
NR 50
TC 205
Z9 255
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 APR 19
PY 2012
VL 484
IS 7394
BP 345
EP U81
DI 10.1038/nature10955
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 927YM
UT WOS:000302946500026
PM 22398446
DA 2026-03-09
ER

PT J
AU Chen, GB
   Bradford, WD
   Seidel, CW
   Li, R
AF Chen, Guangbo
   Bradford, William D.
   Seidel, Chris W.
   Li, Rong
TI Hsp90 stress potentiates rapid cellular adaptation through induction of aneuploidy
SO NATURE
LA English
DT Article
ID saccharomyces-cerevisiae; phenotypic variation; budding yeast; kinetochore; chaperone
AB Aneuploidy-the state of having uneven numbers of chromosomes-is a hallmark of cancer(1) and a feature identified in yeast from diverse habitats(2-5). Recent studies have shown that aneuploidy is a form of large-effect mutation that is able to confer adaptive phenotypes under diverse stress conditions(2,6). Here we investigate whether pleiotropic stress could induce aneuploidy in budding yeast (Saccharomyces cerevisae). We show that whereas diverse stress conditions can induce an increase in chromosome instability, proteotoxic stress, caused by transient Hsp90 (also known as Hsp82 or Hsc82) inhibition or heat shock, markedly increased chromosome instability to produce a cell population with high karyotype diversity. The induced chromosome instability is linked to an evolutionarily conserved role for the Hsp90 chaperone complex in kinetochore assembly(7,8). Continued growth in the presence of an Hsp90 inhibitor resulted in the emergence of drug-resistant colonies with chromosome XV gain. This drug-resistance phenotype is a quantitative trait involving copy number increases of at least two genes located on chromosome XV. Shortterm exposure to Hsp90 stress potentiated fast adaptation to unrelated cytotoxic compounds by means of different aneuploid chromosome stoichiometries. These findings demonstrate that aneuploidy is a form of stress-inducible mutation in eukaryotes, capable of fuelling rapid phenotypic evolution and drug resistance, and reveal a new role for Hsp90 in regulating the emergence of adaptive traits under stress.
C1 [Chen, Guangbo; Bradford, William D.; Seidel, Chris W.; Li, Rong] Stowers Inst Med Res, Kansas City, MO 64110 USA.
   [Chen, Guangbo; Li, Rong] Univ Kansas, Med Ctr, Dept Mol & Integrat Physiol, Kansas City, KS 66160 USA.
C3 Stowers Institute for Medical Research; University of Kansas; University of Kansas Medical Center
RP Li, R (corresponding author), Stowers Inst Med Res, 1000 E 50th St, Kansas City, MO 64110 USA.
EM rli@stowers.org
FU National Institutes of Health [RO1GM059964]
NR 21
TC 206
Z9 240
U1 0
U2 53
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD FEB 9
PY 2012
VL 482
IS 7384
BP 246
EP 250
DI 10.1038/nature10795
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 888HI
UT WOS:000299994100044
PM 22286062
DA 2026-03-09
ER

PT J
AU Stensola, H
   Stensola, T
   Solstad, T
   Froland, K
   Moser, MB
   Moser, EI
AF Stensola, Hanne
   Stensola, Tor
   Solstad, Trygve
   Froland, Kristian
   Moser, May-Britt
   Moser, Edvard I.
TI The entorhinal grid map is discretized
SO NATURE
LA English
DT Article
ID spatial representation; functional architecture; theta oscillations; path-integration; single neurons; cells; interference; direction; cortex; monkey
AB The medial entorhinal cortex (MEC) is part of the brain's circuit for dynamic representation of self-location. The metric of this representation is provided by grid cells, cells with spatial firing fields that tile environments in a periodic hexagonal pattern. Limited anatomical sampling has obscured whether the grid system operates as a unified system or a conglomerate of independent modules. Here we show with recordings from up to 186 grid cells in individual rats that grid cells cluster into a small number of layer-spanning anatomically overlapping modules with distinct scale, orientation, asymmetry and theta-frequency modulation. These modules can respond independently to changes in the geometry of the environment. The discrete topography of the grid-map, and the apparent autonomy of the modules, differ from the graded topography of maps for continuous variables in several sensory systems, raising the possibility that the modularity of the grid map is a product of local self-organizing network dynamics.
C1 [Stensola, Hanne; Stensola, Tor; Solstad, Trygve; Froland, Kristian; Moser, May-Britt; Moser, Edvard I.] Norwegian Univ Sci & Technol, Kavli Inst Syst Neurosci, MTFS, N-7491 Trondheim, Norway.
   [Stensola, Hanne; Stensola, Tor; Solstad, Trygve; Froland, Kristian; Moser, May-Britt; Moser, Edvard I.] Norwegian Univ Sci & Technol, Kavli Inst Syst Neurosci, Ctr Biol Memory, N-7491 Trondheim, Norway.
C3 Norwegian University of Science & Technology (NTNU); Norwegian University of Science & Technology (NTNU)
RP Moser, EI (corresponding author), Norwegian Univ Sci & Technol, Kavli Inst Syst Neurosci, MTFS, Olav Kyrres Gate 9, N-7491 Trondheim, Norway.
EM hanne.stensola@ntnu.no; tor.stensola@ntnu.no; edvard.moser@ntnu.no
FU European Research Council ('CIRCUIT') [232608]; Kavli Foundation; Centre of Excellence scheme of the Research Council of Norway; European Research Council (ERC) [232608] Funding Source: European Research Council (ERC)
NR 50
TC 470
Z9 562
U1 1
U2 118
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 6
PY 2012
VL 492
IS 7427
BP 72
EP 78
DI 10.1038/nature11649
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 048EQ
UT WOS:000311893400047
PM 23222610
DA 2026-03-09
ER

PT J
AU Yue, H
   Lay, T
   Koper, KD
AF Yue, Han
   Lay, Thorne
   Koper, Keith D.
TI En echelon and orthogonal fault ruptures of the 11 April 2012 great intraplate earthquakes
SO NATURE
LA English
DT Article
ID indian-ocean; deformation; sumatra; motion; plate; constraints; seismicity; capricorn; boundary; model
AB The Indo-Australian plate is undergoing distributed internal deformation caused by the lateral transition along its northern boundary-from an environment of continental collision to an island arc subduction zone(1,2). On 11 April 2012, one of the largest strike-slip earthquakes ever recorded (seismic moment magnitude M-w 8.7) occurred about 100-200 kilometres southwest of the Sumatra subduction zone. Occurrence of great intraplate strike-slip faulting located seaward of a subduction zone is unusual. It results from northwest-southeast compression within the plate caused by the India-Eurasia continental collision to the northwest, together with northeast-southwest extension associated with slab pull stresses as the plate underthrusts Sumatra to the northeast. Here we use seismic wave analyses to reveal that the 11 April 2012 event had an extraordinarily complex four-fault rupture lasting about 160 seconds, and was followed approximately two hours later by a great (M-w 8.2) aftershock. The mainshock rupture initially expanded bilaterally with large slip (20-30 metres) on a right-lateral strike-slip fault trending west-northwest to east-southeast (WNW-ESE), and then bilateral rupture was triggered on an orthogonal left-lateral strike-slip fault trending north-northeast to south-southwest (NNE-SSW) that crosses the first fault. This was followed by westward rupture on a second WNW-ESE strike-slip fault offset about 150 kilometres towards the southwest from the first fault. Finally, rupture was triggered on another en echelon WNW-ESE fault about 330 kilometres west of the epicentre crossing the Ninetyeast ridge. The great aftershock, with an epicentre located 185 kilometres to the SSW of the mainshock epicentre, ruptured bilaterally on a NNE-SSW fault. The complex faulting limits our resolution of the slip distribution. These great ruptures on a lattice of strike-slip faults that extend through the crust and a further 30-40 kilometres into the upper mantle represent large lithospheric deformation that may eventually lead to a localized boundary between the Indian and Australian plates.
C1 [Yue, Han; Lay, Thorne] Univ Calif Santa Cruz, Dept Earth & Planetary Sci, Santa Cruz, CA 95064 USA.
   [Koper, Keith D.] Univ Utah, Dept Geol & Geophys, Salt Lake City, UT 84112 USA.
C3 University of California System; University of California Santa Cruz; Utah System of Higher Education; University of Utah
RP Lay, T (corresponding author), Univ Calif Santa Cruz, Dept Earth & Planetary Sci, Santa Cruz, CA 95064 USA.
EM tlay@ucsc.edu
FU NSF [EAR0635570, EAR0951558]; Division Of Earth Sciences; Directorate For Geosciences [0951558] Funding Source: National Science Foundation
NR 35
TC 188
Z9 219
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 OCT 11
PY 2012
VL 490
IS 7419
BP 245
EP +
DI 10.1038/nature11492
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 019IY
UT WOS:000309733300046
PM 23023129
DA 2026-03-09
ER

PT J
AU Angelo, K
   Rancz, EA
   Pimentel, D
   Hundahl, C
   Hannibal, J
   Fleischmann, A
   Pichler, B
   Margrie, TW
AF Angelo, Kamilla
   Rancz, Ede A.
   Pimentel, Diogo
   Hundahl, Christian
   Hannibal, Jens
   Fleischmann, Alexander
   Pichler, Bruno
   Margrie, Troy W.
TI A biophysical signature of network affiliation and sensory processing in mitral cells
SO NATURE
LA English
DT Article
ID hyperpolarization-activated current; pyramidal neurons; olfactory-bulb; i-h; integrative property; entorhinal cortex; diversity; channels; mouse; oscillations
AB One defining characteristic of the mammalian brain is its neuronal diversity(1). For a given region, substructure, layer or even cell type, variability in neuronal morphology and connectivity persists(2-5). Although it is well known that such cellular properties vary considerably according to neuronal type, the substantial biophysical diversity of neurons of the same morphological class is typically averaged out and ignored. Here we show that the amplitude of hyperpolarization-evoked sag of membrane potential recorded in olfactory bulb mitral cells is an emergent, homotypic property of local networks and sensory information processing. Simultaneous whole-cell recordings from pairs of cells show that the amount of hyperpolarization-evoked sag potential and current (I-h)(6) is stereotypic for mitral cells belonging to the same glomerular circuit. This is corroborated by a mosaic, glomerulus-based pattern of expression of the HCN2 (hyperpolarization-activated cyclic nucleotidegated channel 2) subunit of the Ih channel. Furthermore, inter-glomerular differences in both membrane potential sag and HCN2 protein are diminished when sensory input to glomeruli is genetically and globally altered so that only one type of odorant receptor is universally expressed(7). Population diversity in this intrinsic property therefore reflects differential expression between local mitral cell networks processing distinct odour-related information.
C1 [Angelo, Kamilla; Rancz, Ede A.; Pimentel, Diogo; Margrie, Troy W.] UCL, Dept Neurosci Physiol & Pharmacol, London WC1E 6BT, England.
   [Angelo, Kamilla; Hundahl, Christian] Univ Copenhagen, Fac Hlth Sci, Dept Neurosci & Pharmacol, DK-2200 Copenhagen N, Denmark.
   [Rancz, Ede A.; Pichler, Bruno; Margrie, Troy W.] MRC Natl Inst Med Res, Div Neurophysiol, London NW7 1AA, England.
   [Hundahl, Christian; Hannibal, Jens] Univ Copenhagen, Bispebjerg Hosp, Dept Clin Biochem, DK-2200 Copenhagen N, Denmark.
   [Fleischmann, Alexander] Coll France, Ctr Interdisciplinary Res Biol CIRB, F-75231 Paris 05, France.
C3 University of London; University College London; University of Copenhagen; MRC National Institute for Medical Research; University of Copenhagen; Copenhagen University Hospital; Bispebjerg Hospital; Universite PSL; College de France; Institut National de la Sante et de la Recherche Medicale (Inserm)
RP Margrie, TW (corresponding author), UCL, Dept Neurosci Physiol & Pharmacol, Gower St, London WC1E 6BT, England.
EM troy.margrie@nimr.mrc.ac.uk
FU Sir Henry Wellcome Fellowship; Oticon Foundation; Danish Council for Independent Research; Lundbeckfondation; Gulbenkian PhD Programme; Fundacao para a Ciencia e Tecnologia; Wellcome Trust; Medical Research Council [MC_U1175975156]; MRC [MC_U117597156] Funding Source: UKRI; Medical Research Council [MC_U117597156] Funding Source: researchfish
NR 30
TC 67
Z9 73
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 AUG 16
PY 2012
VL 488
IS 7411
BP 375
EP 378
DI 10.1038/nature11291
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 988OS
UT WOS:000307501000041
PM 22820253
DA 2026-03-09
ER

PT J
AU Keppler, F
   Vigano, I
   McLeod, A
   Ott, U
   Früchtl, M
   Röckmann, T
AF Keppler, Frank
   Vigano, Ivan
   McLeod, Andy
   Ott, Ulrich
   Fruchtl, Marion
   Rockmann, Thomas
TI Ultraviolet-radiation-induced methane emissions from meteorites and the Martian atmosphere
SO NATURE
LA English
DT Article
ID organic-compounds; mars; chemistry; nitrogen; carbon; soil
AB Almost a decade after methane was first reported in the atmosphere of Mars(1,2) there is an intensive discussion about both the reliability of the observations(3,4)-particularly the suggested seasonal and latitudinal variations(5,6)-and the sources of methane on Mars. Given that the lifetime of methane in the Martian atmosphere is limited(1,6), a process on or below the planet's surface would need to be continuously producing methane. A biological source would provide support for the potential existence of life on Mars, whereas a chemical origin would imply that there are unexpected geological processes(7). Methane release from carbonaceous meteorites associated with ablation during atmospheric entry is considered negligible(8). Here we show that methane is produced in much larger quantities from the Murchison meteorite (a type CM2 carbonaceous chondrite) when exposed to ultraviolet radiation under conditions similar to those expected at the Martian surface. Meteorites containing several per cent of intact organic matter reach the Martian surface at high rates(9), and our experiments suggest that a significant fraction of the organic matter accessible to ultraviolet radiation is converted to methane. Ultraviolet-radiation-induced methane formation from meteorites could explain a substantial fraction of the most recently estimated atmospheric methane mixing ratios(3,4). Stable hydrogen isotope analysis unambiguously confirms that the methane released from Murchison is of extraterrestrial origin. The stable carbon isotope composition, in contrast, is similar to that of terrestrial microbial origin; hence, measurements of this signature in future Mars missions may not enable an unambiguous identification of biogenic methane.
C1 [Keppler, Frank; Vigano, Ivan; Ott, Ulrich] Max Planck Inst Chem, Dept Atmospher Chem, D-55128 Mainz, Germany.
   [Vigano, Ivan; Fruchtl, Marion; Rockmann, Thomas] Univ Utrecht, Inst Marine & Atmospher Res Utrecht, NL-3584 CC Utrecht, Netherlands.
   [McLeod, Andy] Univ Edinburgh, Sch Geosci, Edinburgh EH9 3JN, Midlothian, Scotland.
   [Ott, Ulrich] Univ W Hungary, H-9700 Szombathely, Hungary.
C3 Max Planck Society; Utrecht University; University of Edinburgh; University of West Hungary
RP Keppler, F (corresponding author), Max Planck Inst Chem, Dept Atmospher Chem, Hahn Meitner Weg 1, D-55128 Mainz, Germany.
EM frank.keppler@mpic.de
FU ESF; DFG [KE 884/2-1]; Dutch NWO [865.07.001]; NERC [NE/F020422/1]; Royal Society Leverhulme Trust; Natural Environment Research Council [NE/F020422/1] Funding Source: researchfish; NERC [NE/F020422/1] Funding Source: UKRI
NR 33
TC 61
Z9 68
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 JUN 7
PY 2012
VL 486
IS 7401
BP 93
EP 96
DI 10.1038/nature11203
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 953GD
UT WOS:000304854000033
PM 22678286
DA 2026-03-09
ER

PT J
AU Hendricks, M
   Ha, H
   Maffey, N
   Zhang, Y
AF Hendricks, Michael
   Ha, Heonick
   Maffey, Nicolas
   Zhang, Yun
TI Compartmentalized calcium dynamics in a C. elegans interneuron encode head movement
SO NATURE
LA English
DT Article
ID caenorhabditis-elegans; glutamate-receptor; nervous-system; behavior; circuit; dendrites; g(q)alpha; release; neurons; pathway
AB The confinement of neuronal activity to specific subcellular regions is a mechanism for expanding the computational properties of neurons. Although the circuit organization underlying compartmentalized activity has been studied in several systems(1-4), its cellular basis is still unknown. Here we characterize compartmentalized activity in Caenorhabditis elegans RIA interneurons, which have multiple reciprocal connections to head motor neurons and receive input from sensory pathways. We show that RIA spatially encodes head movement on a subcellular scale through axonal compartmentalization. This subcellular axonal activity is dependent on acetylcholine release from head motor neurons and is simultaneously present and additive with glutamate-dependent globally synchronized activity evoked by sensory inputs. Postsynaptically, the muscarinic acetylcholine receptor GAR-3 acts in RIA to compartmentalize axonal activity through the mobilization of intracellular calcium stores. The compartmentalized activity functions independently of the synchronized activity to modulate locomotory behaviour.
C1 [Hendricks, Michael; Ha, Heonick; Maffey, Nicolas; Zhang, Yun] Harvard Univ, Ctr Brain Sci, Dept Organism & Evolutionary Biol, Cambridge, MA 02138 USA.
C3 Harvard University
RP Zhang, Y (corresponding author), Harvard Univ, Ctr Brain Sci, Dept Organism & Evolutionary Biol, Cambridge, MA 02138 USA.
EM yzhang@oeb.harvard.edu
FU Esther A. and Joseph Klingenstein Fund; March of Dimes Foundation; Alfred P. Sloan Foundation; John Merck Fund; National Institutes of Health [DC009852]
NR 30
TC 123
Z9 165
U1 0
U2 40
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUL 5
PY 2012
VL 487
IS 7405
BP 99
EP +
DI 10.1038/nature11081
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 968LM
UT WOS:000305982900058
PM 22722842
DA 2026-03-09
ER

PT J
AU Ge, WP
   Miyawaki, A
   Gage, FH
   Jan, YN
   Jan, LY
AF Ge, Woo-Ping
   Miyawaki, Atsushi
   Gage, Fred H.
   Jan, Yuh Nung
   Jan, Lily Yeh
TI Local generation of glia is a major astrocyte source in postnatal cortex
SO NATURE
LA English
DT Article
ID neural stem-cells; subventricular zone; in-vivo; glutamate transporters; nonneuronal cells; rat forebrain; ng2 cells; brain; progenitors; lineage
AB Glial cells constitute nearly 50% of the cells in the human brain(1). Astrocytes, which make up the largest glial population, are crucial to the regulation of synaptic connectivity during postnatal development(2). Because defects in astrocyte generation are associated with severe neurological disorders such as brain tumours(3), it is important to understand how astrocytes are produced. Astrocytes reportedly arise from two sources(4-6): radial glia in the ventricular zone and progenitors in the subventricular zone, with the contribution from each region shifting with time. During the first three weeks of postnatal development, the glial cell population, which contains predominantly astrocytes, expands 6-8-fold in the rodent brain(7). Little is known about the mechanisms underlying this expansion. Here we show that a major source of glia in the postnatal cortex in mice is the local proliferation of differentiated astrocytes. Unlike glial progenitors in the subventricular zone, differentiated astrocytes undergo symmetric division, and their progeny integrate functionally into the existing glial network as mature astrocytes that form endfeet with blood vessels, couple electrically to neighbouring astrocytes, and take up glutamate after neuronal activity.
C1 [Ge, Woo-Ping; Jan, Yuh Nung; Jan, Lily Yeh] Univ Calif San Francisco, Howard Hughes Med Inst, Dept Physiol, San Francisco, CA 94158 USA.
   [Ge, Woo-Ping; Jan, Yuh Nung; Jan, Lily Yeh] Univ Calif San Francisco, Howard Hughes Med Inst, Dept Biochem, San Francisco, CA 94158 USA.
   [Ge, Woo-Ping; Jan, Yuh Nung; Jan, Lily Yeh] Univ Calif San Francisco, Howard Hughes Med Inst, Dept Biophys, San Francisco, CA 94158 USA.
   [Miyawaki, Atsushi] RIKEN, Japan Sci & Technol Agcy, Wako, Saitama 3510198, Japan.
   [Miyawaki, Atsushi] RIKEN, Brain Sci Inst, Wako, Saitama 3510198, Japan.
   [Gage, Fred H.] Salk Inst Biol Studies, Genet Lab, La Jolla, CA 92037 USA.
C3 University of California System; University of California San Francisco; Howard Hughes Medical Institute; University of California System; University of California San Francisco; Howard Hughes Medical Institute; University of California System; University of California San Francisco; Howard Hughes Medical Institute; Japan Science & Technology Agency (JST); RIKEN; RIKEN; Salk Institute
RP Jan, LY (corresponding author), Univ Calif San Francisco, Howard Hughes Med Inst, Dept Physiol, 1550 4th St, San Francisco, CA 94158 USA.
EM lily.jan@ucsf.edu
FU Human Frontier Science Program (HFSP); National Institute of Neurological Disorders and Stroke (NINDS) [1K99NS073735]; National Institute of Mental Health [4R37MH065334]; National Institutes of Health (NIH) [5R01MH084234]; NIH/National Institute on Aging [P01 AG010435, MH090258]; Jeffry M. and Barbara Picower Foundation(JBP); McDonnell Foundation
NR 36
TC 322
Z9 329
U1 1
U2 61
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD APR 19
PY 2012
VL 484
IS 7394
BP 376
EP U381
DI 10.1038/nature10959
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 927YM
UT WOS:000302946500033
DA 2026-03-09
ER

PT J
AU Boström, P
   Wu, J
   Jedrychowski, MP
   Korde, A
   Ye, L
   Lo, JC
   Rasbach, KA
   Boström, EA
   Choi, JH
   Long, JZ
   Kajimura, S
   Zingaretti, MC
   Vind, BF
   Tu, H
   Cinti, S
   Hojlund, K
   Gygi, SP
   Spiegelman, BM
AF Bostroem, Pontus
   Wu, Jun
   Jedrychowski, Mark P.
   Korde, Anisha
   Ye, Li
   Lo, James C.
   Rasbach, Kyle A.
   Bostroem, Elisabeth Almer
   Choi, Jang Hyun
   Long, Jonathan Z.
   Kajimura, Shingo
   Zingaretti, Maria Cristina
   Vind, Birgitte F.
   Tu, Hua
   Cinti, Saverio
   Hojlund, Kurt
   Gygi, Steven P.
   Spiegelman, Bruce M.
TI A PGC1-α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis
SO NATURE
LA English
DT Article
ID skeletal-muscle; exercise; pgc-1-alpha; protects; phosphorylation; coactivator; expression; myoblast; switch; roles
AB Exercise benefits a variety of organ systems in mammals, and some of the best-recognized effects of exercise on muscle are mediated by the transcriptional co-activator PPAR-gamma co-activator-1 alpha (PGC1-alpha). Here we show in mouse that PGC1-alpha expression in muscle stimulates an increase in expression of FNDC5, a membrane protein that is cleaved and secreted as a newly identified hormone, irisin. Irisin acts on white adipose cells in culture and in vivo to stimulate UCP1 expression and a broad program of brown-fat-like development. Irisin is induced with exercise in mice and humans, and mildly increased irisin levels in the blood cause an increase in energy expenditure in mice with no changes in movement or food intake. This results in improvements in obesity and glucose homeostasis. Irisin could be therapeutic for human metabolic disease and other disorders that are improved with exercise.
C1 [Bostroem, Pontus; Wu, Jun; Korde, Anisha; Ye, Li; Lo, James C.; Rasbach, Kyle A.; Choi, Jang Hyun; Long, Jonathan Z.; Spiegelman, Bruce M.] Dana Farber Canc Inst, Boston, MA 02115 USA.
   [Jedrychowski, Mark P.; Gygi, Steven P.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA.
   [Bostroem, Elisabeth Almer] Harvard Univ, Sch Med, Div Renal, Brigham & Womens Hosp, Boston, MA 02115 USA.
   [Kajimura, Shingo] Univ Calif San Francisco, Ctr Diabet, San Francisco, CA 94143 USA.
   [Kajimura, Shingo] Univ Calif San Francisco, Dept Cell & Tissue Biol, San Francisco, CA 94143 USA.
   [Zingaretti, Maria Cristina; Cinti, Saverio] Univ Politecn Marche, Dept Expt & Clin Med, Azienda Osped Riuniti, Electron Microscopy Unit, I-60020 Ancona, Italy.
   [Vind, Birgitte F.; Hojlund, Kurt] Odense Univ Hosp, Diabet Res Ctr, Dept Endocrinol, DK-5000 Odense, Denmark.
   [Tu, Hua] LakePharma Inc, Belmont, CA 94002 USA.
C3 Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard Medical School; University of California System; University of California San Francisco; University of California System; University of California San Francisco; Marche Polytechnic University; University of Southern Denmark; Odense University Hospital
RP Spiegelman, BM (corresponding author), Dana Farber Canc Inst, 3 Blackfan Circle,CLS Bldg,Floor 11, Boston, MA 02115 USA.
EM bruce_spiegelman@dfci.harvard.edu
FU National Institutes of Health [DK54477, DK31405, DK61562]; Wenner-Gren Foundation; Swedish Heart and Lung Foundation; Svenska Sallskapet for Medicinsk Forskning; American Heart Association [09POST2010078]; American Heart Association (AHA) [09POST2010078] Funding Source: American Heart Association (AHA)
NR 26
TC 3935
Z9 4622
U1 12
U2 702
PU NATURE PUBLISHING 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 26
PY 2012
VL 481
IS 7382
BP 463
EP U72
DI 10.1038/nature10777
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 881GY
UT WOS:000299471800031
PM 22237023
DA 2026-03-09
ER

PT J
AU Yoshizaki, A
   Miyagaki, T
   DiLillo, DJ
   Matsushita, T
   Horikawa, M
   Kountikov, EI
   Spolski, R
   Poe, JC
   Leonard, WJ
   Tedder, TF
AF Yoshizaki, Ayumi
   Miyagaki, Tomomitsu
   DiLillo, David J.
   Matsushita, Takashi
   Horikawa, Mayuka
   Kountikov, Evgueni I.
   Spolski, Rosanne
   Poe, Jonathan C.
   Leonard, Warren J.
   Tedder, Thomas F.
TI Regulatory B cells control T-cell autoimmunity through IL-21-dependent cognate interactions
SO NATURE
LA English
DT Article
ID b10 cells; transgenic mice; lymphocyte development; cutting edge; plasma-cells; human cd19; memory b; in-vivo; il-21; il-10
AB B cells regulate immune responses by producing antigen-specific antibodies(1). However, specific B-cell subsets can also negatively regulate T-cell immune responses, and have been termed regulatory B cells(2-4). Human and mouse regulatory B cells (B10 cells) with the ability to express the inhibitory cytokine interleukin-10 (IL-10) have been identified(2-5). Although rare, B10 cells are potent negative regulators of antigen-specific inflammation and T-cell-dependent autoimmune diseases in mice(5-7). How B10-cell IL-10 production and regulation of antigen-specific immune responses are controlled in vivo without inducing systemic immunosuppression is unknown. Using a mouse model for multiple sclerosis, here we show that B10-cell maturation into functional IL-10-secreting effector cells that inhibit in vivo autoimmune disease requires IL-21 and CD40-dependent cognate interactions with T cells. Moreover, the ex vivo provision of CD40 and IL-21 receptor signals can drive B10-cell development and expansion by four-million-fold, and generate B10 effector cells producing IL-10 that markedly inhibit disease symptoms when transferred into mice with established autoimmune disease. The ex vivo expansion and reinfusion of autologous B10 cells may provide a novel and effective in vivo treatment for severe autoimmune diseases that are resistant to current therapies.
C1 [Yoshizaki, Ayumi; Miyagaki, Tomomitsu; DiLillo, David J.; Matsushita, Takashi; Horikawa, Mayuka; Kountikov, Evgueni I.; Poe, Jonathan C.; Tedder, Thomas F.] Duke Univ, Med Ctr, Dept Immunol, Durham, NC 27710 USA.
   [Spolski, Rosanne; Leonard, Warren J.] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA.
C3 Duke University; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI)
RP Tedder, TF (corresponding author), Duke Univ, Med Ctr, Dept Immunol, Durham, NC 27710 USA.
EM thomas.tedder@duke.edu
FU National Institutes of Health (NIH) [AI56363, AI057157]; Lymphoma Research Foundation; Division of Intramural Research, National Heart, Lung, and Blood Institute, NIH; National Heart Lung and Blood Institute [ZIAHL005408] Funding Source: NIH RePORTER
NR 37
TC 527
Z9 618
U1 0
U2 90
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 8
PY 2012
VL 491
IS 7423
BP 264
EP +
DI 10.1038/nature11501
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 033DP
UT WOS:000310774300046
PM 23064231
DA 2026-03-09
ER

PT J
AU Moreno-Razo, JA
   Sambriski, EJ
   Abbott, NL
   Hernández-Ortiz, JP
   de Pablo, JJ
AF Moreno-Razo, J. A.
   Sambriski, E. J.
   Abbott, N. L.
   Hernandez-Ortiz, J. P.
   de Pablo, J. J.
TI Liquid-crystal-mediated self-assembly at nanodroplet interfaces
SO NATURE
LA English
DT Article
ID transitions; model
AB Technological applications of liquid crystals have generally relied on control of molecular orientation at a surface or an interface(1,2). Such control has been achieved through topography, chemistry and the adsorption of monolayers or surfactants(2,3). The role of the substrate or interface has been to impart order over visible length scales and to confine the liquid crystal in a device. Here, we report results from a computational study of a liquid-crystal-based system in which the opposite is true: the liquid crystal is used to impart order on the interfacial arrangement of a surfactant. Recent experiments on macroscopic interfaces have hinted that an interfacial coupling between bulk liquid crystal and surfactant can lead to a two-dimensional phase separation of the surfactant at the interface(4), but have not had the resolution to measure the structure of the resulting phases. To enhance that coupling, we consider the limit of nanodroplets, the interfaces of which are decorated with surfactant molecules that promote local perpendicular orientation of mesogens within the droplet. In the absence of surfactant, mesogens at the interface are all parallel to that interface. As the droplet is cooled, the mesogens undergo a transition from a disordered (isotropic) to an ordered (nematic or smectic) liquid-crystal phase. As this happens, mesogens within the droplet cause a transition of the surfactant at the interface, which forms new ordered nanophases with morphologies dependent on surfactant concentration. Such nanophases are reminiscent of those encountered in block copolymers(5), and include circular, striped and worm-like patterns.
C1 [Abbott, N. L.; de Pablo, J. J.] Univ Wisconsin, Dept Chem & Biol Engn, Madison, WI 53706 USA.
   [Moreno-Razo, J. A.] Univ Autonoma Metropolitana Iztapalapa, Dept Fis, Mexico City 09340, DF, Mexico.
   [Sambriski, E. J.] Delaware Valley Coll, Dept Chem & Biochem, Doylestown, PA 18901 USA.
   [Hernandez-Ortiz, J. P.] Univ Nacl Colombia, Dept Mat, Medellin, Colombia.
C3 University of Wisconsin System; University of Wisconsin Madison; Universidad Autonoma Metropolitana - Mexico; Universidad Nacional de Colombia
RP de Pablo, JJ (corresponding author), Univ Wisconsin, Dept Chem & Biol Engn, Madison, WI 53706 USA.
EM depablo@engr.wisc.edu
FU Department of Energy, Basic Energy Sciences [DE-SC0004025]; National Science Foundation [DMR-1121288]; Direct For Mathematical & Physical Scien; Division Of Materials Research [1121288] Funding Source: National Science Foundation; U.S. Department of Energy (DOE) [DE-SC0004025] Funding Source: U.S. Department of Energy (DOE)
NR 28
TC 92
Z9 108
U1 1
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 MAY 3
PY 2012
VL 485
IS 7396
BP 86
EP 89
DI 10.1038/nature11084
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 934NV
UT WOS:000303451900039
PM 22552096
DA 2026-03-09
ER

PT J
AU Young, GR
   Eksmond, U
   Salcedo, R
   Alexopoulou, L
   Stoye, JP
   Kassiotis, G
AF Young, George R.
   Eksmond, Urszula
   Salcedo, Rosalba
   Alexopoulou, Lena
   Stoye, Jonathan P.
   Kassiotis, George
TI Resurrection of endogenous retroviruses in antibody-deficient mice
SO NATURE
LA English
DT Article
ID murine leukemia-virus; b-cell responses; targeted disruption; receptor; lymphocytes; mouse; retroelements; expression; induction; lipopolysaccharide
AB The mammalian host has developed a long-standing symbiotic relationship with a considerable number of microbial species. These include the microbiota on environmental surfaces, such as the respiratory and gastrointestinal tracts(1), and also endogenous retroviruses (ERVs), comprising a substantial fraction of the mammalian genome(2,3). The long-term consequences for the host of interactions with these microbial species can range from mutualism to parasitism and are not always completely understood. The potential effect of one microbial symbiont on another is even less clear. Here we study the control of ERVs in the commonly used C57BL/6 (B6) mouse strain, which lacks endogenous murine leukaemia viruses (MLVs) able to replicate in murine cells. We demonstrate the spontaneous emergence of fully infectious ecotropic(4) MLV in B6 mice with a range of distinct immune deficiencies affecting antibody production. These recombinant retroviruses establish infection of immunodeficient mouse colonies, and ultimately result in retrovirus-induced lymphomas. Notably, ERV activation in immunodeficient mice is prevented in husbandry conditions associated with reduced or absent intestinal microbiota. Our results shed light onto a previously unappreciated role for immunity in the control of ERVs and provide a potential mechanistic link between immune activation by microbial triggers and a range of pathologies associated with ERVs, including cancer.
C1 [Young, George R.; Eksmond, Urszula; Kassiotis, George] MRC Natl Inst Med Res, Div Immunoregulat, London NW7 1AA, England.
   [Salcedo, Rosalba] SAIC Frederick Inc, Basic Sci Program, NIH, Frederick, MD 21701 USA.
   [Salcedo, Rosalba] NCI, Canc & Inflammat Program, Ctr Canc Res, NIH, Frederick, MD 21701 USA.
   [Alexopoulou, Lena] Aix Marseille Univ, UM2, Ctr Immunol Marseille Luminy CIML,INSERM, U1104,CNRS UMR7280, Marseille, France.
   [Stoye, Jonathan P.] MRC Natl Inst Med Res, Div Virol, London NW7 1AA, England.
C3 MRC National Institute for Medical Research; National Institutes of Health (NIH) - USA; Science Applications International Corporation (SAIC); SAIC-Frederick; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB); Aix-Marseille Universite; Universite de Montpellier; Institut National de la Sante et de la Recherche Medicale (Inserm); MRC National Institute for Medical Research
RP Kassiotis, G (corresponding author), MRC Natl Inst Med Res, Div Immunoregulat, London NW7 1AA, England.
EM gkassio@nimr.mrc.ac.uk
FU UK Medical Research Council [U117581330, U117512710]; Medical Research Council [MC_U117512710, MC_U117581330] Funding Source: researchfish; MRC [MC_U117581330, MC_U117512710] Funding Source: UKRI
NR 59
TC 183
Z9 212
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 29
PY 2012
VL 491
IS 7426
BP 774
EP +
DI 10.1038/nature11599
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 044FY
UT WOS:000311606000049
PM 23103862
DA 2026-03-09
ER

PT J
AU Pross, J
   Contreras, L
   Bijl, PK
   Greenwood, DR
   Bohaty, SM
   Schouten, S
   Bendle, JA
   Röhl, U
   Tauxe, L
   Raine, JI
   Huck, CE
   van de Flierdt, T
   Jamieson, SSR
   Stickley, CE
   van de Schootbrugge, B
   Escutia, C
   Brinkhuis, H
   Dotti, CE
   Klaus, A
   Fehr, A
   Williams, T
   Bendle, JAP
   Carr, SA
   Dunbar, RB
   Gonzàlez, JJ
   Hayden, TG
   Iwai, M
   Jimenez-Espejo, FJ
   Katsuki, K
   Kong, GS
   Mckay, RM
   Nakai, M
   Olney, MP
   Passchier, S
   Pekar, SF
   Pröss, J
   Riesselman, CR
   Rohl, U
   Sakai, T
   Shrivastava, PK
   Stickley, CE
   Sugisaki, S
   Tauxe, L
   Tuo, S
   Van De Flierdt, T
   Welsh, K
   Yamane, M
AF Pross, Joerg
   Contreras, Lineth
   Bijl, Peter K.
   Greenwood, David R.
   Bohaty, Steven M.
   Schouten, Stefan
   Bendle, James A.
   Roehl, Ursula
   Tauxe, Lisa
   Raine, J. Ian
   Huck, Claire E.
   van de Flierdt, Tina
   Jamieson, Stewart S. R.
   Stickley, Catherine E.
   van de Schootbrugge, Bas
   Escutia, Carlota
   Brinkhuis, Henk
   Dotti, Carlota Escutia
   Klaus, Adam
   Fehr, Annick
   Williams, Trevor
   Bendle, James A. P.
   Carr, Stephanie A.
   Dunbar, Robert B.
   Gonzalez, Jhon J.
   Hayden, Travis G.
   Iwai, Masao
   Jimenez-Espejo, Francisco J.
   Katsuki, Kota
   Kong, Gee Soo
   McKay, Robert M.
   Nakai, Mutsumi
   Olney, Matthew P.
   Passchier, Sandra
   Pekar, Stephen F.
   Pross, Jorg
   Riesselman, Christina R.
   Rohl, Ursula
   Sakai, Toyosaburo
   Shrivastava, Prakash K.
   Stickley, Catherine E.
   Sugisaki, Saiko
   Tauxe, Lisa
   Tuo, Shouting
   van de Flierdt, Tina
   Welsh, Kevin
   Yamane, Masako
TI Persistent near-tropical warmth on the Antarctic continent during the early Eocene epoch
SO NATURE
LA English
DT Article
ID terrestrial paleoclimate; polar forests; reconstructions; sensitivity; climates
AB The warmest global climates of the past 65 million years occurred during the early Eocene epoch (about 55 to 48 million years ago), when the Equator-to-pole temperature gradients weremuch smaller than today(1,2) and atmospheric carbon dioxide levels were in excess of one thousand parts per million by volume(3,4). Recently the early Eocene has received considerable interest because it may provide insight into the response of Earth's climate and biosphere to the high atmospheric carbon dioxide levels that are expected in the near future(5) as a consequence of unabated anthropogenic carbon emissions(4,6). Climatic conditions of the early Eocene 'greenhouse world', however, are poorly constrained in critical regions, particularly Antarctica. Here we present a well-dated record of early Eocene climate on Antarctica from an ocean sediment core recovered off the Wilkes Land coast of East Antarctica. The information from biotic climate proxies (pollen and spores) and independent organic geochemical climate proxies (indices based on branched tetraether lipids) yields quantitative, seasonal temperature reconstructions for the early Eocene greenhouse world on Antarctica. We show that the climate in lowland settings along the Wilkes Land coast (at a palaeolatitude of about 70 degrees south) supported the growth of highly diverse, near-tropical forests characterized by mesothermal to megathermal floral elements including palms and Bombacoideae. Notably, winters were extremely mild (warmer than 10 degrees C) and essentially frost-free despite polar darkness, which provides a critical new constraint for the validation of climate models and for understanding the response of high-latitude terrestrial ecosystems to increased carbon dioxide forcing.
C1 [Pross, Joerg; Contreras, Lineth; van de Schootbrugge, Bas] Goethe Univ Frankfurt, Inst Geosci, Paleoenvironm Dynam Grp, Altenhoferallee 1, D-60438 Frankfurt, Germany.
   [Pross, Joerg] Biodivers & Climate Res Ctr, D-60325 Frankfurt, Germany.
   [Bijl, Peter K.; Brinkhuis, Henk] Univ Utrecht, Inst Environm Biol, Lab Palaeobot & Palynol, NL-3584 CD Utrecht, Netherlands.
   [Greenwood, David R.] Brandon Univ, Dept Biol, Brandon, MB R7A 6A9, Canada.
   [Bohaty, Steven M.] Univ Southampton, Natl Oceanog Ctr Southampton, Southampton SO14 3ZH, Hants, England.
   [Schouten, Stefan] NIOZ Royal Netherlands Inst Sea Res, Dept Marine Organ Biogeochem, NL-1790 AB Den Burg, Texel, Netherlands.
   [Bendle, James A.] Univ Glasgow, Sch Geog & Earth Sci, Glasgow Mol Organ Geochem Lab, Glasgow G12 8QQ, Lanark, Scotland.
   [Roehl, Ursula] Univ Bremen, MARUM Ctr Marine Environm Sci, D-28359 Bremen, Germany.
   [Tauxe, Lisa] Univ Calif San Diego, Scripps Inst Oceanog, La Jolla, CA 92093 USA.
   [Raine, J. Ian] GNS Sci, Dept Paleontol, Lower Hutt 6009, New Zealand.
   [Huck, Claire E.; van de Flierdt, Tina] Univ London Imperial Coll Sci Technol & Med, Dept Earth Sci & Engn, London SW7 2AZ, England.
   [Jamieson, Stewart S. R.] Univ Durham, Sci Labs, Dept Geog, Durham DH1 3LE, England.
   [Stickley, Catherine E.] Univ Tromso, Dept Geol, N-9037 Tromso, Norway.
   [Escutia, Carlota] Inst Andaluz Ciencias Tierra, Granada 18100, Spain.
   [Dotti, Carlota Escutia; Gonzalez, Jhon J.] CSIC Univ Granada, Inst Andaluz Ciencias Tierra, Campus Fuentenueva S N, Granada 18002, Spain.
   [Klaus, Adam] Texas A&M Univ, Integrated Ocean Drilling Program, United States Implementing Org, 1000 Discovery Dr, College Stn, TX 77845 USA.
   [Fehr, Annick] Rhein Westfal TH Aachen, Inst Appl Geophys & Geothermal Energy, Mathieustrass 6, D-52074 Aachen, Germany.
   [Williams, Trevor] Lamont Doherty Earth Observ Columbia Univ, Borehole Res Grp, POB 1000,61 Route 9W, Palisades, NY 10964 USA.
   [Bendle, James A. P.] Univ Glasgow, Geog & Earth Sci, Glasgow G128QQ, Lanark, Scotland.
   [Carr, Stephanie A.] Colorado Sch Mines, Dept Chem & Geochem, 1500 Illinois St, Golden, CO 80401 USA.
   [Dunbar, Robert B.; Riesselman, Christina R.] Stanford Univ, Dept Environm Earth Syst Sci, 325 Braun Hall,Bldg 320, Stanford, CA 94305 USA.
   [Hayden, Travis G.] Western Michigan Univ, Dept Geol, 1187 Rood Hall,1903 W Michigan Ave, Kalamazoo, MI 49008 USA.
   [Iwai, Masao] Kochi Univ, Dept Nat Sci, 2-5-1 Akebono cho, Kochi 7808520, Japan.
   [Jimenez-Espejo, Francisco J.] Japan Agcy Marine Earth Sci & Technol, Inst Res Earth Evolut, Natsushima Cho 2-15, Yokosuka, Kanagawa 2370061, Japan.
   [Katsuki, Kota] Kochi Univ, Marine Ctr Adv Core Res, B200 Monobe, Nankoku, Kochi 7838502, Japan.
   [Kong, Gee Soo] Korea Inst Geosci & Mineral Resources, Petr & Marine Res Div, 30 Gajeong Dong, Daejeon 305350, South Korea.
   [McKay, Robert M.] Victoria Univ Wellington, Antarctic Res Ctr, POB 600, Wellington 6140, New Zealand.
   [Nakai, Mutsumi] Daito Bunka Univ, Dept Educ, Itabashi Ku, 1-9-1 Takashima Daira, Tokyo 1758571, Japan.
   [Olney, Matthew P.] Univ S Florida, Dept Geol, 4202 E Fowler Ave, Tampa, FL 33620 USA.
   [Passchier, Sandra] Montclair State Univ, Earth & Environm Studies, 252 Mallory Hall,1 Normal Ave, Montclair, NJ 07043 USA.
   [Pekar, Stephen F.] Queens Coll, Sch Earth & Environm Sci, 65-30 Kissena Blvd, Flushing, NY 11367 USA.
   [Pross, Jorg] Goethe Univ Frankfurt, Inst Geosciences, Paleoenvironmental Dynam Grp, Altenhoferallee 1, D-60438 Frankfurt, Germany.
   [Pross, Jorg] Biodivers & Climate Res Ctr, Senckenberganlage 25, D-60325 Frankfurt, Germany.
   [Rohl, Ursula] Univ Bremen, MARUM, Ctr Marine Environm Sci, Leobener Strasse, D-28359 Bremen, Germany.
   [Sakai, Toyosaburo] Utsunomiya Univ, Dept Geol, 350 Mine Machi, Utsunomiya, Tochigi 3218505, Japan.
   [Shrivastava, Prakash K.] Geol Survey India, Antarct Div, NH5P, NIT, Faridabad 121001, Harlyana, India.
   [Stickley, Catherine E.] Univ Tromso, Dept Geol, N-9037 Tromso, Norway.
   [Sugisaki, Saiko] Grad Univ Adv Study, Dept Polar Sci, 10-3 Midori Cho, Tachikawa, Tokyo 1908518, Japan.
   [Tauxe, Lisa] Univ Calif, Scripps Inst Oceanog, San Diego, CA 92093 USA.
   [Tuo, Shouting] Tongji Univ, Sch Ocean & Earth Sci, 1239 Spring Rd, Shanghai 200092, Peoples R China.
   [van de Flierdt, Tina] Imperial Coll London, Dept Earth Sci & Engn, London SW7 2AZ, England.
   [Welsh, Kevin] Univ Queensland, Sch Earth Sci, St Lucia, Qld 4072, Australia.
   [Yamane, Masako] Univ Tokyo, Earth & Planetary Sci, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1130033, Japan.
   [Jimenez-Espejo, Francisco J.] CSIC Univ Granada, Inst Andaluz Ciencias Tierra, Armilla, Granada 18100, Spain.
   [Riesselman, Christina R.] Eastern Geol & Paleoclimate Sci Ctr, Natl Ctr, US Geol Survey, Reston, VA 20192 USA.
   [Sugisaki, Saiko] Japan Agcy Marine Earth Sci & Technol, Frontier Bldg 4F,2-15 Natsushima Cho, Yokosuka, Kanagawa 2370061, Japan.
C3 Goethe University Frankfurt; Utrecht University; Brandon University; University of Southampton; NERC National Oceanography Centre; Utrecht University; Royal Netherlands Institute for Sea Research (NIOZ); University of Glasgow; University of Bremen; University of California System; University of California San Diego; Scripps Institution of Oceanography; Earth Sciences New Zealand; GNS Science - New Zealand; Imperial College London; Durham University; UiT The Arctic University of Tromso; Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Instituto Andaluz de Ciencias de la Tierra (IACT); University of Granada; Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Instituto Andaluz de Ciencias de la Tierra (IACT); Texas A&M University System; Texas A&M University College Station; RWTH Aachen University; University of Glasgow; Colorado School of Mines; Stanford University; Western Michigan University; Kochi University; Japan Agency for Marine-Earth Science & Technology (JAMSTEC); Kochi University; Korea Institute of Geoscience & Mineral Resources (KIGAM); Victoria University Wellington; State University System of Florida; University of South Florida; Montclair State University; City University of New York (CUNY) System; Queens College NY (CUNY); Goethe University Frankfurt; University of Bremen; Utsunomiya University; Geological Survey India; UiT The Arctic University of Tromso; University of California System; University of California San Diego; Scripps Institution of Oceanography; Tongji University; Imperial College London; University of Queensland; University of Tokyo; Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Instituto Andaluz de Ciencias de la Tierra (IACT); University of Granada; United States Department of the Interior; United States Geological Survey; Japan Agency for Marine-Earth Science & Technology (JAMSTEC)
RP Pross, J (corresponding author), Goethe Univ Frankfurt, Inst Geosci, Paleoenvironm Dynam Grp, Altenhoferallee 1, D-60438 Frankfurt, Germany.
EM joerg.pross@em.uni-frankfurt.de
FU US National Science Foundation; German Research Foundation [PR 651/10, RO 1113/6]; Biodiversity and Climate Research Center of the Hessian Initiative for Scientific and Economic Excellence; Netherlands Organisation for Scientific Research; Natural Sciences and Engineering Research Council of Canada [DG 311934]; Natural Environment Research Council [Ne/J019801/1, Ne/I00646X/1, Ne/I006257/1]; US National Science Foundation [OCE 1058858]; New Zealand Ministry of Science and Innovation; Directorate For Geosciences; Division Of Ocean Sciences [1129101] Funding Source: National Science Foundation; Division Of Ocean Sciences; Directorate For Geosciences [1058858] Funding Source: National Science Foundation; NERC [NE/I00646X/1, NE/J019801/1, NE/H014616/1, NE/H020098/1, NE/I00646X/2, NE/H025162/1, NE/H014144/1, NE/I006257/1] Funding Source: UKRI; Natural Environment Research Council [NE/I006257/1, NE/H025162/1, NE/H014144/1, NE/J019801/1, NE/I00646X/1, NE/H014616/1, NE/I00646X/2, NE/H020098/1] Funding Source: researchfish
NR 30
TC 245
Z9 276
U1 1
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 AUG 2
PY 2012
VL 488
IS 7409
BP 73
EP 77
DI 10.1038/nature11300
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 981ZE
UT WOS:000307010700035
PM 22859204
DA 2026-03-09
ER

PT J
AU James, A
   Pitchford, JW
   Plank, MJ
AF James, Alex
   Pitchford, Jonathan W.
   Plank, Michael J.
TI Disentangling nestedness from models of ecological complexity
SO NATURE
LA English
DT Article
ID mutualistic networks; architecture; biodiversity; ecosystems; stability
AB Complex networks of interactions are ubiquitous(1) and are particularly important in ecological communities, in which large numbers of species exhibit negative (for example, competition or predation) and positive (for example, mutualism) interactions with one another. Nestedness in mutualistic ecological networks is the tendency for ecological specialists to interact with a subset of species that also interact with more generalist species(2). Recent mathematical and computational analysis has suggested that such nestedness increases species richness(3,4). By examining previous results and applying computational approaches to 59 empirical data sets representing mutualistic plant-pollinator networks, we show that this statement is incorrect. A simpler metric-the number of mutualistic partners a species has-is a much better predictor of individual species survival and hence, community persistence. Nestedness is, at best, a secondary covariate rather than a causative factor for biodiversity in mutualistic communities. Analysis of complex networks should be accompanied by analysis of simpler, underpinning mechanisms that drive multiple higher-order network properties.
C1 [James, Alex; Plank, Michael J.] Univ Canterbury, Biomath Res Ctr, Christchurch 8040, New Zealand.
   [Pitchford, Jonathan W.] Univ York, York Ctr Complex Syst Anal, York YO10 5DD, N Yorkshire, England.
   [Pitchford, Jonathan W.] Univ York, Dept Biol, York YO10 5DD, N Yorkshire, England.
   [Pitchford, Jonathan W.] Univ York, Dept Math, York YO10 5DD, N Yorkshire, England.
C3 University of Canterbury; University of York - UK; University of York - UK; University of York - UK
RP James, A (corresponding author), Univ Canterbury, Biomath Res Ctr, Private Bag 4800, Christchurch 8040, New Zealand.
EM alex.james@canterbury.ac.nz
FU Royal Society of New Zealand [08-UOC-034]; University of Canterbury
NR 21
TC 157
Z9 184
U1 2
U2 161
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUL 12
PY 2012
VL 487
IS 7406
BP 227
EP 230
DI 10.1038/nature11214
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 972LP
UT WOS:000306278900038
PM 22722863
DA 2026-03-09
ER

PT J
AU Atasoy, D
   Betley, JN
   Su, HH
   Sternson, SM
AF Atasoy, Deniz
   Betley, J. Nicholas
   Su, Helen H.
   Sternson, Scott M.
TI Deconstruction of a neural circuit for hunger
SO NATURE
LA English
DT Article
ID hypothalamic paraventricular nucleus; neuropeptide-y; parabrachial nucleus; oxytocin neurons; npy/agrp neurons; arcuate nucleus; energy-balance; agrp neurons; protein agrp; release
AB Hunger is a complex behavioural state that elicits intense food seeking and consumption. These behaviours are rapidly recapitulated by activation of starvation-sensitive AGRP neurons, which present an entry point for reverse-engineering neural circuits for hunger. Here we mapped synaptic interactions of AGRP neurons with multiple cell populations in mice and probed the contribution of these distinct circuits to feeding behaviour using optogenetic and pharmacogenetic techniques. An inhibitory circuit with paraventricular hypothalamus (PVH) neurons substantially accounted for acute AGRP neuron-evoked eating, whereas two other prominent circuits were insufficient. Within the PVH, we found that AGRP neurons target and inhibit oxytocin neurons, a small population that is selectively lost in Prader-Willi syndrome, a condition involving insatiable hunger. By developing strategies for evaluating molecularly defined circuits, we show that AGRP neuron suppression of oxytocin neurons is critical for evoked feeding. These experiments reveal a new neural circuit that regulates hunger state and pathways associated with overeating disorders.
C1 [Atasoy, Deniz; Betley, J. Nicholas; Su, Helen H.; Sternson, Scott M.] Howard Hughes Med Inst, Ashburn, VA 20147 USA.
C3 Howard Hughes Medical Institute
RP Sternson, SM (corresponding author), Howard Hughes Med Inst, Janelia Farm Res Campus,19700 Helix Dr, Ashburn, VA 20147 USA.
EM sternsons@janelia.hhmi.org
FU Howard Hughes Medical Institute
NR 53
TC 751
Z9 890
U1 2
U2 179
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD AUG 9
PY 2012
VL 488
IS 7410
BP 172
EP +
DI 10.1038/nature11270
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 985LE
UT WOS:000307267000025
PM 22801496
DA 2026-03-09
ER

PT J
AU Dutta, P
   Courties, G
   Wei, Y
   Leuschner, F
   Gorbatov, R
   Robbins, CS
   Iwamoto, Y
   Thompson, B
   Carlson, AL
   Heidt, T
   Majmudar, MD
   Lasitschka, F
   Etzrodt, M
   Waterman, P
   Waring, MT
   Chicoine, AT
   van der Laan, AM
   Niessen, HWM
   Piek, JJ
   Rubin, BB
   Butany, J
   Stone, JR
   Katus, HA
   Murphy, SA
   Morrow, DA
   Sabatine, MS
   Vinegoni, C
   Moskowitz, MA
   Pittet, MJ
   Libby, P
   Lin, CP
   Swirski, FK
   Weissleder, R
   Nahrendorf, M
AF Dutta, Partha
   Courties, Gabriel
   Wei, Ying
   Leuschner, Florian
   Gorbatov, Rostic
   Robbins, Clinton S.
   Iwamoto, Yoshiko
   Thompson, Brian
   Carlson, Alicia L.
   Heidt, Timo
   Majmudar, Maulik D.
   Lasitschka, Felix
   Etzrodt, Martin
   Waterman, Peter
   Waring, Michael T.
   Chicoine, Adam T.
   van der Laan, Anja M.
   Niessen, Hans W. M.
   Piek, Jan J.
   Rubin, Barry B.
   Butany, Jagdish
   Stone, James R.
   Katus, Hugo A.
   Murphy, Sabina A.
   Morrow, David A.
   Sabatine, Marc S.
   Vinegoni, Claudio
   Moskowitz, Michael A.
   Pittet, Mikael J.
   Libby, Peter
   Lin, Charles P.
   Swirski, Filip K.
   Weissleder, Ralph
   Nahrendorf, Matthias
TI Myocardial infarction accelerates atherosclerosis
SO NATURE
LA English
DT Article
ID hematopoietic stem-cells; acute coronary syndrm; monocyte subsets; progenitor cells; artery-disease; bone-marrow; inflammation; plaques; niche; identification
AB During progression of atherosclerosis, myeloid cells destabilize lipid-rich plaques in the arterial wall and cause their rupture, thus triggering myocardial infarction and stroke. Survivors of acute coronary syndromes have a high risk of recurrent events for unknown reasons. Here we show that the systemic response to ischaemic injury aggravates chronic atherosclerosis. After myocardial infarction or stroke, Apoe(-/-) mice developed larger atherosclerotic lesions with a more advanced morphology. This disease acceleration persisted over many weeks and was associated with markedly increased monocyte recruitment. Seeking the source of surplus monocytes in plaques, we found that myocardial infarction liberated haematopoietic stem and progenitor cells from bone marrow niches via sympathetic nervous system signalling. The progenitors then seeded the spleen, yielding a sustained boost in monocyte production. These observations provide new mechanistic insight into atherogenesis and provide a novel therapeutic opportunity to mitigate disease progression.
C1 [Dutta, Partha; Courties, Gabriel; Leuschner, Florian; Gorbatov, Rostic; Robbins, Clinton S.; Iwamoto, Yoshiko; Thompson, Brian; Carlson, Alicia L.; Heidt, Timo; Majmudar, Maulik D.; Etzrodt, Martin; Waterman, Peter; Stone, James R.; Vinegoni, Claudio; Pittet, Mikael J.; Lin, Charles P.; Swirski, Filip K.; Weissleder, Ralph; Nahrendorf, Matthias] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA.
   [Dutta, Partha; Courties, Gabriel; Leuschner, Florian; Gorbatov, Rostic; Robbins, Clinton S.; Iwamoto, Yoshiko; Thompson, Brian; Carlson, Alicia L.; Heidt, Timo; Majmudar, Maulik D.; Etzrodt, Martin; Waterman, Peter; Stone, James R.; Vinegoni, Claudio; Pittet, Mikael J.; Lin, Charles P.; Swirski, Filip K.; Weissleder, Ralph; Nahrendorf, Matthias] Harvard Univ, Sch Med, Boston, MA 02114 USA.
   [Wei, Ying; Moskowitz, Michael A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,Stroke & Neurovasc Regulat Lab, Charlestown, MA 02129 USA.
   [Wei, Ying; Moskowitz, Michael A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol,Stroke & Neurovasc Regulat Lab, Charlestown, MA 02129 USA.
   [Leuschner, Florian; Katus, Hugo A.] Med Univ Hosp Heidelberg, Dept Cardiol, D-69120 Heidelberg, Germany.
   [Majmudar, Maulik D.; Libby, Peter] Brigham & Womens Hosp, Dept Med, Div Cardiovasc, Boston, MA 02115 USA.
   [Lasitschka, Felix] Univ Heidelberg Hosp, Inst Pathol, D-69120 Heidelberg, Germany.
   [Waring, Michael T.; Chicoine, Adam T.] MIT & Harvard Massachusetts Gen Hosp, Ragon Inst MGH, Charlestown, MA 02129 USA.
   [Waring, Michael T.; Chicoine, Adam T.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA.
   [van der Laan, Anja M.; Piek, Jan J.] Univ Amsterdam, Acad Med Ctr, Dept Cardiol, NL-1105 AZ Amsterdam, Netherlands.
   [Niessen, Hans W. M.] Vrije Univ Amsterdam Med Ctr, ICaR VU, Dept Pathol & Cardiac Surg, NL-1081 HV Amsterdam, Netherlands.
   [Rubin, Barry B.] Univ Toronto, Toronto Gen Hosp, Peter Munk Cardiac Ctr, Div Vasc Surg, Toronto, ON M5G 2C4, Canada.
   [Butany, Jagdish] Univ Toronto, Peter Munk Cardiac Ctr, Dept Pathol, Toronto, ON M5G 2C4, Canada.
   [Stone, James R.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
   [Murphy, Sabina A.; Morrow, David A.; Sabatine, Marc S.] Brigham & Womens Hosp, Div Cardiovasc, Dept Med, TIMI Study Grp, Boston, MA 02145 USA.
   [Weissleder, Ralph] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA.
C3 Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Ruprecht Karls University Heidelberg; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Ruprecht Karls University Heidelberg; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Massachusetts Institute of Technology (MIT); Ragon Institute; Howard Hughes Medical Institute; University of Amsterdam; Academic Medical Center Amsterdam; Vrije Universiteit Amsterdam; Amsterdam University Medical Center; University of Toronto; University Health Network Toronto; Toronto General Hospital; Peter Munk Cardiac Centre; University of Toronto; Peter Munk Cardiac Centre; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard University; Harvard Medical School
RP Nahrendorf, M (corresponding author), Massachusetts Gen Hosp, Ctr Syst Biol, Simches Res Bldg,185 Cambridge St, Boston, MA 02114 USA.
EM rweissleder@mgh.harvard.edu; mnahrendorf@mgh.harvard.edu
FU National Institute of Health [R01-HL096576, R01-HL095629, R01-EB006432, T32-CA79443, P50-CA086355]; Deutsche Forschungsgemeinschaft [SFB 938/Z2]; National Cancer Institute [T32CA079443] Funding Source: NIH RePORTER; National Heart Lung and Blood Institute [T32HL094301] Funding Source: NIH RePORTER
NR 36
TC 899
Z9 992
U1 2
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 JUL 19
PY 2012
VL 487
IS 7407
BP 325
EP 329
DI 10.1038/nature11260
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 975JB
UT WOS:000306506500034
PM 22763456
DA 2026-03-09
ER

PT J
AU Hattori, M
   Gouaux, E
AF Hattori, Motoyuki
   Gouaux, Eric
TI Molecular mechanism of ATP binding and ion channel activation in P2X receptors
SO NATURE
LA English
DT Article
ID pharmacological characterization; recombinant human; structural motif; pore; residues; identification; selectivity; access; site; permeability
AB P2X receptors are trimeric ATP-activated ion channels permeable to Na+, K+ and Ca2+. The seven P2X receptor subtypes are implicated in physiological processes that include modulation of synaptic transmission, contraction of smooth muscle, secretion of chemical transmitters and regulation of immune responses. Despite the importance of P2X receptors in cellular physiology, the three-dimensional composition of the ATP-binding site, the structural mechanism of ATP-dependent ion channel gating and the architecture of the open ion channel pore are unknown. Here we report the crystal structure of the zebrafish P2X(4) receptor in complex with ATP and a new structure of the apo receptor. The agonist-bound structure reveals a previously unseen ATP-binding motif and an open ion channel pore. ATP binding induces cleft closure of the nucleotide-binding pocket, flexing of the lower body beta-sheet and a radial expansion of the extracellular vestibule. The structural widening of the extracellular vestibule is directly coupled to the opening of the ion channel pore by way of an iris-like expansion of the transmembrane helices. The structural delineation of the ATP-binding site and the ion channel pore, together with the conformational changes associated with ion channel gating, will stimulate development of new pharmacological agents.
C1 [Hattori, Motoyuki; Gouaux, Eric] Oregon Hlth & Sci Univ, Vollum Inst, Portland, OR 97239 USA.
   [Gouaux, Eric] Oregon Hlth & Sci Univ, Howard Hughes Med Inst, Portland, OR 97239 USA.
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 Japan Society for the Promotion of Science; American Asthma Foundation; NIH
NR 59
TC 473
Z9 530
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 MAY 10
PY 2012
VL 485
IS 7397
BP 207
EP U91
DI 10.1038/nature11010
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 939HJ
UT WOS:000303799800034
PM 22535247
DA 2026-03-09
ER

PT J
AU Morrison, EA
   DeKoster, GT
   Dutta, S
   Vafabakhsh, R
   Clarkson, MW
   Bahl, A
   Kern, D
   Ha, T
   Henzler-Wildman, KA
AF Morrison, Emma A.
   DeKoster, Gregory T.
   Dutta, Supratik
   Vafabakhsh, Reza
   Clarkson, Michael W.
   Bahl, Arjun
   Kern, Dorothee
   Ha, Taekjip
   Henzler-Wildman, Katherine A.
TI Antiparallel EmrE exports drugs by exchanging between asymmetric structures
SO NATURE
LA English
DT Article
ID multidrug transporter emre; escherichia-coli; conformational-changes; membrane topology; substrate-binding; ligand-binding; proton release; model; state; mechanism
AB Small multidrug resistance transporters provide an ideal system to study the minimal requirements for active transport. EmrE is one such transporter in Escherichia coli. It exports a broad class of polyaromatic cation substrates, thus conferring resistance to drug compounds matching this chemical description. However, a great deal of controversy has surrounded the topology of the EmrE homodimer. Here we show that asymmetric antiparallel EmrE exchanges between inward-and outward-facing states that are identical except that they have opposite orientation in the membrane. We quantitatively measure the global conformational exchange between these two states for substrate-bound EmrE in bicelles using solution NMR dynamics experiments. Forster resonance energy transfer reveals that the monomers within each dimer are antiparallel, and paramagnetic relaxation enhancement NMR experiments demonstrate differential water accessibility of the two monomers within each dimer. Our experiments reveal a 'dynamic symmetry' that reconciles the asymmetric EmrE structure with the functional symmetry of residues in the active site.
C1 [Morrison, Emma A.; DeKoster, Gregory T.; Dutta, Supratik; Bahl, Arjun; Henzler-Wildman, Katherine A.] Washington Univ, Sch Med, Dept Biochem & Mol Biophys, St Louis, MO 63110 USA.
   [Vafabakhsh, Reza; Ha, Taekjip] Univ Illinois, Dept Phys, Urbana, IL 61801 USA.
   [Vafabakhsh, Reza; Ha, Taekjip] Univ Illinois, Howard Hughes Med Inst, Urbana, IL 61801 USA.
   [Clarkson, Michael W.; Kern, Dorothee] Brandeis Univ, Dept Biochem, Waltham, MA 02454 USA.
   [Clarkson, Michael W.; Kern, Dorothee] Brandeis Univ, Howard Hughes Med Inst, Waltham, MA 02454 USA.
C3 Washington University (WUSTL); University of Illinois System; University of Illinois Urbana-Champaign; Howard Hughes Medical Institute; University of Illinois System; University of Illinois Urbana-Champaign; Brandeis University; Howard Hughes Medical Institute; Brandeis University
RP Henzler-Wildman, KA (corresponding author), Washington Univ, Sch Med, Dept Biochem & Mol Biophys, St Louis, MO 63110 USA.
EM khenzler@wustl.edu
FU National Institutes of Health [1R01GM095839]; Searle Scholars Program; US Department of Energy, Office of Basic Energy Sciences; Howard Hughes Medical Institute; NSF [DGE-1143954]
NR 49
TC 184
Z9 215
U1 0
U2 119
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JAN 5
PY 2012
VL 481
IS 7379
BP 45
EP U50
DI 10.1038/nature10703
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 872VD
UT WOS:000298836900025
PM 22178925
DA 2026-03-09
ER

PT J
AU Liu, MK
   Hwang, HY
   Tao, H
   Strikwerda, AC
   Fan, KB
   Keiser, GR
   Sternbach, AJ
   West, KG
   Kittiwatanakul, S
   Lu, JW
   Wolf, SA
   Omenetto, FG
   Zhang, X
   Nelson, KA
   Averitt, RD
AF Liu, Mengkun
   Hwang, Harold Y.
   Tao, Hu
   Strikwerda, Andrew C.
   Fan, Kebin
   Keiser, George R.
   Sternbach, Aaron J.
   West, Kevin G.
   Kittiwatanakul, Salinporn
   Lu, Jiwei
   Wolf, Stuart A.
   Omenetto, Fiorenzo G.
   Zhang, Xin
   Nelson, Keith A.
   Averitt, Richard D.
TI Terahertz-field-induced insulator-to-metal transition in vanadium dioxide metamaterial
SO NATURE
LA English
DT Article
ID mott transition; poole-frenkel; spectroscopy; enhancement; electron; vo2
AB Electron-electron interactions can render an otherwise conducting material insulating(1), with the insulator-metal phase transition in correlated-electron materials being the canonical macroscopic manifestation of the competition between charge-carrier itinerancy and localization. The transition can arise from underlying microscopic interactions among the charge, lattice, orbital and spin degrees of freedom, the complexity of which leads to multiple phase-transition pathways. For example, in many transition metal oxides, the insulator-metal transition has been achieved with external stimuli, including temperature, light, electric field, mechanical strain or magnetic field(2-7). Vanadium dioxide is particularly intriguing because both the lattice and on-site Coulomb repulsion contribute to the insulator-to-metal transition at 340K (ref. 8). Thus, although the precise microscopic origin of the phase transition remains elusive, vanadium dioxide serves as a testbed for correlated-electron phase-transition dynamics. Here we report the observation of an insulator-metal transition in vanadium dioxide induced by a terahertz electric field. This is achieved using metamaterial-enhanced picosecond, high-field terahertz pulses to reduce the Coulomb-induced potential barrier for carrier transport(9). A nonlinear metamaterial response is observed through the phase transition, demonstrating that high-field terahertz pulses provide alternative pathways to induce collective electronic and structural rearrangements. The metamaterial resonators play a dual role, providing sub-wavelength field enhancement that locally drives the nonlinear response, and global sensitivity to the local changes, thereby enabling macroscopic observation of the dynamics(10,11). This methodology provides a powerful platform to investigate low-energy dynamics in condensed matter and, further, demonstrates that integration of metamaterials with complex matter is a viable pathway to realize functional nonlinear electromagnetic composites.
C1 [Hwang, Harold Y.; Nelson, Keith A.] MIT, Dept Chem, Cambridge, MA 02139 USA.
   [Liu, Mengkun; Strikwerda, Andrew C.; Keiser, George R.; Sternbach, Aaron J.; Averitt, Richard D.] Boston Univ, Dept Phys, Boston, MA 02215 USA.
   [Tao, Hu; Omenetto, Fiorenzo G.] Tufts Univ, Medford, MA 02155 USA.
   [Fan, Kebin; Zhang, Xin] Boston Univ, Dept Mech Engn, Boston, MA 02215 USA.
   [West, Kevin G.; Kittiwatanakul, Salinporn; Lu, Jiwei; Wolf, Stuart A.] Univ Virginia, Dept Mat Sci & Engn, Charlottesville, VA 22904 USA.
   [Wolf, Stuart A.] Univ Virginia, Dept Phys, Charlottesville, VA 22904 USA.
C3 Massachusetts Institute of Technology (MIT); Boston University; Tufts University; Boston University; University of Virginia; University of Virginia
RP Nelson, KA (corresponding author), MIT, Dept Chem, Cambridge, MA 02139 USA.
EM kanelson@mit.edu; raveritt@buphy.bu.edu
FU DOE-BES [DE-FG02-09ER46643]; ONR [N00014-09-1-1103]
NR 30
TC 1227
Z9 1378
U1 19
U2 1393
PU NATURE PUBLISHING 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 19
PY 2012
VL 487
IS 7407
BP 345
EP 348
DI 10.1038/nature11231
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 975JB
UT WOS:000306506500038
PM 22801506
DA 2026-03-09
ER

PT J
AU Mudd, PA
   Martins, MA
   Ericsen, AJ
   Tully, DC
   Power, KA
   Bean, AT
   Piaskowski, SM
   Duan, LJ
   Seese, A
   Gladden, AD
   Weisgrau, KL
   Furlott, JR
   Kim, YI
   de Santana, MGV
   Rakasz, E
   Capuano, S
   Wilson, NA
   Bonaldo, MC
   Galler, R
   Allison, DB
   Piatak, M
   Haase, AT
   Lifson, JD
   Allen, TM
   Watkins, DI
AF Mudd, Philip A.
   Martins, Mauricio A.
   Ericsen, Adam J.
   Tully, Damien C.
   Power, Karen A.
   Bean, Alex T.
   Piaskowski, Shari M.
   Duan, Lijie
   Seese, Aaron
   Gladden, Adrianne D.
   Weisgrau, Kim L.
   Furlott, Jessica R.
   Kim, Young-il
   Veloso de Santana, Marlon G.
   Rakasz, Eva
   Capuano, Saverio, III
   Wilson, Nancy A.
   Bonaldo, Myrna C.
   Galler, Ricardo
   Allison, David B.
   Piatak, Michael, Jr.
   Haase, Ashley T.
   Lifson, Jeffrey D.
   Allen, Todd M.
   Watkins, David I.
TI Vaccine-induced CD8+ T cells control AIDS virus replication
SO NATURE
LA English
DT Article
ID mamu-b-asterisk-08-positive macaques; immunodeficiency; siv; responses; hiv; infection; disease; escape; host
AB Developing a vaccine for human immunodeficiency virus(HIV) may be aided by a complete understanding of those rare cases in which some HIV-infected individuals control replication of the virus(1-3). Most of these elite controllers express the histocompatibility alleles HLA-B*57 or HLA-B*27 (ref. 3). These alleles remain by far the most robust associations with low concentrations of plasma virus(4,5), yet the mechanism of control in these individuals is not entirely clear. Here we vaccinate Indian rhesus macaques that express Mamu-B*08, an animal model for HLA-B*27-mediated elite control(6), with three Mamu-B*08-restricted CD8(+) T-cell epitopes, and demonstrate that these vaccinated animals control replication of the highly pathogenic clonal simian immunodeficiency virus (SIV) mac239 virus. High frequencies of CD8(+) T cells against these Vif and Nef epitopes in the blood, lymph nodes and colon were associated with viral control. Moreover, the frequency of the CD8(+) T-cell response against the Nef RL10 epitope (Nef amino acids 137-146) correlated significantly with reduced acute phase viraemia. Finally, two of the eight vaccinees lost control of viral replication in the chronic phase, concomitant with escape in all three targeted epitopes, further implicating these three CD8(+) T-cell responses in the control of viral replication. Our findings indicate that narrowly targeted vaccine-induced virus-specific CD8(+) T-cell responses can control replication of the AIDS virus.
C1 [Martins, Mauricio A.; Watkins, David I.] Univ Miami, Miller Sch Med, Dept Pathol, Miami, FL 33136 USA.
   [Mudd, Philip A.; Ericsen, Adam J.; Bean, Alex T.; Piaskowski, Shari M.; Weisgrau, Kim L.; Furlott, Jessica R.; Wilson, Nancy A.] Univ Wisconsin Madison, Dept Pathol & Lab Med, Madison, WI 53711 USA.
   [Mudd, Philip A.] Univ Wisconsin Madison, Med Scientist Training Program, Madison, WI 53705 USA.
   [Tully, Damien C.; Power, Karen A.; Seese, Aaron; Gladden, Adrianne D.; Allen, Todd M.] Ragon Inst MGH MIT & Harvard, Boston, MA 02129 USA.
   [Duan, Lijie; Haase, Ashley T.] Univ Minnesota, Dept Microbiol, Minneapolis, MN 55455 USA.
   [Kim, Young-il] Univ Alabama Birmingham, Dept Med, Div Prevent Med, Birmingham, AL 35294 USA.
   [Veloso de Santana, Marlon G.; Bonaldo, Myrna C.] Fiocruz MS, Inst Oswaldo Cruz, Lab Biol Mol Flavivirus, BR-21045900 Rio De Janeiro, Brazil.
   [Rakasz, Eva; Capuano, Saverio, III; Wilson, Nancy A.] Univ Wisconsin Madison, Wisconsin Natl Primate Res Ctr, Madison, WI 53711 USA.
   [Galler, Ricardo] Fundacao Oswaldo Cruz, Inst Tecnol Imunobiol, Rio De Janeiro, Brazil.
   [Allison, David B.] Univ Alabama Birmingham, Dept Biostat, Sect Stat Genet, Birmingham, AL 35294 USA.
   [Piatak, Michael, Jr.; Lifson, Jeffrey D.] NCI, AIDS & Canc Virus Program, SAIC Frederick Inc, Frederick, MD 21702 USA.
C3 University of Miami; University of Wisconsin System; University of Wisconsin Madison; University of Wisconsin System; University of Wisconsin Madison; Harvard University; Massachusetts Institute of Technology (MIT); Ragon Institute; University of Minnesota System; University of Minnesota Twin Cities; University of Alabama System; University of Alabama Birmingham; Fundacao Oswaldo Cruz; University of Wisconsin System; University of Wisconsin Madison; Fundacao Oswaldo Cruz; University of Alabama System; University of Alabama Birmingham; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); Science Applications International Corporation (SAIC); SAIC-Frederick
RP Watkins, DI (corresponding author), Univ Miami, Miller Sch Med, Dept Pathol, Miami, FL 33136 USA.
EM dwatkins@med.miami.edu
FU National Institutes of Health (NIH) [R37 AI052056, RO1 AI076114, RR015371, HHSN261200800001E]; FAPERJ; INCTV; CNPq; MCT; FIOCRUZ; NIH Office of the Director [P51OD011106] Funding Source: NIH RePORTER
NR 24
TC 149
Z9 172
U1 0
U2 36
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 1
PY 2012
VL 491
IS 7422
BP 129
EP U152
DI 10.1038/nature11443
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 028PM
UT WOS:000310434500044
PM 23023123
DA 2026-03-09
ER

PT J
AU Balter, V
   Braga, J
   Télouk, P
   Thackeray, JF
AF Balter, Vincent
   Braga, Jose
   Telouk, Philippe
   Thackeray, J. Francis
TI Evidence for dietary change but not landscape use in South African early hominins
SO NATURE
LA English
DT Article
ID ablation icp-ms; plasma-mass spectrometry; trace-elements; tooth enamel; australopithecus; isotopes; teeth; distributions; opportunity; diagenesis
AB The dichotomy between early Homo and Paranthropus is justified partly on morphology(1,2). In terms of diet, it has been suggested that early Homo was a generalist but that Paranthropus was a specialist(3). However, this model is challenged and the issue of the resources used by Australopithecus, the presumed common ancestor, is still unclear. Laser ablation profiles of strontium/calcium, barium/calcium and strontium isotope ratios in tooth enamel are a means to decipher intra-individual diet and habitat changes. Here we show that the home range area was of similar size for species of the three hominin genera but that the dietary breadth was much higher in Australopithecus africanus than in Paranthropus robustus and early Homo. We also confirm that P. robustus relied more on plant-based foodstuffs than early Homo. A South African scenario is emerging in which the broad ecological niche of Australopithecus became split, and was then occupied by Paranthropus and early Homo, both consuming a lower diversity of foods than Australopithecus.
C1 [Balter, Vincent; Telouk, Philippe] Ecole Normale Super Lyon, CNRS, UMR 5276, Lab Geol Lyon, F-69342 Lyon 07, France.
   [Braga, Jose] Univ Toulouse Paul Sabatier, CNRS, UMR 5288, Comp Assisted Palaeoanthropol Team, F-31000 Toulouse, France.
   [Thackeray, J. Francis] Univ Witwatersrand, Inst Human Evolut, ZA-2050 Johannesburg, South Africa.
C3 Ecole Normale Superieure de Lyon (ENS de LYON); Universite Lyon 1; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Earth Sciences & Astronomy (INSU); Centre National de la Recherche Scientifique (CNRS); CNRS - Institute of Ecology & Environment (INEE); Universite de Toulouse; Universite Toulouse III - Paul Sabatier; Universites de Strasbourg Etablissements Associes; Universite de Strasbourg; University of Witwatersrand
RP Balter, V (corresponding author), Ecole Normale Super Lyon, CNRS, UMR 5276, Lab Geol Lyon, 15 Parvis Rene Descartes,BP 7000, F-69342 Lyon 07, France.
EM Vincent.Balter@ens-lyon.fr
FU South African National Research Foundation; French Ministry of Foreign Affairs; French Embassy in South Africa through the Cultural and Cooperation Services; French Institut National des Sciences de l'Univers
NR 26
TC 86
Z9 102
U1 0
U2 159
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD SEP 27
PY 2012
VL 489
IS 7417
BP 558
EP 560
DI 10.1038/nature11349
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 046RG
UT WOS:000311781500002
PM 22878716
DA 2026-03-09
ER

PT J
AU Taylor, CM
   de Jeu, RAM
   Guichard, F
   Harris, PP
   Dorigo, WA
AF Taylor, Christopher M.
   de Jeu, Richard A. M.
   Guichard, Francoise
   Harris, Phil P.
   Dorigo, Wouter A.
TI Afternoon rain more likely over drier soils
SO NATURE
LA English
DT Article
ID boundary layer interactions; part ii; atmospheric controls; diurnal cycle; united-states; moisture; precipitation; land; convection; feedback
AB Land surface properties, such as vegetation cover and soil moisture, influence the partitioning of radiative energy between latent and sensible heat fluxes in daytime hours. During dry periods, soil-water deficit can limit evapotranspiration, leading to warmer and drier conditions in the lower atmosphere(1,2). Soil moisture can influence the development of convective storms through such modifications of low-level atmospheric temperature and humidity(1,3), which in turn feeds back on soil moisture. Yet there is considerable uncertainty in how soil moisture affects convective storms across the world, owing to a lack of observational evidence and uncertainty in large-scale models(4). Here we present a global-scale observational analysis of the coupling between soil moisture and precipitation. We show that across all six continents studied, afternoon rain falls preferentially over soils that are relatively dry compared to the surrounding area. The signal emerges most clearly in the observations over semi-arid regions, where surface fluxes are sensitive to soil moisture, and convective events are frequent. Mechanistically, our results are consistent with enhanced afternoon moist convection driven by increased sensible heat flux over drier soils, and/or mesoscale variability in soil moisture. We find no evidence in our analysis of a positive feedback-that is, a preference for rain over wetter soils-at the spatial scale (50-100 kilometres) studied. In contrast, we find that a positive feedback of soil moisture on simulated precipitation does dominate in six state-of-the-art global weather and climate models-a difference that may contribute to excessive simulated droughts in large-scale models.
C1 [Taylor, Christopher M.; Harris, Phil P.] NERC Ctr Ecol & Hydrol, Wallingford OX10 8BB, Oxon, England.
   [de Jeu, Richard A. M.] Vrije Univ Amsterdam, Dept Earth Sci, Fac Earth & Life Sci, NL-1081 HV Amsterdam, Netherlands.
   [Guichard, Francoise] CNRM GAME CNRS, F-31057 Toulouse, France.
   [Guichard, Francoise] Meteo France, F-31057 Toulouse, France.
   [Dorigo, Wouter A.] Vienna Univ Technol, Inst Photogrammetry & Remote Sensing IPF, A-1040 Vienna, Austria.
C3 UK Centre for Ecology & Hydrology (UKCEH); Vrije Universiteit Amsterdam; Centre National de la Recherche Scientifique (CNRS); Technische Universitat Wien
RP Taylor, CM (corresponding author), NERC Ctr Ecol & Hydrol, Maclean Bldg,Benson Lane, Wallingford OX10 8BB, Oxon, England.
EM cmt@ceh.ac.uk
FU European Union (FP6) WATCH Integrated Project [036946]; UK National Centre for Earth Observation; European Space Agency STSE Water Cycle Multi-mission Observation Strategy (WACMOS) project (ESRIN) [22086/08/I-EC]; Natural Environment Research Council [NE/B505538/1, earth010002, NE/G018499/1] Funding Source: researchfish; NERC [NE/G018499/1, earth010002] Funding Source: UKRI
NR 30
TC 513
Z9 584
U1 9
U2 313
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD SEP 20
PY 2012
VL 489
IS 7416
BP 423
EP 426
DI 10.1038/nature11377
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 007AK
UT WOS:000308860900043
PM 22972193
DA 2026-03-09
ER

PT J
AU Hellmer, HH
   Kauker, F
   Timmermann, R
   Determann, J
   Rae, J
AF Hellmer, Hartmut H.
   Kauker, Frank
   Timmermann, Ralph
   Determann, Juergen
   Rae, Jamie
TI Twenty-first-century warming of a large Antarctic ice-shelf cavity by a redirected coastal current
SO NATURE
LA English
DT Article
ID pine island glacier; sea-ice; weddell sea; ocean circulation; numerical-model; coupled model; transport; deep
AB The Antarctic ice sheet loses mass at its fringes bordering the Southern Ocean. At this boundary, warm circumpolar water can override the continental slope front, reaching the grounding line(1,2) through submarine glacial troughs and causing high rates of melting at the deep ice-shelf bases(3,4). The interplay between ocean currents and continental bathymetry is therefore likely to influence future rates of ice-mass loss. Here we show that a redirection of the coastal current into the Filchner Trough and underneath the Filchner-Ronne Ice Shelf during the second half of the twenty-first century would lead to increased movement of warm waters into the deep southern ice-shelf cavity. Water temperatures in the cavity would increase by more than 2 degrees Celsius and boost average basal melting from 0.2 metres, or 82 billion tonnes, per year to almost 4 metres, or 1,600 billion tonnes, per year. Our results, which are based on the output of a coupled ice-ocean model forced by a range of atmospheric outputs from the HadCM3(5) climate model, suggest that the changes would be caused primarily by an increase in ocean surface stress in the southeastern Weddell Sea due to thinning of the formerly consolidated sea-ice cover. The projected ice loss at the base of the Filchner-Ronne Ice Shelf represents 80 per cent of the present Antarctic surface mass balance(6). Thus, the quantification of basal mass loss under changing climate conditions is important for projections regarding the dynamics of Antarctic ice streams and ice shelves, and global sea level rise.
C1 [Hellmer, Hartmut H.; Kauker, Frank; Timmermann, Ralph; Determann, Juergen] Alfred Wegener Inst Polar & Marine Res, D-27570 Bremerhaven, Germany.
   [Kauker, Frank] OASys, D-22767 Hamburg, Germany.
   [Rae, Jamie] Met Off Hadley Ctr, Exeter EX1 3PB, Devon, England.
C3 Helmholtz Association; Alfred Wegener Institute, Helmholtz Centre for Polar & Marine Research; Met Office - UK; Hadley Centre
RP Hellmer, HH (corresponding author), Alfred Wegener Inst Polar & Marine Res, D-27570 Bremerhaven, Germany.
EM hartmut.hellmer@awi.de
FU European Union [226375]
NR 31
TC 340
Z9 361
U1 2
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 MAY 10
PY 2012
VL 485
IS 7397
BP 225
EP 228
DI 10.1038/nature11064
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 939HJ
UT WOS:000303799800038
PM 22575964
DA 2026-03-09
ER

PT J
AU Coric, I
   List, B
AF Coric, Ilija
   List, Benjamin
TI Asymmetric spiroacetalization catalysed by confined Bronsted acids
SO NATURE
LA English
DT Article
ID transition-metal catalysis; dacus-oleae; spiroketals; transacetalization; phosphoramide; derivatives; pheromone; aldehydes; design
AB Acetals are molecular substructures that contain two oxygencarbon single bonds at the same carbon atom, and are used in cells to construct carbohydrates and numerous other molecules. A distinctive subgroup are spiroacetals, acetals joining two rings, which occur in a broad range of biologically active compounds, including small insect pheromones and more complex macrocycles(1,2). Despite numerous methods for the catalytic asymmetric formation of other commonly occurring stereocentres, there are few approaches that exclusively target the chiral acetal centre and none for spiroacetals(3,4). Here we report the design and synthesis of confined Bronsted acids based on a C-2-symmetric imidodiphosphoric acid motif, enabling a catalytic enantioselective spiroacetalization reaction. These rationally constructed Bronsted acids possess an extremely sterically demanding chiral microenvironment, with a single catalytically relevant and geometrically constrained bifunctional active site. Our catalyst design is expected to be of broad utility in catalytic asymmetric reactions involving small and structurally or functionally unbiased substrates.
C1 [Coric, Ilija; List, Benjamin] Max Planck Inst Kohlenforsch, D-45470 Mulheim, Germany.
C3 Max Planck Society
RP List, B (corresponding author), Max Planck Inst Kohlenforsch, Kaiser Wilhelm Pl 1, D-45470 Mulheim, Germany.
EM list@kofo.mpg.de
FU Max Planck Sociey; European Research Council
NR 30
TC 394
Z9 458
U1 4
U2 344
PU NATURE PUBLISHING 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 15
PY 2012
VL 483
IS 7389
BP 315
EP 319
DI 10.1038/nature10932
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 908HP
UT WOS:000301481800045
PM 22422266
DA 2026-03-09
ER

PT J
AU Papanikolaou, S
   Dimiduk, DM
   Choi, W
   Sethna, JP
   Uchic, MD
   Woodward, CF
   Zapperi, S
AF Papanikolaou, Stefanos
   Dimiduk, Dennis M.
   Choi, Woosong
   Sethna, James P.
   Uchic, Michael D.
   Woodward, Christopher F.
   Zapperi, Stefano
TI Quasi-periodic events in crystal plasticity and the self-organized avalanche oscillator
SO NATURE
LA English
DT Article
ID flow; dynamics; statistics; model; slip
AB When external stresses in a system-physical, social or virtual-are relieved through impulsive events, it is natural to focus on the attributes of these avalanches(1,2). However, during the quiescent periods between them(3), stresses may be relieved through competing processes, such as slowly flowing water between earthquakes(4) or thermally activated dislocation flow(5) between plastic bursts in crystals(6-8). Such smooth responses can in turn have marked effects on the avalanche properties(9). Here we report an experimental investigation of slowly compressed nickel microcrystals, covering three orders of magnitude in nominal strain rate, in which we observe unconventional quasi-periodic avalanche bursts and higher critical exponents as the strain rate is decreased. Our experiments are faithfully reproduced by analytic and computational dislocation avalanche modelling(10,11) that we have extended to incorporate dislocation relaxation, revealing the emergence of the self-organized avalanche oscillator: a novel critical state exhibiting oscillatory approaches towards a depinning critical point(12). This theory suggests that whenever avalanches compete with slow relaxation-in settings ranging from crystal microplasticity to earthquakes-dynamical quasi-periodic scale invariance ought to emerge.
C1 [Papanikolaou, Stefanos] Yale Univ, Dept Mech Engn & Mat Sci, New Haven, CT 06520 USA.
   [Papanikolaou, Stefanos] Yale Univ, Dept Phys, New Haven, CT 06520 USA.
   [Dimiduk, Dennis M.; Uchic, Michael D.; Woodward, Christopher F.] USAF, Res Lab, Mat & Mfg Directorate, AFRL RXCM, Wright Patterson AFB, OH 45433 USA.
   [Choi, Woosong; Sethna, James P.] Cornell Univ, Dept Phys, Atom & Solid State Phys Lab, Ithaca, NY 14853 USA.
   [Zapperi, Stefano] CNR, IENI, I-20125 Milan, Italy.
   [Zapperi, Stefano] ISI Fdn, I-10126 Turin, Italy.
C3 Yale University; Yale University; United States Department of Defense; United States Air Force; US Air Force Research Laboratory; Cornell University; Consiglio Nazionale delle Ricerche (CNR)
RP Papanikolaou, S (corresponding author), Yale Univ, Dept Mech Engn & Mat Sci, New Haven, CT 06520 USA.
EM stefanos.papanikolaou@yale.edu
FU DTRA [1-10-1-0021]; DOE-BES [DE-FG02-07ER-46393]; Air Force Office of Scientific Research; Materials and Manufacturing Directorate; ComplexityNet pilot project LOCAT
NR 37
TC 133
Z9 153
U1 1
U2 130
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 25
PY 2012
VL 490
IS 7421
BP 517
EP +
DI 10.1038/nature11568
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 025NK
UT WOS:000310196200037
PM 23099406
DA 2026-03-09
ER

PT J
AU Shima, S
   Krueger, M
   Weinert, T
   Demmer, U
   Kahnt, J
   Thauer, RK
   Ermler, U
AF Shima, Seigo
   Krueger, Martin
   Weinert, Tobias
   Demmer, Ulrike
   Kahnt, Joerg
   Thauer, Rudolf K.
   Ermler, Ulrich
TI Structure of a methyl-coenzyme M reductase from Black Sea mats that oxidize methane anaerobically
SO NATURE
LA English
DT Article
ID methanotrophic archaea; oxidation; methanogenesis; diversity; mechanism; anme-1; model
AB The anaerobic oxidation of methane (AOM) with sulphate, an area currently generating great interest in microbiology, is accomplished by consortia of methanotrophic archaea (ANME) and sulphate-reducing bacteria(1,2). The enzyme activating methane in methanotrophic archaea has tentatively been identified as a homologue of methyl-coenzyme M reductase (MCR) that catalyses the methane-forming step in methanogenic archaea(3,4). Here we report an X-ray structure of the 280 kDa heterohexameric ANME-1 MCR complex. It was crystallized uniquely from a protein ensemble purified from consortia of microorganisms collected with a submersible from a Black Sea mat catalysing AOM with sulphate(4). Crystals grown from the heterogeneous sample diffract to 2.1 angstrom resolution and consist of a single ANME-1MCR population, demonstrating the strong selective power of crystallization. The structure revealed ANME-1 MCR in complex with coenzyme M and coenzyme B, indicating the same substrates for MCR from methanotrophic and methanogenic archaea. Differences between the highly similar structures of ANME-1MCR and methanogenic MCR include a F-430 modification, a cysteine-rich patch and an altered post-translational amino acid modification pattern, which may tune the enzymes for their functions in different biological contexts.
C1 [Shima, Seigo; Kahnt, Joerg; Thauer, Rudolf K.] Max Planck Inst Terr Microbiol, D-35043 Marburg, Germany.
   [Shima, Seigo] Japan Sci & Technol Agcy JST, PRESTO, Kawaguchi, Saitama 3320012, Japan.
   [Krueger, Martin] Fed Inst Geosci & Resources, D-30655 Hannover, Germany.
   [Weinert, Tobias; Demmer, Ulrike; Ermler, Ulrich] Max Planck Inst Biophys, D-60438 Frankfurt, Germany.
C3 Max Planck Society; Japan Science & Technology Agency (JST); Max Planck Society
RP Shima, S (corresponding author), Max Planck Inst Terr Microbiol, Karl von Frisch Str 10, D-35043 Marburg, Germany.
EM shima@mpi-marburg.mpg.de; ulrich.ermler@biophys.mpg.de
FU Max Planck Society; Fonds der Chemischen Industrie; Deutsche Forschungsgemeinschaft [SPP 1319, ER 222/5-1, KR 3311/6-2]; MUMM; BEBOP; University of Hamburg; PRESTO, Japan Science and Technology Agency (JST)
NR 30
TC 134
Z9 166
U1 5
U2 133
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 5
PY 2012
VL 481
IS 7379
BP 98
EP 101
DI 10.1038/nature10663
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 872VD
UT WOS:000298836900037
PM 22121022
DA 2026-03-09
ER

PT J
AU McCord, TB
   Li, JY
   Combe, JP
   McSween, HY
   Jaumann, R
   Reddy, V
   Tosi, F
   Williams, DA
   Blewett, DT
   Turrini, D
   Palomba, E
   Pieters, CM
   De Sanctis, MC
   Ammannito, E
   Capria, MT
   Le Corre, L
   Longobardo, A
   Nathues, A
   Mittlefehldt, DW
   Schröder, SE
   Hiesinger, H
   Beck, AW
   Capaccioni, F
   Carsenty, U
   Keller, HU
   Denevi, BW
   Sunshine, JM
   Raymond, CA
   Russell, CT
AF McCord, T. B.
   Li, J. -Y.
   Combe, J. -P.
   McSween, H. Y.
   Jaumann, R.
   Reddy, V.
   Tosi, F.
   Williams, D. A.
   Blewett, D. T.
   Turrini, D.
   Palomba, E.
   Pieters, C. M.
   De Sanctis, M. C.
   Ammannito, E.
   Capria, M. T.
   Le Corre, L.
   Longobardo, A.
   Nathues, A.
   Mittlefehldt, D. W.
   Schroeder, S. E.
   Hiesinger, H.
   Beck, A. W.
   Capaccioni, F.
   Carsenty, U.
   Keller, H. U.
   Denevi, B. W.
   Sunshine, J. M.
   Raymond, C. A.
   Russell, C. T.
TI Dark material on Vesta from the infall of carbonaceous volatile-rich material
SO NATURE
LA English
DT Article
ID dawn; heterogeneity; mineralogy; surface; albedo; color
AB Localized dark and bright materials, often with extremely different albedos, were recently found on Vesta's surface(1,2). The range of albedos is among the largest observed on Solar System rocky bodies. These dark materials, often associated with craters, appear in ejecta and crater walls, and their pyroxene absorption strengths are correlated with material brightness. It was tentatively suggested that the dark material on Vesta could be either exogenic, from carbon-rich, low-velocity impactors, or endogenic, from freshly exposed mafic material or impact melt, created or exposed by impacts. Here we report Vesta spectra and images and use them to derive and interpret the properties of the 'pure' dark and bright materials. We argue that the dark material is mainly from infall of hydrated carbonaceous material (like that found in a major class of meteorites and some comet surfaces(3-5)), whereas the bright material is the uncontaminated indigenous Vesta basaltic soil. Dark material from low-albedo impactors is diffused over time through the Vestan regolith by impact mixing, creating broader, diffuse darker regions and finally Vesta's background surface material. This is consistent with howardite-eucrite-diogenite meteorites coming from Vesta.
C1 [McCord, T. B.; Combe, J. -P.] Bear Fight Inst, Winthrop, WA 98862 USA.
   [Li, J. -Y.] Planetary Sci Inst, Tucson, AZ 85719 USA.
   [McSween, H. Y.] Univ Tennessee, Knoxville, TN 37996 USA.
   [Jaumann, R.; Carsenty, U.] Inst Planetary Res, DLR, D-80302 Berlin, Germany.
   [Reddy, V.; Le Corre, L.; Nathues, A.; Schroeder, S. E.] Max Planck Inst Solar Syst Res, D-37191 Katlenburg, Germany.
   [Reddy, V.] Univ N Dakota, Grand Forks, ND 58202 USA.
   [Tosi, F.; Turrini, D.; Palomba, E.; De Sanctis, M. C.; Ammannito, E.; Capria, M. T.; Longobardo, A.; Capaccioni, F.] Ist Nazl Astrofis IASF, I-00133 Rome, Italy.
   [Williams, D. A.] Arizona State Univ, Tempe, AZ 85287 USA.
   [Blewett, D. T.; Denevi, B. W.] Johns Hopkins Univ, Appl Phys Lab, Laurel, MD 20723 USA.
   [Pieters, C. M.] Brown Univ, Providence, RI 02912 USA.
   [Mittlefehldt, D. W.] NASA, Lyndon B Johnson Space Ctr, Astromat Res Off, Houston, TX 77058 USA.
   [Hiesinger, H.] Univ Munster, Inst Planetol, D-48149 Munster, Germany.
   [Beck, A. W.] Smithsonian Natl Museum Nat Hist, Dept Mineral Sci, Washington, DC 20024 USA.
   [Keller, H. U.] Inst Geophys & Extraterr Phys, D-38106 Braunschweig, Germany.
   [Sunshine, J. M.] Univ Maryland, Dept Astron, College Pk, MD 20742 USA.
   [Raymond, C. A.] CALTECH, Jet Prop Lab, Pasadena, CA 91109 USA.
   [Russell, C. T.] Univ Calif Los Angeles, Los Angeles, CA 90095 USA.
C3 University of Tennessee System; University of Tennessee Knoxville; Helmholtz Association; German Aerospace Centre (DLR); Max Planck Society; University of North Dakota Grand Forks; Istituto Nazionale Astrofisica (INAF); Arizona State University; Arizona State University-Tempe; Johns Hopkins University; Johns Hopkins University Applied Physics Laboratory; Brown University; National Aeronautics & Space Administration (NASA); NASA Johnson Space Center; University of Munster; Smithsonian Institution; Smithsonian National Museum of Natural History; University System of Maryland; University of Maryland College Park; National Aeronautics & Space Administration (NASA); NASA Jet Propulsion Laboratory (JPL); California Institute of Technology; University of California System; University of California Los Angeles
RP McCord, TB (corresponding author), Bear Fight Inst, 22 Fiddlers Rd,Box 667, Winthrop, WA 98862 USA.
EM tmccord@bearfightinstitute.com; jean-philippe_combe@bearfightinstitutute.com
FU NASA Dawn Project under UCLA; NASA Dawn at Vesta Participating Scientist program; Italian Space Agency; Max Planck Institute for Solar System Research; Germany Aerospace Agency (DLR)
NR 23
TC 157
Z9 163
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 1
PY 2012
VL 491
IS 7422
BP 83
EP U93
DI 10.1038/nature11561
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 028PM
UT WOS:000310434500034
PM 23128228
DA 2026-03-09
ER

PT J
AU Pozzo, M
   Davies, C
   Gubbins, D
   Alfè, D
AF Pozzo, Monica
   Davies, Chris
   Gubbins, David
   Alfe, Dario
TI Thermal and electrical conductivity of iron at Earth's core conditions
SO NATURE
LA English
DT Article
ID heat-flux; efficiency; convection; geodynamo; metals
AB The Earth acts as a gigantic heat engine driven by the decay of radiogenic isotopes and slow cooling, which gives rise to plate tectonics, volcanoes and mountain building. Another key product is the geomagnetic field, generated in the liquid iron core by a dynamo running on heat released by cooling and freezing (as the solid inner core grows), and on chemical convection (due to light elements expelled from the liquid on freezing). The power supplied to the geodynamo, measured by the heat flux across the core-mantle boundary (CMB), places constraints on Earth's evolution(1). Estimates of CMB heat flux(2-5) depend on properties of iron mixtures under the extreme pressure and temperature conditions in the core, most critically on the thermal and electrical conductivities. These quantities remain poorly known because of inherent experimental and theoretical difficulties. Here we use density functional theory to compute these conductivities in liquid iron mixtures at core conditions from first principles-unlike previous estimates, which relied on extrapolations. The mixtures of iron, oxygen, sulphur and silicon are taken from earlier work(6) and fit the seismologically determined core density and inner-core boundary density jump(7,8). We find both conductivities to be two to three times higher than estimates in current use. The changes are so large that core thermal histories and power requirements need to be reassessed. New estimates indicate that the adiabatic heat flux is 15 to 16 terawatts at the CMB, higher than present estimates of CMB heat flux based on mantle convection(1); the top of the core must be thermally stratified and any convection in the upper core must be driven by chemical convection against the adverse thermal buoyancy or lateral variations in CMB heat flow. Power for the geodynamo is greatly restricted, and future models of mantle evolution will need to incorporate a high CMB heat flux and explain the recent formation of the inner core.
C1 [Pozzo, Monica; Alfe, Dario] UCL, Dept Earth Sci, London WC1E 6BT, England.
   [Pozzo, Monica; Alfe, Dario] UCL, Thomas Young Ctr UCL, London WC1E 6BT, England.
   [Davies, Chris; Gubbins, David] Univ Leeds, Sch Earth & Environm, Leeds LS2 9JT, W Yorkshire, England.
   [Gubbins, David] Univ Calif San Diego, Scripps Inst Oceanog, Inst Geophys & Planetary Phys, La Jolla, CA 92093 USA.
   [Alfe, Dario] UCL, Dept Phys & Astron, London WC1E 6BT, England.
   [Alfe, Dario] UCL, London Ctr Nanotechnol, London WC1E 6BT, England.
C3 University of London; University College London; University of London; University College London; University of Leeds; University of California System; University of California San Diego; Scripps Institution of Oceanography; University of London; University College London; University of London; University College London
RP Alfè, D (corresponding author), UCL, Dept Earth Sci, Gower St, London WC1E 6BT, England.
EM d.alfe@ucl.ac.uk
FU CSEDI from the National Science Foundation [EAR1065597]; Natural Environment Research Council [NE/H01571X/1, NE/H02462X/1]; NERC [NE/H01571X/1, NE/H02462X/1] Funding Source: UKRI; Natural Environment Research Council [NE/H01571X/1, NE/H02462X/1] Funding Source: researchfish
NR 38
TC 466
Z9 517
U1 2
U2 291
PU NATURE PUBLISHING 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 17
PY 2012
VL 485
IS 7398
BP 355
EP U99
DI 10.1038/nature11031
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 943CW
UT WOS:000304099100039
PM 22495307
DA 2026-03-09
ER

PT J
AU Vilchez, D
   Morantte, I
   Liu, Z
   Douglas, PM
   Merkwirth, C
   Rodrigues, APC
   Manning, G
   Dillin, A
AF Vilchez, David
   Morantte, Ianessa
   Liu, Zheng
   Douglas, Peter M.
   Merkwirth, Carsten
   Rodrigues, Ana P. C.
   Manning, Gerard
   Dillin, Andrew
TI RPN-6 determines C. elegans longevity under proteotoxic stress conditions
SO NATURE
LA English
DT Article
ID ubiquitin-proteasome system; heat-shock factor; caenorhabditis-elegans; life-span; stem-cells; daf-16; restriction; metabolism; autophagy; gene
AB Organisms that protect their germ-cell lineages from damage often do so at considerable cost: limited metabolic resources become partitioned away from maintenance of the soma, leaving the ageing somatic tissues to navigate survival amid an environment containing damaged and poorly functioning proteins. Historically, experimental paradigms that limit reproductive investment result in lifespan extension. We proposed that germline-deficient animals might exhibit heightened protection from proteotoxic stressors in somatic tissues. We find that the forced re-investment of resources from the germ line to the soma in Caenorhabditis elegans results in elevated somatic proteasome activity, clearance of damaged proteins and increased longevity. This activity is associated with increased expression of rpn-6, a subunit of the 19S proteasome, by the FOXO transcription factor DAF-16. Ectopic expression of rpn-6 is sufficient to confer proteotoxic stress resistance and extend lifespan, indicating that rpn-6 is a candidate to correct deficiencies in age-related protein homeostasis disorders.
C1 [Vilchez, David; Morantte, Ianessa; Liu, Zheng; Douglas, Peter M.; Merkwirth, Carsten; Dillin, Andrew] Salk Inst Biol Studies, Howard Hughes Med Inst, Glenn Ctr Aging Res, Mol & Cell Biol Lab, La Jolla, CA 92037 USA.
   [Rodrigues, Ana P. C.; Manning, Gerard] Salk Inst Biol Studies, Razavi Newman Ctr Bioinformat, La Jolla, CA 92037 USA.
C3 Salk Institute; Howard Hughes Medical Institute; Salk Institute
RP Dillin, A (corresponding author), Salk Inst Biol Studies, Howard Hughes Med Inst, Glenn Ctr Aging Res, Mol & Cell Biol Lab, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA.
EM dillin@salk.edu
FU HHMI; NIA; F.M. Kirby, Inc. Foundation Postdoctoral Scholar Award; Beatriu de Pinos (AGAUR) fellowship
NR 47
TC 349
Z9 399
U1 1
U2 63
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 13
PY 2012
VL 489
IS 7415
BP 263
EP +
DI 10.1038/nature11315
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 003UC
UT WOS:000308635900035
PM 22922647
DA 2026-03-09
ER

PT J
AU Sasaki, M
   Knobbe, CB
   Munger, JC
   Lind, EF
   Brenner, D
   Brüstle, A
   Harris, IS
   Holmes, R
   Wakeham, A
   Haight, J
   You-Ten, A
   Li, WY
   Schalm, S
   Su, SM
   Virtanen, C
   Reifenberger, G
   Ohashi, PS
   Barber, DL
   Figueroa, ME
   Melnick, A
   Zúñiga-Pflücker, JC
   Mak, TW
AF Sasaki, Masato
   Knobbe, Christiane B.
   Munger, Joshua C.
   Lind, Evan F.
   Brenner, Dirk
   Bruestle, Anne
   Harris, Isaac S.
   Holmes, Roxanne
   Wakeham, Andrew
   Haight, Jillian
   You-Ten, Annick
   Li, Wanda Y.
   Schalm, Stefanie
   Su, Shinsan M.
   Virtanen, Carl
   Reifenberger, Guido
   Ohashi, Pamela S.
   Barber, Dwayne L.
   Figueroa, Maria E.
   Melnick, Ari
   Zuniga-Pfluecker, Juan-Carlos
   Mak, Tak W.
TI IDH1(R132H) mutation increases murine haematopoietic progenitors and alters epigenetics
SO NATURE
LA English
DT Article
ID acute myeloid-leukemia; false discovery rate; oncometabolite 2-hydroxyglutarate; idh2 mutations; stem-cells; notch
AB Mutations in the IDH1 and IDH2 genes encoding isocitrate dehydrogenases are frequently found in human glioblastomas(1) and cytogenetically normal acute myeloid leukaemias (AML)(2). These alterations are gain-of-function mutations in that they drive the synthesis of the 'oncometabolite' R-2-hydroxyglutarate (2HG)(3). It remains unclear how IDH1 and IDH2 mutations modify myeloid cell development and promote leukaemogenesis. Here we report the characterization of conditional knock-in (KI) mice in which the most common IDH1 mutation, IDH1(R132H), is inserted into the endogenous murine Idh1 locus and is expressed in all haematopoietic cells (Vav-KI mice) or specifically in cells of the myeloid lineage (LysM-KI mice). These mutants show increased numbers of early haematopoietic progenitors and develop splenomegaly and anaemia with extramedullary haematopoiesis, suggesting a dysfunctional bone marrow niche. Furthermore, LysM-KI cells have hypermethylated histones and changes to DNA methylation similar to those observed in human IDH1- or IDH2-mutant AML. To our knowledge, our study is the first to describe the generation and characterization of conditional IDH1(R132H)-KI mice, and also the first report to demonstrate the induction of a leukaemic DNA methylation signature in a mouse model. Our report thus sheds light on the mechanistic links between IDH1 mutation and human AML.
C1 [Sasaki, Masato; Knobbe, Christiane B.; Lind, Evan F.; Brenner, Dirk; Bruestle, Anne; Harris, Isaac S.; Wakeham, Andrew; Haight, Jillian; You-Ten, Annick; Li, Wanda Y.; Ohashi, Pamela S.; Mak, Tak W.] Univ Hlth Network, Ontario Canc Inst, Campbell Family Inst Breast Canc Res, Toronto, ON M5G 2C1, Canada.
   [Knobbe, Christiane B.; Reifenberger, Guido] Univ Dusseldorf, Dept Neuropathol, D-40225 Dusseldorf, Germany.
   [Munger, Joshua C.] Univ Rochester, Sch Med & Dent, Rochester, NY 14642 USA.
   [Harris, Isaac S.; Barber, Dwayne L.; Mak, Tak W.] Univ Toronto, Dept Med Biophys, Toronto, ON M5G 2C1, Canada.
   [Holmes, Roxanne; Zuniga-Pfluecker, Juan-Carlos] Univ Toronto, Sunnybrook Res Inst, Dept Immunol, Toronto, ON M4N 3M5, Canada.
   [Virtanen, Carl] Univ Hlth Network, Microarray Ctr, Toronto, ON M5S 1A8, Canada.
   [Figueroa, Maria E.] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA.
   [Melnick, Ari] Cornell Univ, Weill Cornell Med Coll, New York, NY 10021 USA.
   [Schalm, Stefanie; Su, Shinsan M.] Agios Pharmaceut Inc, Cambridge, MA 02139 USA.
C3 University of Toronto; University Health Network Toronto; Heinrich Heine University Dusseldorf; University of Rochester; University of Toronto; University of Toronto; Sunnybrook Research Institute; Sunnybrook Health Science Center; University of Toronto; University Health Network Toronto; University of Michigan System; University of Michigan; Cornell University; Weill Cornell Medicine; Agios Pharmaceuticals
RP Mak, TW (corresponding author), Univ Hlth Network, Ontario Canc Inst, Campbell Family Inst Breast Canc Res, Toronto, ON M5G 2C1, Canada.
EM tmak@uhnres.utoronto.ca
FU Feodor-Lynen Postdoctoral Research Fellowship from the Alexander-von-Humboldt-Foundation, Germany; German Research Foundation (DFG); National Institute of Health [NIH R01AI081773]; Damon Runyon Cancer Research Foundation [DRR-09-10]; Leukemia & Lymphoma Society; Doris Duke Clinical Scientist Development Award; LLS SCOR grant [7132-08]; Burroughs Wellcome Clinical Translational Scientist Award; Starr Cancer Consortium [I4-A442]; Canada Research Chair in Developmental Immunology; Canadian Institutes of Health Research (CIHR); Ontario Ministry of Health and Long Term Care; Terry Fox Foundation
NR 34
TC 438
Z9 530
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 AUG 30
PY 2012
VL 488
IS 7413
BP 656
EP +
DI 10.1038/nature11323
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 996NC
UT WOS:000308095100056
PM 22763442
DA 2026-03-09
ER

PT J
AU Lundberg, DS
   Lebeis, SL
   Paredes, SH
   Yourstone, S
   Gehring, J
   Malfatti, S
   Tremblay, J
   Engelbrektson, A
   Kunin, V
   del Rio, TG
   Edgar, RC
   Eickhorst, T
   Ley, RE
   Hugenholtz, P
   Tringe, SG
   Dangl, JL
AF Lundberg, Derek S.
   Lebeis, Sarah L.
   Paredes, Sur Herrera
   Yourstone, Scott
   Gehring, Jase
   Malfatti, Stephanie
   Tremblay, Julien
   Engelbrektson, Anna
   Kunin, Victor
   del Rio, Tijana Glavina
   Edgar, Robert C.
   Eickhorst, Thilo
   Ley, Ruth E.
   Hugenholtz, Philip
   Tringe, Susannah Green
   Dangl, Jeffery L.
TI Defining the core Arabidopsis thaliana root microbiome
SO NATURE
LA English
DT Article
ID bacterial endophytes; rhizosphere; traits; plants
AB Land plants associate with a root microbiota distinct from the complex microbial community present in surrounding soil. The microbiota colonizing the rhizosphere (immediately surroundingthe root) and the endophytic compartment (within the root) contribute to plant growth, productivity, carbon sequestration and phytoremediation(1-3). Colonization of the root occurs despite a sophisticated plant immune system(4,5), suggesting finely tuned discrimination of mutualists and commensals from pathogens. Genetic principles governing the derivation of host-specific endophyte communities from soil communities are poorly understood. Here we report the pyrosequencing of the bacterial 16S ribosomal RNA gene of more than 600 Arabidopsis thaliana plants to test the hypotheses that the root rhizosphere and endophytic compartmentmicrobiota of plants grown under controlled conditions in natural soils are sufficiently dependent on the host to remain consistent across different soil types and developmental stages, and sufficiently dependent on host genotype to vary between inbred Arabidopsis accessions. We describe different bacterial communities in two geochemically distinct bulk soils and in rhizosphere and endophytic compartments prepared from roots grown in these soils. The communities in each compartment are strongly influenced by soil type. Endophytic compartments fromboth soils feature overlapping, low-complexity communities that are markedly enriched in Actinobacteria and specific families from other phyla, notably Proteobacteria. Some bacteria vary quantitatively between plants of different developmental stage and genotype. Our rigorous definition of an endophytic compartment microbiome should facilitate controlled dissection of plantmicrobe interactions derived from complex soil communities.
C1 [Lundberg, Derek S.; Lebeis, Sarah L.; Paredes, Sur Herrera; Yourstone, Scott; Gehring, Jase; Dangl, Jeffery L.] Univ N Carolina, Dept Biol, Chapel Hill, NC 27599 USA.
   [Lundberg, Derek S.; Dangl, Jeffery L.] Univ N Carolina, Curriculum Genet & Mol Biol, Chapel Hill, NC 27599 USA.
   [Yourstone, Scott] Univ N Carolina, Curriculum Bioinformat & Computat Biol, Chapel Hill, NC 27599 USA.
   [Malfatti, Stephanie; Tremblay, Julien; Engelbrektson, Anna; Kunin, Victor; del Rio, Tijana Glavina; Hugenholtz, Philip; Tringe, Susannah Green] DOE Joint Genome Inst, Walnut Creek, CA 94598 USA.
   [Edgar, Robert C.] Taxon Biosci Inc, Tiburon, CA 94920 USA.
   [Eickhorst, Thilo] Univ Bremen, Fac Biol & Chem, D-28359 Bremen, Germany.
   [Ley, Ruth E.] Cornell Univ, Dept Microbiol, Ithaca, NY 14853 USA.
   [Hugenholtz, Philip] Univ Queensland, Sch Chem & Mol Biosci, Australian Ctr Ecogen, Brisbane, Qld 4072, Australia.
   [Hugenholtz, Philip] Univ Queensland, Inst Mol Biosci, Brisbane, Qld 4072, Australia.
   [Dangl, Jeffery L.] Univ N Carolina, Dept Microbiol & Immunol, Chapel Hill, NC 27599 USA.
   [Dangl, Jeffery L.] Univ N Carolina, Carolina Ctr Genome Sci, Chapel Hill, NC 27599 USA.
   [Dangl, Jeffery L.] Univ N Carolina, Howard Hughes Med Inst, Chapel Hill, NC 27599 USA.
C3 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; United States Department of Energy (DOE); University of Bremen; Cornell University; University of Queensland; University of Queensland; University of North Carolina; University of North Carolina Chapel Hill; University of North Carolina; University of North Carolina Chapel Hill; Howard Hughes Medical Institute; University of North Carolina; University of North Carolina Chapel Hill
RP Dangl, JL (corresponding author), Univ N Carolina, Dept Biol, Chapel Hill, NC 27599 USA.
EM dangl@email.unc.edu
FU US NSF [IOS-0958245]; JGI Director's Discretionary Grand Challenge Program; HHMI-GBMF Plant Science Program; Office of Science of the US Department of Energy [DE-AC02-05CH11231]; National Institutes of Health, Minority Opportunities in Research division of the National Institute of General Medical Sciences [K12GM000678]; National Institute of General Medical Sciences [K12GM000678] Funding Source: NIH RePORTER; Direct For Biological Sciences; Division Of Integrative Organismal Systems [0958184] Funding Source: National Science Foundation; Division Of Integrative Organismal Systems; Direct For Biological Sciences [0958245] Funding Source: National Science Foundation
NR 36
TC 2070
Z9 2487
U1 31
U2 1916
PU NATURE PUBLISHING 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 2
PY 2012
VL 488
IS 7409
BP 86
EP +
DI 10.1038/nature11237
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 981ZE
UT WOS:000307010700038
PM 22859206
DA 2026-03-09
ER

PT J
AU Huang, HS
   Allen, JA
   Mabb, AM
   King, IF
   Miriyala, J
   Taylor-Blake, B
   Sciaky, N
   Dutton, JW
   Lee, HM
   Chen, X
   Jin, J
   Bridges, AS
   Zylka, MJ
   Roth, BL
   Philpot, BD
AF Huang, Hsien-Sung
   Allen, John A.
   Mabb, Angela M.
   King, Ian F.
   Miriyala, Jayalakshmi
   Taylor-Blake, Bonnie
   Sciaky, Noah
   Dutton, J. Walter, Jr.
   Lee, Hyeong-Min
   Chen, Xin
   Jin, Jian
   Bridges, Arlene S.
   Zylka, Mark J.
   Roth, Bryan L.
   Philpot, Benjamin D.
TI Topoisomerase inhibitors unsilence the dormant allele of Ube3a in neurons
SO NATURE
LA English
DT Article
ID angelman syndrome gene; antisense transcript; ubiquitin ligase; i inhibitors; expression; snrpn; camptothecin; ube3a/e6-ap; mutations; deletion
AB Angelman syndrome is a severe neurodevelopmental disorder caused bydeletion ormutation of the maternal allele of the ubiquitin protein ligase E3A (UBE3A)(1-3). In neurons, the paternal allele of UBE3A is intact but epigenetically silenced(4-6), raising the possibility that Angelman syndrome could be treated by activating this silenced allele to restore functional UBE3A protein(7,8). Using an unbiased, high-content screen in primary cortical neurons from mice, we identify twelve topoisomerase I inhibitors and four topoisomerase II inhibitors that unsilence the paternal Ube3a allele. These drugs included topotecan, irinotecan, etoposide and dexrazoxane (ICRF-187). At nanomolar concentrations, topotecan upregulated catalytically active UBE3A in neurons from maternal Ube3a-null mice. Topotecan concomitantly downregulated expression of the Ube3a antisense transcript that overlaps the paternal copy of Ube3a(9-11). These results indicate that topotecan unsilences Ube3a in cis by reducing transcription of an imprinted antisense RNA. When administered in vivo, topotecan unsilenced the paternal Ube3a allele in several regions of the nervous system, including neurons in the hippocampus, neocortex, striatum, cerebellum and spinal cord. Paternal expression of Ube3a remained elevated in a subset of spinal cord neurons for at least 12 weeks after cessation of topotecan treatment, indicating that transient topoisomerase inhibition can have enduring effects on gene expression. Although potential off-target effects remain to be investigated, our findings suggest a therapeutic strategy for reactivating the functional but dormant allele of Ube3a in patients with Angelman syndrome.
C1 [Huang, Hsien-Sung; Mabb, Angela M.; King, Ian F.; Miriyala, Jayalakshmi; Taylor-Blake, Bonnie; Dutton, J. Walter, Jr.; Zylka, Mark J.; Philpot, Benjamin D.] Univ N Carolina, Sch Med, Dept Cell & Mol Physiol, Chapel Hill, NC 27599 USA.
   [Allen, John A.; Sciaky, Noah; Lee, Hyeong-Min; Roth, Bryan L.] Univ N Carolina, Sch Med, Dept Pharmacol, Chapel Hill, NC 27599 USA.
   [Chen, Xin; Jin, Jian] Univ N Carolina, Eshelman Sch Pharm, Ctr Integrat Chem Biol & Drug Discovery, Div Chem Biol & Med Chem, Chapel Hill, NC 27599 USA.
   [Bridges, Arlene S.] Univ N Carolina, Sch Med, Dept Pathol & Lab Med, Chapel Hill, NC 27599 USA.
   [Zylka, Mark J.; Roth, Bryan L.; Philpot, Benjamin D.] Univ N Carolina, Carolina Inst Dev Disabil, Chapel Hill, NC 27599 USA.
   [Zylka, Mark J.; Roth, Bryan L.; Philpot, Benjamin D.] Univ N Carolina, Ctr Neurosci, Chapel Hill, NC 27599 USA.
   [Roth, Bryan L.] Univ N Carolina, Div Chem Biol & Med Chem, Eshelman Sch Pharm, Chapel Hill, NC 27599 USA.
   [Roth, Bryan L.] Univ N Carolina, NIMH, Psychoact Drug Screening Program, Dept Pharmacol,Sch 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 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; 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; University of North Carolina Chapel Hill; University of North Carolina; University of North Carolina Chapel Hill; 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
RP Zylka, MJ (corresponding author), Univ N Carolina, Sch Med, Dept Cell & Mol Physiol, Chapel Hill, NC 27599 USA.
EM zylka@med.unc.edu; bryan_roth@med.unc.edu; bphilpot@med.unc.edu
FU Simons Foundation Autism Research Initiative (SFARI); Angelman Syndrome Foundation; National Institute of Mental Health (NIMH) [R01MH093372]; National Eye Institute [R01EY018323]; NC TraCS [50KR41016, 10KR20910]; National Institute of Neurological Disorders and Stroke (NINDS) [R01NS060725, R01NS067688, 5F32NS067712, 5P30NS045892]; National Institutes of Health (NIH) [HHSN-271-2008-00025-C, T32HD040127-07]; Michael Hooker Distinguished Chair of Pharmacology; National Institute on Drug Abuse (NIDA); Brain and Behavior Research Foundation; University of North Carolina-Carolina Institute for Developmental Disabilities; US Department of Defense [AR093464]; National Institute of Child Health and Human Development (NICHD) [P30HD03110]; Eunice Kennedy Shriver National Institute of Child Health and Human Development [T32HD040127] Funding Source: NIH RePORTER; National Institute of Neurological Disorders and Stroke [P30NS045892] Funding Source: NIH RePORTER
NR 38
TC 301
Z9 377
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 JAN 12
PY 2012
VL 481
IS 7380
BP 185
EP +
DI 10.1038/nature10726
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 874TO
UT WOS:000298981200036
PM 22190039
DA 2026-03-09
ER

PT J
AU Kang, KJ
   Panzano, VC
   Chang, EC
   Ni, LN
   Dainis, AM
   Jenkins, AM
   Regna, K
   Muskavitch, MAT
   Garrity, PA
AF Kang, Kyeongjin
   Panzano, Vincent C.
   Chang, Elaine C.
   Ni, Lina
   Dainis, Alexandra M.
   Jenkins, Adam M.
   Regna, Kimberly
   Muskavitch, Marc A. T.
   Garrity, Paul A.
TI Modulation of TRPA1 thermal sensitivity enables sensory discrimination in Drosophila
SO NATURE
LA English
DT Article
ID ion channels; heat activation; temperature; receptor; thermodynamics; capsaicin; sensation; reveals; trpv1b; taste
AB Discriminating among sensory stimuli is critical for animal survival. This discrimination is particularly essential when evaluating whether a stimulus is noxious or innocuous. From insects to humans, transient receptor potential (TRP) channels are key transducers of thermal, chemical and other sensory cues(1,2). Many TRPs are multimodal receptors that respond to diverse stimuli(1-3), but how animals distinguish sensory inputs activating the same TRP is largely unknown. Here we determine how stimuli activating Drosophila TRPA1 are discriminated. Although Drosophila TRPA1 responds to both noxious chemicals(4) and innocuous warming(5), we find that TRPA1-expressing chemosensory neurons respond to chemicals but not warmth, a specificity conferred by a chemosensory-specific TRPA1 isoform with reduced thermosensitivity compared to the previously described isoform. At the molecular level, this reduction results from a unique region that robustly reduces the channel's thermosensitivity. Cell-type segregation of TRPA1 activity is critical: when the thermosensory isoform is expressed in chemosensors, flies respond to innocuous warming with regurgitation, a nocifensive response. TRPA1 isoform diversity is conserved in malaria mosquitoes, indicating that similar mechanisms may allow discrimination of host-derived warmth-an attractant-from chemical repellents. These findings indicate that reducing thermosensitivity can be critical for TRP channel functional diversification, facilitating their use in contexts in which thermal sensitivity can be maladaptive.
C1 [Kang, Kyeongjin; Panzano, Vincent C.; Chang, Elaine C.; Ni, Lina; Dainis, Alexandra M.; Garrity, Paul A.] Brandeis Univ, Dept Biol, Natl Ctr Behav Genom, Waltham, MA 02454 USA.
   [Kang, Kyeongjin; Panzano, Vincent C.; Chang, Elaine C.; Ni, Lina; Dainis, Alexandra M.; Garrity, Paul A.] Brandeis Univ, Dept Biol, Volen Ctr Complex Syst, Waltham, MA 02454 USA.
   [Jenkins, Adam M.; Regna, Kimberly; Muskavitch, Marc A. T.] Boston Coll, Dept Biol, Newton, MA 02467 USA.
   [Muskavitch, Marc A. T.] Broad Inst, Cambridge, MA 02142 USA.
   [Muskavitch, Marc A. T.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
C3 Brandeis University; Brandeis University; Boston College; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Harvard University; Harvard T.H. Chan School of Public Health
RP Garrity, PA (corresponding author), Brandeis Univ, Dept Biol, Natl Ctr Behav Genom, Waltham, MA 02454 USA.
EM pgarrity@brandeis.edu
FU National Science Foundation [IOS-1025307]; National Institute of Mental Health [EUREKA R01 MH094721]; National Institute of Neurological Disorders and Stroke (NINDS) [PO1 NS044232, F31 NS071897-02]; Boston College; Division Of Integrative Organismal Systems; Direct For Biological Sciences [1025307] Funding Source: National Science Foundation
NR 33
TC 184
Z9 235
U1 5
U2 89
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 5
PY 2012
VL 481
IS 7379
BP 76
EP U82
DI 10.1038/nature10715
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 872VD
UT WOS:000298836900032
PM 22139422
DA 2026-03-09
ER

PT J
AU Campbell, IH
   O'Neill, HSC
AF Campbell, Ian H.
   O'Neill, Hugh St C.
TI Evidence against a chondritic Earth
SO NATURE
LA English
DT Article
ID trace-element systematics; mantle plumes; magma ocean; isotope heterogeneity; early differentiation; collisional erosion; superior province; greenstone-belt; solar-system; lu-hf
AB The Nd-142/Nd-144 ratio of the Earth is greater than the solar ratio as inferred from chondritic meteorites, which challenges a fundamental assumption of modern geochemistry-that the composition of the silicate Earth is 'chondritic', meaning that it has refractory element ratios identical to those found in chondrites. The popular explanation for this and other paradoxes of mantle geochemistry, a hidden layer deep in the mantle enriched in incompatible elements, is inconsistent with the heat flux carried by mantle plumes. Either the matter from which the Earth formed was not chondritic, or the Earth has lost matter by collisional erosion in the later stages of planet formation.
C1 [Campbell, Ian H.; O'Neill, Hugh St C.] Australian Natl Univ, Res Sch Earth Sci, Canberra, ACT 0200, Australia.
C3 Australian National University
RP Campbell, IH (corresponding author), Australian Natl Univ, Res Sch Earth Sci, GPO Box 4, Canberra, ACT 0200, Australia.
EM Ian.Campbell@anu.edu.au
NR 66
TC 102
Z9 117
U1 0
U2 78
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 29
PY 2012
VL 483
IS 7391
BP 553
EP 558
DI 10.1038/nature10901
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 915EF
UT WOS:000302006100030
PM 22460899
DA 2026-03-09
ER

PT J
AU Geu-Flores, F
   Sherden, NH
   Courdavault, V
   Burlat, V
   Glenn, WS
   Wu, C
   Nims, E
   Cui, YH
   O'Connor, SE
AF Geu-Flores, Fernando
   Sherden, Nathaniel H.
   Courdavault, Vincent
   Burlat, Vincent
   Glenn, Weslee S.
   Wu, Cen
   Nims, Ezekiel
   Cui, Yuehua
   O'Connor, Sarah E.
TI An alternative route to cyclic terpenes by reductive cyclization in iridoid biosynthesis
SO NATURE
LA English
DT Article
ID iridane skeleton formation; progesterone 5-beta-reductase; catharanthus-roseus; alkaloid biosynthesis; metabolism; mechanism; genes; secoiridoids; vindoline; p5-beta-r
AB The iridoids comprise a large family of distinctive bicyclic monoterpenes that possess a wide range of pharmacological activities, including anticancer, anti-inflammatory, antifungal and antibacterial activities(1-4). Additionally, certain iridoids are used as sex pheromones in agriculturally important species of aphids, a fact that has underpinned innovative and integrated pest management strategies(5). To harness the biotechnological potential of this natural product class, the enzymes involved in the biosynthetic pathway must be elucidated. Here we report the discovery of iridoid synthase, a plant-derived enzyme that generates the iridoid ring scaffold, as evidenced by biochemical assays, gene silencing, co-expression analysis and localization studies. In contrast to all known monoterpene cyclases, which use geranyl diphosphate as substrate and invoke a cationic intermediate, iridoid synthase uses the linear monoterpene 10-oxogeranial as substrate and probably couples an initial NAD(P) H-dependent reduction step with a subsequent cyclization step via a Diels-Alder cycloaddition or a Michael addition. Our results illustrate how a short-chain reductase was recruited as cyclase for the production of iridoids in medicinal plants. Furthermore, we highlight the prospects of using unrelated reductases to generate artificial cyclic scaffolds. Beyond the recognition of an alternative biochemical mechanism for the biosynthesis of cyclic terpenes, we anticipate that our work will enable the large-scale heterologous production of iridoids in plants and microorganisms for agricultural(5-8) and pharmaceutical(1-4,9) applications.
C1 [Geu-Flores, Fernando; Sherden, Nathaniel H.; Glenn, Weslee S.; O'Connor, Sarah E.] John Innes Ctr Plant Sci Res, Dept Biol Chem, Norwich NR4 7UH, Norfolk, England.
   [Courdavault, Vincent] Univ Tours, Biomol & Biotechnol Vegetales EA2106, F-37200 Tours, France.
   [Burlat, Vincent] Univ Toulouse, UPS, UMR 5546, Lab Rech Sci Vegetales, F-31326 Castanet Tolosan, France.
   [Burlat, Vincent] CNRS, UMR 5546, F-31326 Castanet Tolosan, France.
   [Glenn, Weslee S.; Nims, Ezekiel] MIT, Dept Chem, Cambridge, MA 02139 USA.
   [Wu, Cen; Cui, Yuehua] Michigan State Univ, Dept Stat & Probabil, E Lansing, MI 48824 USA.
   [O'Connor, Sarah E.] Univ E Anglia, Sch Chem, Norwich NR4 7TJ, Norfolk, England.
C3 UK Research & Innovation (UKRI); Biotechnology and Biological Sciences Research Council (BBSRC); John Innes Centre; Universite de Tours; Universite de Toulouse; Universite Toulouse III - Paul Sabatier; 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 Toulouse; Universite Toulouse III - Paul Sabatier; Massachusetts Institute of Technology (MIT); Michigan State University; University of East Anglia
RP O'Connor, SE (corresponding author), John Innes Ctr Plant Sci Res, Dept Biol Chem, Norwich NR4 7UH, Norfolk, England.
EM sarah.o'connor@jic.ac.uk
FU Danish Council for Independent Research (Natural Sciences) [10-082858]; NIH [GM074820]; John Innes Foundation; National Science Foundation; NSF [DMS-1209112]; John Innes Centre; University of East Anglia;  [j004561SRC (BB/J004561/1)];  [BB/J009091/1]; Biotechnology and Biological Sciences Research Council [BB/J009091/1] Funding Source: researchfish; Direct For Mathematical & Physical Scien; Division Of Mathematical Sciences [1209112] Funding Source: National Science Foundation; BBSRC [BB/J009091/1] Funding Source: UKRI
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   Chen F, 2011, PLANT J, V66, P212, DOI 10.1111/j.1365-313X.2011.04520.x
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NR 33
TC 272
Z9 323
U1 4
U2 336
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 6
PY 2012
VL 492
IS 7427
BP 138
EP +
DI 10.1038/nature11692
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 048EQ
UT WOS:000311893400061
PM 23172143
DA 2026-03-09
ER

PT J
AU Illing, PT
   Vivian, JP
   Dudek, NL
   Kostenko, L
   Chen, ZJ
   Bharadwaj, M
   Miles, JJ
   Kjer-Nielsen, L
   Gras, S
   Williamson, NA
   Burrows, SR
   Purcell, AW
   Rossjohn, J
   McCluskey, J
AF Illing, Patricia T.
   Vivian, Julian P.
   Dudek, Nadine L.
   Kostenko, Lyudmila
   Chen, Zhenjun
   Bharadwaj, Mandvi
   Miles, John J.
   Kjer-Nielsen, Lars
   Gras, Stephanie
   Williamson, Nicholas A.
   Burrows, Scott R.
   Purcell, Anthony W.
   Rossjohn, Jamie
   McCluskey, James
TI Immune self-reactivity triggered by drug-modified HLA-peptide repertoire
SO NATURE
LA English
DT Article
ID stevens-johnson-syndrome; t-cell allorecognition; genetic-variations; b region; hypersensitivity; abacavir; hla-b-asterisk-5701; association; complexes; antigens
AB Human leukocyte antigens (HLAs) are highly polymorphic proteins that initiate immunity by presenting pathogen-derived peptides to T cells(1). HLA polymorphisms mostly map to the antigen-binding cleft, thereby diversifying the repertoire of self-derived and pathogen-derived peptide antigens selected by different HLA allotypes(2). A growing number of immunologically based drug reactions, including abacavir hypersensitivity syndrome (AHS) and carbamazepine-induced Stevens-Johnson syndrome (SJS), are associated with specific HLA alleles(3-7). However, little is known about the underlying mechanisms of these associations, including AHS, a prototypical HLA-associated drug reaction occurring exclusively in individuals with the common histocompatibility allele HLA-B*57:01, and with a relative risk of more than 1,000 (refs 6, 7). We show that unmodified abacavir binds non-covalently to HLA-B*57:01, lying across the bottom of the antigen-binding cleft and reaching into the F-pocket, where a carboxy-terminal tryptophan typically anchors peptides bound to HLA-B*57:01. Abacavir binds with exquisite specificity to HLA-B*57:01, changing the shape and chemistry of the antigen-binding cleft, thereby altering the repertoire of endogenous peptides that can bind HLA-B*57:01. In this way, abacavir guides the selection of new endogenous peptides, inducing a marked alteration in 'immunological self'. The resultant peptide-centric 'altered self' activates abacavir-specific T-cells, thereby driving polyclonal CD8 T-cell activation and a systemic reaction manifesting as AHS. We also show that carbamazepine, a widely used anti-epileptic drug associated with hypersensitivity reactions in HLA-B*15:02 individuals, binds to this allotype, producing alterations in the repertoire of presented self peptides. Our findings simultaneously highlight the importance of HLA polymorphism in the evolution of pharmacogenomics and provide a general mechanism for some of the growing number of HLA-linked hypersensitivities that involve small-molecule drugs.
C1 [Illing, Patricia T.; Kostenko, Lyudmila; Chen, Zhenjun; Bharadwaj, Mandvi; Kjer-Nielsen, Lars; McCluskey, James] Univ Melbourne, Dept Microbiol & Immunol, Parkville, Vic 3010, Australia.
   [Illing, Patricia T.; Dudek, Nadine L.; Williamson, Nicholas A.; Purcell, Anthony W.] Univ Melbourne, Dept Biochem & Mol Biol, Parkville, Vic 3010, Australia.
   [Illing, Patricia T.; Dudek, Nadine L.; Williamson, Nicholas A.; Purcell, Anthony W.] Univ Melbourne, Mol Sci & Biotechnol Inst Bio21, Parkville, Vic 3010, Australia.
   [Vivian, Julian P.; Gras, Stephanie; Rossjohn, Jamie] Monash Univ, Sch Biomed Sci, Dept Biochem & Mol Biol, Clayton, Vic 3800, Australia.
   [Miles, John J.; Burrows, Scott R.] Queensland Inst Med Res, Brisbane, Qld 4029, Australia.
   [Miles, John J.; Burrows, Scott R.] Australian Ctr Vaccine Dev, Brisbane, Qld 4029, Australia.
   [Miles, John J.; Rossjohn, Jamie] Cardiff Univ, Sch Med, Inst Infect & Immun, Cardiff CF14 4XN, S Glam, Wales.
   [McCluskey, James] Australian Red Cross Blood Serv, Victorian Transplantat & Immunogenet Serv, W Melbourne, Vic 3003, Australia.
C3 University of Melbourne; University of Melbourne; University of Melbourne; Monash University; QIMR Berghofer Medical Research Institute; Cardiff University; Australian Red Cross Blood Service
RP McCluskey, J (corresponding author), Univ Melbourne, Dept Microbiol & Immunol, Parkville, Vic 3010, Australia.
EM apurcell@unimelb.edu.au; jamie.rossjohn@monash.edu; jamesm1@unimelb.edu.au
FU National Health and Medical Research Council of Australia (NHMRC); Australian Research Council (ARC); Monash University; NHMRC
NR 27
TC 557
Z9 641
U1 0
U2 126
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUN 28
PY 2012
VL 486
IS 7404
BP 554
EP U158
DI 10.1038/nature11147
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 965IJ
UT WOS:000305760600048
PM 22722860
DA 2026-03-09
ER

PT J
AU Sapart, CJ
   Monteil, G
   Prokopiou, M
   van de Wal, RSW
   Kaplan, JO
   Sperlich, P
   Krumhardt, KM
   van der Veen, C
   Houweling, S
   Krol, MC
   Blunier, T
   Sowers, T
   Martinerie, P
   Witrant, E
   Dahl-Jensen, D
   Röckmann, T
AF Sapart, C. J.
   Monteil, G.
   Prokopiou, M.
   van de Wal, R. S. W.
   Kaplan, J. O.
   Sperlich, P.
   Krumhardt, K. M.
   van der Veen, C.
   Houweling, S.
   Krol, M. C.
   Blunier, T.
   Sowers, T.
   Martinerie, P.
   Witrant, E.
   Dahl-Jensen, D.
   Rockmann, T.
TI Natural and anthropogenic variations in methane sources during the past two millennia
SO NATURE
LA English
DT Article
ID northern-hemisphere; holocene; climate; pollution; greenland; records; ice
AB Methane is an important greenhouse gas that is emitted from multiple natural and anthropogenic sources. Atmospheric methane concentrations have varied on a number of time scales in the past, but what has caused these variations is not always well understood(1-8). The different sources and sinks of methane have specific isotopic signatures, and the isotopic composition of methane can therefore help to identify the environmental drivers of variations in atmospheric methane concentrations(9). Here we present high-resolution carbon isotope data (delta C-13 content) for methane from two ice cores from Greenland for the past two millennia. We find that the delta C-13 content underwent pronounced centennial-scale variations between 100 BC and AD 1600. With the help of two-box model calculations, we show that the centennial-scale variations in isotope ratios can be attributed to changes in pyrogenic and biogenic sources. We find correlations between these source changes and both natural climate variability-such as the Medieval Climate Anomaly and the Little Ice Age-and changes in human population and land use, such as the decline of the Roman empire and the Han dynasty, and the population expansion during the medieval period.
C1 [Sapart, C. J.; Monteil, G.; Prokopiou, M.; van de Wal, R. S. W.; van der Veen, C.; Houweling, S.; Krol, M. C.; Rockmann, T.] Univ Utrecht, Inst Marine & Atmospher Res Utrecht, NL-3584 CC Utrecht, Netherlands.
   [Kaplan, J. O.; Krumhardt, K. M.] Ecole Polytech Fed Lausanne, ARVE Grp, Stn 2, CH-1015 Lausanne, Switzerland.
   [Sperlich, P.; Blunier, T.; Dahl-Jensen, D.] Univ Copenhagen, Niels Bohr Inst, Ctr Ice & Climate, DK-2100 Copenhagen, Denmark.
   [Houweling, S.] SRON Netherlands Inst Space Res, NL-3584 CA Utrecht, Netherlands.
   [Sowers, T.] Penn State Univ, Earth & Environm Syst Inst, University Pk, PA 16802 USA.
   [Martinerie, P.] UJF Grenoble 1, CNRS, UMR 5183, LGGE, F-38041 Grenoble, France.
   [Witrant, E.] UJF Grenoble 1, CNRS, UMR 5216, Grenoble Image Parole Signal Automat GIPSA Lab, F-38402 St Martin Dheres, France.
C3 Utrecht University; Swiss Federal Institutes of Technology Domain; Ecole Polytechnique Federale de Lausanne; University of Copenhagen; Niels Bohr Institute; Pennsylvania Commonwealth System of Higher Education (PCSHE); Pennsylvania State University; Pennsylvania State University - University Park; Communaute Universite Grenoble Alpes; Universite Grenoble Alpes (UGA); Centre National de la Recherche Scientifique (CNRS); Centre National de la Recherche Scientifique (CNRS); CNRS - Institute for Information Sciences & Technologies (INS2I); Communaute Universite Grenoble Alpes; Institut National Polytechnique de Grenoble; Universite Grenoble Alpes (UGA)
RP Sapart, CJ (corresponding author), Univ Utrecht, Inst Marine & Atmospher Res Utrecht, Princetonpl 5, NL-3584 CC Utrecht, Netherlands.
EM c.j.sapart@uu.nl
FU Dutch Science Foundation (NOW) [851.30.020, 865.07.001]; Belgium (FNRS-CFB); Belgium (FWO); Canada (NRCan/GSC); China (CAS); Denmark (FIST); France (IPEV); France (CNRS/INSU); France (CEA); France (ANR); Germany (AWI); Iceland (RannIs); Japan (NIPR); Korea (KOPRI); The Netherlands (NWO/ALW); Sweden (VR); Switzerland (SNF); UK (NERC); USA (US NSF, Office of Polar Programs) [ARC0806407]; Swiss National Science Foundation [PP0022_119049]; FIRB project CASTANEA [RBID08LNFJ]; Directorate For Geosciences; Division Of Polar Programs [0944191] Funding Source: National Science Foundation; Office of Polar Programs (OPP); Directorate For Geosciences [0806407] Funding Source: National Science Foundation
NR 30
TC 99
Z9 117
U1 2
U2 212
PU NATURE PUBLISHING 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 4
PY 2012
VL 490
IS 7418
BP 85
EP 88
DI 10.1038/nature11461
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 015LG
UT WOS:000309446800037
PM 23038470
DA 2026-03-09
ER

PT J
AU Crasta, K
   Ganem, NJ
   Dagher, R
   Lantermann, AB
   Ivanova, EV
   Pan, YF
   Nezi, L
   Protopopov, A
   Chowdhury, D
   Pellman, D
AF Crasta, Karen
   Ganem, Neil J.
   Dagher, Regina
   Lantermann, Alexandra B.
   Ivanova, Elena V.
   Pan, Yunfeng
   Nezi, Luigi
   Protopopov, Alexei
   Chowdhury, Dipanjan
   Pellman, David
TI DNA breaks and chromosome pulverization from errors in mitosis
SO NATURE
LA English
DT Article
ID kinetochore-microtubule attachment; tumor-suppressor; nuclear-pore; cancer-cells; replication; instability; aneuploidy; damage; tumorigenesis; complex
AB The involvement of whole-chromosome aneuploidy in tumorigenesis is the subject of debate, in large part because of the lack of insight into underlying mechanisms. Here we identify a mechanism by which errors in mitotic chromosome segregation generate DNA breaks via the formation of structures called micronuclei. Whole-chromosome-containing micronuclei form when mitotic errors produce lagging chromosomes. We tracked the fate of newly generated micronuclei and found that they undergo defective and asynchronous DNA replication, resulting in DNA damage and often extensive fragmentation of the chromosome in the micronucleus. Micronuclei can persist in cells over several generations but the chromosome in the micronucleus can also be distributed to daughter nuclei. Thus, chromosome segregation errors potentially lead to mutations and chromosome rearrangements that can integrate into the genome. Pulverization of chromosomes in micronuclei may also be one explanation for 'chromothripsis' in cancer and developmental disorders, where isolated chromosomes or chromosome arms undergo massive local DNA breakage and rearrangement.
C1 [Crasta, Karen; Ganem, Neil J.; Dagher, Regina; Lantermann, Alexandra B.; Nezi, Luigi; Pellman, David] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
   [Crasta, Karen; Ganem, Neil J.; Dagher, Regina; Pellman, David] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA.
   [Crasta, Karen; Ganem, Neil J.; Dagher, Regina; Pellman, David] Howard Hughes Med Inst, Boston, MA 02115 USA.
   [Ivanova, Elena V.; Protopopov, Alexei] Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, Boston, MA 02115 USA.
   [Pan, Yunfeng; Chowdhury, Dipanjan] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA.
C3 Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard Medical School; Howard Hughes Medical Institute; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute
RP Pellman, D (corresponding author), Dana Farber Canc Inst, Dept Pediat Oncol, 450 Brookline Ave, Boston, MA 02115 USA.
EM david_pellman@dfci.harvard.edu
FU Howard Hughes Medical Institute; NIH [GM083299, 1R01CA142698-01]
NR 50
TC 966
Z9 1137
U1 5
U2 124
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD FEB 2
PY 2012
VL 482
IS 7383
BP 53
EP U70
DI 10.1038/nature10802
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 884RN
UT WOS:000299726000033
PM 22258507
DA 2026-03-09
ER

PT J
AU Sundd, P
   Gutierrez, E
   Koltsova, EK
   Kuwano, Y
   Fukuda, S
   Pospieszalska, MK
   Groisman, A
   Ley, K
AF Sundd, Prithu
   Gutierrez, Edgar
   Koltsova, Ekaterina K.
   Kuwano, Yoshihiro
   Fukuda, Satoru
   Pospieszalska, Maria K.
   Groisman, Alex
   Ley, Klaus
TI 'Slings' enable neutrophil rolling at high shear
SO NATURE
LA English
DT Article
ID selectin glycoprotein ligand-1; intercellular-adhesion molecule-1; slow viscous motion; p-selectin; in-vivo; physiological flow; sphere parallel; plane wall; mice; tethers
AB Most leukocytes can roll along the walls of venules at lowshear stress (1 dyn cm(-2)), but neutrophils have the ability to roll at tenfold higher shear stress in microvessels in vivo(1,2). The mechanisms involved in this shear-resistant rolling are known to involve cell flattening(3) and pulling of long membrane tethers at the rear(4-6). Here we show that these long tethers do not retract as postulated(6,7), but instead persist and appear as 'slings' at the front of rolling cells. We demonstrate slings in a model of acute inflammationin vivo and on P-selectin in vitro, where P-selectin-glycoprotein-ligand-1 (PSGL-1) is found in discrete sticky patches whereas LFA-1 is expressed over the entire length on slings. As neutrophils roll forward, slings wrap around the rolling cells and undergo a step-wise peeling from the P-selectin substrate enabled by the failure of PSGL-1 patches under hydrodynamic forces. The 'step-wise peeling of slings' is distinct from the 'pulling of tethers' reported previously(4-6,8). Each sling effectively lays out a cell-autonomous adhesive substrate in front of neutrophils rolling at high shear stress during inflammation.
C1 [Sundd, Prithu; Koltsova, Ekaterina K.; Kuwano, Yoshihiro; Pospieszalska, Maria K.; Ley, Klaus] La Jolla Inst Allergy & Immunol, Div Inflammat Biol, La Jolla, CA 92037 USA.
   [Gutierrez, Edgar; Groisman, Alex] Univ Calif San Diego, Dept Phys, La Jolla, CA 92093 USA.
   [Kuwano, Yoshihiro] Univ Tokyo, Dept Dermatol, Tokyo 1138655, Japan.
   [Fukuda, Satoru] Univ Tokyo, Lab Electron Microscopy, Tokyo 1138655, Japan.
C3 La Jolla Institute for Immunology; University of California System; University of California San Diego; University of Tokyo; University of Tokyo
RP Ley, K (corresponding author), La Jolla Inst Allergy & Immunol, Div Inflammat Biol, La Jolla, CA 92037 USA.
EM klaus@liai.org
FU American Heart Association [11SDG7340005, 10POST4160142-01]; NIH [EB 02185]; Grants-in-Aid for Scientific Research [24791139] Funding Source: KAKEN; American Heart Association (AHA) [10POST4160142, 11SDG7340005] Funding Source: American Heart Association (AHA)
NR 39
TC 152
Z9 182
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 16
PY 2012
VL 488
IS 7411
BP 399
EP +
DI 10.1038/nature11248
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 988OS
UT WOS:000307501000046
PM 22763437
DA 2026-03-09
ER

PT J
AU Granier, S
   Manglik, A
   Kruse, AC
   Kobilka, TS
   Thian, FS
   Weis, WI
   Kobilka, BK
AF Granier, Sebastien
   Manglik, Aashish
   Kruse, Andrew C.
   Kobilka, Tong Sun
   Thian, Foon Sun
   Weis, William I.
   Kobilka, Brian K.
TI Structure of the δ-opioid receptor bound to naltrindole
SO NATURE
LA English
DT Article
ID selectivity; peptide; site; mutagenesis; ligands
AB The opioid receptor family comprises three members, the mu-, delta- and kappa-opioid receptors, which respond to classical opioid alkaloids such as morphine and heroin as well as to endogenous peptide ligands like endorphins. They belong to the G-protein-coupled receptor (GPCR) superfamily, and are excellent therapeutic targets for pain control. The delta-opioid receptor (delta-OR) has a role in analgesia, as well as in other neurological functions that remain poorly understood(1). The structures of the mu-OR and kappa-OR have recently been solved(2,3). Here we report the crystal structure of the mouse d delta-OR, bound to the subtype-selective antagonist naltrindole. Together with the structures of the mu-OR and kappa-OR, the delta-OR structure provides insights into conserved elements of opioid ligand recognition while also revealing structural features associated with ligand-subtype selectivity. The binding pocket of opioid receptors can be divided into two distinct regions. Whereas the lower part of this pocket is highly conserved among opioid receptors, the upper part contains divergent residues that confer subtype selectivity. This provides a structural explanation and validation for the 'message-address' model of opioid receptor pharmacology(4,5), in which distinct 'message' (efficacy) and 'address' (selectivity) determinants are contained within a single ligand. Comparison of the address region of the delta-OR with other GPCRs reveals that this structural organization may be a more general phenomenon, extending to other GPCR families as well.
C1 [Granier, Sebastien; Manglik, Aashish; Kruse, Andrew C.; Kobilka, Tong Sun; Thian, Foon Sun; Weis, William I.; Kobilka, Brian K.] Stanford Univ, Sch Med, Dept Mol & Cellular Physiol, Stanford, CA 94305 USA.
   [Granier, Sebastien] CNRS, UMR 5203, F-34094 Montpellier, France.
   [Granier, Sebastien] INSERM, U661, F-34094 Montpellier, France.
   [Granier, Sebastien] Univ Montpellier I, Inst Genom Fonctionnelle, F-34094 Montpellier, France.
   [Granier, Sebastien] Univ Montpellier 2, Inst Genom Fonctionnelle, F-34094 Montpellier, France.
   [Weis, William I.] Stanford Univ, Sch Med, Dept Biol Struct, Stanford, CA 94305 USA.
C3 Stanford University; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB); Universite de Montpellier; Universite de Montpellier; Institut National de la Sante et de la Recherche Medicale (Inserm); Universite de Montpellier; Institut National de la Sante et de la Recherche Medicale (Inserm); Universite de Montpellier; Institut National de la Sante et de la Recherche Medicale (Inserm); Stanford University
RP Granier, S (corresponding author), Stanford Univ, Sch Med, Dept Mol & Cellular Physiol, Stanford, CA 94305 USA.
EM granier@stanford.edu; kobilka@stanford.edu
FU INSERM; Stanford Medical Scientist Training Program; National Science Foundation; National Institutes of Health [NS028471, DA031418]; Mathers Foundation; National Institute of General Medical Sciences [R01GM083118] Funding Source: NIH RePORTER; National Institute of Neurological Disorders and Stroke [R01NS028471] Funding Source: NIH RePORTER
NR 24
TC 571
Z9 687
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 MAY 17
PY 2012
VL 485
IS 7398
BP 400
EP U171
DI 10.1038/nature11111
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 943CW
UT WOS:000304099100049
PM 22596164
DA 2026-03-09
ER

PT J
AU Narayan, N
   Lee, IH
   Borenstein, R
   Sun, JH
   Wong, R
   Tong, G
   Fergusson, MM
   Liu, J
   Rovira, II
   Cheng, HL
   Wang, GH
   Gucek, M
   Lombard, D
   Alt, FW
   Sack, MN
   Murphy, E
   Cao, L
   Finkel, T
AF Narayan, Nisha
   Lee, In Hye
   Borenstein, Ronen
   Sun, Junhui
   Wong, Renee
   Tong, Guang
   Fergusson, Maria M.
   Liu, Jie
   Rovira, Ilsa I.
   Cheng, Hwei-Ling
   Wang, Guanghui
   Gucek, Marjan
   Lombard, David
   Alt, Fredrick W.
   Sack, Michael N.
   Murphy, Elizabeth
   Cao, Liu
   Finkel, Toren
TI RETRACTED: The NAD-dependent deacetylase SIRT2 is required for programmed necrosis (Retracted article. See vol. 506, pg. 516, 2014)
SO NATURE
LA English
DT Article; Retracted Publication
ID induced cell-death; apoptosis; rip1; phosphorylation; identification; necroptosis; mechanisms; regulator; autophagy; kinase
AB Although initially viewed as unregulated, increasing evidence suggests that cellular necrosis often proceeds through a specific molecular program. In particular, death ligands such as tumour necrosis factor (TNF)-alpha activate necrosis by stimulating the formation of a complex containing receptor-interacting protein 1 (RIP1) and receptor-interacting protein 3 (RIP3). Relatively little is known regarding how this complex formation is regulated. Here, we show that the NAD-dependent deacetylase SIRT2 binds constitutively to RIP3 and that deletion or knockdown of SIRT2 prevents formation of the RIP1-RIP3 complex in mice. Furthermore, genetic or pharmacological inhibition of SIRT2 blocks cellular necrosis induced by TNF-alpha. We further demonstrate that RIP1 is a critical target of SIRT2-dependent deacetylation. Using gain- and loss-of-function mutants, we demonstrate that acetylation of RIP1 lysine 530 modulates RIP1-RIP3 complex formation and TNF-alpha-stimulated necrosis. In the setting of ischaemia-reperfusion injury, RIP1 is deacetylated in a SIRT2-dependent fashion. Furthermore, the hearts of Sirt2(-/-) mice, or wild-type mice treated with a specific pharmacological inhibitor of SIRT2, show marked protection from ischaemic injury. Taken together, these results implicate SIRT2 as an important regulator of programmed necrosis and indicate that inhibitors of this deacetylase may constitute a novel approach to protect against necrotic injuries, including ischaemic stroke and myocardial infarction.
C1 [Narayan, Nisha; Lee, In Hye; Borenstein, Ronen; Fergusson, Maria M.; Liu, Jie; Rovira, Ilsa I.; Sack, Michael N.; Finkel, Toren] NHLBI, Ctr Mol Med, NIH, Bethesda, MD 20892 USA.
   [Sun, Junhui; Wong, Renee; Tong, Guang; Murphy, Elizabeth] NHLBI, Syst Biol Ctr, NIH, Bethesda, MD 20892 USA.
   [Tong, Guang] Fourth Mil Med Univ, Xijing Hosp, Dept Cardiovasc Surg, Xian 710032, Peoples R China.
   [Cheng, Hwei-Ling; Alt, Fredrick W.] Childrens Hosp, Howard Hughes Med Inst, Program Cellular & Mol Med, Boston, MA 02115 USA.
   [Cheng, Hwei-Ling; Alt, Fredrick W.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
   [Cheng, Hwei-Ling; Alt, Fredrick W.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA.
   [Wang, Guanghui; Gucek, Marjan] NHLBI, Prote Core, NIH, Bethesda, MD 20892 USA.
   [Lombard, David] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA.
   [Lombard, David] Univ Michigan, Inst Gerontol, Ann Arbor, MI 48109 USA.
   [Cao, Liu] China Med Univ, Key Lab Med Cell Biol, Shenyang 110001, Peoples R China.
C3 National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI); National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI); Air Force Medical University; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Program in Cellular & Molecular Medicine (PCMM); Howard Hughes Medical Institute; Harvard University; Harvard Medical School; Harvard University; Harvard Medical School; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI); University of Michigan System; University of Michigan; University of Michigan System; University of Michigan; China Medical University
RP Finkel, T (corresponding author), NHLBI, Ctr Mol Med, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM finkelt@nih.gov
FU NIH; National Heart Lung and Blood Institute [ZIGHL006020, ZIAHL002066, ZIAHL005102] Funding Source: NIH RePORTER
NR 32
TC 117
Z9 134
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 DEC 13
PY 2012
VL 492
IS 7428
BP 199
EP +
DI 10.1038/nature11700
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 053GM
UT WOS:000312259300031
PM 23201684
DA 2026-03-09
ER

PT J
AU Fu, ZQ
   Yan, SP
   Saleh, A
   Wang, W
   Ruble, J
   Oka, N
   Mohan, R
   Spoel, SH
   Tada, Y
   Zheng, N
   Dong, XN
AF Fu, Zheng Qing
   Yan, Shunping
   Saleh, Abdelaty
   Wang, Wei
   Ruble, James
   Oka, Nodoka
   Mohan, Rajinikanth
   Spoel, Steven H.
   Tada, Yasuomi
   Zheng, Ning
   Dong, Xinnian
TI NPR3 and NPR4 are receptors for the immune signal salicylic acid in plants
SO NATURE
LA English
DT Article
ID systemic acquired-resistance; cell-death; pseudomonas-syringae; defense genes; arabidopsis; tobacco; induction; perception; interacts; reveals
AB Salicylic acid (SA) is a plant immune signal produced after pathogen challenge to induce systemic acquired resistance. It is the only major plant hormone for which the receptor has not been firmly identified. Systemic acquired resistance in Arabidopsis requires the transcription cofactor nonexpresser of PR genes 1 (NPR1), the degradation of which acts as a molecular switch. Here we show that the NPR1 paralogues NPR3 and NPR4 are SA receptors that bind SA with different affinities. NPR3 and NPR4 function as adaptors of the Cullin 3 ubiquitin E3 ligase to mediate NPR1 degradation in an SA-regulated manner. Accordingly, the Arabidopsis npr3 npr4 double mutant accumulates higher levels of NPR1, and is insensitive to induction of systemic acquired resistance. Moreover, this mutant is defective in pathogen effector-triggered programmed cell death and immunity. Our study reveals the mechanism of SA perception in determining cell death and survival in response to pathogen challenge.
C1 [Fu, Zheng Qing; Yan, Shunping; Saleh, Abdelaty; Wang, Wei; Mohan, Rajinikanth; Dong, Xinnian] Duke Univ, Howard Hughes Med Inst, Gordon & Betty Moore Fdn, Dept Biol, Durham, NC 27708 USA.
   [Ruble, James; Zheng, Ning] Univ Washington, Howard Hughes Med Inst, Dept Pharmacol, Seattle, WA 98195 USA.
   [Oka, Nodoka] Kagawa Univ, Fac Agr, Miki, Kagawa 7610795, Japan.
   [Spoel, Steven H.] Univ Edinburgh, Inst Mol Plant Sci, Edinburgh EH9 3JR, Midlothian, Scotland.
   [Tada, Yasuomi] Kagawa Univ, Life Sci Res Ctr, Inst Res Promot, Miki, Kagawa 7610795, Japan.
C3 Howard Hughes Medical Institute; Duke University; University of Washington; University of Washington Seattle; Howard Hughes Medical Institute; Kagawa University; University of Edinburgh; Kagawa University
RP Dong, XN (corresponding author), Duke Univ, Howard Hughes Med Inst, Gordon & Betty Moore Fdn, Dept Biol, POB 90338, Durham, NC 27708 USA.
EM xdong@duke.edu
FU Hargitt Fellowship; Ministry of Education, Culture, Sports, Science and Technology of Japan [23120520]; Royal Society [Uf090321];  [GM069594-05];  [CA107134];  [T32GM008268-23]; Direct For Biological Sciences; Div Of Molecular and Cellular Bioscience [0929100] Funding Source: National Science Foundation; Royal Society [UF090321] Funding Source: Royal Society; National Institute of General Medical Sciences [T32GM008268] Funding Source: NIH RePORTER
NR 30
TC 752
Z9 903
U1 15
U2 474
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 14
PY 2012
VL 486
IS 7402
BP 228
EP +
DI 10.1038/nature11162
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 957UH
UT WOS:000305189000028
PM 22699612
DA 2026-03-09
ER

PT J
AU Tsai, A
   Petrov, A
   Marshall, RA
   Korlach, J
   Uemura, S
   Puglisi, JD
AF Tsai, Albert
   Petrov, Alexey
   Marshall, R. Andrew
   Korlach, Jonas
   Uemura, Sotaro
   Puglisi, Joseph D.
TI Heterogeneous pathways and timing of factor departure during translation initiation
SO NATURE
LA English
DT Article
ID transfer-rna; protein-synthesis; guanosine triphosphate; complex-formation; factor if2; real-time; ribosome; bacteria; guides
AB The initiation of translation establishes the reading frame for protein synthesis and is a key point of regulation(1). Initiation involves factor-driven assembly at a start codon of a messenger RNA of an elongation-competent 70S ribosomal particle (in bacteria) from separated 30S and 50S subunits and initiator transfer RNA. Here we establish in Escherichia coli, using direct single-molecule tracking, the timing of initiator tRNA, initiation factor 2 (IF2; encoded by infB) and 50S subunit joining during initiation. Our results show multiple pathways to initiation, with orders of arrival of tRNA and IF2 dependent on factor concentration and composition. IF2 accelerates 50S subunit joining and stabilizes the assembled 70S complex. Transition to elongation is gated by the departure of IF2 after GTP hydrolysis, allowing efficient arrival of elongator tRNAs to the second codon presented in the aminoacyl-tRNA binding site (A site). These experiments highlight the power of single-molecule approaches to delineate mechanisms in complex multicomponent systems.
C1 [Tsai, Albert; Petrov, Alexey; Marshall, R. Andrew; Uemura, Sotaro; Puglisi, Joseph D.] Stanford Univ, Sch Med, Dept Biol Struct, Stanford, CA 94305 USA.
   [Tsai, Albert] Stanford Univ, Dept Appl Phys, Stanford, CA 94305 USA.
   [Marshall, R. Andrew] McKinsey & Co Silicon Valley, Palo Alto, CA 94304 USA.
   [Korlach, Jonas] Pacific Biosci, Menlo Pk, CA 94025 USA.
   [Uemura, Sotaro] RIKEN Yokohama Inst, Omics Sci Ctr, Tsurumi Ku, Yokohama, Kanagawa 2300045, Japan.
   [Puglisi, Joseph D.] Stanford Univ, Sch Med, Stanford Magnet Resonance Lab, Stanford, CA 94305 USA.
C3 Stanford University; Stanford University; RIKEN; Stanford University
RP Uemura, S (corresponding author), Stanford Univ, Sch Med, Dept Biol Struct, Stanford, CA 94305 USA.
EM s-uemura@gsc.riken.jp; puglisi@stanford.edu
FU National Institutes of Health [GM51266]; Japan Science and Technology Agency; National Institute of General Medical Sciences [R01GM051266] Funding Source: NIH RePORTER
NR 18
TC 71
Z9 92
U1 0
U2 19
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUL 19
PY 2012
VL 487
IS 7407
BP 390
EP 394
DI 10.1038/nature11172
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 975JB
UT WOS:000306506500048
PM 22722848
DA 2026-03-09
ER

PT J
AU Creveling, JR
   Mitrovica, JX
   Chan, NH
   Latychev, K
   Matsuyama, I
AF Creveling, J. R.
   Mitrovica, J. X.
   Chan, N. -H.
   Latychev, K.
   Matsuyama, I.
TI Mechanisms for oscillatory true polar wander
SO NATURE
LA English
DT Article
ID elastic lithospheres; rotational stability; mantle convection; earth; dynamics; superswells; planets; plumes; models; tpw
AB Palaeomagnetic studies(1-5) of Palaeoproterozoic to Cretaceous rocks propose a suite of large and relatively rapid (tens of degrees over 10 to 100 million years) excursions of the rotation pole relative to the surface geography, or true polar wander (TPW). These excursions may be linked in an oscillatory, approximately coaxial succession about the centre of the contemporaneous supercontinent(5-7). Within the framework of a standard rotational theory(8,9), in which a delayed viscous adjustment of the rotational bulge acts to stabilize the rotation axis(10), geodynamic models for oscillatory TPW generally appeal to consecutive, opposite loading phases of comparable magnitude(6,11,12). Here we extend a nonlinear rotational stability theory(10) to incorporate the stabilizing effect of TPW-induced elastic stresses in the lithosphere(13,14). We demonstrate that convectively driven inertia perturbations acting on a nearly prolate, non-hydrostatic Earth(6,7) with an effective elastic lithospheric thickness of about 10 kilometres yield oscillatory TPW paths consistent with palaeomagnetic inferences. This estimate of elastic thickness can be reduced, even to zero, if the rotation axis is stabilized by long-term excess ellipticity in the plane of the TPW. We speculate that these sources of stabilization, acting on TPW driven by a time-varying mantle flow field(11,12,15-18), provide a mechanism for linking the distinct, oscillatory TPW events of the past few billion years.
C1 [Creveling, J. R.; Mitrovica, J. X.; Chan, N. -H.] Harvard Univ, Dept Earth & Planetary Sci, Cambridge, MA 02138 USA.
   [Latychev, K.] Univ Toronto, Dept Phys, Toronto, ON M5S 1A7, Canada.
   [Matsuyama, I.] Univ Arizona, Dept Planetary Sci, Lunar & Planetary Lab, Tucson, AZ 85721 USA.
C3 Harvard University; University of Toronto; University of Arizona
RP Creveling, JR (corresponding author), Harvard Univ, Dept Earth & Planetary Sci, 20 Oxford St, Cambridge, MA 02138 USA.
EM jcrevel@gps.caltech.edu
FU Canadian Institute for Advanced Research; Harvard University
NR 36
TC 60
Z9 71
U1 1
U2 46
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD NOV 8
PY 2012
VL 491
IS 7423
BP 244
EP +
DI 10.1038/nature11571
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 033DP
UT WOS:000310774300042
PM 23135471
DA 2026-03-09
ER

PT J
AU Lin, SM
   Tsai, JY
   Hsiao, CD
   Huang, YT
   Chiu, CL
   Liu, MH
   Tung, JY
   Liu, TH
   Pan, RL
   Sun, YJ
AF Lin, Shih-Ming
   Tsai, Jia-Yin
   Hsiao, Chwan-Deng
   Huang, Yun-Tzu
   Chiu, Chen-Liang
   Liu, Mu-Hsuan
   Tung, Jung-Yu
   Liu, Tseng-Huang
   Pan, Rong-Long
   Sun, Yuh-Ju
TI Crystal structure of a membrane-embedded H+-translocating pyrophosphatase
SO NATURE
LA English
DT Article
ID substrate-binding subunit; inorganic pyrophosphatase; molecular-cloning; purification; residues; organization; inhibition; strategy; sequence; domains
AB H+-translocating pyrophosphatases (H+-PPases) are active proton transporters that establish a proton gradient across the endomembrane by means of pyrophosphate (PPi) hydrolysis(1,2). H+-PPases are found primarily as homodimers in the vacuolar membrane of plants and the plasma membrane of several protozoa and prokaryotes(2,3). The three-dimensional structure and detailed mechanisms underlying the enzymatic and proton translocation reactions of H+-PPases are unclear. Here we report the crystal structure of a Vigna radiata H+-PPase (VrH(+)-PPase) in complex with a non-hydrolysable substrate analogue, imidodiphosphate (IDP), at 2.35 angstrom resolution. Each VrH(+)-PPase subunit consists of an integral membrane domain formed by 16 transmembrane helices. IDP is bound in the cytosolic region of each subunit and trapped by numerous charged residues and five Mg2+ ions. A previously undescribed proton translocation pathway is formed by six core transmembrane helices. Proton pumping can be initialized by PPi hydrolysis, and H+ is then transported into the vacuolar lumen through a pathway consisting of Arg 242, Asp 294, Lys 742 and Glu 301. We propose a working model of the mechanism for the coupling between proton pumping and PPi hydrolysis by H+-PPases.
C1 [Lin, Shih-Ming; Huang, Yun-Tzu; Chiu, Chen-Liang; Liu, Mu-Hsuan; Tung, Jung-Yu; Liu, Tseng-Huang; Pan, Rong-Long; Sun, Yuh-Ju] Natl Tsing Hua Univ, Dept Life Sci, Coll Life Sci, Hsinchu 30013, Taiwan.
   [Lin, Shih-Ming; Huang, Yun-Tzu; Chiu, Chen-Liang; Liu, Mu-Hsuan; Tung, Jung-Yu; Liu, Tseng-Huang; Pan, Rong-Long; Sun, Yuh-Ju] Natl Tsing Hua Univ, Inst Bioinformat & Struct Biol, Coll Life Sci, Hsinchu 30013, Taiwan.
   [Tsai, Jia-Yin; Hsiao, Chwan-Deng] Acad Sinica, Inst Mol Biol, Taipei 11529, Taiwan.
C3 National Tsing Hua University; National Tsing Hua University; Academia Sinica - Taiwan
RP Sun, YJ (corresponding author), Natl Tsing Hua Univ, Dept Life Sci, Coll Life Sci, Hsinchu 30013, Taiwan.
EM rlpan@life.nthu.edu.tw; yjsun@life.nthu.edu.tw
FU National Science Council of Taiwan [NSC 99-2311-B-007-007-MY3, NSC 100-2311-B-007-001-MY3, NSC 100-2627-M-007-012]; National Tsing Hua University, Taiwan [99N82416E1]
NR 43
TC 135
Z9 158
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 19
PY 2012
VL 484
IS 7394
BP 399
EP 403
DI 10.1038/nature10963
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 927YM
UT WOS:000302946500038
PM 22456709
DA 2026-03-09
ER

PT J
AU Toledano, H
   D'Alterio, C
   Czech, B
   Levine, E
   Jones, DL
AF Toledano, Hila
   D'Alterio, Cecilia
   Czech, Benjamin
   Levine, Erel
   Jones, D. Leanne
TI The let-7-Imp axis regulates ageing of the Drosophila testis stem-cell niche
SO NATURE
LA English
DT Article
ID rna-binding protein; messenger-rna; self-renewal; microrna; differentiation; expression; identification; contributes; library; region
AB Adult stem cells support tissue homeostasis and repair throughout the life of an individual. During ageing, numerous intrinsic and extrinsic changes occur that result in altered stem-cell behaviour and reduced tissue maintenance and regeneration. In the Drosophila testis, ageing results in a marked decrease in the self-renewal factor Unpaired (Upd), leading to a concomitant loss of germline stem cells. Here we demonstrate that IGF-II messenger RNA binding protein (Imp) counteracts endogenous small interfering RNAs to stabilize upd (also known as os) RNA. However, similar to upd, Imp expression decreases in the hub cells of older males, which is due to the targeting of Imp by the heterochronic microRNA let-7. In the absence of Imp, upd mRNA therefore becomes unprotected and susceptible to degradation. Understanding the mechanistic basis for ageing-related changes in stem-cell behaviour will lead to the development of strategies to treat age-onset diseases and facilitate stem-cell-based therapies in older individuals.
C1 [Toledano, Hila; D'Alterio, Cecilia; Jones, D. Leanne] Salk Inst Biol Studies, Genet Lab, La Jolla, CA 92037 USA.
   [Czech, Benjamin] Cold Spring Harbor Lab, Howard Hughes Med Inst, Watson Sch Biol Sci, Cold Spring Harbor, NY 11724 USA.
   [Levine, Erel] Harvard Univ, Dept Phys, Cambridge, MA 02138 USA.
   [Levine, Erel] Harvard Univ, FAS Ctr Syst Biol, Cambridge, MA 02138 USA.
C3 Salk Institute; Howard Hughes Medical Institute; Cold Spring Harbor Laboratory; Harvard University; Harvard University
RP Jones, DL (corresponding author), Salk Inst Biol Studies, Genet Lab, La Jolla, CA 92037 USA.
EM ljones@salk.edu
FU G. Harold and Leila Y. Mathers Charitable Foundation; Ellison Medical Foundation; Emerald Foundation; American Federation for Aging Research; National Institutes of Health; Boehringer Ingelheim Fonds; National Science Foundation; Div Of Molecular and Cellular Bioscience; Direct For Biological Sciences [1121057] Funding Source: National Science Foundation
NR 45
TC 137
Z9 179
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 31
PY 2012
VL 485
IS 7400
BP 605
EP +
DI 10.1038/nature11061
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 949WP
UT WOS:000304608000040
PM 22660319
DA 2026-03-09
ER

PT J
AU Payandeh, J
   El-Din, TMG
   Scheuer, T
   Zheng, N
   Catterall, WA
AF Payandeh, Jian
   El-Din, Tamer M. Gamal
   Scheuer, Todd
   Zheng, Ning
   Catterall, William A.
TI Crystal structure of a voltage-gated sodium channel in two potentially inactivated states
SO NATURE
LA English
DT Article
ID amino-acid-residues; c-type inactivation; slow inactivation; na+ channels; molecular determinants; local-anesthetics; protein-structure; block; conductance; refinement
AB In excitable cells, voltage-gated sodium (Na-V) channels activate to initiate action potentials and then undergo fast and slow inactivation processes that terminate their ionic conductance(1,2). Inactivation is a hallmark of Na-V channel function and is critical for control of membrane excitability(3), but the structural basis for this process has remained elusive. Here we report crystallographic snapshots of the wild-type Na(V)Ab channel from Arcobacter butzleri captured in two potentially inactivated states at 3.2 angstrom resolution. Compared to previous structures of Na(V)Ab channels with cysteine mutations in the pore-lining S6 helices (ref. 4), the S6 helices and the intracellular activation gate have undergone significant rearrangements: one pair of S6 helices has collapsed towards the central pore axis and the other S6 pair has moved outward to produce a striking dimer-of-dimers configuration. An increase in global structural asymmetry is observed throughout our wild-type Na(V)Ab models, reshaping the ion selectivity filter at the extracellular end of the pore, the central cavity and its residues that are analogous to the mammalian drug receptor site, and the lateral pore fenestrations. The voltage-sensing domains have also shifted around the perimeter of the pore module in wild-type Na(V)Ab, compared to the mutant channel, and local structural changes identify a conserved interaction network that connects distant molecular determinants involved in Na-V channel gating and inactivation. These potential inactivated-state structures provide new insights into Na-V channel gating and novel avenues to drug development and therapy for a range of debilitating Na-V channelopathies.
C1 [Payandeh, Jian; El-Din, Tamer M. Gamal; Scheuer, Todd; Zheng, Ning; Catterall, William A.] Univ Washington, Dept Pharmacol, Seattle, WA 98195 USA.
   [Zheng, Ning] Univ Washington, Howard Hughes Med Inst, Seattle, WA 98195 USA.
C3 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, Seattle, WA 98195 USA.
EM nzheng@uw.edu; wcatt@uw.edu
FU Canadian Institutes of Health Research; National Institutes of Health [R01 NS15751, U01 NS058039]; Howard Hughes Medical Institute; National Heart Lung and Blood Institute [R01HL112808] Funding Source: NIH RePORTER
NR 46
TC 406
Z9 485
U1 0
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 JUN 7
PY 2012
VL 486
IS 7401
BP 135
EP U166
DI 10.1038/nature11077
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 953GD
UT WOS:000304854000043
PM 22678296
DA 2026-03-09
ER

PT J
AU Pawar, S
   Dell, AI
   Savage, V
AF Pawar, Samraat
   Dell, Anthony I.
   Savage, Van M.
TI Dimensionality of consumer search space drives trophic interaction strengths
SO NATURE
LA English
DT Article
ID body-size relationships; terrestrial food webs; population-density; real differences; dynamics; stability; abundance; marine; phytoplankton; constraints
AB Trophic interactions govern biomass fluxes in ecosystems, and stability in food webs. Knowledge of how trophic interaction strengths are affected by differences among habitats is crucial for understanding variation in ecological systems. Here we show how substantial variation in consumption-rate data, and hence trophic interaction strengths, arises because consumers tend to encounter resources more frequently in three dimensions (3D) (for example, arboreal and pelagic zones) than two dimensions (2D) (for example, terrestrial and benthic zones). By combining new theory with extensive data (376 species, with body masses ranging from 5.24 x 10(-14) kg to 800 kg), we find that consumption rates scale sublinearly with consumer body mass (exponent of approximately 0.85) for 2D interactions, but superlinearly (exponent of approximately 1.06) for 3D interactions. These results contradict the currently widespread assumption of a single exponent (of approximately 0.75) in consumer-resource and food-web research. Further analysis of 2,929 consumer-resource interactions shows that dimensionality of consumer search space is probably a major driver of species coexistence, and the stability and abundance of populations.
C1 [Pawar, Samraat; Dell, Anthony I.; Savage, Van M.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Biomath, Los Angeles, CA 90095 USA.
   [Dell, Anthony I.] James Cook Univ, Sch Marine & Trop Biol, Townsville, Qld 4811, Australia.
   [Savage, Van M.] Univ Calif Los Angeles, Dept Ecol & Evolutionary Biol, Los Angeles, CA 90095 USA.
   [Savage, Van M.] Santa Fe Inst, Santa Fe, NM 87501 USA.
C3 University of California System; University of California Los Angeles; University of California Los Angeles Medical Center; David Geffen School of Medicine at UCLA; James Cook University; University of California System; University of California Los Angeles; The Santa Fe Institute
RP Pawar, S (corresponding author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Biomath, Los Angeles, CA 90095 USA.
EM samraat@ucla.edu
FU University of California, Los Angeles; US National Science Foundation Division of Environmental Biology [1021010]; Direct For Biological Sciences; Division Of Environmental Biology [1021010] Funding Source: National Science Foundation
CR Alexander RM, 2003, WALKING RUNNING HOPP, V0, P0
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   Brose U, 2010, FUNCT ECOL, V24, P28, DOI 10.1111/j.1365-2435.2009.01618.x
   Brown JH, 2004, ECOLOGY, V85, P1771, DOI 10.1890/03-9000
   Cermeño P, 2006, ECOL LETT, V9, P1210, DOI 10.1111/j.1461-0248.2006.00973.x
   Chase JM, 2000, TRENDS ECOL EVOL, V15, P408, DOI 10.1016/S0169-5347(00)01942-X
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NR 40
TC 243
Z9 267
U1 1
U2 118
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 28
PY 2012
VL 486
IS 7404
BP 485
EP 489
DI 10.1038/nature11131
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 965IJ
UT WOS:000305760600033
PM 22722834
DA 2026-03-09
ER

PT J
AU Burke, CJ
   Huetteroth, W
   Owald, D
   Perisse, E
   Krashes, MJ
   Das, G
   Gohl, D
   Silies, M
   Certel, S
   Waddell, S
AF Burke, Christopher J.
   Huetteroth, Wolf
   Owald, David
   Perisse, Emmanuel
   Krashes, Michael J.
   Das, Gaurav
   Gohl, Daryl
   Silies, Marion
   Certel, Sarah
   Waddell, Scott
TI Layered reward signalling through octopamine and dopamine in Drosophila
SO NATURE
LA English
DT Article
ID neurons; expression; gene; receptor; protein; memory; marker; family; light; fly
AB Dopamine is synonymous with reward and motivation in mammals(1,2). However, only recently has dopamine been linked to motivated behaviour and rewarding reinforcement in fruitflies(3,4). Instead, octopamine has historically been considered to be the signal for reward in insects(5-7). Here we show, using temporal control of neural function in Drosophila, that only short-term appetitive memory is reinforced by octopamine. Moreover, octopamine-dependent memory formation requires signalling through dopamine neurons. Part of the octopamine signal requires the alpha-adrenergic-like OAMB receptor in an identified subset of mushroom-body-targeted dopamine neurons. Octopamine triggers an increase in intracellular calcium in these dopamine neurons, and their direct activation can substitute for sugar to form appetitive memory, even in flies lacking octopamine. Analysis of the beta-adrenergic-like OCT beta 2R receptor reveals that octopamine-dependent reinforcement also requires an interaction with dopamine neurons that control appetitive motivation. These data indicate that sweet taste engages a distributed octopamine signal that reinforces memory through discrete subsets of mushroom-body-targeted dopamine neurons. In addition, they reconcile previous findings with octopamine and dopamine and suggest that reinforcement systems in flies are more similar to mammals than previously thought.
C1 [Burke, Christopher J.; Krashes, Michael J.; Waddell, Scott] Univ Massachusetts, Sch Med, Dept Neurobiol, Worcester, MA 01605 USA.
   [Huetteroth, Wolf; Owald, David; Perisse, Emmanuel; Das, Gaurav; Waddell, Scott] Univ Oxford, Ctr Neural Circuits & Behav, Oxford OX1 3SR, England.
   [Gohl, Daryl; Silies, Marion] Stanford Univ, Dept Neurobiol, Stanford, CA 94305 USA.
   [Certel, Sarah] Univ Montana, Div Biol Sci, Missoula, MT 59812 USA.
   [Certel, Sarah] Univ Montana, Ctr Struct & Funct Neurosci, Missoula, MT 59812 USA.
C3 University of Massachusetts System; University of Massachusetts Worcester; University of Oxford; Stanford University; University of Montana System; University of Montana; University of Montana System; University of Montana
RP Waddell, S (corresponding author), Univ Massachusetts, Sch Med, Dept Neurobiol, 364 Plantat St, Worcester, MA 01605 USA.
EM scott.waddell@cncb.ox.ac.uk
FU EMBO Long-Term Fellowship; Sir Henry Wellcome Postdoctoral Fellowship; Ruth L. Kirschstein NRSA Postdoctoral Fellowship [F32EY020040]; Jane Coffin Childs Postdoctoral Fellowship; Wellcome Trust Senior Research Fellowship in the Basic Biomedical Sciences; National Institutes of Health [MH069883, MH081982]; Gatsby Charitable Foundation; Oxford Martin School; Wellcome Trust [090309/Z/09/Z] Funding Source: researchfish
NR 37
TC 418
Z9 481
U1 4
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 20
PY 2012
VL 492
IS 7429
BP 433
EP +
DI 10.1038/nature11614
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 056KQ
UT WOS:000312488200057
PM 23103875
DA 2026-03-09
ER

PT J
AU King, MA
   Bingham, RJ
   Moore, P
   Whitehouse, PL
   Bentley, MJ
   Milne, GA
AF King, Matt A.
   Bingham, Rory J.
   Moore, Phil
   Whitehouse, Pippa L.
   Bentley, Michael J.
   Milne, Glenn A.
TI Lower satellite-gravimetry estimates of Antarctic sea-level contribution
SO NATURE
LA English
DT Article
ID glacial isostatic-adjustment; ice-sheet; grace; retreat; driven; signal; model
AB Recent estimates of Antarctica's present-day rate of ice-mass contribution to changes in sea level range from 31 gigatonnes a year (Gt yr(-1); ref. 1) to 246 Gt yr(-1) (ref. 2), a range that cannot be reconciled within formal errors(3). Time-varying rates of mass loss(2,4-6) contribute to this, but substantial technique-specific systematic errors also exist(3). In particular, estimates of secular ice-mass change derived from Gravity Recovery and Climate Experiment (GRACE) satellite data are dominated by significant uncertainty in the accuracy of models of mass change due to glacial isostatic adjustment(7,8) (GIA). Here we adopt a new model of GIA, developed from geological constraints, which produces GIA rates systematically lower than those of previous models, and an improved fit to independent uplift data(9). After applying the model to 99 months (from August 2002 to December 2010) of GRACE data, we estimate a continent-wide ice-mass change of -69 +/- 18 Gt yr(-1) (+0.19 +/- 0.05 mm yr(-1) sea-level equivalent). This is about a third to a half of the most recently published GRACE estimates(2,5), which cover a similar time period but are based on older GIA models. Plausible GIA model uncertainties, and errors relating to removing longitudinal GRACE artefacts ('destriping'), confine our estimate to the range -126 Gt yr(-1) to -29 Gt yr(-1) (0.08-0.35 mm yr(-1) sea-level equivalent). We resolve 26 independent drainage basins and find that Antarctic mass loss, and its acceleration, is concentrated in basins along the Amundsen Sea coast. Outside this region, we find that West Antarctica is nearly in balance and that East Antarctica is gaining substantial mass.
C1 [King, Matt A.; Bingham, Rory J.; Moore, Phil] Newcastle Univ, Sch Civil Engn & Geosci, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.
   [King, Matt A.] Univ Tasmania, Sch Geog & Environm Studies, Hobart, Tas 7001, Australia.
   [Whitehouse, Pippa L.; Bentley, Michael J.] Univ Durham, Dept Geog, Durham DH1 3LE, England.
   [Milne, Glenn A.] Univ Ottawa, Dept Earth Sci, Ottawa, ON K1N 6N5, Canada.
C3 Newcastle University - UK; University of Tasmania; Durham University; University of Ottawa
RP King, MA (corresponding author), Newcastle Univ, Sch Civil Engn & Geosci, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.
EM m.a.king@newcastle.ac.uk
FU NERC; RCUK Academic Fellowship; COST Action [ES0701]; Natural Sciences and Engineering Research Council of Canada; Canada Research Chairs programme; Natural Environment Research Council [NE/F01466X/1, NE/E007023/1, NE/F014260/1, NE/E004806/1, NE/F01452X/1] Funding Source: researchfish; NERC [NE/F014260/1, NE/F01466X/1, NE/E004806/1, NE/F01452X/1, NE/E007023/1] Funding Source: UKRI
NR 37
TC 157
Z9 181
U1 1
U2 111
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 22
PY 2012
VL 491
IS 7425
BP 586
EP +
DI 10.1038/nature11621
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 040RE
UT WOS:000311339800050
PM 23086145
DA 2026-03-09
ER

PT J
AU Harjunmaa, E
   Kallonen, A
   Voutilainen, M
   Hämäläinen, K
   Mikkola, ML
   Jernvall, J
AF Harjunmaa, Enni
   Kallonen, Aki
   Voutilainen, Maria
   Hamalainen, Keijo
   Mikkola, Marja L.
   Jernvall, Jukka
TI On the difficulty of increasing dental complexity
SO NATURE
LA English
DT Article
ID gene-expression; mammalian teeth; tooth; evolution; inhibition; cyclopamine; dentition; patterns; feedback; activin
AB One of the fascinating aspects of the history of life is the apparent increase in morphological complexity through time(1), a well known example being mammalian cheek tooth evolution(2-4). In contrast, experimental studies of development more readily show a decrease in complexity, again well exemplified by mammalian teeth, in which tooth crown features called cusps are frequently lost in mutant and transgenic mice(5-7). Here we report that mouse tooth complexity can be increased substantially by adjusting multiple signalling pathways simultaneously. We cultured teeth in vitro and adjusted ectodysplasin (EDA), activin A and sonic hedgehog (SHH) pathways, all of which are individually required for normal tooth development. We quantified tooth complexity using the number of cusps and a topographic measure of surface complexity(8). The results show that whereas activation of EDA and activin A signalling, and inhibition of SHH signalling, individually cause subtle to moderate increases in complexity, cusp number is doubled when all three pathways are adjusted in unison. Furthermore, the increase in cusp number does not result from an increase in tooth size, but from an altered primary patterning phase of development. The combination of a lack of complex mutants(5-7), the paucity of natural variants with complex phenotypes(9), and our results of greatly increased dental complexity using multiple pathways, suggests that an increase may be inherently different from a decrease in phenotypic complexity.
C1 [Harjunmaa, Enni; Voutilainen, Maria; Mikkola, Marja L.; Jernvall, Jukka] Univ Helsinki, Dev Biol Program, Inst Biotechnol, FIN-00014 Helsinki, Finland.
   [Kallonen, Aki; Hamalainen, Keijo] Univ Helsinki, Dept Phys, Div Mat Phys, FIN-00014 Helsinki, Finland.
C3 University of Helsinki; University of Helsinki
RP Jernvall, J (corresponding author), Univ Helsinki, Dev Biol Program, Inst Biotechnol, POB 56, FIN-00014 Helsinki, Finland.
EM jernvall@fastmail.fm
FU Academy of Finland; Sigrid Juselius Foundation; Finnish Cultural Foundation; graduate school GSBM
NR 34
TC 96
Z9 109
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 MAR 15
PY 2012
VL 483
IS 7389
BP 324
EP +
DI 10.1038/nature10876
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 908HP
UT WOS:000301481800047
PM 22398444
DA 2026-03-09
ER

PT J
AU Smith, ZD
   Chan, MM
   Mikkelsen, TS
   Gu, HC
   Gnirke, A
   Regev, A
   Meissner, A
AF Smith, Zachary D.
   Chan, Michelle M.
   Mikkelsen, Tarjei S.
   Gu, Hongcang
   Gnirke, Andreas
   Regev, Aviv
   Meissner, Alexander
TI A unique regulatory phase of DNA methylation in the early mammalian embryo
SO NATURE
LA English
DT Article
ID non-cpg methylation; gene-expression; paternal genome; mouse embryo; wide; 5-hydroxymethylcytosine; demethylation; cells; pluripotent; patterns
AB DNA methylation is highly dynamic during mammalian embryogenesis. It is broadly accepted that the paternal genome is actively depleted of 5-methylcytosine at fertilization, followed by passive loss that reaches a minimum at the blastocyst stage. However, this model is based on limited data, and so far no base-resolution maps exist to support and refine it. Here we generate genome-scale DNA methylation maps in mouse gametes and from the zygote through post-implantation. We find that the oocyte already exhibits global hypomethylation, particularly at specific families of long interspersed element 1 and long terminal repeat retroelements, which are disparately methylated between gametes and have lower methylation values in the zygote than in sperm. Surprisingly, the oocyte contributes a unique set of differentially methylated regions (DMRs)-including many CpG island promoters-that are maintained in the early embryo but are lost upon specification and absent from somatic cells. In contrast, sperm-contributed DMRs are largely intergenic and become hypermethylated after the blastocyst stage. Our data provide a genome-scale, base-resolution timeline of DNA methylation in the pre-specified embryo, when this epigenetic modification is most dynamic, before returning to the canonical somatic pattern.
C1 [Smith, Zachary D.; Chan, Michelle M.; Mikkelsen, Tarjei S.; Gu, Hongcang; Gnirke, Andreas; Regev, Aviv; Meissner, Alexander] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.
   [Smith, Zachary D.; Mikkelsen, Tarjei S.; Meissner, Alexander] Harvard Stem Cell Inst, Cambridge, MA 02138 USA.
   [Smith, Zachary D.; Meissner, Alexander] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA.
   [Chan, Michelle M.] MIT, Computat & Syst Biol Program, Cambridge, MA 02139 USA.
   [Regev, Aviv] MIT, Dept Biol, Howard Hughes Med Inst, Cambridge, MA 02139 USA.
C3 Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Harvard University; Harvard University; Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); Howard Hughes Medical Institute
RP Meissner, A (corresponding author), Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.
EM alexander_meissner@harvard.edu
FU NIH [5DP1OD003958, 5RC1AA019317, U01ES017155, P01GM099117]; HHMI; Harvard Stem Cell Institute; Massachusetts Life Science Center; Pew Charitable Trusts; Center for Excellence in Genome Science from the NHGRI [1P50HG006193-01]; Burroughs Wellcome Career Award at the Scientific Interface; National Institute of General Medical Sciences [P01GM099117] Funding Source: NIH RePORTER
NR 55
TC 810
Z9 965
U1 0
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 19
PY 2012
VL 484
IS 7394
BP 339
EP U74
DI 10.1038/nature10960
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 927YM
UT WOS:000302946500025
PM 22456710
DA 2026-03-09
ER

PT J
AU Cheung, TH
   Quach, NL
   Charville, GW
   Liu, L
   Park, L
   Edalati, A
   Yoo, B
   Hoang, P
   Rando, TA
AF Cheung, Tom H.
   Quach, Navaline L.
   Charville, Gregory W.
   Liu, Ling
   Park, Lidia
   Edalati, Abdolhossein
   Yoo, Bryan
   Hoang, Phuong
   Rando, Thomas A.
TI Maintenance of muscle stem-cell quiescence by microRNA-489
SO NATURE
LA English
DT Article
ID satellite cells; skeletal-muscle; self-renewal; in-vivo; progression; mechanism; mammals; dek
AB Among the key properties that distinguish adult mammalian stem cells from their more differentiated progeny is the ability of stem cells to remain in a quiescent state for prolonged periods of time(1,2). However, the molecular pathways for the maintenance of stem-cell quiescence remain elusive. Here we use adult mouse muscle stem cells (satellite cells) as a model system and show that the microRNA (miRNA) pathway is essential for the maintenance of the quiescent state. Satellite cells that lack a functional miRNA pathway spontaneously exit quiescence and enter the cell cycle. We identified quiescence-specific miRNAs in the satellite-cell lineage by microarray analysis. Among these, miRNA-489 (miR-489) is highly expressed in quiescent satellite cells and is quickly downregulated during satellite-cell activation. Further analysis revealed that miR-489 functions as a regulator of satellite-cell quiescence, as it post-transcriptionally suppresses the oncogene Dek, the protein product of which localizes to the more differentiated daughter cell during asymmetric division of satellite cells and promotes the transient proliferative expansion of myogenic progenitors. Our results provide evidence of the miRNA pathway in general, and of a specific miRNA, miR-489, in actively maintaining the quiescent state of an adult stem-cell population.
C1 [Cheung, Tom H.; Quach, Navaline L.; Charville, Gregory W.; Liu, Ling; Park, Lidia; Edalati, Abdolhossein; Yoo, Bryan; Hoang, Phuong; Rando, Thomas A.] Stanford Univ, Sch Med, Paul F Glenn Labs Biol Aging, Stanford, CA 94305 USA.
   [Cheung, Tom H.; Quach, Navaline L.; Charville, Gregory W.; Liu, Ling; Park, Lidia; Edalati, Abdolhossein; Yoo, Bryan; Hoang, Phuong; Rando, Thomas A.] Stanford Univ, Sch Med, Dept Neurol & Neurol Sci, Stanford, CA 94305 USA.
   [Charville, Gregory W.] Stanford Univ, Sch Med, Dept Dev Biol, Stanford, CA 94305 USA.
   [Rando, Thomas A.] Vet Affairs Palo Alto Hlth Care Syst, Neurol Serv, Palo Alto, CA 94304 USA.
   [Rando, Thomas A.] Vet Affairs Palo Alto Hlth Care Syst, Rehabil Res & Dev Ctr Excellence, Palo Alto, CA 94304 USA.
C3 Stanford University; Stanford University; Stanford University; US Department of Veterans Affairs; Veterans Health Administration (VHA); VA Palo Alto Health Care System; US Department of Veterans Affairs; Veterans Health Administration (VHA); VA Palo Alto Health Care System
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; National Institutes of Health (NIH) [P01 AG036695, R01 AG23806, R01 AR062185, DP1 OD000392]; Department of Veterans Affairs; National Institute on Aging [P01AG036695] Funding Source: NIH RePORTER
NR 25
TC 372
Z9 449
U1 0
U2 65
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 23
PY 2012
VL 482
IS 7386
BP 524
EP U247
DI 10.1038/nature10834
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 898VM
UT WOS:000300770500050
PM 22358842
DA 2026-03-09
ER

PT J
AU Tzeng, SR
   Kalodimos, CG
AF Tzeng, Shiou-Ru
   Kalodimos, Charalampos G.
TI Protein activity regulation by conformational entropy
SO NATURE
LA English
DT Article
ID catabolite activator protein; molecular recognition; dynamic activation; escherichia-coli; receptor protein; nmr-spectroscopy; order parameters; ligand-binding; free-energy; relaxation
AB How the interplay between protein structure and internal dynamics regulates protein function is poorly understood. Often, ligand binding, post-translational modifications and mutations modify protein activity in a manner that is not possible to rationalize solely on the basis of structural data(1). It is likely that changes in the internal motions of proteins have a major role in regulating protein activity(2-7), but the nature of their contributions remains elusive, especially in quantitative terms. Here we show that changes in conformational entropy can determine whether protein-ligand interactions will occur, even among protein complexes with identical binding interfaces. We have used NMR spectroscopy to determine the changes in structure and internal dynamics that are elicited by the binding of DNA to several variants of the catabolite activator protein (CAP) that differentially populate the inactive and active DNA-binding domain states. We found that the CAP variants have markedly different affinities for DNA, despite the CAP-DNA-binding interfaces being essentially identical in the various complexes. Combined with thermodynamic data, the results show that conformational entropy changes can inhibit the binding of CAP variants that are structurally poised for optimal DNA binding or can stimulate the binding activity of CAP variants that only transiently populate the DNA-binding-domain active state. Collectively, the data show how changes in fast internal dynamics (conformational entropy) and slow internal dynamics (energetically excited conformational states) can regulate binding activity in a way that cannot be predicted on the basis of the protein's ground-state structure.
C1 [Tzeng, Shiou-Ru; Kalodimos, Charalampos G.] Rutgers State Univ, Dept Chem & Chem Biol, Piscataway, NJ 08854 USA.
C3 Rutgers University System; Rutgers University New Brunswick
RP Kalodimos, CG (corresponding author), Rutgers State Univ, Dept Chem & Chem Biol, Piscataway, NJ 08854 USA.
EM babis@rutgers.edu
FU National Science Foundation (NSF) [MCB1121896]; Direct For Biological Sciences; Div Of Molecular and Cellular Bioscience [1121896] Funding Source: National Science Foundation
NR 30
TC 433
Z9 513
U1 2
U2 293
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD AUG 9
PY 2012
VL 488
IS 7410
BP 236
EP 240
DI 10.1038/nature11271
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 985LE
UT WOS:000307267000039
PM 22801505
DA 2026-03-09
ER

PT J
AU Wang, YC
   Khan, Z
   Kaschube, M
   Wieschaus, EF
AF Wang, Yu-Chiun
   Khan, Zia
   Kaschube, Matthias
   Wieschaus, Eric F.
TI Differential positioning of adherens junctions is associated with initiation of epithelial folding
SO NATURE
LA English
DT Article
ID apical constriction; cell-shape; drosophila; bazooka; polarity; par-1; establishment; localization; algorithm; stardust
AB During tissue morphogenesis, simple epithelial sheets undergo folding to form complex structures. The prevailing model underlying epithelial folding involves cell shape changes driven by myosin-dependent apical constriction(1). Here we describe an alternative mechanism that requires differential positioning of adherens junctions controlled by modulation of epithelial apical-basal polarity. Using live embryo imaging, we show that before the initiation of dorsal transverse folds during Drosophila gastrulation, adherens junctions shift basally in the initiating cells, but maintain their original subapical positioning in the neighbouring cells. Junctional positioning in the dorsal epithelium depends on the polarity proteins Bazooka and Par-1. In particular, the basal shift that occurs in the initiating cells is associated with a progressive decrease in Par-1 levels. We show that uniform reduction of the activity of Bazooka or Par-1 results in uniform apical or lateral positioning of junctions and in each case dorsal fold initiation is abolished. In addition, an increase in the Bazooka/Par-1 ratio causes formation of ectopic dorsal folds. The basal shift of junctions not only alters the apical shape of the initiating cells, but also forces the lateral membrane of the adjacent cells to bend towards the initiating cells, thereby facilitating tissue deformation. Our data thus establish a direct link between modification of epithelial polarity and initiation of epithelial folding.
C1 [Wang, Yu-Chiun; Wieschaus, Eric F.] Princeton Univ, Dept Mol Biol, Princeton, NJ 08544 USA.
   [Wang, Yu-Chiun; Wieschaus, Eric F.] Princeton Univ, Howard Hughes Med Inst, Princeton, NJ 08544 USA.
   [Khan, Zia] Princeton Univ, Dept Comp Sci, Princeton, NJ 08540 USA.
   [Khan, Zia; Kaschube, Matthias] Princeton Univ, Lewis Sigler Inst Integrat Genom, Princeton, NJ 08544 USA.
C3 Princeton University; Princeton University; Howard Hughes Medical Institute; Princeton University; Princeton University
RP Wieschaus, EF (corresponding author), Princeton Univ, Dept Mol Biol, Princeton, NJ 08544 USA.
EM efw@princeton.edu
FU Helen Hay Whitney Foundation; National Institutes of Health/National Institute of General Medical Sciences [GM071508]; National Institute of Child Health and Human Development [5R37HD15587]
NR 30
TC 137
Z9 161
U1 0
U2 40
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 19
PY 2012
VL 484
IS 7394
BP 390
EP 393
DI 10.1038/nature10938
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 927YM
UT WOS:000302946500036
PM 22456706
DA 2026-03-09
ER

PT J
AU Mattison, JA
   Roth, GS
   Beasley, TM
   Tilmont, EM
   Handy, AM
   Herbert, RL
   Longo, DL
   Allison, DB
   Young, JE
   Bryant, M
   Barnard, D
   Ward, WF
   Qi, WB
   Ingram, DK
   de Cabo, R
AF Mattison, Julie A.
   Roth, George S.
   Beasley, T. Mark
   Tilmont, Edward M.
   Handy, April M.
   Herbert, Richard L.
   Longo, Dan L.
   Allison, David B.
   Young, Jennifer E.
   Bryant, Mark
   Barnard, Dennis
   Ward, Walter F.
   Qi, Wenbo
   Ingram, Donald K.
   de Cabo, Rafael
TI Impact of caloric restriction on health and survival in rhesus monkeys from the NIA study
SO NATURE
LA English
DT Article
ID t-cell senescence; dietary restriction; life-span; age; mortality; disease; model; rats; mice; inflammation
AB Calorie restriction (CR), a reduction of 10-40% in intake of a nutritious diet, is often reported as the most robust non-genetic mechanism to extend lifespan and healthspan. CR is frequently used as a tool to understand mechanisms behind ageing and age-associated diseases. In addition to and independently of increasing lifespan, CR has been reported to delay or prevent the occurrence of many chronic diseases in a variety of animals. Beneficial effects of CR on outcomes such as immune function(1,2), motor coordination(3) and resistance to sarcopenia(4) in rhesus monkeys have recently been reported. We report here that a CR regimen implemented in young and older age rhesus monkeys at the National Institute on Aging (NIA) has not improved survival outcomes. Our findings contrast with an ongoing study at the Wisconsin National Primate Research Center (WNPRC), which reported improved survival associated with 30% CR initiated in adult rhesus monkeys (7-14 years)(5) and a preliminary report with a small number of CR monkeys(6). Over the years, both NIA and WNPRC have extensively documented beneficial health effects of CR in these two apparently parallel studies. The implications of the WNPRC findings were important as they extended CR findings beyond the laboratory rodent and to a long-lived primate. Our study suggests a separation between health effects, morbidity andmortality, and similar to what has been shown in rodents(7-9), study design, husbandry and diet composition may strongly affect the life-prolonging effect of CR in a long-lived nonhuman primate.
C1 [Mattison, Julie A.; Tilmont, Edward M.; Handy, April M.; Young, Jennifer E.] NIA, Lab Expt Gerontol, NIH, Anim Ctr, Dickerson, MD 20842 USA.
   [Roth, George S.] GeroScience, Pylesville, MD 21132 USA.
   [Beasley, T. Mark] Univ Alabama Birmingham, Dept Biostat, Birmingham, AL 35294 USA.
   [Handy, April M.] SoBran Inc, Burtonsville, MD 20866 USA.
   [Herbert, Richard L.] NIAID, NIH, Anim Ctr, Dickerson, MD 20842 USA.
   [Longo, Dan L.] NIA, Lab Mol Biol & Immunol, NIH, Baltimore, MD 21224 USA.
   [Allison, David B.] Univ Alabama Birmingham, Off Energet, Birmingham, AL 35294 USA.
   [Bryant, Mark; Barnard, Dennis] NIH, Off Director, Diagnost & Res Serv Branch, Bethesda, MD 20814 USA.
   [Ward, Walter F.] Univ Texas Hlth Sci Ctr San Antonio, Dept Physiol, Barshop Inst Longev & Aging Studies, San Antonio, TX 78229 USA.
   [Qi, Wenbo] Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA.
   [Ingram, Donald K.] Louisiana State Univ, Pennington Biomed Res Ctr, Nutr Neurosci & Aging Lab, Baton Rouge, LA 70808 USA.
   [de Cabo, Rafael] NIA, Lab Expt Gerontol, NIH, Baltimore, MD 21224 USA.
C3 National Institutes of Health (NIH) - USA; NIH National Institute on Aging (NIA); University of Alabama System; University of Alabama Birmingham; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID); National Institutes of Health (NIH) - USA; NIH National Institute on Aging (NIA); University of Alabama System; University of Alabama Birmingham; National Institutes of Health (NIH) - USA; NIH Office of the Director; University of Texas System; University of Texas at San Antonio; University of Texas System; University of Texas at San Antonio; Louisiana State University System; Louisiana State University; Pennington Biomedical Research Center; National Institutes of Health (NIH) - USA; NIH National Institute on Aging (NIA)
RP Mattison, JA (corresponding author), NIA, Lab Expt Gerontol, NIH, Anim Ctr, 16701 Elmer Sch Rd,Bldg 103, Dickerson, MD 20842 USA.
EM mattisonj@mail.nih.gov; Donald.Ingram@pbrc.edu; deCaboRa@grc.nia.nih.gov
FU NIH, National Institute on Aging; National Institute of Allergy and Infectious Diseases [ZIGAI001047] Funding Source: NIH RePORTER; National Institute of Diabetes and Digestive and Kidney Diseases [P30DK056336] Funding Source: NIH RePORTER; National Institute on Aging [ZIAAG000368, ZIAAG000371] Funding Source: NIH RePORTER
NR 30
TC 823
Z9 996
U1 1
U2 254
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 13
PY 2012
VL 489
IS 7415
BP 318
EP +
DI 10.1038/nature11432
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 003UC
UT WOS:000308635900047
PM 22932268
DA 2026-03-09
ER

PT J
AU Manglik, A
   Kruse, AC
   Kobilka, TS
   Thian, FS
   Mathiesen, JM
   Sunahara, RK
   Pardo, L
   Weis, WI
   Kobilka, BK
   Granier, S
AF Manglik, Aashish
   Kruse, Andrew C.
   Kobilka, Tong Sun
   Thian, Foon Sun
   Mathiesen, Jesper M.
   Sunahara, Roger K.
   Pardo, Leonardo
   Weis, William I.
   Kobilka, Brian K.
   Granier, Sebastien
TI Crystal structure of the μ-opioid receptor bound to a morphinan antagonist
SO NATURE
LA English
DT Article
ID binding; residues; oligomerization; diprenorphine; etorphine; tolerance; gpcr; loop
AB Opium is one of the world's oldest drugs, and its derivatives morphine and codeine are among the most used clinical drugs to relieve severe pain. These prototypical opioids produce analgesia as well as many undesirable side effects (sedation, apnoea and dependence) by binding to and activating the G-protein-coupled mu-opioid receptor (mu-OR) in the central nervous system. Here we describe the 2.8 angstrom crystal structure of the mouse mu-OR in complex with an irreversible morphinan antagonist. Compared to the buried binding pocket observed in most G-protein-coupled receptors published so far, the morphinan ligand binds deeply within a large solvent-exposed pocket. Of particular interest, the mu-OR crystallizes as a two-fold symmetrical dimer through a four-helix bundle motif formed by transmembrane segments 5 and 6. These high-resolution insights into opioid receptor structure will enable the application of structure-based approaches to develop better drugs for the management of pain and addiction.
C1 [Manglik, Aashish; Kruse, Andrew C.; Kobilka, Tong Sun; Thian, Foon Sun; Mathiesen, Jesper M.; Weis, William I.; Kobilka, Brian K.; Granier, Sebastien] Stanford Univ, Sch Med, Dept Mol & Cellular Physiol, Stanford, CA 94305 USA.
   [Sunahara, Roger K.] Univ Michigan, Sch Med, Dept Pharmacol, Ann Arbor, MI 48109 USA.
   [Pardo, Leonardo] Univ Autonoma Barcelona, Unit Bioestat, Lab Med Computac, Barcelona 08193, Spain.
   [Weis, William I.] Stanford Univ, Sch Med, Dept Biol Struct, Stanford, CA 94305 USA.
   [Granier, Sebastien] CNRS, INSERM, U661, UMR 5203, F-34094 Montpellier, France.
   [Granier, Sebastien] Univ Montpellier 1 & 2, Inst Genom Fonctionnelle, F-34094 Montpellier, France.
C3 Stanford University; University of Michigan System; University of Michigan; Autonomous University of Barcelona; Stanford University; Universite de Montpellier; Institut National de la Sante et de la Recherche Medicale (Inserm); 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 Montpellier
RP Granier, S (corresponding author), Stanford Univ, Sch Med, Dept Mol & Cellular Physiol, Stanford, CA 94305 USA.
EM kobilka@stanford.edu; granier@stanford.edu
FU INSERM; Stanford Medical Scientist Training Program; National Science Foundation; Lundbeck Foundation; National Institutes of Health [NS028471, DA031418]; Mathers Foundation; National Institute of General Medical Sciences [R01GM083118] Funding Source: NIH RePORTER; National Institute of Neurological Disorders and Stroke [R01NS028471] Funding Source: NIH RePORTER
NR 47
TC 1058
Z9 1245
U1 2
U2 356
PU NATURE PUBLISHING 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 17
PY 2012
VL 485
IS 7398
BP 321
EP U170
DI 10.1038/nature10954
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 943CW
UT WOS:000304099100032
PM 22437502
DA 2026-03-09
ER

PT J
AU Fünfschilling, U
   Supplie, LM
   Mahad, D
   Boretius, S
   Saab, AS
   Edgar, J
   Brinkmann, BG
   Kassmann, CM
   Tzvetanova, ID
   Möbius, W
   Diaz, F
   Meijer, D
   Suter, U
   Hamprecht, B
   Sereda, MW
   Moraes, CT
   Frahm, J
   Goebbels, S
   Nave, KA
AF Fuenfschilling, Ursula
   Supplie, Lotti M.
   Mahad, Don
   Boretius, Susann
   Saab, Aiman S.
   Edgar, Julia
   Brinkmann, Bastian G.
   Kassmann, Celia M.
   Tzvetanova, Iva D.
   Moebius, Wiebke
   Diaz, Francisca
   Meijer, Dies
   Suter, Ueli
   Hamprecht, Bernd
   Sereda, Michael W.
   Moraes, Carlos T.
   Frahm, Jens
   Goebbels, Sandra
   Nave, Klaus-Armin
TI Glycolytic oligodendrocytes maintain myelin and long-term axonal integrity
SO NATURE
LA English
DT Article
ID cytochrome-c-oxidase; mice lacking; rat oligodendrocytes; cell-development; optic-nerve; mouse model; lactate; glucose; brain; deficiency
AB Oligodendrocytes, the myelin-forming glial cells of the central nervous system, maintain long-term axonal integrity(1-3). However, the underlying support mechanisms are not understood(4). Here we identify a metabolic component of axon-glia interactions by generating conditional Cox10 (protoheme IX farnesyltransferase) mutant mice, in which oligodendrocytes and Schwann cells fail to assemble stable mitochondrial cytochrome c oxidase (COX, also known as mitochondrial complex IV). In the peripheral nervous system, Cox10 conditional mutants exhibit severe neuropathy with dysmyelination, abnormal Remak bundles, muscle atrophy and paralysis. Notably, perturbing mitochondrial respiration did not cause glial cell death. In the adult central nervous system, we found no signs of demyelination, axonal degeneration or secondary inflammation. Unlike cultured oligodendrocytes, which are sensitive to COX inhibitors(5), post-myelination oligodendrocytes survive well in the absence of COX activity. More importantly, by in vivo magnetic resonance spectroscopy, brain lactate concentrations in mutants were increased compared with controls, but were detectable only in mice exposed to volatile anaesthetics. This indicates that aerobic glycolysis products derived from oligodendrocytes are rapidly metabolized within white matter tracts. Because myelinated axons can use lactate when energy-deprived(6), our findings suggest a model in which axon-glia metabolic coupling serves a physiological function.
C1 [Fuenfschilling, Ursula; Supplie, Lotti M.; Saab, Aiman S.; Edgar, Julia; Brinkmann, Bastian G.; Kassmann, Celia M.; Tzvetanova, Iva D.; Moebius, Wiebke; Hamprecht, Bernd; Sereda, Michael W.; Goebbels, Sandra; Nave, Klaus-Armin] Max Planck Inst Expt Med, Dept Neurogenet, D-37075 Gottingen, Germany.
   [Mahad, Don] Newcastle Univ, Sch Med, Inst Ageing & Hlth, Mitochondrial Res Grp, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England.
   [Boretius, Susann; Frahm, Jens] Max Planck Inst Biophys Chem, Biomed NMR Forsch GmbH, D-37070 Gottingen, Germany.
   [Diaz, Francisca; Moraes, Carlos T.] Univ Miami, Miller Sch Med, Dept Neurol & Cell Biol & Anat, Miami, FL 33136 USA.
   [Meijer, Dies] Erasmus MC, Dept Cell Biol, NL-3000 CA Rotterdam, Netherlands.
   [Suter, Ueli] ETH Honggerberg, Dept Biol, Inst Cell Biol, CH-8093 Zurich, Switzerland.
   [Sereda, Michael W.] Univ Gottingen UMG, Dept Clin Neurophysiol, D-37075 Gottingen, Germany.
C3 Max Planck Society; Newcastle University - UK; Max Planck Society; University of Miami; Erasmus University Rotterdam; Erasmus MC; Swiss Federal Institutes of Technology Domain; ETH Zurich
RP Nave, KA (corresponding author), Max Planck Inst Expt Med, Dept Neurogenet, Hermann Rein Str 3, D-37075 Gottingen, Germany.
EM nave@em.mpg.de
FU BMBF (Leukonet); DFG (CMPB); EU; Oliver's Army; Swiss National Science Foundation; National Center 'Neural Plasticity and Repair'; Swiss National Science Foundation [PAOOA-117479/1]; European Leukodystrophy Association
NR 32
TC 1169
Z9 1356
U1 2
U2 133
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD MAY 24
PY 2012
VL 485
IS 7399
BP 517
EP U130
DI 10.1038/nature11007
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 946IH
UT WOS:000304344500046
PM 22622581
DA 2026-03-09
ER

PT J
AU Anbarasan, P
   Baer, ZC
   Sreekumar, S
   Gross, E
   Binder, JB
   Blanch, HW
   Clark, DS
   Toste, FD
AF Anbarasan, Pazhamalai
   Baer, Zachary C.
   Sreekumar, Sanil
   Gross, Elad
   Binder, Joseph B.
   Blanch, Harvey W.
   Clark, Douglas S.
   Toste, F. Dean
TI Integration of chemical catalysis with extractive fermentation to produce fuels
SO NATURE
LA English
DT Article
ID microbial-production; butanol; recovery; biomass; hydrocarbons; conversion; substrate; biofuels; alkanes; acetone
AB Nearly one hundred years ago, the fermentative production of acetone by Clostridium acetobutylicum provided a crucial alternative source of this solvent for manufacture of the explosive cordite. Today there is a resurgence of interest in solventogenic Clostridium species to produce n-butanol and ethanol for use as renewable alternative transportation fuels(1-3). Acetone, a product of acetone-n-butanol-ethanol (ABE) fermentation, harbours a nucleophilic alpha-carbon, which is amenable to C-C bond formation with the electrophilic alcohols produced in ABE fermentation. This functionality can be used to form higher-molecular-mass hydrocarbons similar to those found in current jet and diesel fuels. Here we describe the integration of biological and chemocatalytic routes to convert ABE fermentation products efficiently into ketones by a palladium-catalysed alkylation. Tuning of the reaction conditions permits the production of either petrol or jet and diesel precursors. Glyceryl tributyrate was used for the in situ selective extraction of both acetone and alcohols to enable the simple integration of ABE fermentation and chemical catalysis, while reducing the energy demand of the overall process. This process provides a means to selectively produce petrol, jet and diesel blend stocks from lignocellulosic and cane sugars at yields near their theoretical maxima.
C1 [Anbarasan, Pazhamalai; Sreekumar, Sanil; Gross, Elad; Toste, F. Dean] Univ Calif Berkeley, Dept Chem, Berkeley, CA 94720 USA.
   [Anbarasan, Pazhamalai; Baer, Zachary C.; Sreekumar, Sanil; Binder, Joseph B.; Blanch, Harvey W.; Clark, Douglas S.; Toste, F. Dean] Univ Calif Berkeley, Energy Biosci Inst, Berkeley, CA 94720 USA.
   [Baer, Zachary C.; Blanch, Harvey W.; Clark, Douglas S.] Univ Calif Berkeley, Dept Chem & Biomol Engn, Berkeley, CA 94720 USA.
   [Gross, Elad; Toste, F. Dean] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Div Chem Sci, Berkeley, CA 94720 USA.
C3 University of California System; University of California Berkeley; University of California System; University of California Berkeley; University of California System; University of California Berkeley; United States Department of Energy (DOE); Lawrence Berkeley National Laboratory; University of California System; University of California Berkeley
RP Toste, FD (corresponding author), Univ Calif Berkeley, Dept Chem, Berkeley, CA 94720 USA.
EM fdtoste@berkeley.edu
FU Office of Science of the US Department of Energy [DE-AC02-05CH11231]; Energy Biosciences Institute
NR 27
TC 346
Z9 399
U1 6
U2 438
PU NATURE PUBLISHING 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 8
PY 2012
VL 491
IS 7423
BP 235
EP 239
DI 10.1038/nature11594
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 033DP
UT WOS:000310774300040
PM 23135469
DA 2026-03-09
ER

PT J
AU Apicella, CL
   Marlowe, FW
   Fowler, JH
   Christakis, NA
AF Apicella, Coren L.
   Marlowe, Frank W.
   Fowler, James H.
   Christakis, Nicholas A.
TI Social networks and cooperation in hunter-gatherers
SO NATURE
LA English
DT Article
ID human altruism; evolution; reciprocity; society; behavior; models
AB Social networks show striking structural regularities(1,2), and both theory and evidence suggest that networks may have facilitated the development of large-scale cooperation in humans(3-7). Here, we characterize the social networks of the Hadza, a population of hunter-gatherers in Tanzania(8). We show that Hadza networks have important properties also seen in modernized social networks, including a skewed degree distribution, degree assortativity, transitivity, reciprocity, geographic decay and homophily. We demonstrate that Hadza camps exhibit high between-group and low within-group variation in public goods game donations. Network ties are also more likely between people who give the same amount, and the similarity in cooperative behaviour extends up to two degrees of separation. Social distance appears to be as important as genetic relatedness and physical proximity in explaining assortativity in cooperation. Our results suggest that certain elements of social network structure may have been present at an early point in human history. Also, early humans may have formed ties with both kin and non-kin, based in part on their tendency to cooperate. Social networks may thus have contributed to the emergence of cooperation.
C1 [Apicella, Coren L.; Christakis, Nicholas A.] Harvard Univ, Inst Quantitat Social Sci, Cambridge, MA 02138 USA.
   [Apicella, Coren L.; Christakis, Nicholas A.] Harvard Univ, Dept Hlth Care Policy, Sch Med, Boston, MA 02115 USA.
   [Marlowe, Frank W.] Univ Cambridge, Dept Anthropol, Cambridge CB2 3DZ, England.
   [Fowler, James H.] Univ Calif San Diego, Div Med Genet, San Diego, CA 92093 USA.
   [Fowler, James H.] Univ Calif San Diego, Dept Polit Sci, San Diego, CA 92093 USA.
   [Christakis, Nicholas A.] Harvard Univ, Dept Sociol, Cambridge, MA 02138 USA.
   [Christakis, Nicholas A.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.
C3 Harvard University; Harvard University; Harvard Medical School; University of Cambridge; University of California System; University of California San Diego; University of California System; University of California San Diego; Harvard University; Harvard University; Harvard Medical School
RP Christakis, NA (corresponding author), Harvard Univ, Inst Quantitat Social Sci, Cambridge, MA 02138 USA.
EM christakis@hcp.med.harvard.edu
FU National Institute on Aging [P01-AG031093]; Science of Generosity Initiative of the University of Notre Dame; John Templeton Foundation; National Institute of General Medical Sciences [P41GM103504] Funding Source: NIH RePORTER
NR 37
TC 509
Z9 629
U1 2
U2 343
PU NATURE PUBLISHING 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 26
PY 2012
VL 481
IS 7382
BP 497
EP U109
DI 10.1038/nature10736
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 881GY
UT WOS:000299471800038
PM 22281599
DA 2026-03-09
ER

PT J
AU Mayer, KFX
   Waugh, R
   Langridge, P
   Close, TJ
   Wise, RP
   Graner, A
   Matsumoto, T
   Sato, K
   Schulman, A
   Muehlbauer, GJ
   Stein, N
   Ariyadasa, R
   Schulte, D
   Poursarebani, N
   Zhou, RN
   Steuernagel, B
   Mascher, M
   Scholz, U
   Shi, BJ
   Langridge, P
   Madishetty, K
   Svensson, JT
   Bhat, P
   Moscou, M
   Resnik, J
   Close, TJ
   Muehlbauer, GJ
   Hedley, P
   Liu, H
   Morris, J
   Waugh, R
   Frenkel, Z
   Korol, A
   Bergès, H
   Graner, A
   Stein, N
   Steuernagel, B
   Taudien, S
   Groth, M
   Felder, M
   Lonardi, S
   Duma, D
   Alpert, M
   Cordero, F
   Beccuti, M
   Ciardo, G
   Ma, Y
   Wanamaker, S
   Stein, N
   Close, TJ
   Platzer, M
   Brown, JWS
   Schulman, A
   Platzer, M
   Fincher, GB
   Muehlbauer, GJ
   Sato, K
   Taudien, S
   Sampath, D
   Swarbreck, D
   Scalabrin, S
   Zuccolo, A
   Vendramin, V
   Morgante, M
   Schulman, A
AF Mayer, Klaus F. X.
   Waugh, Robbie
   Langridge, Peter
   Close, Timothy J.
   Wise, Roger P.
   Graner, Andreas
   Matsumoto, Takashi
   Sato, Kazuhiro
   Schulman, Alan
   Muehlbauer, Gary J.
   Stein, Nils
   Ariyadasa, Ruvini
   Schulte, Daniela
   Poursarebani, Naser
   Zhou, Ruonan
   Steuernagel, Burkhard
   Mascher, Martin
   Scholz, Uwe
   Shi, Bujun
   Langridge, Peter
   Madishetty, Kavitha
   Svensson, Jan T.
   Bhat, Prasanna
   Moscou, Matthew
   Resnik, Josh
   Close, Timothy J.
   Muehlbauer, Gary J.
   Hedley, Pete
   Liu, Hui
   Morris, Jenny
   Waugh, Robbie
   Frenkel, Zeev
   Korol, Avraham
   Berges, Helene
   Graner, Andreas
   Stein, Nils
   Steuernagel, Burkhard
   Taudien, Stefan
   Groth, Marco
   Felder, Marius
   Lonardi, Stefano
   Duma, Denisa
   Alpert, Matthew
   Cordero, Francesa
   Beccuti, Marco
   Ciardo, Gianfranco
   Ma, Yaqin
   Wanamaker, Steve
   Stein, Nils
   Close, Timothy J.
   Platzer, Matthias
   Brown, John W. S.
   Schulman, Alan
   Platzer, Matthias
   Fincher, Geoffrey B.
   Muehlbauer, Gary J.
   Sato, Kazuhiro
   Taudien, Stefan
   Sampath, Dharanya
   Swarbreck, David
   Scalabrin, Simone
   Zuccolo, Andrea
   Vendramin, Vera
   Morgante, Michele
   Schulman, Alan
TI A physical, genetic and functional sequence assembly of the barley genome
SO NATURE
LA English
DT Article
ID messenger-rna decay; mildew resistance locus; hordeum-vulgare l.; noncoding rnas; evolution; map; expression; rice; arabidopsis; reveals
AB Barley (Hordeum vulgare L.) is among the world's earliest domesticated and most important crop plants. It is diploid with a large haploid genome of 5.1 gigabases (Gb). Here we present an integrated and ordered physical, genetic and functional sequence resource that describes the barley gene-space in a structured whole-genome context. We developed a physical map of 4.98 Gb, with more than 3.90 Gb anchored to a high-resolution genetic map. Projecting a deep whole-genome shotgun assembly, complementary DNA and deep RNA sequence data onto this framework supports 79,379 transcript clusters, including 26,159 'high-confidence' genes with homology support from other plant genomes. Abundant alternative splicing, premature termination codons and novel transcriptionally active regions suggest that post-transcriptional processing forms an important regulatory layer. Survey sequences from diverse accessions reveal a landscape of extensive single-nucleotide variation. Our data provide a platform for both genome-assisted research and enabling contemporary crop improvement.
C1 [Mayer, Klaus F. X.] Helmholtz Zentrum Munchen, MIPS IBIS, D-85764 Neuherberg, Germany.
   [Waugh, Robbie; Hedley, Pete; Liu, Hui; Morris, Jenny; Waugh, Robbie] James Hutton Inst, Dundee DD2 5DE, Scotland.
   [Langridge, Peter; Langridge, Peter] Univ Adelaide, Australian Ctr Plant Funct Genom, Glen Osmond, SA 5064, Australia.
   [Wise, Roger P.] Iowa State Univ, USDA, ARS, Dept Plant Pathol & Microbiol, Ames, IA 50011 USA.
   [Graner, Andreas; Stein, Nils; Ariyadasa, Ruvini; Schulte, Daniela; Poursarebani, Naser; Zhou, Ruonan; Steuernagel, Burkhard; Mascher, Martin; Scholz, Uwe; Graner, Andreas; Stein, Nils; Steuernagel, Burkhard] Leibniz Inst Plant Genet & Crop Plant Res IPK, D-06466 Seeland Ot Gatersleben, Germany.
   [Matsumoto, Takashi] Natl Inst Agrobiol Sci, Tsukuba, Ibaraki 3058602, Japan.
   [Sato, Kazuhiro] Okayama Univ, Kurashiki, Okayama 7100046, Japan.
   [Schulman, Alan] Univ Helsinki, MTT Agrifood Res, FIN-00014 Helsinki, Finland.
   [Schulman, Alan] Univ Helsinki, Inst Biotechnol, FIN-00014 Helsinki, Finland.
   [Muehlbauer, Gary J.] Univ Minnesota, Dept Agron & Plant Genet, Dept Plant Biol, St Paul, MN 55108 USA.
   [Frenkel, Zeev; Korol, Avraham] Univ Haifa, Inst Evolut, IL-31905 Haifa, Israel.
   [Close, Timothy J.; Madishetty, Kavitha; Svensson, Jan T.; Bhat, Prasanna; Moscou, Matthew; Resnik, Josh; Close, Timothy J.; Close, Timothy J.] Univ Calif Riverside, Dept Bot & Plant Sci, Riverside, CA 92521 USA.
   [Berges, Helene] INRA CNRGV, Auzeville, France.
   [Taudien, Stefan; Groth, Marco; Felder, Marius; Platzer, Matthias; Platzer, Matthias; Taudien, Stefan] Fritz Lipmann Inst, Leibniz Inst Age Res, D-07745 Jena, Germany.
   [Lonardi, Stefano; Duma, Denisa; Alpert, Matthew; Cordero, Francesa; Beccuti, Marco; Ciardo, Gianfranco; Ma, Yaqin] Univ Calif Riverside, Dept Comp Sci & Engn, Riverside, CA 92521 USA.
   [Scalabrin, Simone; Zuccolo, Andrea] Ist Genom Applicata, I-33100 Udine, Italy.
   [Vendramin, Vera; Morgante, Michele] Univ Udine, Dipartimento Sci Agr & Ambientali, I-33100 Udine, Italy.
   Univ Arizona, Arizona Genom Inst, Tucson, AZ 85721 USA.
   ARS, USDA, Hard Winter Wheat Genet Res Unit, Manhattan, KS 66506 USA.
   Kansas State Univ, Manhattan, KS 66506 USA.
   [Sampath, Dharanya; Swarbreck, David] Genome Anal Ctr, Norwich NR4 7UH, Norfolk, England.
   [Brown, John W. S.] Univ Dundee, James Hutton Inst, Div Plant Sci, Dundee DD2 5DA, Scotland.
   [Fincher, Geoffrey B.] Univ Adelaide, ARC Ctr Excellence Plant Cell Walls, Glen Osmond, SA 5064, Australia.
   Dept Comp Sci, I-10149 Turin, Italy.
C3 Helmholtz Association; Helmholtz-Center Munich - German Research Center for Environmental Health; James Hutton Institute; Adelaide University; University of Adelaide; Australian Centre for Plant Functional Genomics; United States Department of Agriculture (USDA); USDA Agricultural Research Service; Iowa State University; Leibniz Institut fur Pflanzengenetik und Kulturpflanzenforschung; National Institute of Agrobiological Sciences - Japan; Okayama University; Natural Resources Institute Finland (Luke); University of Helsinki; University of Helsinki; University of Minnesota System; University of Minnesota Twin Cities; University of Haifa; University of California System; University of California Riverside; INRAE; Leibniz Association; Leibniz Institut fur Alternsforschung - Fritz-Lipmann-Institut (FLI); University of California System; University of California Riverside; University of Udine; University of Arizona; United States Department of Agriculture (USDA); Kansas State University; UK Research & Innovation (UKRI); Biotechnology and Biological Sciences Research Council (BBSRC); Earlham Institute; James Hutton Institute; University of Dundee; Adelaide University; University of Adelaide
RP Mayer, KFX (corresponding author), Helmholtz Zentrum Munchen, MIPS IBIS, D-85764 Neuherberg, Germany.
EM k.mayer@helmholtz-muenchen.de; Robbie.Waugh@hutton.ac.uk; stein@ipk-gatersleben.de
FU German Ministry of Education and Research (BMBF) [0314000]; Leibniz Association; European project of the 7th framework programme "TriticeaeGenome"; Austrian Wissenschaftsfond (FWF) [SFB F3705]; ERA-NET PG project "BARCODE"; Scottish Government/BBSRC [BB/100663X/1]; National Science Foundation [DBI 0321756, DBI-1062301]; USDA-CSREES-NRI [2006-55606-16722]; Agriculture and Food Research Initiative Plant Genome, Genetics and Breeding Program of USDA-CSREES-NIFA [2009-65300-05645]; BRAIN and NBRP-Japan; Japanese MAFF [TRG1008]; NIFA [688696, 2009-65300-05645] Funding Source: Federal RePORTER; BBSRC [BBS/E/T/000PR6193, BB/I00663X/1, BB/I008357/1] Funding Source: UKRI; Grants-in-Aid for Scientific Research [23380007] Funding Source: KAKEN; Direct For Biological Sciences; Division Of Integrative Organismal Systems [0922746] Funding Source: National Science Foundation; Direct For Biological Sciences; Div Of Biological Infrastructure [1062301] Funding Source: National Science Foundation; Biotechnology and Biological Sciences Research Council [BB/I008357/1, BB/I00663X/1, BBS/E/T/000PR6193] Funding Source: researchfish
NR 65
TC 766
Z9 794
U1 9
U2 420
PU NATURE PUBLISHING 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 29
PY 2012
VL 491
IS 7426
BP 711
EP +
DI 10.1038/nature11543
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 044FY
UT WOS:000311606000035
DA 2026-03-09
ER

PT J
AU Pritchard, HD
   Ligtenberg, SRM
   Fricker, HA
   Vaughan, DG
   van den Broeke, MR
   Padman, L
AF Pritchard, H. D.
   Ligtenberg, S. R. M.
   Fricker, H. A.
   Vaughan, D. G.
   van den Broeke, M. R.
   Padman, L.
TI Antarctic ice-sheet loss driven by basal melting of ice shelves
SO NATURE
LA English
DT Article
ID circumpolar deep-water; inflow; trends; ocean
AB Accurate prediction of global sea-level rise requires that we understand the cause of recent, widespread and intensifying(1,2) glacier acceleration along Antarctic ice-sheet coastal margins(3). Atmospheric and oceanic forcing have the potential to reduce the thickness and extent of floating ice shelves, potentially limiting their ability to buttress the flow of grounded tributary glaciers(4). Indeed, recent ice-shelf collapse led to retreat and acceleration of several glaciers on the Antarctic Peninsula(5). But the extent and magnitude of ice-shelf thickness change, the underlying causes of such change, and its link to glacier flow rate are so poorly understood that its future impact on the ice sheets cannot yet be predicted(3). Here we use satellite laser altimetry and modelling of the surface firn layer to reveal the circum-Antarctic pattern of ice-shelf thinning through increased basal melt. We deduce that this increased melt is the primary control of Antarctic ice-sheet loss, through a reduction in buttressing of the adjacent ice sheet leading to accelerated glacier flow(2). The highest thinning rates occur where warm water at depth can access thick ice shelves via submarine troughs crossing the continental shelf. Wind forcing could explain the dominant patterns of both basal melting and the surface melting and collapse of Antarctic ice shelves, through ocean upwelling in the Amundsen(6) and Bellingshausen(7) seas, and atmospheric warming on the Antarctic Peninsula(8). This implies that climate forcing through changing winds influences Antarctic ice-sheet mass balance, and hence global sea level, on annual to decadal timescales.
C1 [Pritchard, H. D.; Vaughan, D. G.] British Antarctic Survey, Nat Environm Res Council, Cambridge CB3 0ET, England.
   [Ligtenberg, S. R. M.; van den Broeke, M. R.] Univ Utrecht, Inst Marine & Atmospher Res, NL-3508 TA Utrecht, Netherlands.
   [Fricker, H. A.] Univ Calif San Diego, Scripps Inst Oceanog, La Jolla, CA 92093 USA.
   [Padman, L.] Earth & Space Res, Corvallis, OR 97333 USA.
C3 UK Research & Innovation (UKRI); Natural Environment Research Council (NERC); NERC British Antarctic Survey; Utrecht University; University of California System; University of California San Diego; Scripps Institution of Oceanography
RP Pritchard, HD (corresponding author), British Antarctic Survey, Nat Environm Res Council, Madingley Rd, Cambridge CB3 0ET, England.
EM h.pritchard@bas.ac.uk
FU European Union [226375]; Natural Environment Research Council [bas0100027] Funding Source: researchfish; NERC [bas0100027] Funding Source: UKRI
NR 31
TC 1059
Z9 1221
U1 7
U2 469
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 26
PY 2012
VL 484
IS 7395
BP 502
EP 505
DI 10.1038/nature10968
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 931FF
UT WOS:000303200400048
PM 22538614
DA 2026-03-09
ER

PT J
AU Haga, K
   Kruse, AC
   Asada, H
   Yurugi-Kobayashi, T
   Shiroishi, M
   Zhang, C
   Weis, WI
   Okada, T
   Kobilka, BK
   Haga, T
   Kobayashi, T
AF Haga, Kazuko
   Kruse, Andrew C.
   Asada, Hidetsugu
   Yurugi-Kobayashi, Takami
   Shiroishi, Mitsunori
   Zhang, Cheng
   Weis, William I.
   Okada, Tetsuji
   Kobilka, Brian K.
   Haga, Tatsuya
   Kobayashi, Takuya
TI Structure of the human M2 muscarinic acetylcholine receptor bound to an antagonist
SO NATURE
LA English
DT Article
ID beta-adrenergic-receptor; transmembrane domain; scanning mutagenesis; crystal-structure; binding-protein; expression; insights; activation; rhodopsin; complex
AB The parasympathetic branch of the autonomic nervous system regulates the activity of multiple organ systems. Muscarinic receptors are G-protein-coupled receptors that mediate the response to acetylcholine released from parasympathetic nerves(1-5). Their role in the unconscious regulation of organ and central nervous system function makes them potential therapeutic targets for a broad spectrum of diseases. The M2 muscarinic acetylcholine receptor (M2 receptor) is essential for the physiological control of cardiovascular function through activation of G-protein-coupled inwardly rectifying potassium channels, and is of particular interest because of its extensive pharmacological characterization with both orthosteric and allosteric ligands. Here we report the structure of the antagonist-bound human M2 receptor, the first human acetylcholine receptor to be characterized structurally, to our knowledge. The antagonist 3-quinuclidinyl-benzilate binds in the middle of a long aqueous channel extending approximately two-thirds through the membrane. The orthosteric binding pocket is formed by amino acids that are identical in all five muscarinic receptor subtypes, and shares structural homology with other functionally unrelated acetylcholine binding proteins from different species. A layer of tyrosine residues forms an aromatic cap restricting dissociation of the bound ligand. A binding site for allosteric ligands has been mapped to residues at the entrance to the binding pocket near this aromatic cap. The structure of the M2 receptor provides insights into the challenges of developing subtype-selective ligands for muscarinic receptors and their propensity for allosteric regulation.
C1 [Kruse, Andrew C.; Zhang, Cheng; Weis, William I.; Kobilka, Brian K.] Stanford Univ, Sch Med, Dept Mol & Cellular Physiol, Stanford, CA 94305 USA.
   [Haga, Kazuko; Okada, Tetsuji; Haga, Tatsuya] Gakushuin Univ, Dept Life Sci, Fac Sci, Tokyo 1718588, Japan.
   [Asada, Hidetsugu; Yurugi-Kobayashi, Takami; Kobayashi, Takuya] Kyoto Univ, Fac Med, Dept Med Chem & Cell Biol, Sakyo Ku, Kyoto 6068501, Japan.
   [Asada, Hidetsugu; Yurugi-Kobayashi, Takami; Shiroishi, Mitsunori; Kobayashi, Takuya] Japan Sci & Technol Agcy, ERATO, Human Receptor Crystallog Project, Sakyo Ku, Kyoto 6068501, Japan.
   [Shiroishi, Mitsunori] Kyushu Univ, Grad Sch Pharmaceut Sci, Higashi Ku, Fukuoka 8128582, Japan.
   [Weis, William I.] Stanford Univ, Sch Med, Dept Biol Struct, Stanford, CA 94305 USA.
   [Kobayashi, Takuya] Kyoto Univ, Fac Med, Japan Sci & Technol Agcy, Kyoto 6068501, Japan.
C3 Stanford University; Gakushuin University; Kyoto University; Japan Science & Technology Agency (JST); Kyushu University; Stanford University; Kyoto University; Japan Science & Technology Agency (JST)
RP Kobilka, BK (corresponding author), Stanford Univ, Sch Med, Dept Mol & Cellular Physiol, 279 Campus Dr, Stanford, CA 94305 USA.
EM kobilka@stanford.edu; tatsuya.haga@gakushuin.ac.jp; t-coba@mfour.med.kyoto-u.ac.jp
FU Japan Society for the Promotion of Science; Japan Science and Technology Corporation (CREST); Ministry of Education, Culture, Sports, Science and Technology of Japan [15083201]; Japan Science and Technology Corporation (ERATO); Toray Science Foundation; Takeda Science Foundation; Ichiro Kanehara Foundation; Sumitomo Foundation; National Institutes of Health [NS028471, GM083118]; Mathers Foundation; National Science Foundation; National Institute of General Medical Sciences [R01GM083118] Funding Source: NIH RePORTER; National Institute of Neurological Disorders and Stroke [R01NS028471] Funding Source: NIH RePORTER; Grants-in-Aid for Scientific Research [15083201, 23370049, 22659059, 11J40150] Funding Source: KAKEN
NR 39
TC 663
Z9 777
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 FEB 23
PY 2012
VL 482
IS 7386
BP 547
EP U147
DI 10.1038/nature10753
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 898VM
UT WOS:000300770500055
PM 22278061
DA 2026-03-09
ER

PT J
AU Pichlmair, A
   Kandasamy, K
   Alvisi, G
   Mulhern, O
   Sacco, R
   Habjan, M
   Binder, M
   Stefanovic, A
   Eberle, CA
   Goncalves, A
   Bürckstümmer, T
   Müller, AC
   Fauster, A
   Holze, C
   Lindsten, K
   Goodbourn, S
   Kochs, G
   Weber, F
   Bartenschlager, R
   Bowie, AG
   Bennett, KL
   Colinge, J
   Superti-Furga, G
AF Pichlmair, Andreas
   Kandasamy, Kumaran
   Alvisi, Gualtiero
   Mulhern, Orla
   Sacco, Roberto
   Habjan, Matthias
   Binder, Marco
   Stefanovic, Adrijana
   Eberle, Carol-Ann
   Goncalves, Adriana
   Buerckstuemmer, Tilmann
   Mueller, Andre C.
   Fauster, Astrid
   Holze, Cathleen
   Lindsten, Kristina
   Goodbourn, Stephen
   Kochs, Georg
   Weber, Friedemann
   Bartenschlager, Ralf
   Bowie, Andrew G.
   Bennett, Keiryn L.
   Colinge, Jacques
   Superti-Furga, Giulio
TI Viral immune modulators perturb the human molecular network by common and unique strategies
SO NATURE
LA English
DT Article
ID protein; expression; evasion; innate; activation; responses; pathways; reveals; systems; screen
AB Viruses must enter host cells to replicate, assemble and propagate. Because of the restricted size of their genomes, viruses have had to evolve efficient ways of exploiting host cell processes to promote their own life cycles and also to escape host immune defence mechanisms(1,2). Many viral open reading frames (viORFs) with immune-modulating functions essential for productive viral growth have been identified across a range of viral classes(3,4). However, there has been no comprehensive study to identify the host factors with which these viORFs interact for a global perspective of viral perturbation strategies(5-11). Here we show that different viral perturbation patterns of the host molecular defence network can be deduced from a mass-spectrometry-based host-factor survey in a defined human cellular system by using 70 innate immune-modulating viORFs from 30 viral species. The 579 host proteins targeted by the viORFs mapped to an unexpectedly large number of signalling pathways and cellular processes, suggesting yet unknown mechanisms of antiviral immunity. We further experimentally verified the targets heterogeneous nuclear ribonucleoprotein U, phosphatidylinositol-3-OH kinase, the WNK (with-no-lysine) kinase family and USP19 (ubiquitin-specific peptidase 19) as vulnerable nodes in the host cellular defence system. Evaluation of the impact of viral immune modulators on the host molecular network revealed perturbation strategies used by individual viruses and by viral classes. Our data are also valuable for the design of broad and specific antiviral therapies.
C1 [Pichlmair, Andreas; Kandasamy, Kumaran; Sacco, Roberto; Stefanovic, Adrijana; Eberle, Carol-Ann; Goncalves, Adriana; Buerckstuemmer, Tilmann; Mueller, Andre C.; Fauster, Astrid; Bennett, Keiryn L.; Colinge, Jacques; Superti-Furga, Giulio] Austrian Acad Sci, CeMM Res Ctr Mol Med, A-1090 Vienna, Austria.
   [Pichlmair, Andreas; Habjan, Matthias; Holze, Cathleen] Max Planck Inst Biochem, Innate Immun Lab, D-82152 Martinsried, Germany.
   [Alvisi, Gualtiero; Binder, Marco; Bartenschlager, Ralf] Heidelberg Univ, Dept Infect Dis, D-69120 Heidelberg, Germany.
   [Mulhern, Orla; Bowie, Andrew G.] Trinity Coll Dublin, Trinity Biomed Sci Inst, Sch Biochem & Immunol, Dublin 2, Ireland.
   [Habjan, Matthias; Kochs, Georg; Weber, Friedemann] Univ Freiburg, Dept Virol, D-79104 Freiburg, Germany.
   [Lindsten, Kristina] Karolinska Inst, Dept Cell & Mol Biol, S-17177 Stockholm, Sweden.
   [Goodbourn, Stephen] Univ London, Div Basic Med Sci, London SW17 0RE, England.
   [Weber, Friedemann] Univ Freiburg, Ctr Biol Signalling Studies BIOSS, D-79108 Freiburg, Germany.
   [Weber, Friedemann] Univ Marburg, Inst Virol, D-35043 Marburg, Germany.
C3 Austrian Academy of Sciences; CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences; Max Planck Society; Ruprecht Karls University Heidelberg; Trinity College Dublin; University of Freiburg; Karolinska Institutet; University of London; University of Freiburg; Philipps University Marburg
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; i-FIVE European Research Council; European Molecular Biology Organization [ATLF 463-2008]; Science Foundation Ireland [07/IN1/B934]; Deutsche Forschungsgemeinschaft [We2616/5-2, SFB593/B13, Ko1579/5-1, FOR1202]; German Ministry for Education and Research (Suszeptibilitat bei Infektionen) [01KI 0786]; Austrian Ministry of Science and Research (GEN-AU/BIN)
NR 39
TC 216
Z9 248
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 JUL 26
PY 2012
VL 487
IS 7408
BP 486
EP U101
DI 10.1038/nature11289
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 979KD
UT WOS:000306815300039
PM 22810585
DA 2026-03-09
ER

PT J
AU Moreno, JA
   Radford, H
   Peretti, D
   Steinert, JR
   Verity, N
   Martin, MG
   Halliday, M
   Morgan, J
   Dinsdale, D
   Ortori, CA
   Barrett, DA
   Tsaytler, P
   Bertolotti, A
   Willis, AE
   Bushell, M
   Mallucci, GR
AF Moreno, Julie A.
   Radford, Helois
   Peretti, Diego
   Steinert, Joern R.
   Verity, Nicholas
   Martin, Maria Guerra
   Halliday, Mark
   Morgan, Jason
   Dinsdale, David
   Ortori, Catherine A.
   Barrett, David A.
   Tsaytler, Pavel
   Bertolotti, Anne
   Willis, Anne E.
   Bushell, Martin
   Mallucci, Giovanna R.
TI Sustained translational repression by eIF2α-P mediates prion neurodegeneration
SO NATURE
LA English
DT Article
ID endoplasmic-reticulum stress; unfolded protein response; toxicity in-vivo; alzheimers-disease; gene-expression; er stress; mice; prp; proteostasis; dysfunction
AB The mechanisms leading to neuronal death in neurodegenerative disease are poorly understood. Many of these disorders, including Alzheimer's, Parkinson's and prion diseases, are associated with the accumulation of misfolded disease-specific proteins. The unfolded protein response is a protective cellular mechanism triggered by rising levels of misfolded proteins. One arm of this pathway results in the transient shutdown of protein translation, through phosphorylation of the alpha-subunit of eukaryotic translation initiation factor, eIF2. Activation of the unfolded protein response and/or increased eIF2 alpha-P levels are seen in patients with Alzheimer's, Parkinson's and prion diseases(1-4), but how this links to neurodegeneration is unknown. Here we show that accumulation of prion protein during prion replication causes persistent translational repression of global protein synthesis by eIF2 alpha-P, associated with synaptic failure and neuronal loss in prion-diseased mice. Further, we show that promoting translational recovery in hippocampi of prion-infected mice is neuroprotective. Overexpression of GADD34, a specific eIF2 alpha-P phosphatase, as well as reduction of levels of prion protein by lentivirally mediated RNA interference, reduced eIF2 alpha-P levels. As a result, both approaches restored vital translation rates during prion disease, rescuing synaptic deficits and neuronal loss, thereby significantly increasing survival. In contrast, salubrinal, an inhibitor of eIF2 alpha-P dephosphorylation(5), increased eIF2 alpha-P levels, exacerbating neurotoxicity and significantly reducing survival in prion-diseased mice. Given the prevalence of protein misfolding and activation of the unfolded protein response in several neurodegenerative diseases, our results suggest that manipulation of common pathways such as translational control, rather than disease-specific approaches, may lead to new therapies preventing synaptic failure and neuronal loss across the spectrum of these disorders.
C1 [Moreno, Julie A.; Radford, Helois; Peretti, Diego; Steinert, Joern R.; Verity, Nicholas; Martin, Maria Guerra; Halliday, Mark; Morgan, Jason; Dinsdale, David; Willis, Anne E.; Bushell, Martin; Mallucci, Giovanna R.] Univ Leicester, MRC, Toxicol Unit, Leicester LE1 9HN, Leics, England.
   [Ortori, Catherine A.; Barrett, David A.] Univ Nottingham, Sch Pharm, Ctr Analyt Biosci, Nottingham NG7 2RD, England.
   [Tsaytler, Pavel; Bertolotti, Anne] MRC, Mol Biol Lab, Cambridge CB2 0QH, England.
C3 University of Leicester; University of Nottingham; MRC Laboratory Molecular Biology
RP Mallucci, GR (corresponding author), Univ Leicester, MRC, Toxicol Unit, Hodgkin Bldg,Lancaster Rd, Leicester LE1 9HN, Leics, England.
EM grm7@le.ac.uk
FU Medical Research Council, UK; Biotechnology and Biological Sciences Research Council [BB/F02326X/2] Funding Source: researchfish; Medical Research Council [MC_U132692719, MC_UP_A600_1024, MC_U132681855, MC_U105185860, MC_UP_A600_1023, MC_U123160654] Funding Source: researchfish; BBSRC [BB/F02326X/2] Funding Source: UKRI; MRC [MC_U132681855, MC_UP_A600_1023, MC_U132692719, MC_U105185860, MC_U123160654, MC_UP_A600_1024] Funding Source: UKRI
NR 34
TC 514
Z9 605
U1 0
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 24
PY 2012
VL 485
IS 7399
BP 507
EP U119
DI 10.1038/nature11058
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 946IH
UT WOS:000304344500044
PM 22622579
DA 2026-03-09
ER

PT J
AU Grant, KM
   Rohling, EJ
   Bar-Matthews, M
   Ayalon, A
   Medina-Elizalde, M
   Ramsey, CB
   Satow, C
   Roberts, AP
AF Grant, K. M.
   Rohling, E. J.
   Bar-Matthews, M.
   Ayalon, A.
   Medina-Elizalde, M.
   Ramsey, C. Bronk
   Satow, C.
   Roberts, A. P.
TI Rapid coupling between ice volume and polar temperature over the past 150,000 years
SO NATURE
LA English
DT Article
ID sea-level; climate; foraminifera; constraints; chronology
AB Current global warming necessitates a detailed understanding of the relationships between climate and global ice volume. Highly resolved and continuous sea-level records are essential for quantifying ice-volume changes. However, an unbiased study of the timing of past ice-volume changes, relative to polar climate change, has so far been impossible because available sea-level records either were dated by using orbital tuning or ice-core timescales, or were discontinuous in time. Here we present an independent dating of a continuous, high-resolution sea-level record(1,2) in millennial-scale detail throughout the past 150,000 years. We find that the timing of ice-volume fluctuations agrees well with that of variations in Antarctic climate and especially Greenland climate. Amplitudes of ice-volume fluctuations more closely match Antarctic (rather than Greenland) climate changes. Polar climate and ice-volume changes, and their rates of change, are found to covary within centennial response times. Finally, rates of sea-level rise reached at least 1.2 m per century during all major episodes of ice-volume reduction.
C1 [Grant, K. M.; Rohling, E. J.; Medina-Elizalde, M.] Univ Southampton, Sch Ocean & Earth Sci, Natl Oceanog Ctr, Southampton SO14 3ZH, Hants, England.
   [Rohling, E. J.; Roberts, A. P.] Australian Natl Univ, Res Sch Earth Sci, Canberra, ACT 0200, Australia.
   [Bar-Matthews, M.; Ayalon, A.] Geol Survey Israel, IL-95501 Jerusalem, Israel.
   [Ramsey, C. Bronk] Univ Oxford, Res Lab Archaeol & Hist Art, Oxford OX1 3QY, England.
   [Satow, C.] Royal Holloway Univ London, Dept Geog, Egham TW20 0EX, Surrey, England.
C3 NERC National Oceanography Centre; University of Southampton; Australian National University; Geological Survey Israel; University of Oxford; University of London; Royal Holloway University London
RP Grant, KM (corresponding author), Univ Southampton, Sch Ocean & Earth Sci, Natl Oceanog Ctr, European Way, Southampton SO14 3ZH, Hants, England.
EM kxg@noc.soton.ac.uk
FU UK Natural Environment Research Council (NERC) [NE/H004424/1, NE/E01531X/1, NE/I009906/1]; Royal Society Wolfson Research Merit Award; Australian Laureate Fellowship [FL120100050]; NERC [NRCF010002, NE/I009906/1, NE/E01531X/1, NE/E015670/1, bosc01001, NE/H004424/1] Funding Source: UKRI; Natural Environment Research Council [NE/I009906/1, NE/E01531X/1, NRCF010002, NE/H004424/1, bosc01001, NE/E015670/1] Funding Source: researchfish
NR 32
TC 499
Z9 537
U1 1
U2 249
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 29
PY 2012
VL 491
IS 7426
BP 744
EP 747
DI 10.1038/nature11593
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 044FY
UT WOS:000311606000042
PM 23151478
DA 2026-03-09
ER

PT J
AU Yuan, P
   Leonetti, MD
   Hsiung, YC
   MacKinnon, R
AF Yuan, Peng
   Leonetti, Manuel D.
   Hsiung, Yichun
   MacKinnon, Roderick
TI Open structure of the Ca2+ gating ring in the high-conductance Ca2+-activated K+ channel
SO NATURE
LA English
DT Article
ID activated potassium channels; human bk channel; smooth-muscle; rck domain; quaternary ammonium; crystal-structure; calcium; block; mechanism; complex
AB High-conductance voltage-and Ca2+-activated K+ channels function in many physiological processes that link cell membrane voltage and intracellular Ca2+ concentration, including neuronal electrical activity, skeletal and smooth muscle contraction, and hair cell tuning(1-8). Like other voltage-dependent K+ channels, Ca2+-activated K+ channels open when the cell membrane depolarizes, but in contrast to other voltage-dependent K+ channels, they also open when intracellular Ca2+ concentrations rise. Channel opening by Ca2+ is made possible by a structure called the gating ring, which is located in the cytoplasm. Recent structural studies have defined the Ca2+-free, closed, conformation of the gating ring, but the Ca2+-bound, open, conformation is not yet known(9). Here we present the Ca2+-bound conformation of the gating ring. This structure shows how one layer of the gating ring, in response to the binding of Ca2+, opens like the petals of a flower. The degree to which it opens explains how Ca2+ binding can open the transmembrane pore. These findings present a molecular basis for Ca2+ activation of K+ channels and suggest new possibilities for targeting the gating ring to treat conditions such as asthma and hypertension.
C1 [Yuan, Peng; Leonetti, Manuel D.; Hsiung, Yichun; MacKinnon, Roderick] Rockefeller Univ, Howard Hughes Med Inst, Lab Mol Neurobiol & Biophys, New York, NY 10065 USA.
C3 Howard Hughes Medical Institute; Rockefeller University
RP MacKinnon, R (corresponding author), Rockefeller Univ, Howard Hughes Med Inst, Lab Mol Neurobiol & Biophys, 1230 York Ave, New York, NY 10065 USA.
EM mackinn@rockefeller.edu
FU American Asthma Foundation [07-0127]
NR 38
TC 117
Z9 135
U1 0
U2 42
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JAN 5
PY 2012
VL 481
IS 7379
BP 94
EP U105
DI 10.1038/nature10670
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 872VD
UT WOS:000298836900036
PM 22139424
DA 2026-03-09
ER

PT J
AU Blount, ZD
   Barrick, JE
   Davidson, CJ
   Lenski, RE
AF Blount, Zachary D.
   Barrick, Jeffrey E.
   Davidson, Carla J.
   Lenski, Richard E.
TI Genomic analysis of a key innovation in an experimental Escherichia coli population
SO NATURE
LA English
DT Article
ID term experimental evolution; citrate utilization; gene; sequences; promoter; duplication; adaptation; amplification; suppression; contingency
AB Evolutionary novelties have been important in the history of life, but their origins are usually difficult to examine in detail. We previously described the evolution of a novel trait, aerobic citrate utilization (Cit(+)), in an experimental population of Escherichia coli. Here we analyse genome sequences to investigate the history and genetic basis of this trait. At least three distinct clades coexisted for more than 10,000 generations before its emergence. The Cit(+) trait originated in one clade by a tandem duplication that captured an aerobically expressed promoter for the expression of a previously silent citrate transporter. The clades varied in their propensity to evolve this novel trait, although genotypes able to do so existed in all three clades, implying that multiple potentiating mutations arose during the population's history. Our findings illustrate the importance of promoter capture and altered gene regulation in mediating the exaptation events that often underlie evolutionary innovations.
C1 [Blount, Zachary D.; Lenski, Richard E.] Michigan State Univ, Dept Microbiol & Mol Genet, E Lansing, MI 48824 USA.
   [Blount, Zachary D.; Barrick, Jeffrey E.; Lenski, Richard E.] Michigan State Univ, BEACON Ctr Study Evolut Act, E Lansing, MI 48824 USA.
   [Barrick, Jeffrey E.] Univ Texas Austin, Dept Chem & Biochem, Austin, TX 78712 USA.
   [Barrick, Jeffrey E.] Univ Texas Austin, Inst Cellular & Mol Biol, Austin, TX 78712 USA.
   [Davidson, Carla J.] Univ Calgary, Dept Microbiol Immunol & Infect Dis, Calgary, AB T2N 4N1, Canada.
C3 Michigan State University; Michigan State University; University of Texas System; University of Texas Austin; University of Texas System; University of Texas Austin; University of Calgary
RP Blount, ZD (corresponding author), Michigan State Univ, Dept Microbiol & Mol Genet, E Lansing, MI 48824 USA.
EM blountza@msu.edu; lenski@msu.edu
FU US National Science Foundation [DEB-1019989]; BEACON Center for the Study of Evolution in Action [DBI-0939454]; US National Institutes of Health [K99-GM087550]; Defense Advanced Research Projects Agency [HR0011-09-1-0055]; Rudolf Hugh Fellowship; DuVall Family Award; Ronald M. and Sharon Rogowski Fellowship; Barnett Rosenberg Fellowship; Division Of Environmental Biology; Direct For Biological Sciences [1019989] Funding Source: National Science Foundation
NR 52
TC 441
Z9 541
U1 6
U2 263
PU NATURE PUBLISHING 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 27
PY 2012
VL 489
IS 7417
BP 513
EP +
DI 10.1038/nature11514
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 011LT
UT WOS:000309167100040
PM 22992527
DA 2026-03-09
ER

PT J
AU He, XM
   Aizenberg, M
   Kuksenok, O
   Zarzar, LD
   Shastri, A
   Balazs, AC
   Aizenberg, J
AF He, Ximin
   Aizenberg, Michael
   Kuksenok, Olga
   Zarzar, Lauren D.
   Shastri, Ankita
   Balazs, Anna C.
   Aizenberg, Joanna
TI Synthetic homeostatic materials with chemo-mechano-chemical self-regulation
SO NATURE
LA English
DT Article
AB Living organisms have unique homeostatic abilities, maintaining tight control of their local environment through interconversions of chemical and mechanical energy and self-regulating feedback loops organized hierarchically across many length scales(1-7). In contrast, most synthetic materials are incapable of continuous self-monitoring and self-regulating behaviour owing to their limited single-directional chemomechanical(7-12) or mechanochemical(13,14) modes. Applying the concept of homeostasis to the design of autonomous materials(15) would have substantial impacts in areas ranging from medical implants that help stabilize bodily functions to 'smart' materials that regulate energy usage(2,16,17). Here we present a versatile strategy for creating self-regulating, self-powered, homeostatic materials capable of precisely tailored chemo-mechanochemical feedback loops on the nano- or microscale. We design a bilayer system with hydrogel-supported, catalyst-bearing microstructures, which are separated from a reactant-containing 'nutrient' layer. Reconfiguration of the gel in response to a stimulus induces the reversible actuation of the microstructures into and out of the nutrient layer, and serves as a highly precise 'on/off' switch for chemical reactions. We apply this design to trigger organic, inorganic and biochemical reactions that undergo reversible, repeatable cycles synchronized with the motion of the microstructures and the driving external chemical stimulus. By exploiting a continuous feedback loop between various exothermic catalytic reactions in the nutrient layer and the mechanical action of the temperature-responsive gel, we then create exemplary autonomous, self-sustained homeostatic systems that maintain a user-defined parameter-temperature-in a narrow range. The experimental results are validated using computational modelling that qualitatively captures the essential features of the self-regulating behaviour and provides additional criteria for the optimization of the homeostatic function, subsequently confirmed experimentally. This design is highly customizable owing to the broad choice of chemistries, tunable mechanics and its physical simplicity, and may lead to a variety of applications in autonomous systems with chemo-mechano-chemical transduction at their core.
C1 [He, Ximin; Aizenberg, Joanna] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA.
   [He, Ximin; Aizenberg, Michael; Aizenberg, Joanna] Harvard Univ, Wyss Inst Biologically Inspired Engn, Cambridge, MA 02138 USA.
   [Kuksenok, Olga; Balazs, Anna C.] Univ Pittsburgh, Dept Chem & Petr Engn, Pittsburgh, PA 15260 USA.
   [Zarzar, Lauren D.; Shastri, Ankita; Aizenberg, Joanna] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA.
C3 Harvard University; Harvard University; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh; Harvard University
RP Aizenberg, J (corresponding author), Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA.
EM jaiz@seas.harvard.edu
FU US DOE [DE-SC0005247]; US NSF [CMMI-1124839]; Directorate For Engineering; Div Of Civil, Mechanical, & Manufact Inn [1124839] Funding Source: National Science Foundation; Div Of Civil, Mechanical, & Manufact Inn; Directorate For Engineering [1124669] Funding Source: National Science Foundation
NR 33
TC 463
Z9 523
U1 11
U2 665
PU NATURE PUBLISHING 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 12
PY 2012
VL 487
IS 7406
BP 214
EP 218
DI 10.1038/nature11223
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 972LP
UT WOS:000306278900035
PM 22785318
DA 2026-03-09
ER

PT J
AU Plechanovová, A
   Jaffray, EG
   Tatham, MH
   Naismith, JH
   Hay, RT
AF Plechanovova, Anna
   Jaffray, Ellis G.
   Tatham, Michael H.
   Naismith, James H.
   Hay, Ronald T.
TI Structure of a RING E3 ligase and ubiquitin-loaded E2 primed for catalysis
SO NATURE
LA English
DT Article
ID dna-damage; complex; rnf4; degradation; insights; ubiquitylation; determinants; mechanism; pathway; binding
AB Ubiquitin modification is mediated by a large family of specificity determining ubiquitin E3 ligases. To facilitate ubiquitin transfer, RING E3 ligases bind both substrate and a ubiquitin E2 conjugating enzyme linked to ubiquitin via a thioester bond, but the mechanism of transfer has remained elusive. Here we report the crystal structure of the dimeric RING domain of rat RNF4 in complex with E2 (UbcH5A) linked by an isopeptide bond to ubiquitin. While the E2 contacts a single protomer of the RING, ubiquitin is folded back onto the E2 by contacts from both RING protomers. The carboxy-terminal tail of ubiquitin is locked into an active site groove on the E2 by an intricate network of interactions, resulting in changes at the E2 active site. This arrangement is primed for catalysis as it can deprotonate the incoming substrate lysine residue and stabilize the consequent tetrahedral transition-state intermediate.
C1 [Plechanovova, Anna; Jaffray, Ellis G.; Tatham, Michael H.; Hay, Ronald T.] Univ Dundee, Coll Life Sci, Wellcome Trust Ctr Gene Regulat & Express, Dundee DD1 5EH, Scotland.
   [Naismith, James H.] Univ St Andrews, St Andrews KY16 9ST, Fife, Scotland.
C3 University of Dundee; University of St Andrews
RP Hay, RT (corresponding author), Univ Dundee, Coll Life Sci, Wellcome Trust Ctr Gene Regulat & Express, Dundee DD1 5EH, Scotland.
EM r.t.hay@dundee.ac.uk
FU Wellcome Trust; Cancer Research UK; Scottish Funding Council [SULSA]; Wellcome Trust [098391/Z/12/Z] Funding Source: Wellcome Trust; Cancer Research UK [13067] Funding Source: researchfish; Wellcome Trust [098391/Z/12/Z] Funding Source: researchfish
NR 41
TC 445
Z9 538
U1 0
U2 106
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD SEP 6
PY 2012
VL 489
IS 7414
BP 115
EP U135
DI 10.1038/nature11376
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 999WW
UT WOS:000308347000045
PM 22842904
DA 2026-03-09
ER

PT J
AU Buchhave, LA
   Latham, DW
   Johansen, A
   Bizzarro, M
   Torres, G
   Rowe, JF
   Batalha, NM
   Borucki, WJ
   Brugamyer, E
   Caldwell, C
   Bryson, ST
   Ciardi, DR
   Cochran, WD
   Endl, M
   Esquerdo, GA
   Ford, EB
   Geary, JC
   Gilliland, RL
   Hansen, T
   Isaacson, H
   Laird, JB
   Lucas, PW
   Marcy, GW
   Morse, JA
   Robertson, P
   Shporer, A
   Stefanik, RP
   Still, M
   Quinn, SN
AF Buchhave, Lars A.
   Latham, David W.
   Johansen, Anders
   Bizzarro, Martin
   Torres, Guillermo
   Rowe, Jason F.
   Batalha, Natalie M.
   Borucki, William J.
   Brugamyer, Erik
   Caldwell, Caroline
   Bryson, Stephen T.
   Ciardi, David R.
   Cochran, William D.
   Endl, Michael
   Esquerdo, Gilbert A.
   Ford, Eric B.
   Geary, John C.
   Gilliland, Ronald L.
   Hansen, Terese
   Isaacson, Howard
   Laird, John B.
   Lucas, Philip W.
   Marcy, Geoffrey W.
   Morse, Jon A.
   Robertson, Paul
   Shporer, Avi
   Stefanik, Robert P.
   Still, Martin
   Quinn, Samuel N.
TI An abundance of small exoplanets around stars with a wide range of metallicities
SO NATURE
LA English
DT Article
ID planetesimal formation; giant planets; host stars; mass; photoevaporation; candidates; parameters; lifetimes; search; system
AB The abundance of heavy elements (metallicity) in the photospheres of stars similar to the Sun provides a 'fossil' record of the chemical composition of the initial protoplanetary disk. Metal-rich stars are much more likely to harbour gas giant planets(1-4), supporting the model that planets form by accumulation of dust and ice particles(5). Recent ground-based surveys suggest that this correlation is weakened for Neptunian-sized planets(4,6-9). However, how the relationship between size and metallicity extends into the regime of terrestrial-sized exoplanets is unknown. Here we report spectroscopic metallicities of the host stars of 226 small exoplanet candidates discovered by NASA's Kepler mission(10), including objects that are comparable in size to the terrestrial planets in the Solar System. We find that planets with radii less than four Earth radii form around host stars with a wide range of metallicities (but on average a metallicity close to that of the Sun), whereas large planets preferentially form around stars with higher metallicities. This observation suggests that terrestrial planets may be widespread in the disk of the Galaxy, with no special requirement of enhanced metallicity for their formation.
C1 [Buchhave, Lars A.; Hansen, Terese] Univ Copenhagen, Niels Bohr Inst, DK-2100 Copenhagen, Denmark.
   [Buchhave, Lars A.; Bizzarro, Martin] Univ Copenhagen, Ctr Star & Planet Format, Nat Hist Museum Denmark, DK-1350 Copenhagen, Denmark.
   [Latham, David W.; Torres, Guillermo; Esquerdo, Gilbert A.; Geary, John C.; Stefanik, Robert P.; Quinn, Samuel N.] Harvard Smithsonian Ctr Astrophys, Cambridge, MA 02138 USA.
   [Johansen, Anders] Lund Univ, Lund Observ, S-22100 Lund, Sweden.
   [Rowe, Jason F.] NASA, SETI Inst, Ames Res Ctr, Moffett Field, CA 94035 USA.
   [Batalha, Natalie M.] San Jose State Univ, San Jose, CA 95192 USA.
   [Brugamyer, Erik; Caldwell, Caroline; Cochran, William D.; Endl, Michael; Robertson, Paul] Univ Texas Austin, Austin, TX 78712 USA.
   [Ciardi, David R.] CALTECH, NASA Exoplanet Sci Inst, Pasadena, CA 91109 USA.
   [Ford, Eric B.] Univ Florida, Bryant Space Sci Ctr 211, Gainesville, FL 32611 USA.
   [Gilliland, Ronald L.] Space Telescope Sci Inst, Baltimore, MD 21218 USA.
   [Isaacson, Howard; Marcy, Geoffrey W.] Univ Calif Berkeley, Berkeley, CA 94720 USA.
   [Laird, John B.] Bowling Green State Univ, Bowling Green, OH 43403 USA.
   [Lucas, Philip W.] Univ Hertfordshire, Ctr Astrophys, Hatfield AL10 9AB, Herts, England.
   [Morse, Jon A.] Rensselaer Polytech Inst, Dept Phys Appl Phys & Astron, Troy, NY 12180 USA.
   [Shporer, Avi] Las Cumbres Observ, Global Telescope Network, Goleta, CA 93117 USA.
   [Shporer, Avi] Univ Calif Santa Barbara, Dept Phys, Santa Barbara, CA 93106 USA.
   [Still, Martin] NASA, Bay Area Environm Res Inst, Ames Res Ctr, Moffett Field, CA 94035 USA.
C3 University of Copenhagen; Niels Bohr Institute; University of Copenhagen; Smithsonian Institution; Harvard University; Smithsonian Astrophysical Observatory; Lund University; SETI Institute; National Aeronautics & Space Administration (NASA); NASA Ames Research Center; California State University System; San Jose State University; University of Texas System; University of Texas Austin; National Aeronautics & Space Administration (NASA); California Institute of Technology; State University System of Florida; University of Florida; Space Telescope Science Institute; University of California System; University of California Berkeley; University System of Ohio; Bowling Green State University; University of Hertfordshire; Rensselaer Polytechnic Institute; University of California System; University of California Santa Barbara; National Aeronautics & Space Administration (NASA); NASA Ames Research Center
RP Buchhave, LA (corresponding author), Univ Copenhagen, Niels Bohr Inst, Blegdamsvej 17, DK-2100 Copenhagen, Denmark.
EM buchhave@astro.ku.dk
FU NASA's Science Mission Directorate; Danish National Research Foundation; Carlsberg Foundation; European Research Council under ERC Starting Grant agreement [278675-PEBBLE2PLANET]
NR 27
TC 579
Z9 640
U1 0
U2 36
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUN 21
PY 2012
VL 486
IS 7403
BP 375
EP 377
DI 10.1038/nature11121
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 961LV
UT WOS:000305466800037
PM 22722196
DA 2026-03-09
ER

PT J
AU Pietrzynski, G
   Thompson, IB
   Gieren, W
   Graczyk, D
   Stepien, K
   Bono, G
   Moroni, PGP
   Pilecki, B
   Udalski, A
   Soszynski, I
   Preston, GW
   Nardetto, N
   McWilliam, A
   Roederer, IU
   Górski, M
   Konorski, P
   Storm, J
AF Pietrzynski, G.
   Thompson, I. B.
   Gieren, W.
   Graczyk, D.
   Stepien, K.
   Bono, G.
   Moroni, P. G. Prada
   Pilecki, B.
   Udalski, A.
   Soszynski, I.
   Preston, G. W.
   Nardetto, N.
   McWilliam, A.
   Roederer, I. U.
   Gorski, M.
   Konorski, P.
   Storm, J.
TI RR-Lyrae-type pulsations from a 0.26-solar-mass star in a binary system
SO NATURE
LA English
DT Article
ID variables; contact; curves; light; mass
AB RR Lyrae pulsating stars have been extensively used as tracers of old stellar populations for the purpose of determining the ages of galaxies, and as tools to measure distances to nearby galaxies(1-3). There was accordingly considerable interest when the RR Lyrae star OGLE-BLG-RRLYR-02792 (referred to here as RRLYR-02792) was found to be a member of an eclipsing binary system(4), because the mass of the pulsator (hitherto constrained only by models) could be unambiguously determined. Here we report that RRLYR-02792 has a mass of 0.26 solar masses (M-circle dot) and therefore cannot be a classical RR Lyrae star. Using models, we find that its properties are best explained by the evolution of a close binary system that started with 1.4M(circle dot) and 0.8M(circle dot) stars orbiting each other with an initial period of 2.9 days. Mass exchange over 5.4 billion years produced the observed system, which is now in a very short-lived phase where the physical properties of the pulsator happen to place it in the same instability strip of the Hertzsprung-Russell diagram as that occupied by RR Lyrae stars. We estimate that only 0.2 per cent of RR Lyrae stars may be contaminated by systems similar to this one, which implies that distances measured with RR Lyrae stars should not be significantly affected by these binary interlopers.
C1 [Pietrzynski, G.; Gieren, W.; Graczyk, D.; Pilecki, B.; Gorski, M.; Konorski, P.] Univ Concepcion, Dept Astron, Concepcion, Chile.
   [Pietrzynski, G.; Stepien, K.; Pilecki, B.; Udalski, A.; Soszynski, I.; Gorski, M.; Konorski, P.] Univ Warsaw Observ, PL-00478 Warsaw, Poland.
   [Thompson, I. B.; Preston, G. W.; McWilliam, A.; Roederer, I. U.] Carnegie Observ, Pasadena, CA 91101 USA.
   [Bono, G.] Univ Roma Tor Vergata, Dipartimento Fis, I-00133 Rome, Italy.
   [Bono, G.] Osserv Astron Roma, INAF, I-00040 Monte Porzio Catone, Italy.
   [Moroni, P. G. Prada] Univ Pisa, Dipartimento Fis E Fermi, I-56127 Pisa, Italy.
   [Moroni, P. G. Prada] Ist Nazl Fis Nucl, Sez Pisa, I-56127 Pisa, Italy.
   [Nardetto, N.] UNS CNRS OCA, UMR7293, Lab Lagrange, F-06300 Nice, France.
   [Storm, J.] Leibniz Inst Astrophys, D-14482 Potsdam, Germany.
C3 Universidad de Concepcion; University of Warsaw; Warsaw University Observatory; Carnegie Institution for Science; University of Rome Tor Vergata; Istituto Nazionale Astrofisica (INAF); University of Pisa; Istituto Nazionale di Fisica Nucleare (INFN); 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); Leibniz Association; Leibniz Institut fur Astrophysik Potsdam (AIP)
RP Pietrzynski, G (corresponding author), Univ Concepcion, Dept Astron, Casilla 160-C, Concepcion, Chile.
EM pietrzyn@astrouw.edu.pl
FU Chilean Center for Astrophysics FONDAP; BASAL Centro de Astrofisica y Tecnologias Afines (CATA); NSF; Polish Ministry of Science (Ideas Plus); Foundation for Polish Science (FOCUS, TEAM); GEMINI-CONICYT; European Research Council; Las Campanas and ESO Paranal [287.D-5022(A)]
NR 16
TC 107
Z9 110
U1 0
U2 10
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 5
PY 2012
VL 484
IS 7392
BP 75
EP 77
DI 10.1038/nature10966
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 919QN
UT WOS:000302343400036
PM 22481359
DA 2026-03-09
ER

PT J
AU Halpern, BS
   Longo, C
   Hardy, D
   McLeod, KL
   Samhouri, JF
   Katona, SK
   Kleisner, K
   Lester, SE
   O'Leary, J
   Ranelletti, M
   Rosenberg, AA
   Scarborough, C
   Selig, ER
   Best, BD
   Brumbaugh, DR
   Chapin, FS
   Crowder, LB
   Daly, KL
   Doney, SC
   Elfes, C
   Fogarty, MJ
   Gaines, SD
   Jacobsen, KI
   Karrer, LB
   Leslie, HM
   Neeley, E
   Pauly, D
   Polasky, S
   Ris, B
   St Martin, K
   Stone, GS
   Sumaila, UR
   Zeller, D
AF Halpern, Benjamin S.
   Longo, Catherine
   Hardy, Darren
   McLeod, Karen L.
   Samhouri, Jameal F.
   Katona, Steven K.
   Kleisner, Kristin
   Lester, Sarah E.
   O'Leary, Jennifer
   Ranelletti, Marla
   Rosenberg, Andrew A.
   Scarborough, Courtney
   Selig, Elizabeth R.
   Best, Benjamin D.
   Brumbaugh, Daniel R.
   Chapin, F. Stuart
   Crowder, Larry B.
   Daly, Kendra L.
   Doney, Scott C.
   Elfes, Cristiane
   Fogarty, Michael J.
   Gaines, Steven D.
   Jacobsen, Kelsey I.
   Karrer, Leah Bunce
   Leslie, Heather M.
   Neeley, Elizabeth
   Pauly, Daniel
   Polasky, Stephen
   Ris, Bud
   St Martin, Kevin
   Stone, Gregory S.
   Sumaila, U. Rashid
   Zeller, Dirk
TI An index to assess the health and benefits of the global ocean
SO NATURE
LA English
DT Article
ID safe operating space; ecosystem health; indicators; framework; impacts
AB The ocean plays a critical role in supporting human well-being, from providing food, livelihoods and recreational opportunities to regulating the global climate. Sustainable management aimed at maintaining the flow of a broad range of benefits from the ocean requires a comprehensive and quantitative method to measure and monitor the health of coupled human-ocean systems. We created an index comprising ten diverse public goals for a healthy coupled human-ocean system and calculated the index for every coastal country. Globally, the overall index score was 60 out of 100 (range 36-86), with developed countries generally performing better than developing countries, but with notable exceptions. Only 5% of countries scored higher than 70, whereas 32% scored lower than 50. The index provides a powerful tool to raise public awareness, direct resource management, improve policy and prioritize scientific research.
C1 [Halpern, Benjamin S.; Longo, Catherine; Hardy, Darren; O'Leary, Jennifer; Ranelletti, Marla; Scarborough, Courtney] Natl Ctr Ecol Anal & Synth, Santa Barbara, CA 93101 USA.
   [Halpern, Benjamin S.] Univ Calif Santa Barbara, Ctr Marine Assessment & Planning, Santa Barbara, CA 93106 USA.
   [McLeod, Karen L.] Oregon State Univ, Dept Zool, COMPASS, Corvallis, OR 97331 USA.
   [Samhouri, Jameal F.] NOAA, Conservat Biol Div, NW Fisheries Sci Ctr, Natl Marine Fisheries Serv, Seattle, WA 98112 USA.
   [Katona, Steven K.; Rosenberg, Andrew A.; Selig, Elizabeth R.; Karrer, Leah Bunce; Stone, Gregory S.] Conservat Int, Arlington, VA 22202 USA.
   [Kleisner, Kristin; Pauly, Daniel; Sumaila, U. Rashid; Zeller, Dirk] Univ British Columbia, Fisheries Ctr, Sea Us Project, Vancouver, BC V6T 1Z4, Canada.
   [Lester, Sarah E.] Univ Calif Santa Barbara, Inst Marine Sci, Santa Barbara, CA 93106 USA.
   [Lester, Sarah E.; Gaines, Steven D.; Jacobsen, Kelsey I.] Univ Calif Santa Barbara, Bren Sch Environm Sci & Management, Santa Barbara, CA 93106 USA.
   [Best, Benjamin D.] Duke Univ, Nicholas Sch Environm, Durham, NC 27708 USA.
   [Brumbaugh, Daniel R.] Amer Museum Nat Hist, Ctr Biodivers & Conservat, New York, NY 10024 USA.
   [Chapin, F. Stuart] Univ Alaska Fairbanks, Inst Arctic Biol, Fairbanks, AK 99775 USA.
   [Crowder, Larry B.] Stanford Univ, Ctr Ocean Solut, Monterey, CA 93940 USA.
   [Crowder, Larry B.] Stanford Univ, Hopkins Marine Stn, Monterey, CA 93940 USA.
   [Daly, Kendra L.] Univ S Florida, Coll Marine Sci, St Petersburg, FL 33705 USA.
   [Doney, Scott C.] Woods Hole Oceanog Inst, Dept Marine Chem & Geochem, Woods Hole, MA 02543 USA.
   [Elfes, Cristiane] Univ Calif Santa Barbara, Dept Ecol Evolut & Marine Biol, Santa Barbara, CA 93106 USA.
   [Elfes, Cristiane] Conservat Int, IUCN Global Species Programme, Biodivers Assessment Unit, Arlington, VA 22202 USA.
   [Fogarty, Michael J.] NE Fisheries Sci Ctr, Woods Hole, MA 02453 USA.
   [Leslie, Heather M.] Brown Univ, Dept Ecol & Evolutionary Biol, Providence, RI 02912 USA.
   [Leslie, Heather M.] Brown Univ, Ctr Environm Studies, Providence, RI 02912 USA.
   [Neeley, Elizabeth] Univ Washington, Sch Aquat & Fisheries Sci, COMPASS, Seattle, WA 98195 USA.
   [Polasky, Stephen] Univ Minnesota, Dept Appl Econ, St Paul, MN 55108 USA.
   [Ris, Bud] New England Aquarium, Cent Wharf, Boston, MA 02110 USA.
   [St Martin, Kevin] Rutgers State Univ, Dept Geog, Piscataway, NJ 08854 USA.
C3 University of California System; University of California Santa Barbara; University of California System; University of California Santa Barbara; Oregon State University; National Oceanic Atmospheric Admin (NOAA) - USA; Conservation International; University of British Columbia; University of California System; University of California Santa Barbara; University of California System; University of California Santa Barbara; Duke University; American Museum of Natural History (AMNH); University of Alaska System; University of Alaska Fairbanks; Stanford University; Stanford University; State University System of Florida; University of South Florida; Woods Hole Oceanographic Institution; University of California System; University of California Santa Barbara; Conservation International; National Oceanic Atmospheric Admin (NOAA) - USA; Brown University; Brown University; University of Washington; University of Washington Seattle; University of Minnesota System; University of Minnesota Twin Cities; Rutgers University System; Rutgers University New Brunswick
RP Halpern, BS (corresponding author), Natl Ctr Ecol Anal & Synth, 735 State St,Suite 300, Santa Barbara, CA 93101 USA.
EM halpern@nceas.ucsb.edu
FU Pacific Life Foundation; Thomas W. Haas Fund of the New Hampshire Charitable Foundation; Oak Foundation; Akiko Shiraki Dynner Fund for Ocean Exploration and Conservation; Darden Restaurants Inc. Foundation; Conservation International; New England Aquarium; National Geographic; National Center for Ecological Analysis and Synthesis; David and Lucile Packard Foundation; Pew Charitable Trusts; Divn Of Social and Economic Sciences; Direct For Social, Behav & Economic Scie [0949710] Funding Source: National Science Foundation
NR 37
TC 734
Z9 868
U1 8
U2 750
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 30
PY 2012
VL 488
IS 7413
BP 615
EP +
DI 10.1038/nature11397
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 996NC
UT WOS:000308095100048
PM 22895186
DA 2026-03-09
ER

PT J
AU Berger, MF
   Hodis, E
   Heffernan, TP
   Deribe, YL
   Lawrence, MS
   Protopopov, A
   Ivanova, E
   Watson, IR
   Nickerson, E
   Ghosh, P
   Zhang, HL
   Zeid, R
   Ren, XJ
   Cibulskis, K
   Sivachenko, AY
   Wagle, N
   Sucker, A
   Sougnez, C
   Onofrio, R
   Ambrogio, L
   Auclair, D
   Fennell, T
   Carter, SL
   Drier, Y
   Stojanov, P
   Singer, MA
   Voet, D
   Jing, R
   Saksena, G
   Barretina, J
   Ramos, AH
   Pugh, TJ
   Stransky, N
   Parkin, M
   Winckler, W
   Mahan, S
   Ardlie, K
   Baldwin, J
   Wargo, J
   Schadendorf, D
   Meyerson, M
   Gabriel, SB
   Golub, TR
   Wagner, SN
   Lander, ES
   Getz, G
   Chin, L
   Garraway, LA
AF Berger, Michael F.
   Hodis, Eran
   Heffernan, Timothy P.
   Deribe, Yonathan Lissanu
   Lawrence, Michael S.
   Protopopov, Alexei
   Ivanova, Elena
   Watson, Ian R.
   Nickerson, Elizabeth
   Ghosh, Papia
   Zhang, Hailei
   Zeid, Rhamy
   Ren, Xiaojia
   Cibulskis, Kristian
   Sivachenko, Andrey Y.
   Wagle, Nikhil
   Sucker, Antje
   Sougnez, Carrie
   Onofrio, Robert
   Ambrogio, Lauren
   Auclair, Daniel
   Fennell, Timothy
   Carter, Scott L.
   Drier, Yotam
   Stojanov, Petar
   Singer, Meredith A.
   Voet, Douglas
   Jing, Rui
   Saksena, Gordon
   Barretina, Jordi
   Ramos, Alex H.
   Pugh, Trevor J.
   Stransky, Nicolas
   Parkin, Melissa
   Winckler, Wendy
   Mahan, Scott
   Ardlie, Kristin
   Baldwin, Jennifer
   Wargo, Jennifer
   Schadendorf, Dirk
   Meyerson, Matthew
   Gabriel, Stacey B.
   Golub, Todd R.
   Wagner, Stephan N.
   Lander, Eric S.
   Getz, Gad
   Chin, Lynda
   Garraway, Levi A.
TI Melanoma genome sequencing reveals frequent PREX2 mutations
SO NATURE
LA English
DT Article
ID human cancer; malignant-melanoma; somatic mutations; inhibition; patterns; braf; rearrangements; specificity; activation; survival
AB Melanoma is notable for its metastatic propensity, lethality in the advanced setting and association with ultraviolet exposure early in life(1). To obtain a comprehensive genomic view of melanoma in humans, we sequenced the genomes of 25 metastatic melanomas and matched germline DNA. A wide range of point mutation rates was observed: lowest in melanomas whose primaries arose on non-ultraviolet-exposed hairless skin of the extremities (3 and 14 per megabase (Mb) of genome), intermediate in those originating from hair-bearing skin of the trunk (5-55 per Mb), and highest in a patient with a documented history of chronic sun exposure (111 per Mb). Analysis of whole-genome sequence data identified PREX2 (phosphatidylinositol-3,4,5-trisphosphate-dependent Rac exchange factor 2)-a PTEN-interacting protein and negative regulator of PTEN in breast cancer(2)-as a significantly mutated gene with a mutation frequency of approximately 14% in an independent extension cohort of 107 human melanomas. PREX2 mutations are biologically relevant, as ectopic expression of mutant PREX2 accelerated tumour formation of immortalized human melanocytes in vivo. Thus, whole-genome sequencing of human melanoma tumours revealed genomic evidence of ultraviolet pathogenesis and discovered a new recurrently mutated gene in melanoma.
C1 [Berger, Michael F.; Hodis, Eran; Lawrence, Michael S.; Nickerson, Elizabeth; Cibulskis, Kristian; Sivachenko, Andrey Y.; Sougnez, Carrie; Onofrio, Robert; Ambrogio, Lauren; Auclair, Daniel; Fennell, Timothy; Carter, Scott L.; Stojanov, Petar; Voet, Douglas; Jing, Rui; Saksena, Gordon; Barretina, Jordi; Ramos, Alex H.; Pugh, Trevor J.; Stransky, Nicolas; Parkin, Melissa; Winckler, Wendy; Mahan, Scott; Ardlie, Kristin; Baldwin, Jennifer; Meyerson, Matthew; Gabriel, Stacey B.; Golub, Todd R.; Lander, Eric S.; Getz, Gad; Chin, Lynda; Garraway, Levi A.] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA.
   [Heffernan, Timothy P.; Deribe, Yonathan Lissanu; Protopopov, Alexei; Ivanova, Elena; Watson, Ian R.; Ghosh, Papia; Zhang, Hailei; Zeid, Rhamy; Ren, Xiaojia; Wagle, Nikhil; Singer, Meredith A.; Pugh, Trevor J.; Meyerson, Matthew; Chin, Lynda; Garraway, Levi A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
   [Wagle, Nikhil; Ramos, Alex H.; Pugh, Trevor J.; Meyerson, Matthew; Chin, Lynda; Garraway, Levi A.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
   [Sucker, Antje; Schadendorf, Dirk] Univ Hosp Essen, Dept Dermatol, D-45122 Essen, Germany.
   [Drier, Yotam] Weizmann Inst Sci, Dept Phys Complex Syst, IL-76100 Rehovot, Israel.
   [Wargo, Jennifer] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
   [Meyerson, Matthew; Golub, Todd R.; Garraway, Levi A.] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA.
   [Golub, Todd R.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
   [Golub, Todd R.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA.
   [Wagner, Stephan N.] Med Univ Vienna, Dept Dermatol, Div Immunol Allergy & Infect Dis, A-1090 Vienna, Austria.
   [Wagner, Stephan N.] Austrian Acad Sci, CeMM Res Ctr Mol Med, A-1090 Vienna, Austria.
   [Lander, Eric S.] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA.
C3 Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard Medical School; University of Duisburg Essen; Weizmann Institute of Science; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Howard Hughes Medical Institute; Medical University of Vienna; Austrian Academy of Sciences; CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences; Massachusetts Institute of Technology (MIT); Whitehead Institute
RP Chin, L (corresponding author), Univ Texas MD Anderson Canc Ctr, Inst Appl Canc Sci, Dept Genom Med, Houston, TX 77030 USA.
EM LChin@mdanderson.org; levi_garraway@dfci.harvard.edu
FU National Human Genome Research Institute; National Cancer Institute; FWF-Austrian Science Fund; NIH; Melanoma Research Alliance; Starr Cancer Consortium; Burroughs-Wellcome Fund; Austrian Science Fund (FWF) [L 590] Funding Source: researchfish; National Cancer Institute [T32CA009172] Funding Source: NIH RePORTER
NR 29
TC 584
Z9 699
U1 0
U2 79
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD MAY 24
PY 2012
VL 485
IS 7399
BP 502
EP 506
DI 10.1038/nature11071
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 946IH
UT WOS:000304344500043
PM 22622578
DA 2026-03-09
ER

PT J
AU Rohling, EJ
   Sluijs, A
   Dijkstra, HA
   Köhler, P
   de Wal, RSWV
   von der Heydt, AS
   Beerling, DJ
   Berger, A
   Bijl, PK
   Crucifix, M
   DeConto, R
   Drijfhout, SS
   Fedorov, A
   Foster, GL
   Ganopolski, A
   Hansen, J
   Hönisch, B
   Hooghiemstra, H
   Huber, M
   Huybers, P
   Knutti, R
   Lea, DW
   Lourens, LJ
   Lunt, D
   Masson-Demotte, V
   Medina-Elizalde, M
   Otto-Bliesner, B
   Pagani, M
   Pälike, H
   Renssen, H
   Royer, DL
   Siddall, M
   Valdes, P
   Zachos, JC
   Zeebe, RE
AF Rohling, E. J.
   Sluijs, A.
   Dijkstra, H. A.
   Koehler, P.
   de Wal, R. S. W. van
   von der Heydt, A. S.
   Beerling, D. J.
   Berger, A.
   Bijl, P. K.
   Crucifix, M.
   DeConto, R.
   Drijfhout, S. S.
   Fedorov, A.
   Foster, G. L.
   Ganopolski, A.
   Hansen, J.
   Hoenisch, B.
   Hooghiemstra, H.
   Huber, M.
   Huybers, P.
   Knutti, R.
   Lea, D. W.
   Lourens, L. J.
   Lunt, D.
   Masson-Demotte, V.
   Medina-Elizalde, M.
   Otto-Bliesner, B.
   Pagani, M.
   Paelike, H.
   Renssen, H.
   Royer, D. L.
   Siddall, M.
   Valdes, P.
   Zachos, J. C.
   Zeebe, R. E.
TI Making sense of palaeoclimate sensitivity
SO NATURE
LA English
DT Article
ID carbon-dioxide concentration; global climate sensitivity; eocene atmospheric co2; antarctic temperature; earths temperature; geological record; sea-level; future; model; constraints
AB Many palaeoclimate studies have quantified pre-anthropogenic climate change to calculate climate sensitivity (equilibrium temperature change in response to radiative forcing change), but a lack of consistent methodologies produces a wide range of estimates and hinders comparability of results. Here we present a stricter approach, to improve intercomparison of palaeoclimate sensitivity estimates in a manner compatible with equilibrium projections for future climatechange. Over the past 65 million years, this reveals a climate sensitivity (in KW-1 m(2)) of 0.3-1.9 or 0.6-1.3 at 95% or 68% probability, respectively. The latter implies a warming of 2.2-4.8 K per doubling of atmospheric CO2, which agrees with IPCC estimates.
C1 [Rohling, E. J.; Foster, G. L.] Univ Southampton, Sch Ocean & Earth Sci, Natl Oceanog Ctr, Southampton SO14 3ZH, Hants, England.
   [Rohling, E. J.] Australian Natl Univ, Res Sch Earth Sci, Canberra, ACT 0200, Australia.
   [Sluijs, A.; Bijl, P. K.; Lourens, L. J.] Univ Utrecht, Dept Earth Sci, Fac Geosci, NL-3584 CD Utrecht, Netherlands.
   [Dijkstra, H. A.; de Wal, R. S. W. van; von der Heydt, A. S.] Univ Utrecht, Inst Marine & Atmospher Res Utrecht, NL-3584 CC Utrecht, Netherlands.
   [Koehler, P.] Alfred Wegener Inst Polar & Marine Res AWI, D-27515 Bremerhaven, Germany.
   [Beerling, D. J.] Univ Sheffield, Dept Anim & Plant Sci, Sheffield S10 2TN, S Yorkshire, England.
   [Berger, A.; Crucifix, M.] Catholic Univ Louvain, Georges Lemaitre Ctr Earth & Climate Res, Earth & Life Inst, B-1348 Louvain, Belgium.
   [DeConto, R.] Univ Massachusetts, Dept Geosci, Morrill Sci Ctr 233, Amherst, MA 01003 USA.
   [Drijfhout, S. S.] Royal Netherlands Meteorol Inst, NL-3730 AE De Bilt, Netherlands.
   [Fedorov, A.] Yale Univ, Dept Geol & Geophys, New Haven, CT 06520 USA.
   [Ganopolski, A.] Potsdam Inst Climate Impact Res PIK, D-14412 Potsdam, Germany.
   [Hansen, J.] NASA, Goddard Inst Space Studies, New York, NY 10025 USA.
   [Hoenisch, B.] Columbia Univ, Lamont Doherty Earth Observ, Palisades, NY 10964 USA.
   [Hooghiemstra, H.] Univ Amsterdam, Inst Biodivers & Ecosyst Dynam, NL-1098 XH Amsterdam, Netherlands.
   [Huber, M.] Purdue Univ, Dept Earth & Atmospher Sci, W Lafayette, IN 47907 USA.
   [Huybers, P.] Harvard Univ, Dept Earth & Planetary Sci, Cambridge, MA 02138 USA.
   [Knutti, R.] ETH, Inst Atmospher andClimate Sci, CH-8092 Zurich, Switzerland.
   [Lea, D. W.] Univ Calif Santa Barbara, Dept Earth Sci, Santa Barbara, CA 93106 USA.
   [Lunt, D.; Valdes, P.] Univ Bristol, Sch Geog Sci, Bristol BS8 1SS, Avon, England.
   [Masson-Demotte, V.] LCEA Saclay, LSCE IPSL CEA CNRS UVSQ, UMR 8212, F-91191 Gif Sur Yvette, France.
   [Medina-Elizalde, M.] Ctr Invest Cient Yucatan, Unidad Ciencias Agua, Cancun 77500, Quintana Roo, Mexico.
   [Otto-Bliesner, B.] Natl Ctr Atmospher Res, Boulder, CO 80307 USA.
   [Paelike, H.] Univ Bremen, MARUM, D-28359 Bremen, Germany.
   [Renssen, H.] Free Univ Amsterdam, Dept Earth Sci, Fac Earth & Life Sci, NL-1081 HV Amsterdam, Netherlands.
   [Royer, D. L.] Wesleyan Univ, Dept Earth & Environm Sci, Middletown, CT 06459 USA.
   [Siddall, M.] Univ Bristol, Dept Earth Sci, Bristol BS8 1RJ, Avon, England.
   [Zeebe, R. E.] Univ Hawaii Manoa, Sch Ocean & Earth Sci & Technol, Dept Oceanog, Honolulu, HI 96822 USA.
C3 University of Southampton; NERC National Oceanography Centre; Australian National University; Utrecht University; Utrecht University; Helmholtz Association; Alfred Wegener Institute, Helmholtz Centre for Polar & Marine Research; University of Sheffield; Universite Catholique Louvain; University of Massachusetts System; University of Massachusetts Amherst; Royal Netherlands Meteorological Institute; Yale University; Potsdam Institut fur Klimafolgenforschung; National Aeronautics & Space Administration (NASA); NASA Goddard Space Flight Center; Goddard Institute for Space Studies; Columbia University; University of Amsterdam; Purdue University System; Purdue University; Harvard University; Swiss Federal Institutes of Technology Domain; ETH Zurich; University of California System; University of California Santa Barbara; University of Bristol; Universite Paris Saclay; CEA; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Earth Sciences & Astronomy (INSU); Centro de Investigacion Cientifica de Yucatan; National Center Atmospheric Research (NCAR) - USA; University of Bremen; Vrije Universiteit Amsterdam; Wesleyan University; University of Bristol; University of Hawaii System; University of Hawaii Manoa
RP Rohling, EJ (corresponding author), Univ Southampton, Sch Ocean & Earth Sci, Natl Oceanog Ctr, Southampton SO14 3ZH, Hants, England.
EM e.rohling@noc.soton.ac.uk
FU Royal Netherlands Academy of Arts and Sciences (KNAW); UK-NERC consortium iGlass [NE/I009906/1]; Australian Laureate Fellowship [FL120100050]; Royal Society Wolfson Research Merit Awards; European Research Council for ERC [259627]; NSF [0902882]; EU [243908]; European Research Council (ERC) [259627] Funding Source: European Research Council (ERC); NERC [NE/I005595/1, NE/I009906/1, NE/F003641/1] Funding Source: UKRI; Natural Environment Research Council [NE/I009906/1, NE/I005595/1, NE/F003641/1] Funding Source: researchfish; Directorate For Geosciences; Division Of Ocean Sciences [0902882] Funding Source: National Science Foundation; Division Of Earth Sciences; Directorate For Geosciences [1023724] Funding Source: National Science Foundation
NR 99
TC 243
Z9 268
U1 7
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 NOV 29
PY 2012
VL 491
IS 7426
BP 683
EP 691
DI 10.1038/nature11574
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 044FY
UT WOS:000311606000031
PM 23192145
DA 2026-03-09
ER

PT J
AU Rizo, H
   Boyet, M
   Blichert-Toft, J
   O'Neil, J
   Rosing, MT
   Paquette, JL
AF Rizo, Hanika
   Boyet, Maud
   Blichert-Toft, Janne
   O'Neil, Jonathan
   Rosing, Minik T.
   Paquette, Jean-Louis
TI The elusive Hadean enriched reservoir revealed by 142Nd deficits in Isua Archaean rocks
SO NATURE
LA English
DT Article
ID u-th-pb; early differentiation; isotopic evidence; west greenland; lu-hf; mantle; nd; constraints; systematics; earth
AB The first indisputable evidence for very early differentiation of the silicate Earth came from the extinct Sm-146-Nd-142 chronometer. Nd-142 excesses measured in 3.7-billion-year (Gyr)-old rocks from Isua(1,2) (southwest Greenland) relative to modern terrestrial samples imply their derivation from a depleted mantle formed in the Hadean eon (about 4,570-4,000 Gyr ago). As dictated by mass balance, the differentiation event responsible for the formation of the Isua early-depleted reservoir must also have formed a complementary enriched component. However, considerable efforts to find early-enriched mantle components in Isua have so far been unsuccessful(3-7). Here we show that the signature of the Hadean enriched reservoir, complementary to the depleted reservoir in Isua, is recorded in 3.4-Gyr-old mafic dykes intruding into the Early Archaean rocks. Five out of seven dykes carry Nd-142 deficits compared to the terrestrial Nd standard, with three samples yielding resolvable deficits down to -10.6 parts per million. The enriched component that we report here could have been a mantle reservoir that differentiated owing to the crystallization of a magma ocean, or could represent a mafic proto-crust that separated from the mantle more than 4.47 Gyr ago. Our results testify to the existence of an enriched component in the Hadean, and may suggest that the southwest Greenland mantle preserved early-formed heterogeneities until at least 3.4 Gyr ago.
C1 [Rizo, Hanika; Boyet, Maud; O'Neil, Jonathan; Paquette, Jean-Louis] Univ Blaise Pascal, Clermont Univ, Lab Magmas & Volcans, CNRS,UMR 6524,IRDR 163, F-63000 Clermont Ferrand, France.
   [Blichert-Toft, Janne] Ecole Normale Super Lyon, Lab Geol Lyon, F-69007 Lyon, France.
   [Blichert-Toft, Janne] Univ Lyon 1, CNRS, UMR 5276, F-69007 Lyon, France.
   [Rosing, Minik T.] Nat Hist Museum Denmark, DK-1350 Copenhagen, Denmark.
   [Rosing, Minik T.] Univ Copenhagen, Nord Ctr Earth Evolut, DK-1350 Copenhagen, Denmark.
C3 Universite Clermont Auvergne (UCA); 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); 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; University of Copenhagen
RP Rizo, H (corresponding author), Univ Blaise Pascal, Clermont Univ, Lab Magmas & Volcans, CNRS,UMR 6524,IRDR 163, BP 10448, F-63000 Clermont Ferrand, France.
EM h.rizo@opgc.univ-bpclermont.fr
FU European Research Council under the European Community's Seventh Framework Programme; French Programme National de Planetologie of the Institut National des Sciences de l'Univers and Centre National d'Etudes Spatiales; French Agence Nationale de la Recherche; French embassy in Denmark
NR 44
TC 97
Z9 109
U1 1
U2 104
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 1
PY 2012
VL 491
IS 7422
BP 96
EP U109
DI 10.1038/nature11565
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 028PM
UT WOS:000310434500037
PM 23128231
DA 2026-03-09
ER

PT J
AU Yang, J
   Loos, RJF
   Powell, JE
   Medland, SE
   Speliotes, EK
   Chasman, DI
   Rose, LM
   Thorleifsson, G
   Steinthorsdottir, V
   Maegi, R
   Waite, L
   Smith, AV
   Yerges-Armstrong, LM
   Monda, KL
   Hadley, D
   Mahajan, A
   Li, G
   Kapur, K
   Vitart, V
   Huffman, JE
   Wang, SR
   Palmer, C
   Esko, T
   Fischer, K
   Zhao, JH
   Demirkan, A
   Isaacs, A
   Feitosa, MF
   Luan, J
   Heard-Costa, NL
   White, C
   Jackson, AU
   Preuss, M
   Ziegler, A
   Eriksson, J
   Kutalik, Z
   Frau, F
   Nolte, IM
   Van Vliet-Ostaptchouk, JV
   Hottenga, JJ
   Jacobs, KB
   Verweij, N
   Goel, A
   Medina-Gomez, C
   Estrada, K
   Bragg-Gresham, JL
   Sanna, S
   Sidore, C
   Tyrer, J
   Teumer, A
   Prokopenko, I
   Mangino, M
   Lindgren, CM
   Assimes, TL
   Shuldiner, AR
   Hui, J
   Beilby, JP
   McArdle, WL
   Hall, P
   Haritunians, T
   Zgaga, L
   Kolcic, I
   Polasek, O
   Zemunik, T
   Oostra, BA
   Junttila, MJ
   Groenberg, H
   Schreiber, S
   Peters, A
   Hicks, AA
   Stephens, J
   Foad, NS
   Laitinen, J
   Pouta, A
   Kaakinen, M
   Willemsen, G
   Vink, JM
   Wild, SH
   Navis, G
   Asselbergs, FW
   Homuth, G
   John, U
   Iribarren, C
   Harris, T
   Launer, L
   Gudnason, V
   O'Connell, JR
   Boerwinkle, E
   Cadby, G
   Palmer, LJ
   James, AL
   Musk, AW
   Ingelsson, E
   Psaty, BM
   Beckmann, JS
   Waeber, G
   Vollenweider, P
   Hayward, C
   Wright, AF
   Rudan, I
   Groop, LC
   Metspalu, A
   Khaw, KT
   van Duijn, CM
   Borecki, IB
   Province, MA
   Wareham, NJ
   Tardif, JC
   Huikuri, HV
   Cupples, LA
   Atwood, LD
   Fox, CS
   Boehnke, M
   Collins, FS
   Mohlke, KL
   Erdmann, J
   Schunkert, H
   Hengstenberg, C
   Stark, K
   Lorentzon, M
   Ohlsson, C
   Cusi, D
   Staessen, JA
   Van der Klauw, MM
   Pramstaller, PP
   Kathiresan, S
   Jolley, JD
   Ripatti, S
   Jarvelin, MR
   de Geus, EJC
   Boomsma, DI
   Penninx, B
   Wilson, JF
   Campbell, H
   Chanock, SJ
   van der Harst, P
   Hamsten, A
   Watkins, H
   Hofman, A
   Witteman, JC
   Zillikens, MC
   Uitterlinden, AG
   Rivadeneira, F
   Zillikens, MC
   Kiemeney, LA
   Vermeulen, SH
   Abecasis, GR
   Schlessinger, D
   Schipf, S
   Stumvoll, M
   Toenjes, A
   Spector, TD
   North, KE
   Lettre, G
   McCarthy, MI
   Berndt, SI
   Heath, AC
   Madden, PAF
   Nyholt, DR
   Montgomery, GW
   Martin, NG
   McKnight, B
   Strachan, DP
   Hill, WG
   Snieder, H
   Ridker, PM
   Thorsteinsdottir, U
   Stefansson, K
   Frayling, TM
   Hirschhorn, JN
   Goddard, ME
   Visscher, PM
AF Yang, Jian
   Loos, Ruth J. F.
   Powell, Joseph E.
   Medland, Sarah E.
   Speliotes, Elizabeth K.
   Chasman, Daniel I.
   Rose, Lynda M.
   Thorleifsson, Gudmar
   Steinthorsdottir, Valgerdur
   Maegi, Reedik
   Waite, Lindsay
   Smith, Albert Vernon
   Yerges-Armstrong, Laura M.
   Monda, Keri L.
   Hadley, David
   Mahajan, Anubha
   Li, Guo
   Kapur, Karen
   Vitart, Veronique
   Huffman, Jennifer E.
   Wang, Sophie R.
   Palmer, Cameron
   Esko, Toenu
   Fischer, Krista
   Zhao, Jing Hua
   Demirkan, Ayse
   Isaacs, Aaron
   Feitosa, Mary F.
   Luan, Jian'an
   Heard-Costa, Nancy L.
   White, Charles
   Jackson, Anne U.
   Preuss, Michael
   Ziegler, Andreas
   Eriksson, Joel
   Kutalik, Zoltan
   Frau, Francesca
   Nolte, Ilja M.
   Van Vliet-Ostaptchouk, Jana V.
   Hottenga, Jouke-Jan
   Jacobs, Kevin B.
   Verweij, Niek
   Goel, Anuj
   Medina-Gomez, Carolina
   Estrada, Karol
   Bragg-Gresham, Jennifer Lynn
   Sanna, Serena
   Sidore, Carlo
   Tyrer, Jonathan
   Teumer, Alexander
   Prokopenko, Inga
   Mangino, Massimo
   Lindgren, Cecilia M.
   Assimes, Themistocles L.
   Shuldiner, Alan R.
   Hui, Jennie
   Beilby, John P.
   McArdle, Wendy L.
   Hall, Per
   Haritunians, Talin
   Zgaga, Lina
   Kolcic, Ivana
   Polasek, Ozren
   Zemunik, Tatijana
   Oostra, Ben A.
   Junttila, M. Juhani
   Groenberg, Henrik
   Schreiber, Stefan
   Peters, Annette
   Hicks, Andrew A.
   Stephens, Jonathan
   Foad, Nicola S.
   Laitinen, Jaana
   Pouta, Anneli
   Kaakinen, Marika
   Willemsen, Gonneke
   Vink, Jacqueline M.
   Wild, Sarah H.
   Navis, Gerjan
   Asselbergs, Folkert W.
   Homuth, Georg
   John, Ulrich
   Iribarren, Carlos
   Harris, Tamara
   Launer, Lenore
   Gudnason, Vilmundur
   O'Connell, Jeffrey R.
   Boerwinkle, Eric
   Cadby, Gemma
   Palmer, Lyle J.
   James, Alan L.
   Musk, Arthur W.
   Ingelsson, Erik
   Psaty, Bruce M.
   Beckmann, Jacques S.
   Waeber, Gerard
   Vollenweider, Peter
   Hayward, Caroline
   Wright, Alan F.
   Rudan, Igor
   Groop, Leif C.
   Metspalu, Andres
   Khaw, Kay Tee
   van Duijn, Cornelia M.
   Borecki, Ingrid B.
   Province, Michael A.
   Wareham, Nicholas J.
   Tardif, Jean-Claude
   Huikuri, Heikki V.
   Cupples, L. Adrienne
   Atwood, Larry D.
   Fox, Caroline S.
   Boehnke, Michael
   Collins, Francis S.
   Mohlke, Karen L.
   Erdmann, Jeanette
   Schunkert, Heribert
   Hengstenberg, Christian
   Stark, Klaus
   Lorentzon, Mattias
   Ohlsson, Claes
   Cusi, Daniele
   Staessen, Jan A.
   Van der Klauw, Melanie M.
   Pramstaller, Peter P.
   Kathiresan, Sekar
   Jolley, Jennifer D.
   Ripatti, Samuli
   Jarvelin, Marjo-Riitta
   de Geus, Eco J. C.
   Boomsma, Dorret I.
   Penninx, Brenda
   Wilson, James F.
   Campbell, Harry
   Chanock, Stephen J.
   van der Harst, Pim
   Hamsten, Anders
   Watkins, Hugh
   Hofman, Albert
   Witteman, Jacqueline C.
   Zillikens, M. Carola
   Uitterlinden, Andre G.
   Rivadeneira, Fernando
   Zillikens, M. Carola
   Kiemeney, Lambertus A.
   Vermeulen, Sita H.
   Abecasis, Goncalo R.
   Schlessinger, David
   Schipf, Sabine
   Stumvoll, Michael
   Toenjes, Anke
   Spector, Tim D.
   North, Kari E.
   Lettre, Guillaume
   McCarthy, Mark I.
   Berndt, Sonja I.
   Heath, Andrew C.
   Madden, Pamela A. F.
   Nyholt, Dale R.
   Montgomery, Grant W.
   Martin, Nicholas G.
   McKnight, Barbara
   Strachan, David P.
   Hill, William G.
   Snieder, Harold
   Ridker, Paul M.
   Thorsteinsdottir, Unnur
   Stefansson, Kari
   Frayling, Timothy M.
   Hirschhorn, Joel N.
   Goddard, Michael E.
   Visscher, Peter M.
TI FTO genotype is associated with phenotypic variability of body mass index
SO NATURE
LA English
DT Article
ID genome-wide association; environmental sensitivity; physical-activity; genetic-variation; adult obesity; loci; variants; childhood; selection; traits
AB There is evidence across several species for genetic control of phenotypic variation of complex traits(1-4), such that the variance among phenotypes is genotype dependent. Understanding genetic control of variability is important in evolutionary biology, agricultural selection programmes and human medicine, yet for complex traits, no individual genetic variants associated with variance, as opposed to the mean, have been identified. Here we perform a meta-analysis of genome-wide association studies of phenotypic variation using similar to 170,000 samples on height and body mass index (BMI) in human populations. We report evidence that the single nucleotide polymorphism (SNP) rs7202116 at the FTO gene locus, which is known to be associated with obesity (as measured by mean BMI for each rs7202116 genotype)(5-7), is also associated with phenotypic variability. We show that the results are not due to scale effects or other artefacts, and find no other experiment-wise significant evidence for effects on variability, either at loci other than FTO for BMI or at any locus for height. The difference in variance for BMI among individuals with opposite homozygous genotypes at the FTO locus is approximately 7%, corresponding to a difference of similar to 0.5 kilograms in the standard deviation of weight. Our results indicate that genetic variants can be discovered that are associated with variability, and that between-person variability in obesity can partly be explained by the genotype at the FTO locus. The results are consistent with reported FTO by environment interactions for BMI8, possibly mediated by DNA methylation(9,10). Our BMI results for other SNPs and our height results for all SNPs suggest that most genetic variants, including those that influence mean height or mean BMI, are not associated with phenotypic variance, or that their effects on variability are too small to detect even with samples sizes greater than 100,000.
C1 [Yang, Jian; Powell, Joseph E.] Univ Queensland, Diamantina Inst, Princess Alexandra Hosp, Brisbane, Qld 4102, Australia.
   [Yang, Jian; Powell, Joseph E.; Medland, Sarah E.; Nyholt, Dale R.; Montgomery, Grant W.; Martin, Nicholas G.] Queensland Inst Med Res, Brisbane, Qld 4006, Australia.
   [Loos, Ruth J. F.; Zhao, Jing Hua; Luan, Jian'an; Wareham, Nicholas J.] Inst Metab Sci, MRC Epidemiol Unit, Cambridge CB2 0QQ, England.
   [Loos, Ruth J. F.] Mt Sinai Sch Med, New York, NY 10029 USA.
   [Speliotes, Elizabeth K.] Univ Michigan, Dept Internal Med, Div Gastroenterol, Ann Arbor, MI 48109 USA.
   [Speliotes, Elizabeth K.] Univ Michigan, Ctr Computat Med & Bioinformat, Ann Arbor, MI 48109 USA.
   [Chasman, Daniel I.; Rose, Lynda M.; Ridker, Paul M.] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02215 USA.
   [Chasman, Daniel I.] Harvard Univ, Sch Med, Boston, MA 02215 USA.
   [Thorleifsson, Gudmar; Steinthorsdottir, Valgerdur] deCODE Genet, IS-101 Reykjavik, Iceland.
   [Maegi, Reedik; Esko, Toenu; Fischer, Krista; Metspalu, Andres] Univ Tartu, Estonian Genome Ctr, EE-50410 Tartu, Estonia.
   [Maegi, Reedik; Mahajan, Anubha; Lindgren, Cecilia M.; Watkins, Hugh] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.
   [Waite, Lindsay; Frayling, Timothy M.] Hudson Alpha Inst Biotechnol, Huntsville, AL 35806 USA.
   [Smith, Albert Vernon; Gudnason, Vilmundur] Iceland Heart Assoc, IS-201 Kopavogur, Iceland.
   [Smith, Albert Vernon] Univ Iceland, IS-101 Reykjavik, Iceland.
   [Yerges-Armstrong, Laura M.; O'Connell, Jeffrey R.] Univ Maryland, Dept Med, Sch Med, Baltimore, MD 21201 USA.
   [Monda, Keri L.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27514 USA.
   [Hadley, David; Strachan, David P.] Univ London, Div Populat Hlth Sci & Educ, London SW17 0RE, England.
   [Li, Guo] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98101 USA.
   [Kapur, Karen; Kutalik, Zoltan; Jacobs, Kevin B.] Univ Lausanne, Dept Med Genet, CH-1005 Lausanne, Switzerland.
   [Kapur, Karen; Kutalik, Zoltan; Jacobs, Kevin B.] Swiss Inst Bioinformat, CH-1005 Lausanne, Switzerland.
   [Vitart, Veronique; Huffman, Jennifer E.; Hayward, Caroline; Wright, Alan F.] Univ Edinburgh, MRC HGU, MRC IGMM, Edinburgh EH8 9AG, Midlothian, Scotland.
   [Wang, Sophie R.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
   [Wang, Sophie R.; Palmer, Cameron] Childrens Hosp, Div Genet, Boston, MA 02115 USA.
   [Wang, Sophie R.; Palmer, Cameron] Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA.
   [Wang, Sophie R.; Palmer, Cameron] Childrens Hosp, Program Genom, Boston, MA 02115 USA.
   [Wang, Sophie R.; Palmer, Cameron; Hirschhorn, Joel N.] Broad Inst, Metab Initiat, Cambridge, MA 02142 USA.
   [Wang, Sophie R.; Palmer, Cameron; Hirschhorn, Joel N.] Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA.
   [Demirkan, Ayse; Isaacs, Aaron; Oostra, Ben A.; van Duijn, Cornelia M.] Erasmus MC, Dept Epidemiol, Subdiv Genet Epidemiol, Rotterdam, Netherlands.
   [Feitosa, Mary F.] Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA.
   [Jackson, Anne U.; Boehnke, Michael] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.
   [Preuss, Michael] Med Univ Lubeck, Med Klin 2, D-23538 Lubeck, Germany.
   [Preuss, Michael; Ziegler, Andreas; Van Vliet-Ostaptchouk, Jana V.] Med Univ Lubeck, Inst Med Biometrie & Stat, D-23562 Lubeck, Germany.
   [Eriksson, Joel; Hottenga, Jouke-Jan; Lorentzon, Mattias; Ohlsson, Claes] Univ Gothenburg, Ctr Bone & Arthrit Res, Inst Med, Sahlgrenska Acad, S-41345 Gothenburg, Sweden.
   [Frau, Francesca; Verweij, Niek; Cusi, Daniele] Univ Milan, Dept Hlth Sci, I-20133 Milan, Italy.
   [Nolte, Ilja M.; Goel, Anuj; Snieder, Harold] Univ Groningen, Unit Genet Epidemiol & Bioinformat, Dept Epidemiol, Univ Med Ctr Groningen, NL-9700 RB Groningen, Netherlands.
   [Medina-Gomez, Carolina; Van der Klauw, Melanie M.] Univ Groningen, Dept Endocrinol, Univ Med Ctr Groningen, NL-9700 RB Groningen, Netherlands.
   [Medina-Gomez, Carolina] Univ Groningen, LifeLines Cohort Study, Univ Med Ctr Groningen, NL-9700 RB Groningen, Netherlands.
   [Estrada, Karol; Kaakinen, Marika; Willemsen, Gonneke; Vink, Jacqueline M.; de Geus, Eco J. C.; Boomsma, Dorret I.] Vrije Univ Amsterdam, Dept Biol Psychol, NL-1081 BT Amsterdam, Netherlands.
   [Bragg-Gresham, Jennifer Lynn] SAIC Frederick Inc, Core Genotyping Facil, NCI Frederick, Frederick, MD 21702 USA.
   [van der Harst, Pim] Univ Groningen, Dept Cardiol, Univ Med Ctr Groningen, NL-9700 RB Groningen, Netherlands.
   [Zillikens, M. Carola] Erasmus MC, Dept Internal Med, NL-3015 GE Rotterdam, Netherlands.
   [Hofman, Albert; Uitterlinden, Andre G.] Erasmus MC, Dept Epidemiol, NL-3015 GE Rotterdam, Netherlands.
   [Witteman, Jacqueline C.; Rivadeneira, Fernando] Netherlands Consortiumfor Healthy Aging, Netherlands Genom Initiat, NL-2300 RC Leiden, Netherlands.
   [Sanna, Serena; Abecasis, Goncalo R.] Univ Michigan, Biostat Ctr Stat Genet, Ann Arbor, MI 48109 USA.
   [Sidore, Carlo] CNR, Ist Ric Genet & Biomed, I-09042 Monserrato, Italy.
   [Sidore, Carlo] Univ Sassari, Dipartimento Sci Biomed, I-07100 Sassari, Italy.
   [Tyrer, Jonathan] Univ Cambridge, Dept Oncol, Cambridge CB1 8RN, England.
   [Teumer, Alexander; Homuth, Georg] Univ Med Greifswald, Interfac Inst Genet & Funct Genom, D-17487 Greifswald, Germany.
   [Prokopenko, Inga] Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford OX3 7BN, England.
   [Mangino, Massimo; Toenjes, Anke] Kings Coll London, Dept Twin Res & Genet Epidemiol, London SE1 7EH, England.
   [Assimes, Themistocles L.] Stanford Univ, Dept Med, Sch Med, Stanford, CA 94305 USA.
   [Shuldiner, Alan R.] Vet Adm Med Ctr, Geriatr Res & Educ Clin Ctr, Baltimore, MD 21201 USA.
   [Hui, Jennie; Beilby, John P.] Univ Western Australia, PathWest Lab Med WA, Nedlands, WA 6009, Australia.
   [Hui, Jennie] Univ Western Australia, Sch Populat Hlth, Nedlands, WA 6009, Australia.
   [McArdle, Wendy L.] Univ Bristol, Sch Social & Community Med, Bristol BS8 2BN, Avon, England.
   [Hall, Per; Groenberg, Henrik; Ingelsson, Erik] Karolinska Inst, Dept Med Epidemiol & Biostat, SE-17177 Stockholm, Sweden.
   [Haritunians, Talin] Cedars Sinai Med Ctr, Med Genet Inst, Los Angeles, CA 90048 USA.
   [Zgaga, Lina; Wild, Sarah H.; Rudan, Igor; Wilson, James F.; Campbell, Harry] Univ Edinburgh, Ctr Populat Hlth Sci, Sch Med, Edinburgh EH16 4TJ, Midlothian, Scotland.
   [Zgaga, Lina] Univ Zagreb, Sch Med, Andrija Stampar Sch Publ Hlth, Zagreb 41001, Croatia.
   [Kolcic, Ivana; Polasek, Ozren; Zemunik, Tatijana] Univ Split, Fac Med, Split 21000, Croatia.
   [Junttila, M. Juhani; Huikuri, Heikki V.] Univ Oulu, Dept Internal Med, Inst Clin Med, Oulu 90014, Finland.
   [Peters, Annette] Univ Kiel, Inst Klin Mol Biol, D-24098 Kiel, Germany.
   [Peters, Annette] Munich Heart Alliance, D-80802 Munich, Germany.
   [Hicks, Andrew A.] European Acad Bozen Bolzano EURAC, Ctr Biomed, I-39100 Bolzano, Italy.
   [Stephens, Jonathan] Univ Cambridge, Dept Haematol, Cambridge CB2 0PT, England.
   [Stephens, Jonathan; Jolley, Jennifer D.] NHS Blood & Transplant, Cambridge CB2 0PT, England.
   [Foad, Nicola S.] Finnish Inst Occupat Hlth, Oulu 90220, Finland.
   [Laitinen, Jaana] Natl Inst Hlth & Welf, Oulu 90101, Finland.
   [Laitinen, Jaana] Univ Oulu, Dept Clin Sci Obstet & Gynecol, Oulu 90014, Finland.
   [Pouta, Anneli] Univ Oulu, Inst Hlth Sci, Bioctr, Oulu 90014, Finland.
   [Navis, Gerjan] Univ Groningen, Dept Internal Med, Univ Med Ctr Groningen, NL-9700 RB Groningen, Netherlands.
   [Asselbergs, Folkert W.] Univ Med Ctr Utrecht, Dept Cardiol, Div Heart & Lungs, NL-3508 GA Utrecht, Netherlands.
   [John, Ulrich] Univ Med Greifswald, Inst Epidemiol & Social Med, D-17475 Greifswald, Germany.
   [Iribarren, Carlos] Kaiser Permanente No Calif, Div Res, Oakland, CA 94612 USA.
   [Harris, Tamara; Launer, Lenore] NIA, NIH, Bethesda, MD 20892 USA.
   [Boerwinkle, Eric] Univ Texas Houston, Hlth Sci Ctr, Houston, TX 77030 USA.
   [Cadby, Gemma; Palmer, Lyle J.] Ontario Inst Canc Res, Toronto, ON M5G 1L7, Canada.
   [James, Alan L.; Musk, Arthur W.] Univ Western Australia, Sir Charles Gairdner Hosp, Nedlands, WA 6009, Australia.
   [Psaty, Bruce M.] Univ Washington, Cardiovasc Hlth Res Unit, Dept Med, Seattle, WA 98101 USA.
   [Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Seattle, WA 98101 USA.
   [Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98101 USA.
   [Psaty, Bruce M.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA 98101 USA.
   [Beckmann, Jacques S.] CHUV Univ Hosp, Serv Med Genet, CH-1011 Lausanne, Switzerland.
   [Waeber, Gerard; Vollenweider, Peter] Univ Lausanne Hosp, Dept Internal Med, CH-1011 Lausanne, Switzerland.
   [Groop, Leif C.] Lund Univ, Ctr Diabet, Dept Clin Sci, S-20502 Malmo, Sweden.
   [Khaw, Kay Tee] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge CB1 8RN, England.
   [Borecki, Ingrid B.; Province, Michael A.] Washington Univ, Sch Med, Div Biostat, St Louis, MO 63110 USA.
   [Tardif, Jean-Claude] Univ Montreal, Dept Med, Montreal, PQ H4J 1C5, Canada.
   [Tardif, Jean-Claude; Lettre, Guillaume] Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada.
   [Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA.
   [Fox, Caroline S.] Boston Univ, Framingham, MA 01702 USA.
   [Collins, Francis S.] NHGRI, NIH, Bethesda, MD 20892 USA.
   [Mohlke, Karen L.] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA.
   [Erdmann, Jeanette; Schunkert, Heribert] Med Univ Lubeck, Deutsch Zentrum Herz Kreislauf Forsch DZHK, D-23562 Lubeck, Germany.
   [Hengstenberg, Christian; Stark, Klaus] Klin & Poliklin Innere Med II, D-93053 Regensburg, Germany.
   [Staessen, Jan A.] Katholieke Univ Leuven, Dept Cardiovasc Dis, B-3000 Louvain, Belgium.
   [Cupples, L. Adrienne; Staessen, Jan A.] Maastricht Univ, Dept Epidemiol, NL-6200 MD Maastricht, Netherlands.
   [Pramstaller, Peter P.] European Acad Bozen Bolzano EURAC, Ctr Biomed, I-39100 Bolzano, Italy.
   [Pramstaller, Peter P.] Gen Cent Hosp, Dept Neurol, I-39100 Bolzano, Italy.
   [Pramstaller, Peter P.] Med Univ Lubeck, Dept Neurol, D-23562 Lubeck, Germany.
   [Kathiresan, Sekar] Broad Inst Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA.
   [Kathiresan, Sekar] MIT, Cambridge, MA 02142 USA.
   [Kathiresan, Sekar] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
   [Kathiresan, Sekar] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.
   [Kathiresan, Sekar] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
   [Kathiresan, Sekar] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.
   [Ripatti, Samuli] Univ Helsinki, Inst Mol Med Finland, FIMM, FIN-00014 Helsinki, Finland.
   [Ripatti, Samuli] Natl Inst Hlth & Welf, Publ Hlth Genom Unit, Helsinki 00271, Finland.
   [Ripatti, Samuli] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England.
   [Jarvelin, Marjo-Riitta] Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Biostat, MRC HPA Ctr Environm & Hlth, London W2 1PG, England.
   [Penninx, Brenda] Univ Groningen, Dept Psychiat, Univ Med Ctr Groningen, NL-9713 GZ Groningen, Netherlands.
   [Chanock, Stephen J.; Berndt, Sonja I.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20852 USA.
   [Hamsten, Anders] Karolinska Inst, S-17177 Stockholm, Sweden.
   [Hamsten, Anders] Dept Med, Atherosclerosis Res Unit, S-17176 Stockholm, Sweden.
   [Kiemeney, Lambertus A.; Vermeulen, Sita H.] Radboud Univ Nijmegen, Med Ctr, NL-6500 HB Nijmegen, Netherlands.
   [Schlessinger, David] NIA, NIH, Bethesda, MD 20892 USA.
   [Schipf, Sabine] Univ Med Greifswald, Inst Community Med, D-17475 Greifswald, Germany.
   [Stumvoll, Michael] Univ Leipzig, Dept Med, D-04103 Leipzig, Germany.
   [Stumvoll, Michael] Univ Leipzig, IFB Adipos Dis, D-04103 Leipzig, Germany.
   [Spector, Tim D.; North, Kari E.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27514 USA.
   [Spector, Tim D.; North, Kari E.] Univ N Carolina, Carolina Ctr Genome Sci, Chapel Hill, NC 27514 USA.
   [McCarthy, Mark I.] Churchill Hosp, Oxford Natl Inst Hlth Res, Biomed Res Ctr, Oxford OX3 7LJ, England.
   [Heath, Andrew C.; Madden, Pamela A. F.] Washington Univ, Dept Psychiat, St Louis, MO 63110 USA.
   [McKnight, Barbara] Washington Univ, Dept Biostat, St Louis, MO 63110 USA.
   [Hill, William G.] Univ Edinburgh, Inst Evolutionary Biol, Edinburgh EH9 3JT, Midlothian, Scotland.
   [Thorsteinsdottir, Unnur; Stefansson, Kari] Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland.
   [Frayling, Timothy M.] Univ Exeter, Inst Biomed & Clin Sci, Peninsula Med Sch, Exeter EX1 2LU, Devon, England.
   [Goddard, Michael E.] Univ Melbourne, Dept Food & Agr Syst, Melbourne, Vic 3010, Australia.
   [Goddard, Michael E.] Dept Primary Ind, Biosci Res Div, Bundoora, Vic 3083, Australia.
   [Visscher, Peter M.] Univ Queensland, Queensland Brain Inst, Brisbane, Qld 4072, Australia.
C3 Princess Alexandra Hospital; University of Queensland; QIMR Berghofer Medical Research Institute; University of Cambridge; Icahn School of Medicine at Mount Sinai; University of Michigan System; University of Michigan; University of Michigan System; University of Michigan; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard University; Harvard Medical School; Decode Genetics; University of Tartu; University of Oxford; Wellcome Centre for Human Genetics; Icelandic Heart Association; University of Iceland; University System of Maryland; University of Maryland Baltimore; University of North Carolina; University of North Carolina Chapel Hill; University of London; University of Washington; University of Washington Seattle; University of Lausanne; Swiss Institute of Bioinformatics; University of Edinburgh; Harvard University; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Erasmus University Rotterdam; Erasmus MC; Washington University (WUSTL); University of Michigan System; University of Michigan; University of Lubeck; University of Lubeck; University of Gothenburg; University of Milan; University of Groningen; University of Groningen; University of Groningen; Vrije Universiteit Amsterdam; Science Applications International Corporation (SAIC); SAIC-Frederick; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); University of Groningen; Erasmus University Rotterdam; Erasmus MC; Erasmus University Rotterdam; Erasmus MC; University of Michigan System; University of Michigan; Consiglio Nazionale delle Ricerche (CNR); Istituto di Ricerca Genetica e Biomedica (IRGB-CNR); University of Sassari; University of Cambridge; Universitat Greifswald; Greifswald Medical School; University of Oxford; University of London; King's College London; Stanford University; Geriatric Research Education & Clinical Center; US Department of Veterans Affairs; Veterans Health Administration (VHA); University of Western Australia; University of Western Australia; University of Bristol; Karolinska Institutet; Cedars Sinai Medical Center; University of Edinburgh; University of Zagreb; University of Split; University of Oulu; University of Kiel; Munich Heart Alliance; European Academy of Bozen-Bolzano; University of Cambridge; Finnish Institute of Occupational Health; Finland National Institute for Health & Welfare; University of Oulu; University of Oulu; University of Groningen; Utrecht University; Utrecht University Medical Center; Universitat Greifswald; Greifswald Medical School; Kaiser Permanente; National Institutes of Health (NIH) - USA; NIH National Institute on Aging (NIA); University of Texas System; University of Texas Health Science Center Houston; University of Toronto; Ontario Institute for Cancer Research; Sir Charles Gairdner Hospital; University of Western Australia; University of Washington; University of Washington Seattle; University of Washington; University of Washington Seattle; University of Washington; University of Washington Seattle; Group Health Cooperative; University of Lausanne; Centre Hospitalier Universitaire Vaudois (CHUV); University of Lausanne; Centre Hospitalier Universitaire Vaudois (CHUV); Lund University; University of Cambridge; Washington University (WUSTL); Universite de Montreal; Universite de Montreal; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI); Framingham Heart Study; Boston University; National Institutes of Health (NIH) - USA; NIH National Human Genome Research Institute (NHGRI); University of North Carolina; University of North Carolina Chapel Hill; University of Lubeck; German Centre for Cardiovascular Research; KU Leuven; Maastricht University; European Academy of Bozen-Bolzano; Krankenhaus Bozen; University of Lubeck; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Massachusetts Institute of Technology (MIT); Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard Medical School; University of Helsinki; Finland National Institute for Health & Welfare; Wellcome Trust Sanger Institute; Imperial College London; University of Groningen; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); NIH National Cancer Institute- Division of Cancer Epidemiology & Genetics; Karolinska Institutet; Radboud University Nijmegen; National Institutes of Health (NIH) - USA; NIH National Institute on Aging (NIA); Universitat Greifswald; Greifswald Medical School; Leipzig University; Leipzig University; University of North Carolina; University of North Carolina Chapel Hill; University of North Carolina; University of North Carolina Chapel Hill; University of Oxford; Washington University (WUSTL); Washington University (WUSTL); University of Edinburgh; University of Iceland; University of Exeter; University of Melbourne; Department of Primary Industries & Regional Development NSW; University of Queensland
RP Yang, J (corresponding author), Univ Queensland, Diamantina Inst, Princess Alexandra Hosp, Brisbane, Qld 4102, Australia.
FU Australian National Health and Medical Research Council (NHMRC) [241944, 389875, 389891, 389892, 389938, 442915, 442981, 496739, 496688, 552485, 613672, 613601, 1011506]; US National Institutes of Health [AA07535, AA10248, AA014041, AA13320, AA13321, AA13326, DA12854, GM057091]; Australian Research Council (ARC) [DP1093502]; MRC [MC_U127561128, MC_PC_U127561128, G0601261] Funding Source: UKRI; Cancer Research UK [14136] Funding Source: researchfish; Chief Scientist Office [CZB/4/710] Funding Source: researchfish; Medical Research Council [G0601261, G0401527, MC_PC_U127561128, MC_U106179471, G0801056B, G1000143, MC_U127561128] Funding Source: researchfish; National Heart Lung and Blood Institute [R01HL059367, R01HL086694, R01HL105756] Funding Source: NIH RePORTER; National Human Genome Research Institute [ZIAHG000024] Funding Source: NIH RePORTER; National Institute of Diabetes and Digestive and Kidney Diseases [R01DK075787, P30DK020572, R01DK062370, R01DK072193, P30DK063491] Funding Source: NIH RePORTER; National Institute on Aging [ZIAAG000675] Funding Source: NIH RePORTER; National Library of Medicine [R01LM010098] Funding Source: NIH RePORTER
NR 36
TC 325
Z9 372
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 OCT 11
PY 2012
VL 490
IS 7419
BP 267
EP +
DI 10.1038/nature11401
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 019IY
UT WOS:000309733300051
PM 22982992
DA 2026-03-09
ER

PT J
AU Gregory, AP
   Dendrou, CA
   Attfield, KE
   Haghikia, A
   Xifara, DK
   Butter, F
   Poschmann, G
   Kaur, G
   Lambert, L
   Leach, OA
   Prömel, S
   Punwani, D
   Felce, JH
   Davis, SJ
   Gold, R
   Nielsen, FC
   Siegel, RM
   Mann, M
   Bell, JI
   McVean, G
   Fugger, L
AF Gregory, Adam P.
   Dendrou, Calliope A.
   Attfield, Kathrine E.
   Haghikia, Aiden
   Xifara, Dionysia K.
   Butter, Falk
   Poschmann, Gereon
   Kaur, Gurman
   Lambert, Lydia
   Leach, Oliver A.
   Proemel, Simone
   Punwani, Divya
   Felce, James H.
   Davis, Simon J.
   Gold, Ralf
   Nielsen, Finn C.
   Siegel, Richard M.
   Mann, Matthias
   Bell, John I.
   McVean, Gil
   Fugger, Lars
TI TNF receptor 1 genetic risk mirrors outcome of anti-TNF therapy in multiple sclerosis
SO NATURE
LA English
DT Article
ID tumor-necrosis-factor; genome-wide association; experimental autoimmune encephalomyelitis; resonance energy-transfer; susceptibility loci; disease susceptibility; metaanalysis; demyelination; inhibition; mechanisms
AB Although there has been much success in identifying genetic variants associated with common diseases using genome-wide association studies (GWAS)(1), it has been difficult to demonstrate which variants are causal and what role they have in disease. Moreover, the modest contribution that these variants make to disease risk has raised questions regarding their medical relevance(2). Here we have investigated a single nucleotide polymorphism (SNP) in the TNFRSF1A gene, that encodes tumour necrosis factor receptor 1 (TNFR1), which was discovered through GWAS to be associated with multiple sclerosis (MS)(3,4), but not with other autoimmune conditions such as rheumatoid arthritis(5), psoriasis(6) and Crohn's disease(7). By analysing MS GWAS(3,4) data in conjunction with the 1000 Genomes Project data(8) we provide genetic evidence that strongly implicates this SNP, rs1800693, as the causal variant in the TNFRSF1A region. We further substantiate this through functional studies showing that the MS risk allele directs expression of a novel, soluble form of TNFR1 that can block TNF. Importantly, TNF-blocking drugs can promote onset or exacerbation of MS9-11, but they have proven highly efficacious in the treatment of autoimmune diseases for which there is no association with rs1800693. This indicates that the clinical experience with these drugs parallels the disease association of rs1800693, and that the MS-associated TNFR1 variant mimics the effect of TNF-blocking drugs. Hence, our study demonstrates that clinical practice can be informed by comparing GWAS across common autoimmune diseases and by investigating the functional consequences of the disease-associated genetic variation.
C1 [Gregory, Adam P.; Kaur, Gurman; Punwani, Divya; Felce, James H.; Davis, Simon J.; Fugger, Lars] Univ Oxford, Weatherall Inst Mol Med, John Radcliffe Hosp, MRC Human Immunol Unit, Oxford OX3 9DS, England.
   [Dendrou, Calliope A.; Attfield, Kathrine E.; Haghikia, Aiden; Lambert, Lydia; Leach, Oliver A.; Proemel, Simone; Fugger, Lars] Univ Oxford, John Radcliffe Hosp, Div Clin Neurol, Nuffield Dept Clin Neurosci, Oxford OX3 9DS, England.
   [Haghikia, Aiden; Gold, Ralf] Ruhr Univ Bochum, St Josef Hosp Bochum, Dept Neurol, D-44791 Bochum, Germany.
   [Xifara, Dionysia K.; McVean, Gil] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.
   [Butter, Falk; Mann, Matthias] Max Planck Inst Biochem, Dept Prote & Signal Transduct, D-82152 Martinsried, Germany.
   [Poschmann, Gereon] Univ Dusseldorf, Biol Med Forschungszentrum, Mol Prote Lab, D-40225 Dusseldorf, Germany.
   [Nielsen, Finn C.] Univ Copenhagen, Rigshosp, Ctr Genom Med, DK-2100 Copenhagen O, Denmark.
   [Siegel, Richard M.] NIAMSD, Immunoregulat Sect, Autoimmun Branch, NIH, Bethesda, MD 20892 USA.
   [Bell, John I.] Univ Oxford, Oxford OX3 7DG, England.
   [Fugger, Lars] Skejby Sygehus, Aarhus Univ Hosp, Inst Clin, DK-8200 Aarhus N, Denmark.
C3 University of Oxford; University of Oxford; Ruhr University Bochum; University of Oxford; Wellcome Centre for Human Genetics; Max Planck Society; Heinrich Heine University Dusseldorf; Rigshospitalet; University of Copenhagen; National Institutes of Health (NIH) - USA; NIH National Institute of Arthritis & Musculoskeletal & Skin Diseases (NIAMS); University of Oxford; Aarhus University
RP Fugger, L (corresponding author), Univ Oxford, Weatherall Inst Mol Med, John Radcliffe Hosp, MRC Human Immunol Unit, Oxford OX3 9DS, England.
EM lars.fugger@imm.ox.ac.uk
FU UK Medical Research Council (MRC); European Union [FP7/2007-2013]; Naomi Bramson Trust; Wellcome Trust [090532/Z/09/Z, 086084/Z/08/Z]; MRC; Deutsche Forschungsgemeinschaft; Christopher Welch Scholarship; MS Society; Dorothy Hodgkin Postgraduate Award; MRC [MC_UU_12010/3, MC_UU_12010/4] Funding Source: UKRI; Medical Research Council [MC_UU_12010/3, MC_UU_12010/4, G1000800i] Funding Source: researchfish; Rosetrees [M210] Funding Source: researchfish; Wellcome Trust [086084/Z/08/Z] Funding Source: Wellcome Trust
NR 30
TC 307
Z9 346
U1 0
U2 67
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD AUG 23
PY 2012
VL 488
IS 7412
BP 508
EP +
DI 10.1038/nature11307
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 992FS
UT WOS:000307761600036
PM 22801493
DA 2026-03-09
ER

PT J
AU Hayashi, M
   Nakashima, T
   Taniguchi, M
   Kodama, T
   Kumanogoh, A
   Takayanagi, H
AF Hayashi, Mikihito
   Nakashima, Tomoki
   Taniguchi, Masahiko
   Kodama, Tatsuhiko
   Kumanogoh, Atsushi
   Takayanagi, Hiroshi
TI Osteoprotection by semaphorin 3A
SO NATURE
LA English
DT Article
ID terminal differentiation; bone-formation; osteoclast; expression; growth; rankl; wnt; osteoporosis; neuropilin-1; activation
AB The bony skeleton is maintained by local factors that regulate bone-forming osteoblasts and bone-resorbing osteoclasts, in addition to hormonal activity. Osteoprotegerin protects bone by inhibiting osteoclastic bone resorption, but no factor has yet been identified as a local determinant of bone mass that regulates both osteoclasts and osteoblasts. Here we show that semaphorin 3A (Sema3A) exerts an osteoprotective effect by both suppressing osteoclastic bone resorption and increasing osteoblastic bone formation. The binding of Sema3A to neuropilin-1 (Nrp1) inhibited receptor activator of nuclear factor-kappa B ligand (RANKL)-induced osteoclast differentiation by inhibiting the immunoreceptor tyrosine-based activation motif (ITAM) and RhoA signalling pathways. In addition, Sema3A and Nrp1 binding stimulated osteoblast and inhibited adipocyte differentiation through the canonical Wnt/beta-catenin signalling pathway. The osteopenic phenotype in Sema3a(-/-) mice was recapitulated by mice in which the Sema3A-binding site of Nrp1 had been genetically disrupted. Intravenous Sema3A administration in mice increased bone volume and expedited bone regeneration. Thus, Sema3A is a promising new therapeutic agent in bone and joint diseases.
C1 [Hayashi, Mikihito; Nakashima, Tomoki; Takayanagi, Hiroshi] Tokyo Med & Dent Univ, Grad Sch Med & Dent Sci, Dept Cell Signaling, Bunkyo Ku, Tokyo 1138549, Japan.
   [Hayashi, Mikihito; Nakashima, Tomoki; Takayanagi, Hiroshi] Japan Sci & Technol Agcy, Exploratory Res Adv Technol Program, Takayanagi Osteonetwork Project, Bunkyo Ku, Tokyo 1138549, Japan.
   [Hayashi, Mikihito; Nakashima, Tomoki; Takayanagi, Hiroshi] Int Res Ctr Mol Sci Tooth & Bone Dis, Global Ctr Excellence Program, Bunkyo Ku, Tokyo 1138549, Japan.
   [Taniguchi, Masahiko] Sapporo Med Univ, Sch Med, Res Inst Frontier Med, Dept Mol Med Sci,Chuo Ku, Sapporo, Hokkaido 0608556, Japan.
   [Kodama, Tatsuhiko] Univ Tokyo, Dept Mol Biol & Med, Res Ctr Adv Sci & Technol, Lab Syst Biol & Med,Meguro Ku, Tokyo 1538904, Japan.
   [Kumanogoh, Atsushi] Osaka Univ, Grad Sch Med, Dept Resp Med Allergy & Rheumat Dis, Suita, Osaka 5650871, Japan.
   [Kumanogoh, Atsushi] Osaka Univ, Immunol Frontier Res Ctr, Dept Immunopathol, Suita, Osaka 5650871, Japan.
   [Takayanagi, Hiroshi] Univ Western Australia, Sch Surg, Ctr Orthopaed Res, Nedlands, WA 6009, Australia.
C3 Institute of Science Tokyo; Tokyo Medical & Dental University (TMDU); Japan Science & Technology Agency (JST); Sapporo Medical University; University of Tokyo; University of Osaka; University of Osaka; University of Western Australia
RP Takayanagi, H (corresponding author), Tokyo Med & Dent Univ, Grad Sch Med & Dent Sci, Dept Cell Signaling, Bunkyo Ku, Yushima 1-5-45, Tokyo 1138549, Japan.
EM taka.csi@tmd.ac.jp
FU Japan Science and Technology Agency; Japan Society for the Promotion of Science (JSPS); Ministry of Education, Culture, Sports, Science and Technology of Japan; Tokyo Biochemical Research Foundation; Life Science Foundation of Japan; Takeda Science Foundation; Uehara Memorial Foundation; Naito Foundation; BMKK RA; Astellas Foundation for Research on Metabolic Disorders; Grants-in-Aid for Scientific Research [21590196] Funding Source: KAKEN
NR 46
TC 509
Z9 591
U1 0
U2 141
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 3
PY 2012
VL 485
IS 7396
BP 69
EP U96
DI 10.1038/nature11000
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 934NV
UT WOS:000303451900035
PM 22522930
DA 2026-03-09
ER

PT J
AU Huang, JH
   Ofek, G
   Laub, L
   Louder, MK
   Doria-Rose, NA
   Longo, NS
   Imamichi, H
   Bailer, RT
   Chakrabarti, B
   Sharma, SK
   Alam, SM
   Wang, T
   Yang, YP
   Zhang, BS
   Migueles, SA
   Wyatt, R
   Haynes, BF
   Kwong, PD
   Mascola, JR
   Connors, M
AF Huang, Jinghe
   Ofek, Gilad
   Laub, Leo
   Louder, Mark K.
   Doria-Rose, Nicole A.
   Longo, Nancy S.
   Imamichi, Hiromi
   Bailer, Robert T.
   Chakrabarti, Bimal
   Sharma, Shailendra K.
   Alam, S. Munir
   Wang, Tao
   Yang, Yongping
   Zhang, Baoshan
   Migueles, Stephen A.
   Wyatt, Richard
   Haynes, Barton F.
   Kwong, Peter D.
   Mascola, John R.
   Connors, Mark
TI Broad and potent neutralization of HIV-1 by a gp41-specific human antibody
SO NATURE
LA English
DT Article
ID immunodeficiency-virus type-1; proximal external region; monoclonal-antibody; glycoprotein gp41; t-cells; epitope; membrane; binding; 4e10; specificity
AB Characterization of human monoclonal antibodies is providing considerable insight into mechanisms of broad HIV-1 neutralization. Here we report an HIV-1 gp41 membrane-proximal external region (MPER)-specific antibody, named 10E8, which neutralizes similar to 98% of tested viruses. An analysis of sera from 78 healthy HIV-1-infected donors demonstrated that 27% contained MPER-specific antibodies and 8% contained 10E8-like specificities. In contrast to other neutralizing MPER antibodies, 10E8 did not bind phospholipids, was not autoreactive, and bound cell-surface envelope. The structure of 10E8 in complex with the complete MPER revealed a site of vulnerability comprising a narrow stretch of highly conserved gp41-hydrophobic residues and a critical arginine or lysine just before the transmembrane region. Analysis of resistant HIV-1 variants confirmed the importance of these residues for neutralization. The highly conserved MPER is a target of potent, non-self-reactive neutralizing antibodies, suggesting that HIV-1 vaccines should aim to induce antibodies to this region of HIV-1 envelope glycoprotein.
C1 [Huang, Jinghe; Laub, Leo; Imamichi, Hiromi; Migueles, Stephen A.; Connors, Mark] NIAID, HIV Specif Immun Sect, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA.
   [Ofek, Gilad; Louder, Mark K.; Doria-Rose, Nicole A.; Longo, Nancy S.; Bailer, Robert T.; Wang, Tao; Yang, Yongping; Zhang, Baoshan; Kwong, Peter D.; Mascola, John R.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
   [Chakrabarti, Bimal; Sharma, Shailendra K.; Wyatt, Richard] Scripps Res Inst, Dept Immunol & Microbial Sci, IAVI Neutralizing Antibody Ctr, La Jolla, CA 92037 USA.
   [Alam, S. 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; International AIDS Vaccine Initiative; Duke University
RP Connors, M (corresponding author), NIAID, HIV Specif Immun Sect, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA.
EM mconnors@nih.gov
FU NIAID; National Cancer Institute, National Institutes of Health [HHSN261200800001E]; US Department of Energy, Basic Energy Sciences, Office of Science [W-31-109-Eng-38]; National Institute of Allergy and Infectious Diseases [ZIAAI005022, ZIAAI000855, ZIAAI001090] Funding Source: NIH RePORTER; NIH Office of the Director; National Institute of Allergy and Infectious Diseases [ZIAAI005095] Funding Source: NIH RePORTER
NR 56
TC 712
Z9 903
U1 0
U2 139
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD NOV 15
PY 2012
VL 491
IS 7424
BP 406
EP +
DI 10.1038/nature11544
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 036MY
UT WOS:000311031600038
PM 23151583
DA 2026-03-09
ER

PT J
AU Yu, R
   Yin, L
   Sullivan, NS
   Xia, JS
   Huan, C
   Paduan, A
   Oliveira, NF
   Haas, S
   Steppke, A
   Miclea, CF
   Weickert, F
   Movshovich, R
   Mun, ED
   Scott, BL
   Zapf, VS
   Roscilde, T
AF Yu, Rong
   Yin, Liang
   Sullivan, Neil S.
   Xia, J. S.
   Huan, Chao
   Paduan-Filho, Armando
   Oliveira, Nei F., Jr.
   Haas, Stephan
   Steppke, Alexander
   Miclea, Corneliu F.
   Weickert, Franziska
   Movshovich, Roman
   Mun, Eun-Deok
   Scott, Brian L.
   Zapf, Vivien S.
   Roscilde, Tommaso
TI Bose glass and Mott glass of quasiparticles in a doped quantum magnet
SO NATURE
LA English
DT Article
ID einstein condensation; localization; disorder; phase; transition; systems; bosons
AB The low-temperature states of bosonic fluids exhibit fundamental quantum effects at the macroscopic scale: the best-known examples are Bose-Einstein condensation and superfluidity, which have been tested experimentally in a variety of different systems. When bosons interact, disorder can destroy condensation, leading to a 'Bose glass'. This phase has been very elusive in experiments owing to the absence of any broken symmetry and to the simultaneous absence of a finite energy gap in the spectrum. Here we report the observation of a Bose glass of field-induced magnetic quasiparticles in a doped quantum magnet (bromine-doped dichloro-tetrakis-thiourea-nickel, DTN). The physics of DTN in a magnetic field is equivalent to that of a lattice gas of bosons in the grand canonical ensemble; bromine doping introduces disorder into the hopping and interaction strength of the bosons, leading to their localization into a Bose glass down to zero field, where it becomes an incompressible Mott glass. The transition from the Bose glass (corresponding to a gapless spin liquid) to the Bose-Einstein condensate (corresponding to a magnetically ordered phase) is marked by a universal exponent that governs the scaling of the critical temperature with the applied field, in excellent agreement with theoretical predictions. Our study represents a quantitative experimental account of the universal features of disordered bosons in the grand canonical ensemble.
C1 [Roscilde, Tommaso] Ecole Normale Super Lyon, Lab Phys, CNRS, UMR5672, F-69364 Lyon, France.
   [Yu, Rong] Rice Univ, Dept Phys & Astron, Houston, TX 77005 USA.
   [Yin, Liang; Sullivan, Neil S.; Xia, J. S.; Huan, Chao] Univ Florida, Dept Phys, Gainesville, FL 32611 USA.
   [Yin, Liang; Sullivan, Neil S.; Xia, J. S.; Huan, Chao] Univ Florida, Natl High Magnet Field Lab, Gainesville, FL 32611 USA.
   [Paduan-Filho, Armando; Oliveira, Nei F., Jr.] Univ Sao Paulo, Inst Fis, BR-05315970 Sao Paulo, Brazil.
   [Haas, Stephan] Univ So Calif, Dept Phys & Astron, Los Angeles, CA 90089 USA.
   [Steppke, Alexander] Max Planck Inst Chem Phys Solids, D-01187 Dresden, Germany.
   [Miclea, Corneliu F.; Weickert, Franziska; Movshovich, Roman; Mun, Eun-Deok; Scott, Brian L.; Zapf, Vivien S.] Los Alamos Natl Lab, Los Alamos, NM 87545 USA.
   [Miclea, Corneliu F.] Natl Inst Mat Phys, Bucharest 077125, Romania.
C3 Ecole Normale Superieure de Lyon (ENS de LYON); Centre National de la Recherche Scientifique (CNRS); CNRS - Institute of Physics (INP); Universite Paris Cite; Rice University; State University System of Florida; University of Florida; State University System of Florida; University of Florida; Universidade de Sao Paulo; University of Southern California; Max Planck Society; United States Department of Energy (DOE); Los Alamos National Laboratory; National Institute of Materials Physics - Romania
RP Roscilde, T (corresponding author), Ecole Normale Super Lyon, Lab Phys, CNRS, UMR5672, 46 Allee Italie, F-69364 Lyon, France.
EM tommaso.roscilde@ens-lyon.fr
FU FAPESP; CNPq; NSF [DMR 0654118, DMR-1006985]; State of Florida; DOE [20100043DR, DE-FG03-01ER45908, DE-FG02-05ER46240]; UEFISCDI [RP-10]; INCITE of the Office of Science, DOE [MAT013]; Robert A. Welch Foundation [C-1411]
NR 29
TC 112
Z9 121
U1 2
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 SEP 20
PY 2012
VL 489
IS 7416
BP 379
EP 384
DI 10.1038/nature11406
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 007AK
UT WOS:000308860900035
PM 22996552
DA 2026-03-09
ER

PT J
AU Laurance, WF
   Useche, DC
   Rendeiro, J
   Kalka, M
   Bradshaw, CJA
   Sloan, SP
   Laurance, SG
   Campbell, M
   Abernethy, K
   Alvarez, P
   Arroyo-Rodriguez, V
   Ashton, P
   Benítez-Malvido, J
   Blom, A
   Bobo, KS
   Cannon, CH
   Cao, M
   Carroll, R
   Chapman, C
   Coates, R
   Cords, M
   Danielsen, F
   De Dijn, B
   Dinerstein, E
   Donnelly, MA
   Edwards, D
   Edwards, F
   Farwig, N
   Fashing, P
   Forget, PM
   Foster, M
   Gale, G
   Harris, D
   Harrison, R
   Hart, J
   Karpanty, S
   Kress, WJ
   Krishnaswamy, J
   Logsdon, W
   Lovett, J
   Magnusson, W
   Maisels, F
   Marshall, AR
   McClearn, D
   Mudappa, D
   Nielsen, MR
   Pearson, R
   Pitman, N
   van der Ploeg, J
   Plumptre, A
   Poulsen, J
   Quesada, M
   Rainey, H
   Robinson, D
   Roetgers, C
   Rovero, F
   Scatena, F
   Schulze, C
   Sheil, D
   Struhsaker, T
   Terborgh, J
   Thomas, D
   Timm, R
   Urbina-Cardona, JN
   Vasudevan, K
   Wright, SJ
   Arias-G, JC
   Arroyo, L
   Ashton, M
   Auzel, P
   Babaasa, D
   Babweteera, F
   Baker, P
   Banki, O
   Bass, M
   Bila-Isia, I
   Blake, S
   Brockelman, W
   Brokaw, N
   Brühl, CA
   Bunyavejchewin, S
   Chao, JT
   Chave, J
   Chellam, R
   Clark, CJ
   Clavijo, J
   Congdon, R
   Corlett, R
   Dattaraja, HS
   Dave, C
   Davies, G
   Beisiegel, BD
   da Silva, RD
   Di Fiore, A
   Diesmos, A
   Dirzo, R
   Doran-Sheehy, D
   Eaton, M
   Emmons, L
   Estrada, A
   Ewango, C
   Fedigan, L
   Feer, F
   Fruth, B
   Willis, JG
   Goodale, U
   Goodman, S
   Guix, JC
   Guthiga, P
   Haber, W
   Hamer, K
   Herbinger, I
   Hill, J
   Huang, ZL
   Sun, IF
   Ickes, K
   Itoh, A
   Ivanauskas, N
   Jackes, B
   Janovec, J
   Janzen, D
   Mo, JM
   Chen, J
   Jones, T
   Justiniano, H
   Kalko, E
   Kasangaki, A
   Killeen, T
   King, HB
   Klop, E
   Knott, C
   Koné, I
   Kudavidanage, E
   Ribeiro, JLD
   Lattke, J
   Laval, R
   Lawton, R
   Leal, M
   Leighton, M
   Lentino, M
   Leonel, C
   Lindsell, J
   Ling-Ling, L
   Linsenmair, KE
   Losos, E
   Lugo, A
   Lwanga, J
   Mack, AL
   Martins, M
   McGraw, WS
   McNab, R
   Montag, L
   Thompson, JM
   Nabe-Nielsen, J
   Nakagawa, M
   Nepal, S
   Norconk, M
   Novotny, V
   O'Donnell, S
   Opiang, M
   Ouboter, P
   Parker, K
   Parthasarathy, N
   Pisciotta, K
   Prawiradilaga, D
   Pringle, C
   Rajathurai, S
   Reichard, U
   Reinartz, G
   Renton, K
   Reynolds, G
   Reynolds, V
   Riley, E
   Rödel, MO
   Rothman, J
   Round, P
   Sakai, S
   Sanaiotti, T
   Savini, T
   Schaab, G
   Seidensticker, J
   Siaka, A
   Silman, MR
   Smith, TB
   de Almeida, SS
   Sodhi, N
   Stanford, C
   Stewart, K
   Stokes, E
   Stoner, KE
   Sukumar, R
   Surbeck, M
   Tobler, M
   Tscharntke, T
   Turkalo, A
   Umapathy, G
   van Weerd, M
   Rivera, JV
   Venkataraman, M
   Venn, L
   Verea, C
   de Castilho, CV
   Waltert, M
   Wang, B
   Watts, D
   Weber, W
   West, P
   Whitacre, D
   Whitney, K
   Wilkie, D
   Williams, S
   Wright, DD
   Wright, P
   Lu, XK
   Yonzon, P
   Zamzani, F
AF Laurance, William F.
   Useche, D. Carolina
   Rendeiro, Julio
   Kalka, Margareta
   Bradshaw, Corey J. A.
   Sloan, Sean P.
   Laurance, Susan G.
   Campbell, Mason
   Abernethy, Kate
   Alvarez, Patricia
   Arroyo-Rodriguez, Victor
   Ashton, Peter
   Benitez-Malvido, Julieta
   Blom, Allard
   Bobo, Kadiri S.
   Cannon, Charles H.
   Cao, Min
   Carroll, Richard
   Chapman, Colin
   Coates, Rosamond
   Cords, Marina
   Danielsen, Finn
   De Dijn, Bart
   Dinerstein, Eric
   Donnelly, Maureen A.
   Edwards, David
   Edwards, Felicity
   Farwig, Nina
   Fashing, Peter
   Forget, Pierre-Michel
   Foster, Mercedes
   Gale, George
   Harris, David
   Harrison, Rhett
   Hart, John
   Karpanty, Sarah
   Kress, W. John
   Krishnaswamy, Jagdish
   Logsdon, Willis
   Lovett, Jon
   Magnusson, William
   Maisels, Fiona
   Marshall, Andrew R.
   McClearn, Deedra
   Mudappa, Divya
   Nielsen, Martin R.
   Pearson, Richard
   Pitman, Nigel
   van der Ploeg, Jan
   Plumptre, Andrew
   Poulsen, John
   Quesada, Mauricio
   Rainey, Hugo
   Robinson, Douglas
   Roetgers, Christiane
   Rovero, Francesco
   Scatena, Frederick
   Schulze, Christian
   Sheil, Douglas
   Struhsaker, Thomas
   Terborgh, John
   Thomas, Duncan
   Timm, Robert
   Urbina-Cardona, J. Nicolas
   Vasudevan, Karthikeyan
   Wright, S. Joseph
   Arias-G, Juan Carlos
   Arroyo, Luzmila
   Ashton, Mark
   Auzel, Philippe
   Babaasa, Dennis
   Babweteera, Fred
   Baker, Patrick
   Banki, Olaf
   Bass, Margot
   Bila-Isia, Inogwabini
   Blake, Stephen
   Brockelman, Warren
   Brokaw, Nicholas
   Bruehl, Carsten A.
   Bunyavejchewin, Sarayudh
   Chao, Jung-Tai
   Chave, Jerome
   Chellam, Ravi
   Clark, Connie J.
   Clavijo, Jose
   Congdon, Robert
   Corlett, Richard
   Dattaraja, H. S.
   Dave, Chittaranjan
   Davies, Glyn
   Beisiegel, Beatriz de Mello
   da Silva, Rosa de Nazarepaes
   Di Fiore, Anthony
   Diesmos, Arvin
   Dirzo, Rodolfo
   Doran-Sheehy, Diane
   Eaton, Mitchell
   Emmons, Louise
   Estrada, Alejandro
   Ewango, Corneille
   Fedigan, Linda
   Feer, Francois
   Fruth, Barbara
   Willis, Jacalyn Giacalone
   Goodale, Uromi
   Goodman, Steven
   Guix, Juan C.
   Guthiga, Paul
   Haber, William
   Hamer, Keith
   Herbinger, Ilka
   Hill, Jane
   Huang, Zhongliang
   Sun, I. Fang
   Ickes, Kalan
   Itoh, Akira
   Ivanauskas, Natalia
   Jackes, Betsy
   Janovec, John
   Janzen, Daniel
   Mo Jiangming
   Chen Jin
   Jones, Trevor
   Justiniano, Hermes
   Kalko, Elisabeth
   Kasangaki, Aventino
   Killeen, Timothy
   King, Hen-biau
   Klop, Erik
   Knott, Cheryl
   Kone, Inza
   Kudavidanage, Enoka
   Ribeiro, Jose Lahoz da Silva
   Lattke, John
   Laval, Richard
   Lawton, Robert
   Leal, Miguel
   Leighton, Mark
   Lentino, Miguel
   Leonel, Cristiane
   Lindsell, Jeremy
   Ling-Ling, Lee
   Linsenmair, K. Eduard
   Losos, Elizabeth
   Lugo, Ariel
   Lwanga, Jeremiah
   Mack, Andrew L.
   Martins, Marlucia
   McGraw, W. Scott
   McNab, Roan
   Montag, Luciano
   Thompson, Jo Myers
   Nabe-Nielsen, Jacob
   Nakagawa, Michiko
   Nepal, Sanjay
   Norconk, Marilyn
   Novotny, Vojtech
   O'Donnell, Sean
   Opiang, Muse
   Ouboter, Paul
   Parker, Kenneth
   Parthasarathy, N.
   Pisciotta, Katia
   Prawiradilaga, Dewi
   Pringle, Catherine
   Rajathurai, Subaraj
   Reichard, Ulrich
   Reinartz, Gay
   Renton, Katherine
   Reynolds, Glen
   Reynolds, Vernon
   Riley, Erin
   Roedel, Mark-Oliver
   Rothman, Jessica
   Round, Philip
   Sakai, Shoko
   Sanaiotti, Tania
   Savini, Tommaso
   Schaab, Gertrud
   Seidensticker, John
   Siaka, Alhaji
   Silman, Miles R.
   Smith, Thomas B.
   de Almeida, Samuel Soares
   Sodhi, Navjot
   Stanford, Craig
   Stewart, Kristine
   Stokes, Emma
   Stoner, Kathryn E.
   Sukumar, Raman
   Surbeck, Martin
   Tobler, Mathias
   Tscharntke, Teja
   Turkalo, Andrea
   Umapathy, Govindaswamy
   van Weerd, Merlijn
   Rivera, Jorge Vega
   Venkataraman, Meena
   Venn, Linda
   Verea, Carlos
   de Castilho, Carolina Volkmer
   Waltert, Matthias
   Wang, Benjamin
   Watts, David
   Weber, William
   West, Paige
   Whitacre, David
   Whitney, Ken
   Wilkie, David
   Williams, Stephen
   Wright, Debra D.
   Wright, Patricia
   Lu Xiankai
   Yonzon, Pralad
   Zamzani, Franky
TI Averting biodiversity collapse in tropical forest protected areas
SO NATURE
LA English
DT Article
ID extinction; deforestation
AB The rapid disruption of tropical forests probably imperils global biodiversity more than any other contemporary phenomenon(1-3). With deforestation advancing quickly, protected areas are increasingly becoming final refuges for threatened species and natural ecosystem processes. However, many protected areas in the tropics are themselves vulnerable to human encroachment and other environmental stresses(4-9). As pressures mount, it is vital to know whether existing reserves can sustain their biodiversity. A critical constraint in addressing this question has been that data describing a broad array of biodiversity groups have been unavailable for a sufficiently large and representative sample of reserves. Here we present a uniquely comprehensive data set on changes over the past 20 to 30 years in 31 functional groups of species and 21 potential drivers of environmental change, for 60 protected areas stratified across the world's major tropical regions. Our analysis reveals great variation in reserve 'health': about half of all reserves have been effective or performed passably, but the rest are experiencing an erosion of biodiversity that is often alarmingly widespread taxonomically and functionally. Habitat disruption, hunting and forest-product exploitation were the strongest predictors of declining reserve health. Crucially, environmental changes immediately outside reserves seemed nearly as important as those inside in determining their ecological fate, with changes inside reserves strongly mirroring those occurring around them. These findings suggest that tropical protected areas are often intimately linked ecologically to their surrounding habitats, and that a failure to stem broad-scale loss and degradation of such habitats could sharply increase the likelihood of serious biodiversity declines.
C1 [Laurance, William F.; Sloan, Sean P.; Laurance, Susan G.; Campbell, Mason; Edwards, David; Edwards, Felicity; Logsdon, Willis; Roetgers, Christiane] James Cook Univ, Ctr Trop Environm & Sustainabil Sci TESS, Cairns, Qld 4878, Australia.
   [Laurance, William F.; Sloan, Sean P.; Laurance, Susan G.; Campbell, Mason; Edwards, David; Edwards, Felicity; Logsdon, Willis; Roetgers, Christiane] James Cook Univ, Sch Marine & Trop Biol, Cairns, Qld 4878, Australia.
   [Laurance, William F.; Useche, D. Carolina; Rendeiro, Julio; Kalka, Margareta; Wright, S. Joseph] Smithsonian Trop Res Inst, Balboa, Ancon, Panama.
   [Bradshaw, Corey J. A.] Univ Adelaide, Sch Earth & Environm Sci, Adelaide, SA 5005, Australia.
   [Abernethy, Kate; Maisels, Fiona] Univ Stirling, Stirling FK9 4LA, Scotland.
   [Alvarez, Patricia; Pitman, Nigel; Struhsaker, Thomas; Terborgh, John; Clark, Connie J.] Duke Univ, Durham, NC 27705 USA.
   [Arroyo-Rodriguez, Victor; Benitez-Malvido, Julieta; Quesada, Mauricio] UNAM, Morelia, Michoacan, Mexico.
   [Ashton, Peter] Royal Bot Gardens, Richmond TW9 3AB, Surrey, England.
   [Blom, Allard; Carroll, Richard; Dinerstein, Eric] World Wildlife Fund WWF, Washington, DC 20037 USA.
   [Bobo, Kadiri S.] Univ Dschang, Dschang, Cameroon.
   [Cannon, Charles H.; Cao, Min; Harrison, Rhett; Chen Jin] Xishuangbanna Trop Bot Garden, Yunnan 666303, Peoples R China.
   [Chapman, Colin; Auzel, Philippe] McGill Univ, Montreal, PQ H3A 2T7, Canada.
   [Coates, Rosamond; Estrada, Alejandro] Univ Nacl Autonoma Mexico, Estn Biol Trop Los Tuxtlas, Veracruz 95701, Mexico.
   [Cords, Marina; West, Paige] Columbia Univ, New York, NY 10027 USA.
   [Danielsen, Finn] Nord Fdn Dev & Ecol, DK-1159 Copenhagen, Denmark.
   [De Dijn, Bart] Bart De Dijn Environm Consultancy, Paramaribo, Suriname.
   [Donnelly, Maureen A.] Florida Int Univ, Miami, FL 33199 USA.
   [Farwig, Nina] Univ Marburg, D-35043 Marburg, Germany.
   [Fashing, Peter] Calif State Univ Fullerton, Fullerton, CA 92834 USA.
   [Forget, Pierre-Michel; Feer, Francois] Museum Natl Hist Nat, F-91800 Brunoy, France.
   [Foster, Mercedes] US Geol Survey, Smithsonian Inst, Washington, DC 20013 USA.
   [Gale, George; Savini, Tommaso] King Mongkuts Univ Technol Thonburi, Bangkok 10150, Thailand.
   [Harris, David] Royal Bot Garden, Edinburgh EH3 5LR, Midlothian, Scotland.
   [Hart, John] Tshuapa Lomami Lualaba Project, Kinshasa, DEM REP CONGO.
   [Karpanty, Sarah] Virginia Tech Univ, Blacksburg, VA 24061 USA.
   [Kress, W. John; Emmons, Louise] Smithsonian Inst, Natl Museum Nat Hist, Washington, DC 20013 USA.
   [Krishnaswamy, Jagdish] Ashoka Trust Res Ecol & Environm ATREE, Bangalore 560064, Karnataka, India.
   [Lovett, Jon] Univ Twente, NL-7500 AE Enschede, Netherlands.
   [Magnusson, William; Sanaiotti, Tania] INPA, BR-69011970 Manaus, Amazonas, Brazil.
   [Maisels, Fiona; Rainey, Hugo; Blake, Stephen; Stokes, Emma; Weber, William; Wilkie, David] Wildlife Conservat Soc, Bronx, NY 10460 USA.
   [Marshall, Andrew R.; Hill, Jane] Univ York, York YO10 5DD, N Yorkshire, England.
   [McClearn, Deedra] La Selva Biol Stn, San Pedro, Costa Rica.
   [Mudappa, Divya] Nat Conservat Fdn, Mysore 570002, Karnataka, India.
   [Nielsen, Martin R.] Univ Copenhagen, Copenhagen, Denmark.
   [Pearson, Richard; Congdon, Robert; Jackes, Betsy; Williams, Stephen] James Cook Univ, Townsville, Qld 4811, Australia.
   [van der Ploeg, Jan; van Weerd, Merlijn] Leiden Univ, Leiden, Netherlands.
   [Plumptre, Andrew] Wildlife Conservat Soc, Kampala, Uganda.
   [Poulsen, John] Woods Hole Res Ctr, Falmouth, MA 02540 USA.
   [Robinson, Douglas; Thomas, Duncan] Oregon State Univ, Corvallis, OR 97331 USA.
   [Rovero, Francesco] Museo Sci, I-38122 Trento, Italy.
   [Scatena, Frederick; Janzen, Daniel] Univ Penn, Philadelphia, PA 19104 USA.
   [Schulze, Christian] Univ Vienna, A-1030 Vienna, Austria.
   [Sheil, Douglas] Bwindi Impenetrable Natl Pk, Kabale, Uganda.
   [Timm, Robert] Univ Kansas, Lawrence, KS 66045 USA.
   [Urbina-Cardona, J. Nicolas] Pontificia Univ Javeriana, Bogota, Colombia.
   [Vasudevan, Karthikeyan] Wildlife Inst India, Dehra Dun, India.
   [Arias-G, Juan Carlos] Unidad Parques Nacl Nat Colombia, Bogota, Colombia.
   [Arroyo, Luzmila] Museo Hist Nat Noel Kempff, Santa Cruz, Bolivia.
   [Ashton, Mark; Watts, David] Yale Univ, New Haven, CT 06511 USA.
   [Babaasa, Dennis] Inst Trop Forest Conservat, Kabale, Uganda.
   [Babweteera, Fred] Budongo Conservat Field Stn, Masindi, Uganda.
   [Baker, Patrick] Monash Univ, Melbourne, Vic 3800, Australia.
   [Banki, Olaf] Univ Utrecht, Utrecht, Netherlands.
   [Bass, Margot] Finding Species, Takoma Pk, MD 20912 USA.
   [Bila-Isia, Inogwabini] Univ Kent, Canterbury CT2 7NZ, Kent, England.
   [Brockelman, Warren] Mahidol Univ Salaya, Nakhon Pathom 73170, Thailand.
   [Brokaw, Nicholas] Univ Puerto Rico, San Juan, PR 00936 USA.
   [Bruehl, Carsten A.] Univ Koblenz Landau, D-76829 Landau, Germany.
   [Bunyavejchewin, Sarayudh] Dept Natl Pk, Bangkok 10900, Thailand.
   [Chao, Jung-Tai] Taiwan Forestry Res Inst, Taipei 10066, Taiwan.
   [Chave, Jerome] Univ Toulouse 3, F-31062 Toulouse, France.
   [Chellam, Ravi] Wildlife Conservat Soc, Bangalore 560070, Karnataka, India.
   [Clavijo, Jose] Univ Cent Venezuela, Aragua, Venezuela.
   [Corlett, Richard; Kudavidanage, Enoka; Sodhi, Navjot] Natl Univ Singapore, Singapore 117543, Singapore.
   [Dattaraja, H. S.] Indian Inst Sci, Bangalore 560012, Karnataka, India.
   [Dave, Chittaranjan] World Wide Fund Nat WWF, New Delhi 110003, India.
   [Davies, Glyn] World Wide Fund Nat WWF, Surrey GU7 1XR, England.
   [Beisiegel, Beatriz de Mello] Inst Chico Mendes Conservacao Biodiversidade, BR-12952011 Atibaia, Sao Paulo, Brazil.
   [da Silva, Rosa de Nazarepaes] Conselho Reg Engn Arquitetura & Agron Para, Belem, Para, Brazil.
   [Di Fiore, Anthony] Univ Texas Austin, Austin, TX 78712 USA.
   [Diesmos, Arvin] Natl Museum Philippines, Manila, Philippines.
   [Dirzo, Rodolfo] Stanford Univ, Stanford, CA 94305 USA.
   [Doran-Sheehy, Diane] SUNY Stony Brook, Stony Brook, NY 11794 USA.
   [Eaton, Mitchell] Univ Colorado, Boulder, CO 80309 USA.
   [Ewango, Corneille] Wildlife Conservat Soc, Kinshasa, DEM REP CONGO.
   [Fedigan, Linda] Univ Calgary, Calgary, AB T2N 1N4, Canada.
   [Fruth, Barbara; Surbeck, Martin] Max Planck Inst Evolutionary Anthropol, Leipzig, Germany.
   [Willis, Jacalyn Giacalone] Montclair State Univ, Montclair, NJ 07043 USA.
   [Goodale, Uromi] Univ Calif San Diego, San Diego, CA 92093 USA.
   [Goodman, Steven] Field Museum Nat Hist, Chicago, IL 60605 USA.
   [Guix, Juan C.] Univ Barcelona, Barcelona 08028, Spain.
   [Guthiga, Paul] Kenya Inst Publ Policy Res & Anal, Nairobi, Kenya.
   [Haber, William] Missouri Bot Garden, St Louis, MO 63166 USA.
   [Hamer, Keith] Univ Leeds, Leeds LS2 9JT, W Yorkshire, England.
   [Herbinger, Ilka] Wild Chimpanzee Fdn, Abidjan 23, Cote Ivoire.
   [Huang, Zhongliang] Dinghushan Biosphere Reserve, Zhaoqing, Peoples R China.
   [Sun, I. Fang] Tunghai Univ, Taichung 407, Taiwan.
   [Ickes, Kalan] Clemson Univ, Clemson, SC 29634 USA.
   [Itoh, Akira] Osaka City Univ, Osaka 5588585, Japan.
   [Ivanauskas, Natalia] Inst Florestal, BR-02377000 Sao Paulo, SP, Brazil.
   [Janovec, John; Tobler, Mathias] Bot Res Inst Texas, Ft Worth, TX 76107 USA.
   [Lu Xiankai] South China Bot Garden, Guangzhou 510650, Guangdong, Peoples R China.
   [Jones, Trevor] Anglia Ruskin Univ, Cambridge CB1 1PT, England.
   [Justiniano, Hermes] Fdn Conservac Bosque, Chiquitano, Bolivia.
   [Kalko, Elisabeth] Univ Ulm, D-89069 Ulm, Germany.
   [Kasangaki, Aventino] Mbarara Univ Sci & Technol, Mbarara, Uganda.
   [Killeen, Timothy] Conservat Int, Arlington, VA 22202 USA.
   [King, Hen-biau] Soc Subtrop Ecol, Taipei, Taiwan.
   [Klop, Erik] Royal Haskoning Water & Ecol Grp, Groningen, Netherlands.
   [Knott, Cheryl] Boston Univ, Boston, MA 02215 USA.
   [Kone, Inza] Ctr Suisse Rech Sci Cote Ivoire, Abidjan, Cote Ivoire.
   [Ribeiro, Jose Lahoz da Silva] Univ Estadual Londrina, Londrina, Parana, Brazil.
   [Lattke, John] Univ Cent Venezuela, Caracas, Venezuela.
   [Laval, Richard] Bat Jungle, Monteverde, Costa Rica.
   [Lawton, Robert] Univ Alabama, Huntsville, AL 35899 USA.
   [Leal, Miguel] Boite Postale 7847, Libreville, Gabon.
   [Leighton, Mark] 695 Warren Rd, Framingham, MA 01702 USA.
   [Lentino, Miguel] Colecc Ornitol Phelps, Caracas, Venezuela.
   [Leonel, Cristiane] Parque Estadual Horto Florestal, BR-02377000 Sao Paulo, Brazil.
   [Lindsell, Jeremy] Royal Soc Protect Birds, Sandy SG19 2DL, Beds, England.
   [Ling-Ling, Lee] Natl Taiwan Univ, Taipei 10764, Taiwan.
   [Linsenmair, K. Eduard] Univ Wurzburg, D-97074 Wurzburg, Germany.
   [Losos, Elizabeth] Org Trop Studies, Durham, NC 27705 USA.
   [Lugo, Ariel] USDA Int Inst Trop Forestry, Rio Piedras, PR 00926 USA.
   [Lwanga, Jeremiah] Makerere Univ, Kampala, Uganda.
   [Mack, Andrew L.; Wright, Debra D.] Green Capac Inc, New Florence, PA 15944 USA.
   [Martins, Marlucia] Museu Paraense Emilio Goeldi, BR-66040170 Belem, Para, Brazil.
   [McGraw, W. Scott] Ohio State Univ, Columbus, OH 43210 USA.
   [McNab, Roan] Wildlife Conservat Soc, Flores, Guatemala.
   [Montag, Luciano] Fed Univ Para, BR-66040170 Belem, Para, Brazil.
   [Thompson, Jo Myers] Lukuru Wildlife Res Fdn, Kinshasa, DEM REP CONGO.
   [Nabe-Nielsen, Jacob] Aarhus Univ, DK-4000 Roskilde, Denmark.
   [Nakagawa, Michiko] Nagoya Univ, Nagoya, Aichi, Japan.
   [Nepal, Sanjay] Univ Waterloo, Waterloo, ON N2L 3G1, Canada.
   [Norconk, Marilyn] Kent State Univ, Kent, OH 44242 USA.
   [Novotny, Vojtech] Inst Entomol, Ceske Budejovice, Czech Republic.
   [O'Donnell, Sean] Univ Washington, Seattle, WA 98195 USA.
   [Opiang, Muse] PNG Inst Biol Res, Goroka, Papua N Guinea.
   [Ouboter, Paul] Univ Suriname, Paramaribo, Suriname.
   [Parker, Kenneth] 113-3885 Richet Rd, Prince George, BC V2K 2J2, Canada.
   [Parthasarathy, N.] Pondicherry Univ, Pondicherry 605014, India.
   [Pisciotta, Katia] Fundacao Florestal, BR-02377000 Sao Paulo, Brazil.
   [Prawiradilaga, Dewi] Res Ctr Biol, Cibinong 16911, Indonesia.
   [Pringle, Catherine] Univ Georgia, Athens, GA 30602 USA.
   [Rajathurai, Subaraj] Strix Wildlife Consultancy, Singapore, Singapore.
   [Reichard, Ulrich] Southern Illinois Univ, Carbondale, IL 62901 USA.
   [Reinartz, Gay] Zool Soc Milwaukee, Milwaukee, WI 53226 USA.
   [Renton, Katherine; Rivera, Jorge Vega] Univ Nacl Autonoma Mexico, Estn Biol Chamela, Jalisco 48980, Mexico.
   [Reynolds, Glen] Danum Valley Field Ctr, Sabah, Malaysia.
   [Reynolds, Vernon] Univ Oxford, Oxford BN26 5UX, England.
   [Riley, Erin] San Diego State Univ, San Diego, CA 92182 USA.
   [Roedel, Mark-Oliver] Museum Naturkunde, Berlin, Germany.
   [Rothman, Jessica] CUNY, New York, NY 10065 USA.
   [Round, Philip] Mahidol Univ, Bangkok 10400, Thailand.
   [Sakai, Shoko] Res Inst Human & Nat, Kyoto, Japan.
   [Schaab, Gertrud] Karlsruhe Univ Appl Sci, Karlsruhe, Germany.
   [Seidensticker, John] Natl Zool Pk, Washington, DC 20013 USA.
   [Siaka, Alhaji] Gola Forest Programme, Kenema, Sierra Leone.
   [Silman, Miles R.] Wake Forest Univ, Winston Salem, NC 27106 USA.
   [Smith, Thomas B.] Univ Calif Los Angeles, Los Angeles, CA 90095 USA.
   [de Almeida, Samuel Soares] Ave Maalhaes Barata 376, BR-66040170 Belem, Para, Brazil.
   [Stanford, Craig] Univ Southern Calif, Los Angeles, CA 90089 USA.
   [Stewart, Kristine] Inst Appl Ethnobotany, Pompano Beach, FL 33069 USA.
   [Stoner, Kathryn E.] Texas A&M Univ, Kingsville, TX 78363 USA.
   [Sukumar, Raman] Indian Inst Sci, Bangalore, Karnataka, India.
   [Tscharntke, Teja; Waltert, Matthias] Georg August Univ, Gottingen, Germany.
   [Turkalo, Andrea] Wildlife Conservat Soc, Bangui, Cent Afr Republ.
   [Umapathy, Govindaswamy] Ctr Cellular & Mol Biol, Hyderabad, Andhra Pradesh, India.
   [Venkataraman, Meena] 701 Vesta B, Thana, India.
   [Venn, Linda] Paluma Environm Educ Ctr, Paluma, Qld 4816, Australia.
   [Verea, Carlos] Univ Cent Venezuela, Maracay, Venezuela.
   [de Castilho, Carolina Volkmer] Embrapa Roraima, Boa Vista, Roraima, Brazil.
   [Whitacre, David] Treasure Valley Math & Sci Ctr, Boise, ID 83714 USA.
   [Whitney, Ken] Rice Univ, Houston, TX 77005 USA.
   [Wright, Patricia] SUNY Stony Brook, Stony Brook, NY 11794 USA.
   [Yonzon, Pralad] Resources Himalaya Fdn, Kathmandu, Nepal.
   [Zamzani, Franky] Gunung Palung Natl Pk, Kabupaten Ketapang, West Kalimantan, Indonesia.
C3 James Cook University; James Cook University; Smithsonian Institution; Smithsonian Tropical Research Institute; Adelaide University; University of Adelaide; University of Stirling; Duke University; Universidad Nacional Autonoma de Mexico; Royal Botanic Gardens, Kew; World Wildlife Fund; Universite de Dschang; Chinese Academy of Sciences; Xishuangbanna Tropical Botanical Garden, CAS; McGill University; Universidad Nacional Autonoma de Mexico; Columbia University; State University System of Florida; Florida International University; Philipps University Marburg; California State University System; California State University Fullerton; Museum National d'Histoire Naturelle (MNHN); Smithsonian Institution; United States Department of the Interior; United States Geological Survey; King Mongkuts University of Technology Thonburi; Virginia Polytechnic Institute & State University; Smithsonian Institution; Smithsonian National Museum of Natural History; University of Twente; Institute Nacional de Pesquisas da Amazonia; Wildlife Conservation Society; University of York - UK; University of Copenhagen; James Cook University; Leiden University; Leiden University - Excl LUMC; Woodwell Climate Research Center; Oregon State University; University of Pennsylvania; University of Vienna; University of Kansas; Pontificia Universidad Javeriana; Wildlife Institute of India; Yale University; Monash University; Utrecht University; University of Kent; Mahidol University; University of Puerto Rico; RPTU University Kaiserslautern; Universite de Toulouse; Universite Toulouse III - Paul Sabatier; National University of Singapore; Indian Institute of Science (IISC) - Bangalore; University of Texas System; University of Texas Austin; National Museum of the Philippines; Stanford University; State University of New York (SUNY) System; Stony Brook University; University of Colorado System; University of Colorado Boulder; University of Calgary; Max Planck Society; Montclair State University; University of California System; University of California San Diego; Field Museum of Natural History (Chicago); University of Barcelona; Missouri Botanical Gardens; University of Leeds; Tunghai University; Clemson University; Osaka Metropolitan University; Chinese Academy of Sciences; South China Botanical Garden, CAS; Anglia Ruskin University; Ulm University; Mbarara University of Science & Technology; Conservation International; Boston University; Centre Suisse de Recherches Scientifiques en Cote d'Ivoire (CSRS); Universidade Estadual de Londrina; University of Central Venezuela; University of Alabama System; University of Alabama Huntsville; Royal Society for Protection of Birds; National Taiwan University; University of Wurzburg; United States Department of Agriculture (USDA); Makerere University; Museu Paraense Emilio Goeldi; University System of Ohio; Ohio State University; Universidade Federal do Para; Aarhus University; Nagoya University; University of Waterloo; University System of Ohio; Kent State University; Kent State University Kent; Kent State University Salem; Czech Academy of Sciences; University of Washington; University of Washington Seattle; Anton de Kom Universiteit van Suriname; Pondicherry University; University System of Georgia; University of Georgia; Southern Illinois University System; Southern Illinois University; Universidad Nacional Autonoma de Mexico; University of Oxford; California State University System; San Diego State University; Leibniz Institut fur Evolutions und Biodiversitatsforschung; City University of New York (CUNY) System; Mahidol University; Research Institute for Humanity & Nature (RIHN); Karlsruhe University of Applied Sciences; Smithsonian Institution; Smithsonian National Zoological Park & Conservation Biology Institute; Wake Forest University; University of California System; University of California Los Angeles; University of Southern California; Texas A&M University System; Texas A&M University Kingsville; Indian Institute of Science (IISC) - Bangalore; University of Gottingen; Council of Scientific & Industrial Research (CSIR) - India; CSIR - Centre for Cellular & Molecular Biology (CCMB); Empresa Brasileira de Pesquisa Agropecuaria (EMBRAPA); EMBRAPA Roraima; Rice University; State University of New York (SUNY) System; Stony Brook University
RP Laurance, WF (corresponding author), James Cook Univ, Ctr Trop Environm & Sustainabil Sci TESS, Cairns, Qld 4878, Australia.; Laurance, WF (corresponding author), James Cook Univ, Sch Marine & Trop Biol, Cairns, Qld 4878, Australia.
EM bill.laurance@jcu.edu.au
FU James Cook University; Smithsonian Tropical Research Institute; Australian Laureate Fellowship; NSF [RCN-0741956]; Direct For Biological Sciences; Division Of Integrative Organismal Systems [1209072] Funding Source: National Science Foundation; Direct For Social, Behav & Economic Scie; Division Of Behavioral and Cognitive Sci [1028471] Funding Source: National Science Foundation; Direct For Social, Behav & Economic Scie; Division Of Behavioral and Cognitive Sci [1114977] Funding Source: National Science Foundation; Division Of Environmental Biology; Direct For Biological Sciences [0741956, 0743666] Funding Source: National Science Foundation
NR 30
TC 904
Z9 1062
U1 7
U2 1318
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 13
PY 2012
VL 489
IS 7415
BP 290
EP +
DI 10.1038/nature11318
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 003UC
UT WOS:000308635900041
PM 22832582
DA 2026-03-09
ER

PT J
AU Yin, J
   Ren, JG
   Lu, H
   Cao, Y
   Yong, HL
   Wu, YP
   Liu, C
   Liao, SK
   Zhou, F
   Jiang, Y
   Cai, XD
   Xu, P
   Pan, GS
   Jia, JJ
   Huang, YM
   Yin, H
   Wang, JY
   Chen, YA
   Peng, CZ
   Pan, JW
AF Yin, Juan
   Ren, Ji-Gang
   Lu, He
   Cao, Yuan
   Yong, Hai-Lin
   Wu, Yu-Ping
   Liu, Chang
   Liao, Sheng-Kai
   Zhou, Fei
   Jiang, Yan
   Cai, Xin-Dong
   Xu, Ping
   Pan, Ge-Sheng
   Jia, Jian-Jun
   Huang, Yong-Mei
   Yin, Hao
   Wang, Jian-Yu
   Chen, Yu-Ao
   Peng, Cheng-Zhi
   Pan, Jian-Wei
TI Quantum teleportation and entanglement distribution over 100-kilometre free-space channels
SO NATURE
LA English
DT Article
ID high-fidelity transmission; qubits; state
AB Transferring an unknown quantum state over arbitrary distances is essential for large-scale quantum communication and distributed quantum networks. It can be achieved with the help of long-distance quantum teleportation(1,2) and entanglement distribution. The latter is also important for fundamental tests of the laws of quantum mechanics(3,4). Although quantum teleportation(5,6) and entanglement distribution(7-9) over moderate distances have been realized using optical fibre links, the huge photon loss and decoherence in fibres necessitate the use of quantum repeaters(10) for larger distances. However, the practical realization of quantum repeaters remains experimentally challenging(11). Free-space channels, first used for quantum key distribution(12,13), offer a more promising approach because photon loss and decoherence are almost negligible in the atmosphere. Furthermore, by using satellites, ultra-long-distance quantum communication and tests of quantum foundations could be achieved on a global scale. Previous experiments have achieved free-space distribution of entangled photon pairs over distances of 600 metres (ref. 14) and 13 kilometres (ref. 15), and transfer of triggered single photons over a 144-kilometre one-link free-space channel(16). Most recently, following a modified scheme(17), free-space quantum teleportation over 16 kilometres was demonstrated(18) with a single pair of entangled photons. Here we report quantum teleportation of independent qubits over a 97-kilometre one-link free-space channel with multi-photon entanglement. An average fidelity of 80.4 +/- 0.9 per cent is achieved for six distinct states. Furthermore, we demonstrate entanglement distribution over a two-link channel, in which the entangled photons are separated by 101.8 kilometres. Violation of the Clauser-Horne-Shimony-Holt inequality(4) is observed without the locality loophole. Besides being of fundamental interest, our results represent an important step towards a global quantum network. Moreover, the high-frequency and high-accuracy acquiring, pointing and tracking technique developed in our experiment can be directly used for future satellite-based quantum communication and large-scale tests of quantum foundations.
C1 [Yin, Juan; Ren, Ji-Gang; Lu, He; Cao, Yuan; Yong, Hai-Lin; Wu, Yu-Ping; Liu, Chang; Liao, Sheng-Kai; Zhou, Fei; Jiang, Yan; Cai, Xin-Dong; Xu, Ping; Pan, Ge-Sheng; Yin, Hao; Chen, Yu-Ao; Peng, Cheng-Zhi; Pan, Jian-Wei] Univ Sci & Technol China, Natl Lab Phys Sci Microscale, Shanghai Branch, Shanghai 201315, Peoples R China.
   [Yin, Juan; Ren, Ji-Gang; Lu, He; Cao, Yuan; Yong, Hai-Lin; Wu, Yu-Ping; Liu, Chang; Liao, Sheng-Kai; Zhou, Fei; Jiang, Yan; Cai, Xin-Dong; Xu, Ping; Pan, Ge-Sheng; Yin, Hao; Chen, Yu-Ao; Peng, Cheng-Zhi; Pan, Jian-Wei] Univ Sci & Technol China, Dept Modern Phys, Shanghai 201315, Peoples R China.
   [Jia, Jian-Jun; Wang, Jian-Yu] Chinese Acad Sci, Shanghai Inst Tech Phys, Shanghai 200083, Peoples R China.
   [Huang, Yong-Mei] Chinese Acad Sci, Inst Opt & Elect, Chengdu 610209, Peoples R China.
C3 Chinese Academy of Sciences; University of Science & Technology of China, CAS; Chinese Academy of Sciences; University of Science & Technology of China, CAS; Chinese Academy of Sciences; Shanghai Institute of Technical Physics, CAS; Chinese Academy of Sciences; Institute of Optics & Electronics, CAS
RP Chen, YA (corresponding author), Univ Sci & Technol China, Natl Lab Phys Sci Microscale, Shanghai Branch, Shanghai 201315, Peoples R China.
EM yuaochen@ustc.edu.cn; pcz@ustc.edu.cn; pan@ustc.edu.cn
FU Chinese Academy of Sciences; National Natural Science Foundation of China; National Fundamental Research Program [2011CB921300]
NR 23
TC 425
Z9 494
U1 4
U2 329
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 9
PY 2012
VL 488
IS 7410
BP 185
EP 188
DI 10.1038/nature11332
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 985LE
UT WOS:000307267000027
PM 22874963
DA 2026-03-09
ER

PT J
AU Person, AL
   Raman, IM
AF Person, Abigail L.
   Raman, Indira M.
TI Purkinje neuron synchrony elicits time-locked spiking in the cerebellar nuclei
SO NATURE
LA English
DT Article
ID release sites; cells; synapses; single; transmission; organization; inhibition; depression; discharge; networks
AB An unusual feature of the cerebellar cortex is that its output neurons, Purkinje cells, release GABA (gamma-aminobutyric acid). Their high intrinsic firing rates(1) (50 Hz) and extensive convergence(2,3) predict that their target neurons in the cerebellar nuclei would be largely inhibited unless Purkinje cells pause their spiking, yet Purkinje and nuclear neuron firing rates do not always vary inversely(4). One indication of how these synapses transmit information is that populations of Purkinje neurons synchronize their spikes during cerebellar behaviours(5-11). If nuclear neurons respond to Purkinje synchrony, they may encode signals from subsets of inhibitory inputs(7,12-14). Here we show in weanling and adult mice that nuclear neurons transmit the timing of synchronous Purkinje afferent spikes, owing to modest Purkinje-to-nuclear convergence ratios (similar to 40:1), fast inhibitory postsynaptic current kinetics (tau(decay) = 2.5 ms) and high intrinsic firing rates (similar to 90 Hz). In vitro, dynamically clamped asynchronous inhibitory postsynaptic potentials mimicking Purkinje afferents suppress nuclear cell spiking, whereas synchronous inhibitory postsynaptic potentials entrain nuclear cell spiking. With partial synchrony, nuclear neurons time-lock their spikes to the synchronous subpopulation of inputs, even when only 2 out of 40 afferents synchronize. In vivo, nuclear neurons reliably phase-lock to regular trains of molecular layer stimulation. Thus, cerebellar nuclear neurons can preferentially relay the spike timing of synchronized Purkinje cells to downstream premotor areas.
C1 [Person, Abigail L.; Raman, Indira M.] Northwestern Univ, Dept Neurobiol, Evanston, IL 60208 USA.
C3 Northwestern University
RP Raman, IM (corresponding author), Northwestern Univ, Dept Neurobiol, Evanston, IL 60208 USA.
EM a-person@northwestern.edu; i-raman@northwestern.edu
FU NIH [R01-NS39395, F32-NS067831]
NR 30
TC 272
Z9 318
U1 0
U2 23
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JAN 26
PY 2012
VL 481
IS 7382
BP 502
EP U114
DI 10.1038/nature10732
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 881GY
UT WOS:000299471800039
PM 22198670
DA 2026-03-09
ER

PT J
AU Finnigan, GC
   Hanson-Smith, V
   Stevens, TH
   Thornton, JW
AF Finnigan, Gregory C.
   Hanson-Smith, Victor
   Stevens, Tom H.
   Thornton, Joseph W.
TI Evolution of increased complexity in a molecular machine
SO NATURE
LA English
DT Article
ID multiple sequence alignment; membrane h+-atpase; vacuolar; gene; subunit; acidification; algorithm; rotation; accurate; origin
AB Many cellular processes are carried out by molecular 'machines'-assemblies of multiple differentiated proteins that physically interact to execute biological functions(1-8). Despite much speculation, strong evidence of the mechanisms by which these assemblies evolved is lacking. Here we use ancestral gene resurrection(9-11) and manipulative genetic experiments to determine how the complexity of an essential molecular machine-the hexameric transmembrane ring of the eukaryotic V-ATPase proton pump-increased hundreds of millions of years ago. We show that the ring of Fungi, which is composed of three paralogous proteins, evolved from a more ancient two-paralogue complex because of a gene duplication that was followed by loss in each daughter copy of specific interfaces by which it interacts with other ring proteins. These losses were complementary, so both copies became obligate components with restricted spatial roles in the complex. Reintroducing a single historical mutation from each paralogue lineage into the resurrected ancestral proteins is sufficient to recapitulate their asymmetric degeneration and trigger the requirement for the more elaborate three-component ring. Our experiments show that increased complexity in an essential molecular machine evolved because of simple, high-probability evolutionary processes, without the apparent evolution of novel functions. They point to a plausible mechanism for the evolution of complexity in other multi-paralogue protein complexes.
C1 [Hanson-Smith, Victor; Thornton, Joseph W.] Univ Oregon, Inst Ecol & Evolut, Eugene, OR 97403 USA.
   [Finnigan, Gregory C.; Stevens, Tom H.] Univ Oregon, Inst Mol Biol, Eugene, OR 97403 USA.
   [Hanson-Smith, Victor] Univ Oregon, Dept Comp & Informat Sci, Eugene, OR 97403 USA.
   [Thornton, Joseph W.] Univ Oregon, Howard Hughes Med Inst, Eugene, OR 97403 USA.
   [Thornton, Joseph W.] Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA.
   [Thornton, Joseph W.] Univ Chicago, Dept Ecol & Evolut, Chicago, IL 60637 USA.
C3 University of Oregon; University of Oregon; University of Oregon; University of Oregon; Howard Hughes Medical Institute; University of Chicago; University of Chicago
RP Thornton, JW (corresponding author), Univ Oregon, Inst Ecol & Evolut, Eugene, OR 97403 USA.
EM joet@uoregon.edu
FU National Institutes of Health (NIH) [R01-GM081592, R01-GM38006, T32-GM007257]; National Science Foundation (NSF) [IOB-0546906, DEB-0516530]; NSF IGERT [DGE-9972830]; Howard Hughes Medical Institute
NR 47
TC 165
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 JAN 19
PY 2012
VL 481
IS 7381
BP 360
EP U143
DI 10.1038/nature10724
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 877VK
UT WOS:000299210600042
PM 22230956
DA 2026-03-09
ER

PT J
AU Solt, LA
   Wang, YJ
   Banerjee, S
   Hughes, T
   Kojetin, DJ
   Lundasen, T
   Shin, Y
   Liu, J
   Cameron, MD
   Noel, R
   Yoo, SH
   Takahashi, JS
   Butler, AA
   Kamenecka, TM
   Burris, TP
AF Solt, Laura A.
   Wang, Yongjun
   Banerjee, Subhashis
   Hughes, Travis
   Kojetin, Douglas J.
   Lundasen, Thomas
   Shin, Youseung
   Liu, Jin
   Cameron, Michael D.
   Noel, Romain
   Yoo, Seung-Hee
   Takahashi, Joseph S.
   Butler, Andrew A.
   Kamenecka, Theodore M.
   Burris, Thomas P.
TI Regulation of circadian behaviour and metabolism by synthetic REV-ERB agonists
SO NATURE
LA English
DT Article
ID orphan nuclear receptors; alpha; clock; heme; components; ligand; beta; identification; transcription; expression
AB Synchronizing rhythms of behaviour and metabolic processes is important for cardiovascular health and preventing metabolic diseases. The nuclear receptors REV-ERB-alpha and REV-ERB-beta have an integral role in regulating the expression of core clock proteins driving rhythms in activity and metabolism. Here we describe the identification of potent synthetic REV-ERB agonists with in vivo activity. Administration of synthetic REV-ERB ligands alters circadian behaviour and the circadian pattern of core clock gene expression in the hypothalami of mice. The circadian pattern of expression of an array of metabolic genes in the liver, skeletal muscle and adipose tissue was also altered, resulting in increased energy expenditure. Treatment of diet-induced obese mice with a REV-ERB agonist decreased obesity by reducing fat mass and markedly improving dyslipidaemia and hyperglycaemia. These results indicate that synthetic REV-ERB ligands that pharmacologically target the circadian rhythm may be beneficial in the treatment of sleep disorders as well as metabolic diseases.
C1 [Solt, Laura A.; Wang, Yongjun; Banerjee, Subhashis; Hughes, Travis; Kojetin, Douglas J.; Lundasen, Thomas; Liu, Jin; Burris, Thomas P.] Scripps Res Inst, Dept Mol Therapeut, Jupiter, FL 33458 USA.
   [Shin, Youseung; Cameron, Michael D.; Noel, Romain; Kamenecka, Theodore M.] Scripps Res Inst, Translat Res Inst, Jupiter, FL 33458 USA.
   [Yoo, Seung-Hee; Takahashi, Joseph S.] Univ Texas SW Med Ctr Dallas, Howard Hughes Med Inst, Dallas, TX 75390 USA.
   [Yoo, Seung-Hee; Takahashi, Joseph S.] Univ Texas SW Med Ctr Dallas, Dept Neurosci, Dallas, TX 75390 USA.
   [Butler, Andrew A.] Scripps Res Inst, Dept Metab & Aging, Jupiter, FL 33458 USA.
   [Burris, Thomas P.] Scripps Res Inst, Ctr Diabet & Metab Dis, Jupiter, FL 33458 USA.
C3 State University System of Florida; University of Florida; Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology; State University System of Florida; University of Florida; Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology; Howard Hughes Medical Institute; University of Texas System; University of Texas Southwestern Medical Center; University of Texas System; University of Texas Southwestern Medical Center; State University System of Florida; University of Florida; Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology; State University System of Florida; University of Florida; Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology
RP Burris, TP (corresponding author), Scripps Res Inst, Dept Mol Therapeut, Jupiter, FL 33458 USA.
EM tburris@scripps.edu
FU National Institutes of Health [DK080201, MH092769, DK089984]; Howard Hughes Medical Institute; individual National Research Service Award [DK088499]
NR 28
TC 666
Z9 775
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 MAY 3
PY 2012
VL 485
IS 7396
BP 62
EP 68
DI 10.1038/nature11030
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 934NV
UT WOS:000303451900034
PM 22460951
DA 2026-03-09
ER

PT J
AU Druitt, TH
   Costa, F
   Deloule, E
   Dungan, M
   Scaillet, B
AF Druitt, T. H.
   Costa, F.
   Deloule, E.
   Dungan, M.
   Scaillet, B.
TI Decadal to monthly timescales of magma transfer and reservoir growth at a caldera volcano
SO NATURE
LA English
DT Article
ID residence times; ion microprobe; plagioclase; diffusion; santorini; evolution; recharge; trace; sr; emplacement
AB Caldera-forming volcanic eruptions are low-frequency, high-impact events capable of discharging tens to thousands of cubic kilometres of magma explosively on timescales of hours to days, with devastating effects on local and global scales(1). Because no such eruption has been monitored during its long build-up phase, the precursor phenomena are not well understood. Geophysical signals obtained during recent episodes of unrest at calderas such as Yellowstone, USA, and Campi Flegrei, Italy, are difficult to interpret, and the conditions necessary for large eruptions are poorly constrained(2,3). Here we present a study of pre-eruptive magmatic processes and their timescales using chemically zoned crystals from the 'Minoan' caldera-forming eruption of Santorini volcano, Greece(4), which occurred in the late 1600s BC. The results provide insights into how rapidly large silicic systems may pass from a quiescent state to one on the edge of eruption(5,6). Despite the large volume of erupted magma(4) (40-60 cubic kilometres), and the 18,000-year gestation period between the Minoan eruption and the previous major eruption, most crystals in the Minoan magma record processes that occurred less than about 100 years before the eruption. Recharge of the magma reservoir by large volumes of silicic magma (and some mafic magma) occurred during the century before eruption, and mixing between different silicic magma batches was still taking place during the final months. Final assembly of large silicic magma reservoirs may occur on timescales that are geologically very short by comparison with the preceding repose period, with major growth phases immediately before eruption. These observations have implications for the monitoring of long-dormant, but potentially active, caldera systems.
C1 [Druitt, T. H.] Univ Blaise Pascal, Clermont Univ, Lab Magmas & Volcans, F-63000 Clermont Ferrand, France.
   [Druitt, T. H.] CNRS, UMR 6524, LMV, F-63038 Clermont Ferrand, France.
   [Druitt, T. H.] IRD, LMV, F-63038 Clermont Ferrand, France.
   [Costa, F.] Nanyang Technol Univ, Earth Observ Singapore, Singapore 639798, Singapore.
   [Deloule, E.] CRPG CNRS, F-54501 Vandoeuvre Les Nancy, France.
   [Dungan, M.] Univ Geneva, Dept Mineral, CH-1205 Geneva, Switzerland.
   [Scaillet, B.] Univ Tours, Univ Orleans, CNRS, ISTO UMR 6113, F-45071 Orleans, France.
C3 Universite Clermont Auvergne (UCA); Centre National de la Recherche Scientifique (CNRS); Universite Clermont Auvergne (UCA); Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Earth Sciences & Astronomy (INSU); Institut de Recherche pour le Developpement (IRD); Nanyang Technological University; Centre National de la Recherche Scientifique (CNRS); Universite de Lorraine; University of Geneva; Universite de Orleans; Universite de Tours; Centre National de la Recherche Scientifique (CNRS)
RP Druitt, TH (corresponding author), Univ Blaise Pascal, Clermont Univ, Lab Magmas & Volcans, BP 10448, F-63000 Clermont Ferrand, France.
EM t.druitt@opgc.univ-bpclermont.fr
FU French Agence National de Recherche (ANR STOMIXAN) [ANR-08CEA080]
NR 44
TC 313
Z9 353
U1 2
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 FEB 2
PY 2012
VL 482
IS 7383
BP 77
EP U97
DI 10.1038/nature10706
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 884RN
UT WOS:000299726000038
PM 22297973
DA 2026-03-09
ER

PT J
AU Longrich, NR
   Bhullar, BAS
   Gauthier, JA
AF Longrich, Nicholas R.
   Bhullar, Bhart-Anjan S.
   Gauthier, Jacques A.
TI A transitional snake from the Late Cretaceous period of North America
SO NATURE
LA English
DT Article
ID molecular evidence; evolution; origin; skull
AB Snakes are the most diverse group of lizards(1), but their origins and early evolution remain poorly understood owing to a lack of transitional forms. Several major issues remain outstanding, such as whether snakes originated in a marine(2-4) or terrestrial(5,6) environment and how their unique feeding mechanism evolved(1,7,8). The Cretaceous Coniophis precedens was among the first Mesozoic snakes discovered(9), but until now only an isolated vertebra has been described(9,10) and it has therefore been overlooked in discussions of snake evolution. Here we report on previously undescribed material(11) from this ancient snake, including the maxilla, dentary and additional vertebrae. Coniophis is not an anilioid as previously thought(11); a revised phylogenetic analysis of Ophidia shows that it instead represents the most primitive known snake. Accordingly, its morphology and ecology are critical to understanding snake evolution. Coniophis occurs in a continental floodplain environment, consistent with a terrestrial rather than a marine origin; furthermore, its small size and reduced neural spines indicate fossorial habits, suggesting that snakes evolved from burrowing lizards. The skull is intermediate between that of lizards and snakes. Hooked teeth and an intramandibular joint indicate that Coniophis fed on relatively large, soft-bodied prey. However, the maxilla is firmly united with the skull, indicating an akinetic rostrum. Coniophis therefore represents a transitional snake, combining a snake-like body and a lizard-like head. Subsequent to the evolution of a serpentine body and carnivory, snakes evolved a highly specialized, kinetic skull, which was followed by a major adaptive radiation in the Early Cretaceous period. This pattern suggests that the kinetic skull was a key innovation that permitted the diversification of snakes.
C1 [Longrich, Nicholas R.; Gauthier, Jacques A.] Yale Univ, Dept Geol & Geophys, New Haven, CT 06520 USA.
   [Bhullar, Bhart-Anjan S.] Harvard Univ, Dept Organism & Evolutionary Biol, Biol Labs, Cambridge, MA 02138 USA.
C3 Yale University; Harvard University
RP Longrich, NR (corresponding author), Yale Univ, Dept Geol & Geophys, POB 208109, New Haven, CT 06520 USA.
EM nicholas.longrich@yale.edu
FU US NSF [DEB-0132227]; Yale Institute for Biospheric Studies; Division Of Earth Sciences; Directorate For Geosciences [0948842] Funding Source: National Science Foundation
CR Apesteguía S, 2006, NATURE, V440, P1037, DOI 10.1038/nature04413
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   Zaher H, 2009, ZOOL J LINN SOC-LOND, V156, P801, DOI 10.1111/j.1096-3642.2009.00511.x
NR 29
TC 73
Z9 81
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 AUG 9
PY 2012
VL 488
IS 7410
BP 205
EP 208
DI 10.1038/nature11227
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 985LE
UT WOS:000307267000032
PM 22832579
DA 2026-03-09
ER

PT J
AU Huber, S
   Gagliani, N
   Zenewicz, LA
   Huber, FJ
   Bosurgi, L
   Hu, B
   Hedl, M
   Zhang, W
   O'Connor, W
   Murphy, AJ
   Valenzuela, DM
   Yancopoulos, GD
   Booth, CJ
   Cho, JH
   Ouyang, WJ
   Abraham, C
   Flavell, RA
AF Huber, Samuel
   Gagliani, Nicola
   Zenewicz, Lauren A.
   Huber, Francis J.
   Bosurgi, Lidia
   Hu, Bo
   Hedl, Matija
   Zhang, Wei
   O'Connor, William, Jr.
   Murphy, Andrew J.
   Valenzuela, David M.
   Yancopoulos, George D.
   Booth, Carmen J.
   Cho, Judy H.
   Ouyang, Wenjun
   Abraham, Clara
   Flavell, Richard A.
TI IL-22BP is regulated by the inflammasome and modulates tumorigenesis in the intestine
SO NATURE
LA English
DT Article
ID sodium-induced colitis; binding-protein; ulcerative-colitis; crohns-disease; interleukin 22; t-cells; immunity; sulfate; cloning; innate
AB Chronic mucosal inflammation and tissue damage predisposes patients to the development of colorectal cancer(1). This association could be explained by the hypothesis that the same factors and pathways important for wound healing also promote tumorigenesis. A sensor of tissue damage should induce these factors to promote tissue repair and regulate their action to prevent development of cancer. Interleukin 22 (IL-22), a cytokine of the IL-10 superfamily, has an important role in colonic epithelial cell repair, and its levels are increased in the blood and intestine of inflammatory bowel disease patients(2,3). This cytokine can be neutralized by the soluble IL-22 receptor, known as the IL-22 binding protein (IL-22BP, also known as IL22RA2); however, the significance of endogenous IL-22BP in vivo and the pathways that regulate this receptor are unknown(4,5). Here we describe that IL-22BP has a crucial role in controlling tumorigenesis and epithelial cell proliferation in the colon. IL-22BP is highly expressed by dendritic cells in the colon in steady-state conditions. Sensing of intestinal tissue damage via the NLRP3 or NLRP6 inflammasomes led to an IL-18-dependent downregulation of IL-22BP, thereby increasing the ratio of IL-22/IL-22BP. IL-22, which is induced during intestinal tissue damage, exerted protective properties during the peak of damage, but promoted tumour development if uncontrolled during the recovery phase. Thus, the IL-22-IL-22BP axis critically regulates intestinal tissue repair and tumorigenesis in the colon.
C1 [Huber, Samuel; Gagliani, Nicola; Zenewicz, Lauren A.; Bosurgi, Lidia; Hu, Bo; O'Connor, William, Jr.; Flavell, Richard A.] Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT 06520 USA.
   [Huber, Samuel; Huber, Francis J.] Univ Klinikum Hamburg Eppendorf, Med Klin 1, D-20246 Hamburg, Germany.
   [Hedl, Matija; Abraham, Clara] Yale Univ, Sect Digest Dis, Dept Internal Med, New Haven, CT 06520 USA.
   [Zhang, Wei; Cho, Judy H.] Yale Univ, Sch Med, Dept Med, New Haven, CT 06520 USA.
   [Zhang, Wei; Cho, Judy H.] Yale Univ, Sch Med, Dept Genet, Sect Digest Dis, New Haven, CT 06520 USA.
   [Murphy, Andrew J.; Valenzuela, David M.; Yancopoulos, George D.] Regeneron Pharmaceut Inc, Tarrytown, NY 10591 USA.
   [Booth, Carmen J.] Yale Univ, Sch Med, Sect Comparat Med, New Haven, CT 06520 USA.
   [Ouyang, Wenjun] Genentech Inc, Dept Immunol, San Francisco, CA 94080 USA.
   [Flavell, Richard A.] Howard Hughes Med Inst, New Haven, CT 06520 USA.
C3 Yale University; University of Hamburg; University Medical Center Hamburg-Eppendorf; Yale University; Yale University; Yale University; Regeneron; Yale University; Roche Holding; Genentech; Roche Holding USA; Howard Hughes Medical Institute
RP Flavell, RA (corresponding author), Yale Univ, Sch Med, Dept Immunobiol, 333 Cedar St, New Haven, CT 06520 USA.
EM shuber@uke.de; richard.flavell@yale.edu
FU Crohn's and Colitis Foundation of America; Stiftung experimentelle Biomedizin; Ernst Jung Foundation; EMBO; American Cancer Society; DFG [SFB841];  [R01DK077905];  [DK-P30-34989];  [U19-AI082713]; National Institute of Diabetes and Digestive and Kidney Diseases [P30DK034989] Funding Source: NIH RePORTER
NR 35
TC 628
Z9 722
U1 3
U2 120
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD NOV 8
PY 2012
VL 491
IS 7423
BP 259
EP +
DI 10.1038/nature11535
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 033DP
UT WOS:000310774300045
PM 23075849
DA 2026-03-09
ER

PT J
AU Harnett, MT
   Makara, JK
   Spruston, N
   Kath, WL
   Magee, JC
AF Harnett, Mark T.
   Makara, Judit K.
   Spruston, Nelson
   Kath, William L.
   Magee, Jeffrey C.
TI Synaptic amplification by dendritic spines enhances input cooperativity
SO NATURE
LA English
DT Article
ID pyramidal neuron dendrites; electrical compartmentalization; learning rules; plasticity; computation; integration; membrane; signals; model; neck
AB Dendritic spines are the nearly ubiquitous site of excitatory synaptic input onto neurons(1,2) and as such are critically positioned to influence diverse aspects of neuronal signalling. Decades of theoretical studies have proposed that spines may function as highly effective and modifiable chemical and electrical compartments that regulate synaptic efficacy, integration and plasticity(3-8). Experimental studies have confirmed activity-dependent structural dynamics and biochemical compartmentalization by spines(9-12). However, there is a longstanding debate over the influence of spines on the electrical aspects of synaptic transmission and dendritic operation(3-8,13-18). Here we measure the amplitude ratio of spine head to parent dendrite voltage across a range of dendritic compartments and calculate the associated spine neck resistance (R-neck) for spines at apical trunk dendrites in rat hippocampal CA1 pyramidal neurons. We find that R-neck is large enough (similar to 500M Omega) to amplify substantially the spine head depolarization associated with a unitary synaptic input by similar to 1.5- to similar to 45-fold, depending on parent dendritic impedance. A morphologically realistic compartmental model capable of reproducing the observed spatial profile of the amplitude ratio indicates that spines provide a consistently high-impedance input structure throughout the dendritic arborization. Finally, we demonstrate that the amplification produced by spines encourages electrical interaction among coactive inputs through an R-neck-dependent increase in spine head voltage-gated conductance activation. We conclude that the electrical properties of spines promote nonlinear dendritic processing and associated forms of plasticity and storage, thus fundamentally enhancing the computational capabilities of neurons(19-21).
C1 [Harnett, Mark T.; Makara, Judit K.; Spruston, Nelson; Magee, Jeffrey C.] HHMI Janelia Farm Res Campus, Ashburn, VA 20147 USA.
   [Makara, Judit K.] Hungarian Acad Sci, Inst Expt Med, H-1083 Budapest, Hungary.
   [Kath, William L.] Northwestern Univ, Dept Appl Math, Evanston, IL 60208 USA.
   [Kath, William L.] Northwestern Univ, Dept Neurobiol, Evanston, IL 60208 USA.
C3 Howard Hughes Medical Institute; Hungarian Academy of Sciences; HUN-REN; HUN-REN Institute of Experimental Medicine; Northwestern University; Northwestern University
RP Magee, JC (corresponding author), HHMI Janelia Farm Res Campus, Ashburn, VA 20147 USA.
EM mageej@janelia.hhmi.org
FU Howard Hughes Medical Institute; National Institutes of Health [NS-046064, NS-077601]; Wellcome Trust [090915]
NR 39
TC 211
Z9 248
U1 0
U2 73
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD NOV 22
PY 2012
VL 491
IS 7425
BP 599
EP +
DI 10.1038/nature11554
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 040RE
UT WOS:000311339800053
PM 23103868
DA 2026-03-09
ER

PT J
AU Yardimci, H
   Wang, XD
   Loveland, AB
   Tappin, I
   Rudner, DZ
   Hurwitz, J
   van Oijen, AM
   Walter, JC
AF Yardimci, Hasan
   Wang, Xindan
   Loveland, Anna B.
   Tappin, Inger
   Rudner, David Z.
   Hurwitz, Jerard
   van Oijen, Antoine M.
   Walter, Johannes C.
TI Bypass of a protein barrier by a replicative DNA helicase
SO NATURE
LA English
DT Article
ID simian-virus-40 t-antigen; large-tumor-antigen; single-stranded-dna; hexameric helicase; viral origin; sv40 origin; in-vitro; mechanism; fork; translocation
AB Replicative DNA helicases generally unwind DNA as a single hexamer that encircles and translocates along one strand of the duplex while excluding the complementary strand (known as steric exclusion). By contrast, large T antigen, the replicative DNA helicase of the simian virus 40 (SV40), is reported to function as a pair of stacked hexamers that pumps double-stranded DNA through its central channel while laterally extruding single-stranded DNA. Here we use single-molecule and ensemble assays to show that large T antigen assembled on the SV40 origin unwinds DNA efficiently as a single hexamer that translocates on single-stranded DNA in the 3'-to-5' direction. Unexpectedly, large T antigen unwinds DNA past a DNA-protein crosslink on the translocation strand, suggesting that the large T antigen ring can open to bypass bulky adducts. Together, our data underscore the profound conservation among replicative helicase mechanisms, and reveal a new level of plasticity in the interactions of replicative helicases with DNA damage.
C1 [van Oijen, Antoine M.] Univ Groningen, Zernike Inst Adv Mat, NL-9747 AG Groningen, Netherlands.
   [Yardimci, Hasan; Loveland, Anna B.; Walter, Johannes C.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
   [Wang, Xindan; Rudner, David Z.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA 02115 USA.
   [Tappin, Inger; Hurwitz, Jerard] Mem Sloan Kettering Canc Ctr, Program Mol Biol, New York, NY 10065 USA.
C3 University of Groningen; Harvard University; Harvard Medical School; Harvard University; Harvard Medical School; Memorial Sloan Kettering Cancer Center
RP van Oijen, AM (corresponding author), Univ Groningen, Zernike Inst Adv Mat, NL-9747 AG Groningen, Netherlands.
EM a.m.van.oijen@rug.nl; johannes_walter@hms.harvard.edu
FU National Institutes of Health (NIH) [GM62267, HL098316, GM077248, GM5 R01 GM034559, GM086466]; American Cancer Society (ACS) [RSG0823401GMC]; Netherlands Organization for Scientific Research (NWO) [Vici 680-47-607]; National Heart Lung and Blood Institute [R01HL098316] Funding Source: NIH RePORTER; National Institute of General Medical Sciences [R01GM086466] Funding Source: NIH RePORTER
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NR 46
TC 79
Z9 97
U1 0
U2 51
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 13
PY 2012
VL 492
IS 7428
BP 205
EP +
DI 10.1038/nature11730
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 053GM
UT WOS:000312259300032
PM 23201686
DA 2026-03-09
ER

PT J
AU Perez, C
   Koshy, C
   Yildiz, Ö
   Ziegler, C
AF Perez, Camilo
   Koshy, Caroline
   Yildiz, Oezkan
   Ziegler, Christine
TI Alternating-access mechanism in conformationally asymmetric trimers of the betaine transporter BetP
SO NATURE
LA English
DT Article
ID na+/betaine symporter betp; corynebacterium-glutamicum; crystal-structure; molecular-basis; carrier betp; open states; k+; homolog; binding; sodium
AB Betaine and Na+ symport has been extensively studied in the osmotically regulated transporter BetP from Corynebacterium glutamicum, a member of the betaine/choline/carnitine transporter family, which shares the conserved LeuT-like fold of two inverted structural repeats(1). BetP adjusts its transport activity by sensing the cytoplasmic K+ concentration as a measure for hyperosmotic stress via the osmosensing carboxy-terminal domain(2,3). BetP needs to be in a trimeric state for communication between individual protomers through several intratrimeric interaction sites(4). Recently, crystal structures of inward-facing BetP trimers have contributed to our understanding of activity regulation on a molecular level(5,6). Here we report new crystal structures, which reveal two conformationally asymmetric BetP trimers(7), capturing among them three distinct transport states. We observe a total of four new conformations at once: an outward-open apo and an outward-occluded apo state, and two closed transition states-one in complex with betaine and one substrate-free. On the basis of these new structures, we identified local and global conformational changes in BetP that underlie the molecular transport mechanism, which partially resemble structural changes observed in other sodium-coupled LeuT-like fold transporters, but show differences we attribute to the osmolytic nature of betaine, the exclusive substrate specificity and the regulatory properties of BetP.
C1 [Perez, Camilo; Koshy, Caroline; Yildiz, Oezkan; Ziegler, Christine] Max Planck Inst Biophys, Dept Biol Struct, D-60438 Frankfurt, Germany.
   [Ziegler, Christine] Univ Regensburg, Inst Biophys & Biophys Chem, D-93053 Regensburg, Germany.
C3 Max Planck Society; University of Regensburg
RP Ziegler, C (corresponding author), Max Planck Inst Biophys, Dept Biol Struct, D-60438 Frankfurt, Germany.
EM christine.ziegler@biophys.mpg.de
FU International Max-Planck Research School; DFG (German Research Foundation), Collaborative Research Center 807 "Transport and Communication across Biological Membranes"
CR Bourot S, 2000, J BIOL CHEM, V275, P1050, DOI 10.1074/jbc.275.2.1050
   Fang YL, 2009, NATURE, V460, P1040, DOI 10.1038/nature08201
   Gärtner RM, 2011, J MOL BIOL, V414, P327, DOI 10.1016/j.jmb.2011.10.013
   Ge L, 2011, P NATL ACAD SCI USA, V108, PE890, DOI 10.1073/pnas.1109597108
   Hunte C, 2005, NATURE, V435, P1197, DOI 10.1038/nature03692
   Krishnamurthy H, 2012, NATURE, V481, P469, DOI 10.1038/nature10737
   Ott V, 2008, BIOCHEMISTRY-US, V47, P12208, DOI 10.1021/bi801325r
   Perez C, 2011, EMBO REP, V12, P804, DOI 10.1038/embor.2011.102
   Perez C, 2011, EMBO J, V30, P1221, DOI 10.1038/emboj.2011.46
   Ressl S, 2009, NATURE, V458, P47, DOI 10.1038/nature07819
   Rübenhagen R, 2001, EMBO J, V20, P5412, DOI 10.1093/emboj/20.19.5412
   Schiller D, 2004, BIOCHEMISTRY-US, V43, P5583, DOI 10.1021/bi0359628
   Shi L, 2010, BIOPHYS J, V99, PL103, DOI 10.1016/j.bpj.2010.10.003
   Shimamura T, 2010, SCIENCE, V328, P470, DOI 10.1126/science.1186303
   Tsai CJ, 2011, J MOL BIOL, V407, P368, DOI 10.1016/j.jmb.2011.01.028
   Watanabe A, 2010, NATURE, V468, P988, DOI 10.1038/nature09580
   Wetzel KJ, 2011, FEMS IMMUNOL MED MIC, V61, P346, DOI 10.1111/j.1574-695X.2011.00781.x
   Yamashita A, 2005, NATURE, V437, P215, DOI 10.1038/nature03978
   Zhao YF, 2010, NATURE, V465, P188, DOI 10.1038/nature09057
   Ziegler C, 2004, J MOL BIOL, V337, P1137, DOI 10.1016/j.jmb.2004.02.026
   Ziegler C, 2010, MOL MICROBIOL, V78, P13, DOI 10.1111/j.1365-2958.2010.07332.x
NR 21
TC 117
Z9 141
U1 1
U2 44
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD OCT 4
PY 2012
VL 490
IS 7418
BP 126
EP 130
DI 10.1038/nature11403
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 015LG
UT WOS:000309446800046
PM 22940865
DA 2026-03-09
ER

PT J
AU McDole, JR
   Wheeler, LW
   McDonald, KG
   Wang, BM
   Konjufca, V
   Knoop, KA
   Newberry, RD
   Miller, MJ
AF McDole, Jeremiah R.
   Wheeler, Leroy W.
   McDonald, Keely G.
   Wang, Baomei
   Konjufca, Vjollca
   Knoop, Kathryn A.
   Newberry, Rodney D.
   Miller, Mark J.
TI Goblet cells deliver luminal antigen to CD103+ dendritic cells in the small intestine
SO NATURE
LA English
DT Article
ID green fluorescent protein; barrier function; crohns-disease; mice; tight; colitis; lumen; muc2
AB The intestinal immune system is exposed to a mixture of foreign antigens from diet, commensal flora and potential pathogens. Understanding how pathogen-specific immunity is elicited while avoiding inappropriate responses to the background of innocuous antigens is essential for understanding and treating intestinal infections and inflammatory diseases. The ingestion of protein antigen can induce oral tolerance, which is mediated in part by a subset of intestinal dendritic cells (DCs) that promote the development of regulatory T cells(1). The lamina propria (LP) underlies the expansive single-cell absorptive villous epithelium and contains a large population of DCs (CD11c(+) CD11b(+) MHCII+ cells) comprised of two predominant subsets: CD103(+) CX(3)CR1(-) DCs, which promote IgA production, imprint gut homing on lymphocytes and induce the development of regulatory T cells(2-9), and CD103(-) CX(3)CR1(+) DCs (with features of macrophages), which promote tumour necrosis factor-alpha (TNF-alpha) production, colitis, and the development of T(H)17 T cells(5-7,10). However, the mechanisms by which different intestinal LP-DC subsets capture luminal antigens in vivo remains largely unexplored. Using a minimally disruptive in vivo imaging approach we show that in the steady state, small intestine goblet cells (GCs) function as passages delivering low molecular weight soluble antigens from the intestinal lumen to underlying CD103(+) LP-DCs. The preferential delivery of antigens to DCs with tolerogenic properties implies a key role for this GC function in intestinal immune homeostasis.
C1 [McDole, Jeremiah R.; Wang, Baomei; Miller, Mark J.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA.
   [Wheeler, Leroy W.; McDonald, Keely G.; Knoop, Kathryn A.; Newberry, Rodney D.] Washington Univ, Sch Med, Dept Internal Med, St Louis, MO 63110 USA.
   [Konjufca, Vjollca] So Illinois Univ, Dept Microbiol, Carbondale, IL 62901 USA.
C3 Washington University (WUSTL); Washington University (WUSTL); Southern Illinois University System; Southern Illinois University
RP Miller, MJ (corresponding author), Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA.
EM rnewberry@wustl.edu; miller@pathology.wustl.edu
FU NCI Cancer Center [P30 CA91842];  [DK064798];  [AI083538];  [AI095550];  [DK085941];  [AI077600];  [P30-DK52574]; National Cancer Institute [P30CA091842] Funding Source: NIH RePORTER; National Institute of Allergy and Infectious Diseases [R01AI077600] Funding Source: NIH RePORTER; National Institute of Diabetes and Digestive and Kidney Diseases [P30DK052574] Funding Source: NIH RePORTER
NR 32
TC 752
Z9 920
U1 5
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 MAR 15
PY 2012
VL 483
IS 7389
BP 345
EP U141
DI 10.1038/nature10863
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 908HP
UT WOS:000301481800052
PM 22422267
DA 2026-03-09
ER

PT J
AU Ding, L
   Saunders, TL
   Enikolopov, G
   Morrison, SJ
AF Ding, Lei
   Saunders, Thomas L.
   Enikolopov, Grigori
   Morrison, Sean J.
TI Endothelial and perivascular cells maintain haematopoietic stem cells
SO NATURE
LA English
DT Article
ID progenitor cells; self-renewal; expression; gene; mice; maintenance; deletion; niches; transplantation; osteoblasts
AB Several cell types have been proposed to create niches for haematopoietic stem cells (HSCs). However, the expression patterns of HSC maintenance factors have not been systematically studied and no such factor has been conditionally deleted from any candidate niche cell. Thus, the cellular sources of these factors are undetermined. Stem cell factor (SCF; also known as KITL) is a key niche component that maintains HSCs. Here, using Scf(gfp) knock-in mice, we found that Scf was primarily expressed by perivascular cells throughout the bone marrow. HSC frequency and function were not affected when Scf was conditionally deleted from haematopoietic cells, osteoblasts, nestin-cre- or nestin-creER-expressing cells. However, HSCs were depleted from bone marrow when Scf was deleted from endothelial cells or leptin receptor (Lepr)-expressing perivascular stromal cells. Most HSCs were lost when Scf was deleted from both endothelial and Lepr-expressing perivascular cells. Thus, HSCs reside in a perivascular niche in which multiple cell types express factors that promote HSC maintenance.
C1 [Ding, Lei; Morrison, Sean J.] Univ Texas SW Med Ctr Dallas, Howard Hughes Med Inst, Childrens Res Inst, Dept Pediat, Dallas, TX 75390 USA.
   [Saunders, Thomas L.] Univ Michigan, Ann Arbor, MI 48109 USA.
   [Enikolopov, Grigori] Cold Spring Harbor Lab, New York, NY 11724 USA.
C3 Howard Hughes Medical Institute; University of Texas System; University of Texas Southwestern Medical Center; University of Michigan System; University of Michigan; Cold Spring Harbor Laboratory
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 Howard Hughes Medical Institute (HHMI); National Heart, Lung and Blood Institute [5R01HL097760]; Helen Hay Whitney Foundation; National Institute of Aging [R01AG040209]; NYSTEM
NR 43
TC 1549
Z9 1823
U1 0
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 26
PY 2012
VL 481
IS 7382
BP 457
EP U65
DI 10.1038/nature10783
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 881GY
UT WOS:000299471800030
PM 22281595
DA 2026-03-09
ER

PT J
AU Shcheka, SS
   Keppler, H
AF Shcheka, Svyatoslav S.
   Keppler, Hans
TI The origin of the terrestrial noble-gas signature
SO NATURE
LA English
DT Article
ID magnesium-silicate perovskite; aluminum substitution; xenon; water; atmospheres; evolution; mgsio3; argon; laser; earth
AB In the atmospheres of Earth and Mars, xenon is strongly depleted relative to argon, when compared to the abundances in chondritic meteorites(1,2). The origin of this depletion is poorly understood(3-13). Here we show that more than one weight per cent of argon may be dissolved in MgSiO3 perovskite, the most abundant phase of Earth's lower mantle, whereas the xenon solubility in MgSiO3 perovskite is orders of magnitude lower. We therefore suggest that crystallization of perovskite from a magma ocean in the very early stages of Earth's history concentrated argon in the lower mantle. After most of the primordial atmosphere had been lost, degassing of the lower mantle replenished argon and krypton, but not xenon, in the atmosphere. Our model implies that the depletion of xenon relative to argon indicates that perovskite crystallized from a magma ocean in the early history of Earth and perhaps also Mars.
C1 [Shcheka, Svyatoslav S.; Keppler, Hans] Univ Bayreuth, Bayer Geoinst, D-95440 Bayreuth, Germany.
C3 University of Bayreuth
RP Shcheka, SS (corresponding author), Univ Bayreuth, Bayer Geoinst, POB 101251, D-95440 Bayreuth, Germany.
EM svyatoslav.shcheka@uni-bayreuth.de
FU German Science Foundation (DFG) [SPP 1236]
NR 32
TC 54
Z9 62
U1 3
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 OCT 25
PY 2012
VL 490
IS 7421
BP 531
EP +
DI 10.1038/nature11506
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 025NK
UT WOS:000310196200040
PM 23051754
DA 2026-03-09
ER

PT J
AU Sun, JY
   Zhao, XH
   Illeperuma, WRK
   Chaudhuri, O
   Oh, KH
   Mooney, DJ
   Vlassak, JJ
   Suo, ZG
AF Sun, Jeong-Yun
   Zhao, Xuanhe
   Illeperuma, Widusha R. K.
   Chaudhuri, Ovijit
   Oh, Kyu Hwan
   Mooney, David J.
   Vlassak, Joost J.
   Suo, Zhigang
TI Highly stretchable and tough hydrogels
SO NATURE
LA English
DT Article
ID double-network gels; high mechanical strength; large-strain; fracture; hysteresis; fatigue; model
AB Hydrogels are used as scaffolds for tissue engineering(1), vehicles for drug delivery(2), actuators for optics and fluidics(3), and model extracellular matrices for biological studies(4). The scope of hydrogel applications, however, is often severely limited by their mechanical behaviour(5). Most hydrogels do not exhibit high stretchability; for example, an alginate hydrogel ruptures when stretched to about 1.2 times its original length. Some synthetic elastic hydrogels(6,7) have achieved stretches in the range 10-20, but these values are markedly reduced in samples containing notches. Most hydrogels are brittle, with fracture energies of about 10 J m(-2) (ref. 8), as compared with similar to 1,000 J m(-2) for cartilage(9) and similar to 10,000 J m(-2) for natural rubbers(10). Intense efforts are devoted to synthesizing hydrogels with improved mechanical properties(11-18); certain synthetic gels have reached fracture energies of 100-1,000 J m(-2) (refs 11, 14, 17). Here we report the synthesis of hydrogels from polymers forming ionically and covalently crosslinked networks. Although such gels contain similar to 90% water, they can be stretched beyond 20 times their initial length, and have fracture energies of similar to 9,000 J m(-2). Even for samples containing notches, a stretch of 17 is demonstrated. We attribute the gels' toughness to the synergy of two mechanisms: crack bridging by the network of covalent crosslinks, and hysteresis by unzipping the network of ionic crosslinks. Furthermore, the network of covalent crosslinks preserves the memory of the initial state, so that much of the large deformation is removed on unloading. The unzipped ionic crosslinks cause internal damage, which heals by re-zipping. These gels may serve as model systems to explore mechanisms of deformation and energy dissipation, and expand the scope of hydrogel applications.
C1 [Sun, Jeong-Yun; Illeperuma, Widusha R. K.; Chaudhuri, Ovijit; Mooney, David J.; Vlassak, Joost J.; Suo, Zhigang] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA.
   [Sun, Jeong-Yun; Oh, Kyu Hwan] Seoul Natl Univ, Dept Mat Sci & Engn, Seoul 151742, South Korea.
   [Zhao, Xuanhe] Duke Univ, Dept Mech Engn & Mat Sci, Durham, NC 27708 USA.
   [Mooney, David J.] Harvard Univ, Wyss Inst Biologically Inspired Engn, Cambridge, MA 02138 USA.
   [Suo, Zhigang] Harvard Univ, Kavli Inst Bionano Sci & Technol, Cambridge, MA 02138 USA.
C3 Harvard University; Seoul National University (SNU); Duke University; Harvard University; Harvard University
RP Suo, ZG (corresponding author), Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA.
EM suo@seas.harvard.edu
FU ARO [W911NF-09-1-0476]; NSF [CMMI-0800161]; DARPA [W911NF-10-1-0113]; NIH [R37 DE013033]; MRSEC [DMR-0820484]; NSF Research Triangle MRSEC [DMR-1121107]; Haythornthwaite Research Initiation grants; National Research Foundation of Korea (NRF); Ministry of Education, Science and Technology [R11-2005-065]; Alexander von Humboldt Award; Harvard University
NR 30
TC 4823
Z9 5416
U1 185
U2 7933
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD SEP 6
PY 2012
VL 489
IS 7414
BP 133
EP 136
DI 10.1038/nature11409
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 999WW
UT WOS:000308347000049
PM 22955625
DA 2026-03-09
ER

PT J
AU Ahrens, MB
   Li, JM
   Orger, MB
   Robson, DN
   Schier, AF
   Engert, F
   Portugues, R
AF Ahrens, Misha B.
   Li, Jennifer M.
   Orger, Michael B.
   Robson, Drew N.
   Schier, Alexander F.
   Engert, Florian
   Portugues, Ruben
TI Brain-wide neuronal dynamics during motor adaptation in zebrafish
SO NATURE
LA English
DT Article
ID functional ground plan; cellular resolution; odor representations; neural activity; hindbrain; behavior; drosophila; motion; cerebellum; expression
AB A fundamental question in neuroscience is how entire neural circuits generate behaviour and adapt it to changes in sensory feedback. Here we use two-photon calcium imaging to record the activity of large populations of neurons at the cellular level, throughout the brain of larval zebrafish expressing a genetically encoded calcium sensor, while the paralysed animals interact fictively with a virtual environment and rapidly adapt their motor output to changes in visual feedback. We decompose the network dynamics involved in adaptive locomotion into four types of neuronal response properties, and provide anatomical maps of the corresponding sites. A subset of these signals occurred during behavioural adjustments and are candidates for the functional elements that drive motor learning. Lesions to the inferior olive indicate a specific functional role for olivocerebellar circuitry in adaptive locomotion. This study enables the analysis of brain-wide dynamics at single-cell resolution during behaviour.
C1 [Ahrens, Misha B.; Li, Jennifer M.; Robson, Drew N.; Schier, Alexander F.; Engert, Florian; Portugues, Ruben] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA.
   [Ahrens, Misha B.] Univ Cambridge, Dept Engn, Computat & Biol Learning Lab, Cambridge CB2 1PZ, England.
   [Orger, Michael B.] Champalimaud Ctr Unknown, Champalimaud Neurosci Programme, P-1400038 Lisbon, Portugal.
C3 Harvard University; University of Cambridge; Fundacao Champalimaud
RP Engert, F (corresponding author), Harvard Univ, Dept Mol & Cellular Biol, 16 Divin Ave, Cambridge, MA 02138 USA.
EM florian@mcb.harvard.edu
FU Wellcome Trust; K99 [5K99NS62780-2]; National Institutes of Health [5R01EY014429, RC2NS069407]
NR 52
TC 493
Z9 595
U1 2
U2 174
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 24
PY 2012
VL 485
IS 7399
BP 471
EP U80
DI 10.1038/nature11057
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 946IH
UT WOS:000304344500036
PM 22622571
DA 2026-03-09
ER

PT J
AU Northcott, PA
   Shih, DJH
   Peacock, J
   Garzia, L
   Morrissy, AS
   Zichner, T
   Stütz, AM
   Korshunov, A
   Reimand, J
   Schumacher, SE
   Beroukhim, R
   Ellison, DW
   Marshall, CR
   Lionel, AC
   Mack, S
   Dubuc, A
   Yao, Y
   Ramaswamy, V
   Luu, B
   Rolider, A
   Cavalli, FMG
   Wang, X
   Remke, M
   Wu, XC
   Chiu, RYB
   Chu, A
   Chuah, E
   Corbett, RD
   Hoad, GR
   Jackman, SD
   Li, YS
   Lo, A
   Mungall, KL
   Nip, KM
   Qian, JQ
   Raymond, AGJ
   Thiessen, N
   Varhol, RJ
   Birol, I
   Moore, RA
   Mungall, AJ
   Holt, R
   Kawauchi, D
   Roussel, MF
   Kool, M
   Jones, DTW
   Witt, H
   Fernandez-L, A
   Kenney, AM
   Wechsler-Reya, RJ
   Dirks, P
   Aviv, T
   Grajkowska, WA
   Perek-Polnik, M
   Haberler, CC
   Delattre, O
   Reynaud, SS
   Doz, FF
   Pernet-Fattet, SS
   Cho, BK
   Kim, SK
   Wang, KC
   Scheurlen, W
   Eberhart, CG
   Fèvre-Montange, M
   Jouvet, A
   Pollack, IF
   Fan, X
   Muraszko, KM
   Gillespie, GY
   Di Rocco, C
   Massimi, L
   Michiels, EMC
   Kloosterhof, NK
   French, PJ
   Kros, JM
   Olson, JM
   Ellenbogen, RG
   Zitterbart, K
   Kren, L
   Thompson, RC
   Cooper, MK
   Lach, B
   McLendon, RE
   Bigner, DD
   Fontebasso, A
   Albrecht, S
   Jabado, N
   Lindsey, JC
   Bailey, S
   Gupta, N
   Weiss, WA
   Bognár, L
   Klekner, A
   Van Meter, TE
   Kumabe, T
   Tominaga, T
   Elbabaa, SK
   Leonard, JR
   Rubin, JB
   Liau, LM
   Van Meir, EG
   Fouladi, M
   Nakamura, H
   Cinalli, G
   Garami, M
   Hauser, P
   Saad, AG
   Iolascon, A
   Jung, S
   Carlotti, CG
   Vibhakar, R
   Ra, YS
   Robinson, S
   Zollo, M
   Faria, CC
   Chan, JA
   Levy, ML
   Sorensen, PHB
   Meyerson, M
   Pomeroy, SL
   Cho, YJ
   Bader, GD
   Tabori, U
   Hawkins, CE
   Bouffet, E
   Scherer, SW
   Rutka, JT
   Malkin, D
   Clifford, SC
   Jones, SJM
   Korbel, JO
   Pfister, SM
   Marra, MA
   Taylor, MD
AF Northcott, Paul A.
   Shih, David J. H.
   Peacock, John
   Garzia, Livia
   Morrissy, A. Sorana
   Zichner, Thomas
   Stuetz, Adrian M.
   Korshunov, Andrey
   Reimand, Jueri
   Schumacher, Steven E.
   Beroukhim, Rameen
   Ellison, David W.
   Marshall, Christian R.
   Lionel, Anath C.
   Mack, Stephen
   Dubuc, Adrian
   Yao, Yuan
   Ramaswamy, Vijay
   Luu, Betty
   Rolider, Adi
   Cavalli, Florence M. G.
   Wang, Xin
   Remke, Marc
   Wu, Xiaochong
   Chiu, Readman Y. B.
   Chu, Andy
   Chuah, Eric
   Corbett, Richard D.
   Hoad, Gemma R.
   Jackman, Shaun D.
   Li, Yisu
   Lo, Allan
   Mungall, Karen L.
   Nip, Ka Ming
   Qian, Jenny Q.
   Raymond, Anthony G. J.
   Thiessen, Nina
   Varhol, Richard J.
   Birol, Inanc
   Moore, Richard A.
   Mungall, Andrew J.
   Holt, Robert
   Kawauchi, Daisuke
   Roussel, Martine F.
   Kool, Marcel
   Jones, David T. W.
   Witt, Hendrick
   Fernandez-L, Africa
   Kenney, Anna M.
   Wechsler-Reya, Robert J.
   Dirks, Peter
   Aviv, Tzvi
   Grajkowska, Wieslawa A.
   Perek-Polnik, Marta
   Haberler, Christine C.
   Delattre, Olivier
   Reynaud, Stephanie S.
   Doz, Francois F.
   Pernet-Fattet, Sarah S.
   Cho, Byung-Kyu
   Kim, Seung-Ki
   Wang, Kyu-Chang
   Scheurlen, Wolfram
   Eberhart, Charles G.
   Fevre-Montange, Michelle
   Jouvet, Anne
   Pollack, Ian F.
   Fan, Xing
   Muraszko, Karin M.
   Gillespie, G. Yancey
   Di Rocco, Concezio
   Massimi, Luca
   Michiels, Erna M. C.
   Kloosterhof, Nanne K.
   French, Pim J.
   Kros, Johan M.
   Olson, James M.
   Ellenbogen, Richard G.
   Zitterbart, Karel
   Kren, Leos
   Thompson, Reid C.
   Cooper, Michael K.
   Lach, Boleslaw
   McLendon, Roger E.
   Bigner, Darell D.
   Fontebasso, Adam
   Albrecht, Steffen
   Jabado, Nada
   Lindsey, Janet C.
   Bailey, Simon
   Gupta, Nalin
   Weiss, William A.
   Bognar, Laszlo
   Klekner, Almos
   Van Meter, Timothy E.
   Kumabe, Toshihiro
   Tominaga, Teiji
   Elbabaa, Samer K.
   Leonard, Jeffrey R.
   Rubin, Joshua B.
   Liau, Linda M.
   Van Meir, Erwin G.
   Fouladi, Maryam
   Nakamura, Hideo
   Cinalli, Giuseppe
   Garami, Miklos
   Hauser, Peter
   Saad, Ali G.
   Iolascon, Achille
   Jung, Shin
   Carlotti, Carlos G.
   Vibhakar, Rajeev
   Ra, Young Shin
   Robinson, Shenandoah
   Zollo, Massimo
   Faria, Claudia C.
   Chan, Jennifer A.
   Levy, Michael L.
   Sorensen, Poul H. B.
   Meyerson, Matthew
   Pomeroy, Scott L.
   Cho, Yoon-Jae
   Bader, Gary D.
   Tabori, Uri
   Hawkins, Cynthia E.
   Bouffet, Eric
   Scherer, Stephen W.
   Rutka, James T.
   Malkin, David
   Clifford, Steven C.
   Jones, Steven J. M.
   Korbel, Jan O.
   Pfister, Stefan M.
   Marra, Marco A.
   Taylor, Michael D.
TI Subgroup-specific structural variation across 1,000 medulloblastoma genomes
SO NATURE
LA English
DT Article
ID hedgehog pathway inhibitor; copy-number alteration; alpha-synuclein; beta family; synphilin-1; protein; myc; landscape; mutation; targets
AB Medulloblastoma, the most common malignant paediatric brain tumour, is currently treated with nonspecific cytotoxic therapies including surgery, whole-brain radiation, and aggressive chemotherapy. As medulloblastoma exhibits marked intertumoural heterogeneity, with at least four distinct molecular variants, previous attempts to identify targets for therapy have been underpowered because of small samples sizes. Here we report somatic copy number aberrations (SCNAs) in 1,087 unique medulloblastomas. SCNAs are common in medulloblastoma, and are predominantly subgroup-enriched. The most common region of focal copy number gain is a tandem duplication of SNCAIP, a gene associated with Parkinson's disease, which is exquisitely restricted to Group 4 alpha. Recurrent translocations of PVT1, including PVT1-MYC and PVT1-NDRG1, that arise through chromothripsis are restricted to Group 3. Numerous targetable SCNAs, including recurrent events targeting TGF-beta signalling in Group 3, and NF-kappa B signalling in Group 4, suggest future avenues for rational, targeted therapy.
C1 [Holt, Robert; Marra, Marco A.] Michael Smith Genome Sci Ctr, BC Canc Agcy, Vancouver, BC V5Z 1L3, Canada.
   [Northcott, Paul A.; Shih, David J. H.; Peacock, John; Garzia, Livia; Morrissy, A. Sorana; Mack, Stephen; Dubuc, Adrian; Yao, Yuan; Ramaswamy, Vijay; Luu, Betty; Rolider, Adi; Cavalli, Florence M. G.; Wang, Xin; Remke, Marc; Wu, Xiaochong; Taylor, Michael D.] Hosp Sick Children, Dev & Stem Cell Biol Program, Toronto, ON M5G 1L7, Canada.
   [Northcott, Paul A.; Kool, Marcel; Jones, David T. W.; Pfister, Stefan M.] German Canc Res Ctr, Div Pediat Neurooncol, D-69120 Heidelberg, Germany.
   [Shih, David J. H.; Peacock, John; Mack, Stephen; Dubuc, Adrian; Yao, Yuan; Ramaswamy, Vijay; Wang, Xin; Taylor, Michael D.] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON M5S 1A8, Canada.
   [Zichner, Thomas; Stuetz, Adrian M.; Korbel, Jan O.] European Mol Biol Lab, D-69117 Heidelberg, Germany.
   [Korshunov, Andrey] Heidelberg Univ, German Canc Res Ctr DKFZ, Dept Neuropathol, CCU Neuropathol, D-69120 Heidelberg, Germany.
   [Reimand, Jueri; Bader, Gary D.] Univ Toronto, Donnelly Ctr, Toronto, ON M5S 3E1, Canada.
   [Schumacher, Steven E.; Beroukhim, Rameen] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA.
   [Beroukhim, Rameen; Meyerson, Matthew] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA.
   [Beroukhim, Rameen] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.
   [Beroukhim, Rameen] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
   [Beroukhim, Rameen] Broad Inst, Canc Program, Cambridge, MA 02142 USA.
   [Beroukhim, Rameen] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02215 USA.
   [Ellison, David W.; Kawauchi, Daisuke; Roussel, Martine F.] St Jude Childrens Res Hosp, Memphis, TN 38105 USA.
   [Marshall, Christian R.; Bader, Gary D.; Scherer, Stephen W.] Univ Toronto, McLaughlin Ctr, Toronto, ON M5G 1L7, Canada.
   [Marshall, Christian R.; Bader, Gary D.; Scherer, Stephen W.] Univ Toronto, Dept Mol Genet, Toronto, ON M5G 1L7, Canada.
   [Lionel, Anath C.; Scherer, Stephen W.] Hosp Sick Children, Ctr Appl Genom & Program Genet & Genome Biol, Toronto, ON M5G 1L7, Canada.
   [Chiu, Readman Y. B.; Chu, Andy; Chuah, Eric; Corbett, Richard D.; Hoad, Gemma R.; Jackman, Shaun D.; Li, Yisu; Lo, Allan; Mungall, Karen L.; Nip, Ka Ming; Qian, Jenny Q.; Raymond, Anthony G. J.; Thiessen, Nina; Varhol, Richard J.; Birol, Inanc; Moore, Richard A.; Mungall, Andrew J.; Jones, Steven J. M.] Michael Smith Genome Sci Ctr, BC Canc Agcy, Vancouver, BC V5Z 4S6, Canada.
   [Witt, Hendrick; Pfister, Stefan M.] Univ Heidelberg Hosp, Dept Pediat Oncol, D-69120 Heidelberg, Germany.
   [Witt, Hendrick] Univ Heidelberg Hosp, Dept Hematol, D-69120 Heidelberg, Germany.
   [Witt, Hendrick] Univ Heidelberg Hosp, Dept Immunol, D-69120 Heidelberg, Germany.
   [Fernandez-L, Africa] Mem Sloan Kettering Canc Ctr, Pediat Clin Trials Off, New York, NY 10174 USA.
   [Wechsler-Reya, Robert J.] Sanford Burnham Med Res Inst, La Jolla, CA 92037 USA.
   [Dirks, Peter; Rutka, James T.; Taylor, Michael D.] Hosp Sick Children, Dept Surg, Div Neurosurg, Toronto, ON M5G 1X8, Canada.
   [Dirks, Peter; Rutka, James T.; Taylor, Michael D.] Hosp Sick Children, Labatt Brain Tumour Res Ctr, Toronto, ON M5G 1X8, Canada.
   [Grajkowska, Wieslawa A.] Childrens Mem Hlth Inst, Dept Pathol, PL-04730 Warsaw, Poland.
   [Perek-Polnik, Marta] Childrens Mem Hlth Inst, Dept Oncol, Warsaw, Poland.
   [Haberler, Christine C.] Med Univ Vienna, Inst Neurol, A-1097 Vienna, Austria.
   [Delattre, Olivier] Inst Curie, INSERM, U830, F-75238 Paris 5, France.
   [Reynaud, Stephanie S.] Inst Curie, Unit Somat Genet, F-75238 Paris 5, France.
   [Doz, Francois F.] Inst Curie, Dept Pediat Oncol, F-75248 Paris 5, France.
   [Pernet-Fattet, Sarah S.] CHUV Univ Hosp, CH-1011 Lausanne, Switzerland.
   [Cho, Byung-Kyu; Kim, Seung-Ki; Wang, Kyu-Chang] Seoul Natl Univ, Childrens Hosp, Dept Neurosurg, Div Pediat Neurosurg, Seoul 110744, South Korea.
   [Scheurlen, Wolfram] Cnopfsche Kinderklin, D-90419 Nurnberg, Germany.
   [Eberhart, Charles G.] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA.
   [Eberhart, Charles G.] Johns Hopkins Univ, Sch Med, Dept Ophthalmol & Oncol, Baltimore, MD 21205 USA.
   [Fevre-Montange, Michelle] Univ Lyon, Ctr Rech Neurosci, CNRS UMR5292, INSERM U1028, F-69336 Lyon, France.
   [Jouvet, Anne] Univ Lyon, Grp Hosp EST, Ctr Pathol EST, F-69500 Bron, France.
   [Pollack, Ian F.] Univ Pittsburgh, Sch Med, Dept Neurol Surg, Pittsburgh, PA 15224 USA.
   [Fan, Xing; Muraszko, Karin M.] Univ Michigan, Sch Med, Dept Neurosurg, Ann Arbor, MI 48109 USA.
   [Fan, Xing] Univ Michigan, Sch Med, Dept Cell & Dev Biol, Ann Arbor, MI 48109 USA.
   [Gillespie, G. Yancey] Univ Alabama Birmingham, Dept Surg, Div Neurosurg, Birmingham, AL 35294 USA.
   [Di Rocco, Concezio; Massimi, Luca] Catholic Univ, Sch Med, I-00186 Rome, Italy.
   [Michiels, Erna M. C.; Kloosterhof, Nanne K.] Erasmus MC, Dept Pediat Oncol & Hematol, NL-3000 Rotterdam, Netherlands.
   [Kloosterhof, Nanne K.; French, Pim J.] Erasmus MC, Dept Neurol, NL-3000 CA Rotterdam, Netherlands.
   [Kros, Johan M.] Erasmus MC, Dept Pathol, NL-3015 GE Rotterdam, Netherlands.
   [Olson, James M.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98109 USA.
   [Olson, James M.] Seattle Childrens Hosp, Seattle, WA 98104 USA.
   [Ellenbogen, Richard G.] Univ Washington, Sch Med, Harborview Med Ctr, Seattle, WA 98104 USA.
   [Zitterbart, Karel] Masaryk Univ, Sch Med, Dept Pediat Oncol, Brno 61300, Czech Republic.
   [Zitterbart, Karel] Univ Hosp Brno, Dept Pediat Oncol, Brno 62500, Czech Republic.
   [Kren, Leos] Univ Hosp Brno, Dept Pathol, Brno 62500, Czech Republic.
   [Cooper, Michael K.] Vanderbilt Univ Sch Med, Dept Neurol, Nashville, TN 37232 USA.
   [Lach, Boleslaw] McMaster Univ, Dept Pathol & Mol Med, Div Anat Pathol, Hamilton, ON L8S 4L8, Canada.
   [Lach, Boleslaw] Hamilton Gen Hosp, Dept Pathol, Hamilton, ON L8L 2X2, Canada.
   [Lach, Boleslaw] Hamilton Gen Hosp, Lab Med, Hamilton, ON L8L 2X2, Canada.
   [McLendon, Roger E.; Bigner, Darell D.] Duke Univ, Dept Pathol, DUMC 3712, Durham, NC 27710 USA.
   [Fontebasso, Adam; Jabado, Nada] McGill Univ, Div Expt Med, Montreal, PQ H3Z 2Z3, Canada.
   [Albrecht, Steffen] McGill Univ, Dept Pathol, Montreal, PQ H3A 2B4, Canada.
   [Albrecht, Steffen] Montreal Childrens Hosp, Dept Pathol, Montreal, PQ H3H 1P3, Canada.
   [Jabado, Nada] McGill Univ, Dept Pediat, Div Hemato Oncol, Montreal, PQ H3H 1P3, Canada.
   [Lindsey, Janet C.; Bailey, Simon; Clifford, Steven C.] Newcastle Univ, No Inst Canc Res, Newcastle Upon Tyne NE1 4LP, Tyne & Wear, England.
   [Gupta, Nalin] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 94143 USA.
   [Gupta, Nalin] Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA.
   [Weiss, William A.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94158 USA.
   [Weiss, William A.] Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94158 USA.
   [Weiss, William A.] Univ Calif San Francisco, Dept Neurosurg, San Francisco, CA 94158 USA.
   [Bognar, Laszlo; Klekner, Almos] Univ Debrecen, Med & Hlth Sci Ctr, Dept Neurosurg, H-4032 Debrecen, Hungary.
   [Van Meter, Timothy E.] Virginia Commonwealthy Univ, Sch Med, Richmond, VA 23298 USA.
   [Kumabe, Toshihiro; Tominaga, Teiji] Tohoku Univ, Grad Sch Med, Dept Neurosurg, Aoba Ku, Sendai, Miyagi 9808574, Japan.
   [Elbabaa, Samer K.] St Louis Univ, Sch Med, Dept Neurosurg, Div Pediat Neurosurg, St Louis, MO 63104 USA.
   [Leonard, Jeffrey R.] Washington Univ, Sch Med, Dept Neurosurg, Div Pediat Neurosurg, St Louis, MO 63110 USA.
   [Leonard, Jeffrey R.; Rubin, Joshua B.] St Louis Childrens Hosp, St Louis, MO 63110 USA.
   [Rubin, Joshua B.] Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA.
   [Rubin, Joshua B.] Washington Univ, Sch Med, Dept Anat & Neurobiol, St Louis, MO 63110 USA.
   [Liau, Linda M.] David Geffen Sch Med UCLA, Dept Neurosurg, Los Angeles, CA 90095 USA.
   [Van Meir, Erwin G.] Emory Univ, Dept Neurosurg, Mol Neurooncol Lab, Atlanta, GA 30322 USA.
   [Van Meir, Erwin G.] Emory Univ, Sch Med, Dept Hematol & Med Oncol, Atlanta, GA 30322 USA.
   [Van Meir, Erwin G.] Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA.
   [Fouladi, Maryam] Univ Cincinnati, Cincinnati Childrens Hosp, Med Ctr, Div Oncol, Cincinnati, OH 45229 USA.
   [Nakamura, Hideo] Kumamoto Univ, Grad Sch Med Sci, Dept Neurosurg, Honjo, Kumamoto 8608556, Japan.
   [Cinalli, Giuseppe] Osped Santobono Pausilipon, I-80145 Naples, Italy.
   [Garami, Miklos; Hauser, Peter] Semmelweis Univ, Dept Pediat 2, H-1085 Budapest, Hungary.
   [Saad, Ali G.] Univ Arkansas Med Sci, Little Rock, AR 72202 USA.
   [Iolascon, Achille; Zollo, Massimo] Univ Naples Federico II, Dipartimento Biochim & Biotecnol Med, I-80145 Naples, Italy.
   [Iolascon, Achille; Zollo, Massimo] CEINGE Biotecnol Avanzate, I-80145 Naples, Italy.
   [Jung, Shin] Chonnam Natl Univ, Hwasun Hosp, Res Inst Med Sci, Dept Neurosci, Chungnam 519763, South Korea.
   [Jung, Shin] Sch Med, Chungnam 519763, South Korea.
   [Carlotti, Carlos G.] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Surg & Anat, BR-14049900 Sao Paulo, Brazil.
   [Vibhakar, Rajeev] Univ Colorado Denver, Aurora, CO 80045 USA.
   [Ra, Young Shin] Univ Ulsan, Asan Med Ctr, Dept Neurosurg, Seoul 138736, South Korea.
   [Robinson, Shenandoah] Div Pediat Neurosurg, Cleveland, OH 44106 USA.
   [Faria, Claudia C.] Hosp Santa Maria, Ctr Hosp Lisboa Norte EPE, Div Neurosurg, P-1169050 Lisbon, Portugal.
   [Faria, Claudia C.] Hosp Sick Children, Cell Biol Program, Toronto, ON MSG 1L7, Canada.
   [Chan, Jennifer A.] Univ Calgary, Dept Pathol, Calgary, AB T2N 4N1, Canada.
   [Chan, Jennifer A.] Univ Calgary, Lab Med, Calgary, AB T2N 4N1, Canada.
   [Levy, Michael L.] Rady Childrens Hosp San Diego, UCSD Div Neurosurg, San Diego, CA 92123 USA.
   [Sorensen, Poul H. B.] British Columbia Canc Res Ctr, Dept Mol Oncol, Vancouver, BC V5Z 1L3, Canada.
   [Pomeroy, Scott L.] Harvard Univ, Sch Med, Childrens Hosp Boston, Dept Neurol, Boston, MA 02115 USA.
   [Cho, Yoon-Jae] Stanford Univ, Sch Med, Dept Neurol & Neurol Sci, Stanford, CA 94305 USA.
   [Bader, Gary D.] Univ Toronto, Banting & Best Dept Med Res, Toronto, ON M5G 1L6, Canada.
   [Bader, Gary D.] Univ Toronto, Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON MSG 1X5, Canada.
   [Tabori, Uri; Bouffet, Eric; Malkin, David] Hosp Sick Children, Dept Haematol & Oncol, Toronto, ON M5G 1X8, Canada.
   [Hawkins, Cynthia E.] Hosp Sick Children, Dept Pathol, Toronto, ON M5G 1X8, Canada.
   [Malkin, David] Univ Toronto, Dept Pediat, Toronto, ON M5G 1X8, Canada.
   [Marra, Marco A.] Univ British Columbia, Dept Med Genet, Vancouver, BC V5Z 1L3, Canada.
C3 British Columbia Cancer Agency; University of Toronto; Hospital for Sick Children (SickKids); Helmholtz Association; German Cancer Research Center (DKFZ); University of Toronto; European Molecular Biology Laboratory (EMBL); Ruprecht Karls University Heidelberg; Helmholtz Association; German Cancer Research Center (DKFZ); University of Toronto; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; St Jude Children's Research Hospital; University of Toronto; University of Toronto; University of Toronto; Hospital for Sick Children (SickKids); British Columbia Cancer Agency; Ruprecht Karls University Heidelberg; Ruprecht Karls University Heidelberg; Ruprecht Karls University Heidelberg; Memorial Sloan Kettering Cancer Center; Sanford Burnham Prebys Medical Discovery Institute; University of Toronto; Hospital for Sick Children (SickKids); University of Toronto; Hospital for Sick Children (SickKids); Children's Memorial Health Institute; Children's Memorial Health Institute; Medical University of Vienna; Universite PSL; UNICANCER; Institut Curie; Institut National de la Sante et de la Recherche Medicale (Inserm); UNICANCER; Universite PSL; Institut Curie; UNICANCER; Universite PSL; Institut Curie; University of Lausanne; Centre Hospitalier Universitaire Vaudois (CHUV); Seoul National University (SNU); Seoul National University Hospital; Johns Hopkins University; Johns Hopkins University; Universite Lyon 1; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB); Universite Jean Monnet; Institut National de la Sante et de la Recherche Medicale (Inserm); CHU Lyon; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh; University of Michigan System; University of Michigan; University of Michigan System; University of Michigan; University of Alabama System; University of Alabama Birmingham; Catholic University of the Sacred Heart; IRCCS Policlinico Gemelli; Erasmus University Rotterdam; Erasmus MC; Erasmus University Rotterdam; Erasmus MC; Erasmus University Rotterdam; Erasmus MC; Fred Hutchinson Cancer Center; Seattle Children's Hospital; Harborview Medical Center; University of Washington; University of Washington Seattle; Masaryk University; University Hospital Brno; University Hospital Brno; Vanderbilt University; McMaster University; McMaster University; McMaster University Hospital; McMaster University; McMaster University Hospital; Duke University; McGill University; McGill University; McGill University; McGill University; Newcastle University - UK; 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 Debrecen; Tohoku University; Saint Louis University; Washington University (WUSTL); Washington University (WUSTL); St. Louis Children's Hospital; Washington University (WUSTL); Washington University (WUSTL); University of California System; University of California Los Angeles; University of California Los Angeles Medical Center; David Geffen School of Medicine at UCLA; Emory University; Emory University; Emory University; University System of Ohio; University of Cincinnati; Cincinnati Children's Hospital Medical Center; Kumamoto University; Semmelweis University; University of Arkansas System; University of Arkansas Medical Sciences; University of Naples Federico II; CEINGE Biotecnologie Avanzate; Chonnam National University; Universidade de Sao Paulo; University of Colorado System; University of Colorado Anschutz Medical Campus; Children's Hospital Colorado; University of Ulsan; Asan Medical Center; Universidade de Lisboa; Hospital Santa Maria; Centro Hospitalar de Lisboa Ocidental, EPE; University of Toronto; Hospital for Sick Children (SickKids); University of Calgary; University of Calgary; Rady Childrens Hospital San Diego; British Columbia Cancer Agency; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Harvard Medical School; Stanford University; University of Toronto; University of Toronto; Sinai Health System Toronto; Lunenfeld Tanenbaum Research Institute; University of Toronto; Hospital for Sick Children (SickKids); University of Toronto; Hospital for Sick Children (SickKids); University of Toronto; University of British Columbia
RP Marra, MA (corresponding author), Michael Smith Genome Sci Ctr, BC Canc Agcy, 675 W 10th Ave, Vancouver, BC V5Z 1L3, Canada.
EM mmarra@bcgsc.ca; mdtaylor@sickkids.ca
FU CIHR Clinician-Scientist Phase II award; Sontag Foundation; Pediatric Brain Tumour Foundation; National Institutes of Health [CA159859]; The Family of Kathleen Lorette; Clark H. Smith Brain Tumour Centre; Montreal Children's Hospital Foundation; Hospital for Sick Children: Sonia and Arthur Labatt Brain Tumour Research Centre; Chief of Research Fund; Cancer Genetics Program; Garron Family Cancer Centre; B.R.A.I.N. Child; CIHR [ATE-110814]; University of Toronto McLaughlin Centre; CIHR Institute of Cancer Research [AT1-112286]; BC Cancer Foundation; Children's Discovery Institute; Restracomp Fellowship (Hospital for Sick Children); Ontario Institute for Cancer Research; Government of Ontario; NIH [CA86335, CA116804, CA138292]; NCI [28XS100, 29XS193]; Southeastern Brain Tumour Foundation; Brain Tumour Foundation for Children; UK Children's Cancer and Leukaemia Group (CCLG) [BS-2007-04]; German Cancer Aid [109252]; National Cancer Institute [R01CA159859, R01CA114567, P30CA138292] Funding Source: NIH RePORTER; National Institute of General Medical Sciences [P41GM103504] Funding Source: NIH RePORTER; Cancer Research UK [13457] Funding Source: researchfish; The Brain Tumour Charity [16/92] Funding Source: researchfish
NR 40
TC 724
Z9 840
U1 5
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 AUG 2
PY 2012
VL 488
IS 7409
BP 49
EP 56
DI 10.1038/nature11327
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 981ZE
UT WOS:000307010700030
PM 22832581
DA 2026-03-09
ER

PT J
AU Tritsch, NX
   Ding, JB
   Sabatini, BL
AF Tritsch, Nicolas X.
   Ding, Jun B.
   Sabatini, Bernardo L.
TI Dopaminergic neurons inhibit striatal output through non-canonical release of GABA
SO NATURE
LA English
DT Article
ID nucleus-accumbens; dorsal striatum; glutamate; rat; corelease; neurotransmission; colocalization; expression; circuits; pathway
AB The substantia nigra pars compacta and ventral tegmental area contain the two largest populations of dopamine-releasing neurons in the mammalian brain. These neurons extend elaborate projections in the striatum, a large subcortical structure implicated in motor planning and reward-based learning. Phasic activation of dopaminergic neurons in response to salient or reward-predicting stimuli is thought to modulate striatal output through the release of dopamine to promote and reinforce motor action(1-4). Here we show that activation of dopamine neurons in striatal slices rapidly inhibits action potential firing in both direct-and indirect-pathway striatal projection neurons through vesicular release of the inhibitory transmitter GABA (gamma-aminobutyric acid). GABA is released directly from dopaminergic axons but in a manner that is independent of the vesicular GABA transporter VGAT. Instead, GABA release requires activity of the vesicular monoamine transporter VMAT2, which is the vesicular transporter for dopamine. Furthermore, VMAT2 expression in GABAergic neurons lacking VGAT is sufficient to sustain GABA release. Thus, these findings expand the repertoire of synaptic mechanisms used by dopamine neurons to influence basal ganglia circuits, show a new substrate whose transport is dependent on VMAT2 and demonstrate that GABA can function as a bona fide co-transmitter in monoaminergic neurons.
C1 [Tritsch, Nicolas X.; Ding, Jun B.; Sabatini, Bernardo L.] Harvard Univ, Sch Med, Howard Hughes Med Inst, Dept Neurobiol, Boston, MA 02115 USA.
C3 Howard Hughes Medical Institute; Harvard University; Harvard Medical School
RP Sabatini, BL (corresponding author), Harvard Univ, Sch Med, Howard Hughes Med Inst, Dept Neurobiol, 220 Longwood Ave, Boston, MA 02115 USA.
EM bsabatini@hms.harvard.edu
FU Nancy Lurie Marks Family Foundation; National Institutes of Health [NS046579, 4R00NS075136]
NR 36
TC 449
Z9 609
U1 2
U2 117
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD OCT 11
PY 2012
VL 490
IS 7419
BP 262
EP +
DI 10.1038/nature11466
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 019IY
UT WOS:000309733300050
PM 23034651
DA 2026-03-09
ER

PT J
AU Mallam, AL
   Del Campo, M
   Gilman, B
   Sidote, DJ
   Lambowitz, AM
AF Mallam, Anna L.
   Del Campo, Mark
   Gilman, Benjamin
   Sidote, David J.
   Lambowitz, Alan M.
TI Structural basis for RNA-duplex recognition and unwinding by the DEAD-box helicase Mss116p
SO NATURE
LA English
DT Article
ID crystal-structure; protein mss116p; atp hydrolysis; group-i; activation; mechanism; ribose; roles
AB DEAD-box proteins are the largest family of nucleic acid helicases, and are crucial to RNA metabolism throughout all domains of life(1,2). They contain a conserved 'helicase core' of two RecA-like domains (domains (D)1 and D2), which uses ATP to catalyse the unwinding of short RNA duplexes by non-processive, local strand separation(3). This mode of action differs from that of translocating helicases and allows DEAD-box proteins to remodel large RNAs and RNA-protein complexes without globally disrupting RNA structure(4). However, the structural basis for this distinctive mode of RNA unwinding remains unclear. Here, structural, biochemical and genetic analyses of the yeast DEAD-box protein Mss116p indicate that the helicase core domains have modular functions that enable a novel mechanism for RNA-duplex recognition and unwinding. By investigating D1 and D2 individually and together, we find that D1 acts as an ATP-binding domain and D2 functions as an RNA-duplex recognition domain. D2 contains a nucleic-acid-binding pocket that is formed by conserved DEAD-box protein sequence motifs and accommodates A-form but not B-form duplexes, providing a basis for RNA substrate specificity. Upon a conformational change in which the two core domains join to form a 'closed state' with an ATPase active site, conserved motifs in D1 promote the unwinding of duplex substrates bound to D2 by excluding one RNA strand and bending the other. Our results provide a comprehensive structural model for how DEAD-box proteins recognize and unwind RNA duplexes. This model explains key features of DEAD-box protein function and affords a new perspective on how the evolutionarily related cores of other RNA and DNA helicases diverged to use different mechanisms.
C1 [Mallam, Anna L.; Del Campo, Mark; Gilman, Benjamin; Sidote, David J.; Lambowitz, Alan M.] Univ Texas Austin, Dept Chem & Biochem, Inst Cellular & Mol Biol, Austin, TX 78712 USA.
   [Mallam, Anna L.; Del Campo, Mark; Gilman, Benjamin; Sidote, David J.; Lambowitz, Alan M.] Univ Texas Austin, Sch Biol Sci, Sect Mol Genet & Microbiol, Austin, TX 78712 USA.
C3 University of Texas System; University of Texas Austin; University of Texas System; University of Texas Austin
RP Lambowitz, AM (corresponding author), Univ Texas Austin, Dept Chem & Biochem, Inst Cellular & Mol Biol, Austin, TX 78712 USA.
EM lambowitz@austin.utexas.edu
FU National Institutes of Health (NIH), National Institute of General Medical Sciences; Howard Hughes Medical Institute; Office of Science, Office of Basic Energy Sciences, of the US Department of Energy [DE-AC02-05CH11231]; EMBO [ALTF 389-2010]; NIH [GM037951]
NR 41
TC 100
Z9 127
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 4
PY 2012
VL 490
IS 7418
BP 121
EP +
DI 10.1038/nature11402
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 015LG
UT WOS:000309446800045
PM 22940866
DA 2026-03-09
ER

PT J
AU Dominissini, D
   Moshitch-Moshkovitz, S
   Schwartz, S
   Salmon-Divon, M
   Ungar, L
   Osenberg, S
   Cesarkas, K
   Jacob-Hirsch, J
   Amariglio, N
   Kupiec, M
   Sorek, R
   Rechavi, G
AF Dominissini, Dan
   Moshitch-Moshkovitz, Sharon
   Schwartz, Schraga
   Salmon-Divon, Mali
   Ungar, Lior
   Osenberg, Sivan
   Cesarkas, Karen
   Jacob-Hirsch, Jasmine
   Amariglio, Ninette
   Kupiec, Martin
   Sorek, Rotem
   Rechavi, Gideon
TI Topology of the human and mouse m6A RNA methylomes revealed by m6A-seq
SO NATURE
LA English
DT Article
ID nucleic-acid complexes; messenger-rna; n-6-methyladenosine residues; immunospecific retention; methylated constituents; dna methylation; factor-alpha; in-vitro; cell; binding
AB An extensive repertoire of modifications is known to underlie the versatile coding, structural and catalytic functions of RNA, but it remains largely uncharted territory. Although biochemical studies indicate that N-6-methyladenosine (m(6)A) is the most prevalent internal modification in messenger RNA, an in-depth study of its distribution and functions has been impeded by a lack of robust analytical methods. Here we present the human and mouse m(6)A modification landscape in a transcriptome-wide manner, using a novel approach, m(6)A-seq, based on antibody-mediated capture and massively parallel sequencing. We identify over 12,000 m(6)A sites characterized by a typical consensus in the transcripts of more than 7,000 human genes. Sites preferentially appear in two distinct landmarks-around stop codons and within long internal exons-and are highly conserved between human and mouse. Although most sites are well preserved across normal and cancerous tissues and in response to various stimuli, a subset of stimulus-dependent, dynamically modulated sites is identified. Silencing the m(6)A methyltransferase significantly affects gene expression and alternative splicing patterns, resulting in modulation of the p53 (also known as TP53) signalling pathway and apoptosis. Our findings therefore suggest that RNA decoration by m(6)A has a fundamental role in regulation of gene expression.
C1 [Dominissini, Dan; Moshitch-Moshkovitz, Sharon; Salmon-Divon, Mali; Osenberg, Sivan; Cesarkas, Karen; Jacob-Hirsch, Jasmine; Amariglio, Ninette; Rechavi, Gideon] Chaim Sheba Med Ctr, Canc Res Ctr, IL-52621 Tel Hashomer, Israel.
   [Dominissini, Dan; Ungar, Lior; Osenberg, Sivan; Rechavi, Gideon] Tel Aviv Univ, Sackler Sch Med, IL-69978 Tel Aviv, Israel.
   [Schwartz, Schraga; Sorek, Rotem] Weizmann Inst Sci, Dept Mol Genet, IL-76100 Rehovot, Israel.
   [Ungar, Lior; Kupiec, Martin] Tel Aviv Univ, Dept Mol Microbiol & Biotechnol, IL-69978 Tel Aviv, Israel.
C3 Tel Aviv University; Chaim Sheba Medical Center; Tel Aviv University; Sackler Faculty of Medicine; Weizmann Institute of Science; Tel Aviv University
RP Rechavi, G (corresponding author), Chaim Sheba Med Ctr, Canc Res Ctr, IL-52621 Tel Hashomer, Israel.
EM Gidi.Rechavi@sheba.health.gov.il
FU Flight Attendant Medical Research Institute (FAMRI); Bio-Med Morasha ISF [1942/08]; Israel Ministry for Science and Technology; ERC-StG [260432]
NR 64
TC 3988
Z9 4550
U1 18
U2 803
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 10
PY 2012
VL 485
IS 7397
BP 201
EP U84
DI 10.1038/nature11112
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 939HJ
UT WOS:000303799800033
PM 22575960
DA 2026-03-09
ER

PT J
AU Keleman, K
   Vrontou, E
   Krüttner, S
   Yu, JY
   Kurtovic-Kozaric, A
   Dickson, BJ
AF Keleman, Krystyna
   Vrontou, Eleftheria
   Kruettner, Sebastian
   Yu, Jai Y.
   Kurtovic-Kozaric, Amina
   Dickson, Barry J.
TI Dopamine neurons modulate pheromone responses in Drosophila courtship learning
SO NATURE
LA English
DT Article
ID sex-peptide; expression; behavior; memory; females
AB Learning through trial-and-error interactions allows animals to adapt innate behavioural 'rules of thumb' to the local environment, improving their prospects for survival and reproduction. Naive Drosophila melanogaster males, for example, court both virgin and mated females, but learn through experience to selectively suppress futile courtship towards females that have already mated(1). Here we show that courtship learning reflects an enhanced response to the male pheromone cis-vaccenyl acetate (cVA), which is deposited on females during mating and thus distinguishes mated females from virgins. Dissociation experiments suggest a simple learning rule in which unsuccessful courtship enhances sensitivity to cVA. The learning experience can be mimicked by artificial activation of dopaminergic neurons, and we identify a specific class of dopaminergic neuron that is critical for courtship learning. These neurons provide input to the mushroom body (MB) gamma lobe, and the DopR1 dopamine receptor is required in MB gamma neurons for both natural and artificial courtship learning. Our work thus reveals critical behavioural, cellular and molecular components of the learning rule by which Drosophila adjusts its innate mating strategy according to experience.
C1 [Keleman, Krystyna; Vrontou, Eleftheria; Kruettner, Sebastian; Yu, Jai Y.; Kurtovic-Kozaric, Amina; Dickson, Barry J.] Res Inst Mol Pathol, A-1030 Vienna, Austria.
C3 Vienna Biocenter (VBC); Research Institute of Molecular Pathology (IMP)
RP Keleman, K (corresponding author), Res Inst Mol Pathol, Dr Bohr Gasse 7, A-1030 Vienna, Austria.
EM keleman@imp.ac.at; dickson@imp.ac.at
FU European Research Council; Austrian Science Fund; European Molecular Biology Organization; Boehringer Ingelheim GmbH
NR 35
TC 167
Z9 201
U1 3
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 SEP 6
PY 2012
VL 489
IS 7414
BP 145
EP U210
DI 10.1038/nature11345
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 999WW
UT WOS:000308347000052
PM 22902500
DA 2026-03-09
ER

PT J
AU Herman, MA
   Peroni, OD
   Villoria, J
   Schön, MR
   Abumrad, NA
   Blüher, M
   Klein, S
   Kahn, BB
AF Herman, Mark A.
   Peroni, Odile D.
   Villoria, Jorge
   Schoen, Michael R.
   Abumrad, Nada A.
   Blueher, Matthias
   Klein, Samuel
   Kahn, Barbara B.
TI A novel ChREBP isoform in adipose tissue regulates systemic glucose metabolism
SO NATURE
LA English
DT Article
ID carbohydrate-response element; fatty-acid synthesis; binding-protein chrebp; ucsc genome browser; insulin-resistance; diabetes-mellitus; transgenic mice; liver; gene; lipogenesis
AB The prevalence of obesity and type 2 diabetes is increasing worldwide and threatens to shorten lifespan. Impaired insulin action in peripheral tissues is a major pathogenic factor. Insulin stimulates glucose uptake in adipose tissue through the GLUT4 (also known as SLC2A4) glucose transporter, and alterations in adipose tissue GLUT4 expression or function regulate systemic insulin sensitivity. Downregulation of human and mouse adipose tissue GLUT4 occurs early in diabetes development. Here we report that adipose tissue GLUT4 regulates the expression of carbohydrate-responsive-element-binding protein (ChREBP; also known as MLXIPL), a transcriptional regulator of lipogenic and glycolytic genes. Furthermore, adipose ChREBP is a major determinant of adipose tissue fatty acid synthesis and systemic insulin sensitivity. We find a new mechanism for glucose regulation of ChREBP: glucose-mediated activation of the canonical ChREBP isoform (ChREBP-alpha) induces expression of a novel, potent isoform (ChREBP-beta) that is transcribed from an alternative promoter. ChREBP-beta expression in human adipose tissue predicts insulin sensitivity, indicating that it may be an effective target for treating diabetes.
C1 [Herman, Mark A.; Peroni, Odile D.; Villoria, Jorge; Kahn, Barbara B.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Endocrinol Diabet & Metab, Boston, MA 02215 USA.
   [Herman, Mark A.; Peroni, Odile D.; Villoria, Jorge; Kahn, Barbara B.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA.
   [Schoen, Michael R.] Stadt Klinikum Karlsruhe, Clin Visceral Surg, D-76133 Karlsruhe, Germany.
   [Abumrad, Nada A.; Klein, Samuel] Washington Univ, Sch Med, Ctr Human Nutr, St Louis, MO 63110 USA.
   [Blueher, Matthias] Univ Leipzig, Dept Med, D-04103 Leipzig, Germany.
C3 Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Beth Israel Deaconess Medical Center; Harvard University; Harvard Medical School; Municipal Hospital Karlsruhe; Washington University (WUSTL); Leipzig University
RP Kahn, BB (corresponding author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Endocrinol Diabet & Metab, Boston, MA 02215 USA.
EM bkahn@bidmc.harvard.edu
FU NIH [R37 DK43051, K08 DK076726]; BADERC [DK057521]; BNORC [DK046200]; Picower and JPB Foundations; Radcliffe Institute for Advanced Study; Nutrition and Obesity Research Unit [DK056341, DK037948]; Deutsche Forschungsgemeinschft DFG [KFO152, BL833/1]; National Institute of Diabetes and Digestive and Kidney Diseases [P30DK046200, P30DK056341] Funding Source: NIH RePORTER
NR 46
TC 490
Z9 567
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 APR 19
PY 2012
VL 484
IS 7394
BP 333
EP U66
DI 10.1038/nature10986
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 927YM
UT WOS:000302946500024
PM 22466288
DA 2026-03-09
ER

PT J
AU Waggoner, SN
   Cornberg, M
   Selin, LK
   Welsh, RM
AF Waggoner, Stephen N.
   Cornberg, Markus
   Selin, Liisa K.
   Welsh, Raymond M.
TI Natural killer cells act as rheostats modulating antiviral T cells
SO NATURE
LA English
DT Article
ID lymphocytic choriomeningitis virus; infection; responses; mice; hla; identification; pathogenesis; chain
AB Antiviral T cells are thought to regulate whether hepatitis C virus (HCV) and human immunodeficiency virus (HIV) infections result in viral control, asymptomatic persistence or severe disease, although the reasons for these different outcomes remain unclear. Recent genetic evidence, however, has indicated a correlation between certain natural killer (NK)-cell receptors and progression of both HIV and HCV infection(1-3), implying that NK cells have a role in these T-cell-associated diseases. Although direct NK-cell-mediated lysis of virus-infected cells may contribute to antiviral defence during some virus infections-especially murine cytomegalovirus (MCMV) infections in mice and perhaps HIV in humans(4,5)-NK cells have also been suspected of having immunoregulatory functions. For instance, NK cells may indirectly regulate T-cell responses by lysing MCMV-infected antigen-presenting cells(6,7). In contrast to MCMV, lymphocytic choriomeningitis virus (LCMV) infection in mice seems to be resistant to any direct antiviral effects of NK cells(5,8). Here we examine the roles of NK cells in regulating T-cell-dependent viral persistence and immunopathology in mice infected with LCMV, an established model for HIV and HCV infections in humans. We describe a three-way interaction, whereby activated NK cells cytolytically eliminate activated CD4 T cells that affect CD8 T-cell function and exhaustion. At high virus doses, NK cells prevented fatal pathology while enabling T-cell exhaustion and viral persistence, but at medium doses NK cells paradoxically facilitated lethal T-cell-mediated pathology. Thus, NK cells can act as rheostats, regulating CD4 T-cell-mediated support for the antiviral CD8 T cells that control viral pathogenesis and persistence.
C1 [Waggoner, Stephen N.; Selin, Liisa K.; Welsh, Raymond M.] Univ Massachusetts, Sch Med, Dept Pathol, Worcester, MA 01655 USA.
   [Waggoner, Stephen N.; Selin, Liisa K.; Welsh, Raymond M.] Univ Massachusetts, Sch Med, Program Immunol & Virol, Worcester, MA 01655 USA.
   [Cornberg, Markus] Hannover Med Sch, Dept Gastroenterol & Hepatol, D-30625 Hannover, Germany.
C3 University of Massachusetts System; University of Massachusetts Worcester; University of Massachusetts System; University of Massachusetts Worcester; Hannover Medical School
RP Welsh, RM (corresponding author), Univ Massachusetts, Sch Med, Dept Pathol, Worcester, MA 01655 USA.
EM Raymond.Welsh@umassmed.edu
FU National Institutes of Health (NIH) [AI07349, AI-17672, AI-081675, CA34461, AI46578]; German Research Foundation [CO310-2/1]; institutional Diabetes Endocrinology Research Center (DERC) [DK52530]; National Institute of Allergy and Infectious Diseases [T32AI007349] Funding Source: NIH RePORTER
NR 36
TC 490
Z9 574
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 JAN 19
PY 2012
VL 481
IS 7381
BP 394
EP U183
DI 10.1038/nature10624
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 877VK
UT WOS:000299210600049
PM 22101430
DA 2026-03-09
ER

PT J
AU Doege, CA
   Inoue, K
   Yamashita, T
   Rhee, DB
   Travis, S
   Fujita, R
   Guarnieri, P
   Bhagat, G
   Vanti, WB
   Shih, A
   Levine, RL
   Nik, S
   Chen, EI
   Abeliovich, A
AF Doege, Claudia A.
   Inoue, Keiichi
   Yamashita, Toru
   Rhee, David B.
   Travis, Skylar
   Fujita, Ryousuke
   Guarnieri, Paolo
   Bhagat, Govind
   Vanti, William B.
   Shih, Alan
   Levine, Ross L.
   Nik, Sara
   Chen, Emily I.
   Abeliovich, Asa
TI Early-stage epigenetic modification during somatic cell reprogramming by Parp1 and Tet2
SO NATURE
LA English
DT Article
ID chromatin-structure; dna demethylation; self-renewal; 5-hydroxymethylcytosine; maps; 5-methylcytosine; pluripotent; conversion; reveals; genes
AB Somatic cells can be reprogrammed into induced pluripotent stem cells (iPSCs) by using the pluripotency factors Oct4, Sox2, Klf4 and c-Myc (together referred to as OSKM)(1). iPSC reprogramming erases somatic epigenetic signatures-as typified by DNA methylation or histone modification at silent pluripotency loci-and establishes alternative epigenetic marks of embryonic stem cells (ESCs)(2). Here we describe an early and essential stage of somatic cell reprogramming, preceding the induction of transcription at endogenous pluripotency loci such as Nanog and Esrrb. By day 4 after transduction with OSKM, two epigenetic modification factors necessary for iPSC generation, namely poly(ADP-ribose) polymerase-1 (Parp1) and ten-eleven translocation-2 (Tet2), are recruited to the Nanog and Esrrb loci. These epigenetic modification factors seem to have complementary roles in the establishment of early epigenetic marks during somatic cell reprogramming: Parp1 functions in the regulation of 5-methylcytosine (5mC) modification, whereas Tet2 is essential for the early generation of 5-hydroxymethylcytosine (5hmC) by the oxidation of 5mC (refs 3,4). Although 5hmC has been proposed to serve primarily as an intermediate in 5mC demethylation to cytosine in certain contexts(5-7), our data, and also studies of Tet2-mutant human tumour cells(8), argue in favour of a role for 5hmC as an epigenetic mark distinct from 5mC. Consistent with this, Parp1 and Tet2 are each needed for the early establishment of histone modifications that typify an activated chromatin state at pluripotency loci, whereas Parp1 induction further promotes accessibility to the Oct4 reprogramming factor. These findings suggest that Parp1 and Tet2 contribute to an epigenetic program that directs subsequent transcriptional induction at pluripotency loci during somatic cell reprogramming.
C1 [Doege, Claudia A.; Inoue, Keiichi; Yamashita, Toru; Rhee, David B.; Travis, Skylar; Fujita, Ryousuke; Bhagat, Govind; Vanti, William B.; Abeliovich, Asa] Columbia Univ, Dept Pathol & Cell Biol, Taub Inst Aging, New York, NY 10032 USA.
   [Doege, Claudia A.; Inoue, Keiichi; Yamashita, Toru; Rhee, David B.; Travis, Skylar; Fujita, Ryousuke; Bhagat, Govind; Vanti, William B.; Abeliovich, Asa] Columbia Univ, Dept Neurol, Taub Inst Aging, New York, NY 10032 USA.
   [Guarnieri, Paolo] Columbia Univ, Bioinformat Div, New York, NY 10032 USA.
   [Guarnieri, Paolo; Bhagat, Govind] Columbia Univ, Herbert Irving Comprehens Canc Ctr, New York, NY 10032 USA.
   [Shih, Alan; Levine, Ross L.] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10016 USA.
   [Nik, Sara; Chen, Emily I.] SUNY Stony Brook, Dept Pharmacol Sci, Stony Brook, NY 11794 USA.
   [Chen, Emily I.] SUNY Stony Brook, Prote Ctr, Sch Med, Stony Brook, NY 11794 USA.
C3 Columbia University; Columbia University; Columbia University; Columbia University; Memorial Sloan Kettering Cancer Center; State University of New York (SUNY) System; Stony Brook University; State University of New York (SUNY) System; Stony Brook University
RP Abeliovich, A (corresponding author), Columbia Univ, Dept Pathol & Cell Biol, Taub Inst Aging, New York, NY 10032 USA.
EM aa900@columbia.edu
FU New York State Stem Cell Science (NYSTEM) [C024402, C024403]; National Institutes of Health (NIH) [RO1 NS064433]; NYSTEM Institution Development [N08G-071]; NIH [RO1 138424]; NIH/National Center for Research Resources [1 S10 RR023680-1]; National Cancer Institute [R01CA173636, P30CA008748] Funding Source: NIH RePORTER
NR 30
TC 327
Z9 373
U1 0
U2 88
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 30
PY 2012
VL 488
IS 7413
BP 652
EP 655
DI 10.1038/nature11333
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 996NC
UT WOS:000308095100055
PM 22902501
DA 2026-03-09
ER

PT J
AU Liu, LJ
   Stegman, DR
AF Liu, Lijun
   Stegman, Dave R.
TI Origin of Columbia River flood basalt controlled by propagating rupture of the Farallon slab
SO NATURE
LA English
DT Article
ID north-america; pacific-northwest; coast range; plume; subduction; genesis; oregon; evolution; history; models
AB The origin of the Steens-Columbia River (SCR) flood basalts, which is presumed to be the onset of Yellowstone volcanism, has remained controversial, with the proposed conceptual models involving either a mantle plume(1-5) or back-arc processes(6-8). Recent tomographic inversions based on the US Array data reveal unprecedented detail of upper-mantle structures of the western USA(9) and tightly constrain geodynamic models simulating Farallon subduction, which has been proposed to influence the Yellowstone volcanism(5,6). Here we show that the best-fitting geodynamic model(10) depicts an episode of slab tearing about 17 million years ago under eastern Oregon, where an associated sub-slab asthenospheric upwelling thermally erodes the Farallon slab, leading to formation of a slab gap at shallow depth. Driven by a gradient of dynamic pressure, the tear ruptured quickly north and south and within about two million years covering a distance of around 900 kilometres along all of eastern Oregon and northern Nevada. This tear would be consistent with the occurrence of major volcanic dikes during the SCR-Northern Nevada Rift flood basalt event both in space and time. The model predicts a petrogenetic sequence for the flood basalt with sources of melt starting from the base of the slab, at first remelting oceanic lithosphere and then evolving upwards, ending with remelting of oceanic crust. Such a progression helps to reconcile the existing controversies on the interpretation of SCR geochemistry and the involvement of the putative Yellowstone plume. Our study suggests a new mechanism for the formation of large igneous provinces.
C1 [Liu, Lijun; Stegman, Dave R.] Univ Calif San Diego, Scripps Inst Oceanog, IGPP, La Jolla, CA 92093 USA.
C3 University of California System; University of California San Diego; Scripps Institution of Oceanography
RP Liu, LJ (corresponding author), Univ Calif San Diego, Scripps Inst Oceanog, IGPP, La Jolla, CA 92093 USA.
EM lil019@ucsd.edu
FU XSEDE [EAR100021]; John Miles Fellowship; Cecil and Ida Green Foundation; G. Unger Vetlesen Foundation
NR 33
TC 138
Z9 173
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 FEB 16
PY 2012
VL 482
IS 7385
BP 386
EP U1508
DI 10.1038/nature10749
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 892LG
UT WOS:000300287100043
PM 22337059
DA 2026-03-09
ER

PT J
AU Jones, FC
   Grabherr, MG
   Chan, YF
   Russell, P
   Mauceli, E
   Johnson, J
   Swofford, R
   Pirun, M
   Zody, MC
   White, S
   Birney, E
   Searle, S
   Schmutz, J
   Grimwood, J
   Dickson, MC
   Myers, RM
   Miller, CT
   Summers, BR
   Knecht, AK
   Brady, SD
   Zhang, HL
   Pollen, AA
   Howes, T
   Amemiya, C
   Lander, ES
   Di Palma, F
   Lindblad-Toh, K
   Kingsley, DM
AF Jones, Felicity C.
   Grabherr, Manfred G.
   Chan, Yingguang Frank
   Russell, Pamela
   Mauceli, Evan
   Johnson, Jeremy
   Swofford, Ross
   Pirun, Mono
   Zody, Michael C.
   White, Simon
   Birney, Ewan
   Searle, Stephen
   Schmutz, Jeremy
   Grimwood, Jane
   Dickson, Mark C.
   Myers, Richard M.
   Miller, Craig T.
   Summers, Brian R.
   Knecht, Anne K.
   Brady, Shannon D.
   Zhang, Haili
   Pollen, Alex A.
   Howes, Timothy
   Amemiya, Chris
   Lander, Eric S.
   Di Palma, Federica
   Lindblad-Toh, Kerstin
   Kingsley, David M.
TI The genomic basis of adaptive evolution in threespine sticklebacks
SO NATURE
LA English
DT Article
ID genetic architecture; parallel evolution; regulatory changes; signaling pathway; pelvic reduction; evo-devo; vertebrate; duplication; adaptation; inversions
AB Marine stickleback fish have colonized and adapted to thousands of streams and lakes formed since the last ice age, providing an exceptional opportunity to characterize genomic mechanisms underlying repeated ecological adaptation in nature. Here we develop a high-quality reference genome assembly for threespine sticklebacks. By sequencing the genomes of twenty additional individuals from a global set of marine and freshwater populations, we identify a genome-wide set of loci that are consistently associated with marine-freshwater divergence. Our results indicate that reuse of globally shared standing genetic variation, including chromosomal inversions, has an important role in repeated evolution of distinct marine and freshwater sticklebacks, and in the maintenance of divergent ecotypes during early stages of reproductive isolation. Both coding and regulatory changes occur in the set of loci underlying marine-freshwater evolution, but regulatory changes appear to predominate in this well known example of repeated adaptive evolution in nature.
C1 [Grabherr, Manfred G.; Russell, Pamela; Mauceli, Evan; Johnson, Jeremy; Swofford, Ross; Pirun, Mono; Zody, Michael C.; Lander, Eric S.; Di Palma, Federica; Lindblad-Toh, Kerstin] Broad Inst MIT & Harvard, Cambridge Ctr 7, Cambridge, MA 02142 USA.
   [Jones, Felicity C.; Chan, Yingguang Frank; Miller, Craig T.; Summers, Brian R.; Knecht, Anne K.; Brady, Shannon D.; Zhang, Haili; Pollen, Alex A.; Howes, Timothy; Kingsley, David M.] Stanford Univ, Sch Med, Dept Dev Biol, Beckman Ctr B300, Stanford, CA 94305 USA.
   [Grabherr, Manfred G.; Lindblad-Toh, Kerstin] Uppsala Univ, Dept Med Biochem & Microbiol, Sci Life Lab Uppsala, S-75123 Uppsala, Sweden.
   [White, Simon; Searle, Stephen] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England.
   [Birney, Ewan] European Bioinformat Inst, Cambridge CB10 1SA, England.
   [Schmutz, Jeremy; Grimwood, Jane; Dickson, Mark C.; Myers, Richard M.] HudsonAlpha Inst Biotechnol, Huntsville, AL 35806 USA.
   [Amemiya, Chris] Benaroya Res Inst Virginia Mason, Dept Mol Genet, Seattle, WA 98101 USA.
   [Kingsley, David M.] Stanford Univ, Howard Hughes Med Inst, Stanford, CA 94305 USA.
C3 Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Stanford University; Uppsala University; Wellcome Trust Sanger Institute; European Molecular Biology Laboratory (EMBL); European Bioinformatics Institute; HudsonAlpha Institute for Biotechnology; Virginia Mason Medical Center; Benaroya Research Institute; Howard Hughes Medical Institute; Stanford University
RP Lindblad-Toh, K (corresponding author), Broad Inst MIT & Harvard, Cambridge Ctr 7, Cambridge, MA 02142 USA.
EM kersli@broad.mit.edu; kingsley@stanford.edu
FU National Human Genome Research Institute (NHGRI); NHGRI CEGS [P50-HG002568]; Stanford Affymetrix Bio-X; Jane Coffins Childs Fund; NSF; NDSEG; ESF
NR 50
TC 1400
Z9 1643
U1 8
U2 668
PU NATURE PUBLISHING 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 5
PY 2012
VL 484
IS 7392
BP 55
EP 61
DI 10.1038/nature10944
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 919QN
UT WOS:000302343400033
PM 22481358
DA 2026-03-09
ER

PT J
AU Goodarzi, H
   Najafabadi, HS
   Oikonomou, P
   Greco, TM
   Fish, L
   Salavati, R
   Cristea, IM
   Tavazoie, S
AF Goodarzi, Hani
   Najafabadi, Hamed S.
   Oikonomou, Panos
   Greco, Todd M.
   Fish, Lisa
   Salavati, Reza
   Cristea, Ileana M.
   Tavazoie, Saeed
TI Systematic discovery of structural elements governing stability of mammalian messenger RNAs
SO NATURE
LA English
DT Article
ID gene-expression; secondary structure; prediction; motifs; chip
AB Decoding post-transcriptional regulatory programs in RNA is a critical step towards the larger goal of developing predictive dynamical models of cellular behaviour. Despite recent efforts(1-3), the vast landscape of RNA regulatory elements remains largely uncharacterized. A long-standing obstacle is the contribution of local RNA secondary structure to the definition of interaction partners in a variety of regulatory contexts, including-but not limited to-transcript stability(3), alternative splicing(4) and localization(3). There are many documented instances where the presence of a structural regulatory element dictates alternative splicing patterns (for example, human cardiac troponin T) or affects other aspects of RNA biology(5). Thus, a full characterization of post-transcriptional regulatory programs requires capturing information provided by both local secondary structures and the underlying sequence(3,6). Here we present a computational framework based on context-free grammars(3,7) and mutual information(2) that systematically explores the immense space of small structural elements and reveals motifs that are significantly informative of genome-wide measurements of RNA behaviour. By applying this framework to genome-wide human mRNA stability data, we reveal eight highly significant elements with substantial structural information, for the strongest of which we show a major role in global mRNA regulation. Through biochemistry, mass spectrometry and in vivo binding studies, we identified human HNRPA2B1 (heterogeneous nuclear ribonucleoprotein A2/B1, also known as HNRNPA2B1) as the key regulator that binds this element and stabilizes a large number of its target genes. We created a global post-transcriptional regulatory map based on the identity of the discovered linear and structural cis-regulatory elements, their regulatory interactions and their target pathways. This approach could also be used to reveal the structural elements that modulate other aspects of RNA behaviour.
C1 [Goodarzi, Hani; Oikonomou, Panos; Tavazoie, Saeed] Princeton Univ, Lewis Sigler Inst Integrat Genom, Princeton, NJ 08540 USA.
   [Goodarzi, Hani; Oikonomou, Panos; Greco, Todd M.; Cristea, Ileana M.; Tavazoie, Saeed] Princeton Univ, Dept Mol Biol, Princeton, NJ 08540 USA.
   [Najafabadi, Hamed S.; Salavati, Reza] McGill Univ, Inst Parasitol, Montreal, PQ H3G 1Y6, Canada.
   [Najafabadi, Hamed S.; Salavati, Reza] McGill Univ, McGill Ctr Bioinformat, Montreal, PQ H3G 1Y6, Canada.
   [Fish, Lisa] Rockefeller Univ, Lab Syst Canc Biol, New York, NY 10065 USA.
   [Salavati, Reza] McGill Univ, Dept Biochem, Montreal, PQ H3G 1Y6, Canada.
C3 Princeton University; Princeton University; McGill University; McGill University; Rockefeller University; McGill University
RP Tavazoie, S (corresponding author), Columbia Univ, Dept Biochem & Mol Biophys, 630 W 168th St, New York, NY 10032 USA.
EM st2744@columbia.edu
FU Ruth L. Kirschstein National Research Service Award [T32-GM066699]; NHGRI [2R01HG003219]; NIH; National Institute of General Medical Sciences [T32GM066699] Funding Source: NIH RePORTER
NR 26
TC 136
Z9 179
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 MAY 10
PY 2012
VL 485
IS 7397
BP 264
EP U160
DI 10.1038/nature11013
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 939HJ
UT WOS:000303799800047
PM 22495308
DA 2026-03-09
ER

PT J
AU Gehrig, SM
   van der Poel, C
   Sayer, TA
   Schertzer, JD
   Henstridge, DC
   Church, JE
   Lamon, S
   Russell, AP
   Davies, KE
   Febbraio, MA
   Lynch, GS
AF Gehrig, Stefan M.
   van der Poel, Chris
   Sayer, Timothy A.
   Schertzer, Jonathan D.
   Henstridge, Darren C.
   Church, Jarrod E.
   Lamon, Severine
   Russell, Aaron P.
   Davies, Kay E.
   Febbraio, Mark A.
   Lynch, Gordon S.
TI Hsp72 preserves muscle function and slows progression of severe muscular dystrophy
SO NATURE
LA English
DT Article
ID kappa-b; mdx; skeletal; protein; mice; activation; stress; overexpression; contraction; myopathy
AB Duchenne muscular dystrophy (DMD) is a severe and progressive muscle wasting disorder caused by mutations in the dystrophin gene that result in the absence of the membrane-stabilizing protein dystrophin(1-3). Dystrophin-deficient muscle fibres are fragile and susceptible to an influx of Ca2+, which activates inflammatory and muscle degenerative pathways(4-6). At present there is no cure for DMD, and existing therapies are ineffective. Here we show that increasing the expression of intramuscular heat shock protein 72 (Hsp72) preserves muscle strength and ameliorates the dystrophic pathology in two mouse models of muscular dystrophy. Treatment with BGP-15 (a pharmacological inducer of Hsp72 currently in clinical trials for diabetes) improved muscle architecture, strength and contractile function in severely affected diaphragm muscles in mdx dystrophic mice. In dko mice, a phenocopy of DMD that results in severe spinal curvature (kyphosis), muscle weakness and premature death(7,8), BGP-15 decreased kyphosis, improved the dystrophic pathophysiology in limb and diaphragm muscles and extended lifespan. We found that the sarcoplasmic/endoplasmic reticulum Ca2+-ATPase (SERCA, the main protein responsible for the removal of intracellular Ca2+) is dysfunctional in severely affected muscles of mdx and dko mice, and that Hsp72 interacts with SERCA to preserve its function under conditions of stress, ultimately contributing to the decreased muscle degeneration seen with Hsp72 upregulation. Treatment with BGP-15 similarly increased SERCA activity in dystrophic skeletal muscles. Our results provide evidence that increasing the expression of Hsp72 in muscle (through the administration of BGP-15) has significant therapeutic potential for DMD and related conditions, either as a self-contained therapy or as an adjuvant with other potential treatments, including gene, cell and pharmacological therapies.
C1 [Gehrig, Stefan M.; van der Poel, Chris; Sayer, Timothy A.; Schertzer, Jonathan D.; Church, Jarrod E.; Lynch, Gordon S.] Univ Melbourne, Basic & Clin Myol Lab, Dept Physiol, Melbourne, Vic 3010, Australia.
   [Henstridge, Darren C.; Febbraio, Mark A.] Baker IDI Heart & Diabet Inst, Cellular & Mol Metab Lab, Melbourne, Vic 8008, Australia.
   [Lamon, Severine; Russell, Aaron P.] Deakin Univ, Ctr Phys Act & Nutr Res, Sch Exercise & Nutr Sci, Burwood, Vic 3125, Australia.
   [Davies, Kay E.] Univ Oxford, MRC Funct Genom Unit, Dept Physiol Anat & Genet, Oxford OX1 3QX, England.
C3 University of Melbourne; Baker Heart and Diabetes Institute; Deakin University; University of Oxford
RP Lynch, GS (corresponding author), Univ Melbourne, Basic & Clin Myol Lab, Dept Physiol, Melbourne, Vic 3010, Australia.
EM gsl@unimelb.edu.au
FU National Health and Medical Research Council (NHMRC) [1009114, 472650, 1004441]; Association Francaise contre les Myopathies (France); Muscular Dystrophy Association (USA); Swiss National Science Foundation; National Heart Foundation (Australia); National Heart Foundation; Fondazione Telethon Funding Source: Custom; National Health and Medical Research Council (NHMRC) [472650, 1004441, 1009114] Funding Source: National Health and Medical Research Council (NHMRC); Medical Research Council [MC_U137761449] Funding Source: researchfish; MRC [MC_U137761449] Funding Source: UKRI
NR 43
TC 222
Z9 266
U1 0
U2 44
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 19
PY 2012
VL 484
IS 7394
BP 394
EP 398
DI 10.1038/nature10980
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 927YM
UT WOS:000302946500037
PM 22495301
DA 2026-03-09
ER

PT J
AU Neph, S
   Vierstra, J
   Stergachis, AB
   Reynolds, AP
   Haugen, E
   Vernot, B
   Thurman, RE
   John, S
   Sandstrom, R
   Johnson, AK
   Maurano, MT
   Humbert, R
   Rynes, E
   Wang, H
   Vong, S
   Lee, K
   Bates, D
   Diegel, M
   Roach, V
   Dunn, D
   Neri, J
   Schafer, A
   Hansen, RS
   Kutyavin, T
   Giste, E
   Weaver, M
   Canfield, T
   Sabo, P
   Zhang, MH
   Balasundaram, G
   Byron, R
   MacCoss, MJ
   Akey, JM
   Bender, MA
   Groudine, M
   Kaul, R
   Stamatoyannopoulos, JA
AF Neph, Shane
   Vierstra, Jeff
   Stergachis, Andrew B.
   Reynolds, Alex P.
   Haugen, Eric
   Vernot, Benjamin
   Thurman, Robert E.
   John, Sam
   Sandstrom, Richard
   Johnson, Audra K.
   Maurano, Matthew T.
   Humbert, Richard
   Rynes, Eric
   Wang, Hao
   Vong, Shinny
   Lee, Kristen
   Bates, Daniel
   Diegel, Morgan
   Roach, Vaughn
   Dunn, Douglas
   Neri, Jun
   Schafer, Anthony
   Hansen, R. Scott
   Kutyavin, Tanya
   Giste, Erika
   Weaver, Molly
   Canfield, Theresa
   Sabo, Peter
   Zhang, Miaohua
   Balasundaram, Gayathri
   Byron, Rachel
   MacCoss, Michael J.
   Akey, Joshua M.
   Bender, M. A.
   Groudine, Mark
   Kaul, Rajinder
   Stamatoyannopoulos, John A.
TI An expansive human regulatory lexicon encoded in transcription factor footprints
SO NATURE
LA English
DT Article
ID in-vivo; dna; protein; gene; expression; chromatin; differentiation; erythropoiesis; induction; requires
AB Regulatory factor binding to genomic DNA protects the underlying sequence from cleavage by DNase I, leaving nucleotide-resolution 'footprints'. Using genomic DNase I footprinting across 41 diverse cell and tissue types, we detected 45 million transcription factor occupancy events within regulatory regions, representing differential binding to 8.4 million distinct short sequence elements. Here we show that this small genomic sequence compartment, roughly twice the size of the exome, encodes an expansive repertoire of conserved recognition sequences for DNA-binding proteins that nearly doubles the size of the human cis-regulatory lexicon. We find that genetic variants affecting allelic chromatin states are concentrated in footprints, and that these elements are preferentially sheltered from DNA methylation. High-resolution DNase I cleavage patterns mirror nucleotide-level evolutionary conservation and track the crystallographic topography of protein-DNA interfaces, indicating that transcription factor structure has been evolutionarily imprinted on the human genome sequence. We identify a stereotyped 50-base-pair footprint that precisely defines the site of transcript origination within thousands of human promoters. Finally, we describe a large collection of novel regulatory factor recognition motifs that are highly conserved in both sequence and function, and exhibit cell-selective occupancy patterns that closely parallel major regulators of development, differentiation and pluripotency.
C1 [Neph, Shane; Vierstra, Jeff; Stergachis, Andrew B.; Reynolds, Alex P.; Haugen, Eric; Vernot, Benjamin; Thurman, Robert E.; John, Sam; Sandstrom, Richard; Johnson, Audra K.; Maurano, Matthew T.; Humbert, Richard; Rynes, Eric; Wang, Hao; Vong, Shinny; Lee, Kristen; Bates, Daniel; Diegel, Morgan; Roach, Vaughn; Dunn, Douglas; Neri, Jun; Schafer, Anthony; Hansen, R. Scott; Kutyavin, Tanya; Giste, Erika; Weaver, Molly; Canfield, Theresa; Sabo, Peter; MacCoss, Michael J.; Akey, Joshua M.; Kaul, Rajinder; Stamatoyannopoulos, John A.] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA.
   [Hansen, R. Scott; Kaul, Rajinder] Univ Washington, Dept Med, Div Med Genet, Seattle, WA 98195 USA.
   [Zhang, Miaohua; Balasundaram, Gayathri; Byron, Rachel; Bender, M. A.; Groudine, Mark] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA.
   [Bender, M. A.] Univ Washington, Dept Pediat, Seattle, WA 98195 USA.
   [Groudine, Mark] Univ Washington, Dept Med, Dept Radiat Oncol, Seattle, WA 98195 USA.
   [Stamatoyannopoulos, John A.] Univ Washington, Dept Med, Div Oncol, Seattle, WA 98195 USA.
C3 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; University of Washington; University of Washington Seattle
RP Stamatoyannopoulos, JA (corresponding author), Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA.
EM jstam@uw.edu
FU National Institutes of Health (NIH) [HG004592, RC2HG005654]; National Science Foundation [DGE-071824]; University of Washington Proteomics Resource [UWPR95794]; National Cancer Institute [P30CA015704] Funding Source: NIH RePORTER
NR 42
TC 570
Z9 751
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 SEP 6
PY 2012
VL 489
IS 7414
BP 83
EP 90
DI 10.1038/nature11212
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 999WW
UT WOS:000308347000041
PM 22955618
DA 2026-03-09
ER

PT J
AU Rolland, M
   Edlefsen, PT
   Larsen, BB
   Tovanabutra, S
   Sanders-Buell, E
   Hertz, T
   deCamp, AC
   Carrico, C
   Menis, S
   Magaret, CA
   Ahmed, H
   Juraska, M
   Chen, L
   Konopa, P
   Nariya, S
   Stoddard, JN
   Wong, K
   Zhao, H
   Deng, WJ
   Maust, BS
   Bose, M
   Howell, S
   Bates, A
   Lazzaro, M
   O'Sullivan, A
   Lei, E
   Bradfield, A
   Ibitamuno, G
   Assawadarachai, V
   O'Connell, RJ
   deSouza, MS
   Nitayaphan, S
   Rerks-Ngarm, S
   Robb, ML
   McLellan, JS
   Georgiev, I
   Kwong, PD
   Carlson, JM
   Michael, NL
   Schief, WR
   Gilbert, PB
   Mullins, JI
   Kim, JH
AF Rolland, Morgane
   Edlefsen, Paul T.
   Larsen, Brendan B.
   Tovanabutra, Sodsai
   Sanders-Buell, Eric
   Hertz, Tomer
   deCamp, Allan C.
   Carrico, Chris
   Menis, Sergey
   Magaret, Craig A.
   Ahmed, Hasan
   Juraska, Michal
   Chen, Lennie
   Konopa, Philip
   Nariya, Snehal
   Stoddard, Julia N.
   Wong, Kim
   Zhao, Hong
   Deng, Wenjie
   Maust, Brandon S.
   Bose, Meera
   Howell, Shana
   Bates, Adam
   Lazzaro, Michelle
   O'Sullivan, Annemarie
   Lei, Esther
   Bradfield, Andrea
   Ibitamuno, Grace
   Assawadarachai, Vatcharain
   O'Connell, Robert J.
   deSouza, Mark S.
   Nitayaphan, Sorachai
   Rerks-Ngarm, Supachai
   Robb, Merlin L.
   McLellan, Jason S.
   Georgiev, Ivelin
   Kwong, Peter D.
   Carlson, Jonathan M.
   Michael, Nelson L.
   Schief, William R.
   Gilbert, Peter B.
   Mullins, James I.
   Kim, Jerome H.
TI Increased HIV-1 vaccine efficacy against viruses with genetic signatures in Env V2
SO NATURE
LA English
DT Article
ID competing risks; subtype-c; trial; neutralization; protection; infection; sequences; epitopes; thailand; aidsvax
AB The RV144 trial demonstrated 31% vaccine efficacy at preventing human immunodeficiency virus (HIV)-1 infection(1). Antibodies against the HIV-1 envelope variable loops 1 and 2 (Env V1 and V2) correlated inversely with infection risk(2). We proposed that vaccine-induced immune responses against V1/V2 would have a selective effect against, or sieve, HIV-1 breakthrough viruses. A total of 936 HIV-1 genome sequences from 44 vaccine and 66 placebo recipients were examined. We show that vaccine-induced immune responses were associated with two signatures in V2 at amino acid positions 169 and 181. Vaccine efficacy against viruses matching the vaccine at position 169 was 48% (confidence interval 18% to 66%; P = 0.0036), whereas vaccine efficacy against viruses mismatching the vaccine at position 181 was 78% (confidence interval 35% to 93%; P = 0.0028). Residue 169 is in a cationic glycosylated region recognized by broadly neutralizing and RV144-derived antibodies. The predicted distance between the two signature sites (21 +/- 7 angstrom) and their match/mismatch dichotomy indicate that multiple factors may be involved in the protection observed in RV144. Genetic signatures of RV144 vaccination in V2 complement the finding of an association between high V1/V2-binding antibodies and reduced risk of HIV-1 acquisition, and provide evidence that vaccine-induced V2 responses plausibly had a role in the partial protection conferred by the RV144 regimen.
C1 [Rolland, Morgane; Tovanabutra, Sodsai; Sanders-Buell, Eric; Bose, Meera; Howell, Shana; Bates, Adam; Lazzaro, Michelle; O'Sullivan, Annemarie; Lei, Esther; Bradfield, Andrea; Ibitamuno, Grace; O'Connell, Robert J.; Robb, Merlin L.; Michael, Nelson L.; Kim, Jerome H.] US Mil HIV Res Program, Silver Spring, MD 20910 USA.
   [Edlefsen, Paul T.; Hertz, Tomer; deCamp, Allan C.; Magaret, Craig A.; Ahmed, Hasan; Juraska, Michal; Gilbert, Peter B.] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, Stat Ctr HIV AIDS Res & Prevent, Seattle, WA 98109 USA.
   [Larsen, Brendan B.; Chen, Lennie; Konopa, Philip; Nariya, Snehal; Stoddard, Julia N.; Wong, Kim; Zhao, Hong; Deng, Wenjie; Maust, Brandon S.; Mullins, James I.] Univ Washington, Dept Microbiol, Seattle, WA 98195 USA.
   [Carrico, Chris; Menis, Sergey; Schief, William R.] Univ Washington, Dept Biochem, Seattle, WA 98195 USA.
   [Carrico, Chris; Menis, Sergey; Schief, William R.] Scripps Res Inst, IAVI Neutralizing Antibody Ctr, La Jolla, CA 92037 USA.
   [Carrico, Chris; Menis, Sergey; Schief, William R.] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA.
   [Assawadarachai, Vatcharain; deSouza, Mark S.; Nitayaphan, Sorachai] Royal Thai Army Component, AFRIMS, Bangkok 10400, Thailand.
   [Rerks-Ngarm, Supachai] Thai Minist Publ Hlth, Nonthaburi 11000, Thailand.
   [McLellan, Jason S.; Georgiev, Ivelin; Kwong, Peter D.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
   [Carlson, Jonathan M.] Microsoft Res, Redmond, WA 98052 USA.
C3 Walter Reed Army Institute of Research (WRAIR); Fred Hutchinson Cancer Center; University of Washington; University of Washington Seattle; University of Washington; University of Washington Seattle; International AIDS Vaccine Initiative; Scripps Research Institute; Scripps Research Institute; Walter Reed Army Institute of Research (WRAIR); Armed Forces Research Institute of Medical Science (AFRIMS); Ministry of Public Health - Thailand; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID); Microsoft
RP Rolland, M (corresponding author), US Mil HIV Res Program, Silver Spring, MD 20910 USA.
EM mrolland@hivresearch.org
FU US Army Medical Research and Material Command (USAMRMC) [Y1-AI-2642-12]; National Institutes of Allergy and Infectious Diseases [Y1-AI-2642-12]; Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc. [W81XWH-07-2-0067]; US Department of Defense (DOD) [W81XWH-07-2-0067]; NIH [2R37AI05465-10]; National Institute of Allergy and Infectious Diseases [ZIAAI005023, R37AI054165, UM1AI068635] Funding Source: NIH RePORTER
NR 30
TC 352
Z9 412
U1 1
U2 86
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD OCT 18
PY 2012
VL 490
IS 7420
BP 417
EP +
DI 10.1038/nature11519
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 021XI
UT WOS:000309918500049
PM 22960785
DA 2026-03-09
ER

PT J
AU Kourtis, N
   Nikoletopoulou, V
   Tavernarakis, N
AF Kourtis, Nikos
   Nikoletopoulou, Vassiliki
   Tavernarakis, Nektarios
TI Small heat-shock proteins protect from heat-stroke-associated neurodegeneration
SO NATURE
LA English
DT Article
ID necrotic cell-death; caenorhabditis-elegans; c-elegans; endoplasmic-reticulum; golgi-apparatus; life-span; molecular chaperones; stress-response; neurons; gene
AB Heat stroke is a life-threatening condition, characterized by catastrophic collapse of thermoregulation and extreme hyperthermia. In recent years, intensification of heat waves has caused a surge of heat-stroke fatalities. The mechanisms underlying heat-related pathology are poorly understood. Here we show that heat stroke triggers pervasive necrotic cell death and neurodegeneration in Caenorhabditis elegans. Preconditioning of animals at a mildly elevated temperature strongly protects from heat-induced necrosis. The heat-shock transcription factor HSF-1 and the small heat-shock protein HSP-16.1 mediate cytoprotection by preconditioning. HSP-16.1 localizes to the Golgi, where it functions with the Ca2+- and Mn2+-transporting ATPase PMR-1 to maintain Ca2+ homeostasis under heat stroke. Preconditioning also suppresses cell death inflicted by diverse insults, and protects mammalian neurons from heat cytotoxicity. These findings reveal an evolutionarily conserved mechanism that defends against diverse necrotic stimuli, and may be relevant to heat stroke and other pathological conditions involving necrosis in humans.
C1 [Kourtis, Nikos; Nikoletopoulou, Vassiliki; Tavernarakis, Nektarios] Fdn Res & Technol, Inst Mol Biol & Biotechnol, Iraklion 71110, Crete, Greece.
RP Tavernarakis, N (corresponding author), Fdn Res & Technol, Inst Mol Biol & Biotechnol, Iraklion 71110, Crete, Greece.
EM tavernarakis@imbb.forth.gr
FU National Center for Research Resources (NCRR) of the National Institutes of Health (NIH); National Bioresource Project in Japan; European Molecular Biology Organization (EMBO) Long Term Fellowship; European Research Council (ERC); European Commission 7th Framework Programme
NR 56
TC 142
Z9 179
U1 3
U2 90
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD OCT 11
PY 2012
VL 490
IS 7419
BP 213
EP +
DI 10.1038/nature11417
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 019IY
UT WOS:000309733300040
PM 22972192
DA 2026-03-09
ER

PT J
AU Bell, RD
   Winkler, EA
   Singh, I
   Sagare, AP
   Deane, R
   Wu, ZH
   Holtzman, DM
   Betsholtz, C
   Armulik, A
   Sallstrom, J
   Berk, BC
   Zlokovic, BV
AF Bell, Robert D.
   Winkler, Ethan A.
   Singh, Itender
   Sagare, Abhay P.
   Deane, Rashid
   Wu, Zhenhua
   Holtzman, David M.
   Betsholtz, Christer
   Armulik, Annika
   Sallstrom, Jan
   Berk, Bradford C.
   Zlokovic, Berislav V.
TI Apolipoprotein E controls cerebrovascular integrity via cyclophilin A
SO NATURE
LA English
DT Article
ID blood-brain-barrier; alzheimers-disease; cognitive impairment; oxidative stress; apoe; dementia; protein; mice; neurodegeneration; expression
AB Human apolipoprotein E has three isoforms: APOE2, APOE3 and APOE4(1). APOE4 is a major genetic risk factor for Alzheimer's disease(2,3) and is associated with Down's syndrome dementia and poor neurological outcome after traumatic brain injury and haemorrhage(3). Neurovascular dysfunction is present in normal APOE4 carriers(4-6) and individuals with APOE4-associated disorders(3,7-10). In mice, lack of Apoe leads to blood-brain barrier (BBB) breakdown(11,12), whereas APOE4 increases BBB susceptibility to injury(13). How APOE genotype affects brain microcirculation remains elusive. Using different APOE transgenic mice, including mice with ablation and/or inhibition of cyclophilin A (CypA), here we show that expression of APOE4 and lack of murine Apoe, but not APOE2 and APOE3, leads to BBB breakdown by activating a proinflammatory CypA-nuclear factor-kappa B-matrix-metalloproteinase-9 pathway in pericytes. This, in turn, leads to neuronal uptake of multiple blood-derived neurotoxic proteins, and microvascular and cerebral blood flow reductions. We show that the vascular defects in Apoe-deficient and APOE4-expressing mice precede neuronal dysfunction and can initiate neurodegenerative changes. Astrocyte-secreted APOE3, but not APOE4, suppressed the CypA-nuclear factor-kappa B-matrix-metalloproteinase-9 pathway in pericytes through a lipoprotein receptor. Our data suggest that CypA is a key target for treating APOE4-mediated neurovascular injury and the resulting neuronal dysfunction and degeneration.
C1 [Bell, Robert D.; Winkler, Ethan A.; Singh, Itender; Sagare, Abhay P.; Deane, Rashid; Wu, Zhenhua; Sallstrom, Jan; Zlokovic, Berislav V.] Univ Rochester, Med Ctr, Ctr Neurodegenerat & Vasc Brain Disorders, Rochester, NY 14642 USA.
   [Bell, Robert D.; Berk, Bradford C.] Univ Rochester, Med Ctr, Aab Cardiovasc Res Inst, Rochester, NY 14642 USA.
   [Holtzman, David M.] Washington Univ, Sch Med, Knight Alzheimers Dis Res Ctr, Hope Ctr Neurol Disorders,Dept Neurol, St Louis, MO 63110 USA.
   [Betsholtz, Christer; Armulik, Annika] Karolinska Inst, Dept Med Biochem & Biophys, Div Vasc Biol, SE-17177 Stockholm, Sweden.
   [Armulik, Annika] Univ Zurich Hosp, Inst Neuropathol, CH-8091 Zurich, Switzerland.
   [Zlokovic, Berislav V.] Univ So Calif, Keck Sch Med, Zilkha Neurogenet Inst, Ctr Neurodegenerat & Regenerat, Los Angeles, CA 90089 USA.
   [Zlokovic, Berislav V.] Univ So Calif, Keck Sch Med, Dept Physiol & Biophys, Los Angeles, CA 90089 USA.
C3 University of Rochester; University of Rochester; Washington University (WUSTL); Karolinska Institutet; University of Zurich; University Zurich Hospital; University of Southern California; University of Southern California
RP Zlokovic, BV (corresponding author), Univ Rochester, Med Ctr, Ctr Neurodegenerat & Vasc Brain Disorders, Rochester, NY 14642 USA.
EM zlokovic@usc.edu
FU National Institute of Health [R37NS34467, R37AG23084, RO1AG039452, R37AG13956]; National Institute of Neurological Disorders and Stroke; National Institute on Aging [R01NS034467] Funding Source: NIH RePORTER
NR 30
TC 1069
Z9 1231
U1 5
U2 229
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD MAY 24
PY 2012
VL 485
IS 7399
BP 512
EP 516
DI 10.1038/nature11087
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 946IH
UT WOS:000304344500045
PM 22622580
DA 2026-03-09
ER

PT J
AU Prüfer, K
   Munch, K
   Hellmann, I
   Akagi, K
   Miller, JR
   Walenz, B
   Koren, S
   Sutton, G
   Kodira, C
   Winer, R
   Knight, JR
   Mullikin, JC
   Meader, SJ
   Ponting, CP
   Lunter, G
   Higashino, S
   Hobolth, A
   Dutheil, J
   Karakoç, E
   Alkan, C
   Sajjadian, S
   Catacchio, CR
   Ventura, M
   Marques-Bonet, T
   Eichler, EE
   André, C
   Atencia, R
   Mugisha, L
   Junhold, J
   Patterson, N
   Siebauer, M
   Good, JM
   Fischer, A
   Ptak, SE
   Lachmann, M
   Symer, DE
   Mailund, T
   Schierup, MH
   Andrés, AM
   Kelso, J
   Pääbo, S
AF Pruefer, Kay
   Munch, Kasper
   Hellmann, Ines
   Akagi, Keiko
   Miller, Jason R.
   Walenz, Brian
   Koren, Sergey
   Sutton, Granger
   Kodira, Chinnappa
   Winer, Roger
   Knight, James R.
   Mullikin, James C.
   Meader, Stephen J.
   Ponting, Chris P.
   Lunter, Gerton
   Higashino, Saneyuki
   Hobolth, Asger
   Dutheil, Julien
   Karakoc, Emre
   Alkan, Can
   Sajjadian, Saba
   Catacchio, Claudia Rita
   Ventura, Mario
   Marques-Bonet, Tomas
   Eichler, Evan E.
   Andre, Claudine
   Atencia, Rebeca
   Mugisha, Lawrence
   Junhold, Joerg
   Patterson, Nick
   Siebauer, Michael
   Good, Jeffrey M.
   Fischer, Anne
   Ptak, Susan E.
   Lachmann, Michael
   Symer, David E.
   Mailund, Thomas
   Schierup, Mikkel H.
   Andres, Aida M.
   Kelso, Janet
   Paeaebo, Svante
TI The bonobo genome compared with the chimpanzee and human genomes
SO NATURE
LA English
DT Article
ID landscape
AB Two African apes are the closest living relatives of humans: the chimpanzee (Pan troglodytes) and the bonobo (Pan paniscus). Although they are similar in many respects, bonobos and chimpanzees differ strikingly in key social and sexual behaviours(1-4), and for some of these traits they show more similarity with humans than with each other. Here we report the sequencing and assembly of the bonobo genome to study its evolutionary relationship with the chimpanzee and human genomes. We find that more than three per cent of the human genome is more closely related to either the bonobo or the chimpanzee genome than these are to each other. These regions allow various aspects of the ancestry of the two ape species to be reconstructed. In addition, many of the regions that overlap genes may eventually help us understand the genetic basis of phenotypes that humans share with one of the two apes to the exclusion of the other.
C1 [Pruefer, Kay; Siebauer, Michael; Good, Jeffrey M.; Fischer, Anne; Ptak, Susan E.; Lachmann, Michael; Andres, Aida M.; Kelso, Janet; Paeaebo, Svante] Max Planck Inst Evolutionary Anthropol, D-04103 Leipzig, Germany.
   [Munch, Kasper; Hobolth, Asger; Dutheil, Julien; Mailund, Thomas; Schierup, Mikkel H.] Aarhus Univ, Bioinformat Res Ctr, DK-8000 Aarhus C, Denmark.
   [Hellmann, Ines] Univ Vienna, Max F Perutz Labs, A-1030 Vienna, Austria.
   [Akagi, Keiko; Symer, David E.] Ohio State Univ, Ctr Comprehens Canc, Human Canc Genet Program, Columbus, OH 43210 USA.
   [Akagi, Keiko; Symer, David E.] Ohio State Univ, Ctr Comprehens Canc, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43210 USA.
   [Miller, Jason R.; Walenz, Brian; Sutton, Granger] J Craig Venter Inst, Rockville, MD 20850 USA.
   [Koren, Sergey] Univ Maryland, College Pk, MD 20742 USA.
   [Kodira, Chinnappa; Winer, Roger; Knight, James R.] 454 Life Sci, Branford, CT 06405 USA.
   [Mullikin, James C.] NHGRI, Genome Technol Branch, Natl Inst Hlth, Bethesda, MD 20892 USA.
   [Meader, Stephen J.; Ponting, Chris P.] Univ Oxford, Dept Physiol Anat & Genet, MRC Funct Genom Unit, Oxford OX1 3QX, England.
   [Lunter, Gerton] Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.
   [Higashino, Saneyuki] Tokyo Inst Technol, Grad Sch Biosci & Biotechnol, Kanagawa 2268503, Japan.
   [Karakoc, Emre; Alkan, Can; Sajjadian, Saba; Ventura, Mario; Marques-Bonet, Tomas; Eichler, Evan E.] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA.
   [Karakoc, Emre; Alkan, Can; Sajjadian, Saba; Ventura, Mario; Marques-Bonet, Tomas; Eichler, Evan E.] Howard Hughes Med Inst, Seattle, WA 98195 USA.
   [Catacchio, Claudia Rita; Ventura, Mario] Univ Bari, Dipartimento Anat Patol & Genet, Sez Genet, I-70125 Bari, Italy.
   [Marques-Bonet, Tomas] UPF CSIC, Inst Biol Evolutiva, ICREA, Barcelona 08003, Catalonia, Spain.
   [Atencia, Rebeca] Jane Goodall Inst, Pointe Noire, DEM REP CONGO.
   [Mugisha, Lawrence] CSWCT, Entebbe, Uganda.
   [Junhold, Joerg] Zoo Leipzig, D-04105 Leipzig, Germany.
   [Patterson, Nick] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
   [Good, Jeffrey M.] Univ Montana, Div Biol Sci, Missoula, MT 59812 USA.
   [Fischer, Anne] Int Ctr Insect Physiol & Ecol, Nairobi 00100, Kenya.
   [Schierup, Mikkel H.] Aarhus Univ, Dept Biosci, DK-8000 Aarhus C, Denmark.
C3 Max Planck Society; Aarhus University; University of Vienna; Vienna Biocenter (VBC); Max F. Perutz Laboratories (MFPL); University System of Ohio; Ohio State University; James Cancer Hospital & Solove Research Institute; James Cancer Hospital & Solove Research Institute; University System of Ohio; Ohio State University; J. Craig Venter Institute; University System of Maryland; University of Maryland College Park; National Institutes of Health (NIH) - USA; NIH National Human Genome Research Institute (NHGRI); University of Oxford; University of Oxford; Wellcome Centre for Human Genetics; Institute of Science Tokyo; Tokyo Institute of Technology; University of Washington; University of Washington Seattle; Howard Hughes Medical Institute; Universita degli Studi di Bari Aldo Moro; Consejo Superior de Investigaciones Cientificas (CSIC); CSIC-UPF - Institut de Biologia Evolutiva (IBE); Pompeu Fabra University; ICREA; Harvard University; Harvard Medical School; University of Montana System; University of Montana; International Centre of Insect Physiology & Ecology (ICIPE); Aarhus University
RP Prüfer, K (corresponding author), Max Planck Inst Evolutionary Anthropol, D-04103 Leipzig, Germany.
EM pruefer@eva.mpg.de; paabo@eva.mpg.de
FU ERC [233297, StG_20091118]; National Institutes of Health [2R01GM077117-04A1, HG002385]; Ramon y Cajal grant (MICINN-RYC); Ohio State University Comprehensive Cancer Center; Ohio Supercomputer Center [PAS0425]; Ohio Cancer Research Associates [GRT00024299]; Wellcome Trust [090532/Z/09/Z]; US National Science Foundation [OISE-0754461]; Danish Council for Independent Research \ Natural Sciences [09-062535]; National Human Genome Research Institute [ZIAHG200330, R01HG002385] Funding Source: NIH RePORTER; Medical Research Council [MC_U137761446] Funding Source: researchfish; MRC [MC_U137761446] Funding Source: UKRI; ICREA Funding Source: Custom; European Research Council (ERC) [233297] Funding Source: European Research Council (ERC)
NR 30
TC 373
Z9 435
U1 2
U2 248
PU NATURE PUBLISHING 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 28
PY 2012
VL 486
IS 7404
BP 527
EP 531
DI 10.1038/nature11128
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 965IJ
UT WOS:000305760600042
PM 22722832
DA 2026-03-09
ER

PT J
AU Francia, S
   Michelini, F
   Saxena, A
   Tang, D
   de Hoon, M
   Anelli, V
   Mione, M
   Carninci, P
   di Fagagna, FD
AF Francia, Sofia
   Michelini, Flavia
   Saxena, Alka
   Tang, Dave
   de Hoon, Michiel
   Anelli, Viviana
   Mione, Marina
   Carninci, Piero
   di Fagagna, Fabrizio d'Adda
TI Site-specific DICER and DROSHA RNA products control the DNA-damage response
SO NATURE
LA English
DT Article
ID double-strand breaks; noncoding rnas; cellular senescence; chromatin; proteins; heterochromatin; biogenesis; reveals; disease; complex
AB Non-coding RNAs (ncRNAs) are involved in an increasingly recognized number of cellular events(1). Some ncRNAs are processed by DICER and DROSHA RNases to give rise to small double-stranded RNAs involved in RNA interference (RNAi)(2). The DNA-damage response (DDR) is a signalling pathway that originates from a DNA lesion and arrests cell proliferation(3). So far, DICER and DROSHA RNA products have not been reported to control DDR activation. Here we show, in human, mouse and zebrafish, that DICER and DROSHA, but not downstream elements of the RNAi pathway, are necessary to activate the DDR upon exogenous DNA damage and oncogene-induced genotoxic stress, as studied by DDR foci formation and by checkpoint assays. DDR foci are sensitive to RNase A treatment, and DICER-and DROSHA-dependent RNA products are required to restore DDR foci in RNase-A-treated cells. Through RNA deep sequencing and the study of DDR activation at a single inducible DNA double-strand break, we demonstrate that DDR foci formation requires site-specific DICER- and DROSHA-dependent small RNAs, named DDRNAs, which act in a MRE11-RAD50-NBS1-complex-dependent manner (MRE11 also known as MRE11A; NBS1 also known as NBN). DDRNAs, either chemically synthesized or in vitro generated by DICER cleavage, are sufficient to restore the DDR in RNase-A-treated cells, also in the absence of other cellular RNAs. Our results describe an unanticipated direct role of a novel class of ncRNAs in the control of DDR activation at sites of DNA damage.
C1 [Francia, Sofia; Michelini, Flavia; Anelli, Viviana; Mione, Marina; di Fagagna, Fabrizio d'Adda] IFOM Fdn FIRC Inst Mol Oncol Fdn, I-20139 Milan, Italy.
   [Francia, Sofia] Ist Italiano Tecnol, IIT SEMM, Center Genom Sci, I-20139 Milan, Italy.
   [Saxena, Alka; Tang, Dave; de Hoon, Michiel; Carninci, Piero] RIKEN Yokohama Inst, Om Sci Ctr, Tsurumi Ku, Yokohama, Kanagawa 2300045, Japan.
   [di Fagagna, Fabrizio d'Adda] CNR, Ist Genet Mol, I-27100 Pavia, Italy.
C3 IFOM - FIRC Institute of Molecular Oncology; Istituto Italiano di Tecnologia - IIT; Center for Genomic Science IIT; RIKEN; Consiglio Nazionale delle Ricerche (CNR); Istituto di Genetica Molecolare (IGM-CNR)
RP di Fagagna, FD (corresponding author), IFOM Fdn FIRC Inst Mol Oncol Fdn, Via Adamello 16, I-20139 Milan, Italy.
EM fabrizio.dadda@ifom-ieo-campus.it
FU Fondazione Italiana Ricerca Sul Cancro (FIRC); Associazione Italiana Ricerca sul Cancro (AIRC) European Community's 7th Framework Programme [202230]; Telethon [GGP08183]; 7th Framework of the European Union commission, Funding Program for the Next Generation World-Leading Researchers (NEXT Program) [20241047]; MEXT; Center for Genomic Science of IIT@SEMM (Scuola Europea di Medicina Molecolare); AIRC; Cariplo [2007-5500]; JSPS [P09745]; European Union 7th Framework Programme [FP7-People-ITN-2008-238055]
NR 30
TC 443
Z9 500
U1 0
U2 52
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD AUG 9
PY 2012
VL 488
IS 7410
BP 231
EP +
DI 10.1038/nature11179
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 985LE
UT WOS:000307267000038
PM 22722852
DA 2026-03-09
ER

PT J
AU Carvunis, AR
   Rolland, T
   Wapinski, I
   Calderwood, MA
   Yildirim, MA
   Simonis, N
   Charloteaux, B
   Hidalgo, CA
   Barbette, J
   Santhanam, B
   Brar, GA
   Weissman, JS
   Regev, A
   Thierry-Mieg, N
   Cusick, ME
   Vidal, M
AF Carvunis, Anne-Ruxandra
   Rolland, Thomas
   Wapinski, Ilan
   Calderwood, Michael A.
   Yildirim, Muhammed A.
   Simonis, Nicolas
   Charloteaux, Benoit
   Hidalgo, Cesar A.
   Barbette, Justin
   Santhanam, Balaji
   Brar, Gloria A.
   Weissman, Jonathan S.
   Regev, Aviv
   Thierry-Mieg, Nicolas
   Cusick, Michael E.
   Vidal, Marc
TI Proto-genes and de novo gene birth
SO NATURE
LA English
DT Article
ID saccharomyces-cerevisiae; yeast genome; evolution; adaptation; selection; proteins; sequence; origin; dna
AB Novel protein-coding genes can arise either through re-organization of pre-existing genes or de novo(1,2). Processes involving re-organization of pre-existing genes, notably after gene duplication, have been extensively described(1,2). In contrast, de novo gene birth remains poorly understood, mainly because translation of sequences devoid of genes, or 'non-genic' sequences, is expected to produce insignificant polypeptides rather than proteins with specific biological functions(1,3-6). Here we formalize an evolutionary model according to which functional genes evolve de novo through transitory proto-genes(4) generated by widespread translational activity in non-genic sequences. Testing this model at the genome scale in Saccharomyces cerevisiae, we detect translation of hundreds of short species-specific open reading frames (ORFs) located in non-genic sequences. These translation events seem to provide adaptive potential(7), as suggested by their differential regulation upon stress and by signatures of retention by natural selection. In line with our model, we establish that S. cerevisiae ORFs can be placed within an evolutionary continuum ranging from non-genic sequences to genes. We identify similar to 1,900 candidate proto-genes among S. cerevisiae ORFs and find that de novo gene birth from such a reservoir may be more prevalent than sporadic gene duplication. Our work illustrates that evolution exploits seemingly dispensable sequences to generate adaptive functional innovation.
C1 [Carvunis, Anne-Ruxandra; Rolland, Thomas; Calderwood, Michael A.; Simonis, Nicolas; Charloteaux, Benoit; Barbette, Justin; Santhanam, Balaji; Cusick, Michael E.; Vidal, Marc] Dana Farber Canc Inst, Ctr Canc Syst Biol CCSB, Boston, MA 02215 USA.
   [Carvunis, Anne-Ruxandra; Rolland, Thomas; Calderwood, Michael A.; Simonis, Nicolas; Charloteaux, Benoit; Barbette, Justin; Santhanam, Balaji; Cusick, Michael E.; Vidal, Marc] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA.
   [Carvunis, Anne-Ruxandra; Rolland, Thomas; Calderwood, Michael A.; Simonis, Nicolas; Charloteaux, Benoit; Barbette, Justin; Santhanam, Balaji; Cusick, Michael E.; Vidal, Marc] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
   [Carvunis, Anne-Ruxandra; Thierry-Mieg, Nicolas] UJF Grenoble 1, CNRS, TIMC IMAG, UMR 5525,Computat & Math Biol Grp, F-38031 Grenoble, France.
   [Wapinski, Ilan] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA.
   [Yildirim, Muhammed A.] Harvard Univ, Cambridge, MA 02138 USA.
   [Yildirim, Muhammed A.] Ctr Int Dev, Cambridge, MA 02138 USA.
   [Charloteaux, Benoit] Univ Liege, GIGA R, Unit Anim Genom, B-4000 Liege, Wallonia Brusse, Belgium.
   [Hidalgo, Cesar A.] MIT, MIT Media Lab, Cambridge, MA 02142 USA.
   [Brar, Gloria A.; Weissman, Jonathan S.] Univ Calif San Francisco, Howard Hughes Med Inst, Dept Cell & Mol Pharmacol, San Francisco, CA 94158 USA.
   [Brar, Gloria A.; Weissman, Jonathan S.] Calif Inst Quantitat Biosci, San Francisco, CA 94158 USA.
   [Regev, Aviv] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.
   [Regev, Aviv] MIT, Howard Hughes Med Inst, Dept Biol, Cambridge, MA 02139 USA.
   [Charloteaux, Benoit] Univ Liege, Fac Vet Med, B-4000 Liege, Belgium.
C3 Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard Medical School; Communaute Universite Grenoble Alpes; Institut National Polytechnique de Grenoble; Universite Grenoble Alpes (UGA); Centre National de la Recherche Scientifique (CNRS); CNRS - Institute for Engineering & Systems Sciences (INSIS); Harvard University; Harvard Medical School; Harvard University; University of Liege; Massachusetts Institute of Technology (MIT); University of California System; University of California San Francisco; Howard Hughes Medical Institute; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Howard Hughes Medical Institute; Massachusetts Institute of Technology (MIT); University of Liege
RP Vidal, M (corresponding author), Dana Farber Canc Inst, Ctr Canc Syst Biol CCSB, Boston, MA 02215 USA.
EM marc_vidal@dfci.harvard.edu
FU National Institute of Health; Scientific Interface from the Burroughs Wellcome Fund; Howard Hughes Medical Institute (HHMI); American Cancer Society [117945-PF-09-136-01-RMC]; National Human Genome Research Institute [R01-HG006061]
NR 30
TC 480
Z9 543
U1 1
U2 118
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUL 19
PY 2012
VL 487
IS 7407
BP 370
EP 374
DI 10.1038/nature11184
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 975JB
UT WOS:000306506500044
PM 22722833
DA 2026-03-09
ER

PT J
AU Deegan, LA
   Johnson, DS
   Warren, RS
   Peterson, BJ
   Fleeger, JW
   Fagherazzi, S
   Wollheim, WM
AF Deegan, Linda A.
   Johnson, David Samuel
   Warren, R. Scott
   Peterson, Bruce J.
   Fleeger, John W.
   Fagherazzi, Sergio
   Wollheim, Wilfred M.
TI Coastal eutrophication as a driver of salt marsh loss
SO NATURE
LA English
DT Article
ID nutrient enrichment; nitrogen; denitrification; water; pseudoreplication; vegetation; reduction; stability; seagrass; ecology
AB Salt marshes are highly productive coastal wetlands that provide important ecosystem services such as storm protection for coastal cities, nutrient removal and carbon sequestration. Despite protective measures, however, worldwide losses of these ecosystems have accelerated in recent decades(1). Here we present data from a nine-year whole-ecosystem nutrient-enrichment experiment. Our study demonstrates that nutrient enrichment, a global problem for coastal ecosystems(2-4), can be a driver of salt marsh loss. We show that nutrient levels commonly associated with coastal eutrophication increased above-ground leaf biomass, decreased the dense, below-ground biomass of bank-stabilizing roots, and increased microbial decomposition of organic matter. Alterations in these key ecosystem properties reduced geomorphic stability, resulting in creek-bank collapse with significant areas of creek-bank marsh converted to unvegetated mud. This pattern of marsh loss parallels observations for anthropogenically nutrient-enriched marshes worldwide, with creek-edge and bay-edge marsh evolving into mudflats and wider creeks(5-7). Our work suggests that current nutrient loading rates to many coastal ecosystems have overwhelmed the capacity of marshes to remove nitrogen without deleterious effects. Projected increases in nitrogen flux to the coast, related to increased fertilizer use required to feed an expanding human population, may rapidly result in a coastal landscape with less marsh, which would reduce the capacity of coastal regions to provide important ecological and economic services.
C1 [Deegan, Linda A.; Johnson, David Samuel; Peterson, Bruce J.] Marine Biol Lab, Ctr Ecosyst, Woods Hole, MA 02543 USA.
   [Johnson, David Samuel] Sewanee Univ S, Dept Biol, Sewanee, TN 37383 USA.
   [Warren, R. Scott] Connecticut Coll, Dept Bot, New London, CT 06320 USA.
   [Fleeger, John W.] Louisiana State Univ, Dept Biol Sci, Baton Rouge, LA 70803 USA.
   [Fagherazzi, Sergio] Boston Univ, Dept Earth & Environm, Boston, MA 02215 USA.
   [Wollheim, Wilfred M.] Univ New Hampshire, Dept Nat Resources & Environm, Durham, NH 03824 USA.
C3 Marine Biological Laboratory - Woods Hole; Sewanee: University of the South; Connecticut College; Louisiana State University System; Louisiana State University; Boston University; University System Of New Hampshire; University of New Hampshire
RP Deegan, LA (corresponding author), Marine Biol Lab, Ctr Ecosyst, 7 MBL St, Woods Hole, MA 02543 USA.
EM ldeegan@mbl.edu
FU NSF [DEB0816963, DEB0213767, OCE0923689, OCE 0423565, OCE0924287]; NOAA; Mellon Foundation; Direct For Biological Sciences; Div Of Biological Infrastructure [0816963] Funding Source: National Science Foundation; Directorate For Geosciences; Division Of Ocean Sciences [0924287, 1058747, 0923689] Funding Source: National Science Foundation; Division Of Environmental Biology; Direct For Biological Sciences [0815398] Funding Source: National Science Foundation; Division Of Ocean Sciences; Directorate For Geosciences [1238212] Funding Source: National Science Foundation; Office Of The Director; EPSCoR [1101245] Funding Source: National Science Foundation
NR 57
TC 845
Z9 1070
U1 19
U2 1143
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 18
PY 2012
VL 490
IS 7420
BP 388
EP +
DI 10.1038/nature11533
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 021XI
UT WOS:000309918500043
PM 23075989
DA 2026-03-09
ER

PT J
AU Simmons, EM
   Hartwig, JF
AF Simmons, Eric M.
   Hartwig, John F.
TI Catalytic functionalization of unactivated primary C-H bonds directed by an alcohol
SO NATURE
LA English
DT Article
ID methyl-groups; hydroxylation; complexes; oxidation; terpenes
AB New synthetic methods for the catalytic functionalization of C-H bonds have the potential to revolutionize the synthesis of complex molecules(1-4). However, the realization of this synthetic potential requires the ability to functionalize selectively one C-H bond in a compound containing many such bonds and an array of functional groups. The site-selective functionalization of aliphatic C-H bonds is one of the greatest challenges that must be met for C-H bond functionalization to be used widely in complex-molecule synthesis(1,3,5,6), and processes catalysed by transition-metals provide the opportunity to control selectivity(7,8). Current methods for catalytic, aliphatic C-H bond functionalization typically rely on the presence of one inherently reactive C-H bond(9,10), or on installation and subsequent removal of directing groups that are not components of the desired molecule(8). To overcome these limitations, we sought catalysts and reagents that would facilitate aliphatic C-H bond functionalization at a single site, with chemoselectivity derived from the properties of the catalyst and site-selectivity directed by common functional groups(11) contained in both the reactant and the desired product. Here we show that the combination of an iridium-phenanthroline catalyst and a dihydridosilane reagent leads to the site-selective gamma-functionalization of primary C-H bonds controlled by a hydroxyl group, the most common functional group in natural products(12). The scope of the reaction encompasses alcohols and ketones bearing many substitution patterns and auxiliary functional groups; this broad scope suggests that this methodology will be suitable for the site-selective and diastereoselective functionalization of complex natural products.
C1 [Simmons, Eric M.; Hartwig, John F.] Univ Illinois, Dept Chem, Urbana, IL 61801 USA.
C3 University of Illinois System; University of Illinois Urbana-Champaign
RP Hartwig, JF (corresponding author), Univ Calif Berkeley, Dept Chem, Berkeley, CA 91820 USA.
EM jhartwig@berkeley.edu
FU US National Science Foundation [CHE-0910641]; US National Institutes of Health [GM087901]; Division Of Chemistry; Direct For Mathematical & Physical Scien [1156496] Funding Source: National Science Foundation
NR 30
TC 338
Z9 392
U1 2
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 1
PY 2012
VL 483
IS 7387
BP 70
EP 73
DI 10.1038/nature10785
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 900HP
UT WOS:000300877900046
PM 22382981
DA 2026-03-09
ER

PT J
AU Cappellari, M
   McDermid, RM
   Alatalo, K
   Blitz, L
   Bois, M
   Bournaud, F
   Bureau, M
   Crocker, AF
   Davies, RL
   Davis, TA
   de Zeeuw, PT
   Duc, PA
   Emsellem, E
   Khochfar, S
   Krajnovic, D
   Kuntschner, H
   Lablanche, PY
   Morganti, R
   Naab, T
   Oosterloo, T
   Sarzi, M
   Scott, N
   Serra, P
   Weijmans, AM
   Young, LM
AF Cappellari, Michele
   McDermid, Richard M.
   Alatalo, Katherine
   Blitz, Leo
   Bois, Maxime
   Bournaud, Frederic
   Bureau, M.
   Crocker, Alison F.
   Davies, Roger L.
   Davis, Timothy A.
   de Zeeuw, P. T.
   Duc, Pierre-Alain
   Emsellem, Eric
   Khochfar, Sadegh
   Krajnovic, Davor
   Kuntschner, Harald
   Lablanche, Pierre-Yves
   Morganti, Raffaella
   Naab, Thorsten
   Oosterloo, Tom
   Sarzi, Marc
   Scott, Nicholas
   Serra, Paolo
   Weijmans, Anne-Marie
   Young, Lisa M.
TI Systematic variation of the stellar initial mass function in early-type galaxies
SO NATURE
LA English
DT Article
ID dark-matter halos; to-light ratios; population synthesis; models; simulation; project; stars
AB Much of our knowledge of galaxies comes from analysing the radiation-emitted by their stars, which depends on the present number of each type of star in the galaxy. The present number depends on the stellar initial mass function (IMF), which describes the distribution of stellar masses when the population formed, and knowledge of it is critical to almost every aspect of galaxy evolution. More than 50 years after the first IMF determination(1), no consensus has emerged on whether it is universal among different types of galaxies(2). Previous studies indicated that the IMF and the dark matter fraction in galaxy centres cannot both be universal(3-7), but they could not convincingly discriminate between the two possibilities. Only recently were indications found that massive elliptical galaxies may not have the same IMF as the Milky Way(8). Here we report a study of the two-dimensional stellar kinematics for the large representative ATLAS(3D) sample(9) of nearby early-type galaxies spanning two orders of magnitude in stellar mass, using detailed dynamical models. We find a strong systematic variation in IMF in early-type galaxies as a function of their stellar mass-to-light ratios, producing differences of a factor of up to three in galactic stellar mass. This implies that a galaxy's IMF depends intimately on the galaxy's formation history.
C1 [Cappellari, Michele; Bureau, M.; Davies, Roger L.; Davis, Timothy A.; Scott, Nicholas] Univ Oxford, Dept Phys, Subdept Astrophys, Oxford OX1 3RH, England.
   [McDermid, Richard M.] Gemini Observ, No Operat Ctr, Hilo, HI 96720 USA.
   [Alatalo, Katherine; Blitz, Leo] Univ Calif Berkeley, Dept Astron, Berkeley, CA 94720 USA.
   [Bois, Maxime] Observ Paris, LERMA, F-75014 Paris, France.
   [Bois, Maxime] CNRS, F-75014 Paris, France.
   [Bournaud, Frederic; Duc, Pierre-Alain] Univ Paris Diderot, CNRS, CEA IRFU SAp, Lab AIM Paris Saclay, F-91191 Gif Sur Yvette, France.
   [Crocker, Alison F.] Univ Massachusetts, Dept Astrophys, Amherst, MA 01003 USA.
   [Davis, Timothy A.; de Zeeuw, P. T.; Emsellem, Eric; Krajnovic, Davor; Kuntschner, Harald; Lablanche, Pierre-Yves] European So Observ, D-85748 Garching, Germany.
   [de Zeeuw, P. T.] Leiden Univ, Sterrewacht Leiden, NL-2300 RA Leiden, Netherlands.
   [Emsellem, Eric; Lablanche, Pierre-Yves] Univ Lyon 1, Observ Lyon, Ctr Rech Astrophys Lyon, F-69230 St Genis Laval, France.
   [Emsellem, Eric; Lablanche, Pierre-Yves] Ecole Normale Super Lyon, F-69230 St Genis Laval, France.
   [Khochfar, Sadegh] Max Planck Inst Extraterr Phys, D-85478 Garching, Germany.
   [Morganti, Raffaella; Oosterloo, Tom; Serra, Paolo] Netherlands Inst Radio Astron, NL-7990 AA Dwingeloo, Netherlands.
   [Morganti, Raffaella; Oosterloo, Tom] Univ Groningen, Kapteyn Astron Inst, NL-9700 AV Groningen, Netherlands.
   [Naab, Thorsten] Max Planck Inst Astrophys, D-85741 Garching, Germany.
   [Sarzi, Marc] Univ Hertfordshire, Ctr Astrophys Res, Hatfield AL1 9AB, Herts, England.
   [Scott, Nicholas] Swinburne Univ Technol, Ctr Astrophys & Supercomp, Hawthorn, Vic 3122, Australia.
   [Weijmans, Anne-Marie] Univ Toronto, Dunlap Inst Astron & Astrophys, Toronto, ON M5S 3H4, Canada.
   [Young, Lisa M.] New Mexico Inst Min & Technol, Dept Phys, Socorro, NM 87801 USA.
C3 University of Oxford; University of California System; University of California Berkeley; Universite PSL; Observatoire de Paris; Centre National de la Recherche Scientifique (CNRS); Universite Paris Saclay; CEA; Centre National de la Recherche Scientifique (CNRS); Universite Paris Cite; University of Massachusetts System; University of Massachusetts Amherst; European Southern Observatory; Leiden University; Leiden University - Excl LUMC; Ecole Normale Superieure de Lyon (ENS de LYON); Universite Lyon 1; Ecole Normale Superieure de Lyon (ENS de LYON); Max Planck Society; University of Groningen; Kapteyn Astronomical Institute; Max Planck Society; University of Hertfordshire; Swinburne University of Technology; University of Toronto; New Mexico Institute of Mining Technology
RP Cappellari, M (corresponding author), Univ Oxford, Dept Phys, Subdept Astrophys, Denys Wilkinson Bldg,Keble Rd, Oxford OX1 3RH, England.
EM cappellari@astro.ox.ac.uk
FU Royal Society; UK Research Councils; Christ Church College, Oxford University; Gemini Observatory; DFG Cluster of Excellence 'Origin and Structure of the Universe'; STFC; Science and Technology Facilities Council [ST/I003673/1, PP/E003427/1, ST/G004331/1, ST/F009186/1, ST/H002456/1] Funding Source: researchfish; STFC [ST/F009186/1, ST/H002456/1, ST/I003673/1, PP/E003427/1, ST/G004331/1] Funding Source: UKRI
NR 30
TC 529
Z9 577
U1 0
U2 20
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD APR 26
PY 2012
VL 484
IS 7395
BP 485
EP 488
DI 10.1038/nature10972
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 931FF
UT WOS:000303200400044
PM 22538610
DA 2026-03-09
ER

PT J
AU Wu, D
   Hu, Q
   Yan, Z
   Chen, W
   Yan, CY
   Huang, X
   Zhang, J
   Yang, PY
   Deng, HT
   Wang, JW
   Deng, XW
   Shi, YG
AF Wu, Di
   Hu, Qi
   Yan, Zhen
   Chen, Wen
   Yan, Chuangye
   Huang, Xi
   Zhang, Jing
   Yang, Panyu
   Deng, Haiteng
   Wang, Jiawei
   Deng, XingWang
   Shi, Yigong
TI Structural basis of ultraviolet-B perception by UVR8
SO NATURE
LA English
DT Article
ID cation-pi interactions; plant photoreceptor domain; blue; cryptochrm; phytochrome; regulator; software; reveals
AB The Arabidopsis thaliana protein UVR8 is a photoreceptor for ultraviolet-B. Upon ultraviolet-B irradiation, UVR8 undergoes an immediate switch from homodimer to monomer, which triggers a signalling pathway for ultraviolet protection. The mechanism by which UVR8 senses ultraviolet-B remains largely unknown. Here we report the crystal structure of UVR8 at 1.8 angstrom resolution, revealing a symmetric homodimer of seven-bladed beta-propeller that is devoid of any external cofactor as the chromophore. Arginine residues that stabilize the homodimeric interface, principally Arg 286 and Arg 338, make elaborate intramolecular cation-pi interactions with surrounding tryptophan amino acids. Two of these tryptophans, Trp 285 and Trp 233, collectively serve as the ultraviolet-B chromophore. Our structural and biochemical analyses identify the molecular mechanism for UVR8-mediated ultraviolet-B perception, in which ultraviolet-B radiation results in destabilization of the intramolecular cation-pi interactions, causing disruption of the critical intermolecular hydrogen bonds mediated by Arg 286 and Arg 338 and subsequent dissociation of the UVR8 homodimer.
C1 [Wu, Di; Hu, Qi; Yan, Zhen; Zhang, Jing; Deng, Haiteng; Shi, Yigong] Tsinghua Univ, Tsinghua Peking Ctr Life Sci, Struct Biol Ctr, Sch Life Sci, Beijing 100084, Peoples R China.
   [Wu, Di; Hu, Qi; Yan, Zhen; Yan, Chuangye; Zhang, Jing; Deng, Haiteng; Wang, Jiawei; Shi, Yigong] Tsinghua Univ, Sch Med, Beijing 100084, Peoples R China.
   [Chen, Wen; Huang, Xi; Yang, Panyu; Deng, XingWang] Peking Univ, Coll Life Sci, Beijing 100871, Peoples R China.
   [Yan, Chuangye; Wang, Jiawei] Tsinghua Univ, State Key Lab Biomembrane & Membrane Biotechnol, Struct Biol Ctr, Sch Life Sci, Beijing 100084, Peoples R China.
   [Huang, Xi; Yang, Panyu; Deng, XingWang] Peking Univ, Peking Yale Joint Ctr Plant Mol Genet & Agrobiote, State Key Lab Prot & Plant Gene Res, Beijing 100871, Peoples R China.
C3 Tsinghua University; Tsinghua University; Peking University; Tsinghua University; Peking University
RP Shi, YG (corresponding author), Tsinghua Univ, Tsinghua Peking Ctr Life Sci, Struct Biol Ctr, Sch Life Sci, Beijing 100084, Peoples R China.
EM shi-lab@tsinghua.edu.cn
FU Ministry of Science and Technology [2009CB918801, 2012CB910900]; National Natural Science Foundation; Beijing Municipal Commission of Education; Beijing Municipal Commission of Science; Beijing Municipal Commission of Technology
NR 40
TC 426
Z9 571
U1 9
U2 292
PU NATURE PUBLISHING 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 12
PY 2012
VL 484
IS 7393
BP 214
EP U96
DI 10.1038/nature10931
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 930OV
UT WOS:000303149900029
PM 22388820
DA 2026-03-09
ER

PT J
AU Watson, PJ
   Fairall, L
   Santos, GM
   Schwabe, JWR
AF Watson, Peter J.
   Fairall, Louise
   Santos, Guilherme M.
   Schwabe, John W. R.
TI Structure of HDAC3 bound to co-repressor and inositol tetraphosphate
SO NATURE
LA English
DT Article
ID nuclear receptor corepressor; histone deacetylase; n-cor; protein complexes; smrt; kinase; acetylation; alpha; 1,4,5-trisphosphate; transcription
AB Histone deacetylase enzymes (HDACs) are emerging cancer drug targets. They regulate gene expression by removing acetyl groups from lysine residues in histone tails, resulting in chromatin condensation. The enzymatic activity of most class I HDACs requires recruitment into multi-subunit co-repressor complexes, which are in turn recruited to chromatin by repressive transcription factors. Here we report the structure of a complex between an HDAC and a co-repressor, namely, human HDAC3 with the deacetylase activation domain (DAD) from the human SMRT co-repressor (also known as NCOR2). The structure reveals two remarkable features. First, the SMRT-DAD undergoes a large structural rearrangement on forming the complex. Second, there is an essential inositol tetraphosphate molecule-D-myo-inositol-(1,4,5,6)-tetrakisphosphate (Ins(1,4,5,6)P-4)-acting as an 'intermolecular glue' between the two proteins. Assembly of the complex is clearly dependent on the Ins(1,4,5,6)P-4, which may act as a regulator-potentially explaining why inositol phosphates and their kinases have been found to act as transcriptional regulators. This mechanism for the activation of HDAC3 appears to be conserved in class I HDACs from yeast to humans, and opens the way to novel therapeutic opportunities.
C1 [Watson, Peter J.; Fairall, Louise; Santos, Guilherme M.; Schwabe, John W. R.] Univ Leicester, Dept Biochem, Henry Wellcome Labs Struct Biol, Leicester LE1 9HN, Leics, England.
C3 University of Leicester
RP Schwabe, JWR (corresponding author), Univ Leicester, Dept Biochem, Henry Wellcome Labs Struct Biol, Leicester LE1 9HN, Leics, England.
EM john.schwabe@le.ac.uk
FU Wellcome Trust [WT085408]
NR 50
TC 424
Z9 499
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 JAN 19
PY 2012
VL 481
IS 7381
BP 335
EP U114
DI 10.1038/nature10728
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 877VK
UT WOS:000299210600036
PM 22230954
DA 2026-03-09
ER

PT J
AU Bell, JC
   Plank, JL
   Dombrowski, CC
   Kowalczykowski, SC
AF Bell, Jason C.
   Plank, Jody L.
   Dombrowski, Christopher C.
   Kowalczykowski, Stephen C.
TI Direct imaging of RecA nucleation and growth on single molecules of SSB-coated ssDNA
SO NATURE
LA English
DT Article
ID dna-binding-protein; stranded nucleic-acids; escherichia-coli; genetic-recombination; e. coli; filaments; exchange; mechanism; dynamics; kinetics
AB Escherichia coli RecA is the defining member of a ubiquitous class of DNA strand-exchange proteins that are essential for homologous recombination, a pathway that maintains genomic integrity by repairing broken DNA(1). To function, filaments of RecA must nucleate and grow on single-stranded DNA (ssDNA) in direct competition with ssDNA-binding protein (SSB), which rapidly binds and continuously sequesters ssDNA, kinetically blocking RecA assembly(2,3). This dynamic self-assembly on a DNA lattice, in competition with another protein, is unique for the RecA family compared to other filament-forming proteins such as actin and tubulin. The complexity of this process has hindered our understanding of RecA filament assembly because ensemble measurements cannot reliably distinguish between the nucleation and growth phases, despite extensive and diverse attempts(2-5). Previous single-molecule assays have measured the nucleation and growth of RecA-and its eukaryotic homologue RAD51-on naked double-stranded DNA and ssDNA(6-12); however, the template for RecA self-assembly in vivo is SSB-coated ssDNA(3). Using single-molecule microscopy, here we directly visualize RecA filament assembly on single molecules of SSB-coated ssDNA, simultaneously measuring nucleation and growth. We establish that a dimer of RecA is required for nucleation, followed by growth of the filament through monomer addition, consistent with the finding that nucleation, but not growth, is modulated by nucleotide and magnesium ion cofactors. Filament growth is bidirectional, albeit faster in the 5'-> 3' direction. Both nucleation and growth are repressed at physiological conditions, highlighting the essential role of recombination mediators in potentiating assembly in vivo. We define a two-step kinetic mechanism in which RecA nucleates on transiently exposed ssDNA during SSB sliding and/or partial dissociation (DNA unwrapping) and then the RecA filament grows. We further demonstrate that the recombination mediator protein pair, RecOR (RecO and RecR), accelerates both RecA nucleation and filament growth, and that the introduction of RecF further stimulates RecA nucleation.
C1 [Bell, Jason C.; Plank, Jody L.; Dombrowski, Christopher C.; Kowalczykowski, Stephen C.] Univ Calif Davis, Dept Microbiol, Davis, CA 95616 USA.
   [Bell, Jason C.; Plank, Jody L.; Dombrowski, Christopher C.; Kowalczykowski, Stephen C.] Univ Calif Davis, Dept Mol & Cellular Biol, Davis, CA 95616 USA.
   [Bell, Jason C.; Kowalczykowski, Stephen C.] Univ Calif Davis, Biochem & Mol Biol Grad Grp, Davis, CA 95616 USA.
C3 University of California System; University of California Davis; University of California System; University of California Davis; University of California System; University of California Davis
RP Kowalczykowski, SC (corresponding author), Univ Calif Davis, Dept Microbiol, Davis, CA 95616 USA.
EM sckowalczykowski@ucdavis.edu
FU National Institutes of Health (NIH) [T32 GM007377, CA10052159, CA136103, GM62653, GM64745]; National Institute of General Medical Sciences [T32GM007377] Funding Source: NIH RePORTER
NR 35
TC 136
Z9 167
U1 0
U2 118
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD NOV 8
PY 2012
VL 491
IS 7423
BP 274
EP U144
DI 10.1038/nature11598
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 033DP
UT WOS:000310774300048
PM 23103864
DA 2026-03-09
ER

PT J
AU Tayi, AS
   Shveyd, AK
   Sue, ACH
   Szarko, JM
   Rolczynski, BS
   Cao, D
   Kennedy, TJ
   Sarjeant, AA
   Stern, CL
   Paxton, WF
   Wu, W
   Dey, SK
   Fahrenbach, AC
   Guest, JR
   Mohseni, H
   Chen, LX
   Wang, KL
   Stoddart, JF
   Stupp, SI
AF Tayi, Alok S.
   Shveyd, Alexander K.
   Sue, Andrew C-H
   Szarko, Jodi M.
   Rolczynski, Brian S.
   Cao, Dennis
   Kennedy, T. Jackson
   Sarjeant, Amy A.
   Stern, Charlotte L.
   Paxton, Walter F.
   Wu, Wei
   Dey, Sanjeev K.
   Fahrenbach, Albert C.
   Guest, Jeffrey R.
   Mohseni, Hooman
   Chen, Lin X.
   Wang, Kang L.
   Stoddart, J. Fraser
   Stupp, Samuel I.
TI Room-temperature ferroelectricity in supramolecular networks of charge-transfer complexes
SO NATURE
LA English
DT Article
ID ionic phase-transition; tetrathiafulvalene-chloranil; molecular-crystal; stack
AB Materials exhibiting a spontaneous electrical polarization(1,2) that can be switched easily between antiparallel orientations are of potential value for sensors, photonics and energy-efficient memories. In this context, organic ferroelectrics(3,4) are of particular interest because they promise to be lightweight, inexpensive and easily processed into devices. A recently identified family of organic ferroelectric structures is based on intermolecular charge transfer, where donor and acceptor molecules co-crystallize in an alternating fashion known as a mixed stack(5-8): in the crystalline lattice, a collective transfer of electrons from donor to acceptor molecules results in the formation of dipoles that can be realigned by an external field as molecules switch partners in the mixed stack. Although mixed stacks have been investigated extensively, only three systems are known(9,10) to show ferroelectric switching, all below 71 kelvin. Here we describe supramolecular charge-transfer networks that undergo ferroelectric polarization switching with a ferroelectric Curie temperature above room temperature. These polar and switchable systems utilize a structural synergy between a hydrogen-bonded network and charge-transfer complexation of donor and acceptor molecules in a mixed stack. This supramolecular motif could help guide the development of other functional organic systems that can switch polarization under the influence of electric fields at ambient temperatures.
C1 [Shveyd, Alexander K.; Sue, Andrew C-H; Szarko, Jodi M.; Rolczynski, Brian S.; Cao, Dennis; Sarjeant, Amy A.; Stern, Charlotte L.; Paxton, Walter F.; Dey, Sanjeev K.; Fahrenbach, Albert C.; Chen, Lin X.; Stoddart, J. Fraser; Stupp, Samuel I.] Northwestern Univ, Dept Chem, Evanston, IL 60208 USA.
   [Tayi, Alok S.; Stupp, Samuel I.] Northwestern Univ, Dept Mat Sci & Engn, Evanston, IL 60208 USA.
   [Sue, Andrew C-H; Wang, Kang L.] Univ Calif Los Angeles, Dept Elect Engn, Los Angeles, CA 90095 USA.
   [Szarko, Jodi M.; Rolczynski, Brian S.; Chen, Lin X.] Northwestern Univ, ANSER Ctr, Evanston, IL 60208 USA.
   [Szarko, Jodi M.; Rolczynski, Brian S.; Chen, Lin X.] Argonne Natl Lab, Chem Sci & Engn Div, Argonne, IL 60439 USA.
   [Cao, Dennis; Fahrenbach, Albert C.; Stoddart, J. Fraser] Korea Adv Inst Sci & Technol, Grad Sch EEWS, Taejon 305701, South Korea.
   [Kennedy, T. Jackson] Northwestern Univ, Dept Phys, Evanston, IL 60208 USA.
   [Wu, Wei; Mohseni, Hooman] Northwestern Univ, Dept Elect Engn, Evanston, IL 60208 USA.
   [Guest, Jeffrey R.] Argonne Natl Lab, Ctr Nanoscale Mat, Argonne, IL 60439 USA.
   [Stupp, Samuel I.] Northwestern Univ, Dept Med, Chicago, IL 60611 USA.
   [Stupp, Samuel I.] Northwestern Univ, Inst BioNanotechnol Med, Chicago, IL 60611 USA.
C3 Northwestern University; Northwestern University; University of California System; University of California Los Angeles; Northwestern University; United States Department of Energy (DOE); Argonne National Laboratory; Korea Advanced Institute of Science & Technology (KAIST); Northwestern University; Northwestern University; United States Department of Energy (DOE); Argonne National Laboratory; Northwestern University; Northwestern University
RP Stoddart, JF (corresponding author), Northwestern Univ, Dept Chem, 2145 Sheridan Rd, Evanston, IL 60208 USA.
EM stoddart@northwestern.edu; s-stupp@northwestern.edu
FU Non-equilibrium Energy Research Center (NERC) at Northwestern University; US Department of Energy (DOE), Office of Basic Energy Sciences [DE-SC0000989]; Materials Research Science and Engineering Centre (MRSEC) at Northwestern University; National Science Foundation (NSF); WCU program at KAIST in Korea [R-31-2008-000-10055-0]; US Department of Energy, Office of Science, Office of Basic Energy Sciences [DE-AC02-06CH11357]; NERC; Initiative for Sustainability and Energy at Northwestern (ISEN)
NR 24
TC 456
Z9 505
U1 7
U2 628
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD AUG 23
PY 2012
VL 488
IS 7412
BP 485
EP 489
DI 10.1038/nature11395
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 992FS
UT WOS:000307761600031
PM 22914165
DA 2026-03-09
ER

PT J
AU Astafiev, OV
   Ioffe, LB
   Kafanov, S
   Pashkin, YA
   Arutyunov, KY
   Shahar, D
   Cohen, O
   Tsai, JS
AF Astafiev, O. V.
   Ioffe, L. B.
   Kafanov, S.
   Pashkin, Yu. A.
   Arutyunov, K. Yu.
   Shahar, D.
   Cohen, O.
   Tsai, J. S.
TI Coherent quantum phase slip
SO NATURE
LA English
DT Article
ID superconductivity; suppression; nanowires
AB A hundred years after the discovery of superconductivity, one fundamental prediction of the theory, coherent quantum phase slip (CQPS), has not been observed. CQPS is a phenomenon exactly dual(1) to the Josephson effect; whereas the latter is a coherent transfer of charges between superconducting leads(2,3), the former is a coherent transfer of vortices or fluxes across a superconducting wire. In contrast to previously reported observations(4-8) of incoherent phase slip, CQPS has been only a subject of theoretical study(9-12). Its experimental demonstration is made difficult by quasiparticle dissipation due to gapless excitations in nanowires or in vortex cores. This difficulty might be overcome by using certain strongly disordered superconductors near the superconductor-insulator transition. Here we report direct observation of CQPS in a narrow segment of a superconducting loop made of strongly disordered indium oxide; the effect is made manifest through the superposition of quantum states with different numbers of flux quanta(13). As with the Josephson effect, our observation should lead to new applications in superconducting electronics and quantum metrology(1,10,11).
C1 [Astafiev, O. V.; Kafanov, S.; Pashkin, Yu. A.; Tsai, J. S.] NEC Green Innovat Res Labs, Tsukuba, Ibaraki 3058501, Japan.
   [Astafiev, O. V.; Kafanov, S.; Pashkin, Yu. A.; Tsai, J. S.] Inst Phys & Chem Res RIKEN, Tsukuba, Ibaraki 3058501, Japan.
   [Ioffe, L. B.] Rutgers State Univ, Dept Phys & Astron, Ctr Mat Theory, Piscataway, NJ 08854 USA.
   [Pashkin, Yu. A.] Univ Lancaster, Dept Phys, Lancaster LA1 4YB, England.
   [Arutyunov, K. Yu.] Univ Jyvaskyla, Dept Phys, Jyvaskyla 40014, Finland.
   [Arutyunov, K. Yu.] Moscow MV Lomonosov State Univ, Inst Nucl Phys, Moscow 119899, Russia.
   [Shahar, D.; Cohen, O.] Weizmann Inst Sci, Dept Condensed Matter Phys, IL-76100 Rehovot, Israel.
C3 RIKEN; Rutgers University System; Rutgers University New Brunswick; Lancaster University; University of Jyvaskyla; National Research Centre - Kurchatov Institute; Institute of High Energy Physics - IHEP; Lomonosov Moscow State University; Weizmann Institute of Science
RP Astafiev, OV (corresponding author), NEC Green Innovat Res Labs, 34 Miyukigaoka, Tsukuba, Ibaraki 3058501, Japan.
EM astf@zb.jp.nec.com
FU MEXT KAKENHI; Ministry of Science and Education of Russian Federation [2010-1.5-508-005-037]; ARO [W911NF-09-1-0395]; DARPA [HR0011-09-1- 0009]; NIRT [ECS-0608842]; Minerva Fund; Grants-in-Aid for Scientific Research [21102002] Funding Source: KAKEN
NR 30
TC 236
Z9 266
U1 1
U2 159
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD APR 19
PY 2012
VL 484
IS 7394
BP 355
EP 358
DI 10.1038/nature10930
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 927YM
UT WOS:000302946500028
PM 22517162
DA 2026-03-09
ER

PT J
AU Seifert, AW
   Kiama, SG
   Seifert, MG
   Goheen, JR
   Palmer, TM
   Maden, M
AF Seifert, Ashley W.
   Kiama, Stephen G.
   Seifert, Megan G.
   Goheen, Jacob R.
   Palmer, Todd M.
   Maden, Malcolm
TI Skin shedding and tissue regeneration in African spiny mice (Acomys)
SO NATURE
LA English
DT Article
ID hair follicle development; limb regeneration; wound repair; differentiation; expression; autotomy; newt
AB Evolutionary modification has produced a spectrum of animal defence traits to escape predation, including the ability to autotomize body parts to elude capture(1,2). After autotomy, the missing part is either replaced through regeneration (for example, in urodeles, lizards, arthropods and crustaceans) or permanently lost (such as in mammals). Although most autotomy involves the loss of appendages (legs, chelipeds, antennae or tails, for example), skin autotomy can occur in certain taxa of scincid and gekkonid lizards(3). Here we report the first demonstration of skin autotomy in Mammalia (African spiny mice, Acomys). Mechanical testing showed a propensity for skin to tear under very low tension and the absence of a fracture plane. After skin loss, rapid wound contraction was followed by hair follicle regeneration in dorsal skin wounds. Notably, we found that regenerative capacity in Acomys was extended to ear holes, where the mice exhibited complete regeneration of hair follicles, sebaceous glands, dermis and cartilage. Salamanders capable of limb regeneration form a blastema (a mass of lineage-restricted progenitor cells(4)) after limb loss, and our findings suggest that ear tissue regeneration in Acomys may proceed through the assembly of a similar structure. This study underscores the importance of investigating regenerative phenomena outside of conventional model organisms, and suggests that mammals may retain a higher capacity for regeneration than was previously believed. As re-emergent interest in regenerative medicine seeks to isolate molecular pathways controlling tissue regeneration in mammals, Acomys may prove useful in identifying mechanisms to promote regeneration in lieu of fibrosis and scarring.
C1 [Seifert, Ashley W.; Seifert, Megan G.; Palmer, Todd M.; Maden, Malcolm] Univ Florida, Dept Biol, Gainesville, FL 32610 USA.
   [Seifert, Ashley W.; Kiama, Stephen G.] Univ Nairobi, Dept Vet Anat & Physiol, Nairobi 00010, Kenya.
   [Seifert, Ashley W.; Seifert, Megan G.; Goheen, Jacob R.; Palmer, Todd M.] Mpala Res Ctr, Nanyuki 10400, Kenya.
   [Goheen, Jacob R.] Univ Wyoming, Dept Zool & Physiol, Laramie, WY 82071 USA.
   [Goheen, Jacob R.] Univ Wyoming, Dept Bot, Laramie, WY 82071 USA.
C3 State University System of Florida; University of Florida; University of Nairobi; University of Wyoming; University of Wyoming
RP Seifert, AW (corresponding author), Univ Florida, Dept Biol, 223 Bartram Hall,POB 118525, Gainesville, FL 32610 USA.
EM seifert@ufl.edu
FU National Institute of Diabetes and Digestive and Kidney Diseases [T32DK074367] Funding Source: NIH RePORTER; NIDDK NIH HHS [T32 DK074367] Funding Source: Medline
NR 31
TC 442
Z9 515
U1 1
U2 368
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD SEP 27
PY 2012
VL 489
IS 7417
BP 561
EP +
DI 10.1038/nature11499
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 046RG
UT WOS:000311781500003
PM 23018966
DA 2026-03-09
ER

PT J
AU Lafaille, FG
   Pessach, IM
   Zhang, SY
   Ciancanelli, MJ
   Herman, M
   Abhyankar, A
   Ying, SW
   Keros, S
   Goldstein, PA
   Mostoslavsky, G
   Ordovas-Montanes, J
   Jouanguy, E
   Plancoulaine, S
   Tu, E
   Elkabetz, Y
   Al-Muhsen, S
   Tardieu, M
   Schlaeger, TM
   Daley, GQ
   Abel, L
   Casanova, JL
   Studer, L
   Notarangelo, LD
AF Lafaille, Fabien G.
   Pessach, Itai M.
   Zhang, Shen-Ying
   Ciancanelli, Michael J.
   Herman, Melina
   Abhyankar, Avinash
   Ying, Shui-Wang
   Keros, Sotirios
   Goldstein, Peter A.
   Mostoslavsky, Gustavo
   Ordovas-Montanes, Jose
   Jouanguy, Emmanuelle
   Plancoulaine, Sabine
   Tu, Edmund
   Elkabetz, Yechiel
   Al-Muhsen, Saleh
   Tardieu, Marc
   Schlaeger, Thorsten M.
   Daley, George Q.
   Abel, Laurent
   Casanova, Jean-Laurent
   Studer, Lorenz
   Notarangelo, Luigi D.
TI Impaired intrinsic immunity to HSV-1 in human iPSC-derived TLR3-deficient CNS cells
SO NATURE
LA English
DT Article
ID herpes-simplex encephalitis; embryonic stem-cells; toll-like receptor-3; reticular thalamic neurons; central-nervous-system; double-stranded-rna; tlr3 deficiency; human es; protective immunity; virus encephalitis
AB In the course of primary infection with herpes simplex virus 1 (HSV-1), children with inborn errors of toll-like receptor 3 (TLR3) immunity are prone to HSV-1 encephalitis (HSE)(1-3). We tested the hypothesis that the pathogenesis of HSE involves non-haematopoietic CNS-resident cells. We derived induced pluripotent stem cells (iPSCs) from the dermal fibroblasts of TLR3- and UNC-93B-deficient patients and from controls. These iPSCs were differentiated into highly purified populations of neural stem cells (NSCs), neurons, astrocytes and oligodendrocytes. The induction of interferon-beta (IFN-beta) and/or IFN-lambda 1 in response to stimulation by the dsRNA analogue polyinosinic: polycytidylic acid (poly(I:C)) was dependent on TLR3 and UNC-93B in all cells tested. However, the induction of IFN-beta and IFN-lambda 1 in response to HSV-1 infection was impaired selectively in UNC-93B-deficient neurons and oligodendrocytes. These cells were also much more susceptible to HSV-1 infection than control cells, whereas UNC-93B-deficient NSCs and astrocytes were not. TLR3-deficient neurons were also found to be susceptible to HSV-1 infection. The rescue of UNC-93B- and TLR3-deficient cells with the corresponding wild-type allele showed that the genetic defect was the cause of the poly(I:C) and HSV-1 phenotypes. The viral infection phenotype was rescued further by treatment with exogenous IFN-alpha or IFN-beta (IFN-alpha/beta) but not IFN-lambda 1. Thus, impaired TLR3- and UNC-93B-dependent IFN-alpha/beta intrinsic immunity to HSV-1 in the CNS, in neurons and oligodendrocytes in particular, may underlie the pathogenesis of HSE in children with TLR3-pathway deficiencies.
C1 [Zhang, Shen-Ying; Ciancanelli, Michael J.; Herman, Melina; Abhyankar, Avinash; Abel, Laurent; Casanova, Jean-Laurent] Rockefeller Univ, St Giles Lab Human Genet Infect Dis, New York, NY 10065 USA.
   [Lafaille, Fabien G.; Studer, Lorenz] Sloan Kettering Inst Canc Res, Ctr Stem Cell Biol, New York, NY 10065 USA.
   [Lafaille, Fabien G.; Studer, Lorenz] Sloan Kettering Inst Canc Res, Dev Biol Program, New York, NY 10065 USA.
   [Pessach, Itai M.; Ordovas-Montanes, Jose; Notarangelo, Luigi D.] Harvard Univ, Childrens Hosp, Div Immunol, Sch Med, Boston, MA 02115 USA.
   [Pessach, Itai M.] Chaim Sheba Med Ctr, Talpiot Med Leadership Program, Edmond & Lily Safra Childrens Hosp, IL-52621 Tel Hashomer, Israel.
   [Pessach, Itai M.] Tel Aviv Univ, Sackler Fac Med, IL-52621 Tel Aviv, Israel.
   [Zhang, Shen-Ying; Herman, Melina; Jouanguy, Emmanuelle; Abel, Laurent; Casanova, Jean-Laurent] Univ Paris 05, Lab Human Genet Infect Dis, Inst Natl Sante & Rech Med, Necker Med Sch,U980, F-75015 Paris, France.
   [Ying, Shui-Wang; Goldstein, Peter A.] Weill Cornell Med Coll, CV Starr Lab Mol Neuropharmacol, Dept Anesthesiol, New York, NY 10065 USA.
   [Keros, Sotirios] Weill Cornell Med Coll, Div Pediat Neurol, Dept Pediat, New York, NY 10065 USA.
   [Mostoslavsky, Gustavo] Boston Univ, Sch Med, Sect Gastroenterol, Dept Med, Boston, MA 02118 USA.
   [Elkabetz, Yechiel] Tel Aviv Univ, Lab Pluripotent & Neural Stem Cell Biol, Dept Cell & Dev Biol, Sackler Sch Med, IL-69978 Tel Aviv, Israel.
   [Al-Muhsen, Saleh] King Saud Univ, Prince Naif Ctr Immunol Res, Dept Pediat, Coll Med, Riyadh 11451, Saudi Arabia.
   [Tardieu, Marc] Hop Bicetre, Assistance Publ Hop Paris, Dept Pediat Neurol, F-94275 Le Kremlin Bicetre, France.
   [Schlaeger, Thorsten M.; Daley, George Q.] Childrens Hosp, Div Pediat Hematol Oncol, Boston, MA 02115 USA.
   [Schlaeger, Thorsten M.; Daley, George Q.] Dana Farber Canc Inst, Boston, MA 02115 USA.
   [Casanova, Jean-Laurent] Hop Necker Enfants Malad, Pediat Hematol Immunol Unit, F-75015 Paris, France.
   [Notarangelo, Luigi D.] Childrens Hosp, Manton Ctr Orphan Dis Res, Boston, MA 02115 USA.
C3 Rockefeller University; Memorial Sloan Kettering Cancer Center; Memorial Sloan Kettering Cancer Center; Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Boston Children's Hospital; Tel Aviv University; Chaim Sheba Medical Center; Tel Aviv University; Sackler Faculty of Medicine; Institut National de la Sante et de la Recherche Medicale (Inserm); Universite Paris Cite; Cornell University; Weill Cornell Medicine; Cornell University; Weill Cornell Medicine; Boston University; Tel Aviv University; Sackler Faculty of Medicine; King Saud University; Assistance Publique Hopitaux Paris (APHP); Universite Paris Cite; Hopital Universitaire Saint-Louis - APHP; Universite Paris Saclay; Hopital Universitaire Antoine-Beclere - APHP; Hopital Universitaire Bicetre - APHP; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Assistance Publique Hopitaux Paris (APHP); Universite Paris Cite; Hopital Universitaire Necker-Enfants Malades - APHP; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital
RP Zhang, SY (corresponding author), Rockefeller Univ, St Giles Lab Human Genet Infect Dis, New York, NY 10065 USA.
EM shzh289@rockefeller.edu; jean-laurent.casanova@rockefeller.edu
FU National Center for Translational Sciences (NCATS) [8UL1TR000043]; National Institutes of Health (NIH); Rockefeller University; St. Giles Foundation; ANR; INSERM; Paris Descartes University; March of Dimes; NIH [5R01NS072381-02, 1R03AI0883502-01, 1R01NS066390]; Manton Foundation; Israeli Centers of Research Excellence (I-CORE); Gene Regulation in Complex Human Disease [41/11]; New York Stem Cell Foundation
NR 42
TC 274
Z9 307
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 NOV 29
PY 2012
VL 491
IS 7426
BP 769
EP +
DI 10.1038/nature11583
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 044FY
UT WOS:000311606000048
PM 23103873
DA 2026-03-09
ER

PT J
AU Moon, TS
   Lou, CB
   Tamsir, A
   Stanton, BC
   Voigt, CA
AF Moon, Tae Seok
   Lou, Chunbo
   Tamsir, Alvin
   Stanton, Brynne C.
   Voigt, Christopher A.
TI Genetic programs constructed from layered logic gates in single cells
SO NATURE
LA English
DT Article
ID iii secretion system; synthetic biology; activation
AB Genetic programs function to integrate environmental sensors, implement signal processing algorithms and control expression dynamics(1). These programs consist of integrated genetic circuits that individually implement operations ranging from digital logic to dynamic circuits(2-6), and they have been used in various cellular engineering applications, including the implementation of process control in metabolic networks and the coordination of spatial differentiation in artificial tissues. A key limitation is that the circuits are based on biochemical interactions occurring in the confined volume of the cell, so the size of programs has been limited to a few circuits(1,7). Here we apply part mining and directed evolution to build a set of transcriptional AND gates in Escherichia coli. Each AND gate integrates two promoter inputs and controls one promoter output. This allows the gates to be layered by having the output promoter of an upstream circuit serve as the input promoter for a downstream circuit. Each gate consists of a transcription factor that requires a second chaperone protein to activate the output promoter. Multiple activator-chaperone pairs are identified from type III secretion pathways in different strains of bacteria. Directed evolution is applied to increase the dynamic range and orthogonality of the circuits. These gates are connected in different permutations to form programs, the largest of which is a 4-input AND gate that consists of 3 circuits that integrate 4 inducible systems, thus requiring 11 regulatory proteins. Measuring the performance of individual gates is sufficient to capture the behaviour of the complete program. Errors in the output due to delays (faults), a common problem for layered circuits, are not observed. This work demonstrates the successful layering of orthogonal logic gates, a design strategy that could enable the construction of large, integrated circuits in single cells.
C1 [Moon, Tae Seok; Lou, Chunbo; Stanton, Brynne C.; Voigt, Christopher A.] MIT, Dept Biol Engn, Synthet Biol Ctr, Cambridge, MA 02139 USA.
   [Tamsir, Alvin] Univ Calif San Francisco, Tetrad Grad Program, San Francisco, CA 94158 USA.
C3 Massachusetts Institute of Technology (MIT); University of California System; University of California San Francisco
RP Voigt, CA (corresponding author), MIT, Dept Biol Engn, Synthet Biol Ctr, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
EM cavoigt@gmail.com
FU Life Technologies; Defense Advanced Research Projects Agency Chronicle of Lineage Indicative of Origins (DARPA) [CLIO N66001-12-C-4018]; Office of Naval Research [N00014-10-1-0245]; National Science Foundation (NSF) [CCF-0943385]; National Institutes of Health [AI067699]; NSF Synthetic Biology Engineering Research Center (SynBERC) [SA5284-11210]; Direct For Computer & Info Scie & Enginr [0943385] Funding Source: National Science Foundation; Direct For Computer & Info Scie & Enginr; Division of Computing and Communication Foundations [0943269] Funding Source: National Science Foundation; Directorate For Engineering; Div Of Chem, Bioeng, Env, & Transp Sys [1224898] Funding Source: National Science Foundation; Division of Computing and Communication Foundations [0943385] Funding Source: National Science Foundation
NR 28
TC 447
Z9 618
U1 3
U2 341
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 8
PY 2012
VL 491
IS 7423
BP 249
EP 253
DI 10.1038/nature11516
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 033DP
UT WOS:000310774300043
PM 23041931
DA 2026-03-09
ER

PT J
AU Hino, T
   Arakawa, T
   Iwanari, H
   Yurugi-Kobayashi, T
   Ikeda-Suno, C
   Nakada-Nakura, Y
   Kusano-Arai, O
   Weyand, S
   Shimamura, T
   Nomura, N
   Cameron, AD
   Kobayashi, T
   Hamakubo, T
   Iwata, S
   Murata, T
AF Hino, Tomoya
   Arakawa, Takatoshi
   Iwanari, Hiroko
   Yurugi-Kobayashi, Takami
   Ikeda-Suno, Chiyo
   Nakada-Nakura, Yoshiko
   Kusano-Arai, Osamu
   Weyand, Simone
   Shimamura, Tatsuro
   Nomura, Norimichi
   Cameron, Alexander D.
   Kobayashi, Takuya
   Hamakubo, Takao
   Iwata, So
   Murata, Takeshi
TI G-protein-coupled receptor inactivation by an allosteric inverse-agonist antibody
SO NATURE
LA English
DT Article
ID adenosine a(2a) receptor; crystal-structure; complex; gpcr; validation; expression; rhodopsin; models
AB G-protein-coupled receptors are the largest class of cell-surface receptors, and these membrane proteins exist in equilibrium between inactive and active states(1-13). Conformational changes induced by extracellular ligands binding to G-protein-coupled receptors result in a cellular response through the activation of G proteins. The A(2A) adenosine receptor (A(2A)AR) is responsible for regulating blood flow to the cardiac muscle and is important in the regulation of glutamate and dopamine release in the brain(14). Here we report the raising of a mouse monoclonal antibody against human A(2A)AR that prevents agonist but not antagonist binding to the extracellular ligand-binding pocket, and describe the structure of A(2A)AR in complex with the antibody Fab fragment (Fab2838). This structure reveals that Fab2838 recognizes the intracellular surface of A(2A)AR and that its complementarity-determining region, CDR-H3, penetrates into the receptor. CDR-H3 is located in a similar position to the G-protein carboxy-terminal fragment in the active opsin structure(1) and to CDR-3 of the nanobody in the active beta(2)-adrenergic receptor structure(2), but locks A(2A)AR in an inactive conformation. These results suggest a new strategy to modulate the activity of G-protein-coupled receptors.
C1 [Hino, Tomoya; Arakawa, Takatoshi; Yurugi-Kobayashi, Takami; Ikeda-Suno, Chiyo; Weyand, Simone; Shimamura, Tatsuro; Nomura, Norimichi; Cameron, Alexander D.; Kobayashi, Takuya; Iwata, So; Murata, Takeshi] Japan Sci & Technol Agcy, Iwata Human Receptor Crystallog Project, ERATO, Sakyo Ku, Kyoto 6068501, Japan.
   [Hino, Tomoya; Arakawa, Takatoshi; Yurugi-Kobayashi, Takami; Ikeda-Suno, Chiyo; Shimamura, Tatsuro; Nomura, Norimichi; Kobayashi, Takuya; Iwata, So; Murata, Takeshi] Kyoto Univ, Dept Cell Biol, Grad Sch Med, Sakyo Ku, Kyoto 6068501, Japan.
   [Iwanari, Hiroko; Nakada-Nakura, Yoshiko; Kusano-Arai, Osamu; Hamakubo, Takao] Univ Tokyo, Dept Mol Biol & Med, Res Ctr Adv Sci & Technol, Meguro Ku, Tokyo 1538904, Japan.
   [Nakada-Nakura, Yoshiko] Perseus Proteom Inc, Meguro Ku, Tokyo 1530041, Japan.
   [Kusano-Arai, Osamu] Inst Immunol Co Ltd, Bunkyo Ku, Tokyo 1120004, Japan.
   [Weyand, Simone; Cameron, Alexander D.; Iwata, So] Univ London Imperial Coll Sci Technol & Med, Div Mol Biosci, Membrane Prot Crystallog Grp, London SW7 2AZ, England.
   [Weyand, Simone; Cameron, Alexander D.; Iwata, So] Diamond Light Source, Membrane Prot Lab, Didcot OX11 0DE, Oxon, England.
   [Weyand, Simone; Cameron, Alexander D.; Iwata, So] Rutherford Appleton Lab, Didcot OX11 0FA, Oxon, England.
   [Kobayashi, Takuya] Kyoto Univ, Fac Med, Japan Sci & Technol Agcy, Kyoto 6068501, Japan.
   [Iwata, So; Murata, Takeshi] RIKEN, Syst & Struct Biol Ctr, Tsurumi Ku, Yokohama, Kanagawa 2300045, Japan.
   [Murata, Takeshi] Chiba Univ, Grad Sch Sci, Dept Chem, Chiba 2638522, Japan.
C3 Japan Science & Technology Agency (JST); Kyoto University; University of Tokyo; Imperial College London; UK Research & Innovation (UKRI); Science & Technology Facilities Council (STFC); STFC Rutherford Appleton Laboratory; Diamond Light Source; UK Research & Innovation (UKRI); Science & Technology Facilities Council (STFC); STFC Rutherford Appleton Laboratory; Kyoto University; Japan Science & Technology Agency (JST); RIKEN; Chiba University
RP Iwata, S (corresponding author), Japan Sci & Technol Agcy, Iwata Human Receptor Crystallog Project, ERATO, Sakyo Ku, Yoshidakonoe Cho, Kyoto 6068501, Japan.
EM so_iwata@mac.com; t.murata@faculty.chiba-u.jp
FU Japan Science and Technology Agency; MEXT, Japan; Development of New Functional Antibody Technologies (New Energy and Industrial Technology Development Organization, Japan); Biotechnology and Biological Sciences Research Council [BB/G023425/1]; Wellcome Trust at the Diamond Light Source, UK [062164/Z/00/Z]; Biotechnology and Biological Sciences Research Council [BB/G023425/1] Funding Source: researchfish; Grants-in-Aid for Scientific Research [22570114, 11J40150, 20221010, 22659059, 23370049] Funding Source: KAKEN; BBSRC [BB/G023425/1] Funding Source: UKRI
NR 35
TC 248
Z9 296
U1 0
U2 90
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 9
PY 2012
VL 482
IS 7384
BP 237
EP U130
DI 10.1038/nature10750
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 888HI
UT WOS:000299994100042
PM 22286059
DA 2026-03-09
ER

PT J
AU Freitag, J
   Ast, J
   Bölker, M
AF Freitag, Johannes
   Ast, Julia
   Boelker, Michael
TI Cryptic peroxisomal targeting via alternative splicing and stop codon read-through in fungi
SO NATURE
LA English
DT Article
ID saccharomyces-cerevisiae; proteins; yeast; identification; dehydrogenase; coordination; microbody; transport; membrane; signal-1
AB Peroxisomes are eukaryotic organelles important for the metabolism of long-chain fatty acids(1,2). Here we show that in numerous fungal species, several core enzymes of glycolysis, including glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and 3-phosphoglycerate kinase (PGK), reside in both the cytoplasm and peroxisomes. We detected in these enzymes cryptic type 1 peroxisomal targeting signals (PTS1)(3), which are activated by post-transcriptional processes. Notably, the molecular mechanisms that generate the peroxisomal isoforms vary considerably among different species. In the basidiomycete plant pathogen Ustilago maydis, peroxisomal targeting of Pgk1 results from ribosomal read-through, whereas alternative splicing generates the PTS1 of Gapdh. In the filamentous ascomycete Aspergillus nidulans, peroxisomal targeting of these enzymes is achieved by exactly the opposite mechanisms. We also detected PTS1 motifs in the glycolytic enzymes triose-phosphate isomerase and fructose-bisphosphate aldolase. U. maydis mutants lacking the peroxisomal isoforms of Gapdh or Pgk1 showed reduced virulence. In addition, mutational analysis suggests that GAPDH, together with other peroxisomal NADH-dependent dehydrogenases, has a role in redox homeostasis. Owing to its hidden nature, partial peroxisomal targeting of well-studied cytoplasmic enzymes has remained undetected. Thus, we anticipate that further bona fide cytoplasmic proteins exhibit similar dual targeting.
C1 [Freitag, Johannes; Ast, Julia; Boelker, Michael] Univ Marburg, Dept Biol, D-35032 Marburg, Germany.
C3 Philipps University Marburg
RP Bölker, M (corresponding author), Univ Marburg, Dept Biol, Karl von Frisch Str 8, D-35032 Marburg, Germany.
EM boelker@uni-marburg.de
FU Deutsche Forschungsgemeinschaft [DFG-GK1216]; Marburg University Research Academy (MARA)
NR 40
TC 137
Z9 161
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 MAY 24
PY 2012
VL 485
IS 7399
BP 522
EP U135
DI 10.1038/nature11051
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 946IH
UT WOS:000304344500047
PM 22622582
DA 2026-03-09
ER

PT J
AU Hakim, O
   Resch, W
   Yamane, A
   Klein, I
   Kieffer-Kwon, KR
   Jankovic, M
   Oliveira, T
   Bothmer, A
   Voss, TC
   Ansarah-Sobrinho, C
   Mathe, E
   Liang, GQ
   Cobell, J
   Nakahashi, H
   Robbiani, DF
   Nussenzweig, A
   Hager, GL
   Nussenzweig, MC
   Casellas, R
AF Hakim, Ofir
   Resch, Wolfgang
   Yamane, Arito
   Klein, Isaac
   Kieffer-Kwon, Kyong-Rim
   Jankovic, Mila
   Oliveira, Thiago
   Bothmer, Anne
   Voss, Ty C.
   Ansarah-Sobrinho, Camilo
   Mathe, Ewy
   Liang, Genqing
   Cobell, Jesse
   Nakahashi, Hirotaka
   Robbiani, Davide F.
   Nussenzweig, Andre
   Hager, Gordon L.
   Nussenzweig, Michel C.
   Casellas, Rafael
TI DNA damage defines sites of recurrent chromosomal translocations in B lymphocytes
SO NATURE
LA English
DT Article
ID class-switch recombination; sequencing reveals; human genome; breaks; cells; aid; identification; rearrangements; organization; mechanisms
AB Recurrent chromosomal translocations underlie both haematopoietic and solid tumours. Their origin has been ascribed to selection of random rearrangements, targeted DNA damage, or frequent nuclear interactions between translocation partners; however, the relative contribution of each of these elements has not been measured directly or on a large scale. Here we examine the role of nuclear architecture and frequency of DNA damage in the genesis of chromosomal translocations by measuring these parameters simultaneously in cultured mouse B lymphocytes. In the absence of recurrent DNA damage, translocations between Igh or Myc and all other genes are directly related to their contact frequency. Conversely, translocations associated with recurrent site-directed DNA damage are proportional to the rate of DNA break formation, as measured by replication protein A accumulation at the site of damage. Thus, non-targeted rearrangements reflect nuclear organization whereas DNA break formation governs the location and frequency of recurrent translocations, including those driving B-cell malignancies.
C1 [Klein, Isaac; Jankovic, Mila; Oliveira, Thiago; Bothmer, Anne; Robbiani, Davide F.; Nussenzweig, Michel C.] Rockefeller Univ, Lab Mol Immunol, New York, NY 10065 USA.
   [Hakim, Ofir; Voss, Ty C.; Hager, Gordon L.] NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA.
   [Resch, Wolfgang; Yamane, Arito; Kieffer-Kwon, Kyong-Rim; Ansarah-Sobrinho, Camilo; Liang, Genqing; Cobell, Jesse; Nakahashi, Hirotaka; Casellas, Rafael] NCI, NIAMS, NIH, Bethesda, MD 20892 USA.
   [Oliveira, Thiago] Univ Sao Paulo, Med Sch Ribeirao Preto, Dept Genet, Natl Inst Sci & Technol Stem Cells & Cell Therapy, BR-14051140 Ribeirao Preto, SP, Brazil.
   [Oliveira, Thiago] Ctr Cell Based Therapy, BR-14051140 Ribeirao Preto, SP, Brazil.
   [Nussenzweig, Andre] NCI, Lab Genome Integr, NIH, Bethesda, MD 20892 USA.
   [Nussenzweig, Michel C.] Rockefeller Univ, Howard Hughes Med Inst, New York, NY 10065 USA.
   [Casellas, Rafael] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
C3 Rockefeller University; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); NIH National Institute of Arthritis & Musculoskeletal & Skin Diseases (NIAMS); Universidade de Sao Paulo; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); Howard Hughes Medical Institute; Rockefeller University; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI)
RP Nussenzweig, MC (corresponding author), Rockefeller Univ, Lab Mol Immunol, New York, NY 10065 USA.
EM nussen@rockefeller.edu; casellar@mail.nih.gov
FU Starr Foundation; NIH [AI037526]; NIAMS; NCI, NIH; National Cancer Institute [ZIABC010959, ZIABC010283, ZIABC010027] Funding Source: NIH RePORTER; National Institute of Allergy and Infectious Diseases [R37AI037526] Funding Source: NIH RePORTER; National Institute of Arthritis and Musculoskeletal and Skin Diseases [ZIAAR041148] Funding Source: NIH RePORTER
NR 28
TC 169
Z9 197
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 APR 5
PY 2012
VL 484
IS 7392
BP 69
EP +
DI 10.1038/nature10909
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 919QN
UT WOS:000302343400035
PM 22314321
DA 2026-03-09
ER

PT J
AU Ferraro, FR
   Lanzoni, B
   Dalessandro, E
   Beccari, G
   Pasquato, M
   Miocchi, P
   Rood, RT
   Sigurdsson, S
   Sills, A
   Vesperini, E
   Mapelli, M
   Contreras, R
   Sanna, N
   Mucciarelli, A
AF Ferraro, F. R.
   Lanzoni, B.
   Dalessandro, E.
   Beccari, G.
   Pasquato, M.
   Miocchi, P.
   Rood, R. T.
   Sigurdsson, S.
   Sills, A.
   Vesperini, E.
   Mapelli, M.
   Contreras, R.
   Sanna, N.
   Mucciarelli, A.
TI Dynamical age differences among coeval star clusters as revealed by blue stragglers
SO NATURE
LA English
DT Article
ID galactic globular-clusters; stellar collisions; omega-centauri; main-sequence; 47 tucanae; population; mass; core; simulations; parameters
AB Globular star clusters that formed at the same cosmic time may have evolved rather differently from the dynamical point of view(because that evolution depends on the internal environment) through a variety of processes that tend progressively to segregate stars more massive than the average towards the cluster centre(1). Therefore clusters with the same chronological age may have reached quite different stages of their dynamical history (that is, they may have different 'dynamical ages'). Blue straggler stars have masses greater(2) than those at the turn-off point on the main sequence and therefore must be the result of either a collision(3,4) or a mass-transfer event(5-7). Because they are among the most massive and luminous objects in old clusters, they can be used as test particles with which to probe dynamical evolution. Here we report that globular clusters can be grouped into a few distinct families on the basis of the radial distribution of blue stragglers. This grouping corresponds well to an effective ranking of the dynamical stage reached by stellar systems, thereby permitting a direct measure of the cluster dynamical age purely from observed properties.
C1 [Ferraro, F. R.; Lanzoni, B.; Dalessandro, E.; Pasquato, M.; Miocchi, P.; Contreras, R.; Sanna, N.; Mucciarelli, A.] Univ Bologna, Dept Phys & Astron, I-40127 Bologna, Italy.
   [Beccari, G.] European So Observ, D-85748 Garching, Germany.
   [Rood, R. T.] Univ Virginia, Dept Astron, Charlottesville, VA 22904 USA.
   [Sigurdsson, S.] Penn State Univ, Dept Astron & Astrophys, Davey Lab 525, University Pk, PA 16802 USA.
   [Sills, A.] McMaster Univ, Dept Phys & Astron, Hamilton, ON L8S 4M1, Canada.
   [Vesperini, E.] Indiana Univ, Dept Astron, Bloomington, IN 47405 USA.
   [Mapelli, M.] Osserv Astron Padova, INAF, I-35122 Padua, Italy.
C3 University of Bologna; European Southern Observatory; University of Virginia; Pennsylvania Commonwealth System of Higher Education (PCSHE); Pennsylvania State University; Pennsylvania State University - University Park; McMaster University; Indiana University System; Indiana University Bloomington; University of Padua; Istituto Nazionale Astrofisica (INAF)
RP Ferraro, FR (corresponding author), Univ Bologna, Dept Phys & Astron, Viale Berti Pichat 6-2, I-40127 Bologna, Italy.
EM francesco.ferraro3@unibo.it
FU European Research Council [ERC-2010-AdG-267675]; European Community [229517]; ESO Visiting Scientist Programme; Space Telescope Science Institute [GO-11975, GO-10524, GO-8709, GO-6607, GO-5903]; NASA [NAS5-26555]; ESO [62.L-0354, 64.L-0439, 59.A-002(A), 69.D-0582(A), 079.D-0220(A), 079.D-0782(A)]
NR 29
TC 188
Z9 196
U1 0
U2 10
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD DEC 20
PY 2012
VL 492
IS 7429
BP 393
EP 395
DI 10.1038/nature11686
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 056KQ
UT WOS:000312488200048
PM 23257880
DA 2026-03-09
ER

PT J
AU Grosskopf, T
   Mohr, W
   Baustian, T
   Schunck, H
   Gill, D
   Kuypers, MMM
   Lavik, G
   Schmitz, RA
   Wallace, DWR
   LaRoche, J
AF Grosskopf, Tobias
   Mohr, Wiebke
   Baustian, Tina
   Schunck, Harald
   Gill, Diana
   Kuypers, Marcel M. M.
   Lavik, Gaute
   Schmitz, Ruth A.
   Wallace, Douglas W. R.
   LaRoche, Julie
TI Doubling of marine dinitrogen-fixation rates based on direct measurements
SO NATURE
LA English
DT Article
ID tropical north-atlantic; nitrogen-fixation; n-2 fixation; ocean; sequestration; distributions; cycle; iron
AB Biological dinitrogen fixation provides the largest input of nitrogen to the oceans, therefore exerting important control on the ocean's nitrogen inventory and primary productivity(1-3). Nitrogen-isotope data from ocean sediments suggest that the marine-nitrogen inventory has been balanced for the past 3,000 years (ref. 4). Producing a balanced marine-nitrogen budget based on direct measurements has proved difficult, however, with nitrogen loss exceeding the gain from dinitrogen fixation by approximately 200 TgNyr(-1) (refs 5, 6). Here we present data from the Atlantic Ocean and show that the most widely used method of measuring oceanic N-2-fixation rates(7) underestimates the contribution of N-2-fixing microorganisms (diazotrophs) relative to a newly developed method(8). Using molecular techniques to quantify the abundance of specific clades of diazotrophs in parallel with rates of N-15(2) incorporation into particulate organic matter, we suggest that the difference between N-2-fixation rates measured with the established method(7) and those measured with the new method8 can be related to the composition of the diazotrophic community. Our data show that in areas dominated by Trichodesmium, the established method underestimates N-2-fixation rates by an average of 62%. We also find that the newly developed method yields N-2-fixation rates more than six times higher than those from the established method when unicellular, symbiotic cyanobacteria and c-proteobacteria dominate the diazotrophic community. On the basis of average areal rates measured over the Atlantic Ocean, we calculated basin-wide N-2-fixation rates of 14 +/- 1 Tg N yr(-1) and 24 +/- 1 Tg N yr(-1) for the established and new methods, respectively. If our findings can be extrapolated to other ocean basins, this suggests that the global marine N-2-fixation rate derived from direct measurements may increase from 103 +/- 8 Tg N yr(-1) to 177 +/- 8 Tg N yr(-1), and that the contribution of N-2 fixers other than Trichodesmium is much more significant than was previously thought.
C1 [Grosskopf, Tobias; Mohr, Wiebke; Baustian, Tina; Schunck, Harald; Gill, Diana; LaRoche, Julie] Helmholtz Ctr Ocean Res Kiel GEOMAR, D-24105 Kiel, Germany.
   [Kuypers, Marcel M. M.; Lavik, Gaute] Max Planck Inst Marine Microbiol, D-28359 Bremen, Germany.
   [Schmitz, Ruth A.] Univ Kiel, Inst Gen Microbiol, D-24118 Kiel, Germany.
   [Wallace, Douglas W. R.] Dalhousie Univ, Dept Oceanog, Halifax, NS B3H 4R2, Canada.
C3 Helmholtz Association; GEOMAR Helmholtz Center for Ocean Research Kiel; Max Planck Society; University of Kiel; Dalhousie University
RP LaRoche, J (corresponding author), Dalhousie Univ, Dept Biol, 1355 Oxford St,POB 1500, Halifax, NS B3H 4R2, Canada.
EM tgrosskopf@geomar.de; julie.laroche@dal.ca
FU Deutsche Forschungsgemeinschaft [Sonderforschungsbereich 754]; Max Planck Gesellschaft; Bundesministerium fur Bildung und Forschung (BMBF) [03F0611A]
NR 28
TC 259
Z9 280
U1 4
U2 239
PU NATURE PUBLISHING 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 16
PY 2012
VL 488
IS 7411
BP 361
EP 364
DI 10.1038/nature11338
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 988OS
UT WOS:000307501000038
PM 22878720
DA 2026-03-09
ER

PT J
AU Lander, GC
   Estrin, E
   Matyskiela, ME
   Bashore, C
   Nogales, E
   Martin, A
AF Lander, Gabriel C.
   Estrin, Eric
   Matyskiela, Mary E.
   Bashore, Charlene
   Nogales, Eva
   Martin, Andreas
TI Complete subunit architecture of the proteasome regulatory particle
SO NATURE
LA English
DT Article
ID ubiquitin chains; new-generation; translocation; degradation; proteins; docking; rpn1; atp; deubiquitination; identification
AB The proteasome is the major ATP-dependent protease in eukaryotic cells, but limited structural information restricts a mechanistic understanding of its activities. The proteasome regulatory particle, consisting of the lid and base subcomplexes, recognizes and processes polyubiquitinated substrates. Here we used electron microscopy and a new heterologous expression system for the lid to delineate the complete subunit architecture of the regulatory particle from yeast. Our studies reveal the spatial arrangement of ubiquitin receptors, deubiquitinating enzymes and the protein unfolding machinery at subnanometre resolution, outlining the substrate's path to degradation. Unexpectedly, the ATPase subunits within the base unfoldase are arranged in a spiral staircase, providing insight into potential mechanisms for substrate translocation through the central pore. Large conformational rearrangements of the lid upon holoenzyme formation suggest allosteric regulation of deubiquitination. We provide a structural basis for the ability of the proteasome to degrade a diverse set of substrates and thus regulate vital cellular processes.
C1 [Estrin, Eric; Matyskiela, Mary E.; Bashore, Charlene; Martin, Andreas] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA.
   [Lander, Gabriel C.; Nogales, Eva] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Div Life Sci, Berkeley, CA 94720 USA.
   [Nogales, Eva] Univ Calif Berkeley, Howard Hughes Med Inst, Berkeley, CA 94720 USA.
   [Nogales, Eva; Martin, Andreas] Univ Calif Berkeley, Inst QB3, Berkeley, CA 94720 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; Howard Hughes Medical Institute; University of California System; University of California Berkeley; University of California System; University of California Berkeley
RP Martin, A (corresponding author), Univ Calif Berkeley, Dept Mol & Cell Biol, 229 Stanley Hall, Berkeley, CA 94720 USA.
EM a.martin@berkeley.edu
FU Damon Runyon Cancer Research Foundation; American Cancer Society [121453-PF-11-178-01-TBE]; NSF; Searle Scholars Program; UC Berkeley MCB Department; NIH [R01-GM094497-01A1]; Lawrence Berkeley National Laboratory; Howard Hughes Medical Institute; NIH through the NCRR [RR017573]; National Institute of General Medical Sciences [T32GM007232, R01GM094497] Funding Source: NIH RePORTER
NR 56
TC 510
Z9 655
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 FEB 9
PY 2012
VL 482
IS 7384
BP 186
EP U75
DI 10.1038/nature10774
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 888HI
UT WOS:000299994100031
PM 22237024
DA 2026-03-09
ER

PT J
AU Shiba, Y
   Fernandes, S
   Zhu, WZ
   Filice, D
   Muskheli, V
   Kim, J
   Palpant, NJ
   Gantz, J
   Moyes, KW
   Reinecke, H
   Van Biber, B
   Dardas, T
   Mignone, JL
   Izawa, A
   Hanna, R
   Viswanathan, M
   Gold, JD
   Kotlikoff, MI
   Sarvazyan, N
   Kay, MW
   Murry, CE
   Laflamme, MA
AF Shiba, Yuji
   Fernandes, Sarah
   Zhu, Wei-Zhong
   Filice, Dominic
   Muskheli, Veronica
   Kim, Jonathan
   Palpant, Nathan J.
   Gantz, Jay
   Moyes, Kara White
   Reinecke, Hans
   Van Biber, Benjamin
   Dardas, Todd
   Mignone, John L.
   Izawa, Atsushi
   Hanna, Ramy
   Viswanathan, Mohan
   Gold, Joseph D.
   Kotlikoff, Michael I.
   Sarvazyan, Narine
   Kay, Matthew W.
   Murry, Charles E.
   Laflamme, Michael A.
TI Human ES-cell-derived cardiomyocytes electrically couple and suppress arrhythmias in injured hearts
SO NATURE
LA English
DT Article
ID embryonic stem-cells; rat hearts; infarction; transplantation; blebbistatin; reperfusion; integration; myocardium; indicators; myocytes
AB Transplantation studies in mice and rats have shown that human embryonic-stem-cell-derived cardiomyocytes (hESC-CMs) can improve the function of infarcted hearts(1-3), but two critical issues related to their electrophysiological behaviour in vivo remain unresolved. First, the risk of arrhythmias following hESC-CM transplantation in injured hearts has not been determined. Second, the electromechanical integration of hESC-CMs in injured hearts has not been demonstrated, so it is unclear whether these cells improve contractile function directly through addition of new force-generating units. Here we use a guinea-pig model to show that hESC-CM grafts in injured hearts protect against arrhythmias and can contract synchronously with host muscle. Injured hearts with hESC-CM grafts show improved mechanical function and a significantly reduced incidence of both spontaneous and induced ventricular tachycardia. To assess the activity of hESC-CM grafts in vivo, we transplanted hESC-CMs expressing the genetically encoded calcium sensor, GCaMP3 (refs 4, 5). By correlating the GCaMP3 fluorescent signal with the host ECG, we found that grafts in uninjured hearts have consistent 1:1 host-graft coupling. Grafts in injured hearts are more heterogeneous and typically include both coupled and uncoupled regions. Thus, human myocardial grafts meet physiological criteria for true heart regeneration, providing support for the continued development of hESC-based cardiac therapies for both mechanical and electrical repair.
C1 [Shiba, Yuji; Fernandes, Sarah; Zhu, Wei-Zhong; Filice, Dominic; Muskheli, Veronica; Kim, Jonathan; Palpant, Nathan J.; Gantz, Jay; Moyes, Kara White; Reinecke, Hans; Van Biber, Benjamin; Murry, Charles E.; Laflamme, Michael A.] Univ Washington, Dept Pathol, Ctr Cardiovasc Biol, Inst Stem Cell & Regenerat Med, Seattle, WA 98109 USA.
   [Shiba, Yuji; Izawa, Atsushi] Shinshu Univ, Dept Cardiovasc Med, Matsumoto, Nagano 3908621, Japan.
   [Filice, Dominic; Gantz, Jay; Murry, Charles E.] Univ Washington, Inst Stem Cell & Regenerat Med, Ctr Cardiovasc Biol, Dept Bioengn, Seattle, WA 98109 USA.
   [Dardas, Todd; Mignone, John L.; Hanna, Ramy; Viswanathan, Mohan; Murry, Charles E.] Univ Washington, Inst Stem Cell & Regenerat Med, Ctr Cardiovasc Biol, Dept Med & Cardiol, Seattle, WA 98195 USA.
   [Gold, Joseph D.] Geron Corp, Menlo Pk, CA 94025 USA.
   [Kotlikoff, Michael I.] Cornell Univ, Coll Vet Med, Dept Biomed Sci, Ithaca, NY 14853 USA.
   [Sarvazyan, Narine; Kay, Matthew W.] George Washington Univ, Dept Pharmacol & Physiol, Washington, DC 20037 USA.
   [Kay, Matthew W.] George Washington Univ, Dept Elect & Comp Engn, Washington, DC 20037 USA.
C3 University of Washington; University of Washington Seattle; Shinshu University; University of Washington; University of Washington Seattle; University of Washington; University of Washington Seattle; Geron Corporation; Cornell University; George Washington University; George Washington University
RP Laflamme, MA (corresponding author), Univ Washington, Dept Pathol, Ctr Cardiovasc Biol, Inst Stem Cell & Regenerat Med, 850 Republican St, Seattle, WA 98109 USA.
EM murry@uw.edu; laflamme@u.washington.edu
FU Geron Corporation; US National Institutes of Health [K08-HL80431, R01-HL064387, P01-HL094374, R01-HL084642, P01-GM81619, U01-HL100405, R01-HL095828]; University of Washington's Mouse Metabolic Phenotyping Center [U24-DK076126]; Grants-in-Aid for Scientific Research [23591035, 24790750, 24591042] Funding Source: KAKEN
NR 40
TC 591
Z9 734
U1 1
U2 124
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 13
PY 2012
VL 489
IS 7415
BP 322
EP +
DI 10.1038/nature11317
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 003UC
UT WOS:000308635900048
PM 22864415
DA 2026-03-09
ER

PT J
AU Krishnamurthy, H
   Gouaux, E
AF Krishnamurthy, Harini
   Gouaux, Eric
TI X-ray structures of LeuT in substrate-free outward-open and apo inward-open states
SO NATURE
LA English
DT Article
ID aminobutyric-acid transporter; serotonin transporter; dopamine transporter; bacterial homolog; membrane-transport; permeation pathway; alternating access; protein-structure; crystal-structure; sodium symporter
AB Neurotransmitter sodium symporters are integral membrane proteins that remove chemical transmitters from the synapse and terminate neurotransmission mediated by serotonin, dopamine, noradrenaline, glycine and GABA (gamma-aminobutyric acid). Crystal structures of the bacterial homologue, LeuT, in substrate-bound outward-occluded and competitive inhibitor-bound outward-facing states have advanced our mechanistic understanding of neurotransmitter sodium symporters but have left fundamental questions unanswered. Here we report crystal structures of LeuT mutants in complexes with conformation-specific antibody fragments in the outward-open and inward-open states. In the absence of substrate but in the presence of sodium the transporter is outward-open, illustrating how the binding of substrate closes the extracellular gate through local conformational changes: hinge-bending movements of the extracellular halves of transmembrane domains 1, 2 and 6, together with translation of extracellular loop 4. The inward-open conformation, by contrast, involves large-scale conformational changes, including a reorientation of transmembrane domains 1, 2, 5, 6 and 7, a marked hinge bending of transmembrane domain 1a and occlusion of the extracellular vestibule by extracellular loop 4. These changes close the extracellular gate, open an intracellular vestibule, and largely disrupt the two sodium sites, thus providing a mechanism by which ions and substrate are released to the cytoplasm. The new structures establish a structural framework for the mechanism of neurotransmitter sodium symporters and their modulation by therapeutic and illicit substances.
C1 [Krishnamurthy, Harini; Gouaux, Eric] Oregon Hlth & Sci Univ, Vollum Inst, Portland, OR 97239 USA.
   [Gouaux, Eric] Oregon Hlth & Sci Univ, Howard Hughes Med Inst, Portland, OR 97239 USA.
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 National Institutes of Health
NR 61
TC 436
Z9 503
U1 1
U2 76
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 26
PY 2012
VL 481
IS 7382
BP 469
EP U80
DI 10.1038/nature10737
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 881GY
UT WOS:000299471800032
PM 22230955
DA 2026-03-09
ER

PT J
AU Som, SM
   Catling, DC
   Harnmeijer, JP
   Polivka, PM
   Buick, R
AF Som, Sanjoy M.
   Catling, David C.
   Harnmeijer, Jelte P.
   Polivka, Peter M.
   Buick, Roger
TI Air density 2.7 billion years ago limited to less than twice modern levels by fossil raindrop imprints
SO NATURE
LA English
DT Article
ID greenhouse; oxygen; temperature; supergroup; atmosphere; climate; drops; cycle; rise
AB According to the 'Faint Young Sun' paradox, during the late Archaean eon a Sun approximately 20% dimmer warmed the early Earth such that it had liquid water and a clement climate(1). Explanations for this phenomenon have invoked a denser atmosphere that provided warmth by nitrogen pressure broadening(1) or enhanced greenhouse gas concentrations(2). Such solutions are allowed by geochemical studies and numerical investigations that place approximate concentration limits on Archaean atmospheric gases, including methane, carbon dioxide and oxygen(2-7). But no field data constraining ground-level air density and barometric pressure have been reported, leaving the plausibility of these various hypotheses in doubt. Here we show that raindrop imprints in tuffs of the Ventersdorp Supergroup, South Africa, constrain surface air density 2.7 billion years ago to less than twice modern levels. We interpret the raindrop fossils using experiments in which water droplets of known size fall at terminal velocity into fresh and weathered volcanic ash, thus defining a relationship between imprint size and raindrop impact momentum. Fragmentation following raindrop flattening limits raindrop size to a maximum value independent of air density, whereas raindrop terminal velocity varies as the inverse of the square root of air density. If the Archaean raindrops reached the modern maximum measured size, air density must have been less than 2.3 kg m(-3), compared to today's 1.2 kg m(-3), but because such drops rarely occur, air density was more probably below 1.3 kg m(-3). The upper estimate for air density renders the pressure broadening explanation(1) possible, but it is improbable under the likely lower estimates. Our results also disallow the extreme CO2 levels required for hot Archaean climates(8).
C1 [Som, Sanjoy M.; Catling, David C.; Harnmeijer, Jelte P.; Polivka, Peter M.; Buick, Roger] Univ Washington, Dept Earth & Space Sci, Seattle, WA 98195 USA.
   [Som, Sanjoy M.; Catling, David C.; Harnmeijer, Jelte P.; Polivka, Peter M.; Buick, Roger] Univ Washington, Astrobiol Program, Seattle, WA 98195 USA.
   [Som, Sanjoy M.] Blue Marble Space Inst Sci, Seattle, WA 98145 USA.
   [Harnmeijer, Jelte P.] Edinburgh Ctr Low Carbon Innovat, Sustainable Community Energy Network, Edinburgh EH8 9AA, Midlothian, Scotland.
   [Polivka, Peter M.] Univ Washington, Dept Civil & Environm Engn, 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
RP Som, SM (corresponding author), NASA, Exobiol Branch, Ames Res Ctr, Moffett Field, CA 94035 USA.
EM sanjoy.m.som@nasa.gov
FU NASA [NNX08AP56G, NNX10AQ90G]; Coordination Action for Research Activities on life in Extreme Environments (CAREX); European Commission; University of Washington Department of Earth and Space Sciences, and its Geoclub; NASA [NNX10AQ90G, 125485, 95844, NNX08AP56G] Funding Source: Federal RePORTER; Division Of Earth Sciences; Directorate For Geosciences [0921580] Funding Source: National Science Foundation
NR 31
TC 152
Z9 175
U1 0
U2 68
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 19
PY 2012
VL 484
IS 7394
BP 359
EP 362
DI 10.1038/nature10890
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 927YM
UT WOS:000302946500029
PM 22456703
DA 2026-03-09
ER

PT J
AU Hernández, JIG
   Ruiz-Lapuente, P
   Tabernero, HM
   Montes, D
   Canal, R
   Méndez, J
   Bedin, LR
AF Gonzalez Hernandez, Jonay I.
   Ruiz-Lapuente, Pilar
   Tabernero, Hugo M.
   Montes, David
   Canal, Ramon
   Mendez, Javier
   Bedin, Luigi R.
TI No surviving evolved companions of the progenitor of SN 1006
SO NATURE
LA English
DT Article
ID ia supernovae; chemical abundances; binary companions; sn-1006 remnant; white-dwarfs; star; impact; spectroscopy; search; 2011fe
AB Type Ia supernovae are thought to occur when a white dwarf made of carbon and oxygen accretes sufficient mass to trigger a thermonuclear explosion(1). The accretion could be slow, from an unevolved (main-sequence) or evolved (subgiant or giant) star(2,3) (the single-degenerate channel), or rapid, as the primary star breaks up a smaller orbiting white dwarf(3,4) (the double-degenerate channel). A companion star will survive the explosion only in the single-degenerate channel(5). Both channels might contribute to the production of type Ia supernovae(6,7), but the relative proportions of their contributions remain a fundamental puzzle in astronomy. Previous searches for remnant companions have revealed one possible case for SN 1572 (refs 8, 9), although that has been questioned(10). More recently, observations have restricted surviving companions to be small, main-sequence stars(11-13), ruling out giant companions but still allowing the single-degenerate channel. Here we report the results of a search for surviving companions of the progenitor of SN 1006 (ref. 14). None of the stars within 4 arc minutes of the apparent site of the explosion is associated with the supernova remnant, and we can firmly exclude all giant and subgiant stars from being companions of the progenitor. In combination with previous results, our findings indicate that fewer than 20 per cent of type Ia supernovae occur through the single-degenerate channel.
C1 [Gonzalez Hernandez, Jonay I.] Inst Astrofis Canarias, E-38205 Tenerife, Spain.
   [Gonzalez Hernandez, Jonay I.] Univ La Laguna, Dept Astrofis, E-38206 Tenerife, Spain.
   [Ruiz-Lapuente, Pilar] CSIC, Inst Fis Fundamental, E-28006 Madrid, Spain.
   [Ruiz-Lapuente, Pilar; Canal, Ramon; Mendez, Javier] Univ Barcelona, Dept Astron, Inst Ciencies Cosmos, E-08028 Barcelona, Spain.
   [Tabernero, Hugo M.; Montes, David] Univ Complutense Madrid, Dept Astrofis & Ciencias Atmosfera, Fac Ciencias Fis, E-28040 Madrid, Spain.
   [Mendez, Javier] Isaac Newton Grp Telescopes, Santa Cruz De La Palma, Spain.
   [Bedin, Luigi R.] INAF Osservatorio Astron Padova, I-35122 Padua, Italy.
C3 Instituto de Astrofisica de Canarias; Universidad de la Laguna; Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Instituto de Fisica Fundamental (IFF); University of Barcelona; Complutense University of Madrid; Isaac Newton Group of Telescopes; Istituto Nazionale Astrofisica (INAF)
RP Hernández, JIG (corresponding author), Inst Astrofis Canarias, E-38205 Tenerife, Spain.
EM jonay@iac.es; pilar@am.ub.es
FU Spanish Ministerio de Ciencia e Innovacion (MICINN); Universidad Complutense de Madrid (UCM); Comunidad de Madrid
NR 30
TC 84
Z9 92
U1 0
U2 10
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD SEP 27
PY 2012
VL 489
IS 7417
BP 533
EP 536
DI 10.1038/nature11447
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 011LT
UT WOS:000309167100043
PM 23018963
DA 2026-03-09
ER

PT J
AU van der Sar, T
   Wang, ZH
   Blok, MS
   Bernien, H
   Taminiau, TH
   Toyli, DM
   Lidar, DA
   Awschalom, DD
   Hanson, R
   Dobrovitski, VV
AF van der Sar, T.
   Wang, Z. H.
   Blok, M. S.
   Bernien, H.
   Taminiau, T. H.
   Toyli, D. M.
   Lidar, D. A.
   Awschalom, D. D.
   Hanson, R.
   Dobrovitski, V. V.
TI Decoherence-protected quantum gates for a hybrid solid-state spin register
SO NATURE
LA English
DT Article
ID nuclear-spin; coherent dynamics; diamond; memory; electron; bath
AB Protecting the dynamics of coupled quantum systems from decoherence by the environment is a key challenge for solid-state quantum information processing(1,2). An idle quantum bit (qubit) can be efficiently insulated from the outside world by dynamical decoupling(3), as has recently been demonstrated for individual solid-state qubits(4-9). However, protecting qubit coherence during a multi-qubit gate is a non-trivial problem(3,10,11): in general, the decoupling disrupts the interqubit dynamics and hence conflicts with gate operation. This problem is particularly salient for hybrid systems(12-22), in which different types of qubit evolve and decohere at very different rates. Here we present the integration of dynamical decoupling into quantum gates for a standard hybrid system, the electron-nuclear spin register. Our design harnesses the internal resonance in the coupled-spin system to resolve the conflict between gate operation and decoupling. We experimentally demonstrate these gates using a two-qubit register in diamond operating at room temperature. Quantum tomography reveals that the qubits involved in the gate operation are protected as accurately as idle qubits. We also perform Grover's quantum search algorithm(1), and achieve fidelities of more than 90% even though the algorithm run-time exceeds the electron spin dephasing time by two orders of magnitude. Our results directly allow decoherence-protected interface gates between different types of solid-state qubit. Ultimately, quantum gates with integrated decoupling may reach the accuracy threshold for fault-tolerant quantum information processing with solid-state devices(1,11).
C1 [Wang, Z. H.; Dobrovitski, V. V.] Ames Lab, Ames, IA 50011 USA.
   [Wang, Z. H.; Dobrovitski, V. V.] Iowa State Univ, Ames, IA 50011 USA.
   [van der Sar, T.; Blok, M. S.; Bernien, H.; Taminiau, T. H.; Hanson, R.] Delft Univ Technol, Kavli Inst Nanosci, NL-2600 GA Delft, Netherlands.
   [Toyli, D. M.; Awschalom, D. D.] Univ Calif Santa Barbara, Ctr Spintron & Quantum Computat, Santa Barbara, CA 93106 USA.
   [Lidar, D. A.] Univ So Calif, Dept Elect Engn, Los Angeles, CA 90089 USA.
   [Lidar, D. A.] Univ So Calif, Dept Chem, Los Angeles, CA 90089 USA.
   [Lidar, D. A.] Univ So Calif, Dept Phys, Los Angeles, CA 90089 USA.
   [Lidar, D. A.] Univ So Calif, Ctr Quantum Informat Sci & Technol, Los Angeles, CA 90089 USA.
C3 United States Department of Energy (DOE); Ames National Laboratory; Iowa State University; Delft University of Technology; University of California System; University of California Santa Barbara; University of Southern California; University of Southern California; University of Southern California; University of Southern California
RP Dobrovitski, VV (corresponding author), Ames Lab, Ames, IA 50011 USA.
EM slava@ameslab.gov
FU Dutch Organization for Fundamental Research on Matter; Netherlands Organization for Scientific Research; DARPA QuEST; AFOSR; ARO MURI; National Science Foundation [CHM-924318, CHM-1037992, PHY-0969969]; ARO MURI [W911NF-11-1-0268]; US Department of Defense; Department of Energy, Basic Energy Sciences [DE-AC02-07CH11358]; Division Of Chemistry; Direct For Mathematical & Physical Scien [1037992, 0924318] Funding Source: National Science Foundation; Division Of Physics; Direct For Mathematical & Physical Scien [0969969] Funding Source: National Science Foundation
NR 30
TC 347
Z9 390
U1 2
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 5
PY 2012
VL 484
IS 7392
BP 82
EP 86
DI 10.1038/nature10900
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 919QN
UT WOS:000302343400038
PM 22481361
DA 2026-03-09
ER

PT J
AU Vilchez, D
   Boyer, L
   Morantte, I
   Lutz, M
   Merkwirth, C
   Joyce, D
   Spencer, B
   Page, L
   Masliah, E
   Berggren, WT
   Gage, FH
   Dillin, A
AF Vilchez, David
   Boyer, Leah
   Morantte, Ianessa
   Lutz, Margaret
   Merkwirth, Carsten
   Joyce, Derek
   Spencer, Brian
   Page, Lesley
   Masliah, Eliezer
   Berggren, W. Travis
   Gage, Fred H.
   Dillin, Andrew
TI Increased proteasome activity in human embryonic stem cells is regulated by PSMD11
SO NATURE
LA English
DT Article
ID differentiation; proteostasis; subunit; mutant; rpn6p; core
AB Embryonic stem cells can replicate continuously in the absence of senescence and, therefore, are immortal in culture(1,2). Although genome stability is essential for the survival of stem cells, proteome stability may have an equally important role in stem-cell identity and function. Furthermore, with the asymmetric divisions invoked by stem cells, the passage of damaged proteins to daughter cells could potentially destroy the resulting lineage of cells. Therefore, a firm understanding of how stem cells maintain their proteome is of central importance. Here we show that human embryonic stem cells (hESCs) exhibit high proteasome activity that is correlated with increased levels of the 19S proteasome subunit PSMD11 (known as RPN-6 in Caenorhabditis elegans)(3-5) and a corresponding increased assembly of the 26S/30S proteasome. Ectopic expression of PSMD11 is sufficient to increase proteasome assembly and activity. FOXO4, an insulin/insulin-like growth factor-I (IGF-I) responsive transcription factor associated with long lifespan in invertebrates(6,7), regulates proteasome activity by modulating the expression of PSMD11 in hESCs. Proteasome inhibition in hESCs affects the expression of pluripotency markers and the levels of specific markers of the distinct germ layers. Our results suggest a new regulation of proteostasis in hESCs that links longevity and stress resistance in invertebrates to hESC function and identity.
C1 [Vilchez, David; Morantte, Ianessa; Merkwirth, Carsten; Joyce, Derek; Dillin, Andrew] Salk Inst Biol Studies, Howard Hughes Med Inst, Glenn Ctr Aging Res, Mol & Cell Biol Lab, La Jolla, CA 92037 USA.
   [Boyer, Leah; Gage, Fred H.] Salk Inst Biol Studies, Genet Lab, La Jolla, CA 92037 USA.
   [Lutz, Margaret; Berggren, W. Travis] Salk Inst Biol Studies, Stem Cell Core, La Jolla, CA 92037 USA.
   [Spencer, Brian; Masliah, Eliezer] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA.
   [Page, Lesley] Scripps Res Inst, Dept Cell Biol, La Jolla, CA 92037 USA.
C3 Howard Hughes Medical Institute; Salk Institute; Salk Institute; Salk Institute; University of California System; University of California San Diego; Scripps Research Institute
RP Dillin, A (corresponding author), Salk Inst Biol Studies, Howard Hughes Med Inst, Glenn Ctr Aging Res, Mol & Cell Biol Lab, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA.
EM dillin@salk.edu
FU Howard Hughes Medical Institute; F.M. Kirby, Inc. Foundation Postdoctoral Scholar Award; Beatriu de Pinos (AGAUR) fellowship
NR 26
TC 329
Z9 389
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 SEP 13
PY 2012
VL 489
IS 7415
BP 304
EP +
DI 10.1038/nature11468
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 003UC
UT WOS:000308635900044
PM 22972301
DA 2026-03-09
ER

PT J
AU Schmitz, R
   Young, RM
   Ceribelli, M
   Jhavar, S
   Xiao, WM
   Zhang, MZ
   Wright, G
   Shaffer, AL
   Hodson, DJ
   Buras, E
   Liu, XL
   Powell, J
   Yang, YD
   Xu, WH
   Zhao, H
   Kohlhammer, H
   Rosenwald, A
   Kluin, P
   Müller-Hermelink, HK
   Ott, G
   Gascoyne, RD
   Connors, JM
   Rimsza, LM
   Campo, E
   Jaffe, ES
   Delabie, J
   Smeland, EB
   Ogwang, MD
   Reynolds, SJ
   Fisher, RI
   Braziel, RM
   Tubbs, RR
   Cook, JR
   Weisenburger, DD
   Chan, WC
   Pittaluga, S
   Wilson, W
   Waldmann, TA
   Rowe, M
   Mbulaiteye, SM
   Rickinson, AB
   Staudt, LM
AF Schmitz, Roland
   Young, Ryan M.
   Ceribelli, Michele
   Jhavar, Sameer
   Xiao, Wenming
   Zhang, Meili
   Wright, George
   Shaffer, Arthur L.
   Hodson, Daniel J.
   Buras, Eric
   Liu, Xuelu
   Powell, John
   Yang, Yandan
   Xu, Weihong
   Zhao, Hong
   Kohlhammer, Holger
   Rosenwald, Andreas
   Kluin, Philip
   Mueller-Hermelink, Hans Konrad
   Ott, German
   Gascoyne, Randy D.
   Connors, Joseph M.
   Rimsza, Lisa M.
   Campo, Elias
   Jaffe, Elaine S.
   Delabie, Jan
   Smeland, Erlend B.
   Ogwang, Martin D.
   Reynolds, Steven J.
   Fisher, Richard I.
   Braziel, Rita M.
   Tubbs, Raymond R.
   Cook, James R.
   Weisenburger, Dennis D.
   Chan, Wing C.
   Pittaluga, Stefania
   Wilson, Wyndham
   Waldmann, Thomas A.
   Rowe, Martin
   Mbulaiteye, Sam M.
   Rickinson, Alan B.
   Staudt, Louis M.
TI Burkitt lymphoma pathogenesis and therapeutic targets from structural and functional genomics
SO NATURE
LA English
DT Article
ID cell; immunoglobulin; region
AB Burkitt's lymphoma (BL) can often be cured by intensive chemotherapy, but the toxicity of such therapy precludes its use in the elderly and in patients with endemic BL in developing countries, necessitating new strategies(1). The normal germinal centre B cell is the presumed cell of origin for both BL and diffuse large B-cell lymphoma (DLBCL), yet gene expression analysis suggests that these malignancies may use different oncogenic pathways(2). BL is subdivided into a sporadic subtype that is diagnosed in developed countries, the Epstein-Barr-virus-associated endemic subtype, and an HIV-associated subtype, but it is unclear whether these subtypes use similar or divergent oncogenic mechanisms. Here we used high-throughput RNA sequencing and RNA interference screening to discover essential regulatory pathways in BL that cooperate with MYC, the defining oncogene of this cancer. In 70% of sporadic BL cases, mutations affecting the transcription factor TCF3 (E2A) or its negative regulator ID3 fostered TCF3 dependency. TCF3 activated the pro-survival phosphatidylinositol-3-OH kinase pathway in BL, in part by augmenting tonic B-cell receptor signalling. In 38% of sporadic BL cases, oncogenic CCND3 mutations produced highly stable cyclin D3 isoforms that drive cell cycle progression. These findings suggest opportunities to improve therapy for patients with BL.
C1 [Schmitz, Roland; Young, Ryan M.; Ceribelli, Michele; Jhavar, Sameer; Zhang, Meili; Shaffer, Arthur L.; Hodson, Daniel J.; Buras, Eric; Yang, Yandan; Xu, Weihong; Zhao, Hong; Kohlhammer, Holger; Wilson, Wyndham; Waldmann, Thomas A.; Staudt, Louis M.] NCI, Metab Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
   [Xiao, Wenming; Liu, Xuelu; Powell, John] NIH, Bioinformat & Mol Anal Sect, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA.
   [Wright, George] NCI, Biometr Res Branch, DCTD, NIH, Bethesda, MD 20892 USA.
   [Rosenwald, Andreas; Mueller-Hermelink, Hans Konrad] Univ Wurzburg, Dept Pathol, D-97080 Wurzburg, Germany.
   [Kluin, Philip] Univ Groningen, Univ Med Ctr Groningen, Dept Pathol & Med Biol, NL-9713 GZ Groningen, Netherlands.
   [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.; Connors, Joseph M.] 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.; Pittaluga, Stefania] 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 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.
   [Ogwang, Martin D.] St Marys Hosp Lacor, Gulu 256, Uganda.
   [Reynolds, Steven J.] NIAID, Div Intramural Res, NIH, Bethesda, MD 20892 USA.
   [Fisher, Richard I.] Univ Rochester, Sch Med, James P Wilmot Canc Ctr, Rochester, NY 14642 USA.
   [Braziel, Rita M.] Oregon Hlth & Sci Univ, Portland, OR 97239 USA.
   [Tubbs, Raymond R.; Cook, James R.] Cleveland Clin, Pathol & Lab Med Inst, Cleveland, OH 44195 USA.
   [Weisenburger, Dennis D.; Chan, Wing C.] Univ Nebraska Med Ctr, Dept Pathol, Omaha, NE 68198 USA.
   [Weisenburger, Dennis D.; Chan, Wing C.] Univ Nebraska Med Ctr, Dept Microbiol, Omaha, NE 68198 USA.
   [Rowe, Martin; Rickinson, Alan B.] Univ Birmingham, Birmingham Canc Res UK Ctr, Sch Canc Sci, Birmingham B15 2TT, W Midlands, England.
   [Mbulaiteye, Sam M.] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, NIH,US Dept HHS, Rockville, MD 20852 USA.
C3 National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); National Institutes of Health (NIH) - USA; NIH Center for Information Technology (CIT); National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); University of Wurzburg; University of Groningen; 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; National Institutes of Health (NIH) - USA; Division of Intramural Research (DIR); NIH National Institute of Allergy & Infectious Diseases (NIAID); University of Rochester; Oregon Health & Science University; Cleveland Clinic Foundation; University of Nebraska System; University of Nebraska Medical Center; University of Nebraska System; University of Nebraska Medical Center; University of Birmingham; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); NIH National Cancer Institute- Division of Cancer Epidemiology & Genetics
RP Staudt, LM (corresponding author), NCI, Metab Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM lstaudt@mail.nih.gov
FU NIH, National Cancer Institute, Center for Cancer Research, an NCI SPECS grant [UO1-CA 114778]; Foundation for NIH; Cancer Research UK; Lymphoma/Leukemia Molecular Profiling Project (LLMPP); Dr Mildred Scheel Stiftung fur Krebsforschung (Deutsche Krebshilfe); NCI [N01-C0-12400]; Medical Research Council [G9818340B] Funding Source: researchfish; National Cancer Institute [ZIASC000550, ZIACP010176, ZIASC004002] Funding Source: NIH RePORTER; National Institute of Allergy and Infectious Diseases [ZIAAI000361, ZIAAI001040] Funding Source: NIH RePORTER
NR 21
TC 687
Z9 787
U1 1
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 OCT 4
PY 2012
VL 490
IS 7418
BP 116
EP 120
DI 10.1038/nature11378
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 015LG
UT WOS:000309446800044
PM 22885699
DA 2026-03-09
ER

PT J
AU Foreman, BZ
   Heller, PL
   Clementz, MT
AF Foreman, Brady Z.
   Heller, Paul L.
   Clementz, Mark T.
TI Fluvial response to abrupt global warming at the Palaeocene/Eocene boundary
SO NATURE
LA English
DT Article
ID eocene thermal maximum; climate; basin; model; colorado; petm
AB Climate strongly affects the production of sediment from mountain catchments as well as its transport and deposition within adjacent sedimentary basins(1-3). However, identifying climatic influences on basin stratigraphy is complicated by nonlinearities, feedback loops, lag times, buffering and convergence among processes within the sediment routeing system(3,4). The Palaeocene/Eocene thermal maximum (PETM) arguably represents the most abrupt and dramatic instance of global warming in the Cenozoic era and has been proposed to be a geologic analogue for anthropogenic climate change(5). Here we evaluate the fluvial response in western Colorado to the PETM. Concomitant with the carbon isotope excursion marking the PETM we document a basin-wide shift to thick, multistoried, sheets of sandstone characterized by variable channel dimensions, dominance of upper flow regime sedimentary structures, and prevalent crevasse splay deposits. This progradation of coarse-grained lithofacies matches model predictions for rapid increases in sediment flux and discharge(1,3), instigated by regional vegetation overturn(5,6) and enhanced monsoon precipitation(7,8). Yet the change in fluvial deposition persisted long after the approximately 200,000-year-long PETM9 with its increased carbon dioxide levels in the atmosphere, emphasizing the strong role the protracted transmission of catchment responses to distant depositional systems has in constructing large-scale basin stratigraphy. Our results, combined with evidence for increased dissolved loads(10) and terrestrial clay export(5,11,12) to world oceans, indicate that the transient hyper-greenhouse climate of the PETM may represent a major geomorphic 'system-clearing event'(13), involving a global mobilization of dissolved and solid sediment loads on Earth's surface.
C1 [Foreman, Brady Z.; Heller, Paul L.; Clementz, Mark T.] Univ Wyoming, Dept Geol & Geophys, Laramie, WY 82071 USA.
C3 University of Wyoming
RP Foreman, BZ (corresponding author), Univ Wyoming, Dept Geol & Geophys, 1000 E Univ Ave, Laramie, WY 82071 USA.
EM bforema1@uwyo.edu
FU International Association of Sedimentologists; Tobacco Root Geological Society; Colorado Scientific Society; Chevron Energy Technology Company; NSF Graduate Research Fellowship; Wyoming NASA Space Grant Consortium Fellowship
NR 30
TC 189
Z9 238
U1 6
U2 136
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 1
PY 2012
VL 491
IS 7422
BP 92
EP 95
DI 10.1038/nature11513
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 028PM
UT WOS:000310434500036
PM 23128230
DA 2026-03-09
ER

PT J
AU Murakami, M
   Ohishi, Y
   Hirao, N
   Hirose, K
AF Murakami, Motohiko
   Ohishi, Yasuo
   Hirao, Naohisa
   Hirose, Kei
TI A perovskitic lower mantle inferred from high-pressure, high-temperature sound velocity data
SO NATURE
LA English
DT Article
ID aluminous mgsio3 perovskite; earths lower mantle; equation-of-state; chemical-composition; elasticity; phase; gpa; ferropericlase; heterogeneity; transition
AB The determination of the chemical composition of Earth's lower mantle is a long-standing challenge in earth science. Accurate knowledge of sound velocities in the lower-mantle minerals under relevant high-pressure, high-temperature conditions is essential in constraining the mineralogy and chemical composition using seismological observations(1), but previous acoustic measurements were limited to a range of low pressures and temperatures. Here we determine the shear-wave velocities for silicate perovskite and ferropericlase under the pressure and temperature conditions of the deep lower mantle using Brillouin scattering spectroscopy(2). The mineralogical model that provides the best fit to a global seismic velocity profile(1) indicates that perovskite constitutes more than 93 per cent by volume of the lower mantle, which is a much higher proportion than that predicted by the conventional peridotitic mantle model. It suggests that the lower mantle is enriched in silicon relative to the upper mantle, which is consistent with the chondritic Earth model. Such chemical stratification implies layered-mantle convection with limited mass transport between the upper and the lower mantle.
C1 [Murakami, Motohiko] Tohoku Univ, Grad Sch Sci, Dept Earth & Planetary Mat Sci, Sendai, Miyagi 9808578, Japan.
   [Ohishi, Yasuo; Hirao, Naohisa] Japan Synchrotron Radiat Res Inst, Sayo, Hyogo 6795198, Japan.
   [Hirose, Kei] Tokyo Inst Technol, Dept Earth & Planetary Sci, Meguro Ku, Tokyo 1528551, Japan.
   [Hirose, Kei] Japan Agcy Marine Earth Sci & Technol, Inst Res Earth Evolut, Yokosuka, Kanagawa 2370061, Japan.
C3 Tohoku University; Japan Synchrotron Radiation Research Institute; Institute of Science Tokyo; Tokyo Institute of Technology; Japan Agency for Marine-Earth Science & Technology (JAMSTEC)
RP Murakami, M (corresponding author), Tohoku Univ, Grad Sch Sci, Dept Earth & Planetary Mat Sci, Sendai, Miyagi 9808578, Japan.
EM motohiko@m.tohoku.ac.jp
FU SPring-8 [2008B0099, 2009A0087]; Grants-in-Aid for Scientific Research [24654170, 22340164, 19674003, 22684028] Funding Source: KAKEN
NR 38
TC 217
Z9 252
U1 2
U2 183
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 3
PY 2012
VL 485
IS 7396
BP 90
EP U118
DI 10.1038/nature11004
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 934NV
UT WOS:000303451900040
PM 22552097
DA 2026-03-09
ER

PT J
AU Pérez-Mancera, PA
   Rust, AG
   van der Weyden, L
   Kristiansen, G
   Li, A
   Sarver, AL
   Silverstein, KAT
   Grützmann, R
   Aust, D
   Rümmele, P
   Knösel, T
   Herd, C
   Stemple, DL
   Kettleborough, R
   Brosnan, JA
   Li, A
   Morgan, R
   Knight, S
   Yu, J
   Stegeman, S
   Collier, LS
   ten Hoeve, JJ
   de Ridder, J
   Klein, AP
   Goggins, M
   Hruban, RH
   Chang, DK
   Biankin, AV
   Grimmond, SM
   Wessels, LFA
   Wood, SA
   Iacobuzio-Donahue, CA
   Pilarsky, C
   Largaespada, DA
   Adams, DJ
   Tuveson, DA
AF Perez-Mancera, Pedro A.
   Rust, Alistair G.
   van der Weyden, Louise
   Kristiansen, Glen
   Li, Allen
   Sarver, Aaron L.
   Silverstein, Kevin A. T.
   Gruetzmann, Robert
   Aust, Daniela
   Ruemmele, Petra
   Knoesel, Thomas
   Herd, Colin
   Stemple, Derek L.
   Kettleborough, Ross
   Brosnan, Jacqueline A.
   Li, Ang
   Morgan, Richard
   Knight, Spencer
   Yu, Jun
   Stegeman, Shane
   Collier, Lara S.
   ten Hoeve, Jelle J.
   de Ridder, Jeroen
   Klein, Alison P.
   Goggins, Michael
   Hruban, Ralph H.
   Chang, David K.
   Biankin, Andrew V.
   Grimmond, Sean M.
   Wessels, Lodewyk F. A.
   Wood, Stephen A.
   Iacobuzio-Donahue, Christine A.
   Pilarsky, Christian
   Largaespada, David A.
   Adams, David J.
   Tuveson, David A.
TI The deubiquitinase USP9X suppresses pancreatic ductal adenocarcinoma
SO NATURE
LA English
DT Article
ID somatic mutations; insertion sites; k-ras; gene; cancer; mouse; mutagenesis; carcinoma; expression; stabilization
AB Pancreatic ductal adenocarcinoma (PDA) remains a lethal malignancy despite much progress concerning its molecular characterization. PDA tumours harbour four signature somatic mutations(1-4) in addition to numerous lower frequency genetic events of uncertain significance(5). Here we use Sleeping Beauty (SB) transposon-mediated insertional mutagenesis(6,7) in a mouse model of pancreatic ductal preneoplasia(8) to identify genes that cooperate with oncogenic Kras(G12D) to accelerate tumorigenesis and promote progression. Our screen revealed new candidate genes for PDA and confirmed the importance of many genes and pathways previously implicated in human PDA. The most commonly mutated gene was the X-linked deubiquitinase Usp9x, which was inactivated in over 50% of the tumours. Although previous work had attributed a pro-survival role to USP9X in human neoplasia(9), we found instead that loss of Usp9x enhances transformation and protects pancreatic cancer cells from anoikis. Clinically, low USP9X protein and messenger RNA expression in PDA correlates with poor survival after surgery, and USP9X levels are inversely associated with metastatic burden in advanced disease. Furthermore, chromatin modulation with trichostatin A or 5-aza-2'-deoxycytidine elevates USP9X expression in human PDA cell lines, indicating a clinical approach for certain patients. The conditional deletion of Usp9x cooperated with Kras(G12D) to accelerate pancreatic tumorigenesis in mice, validating their genetic interaction. We propose that USP9X is a major tumour suppressor gene with prognostic and therapeutic relevance in PDA.
C1 [Rust, Alistair G.; van der Weyden, Louise; Herd, Colin; Stemple, Derek L.; Kettleborough, Ross; Adams, David J.] Wellcome Trust Sanger Inst, Hinxton CB10 1SA, England.
   [Perez-Mancera, Pedro A.; Tuveson, David A.] Canc Res UK, Li Ka Shing Ctr, Cambridge Res Inst, Cambridge CB2 0RE, England.
   [Perez-Mancera, Pedro A.; Tuveson, David A.] Dept Oncol, Cambridge CB2 0RE, England.
   [Kristiansen, Glen] Univ Hosp Bonn, Inst Pathol, D-53127 Bonn, Germany.
   [Li, Allen; Brosnan, Jacqueline A.; Li, Ang; Morgan, Richard; Knight, Spencer; Yu, Jun; Klein, Alison P.; Goggins, Michael; Hruban, Ralph H.; Iacobuzio-Donahue, Christine A.] Johns Hopkins Med Inst, Dept Oncol, Sol Goldman Pancreat Canc Res Ctr, Baltimore, MD 21231 USA.
   [Li, Allen; Brosnan, Jacqueline A.; Li, Ang; Morgan, Richard; Knight, Spencer; Yu, Jun; Klein, Alison P.; Goggins, Michael; Hruban, Ralph H.; Iacobuzio-Donahue, Christine A.] Johns Hopkins Med Inst, Dept Pathol, Sol Goldman Pancreat Canc Res Ctr, Baltimore, MD 21231 USA.
   [Sarver, Aaron L.; Silverstein, Kevin A. T.; Largaespada, David A.] Univ Minnesota, Mason Canc Ctr, Minneapolis, MN 55455 USA.
   [Gruetzmann, Robert; Pilarsky, Christian] Univ Hosp Dresden, Dept Surg, D-01307 Dresden, Germany.
   [Aust, Daniela] Univ Hosp Dresden, Inst Pathol, D-01307 Dresden, Germany.
   [Ruemmele, Petra] Univ Regensburg, Inst Pathol, D-93053 Regensburg, Germany.
   [Knoesel, Thomas] Univ Hosp Jena, Inst Pathol, D-07743 Jena, Germany.
   [Knoesel, Thomas] Univ Munich, Inst Pathol, D-80337 Munich, Germany.
   [Stegeman, Shane; Wood, Stephen A.] Griffith Univ, Eskitis Inst Cell & Mol Therapies, Nathan, Qld 4111, Australia.
   [Collier, Lara S.] Univ Wisconsin, Sch Pharm, Madison, WI 53705 USA.
   [ten Hoeve, Jelle J.; de Ridder, Jeroen; Wessels, Lodewyk F. A.] Delft Univ Technol, Delft Bioinformat Lab, Fac EEMCS, NL-2628 CD Delft, Netherlands.
   [ten Hoeve, Jelle J.; Wessels, Lodewyk F. A.] Netherlands Canc Inst, NL-1066 CX Amsterdam, Netherlands.
   [Chang, David K.; Biankin, Andrew V.] Garvan Inst Med Res, Kinghorn Canc Ctr, Canc Res Program, Sydney, NSW 2010, Australia.
   [Chang, David K.; Biankin, Andrew V.] Bankstown Hosp, Dept Surg, Sydney, NSW 2200, Australia.
   [Chang, David K.; Biankin, Andrew V.] Univ NSW, S Western Sydney Clin Sch, Fac Med, Liverpool, NSW 2170, Australia.
   [Grimmond, Sean M.] Univ Queensland, Queensland Ctr Med Genom, Inst Mol Biosci, Brisbane, Qld 4072, Australia.
C3 Wellcome Trust Sanger Institute; CRUK Cambridge Institute; Cancer Research UK; University of Cambridge; University of Bonn; Johns Hopkins University; Johns Hopkins Medicine; Johns Hopkins University; Johns Hopkins Medicine; University of Minnesota System; University of Minnesota Twin Cities; Technische Universitat Dresden; Carl Gustav Carus University Hospital; Technische Universitat Dresden; Carl Gustav Carus University Hospital; University of Regensburg; Friedrich Schiller University of Jena; University of Munich; Griffith University; University of Wisconsin System; University of Wisconsin Madison; Delft University of Technology; Netherlands Cancer Institute; Garvan Institute of Medical Research; The Kinghorn Cancer Centre; NSW Health; Bankstown Lidcombe Hospital; University of Queensland
RP Adams, DJ (corresponding author), Wellcome Trust Sanger Inst, Hinxton CB10 1SA, England.
EM da1@sanger.ac.uk; david.tuveson@cancer.org.uk
FU University of Cambridge; Cancer Research UK; Li Ka Shing Foundation; Hutchison Whampoa Limited; NIHR Cambridge Biomedical Research Centre; NIH [2P50CA101955, CA62924, CA128920, CA106610, P50CA62924, CA122183]; Wellcome Trust; Kay Kendall Leukemia Fund; Wilhelm Sander Stiftung [2009.039.1]; Deutsche Forschungsgemeinschaft [PI 341/5-1]; National Health and Medical research Council of Australia (NHMRC); Queensland Government; Cancer Council NSW; Australian Cancer Research Foundation; Cancer Institute NSW; Avner Nahmani Pancreatic Cancer Research Foundation; R.T. Hall Trust; Cancer Research UK [13031] Funding Source: researchfish; National Cancer Institute [P50CA062924] Funding Source: NIH RePORTER
NR 38
TC 275
Z9 311
U1 0
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 JUN 14
PY 2012
VL 486
IS 7402
BP 266
EP +
DI 10.1038/nature11114
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 957UH
UT WOS:000305189000037
PM 22699621
DA 2026-03-09
ER

PT J
AU Phrampus, BJ
   Hornbach, MJ
AF Phrampus, Benjamin J.
   Hornbach, Matthew J.
TI Recent changes to the Gulf Stream causing widespread gas hydrate destabilization
SO NATURE
LA English
DT Article
ID ocean; flow
AB The Gulf Stream is an ocean current that modulates climate in the Northern Hemisphere by transporting warm waters from the Gulf of Mexico into the North Atlantic and Arctic oceans(1,2). A changing Gulf Stream has the potential to thaw and convert hundreds of gigatonnes of frozen methane hydrate trapped below the sea floor into methane gas, increasing the risk of slope failure and methane release(3-9). How the Gulf Stream changes with time and what effect these changes have on methane hydrate stability is unclear. Here, using seismic data combined with thermal models, we show that recent changes in intermediate-depth ocean temperature associated with the Gulf Stream are rapidly destabilizing methane hydrate along a broad swathe of the North American margin. The area of active hydrate destabilization covers at least 10,000 square kilometres of the United States eastern margin, and occurs in a region prone to kilometre-scale slope failures. Previous hypothetical studies(3,5) postulated that an increase of five degrees Celsius in intermediate-depth ocean temperatures could release enough methane to explain extreme global warming events like the Palaeocene-Eocene thermal maximum (PETM) and trigger widespread ocean acidification(7). Our analysis suggests that changes in Gulf Stream flow or temperature within the past 5,000 years or so are warming the western North Atlantic margin by up to eight degrees Celsius and are now triggering the destabilization of 2.5 gigatonnes of methane hydrate (about 0.2 per cent of that required to cause the PETM). This destabilization extends along hundreds of kilometres of the margin and may continue for centuries. It is unlikely that the western North Atlantic margin is the only area experiencing changing ocean currents(10-12); our estimate of 2.5 gigatonnes of destabilizing methane hydrate may therefore represent only a fraction of the methane hydrate currently destabilizing globally. The transport from ocean to atmosphere of any methane released-and thus its impact on climate-remains uncertain.
C1 [Phrampus, Benjamin J.; Hornbach, Matthew J.] So Methodist Univ, Huffington Dept Earth Sci, Dallas, TX 75275 USA.
C3 Southern Methodist University
RP Phrampus, BJ (corresponding author), So Methodist Univ, Huffington Dept Earth Sci, Dallas, TX 75275 USA.
EM bphrampus@mail.smu.edu
NR 30
TC 161
Z9 182
U1 2
U2 186
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 25
PY 2012
VL 490
IS 7421
BP 527
EP +
DI 10.1038/nature11528
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 025NK
UT WOS:000310196200039
PM 23099408
DA 2026-03-09
ER

PT J
AU Dunham, I
   Kundaje, A
   Aldred, SF
   Collins, PJ
   Davis, C
   Doyle, F
   Epstein, CB
   Frietze, S
   Harrow, J
   Kaul, R
   Khatun, J
   Lajoie, BR
   Landt, SG
   Lee, BK
   Pauli, F
   Rosenbloom, KR
   Sabo, P
   Safi, A
   Sanyal, A
   Shoresh, N
   Simon, JM
   Song, L
   Trinklein, ND
   Altshuler, RC
   Birney, E
   Brown, JB
   Cheng, C
   Djebali, S
   Dong, XJ
   Dunham, I
   Ernst, J
   Furey, TS
   Gerstein, M
   Giardine, B
   Greven, M
   Hardison, RC
   Harris, RS
   Herrero, J
   Hoffman, MM
   Iyer, S
   Kellis, M
   Khatun, J
   Kheradpour, P
   Kundaje, A
   Lassmann, T
   Li, QH
   Lin, X
   Marinov, GK
   Merkel, A
   Mortazavi, A
   Parker, SCJ
   Reddy, TE
   Rozowsky, J
   Schlesinger, F
   Thurman, RE
   Wang, J
   Ward, LD
   Whitfield, TW
   Wilder, SP
   Wu, W
   Xi, HLS
   Yip, KY
   Zhuang, JL
   Bernstein, BE
   Birney, E
   Dunham, I
   Green, ED
   Gunter, C
   Snyder, M
   Pazin, MJ
   Lowdon, RF
   Dillon, LAL
   Adams, LB
   Kelly, CJ
   Zhang, J
   Wexler, JR
   Green, ED
   Good, PJ
   Feingold, EA
   Bernstein, BE
   Birney, E
   Crawford, GE
   Dekker, J
   Elnitski, L
   Farnham, PJ
   Gerstein, M
   Giddings, MC
   Gingeras, TR
   Green, ED
   Guigo, R
   Hardison, RC
   Hubbard, TJ
   Kellis, M
   Kent, WJ
   Lieb, JD
   Margulies, EH
   Myers, RM
   Snyder, M
   Stamatoyannopoulos, JA
   Tenenbaum, SA
   Weng, ZP
   White, KP
   Wold, B
   Khatun, J
   Yu, Y
   Wrobel, J
   Risk, BA
   Gunawardena, HP
   Kuiper, HC
   Maier, CW
   Xie, L
   Chen, X
   Giddings, MC
   Bernstein, BE
   Epstein, CB
   Shoresh, N
   Ernst, J
   Kheradpour, P
   Mikkelsen, TS
   Gillespie, S
   Goren, A
   Ram, O
   Zhang, XL
   Wang, L
   Issner, R
   Coyne, MJ
   Durham, T
   Ku, M
   Truong, T
   Ward, LD
   Altshuler, RC
   Eaton, ML
   Kellis, M
   Djebali, S
   Davis, CA
   Merkel, A
   Dobin, A
   Lassmann, T
   Mortazavi, A
   Tanzer, A
   Lagarde, J
   Lin, W
   Schlesinger, F
   Xue, CH
   Marinov, GK
   Khatun, J
   Williams, BA
   Zaleski, C
   Rozowsky, J
   Roeder, M
   Kokocinski, F
   Abdelhamid, RF
   Alioto, T
   Antoshechkin, I
   Baer, MT
   Batut, P
   Bell, I
   Bell, K
   Chakrabortty, S
   Chen, X
   Chrast, J
   Curado, J
   Derrien, T
   Drenkow, J
   Dumais, E
   Dumais, J
   Duttagupta, R
   Fastuca, M
   Fejes-Toth, K
   Ferreira, P
   Foissac, S
   Fullwood, MJ
   Gao, H
   Gonzalez, D
   Gordon, A
   Gunawardena, HP
   Howald, C
   Jha, S
   Johnson, R
   Kapranov, P
   King, B
   Kingswood, C
   Li, GL
   Luo, OJ
   Park, E
   Preall, JB
   Presaud, K
   Ribeca, P
   Risk, BA
   Robyr, D
   Ruan, XA
   Sammeth, M
   Sandhu, KS
   Schaeffer, L
   See, LH
   Shahab, A
   Skancke, J
   Suzuki, AM
   Takahashi, H
   Tilgner, H
   Trout, D
   Walters, N
   Wang, HE
   Wrobel, J
   Yu, YB
   Hayashizaki, Y
   Harrow, J
   Gerstein, M
   Hubbard, TJ
   Reymond, A
   Antonarakis, SE
   Hannon, GJ
   Giddings, MC
   Ruan, YJ
   Wold, B
   Carninci, P
   Guigo, R
   Gingeras, TR
   Rosenbloom, KR
   Sloan, CA
   Learned, K
   Malladi, VS
   Wong, MC
   Barber, G
   Cline, MS
   Dreszer, TR
   Heitner, SG
   Karolchik, D
   Kent, WJ
   Kirkup, VM
   Meyer, LR
   Long, JC
   Maddren, M
   Raney, BJ
   Furey, TS
   Song, LY
   Grasfeder, LL
   Giresi, PG
   Lee, BK
   Battenhouse, A
   Sheffield, NC
   Simon, JM
   Showers, KA
   Safi, A
   London, D
   Bhinge, AA
   Shestak, C
   Schaner, MR
   Kim, SK
   Zhang, ZZZ
   Mieczkowski, PA
   Mieczkowska, JO
   Liu, Z
   McDaniell, RM
   Ni, YY
   Rashid, NU
   Kim, MJ
   Adar, S
   Zhang, ZC
   Wang, TY
   Winter, D
   Keefe, D
   Birney, E
   Iyer, VR
   Lieb, JD
   Crawford, GE
   Li, GL
   Sandhu, KS
   Zheng, MZ
   Wang, P
   Luo, OJ
   Shahab, A
   Fullwood, MJ
   Ruan, XA
   Ruan, YJ
   Myers, RM
   Pauli, F
   Williams, BA
   Gertz, J
   Marinov, GK
   Reddy, TE
   Vielmetter, J
   Partridge, EC
   Trout, D
   Varley, KE
   Gasper, C
   Bansal, A
   Pepke, S
   Jain, P
   Amrhein, H
   Bowling, KM
   Anaya, M
   Cross, MK
   King, B
   Muratet, MA
   Antoshechkin, I
   Newberry, KM
   Mccue, K
   Nesmith, AS
   Fisher-Aylor, KI
   Pusey, B
   DeSalvo, G
   Parker, SL
   Balasubramanian, S
   Davis, NS
   Meadows, SK
   Eggleston, T
   Gunter, C
   Newberry, JS
   Levy, SE
   Absher, DM
   Mortazavi, A
   Wong, WH
   Wold, B
   Blow, MJ
   Visel, A
   Pennachio, LA
   Elnitski, L
   Margulies, EH
   Parker, SCJ
   Petrykowska, HM
   Abyzov, A
   Aken, B
   Barrell, D
   Barson, G
   Berry, A
   Bignell, A
   Boychenko, V
   Bussotti, G
   Chrast, J
   Davidson, C
   Derrien, T
   Despacio-Reyes, G
   Diekhans, M
   Ezkurdia, I
   Frankish, A
   Gilbert, J
   Gonzalez, JM
   Griffiths, E
   Harte, R
   Hendrix, DA
   Howald, C
   Hunt, T
   Jungreis, I
   Kay, M
   Khurana, E
   Kokocinski, F
   Leng, J
   Lin, MF
   Loveland, J
   Lu, Z
   Manthravadi, D
   Mariotti, M
   Mudge, J
   Mukherjee, G
   Notredame, C
   Pei, BK
   Rodriguez, JM
   Saunders, G
   Sboner, A
   Searle, S
   Sisu, C
   Snow, C
   Steward, C
   Tanzer, A
   Tapanari, E
   Tress, ML
   van Baren, MJ
   Walters, N
   Washietl, S
   Wilming, L
   Zadissa, A
   Zhang, ZD
   Brent, M
   Haussler, D
   Kellis, M
   Valencia, A
   Gerstein, M
   Reymond, A
   Guigo, R
   Harrow, J
   Hubbard, TJ
   Landt, SG
   Frietze, S
   Abyzov, A
   Addleman, N
   Alexander, RP
   Auerbach, RK
   Balasubramanian, S
   Bettinger, K
   Bhardwaj, N
   Boyle, AP
   Cao, AR
   Cayting, P
   Charos, A
   Cheng, Y
   Cheng, C
   Eastman, C
   Euskirchen, G
   Fleming, JD
   Grubert, F
   Habegger, L
   Hariharan, M
   Harmanci, A
   Iyengar, S
   Jin, VX
   Karczewski, KJ
   Kasowski, M
   Lacroute, P
   Lam, H
   Lamarre-Vincent, N
   Leng, J
   Lian, J
   Lindahl-Allen, M
   Min, RQ
   Miotto, B
   Monahan, H
   Moqtaderi, Z
   Mu, XMJ
   O'Geen, H
   Ouyang, ZQ
   Patacsil, D
   Pei, BK
   Raha, D
   Ramirez, L
   Reed, B
   Rozowsky, J
   Sboner, A
   Shi, MY
   Sisu, C
   Slifer, T
   Witt, H
   Wu, LF
   Xu, XQ
   Yan, KK
   Yang, XQ
   Yip, KY
   Zhang, ZD
   Struhl, K
   Weissman, SM
   Gerstein, M
   Farnham, PJ
   Snyder, M
   Tenenbaum, SA
   Penalva, LO
   Doyle, F
   Karmakar, S
   Landt, SG
   Bhanvadia, RR
   Choudhury, A
   Domanus, M
   Ma, LJ
   Moran, J
   Patacsil, D
   Slifer, T
   Victorsen, A
   Yang, XQ
   Snyder, M
   White, KP
   Auer, T
   Centanin, L
   Eichenlaub, M
   Gruhl, F
   Heermann, S
   Hoeckendorf, B
   Inoue, D
   Kellner, T
   Kirchmaier, S
   Mueller, C
   Reinhardt, R
   Schertel, L
   Schneider, S
   Sinn, R
   Wittbrodt, B
   Wittbrodt, J
   Weng, ZP
   Whitfield, TW
   Wang, J
   Collins, PJ
   Aldred, SF
   Trinklein, ND
   Partridge, EC
   Myers, RM
   Dekker, J
   Jain, G
   Lajoie, BR
   Sanyal, A
   Balasundaram, G
   Bates, DL
   Byron, R
   Canfield, TK
   Diegel, MJ
   Dunn, D
   Ebersol, AK
   Frum, T
   Garg, K
   Gist, E
   Hansen, RS
   Boatman, L
   Haugen, E
   Humbert, R
   Jain, G
   Johnson, AK
   Johnson, EM
   Kutyavin, TV
   Lajoie, BR
   Lee, K
   Lotakis, D
   Maurano, MT
   Neph, SJ
   Neri, FV
   Nguyen, ED
   Qu, HZ
   Reynolds, AP
   Roach, V
   Rynes, E
   Sabo, P
   Sanchez, ME
   Sandstrom, RS
   Sanyal, A
   Shafer, AO
   Stergachis, AB
   Thomas, S
   Thurman, RE
   Vernot, B
   Vierstra, J
   Vong, S
   Wang, H
   Weaver, MA
   Yan, YQ
   Zhang, MH
   Akey, JM
   Bender, M
   Dorschner, MO
   Groudine, M
   MacCoss, MJ
   Navas, P
   Stamatoyannopoulos, G
   Kaul, R
   Dekker, J
   Stamatoyannopoulos, JA
   Dunham, I
   Beal, K
   Brazma, A
   Flicek, P
   Herrero, J
   Johnson, N
   Keefe, D
   Lukk, M
   Luscombe, NM
   Sobral, D
   Vaquerizas, JM
   Wilder, SP
   Batzoglou, S
   Sidow, A
   Hussami, N
   Kyriazopoulou-Panagiotopoulou, S
   Libbrecht, MW
   Schaub, MA
   Kundaje, A
   Hardison, RC
   Miller, W
   Giardine, B
   Harris, RS
   Wu, W
   Bickel, PJ
   Banfai, B
   Boley, NP
   Brown, JB
   Huang, HY
   Li, QH
   Li, JJ
   Noble, WS
   Bilmes, JA
   Buske, OJ
   Hoffman, MM
   Sahu, AD
   Kharchenko, PV
   Park, PJ
   Baker, D
   Taylor, J
   Weng, ZP
   Iyer, S
   Dong, XJ
   Greven, M
   Lin, XY
   Wang, J
   Xi, HLS
   Zhuang, JL
   Gerstein, M
   Alexander, RP
   Balasubramanian, S
   Cheng, C
   Harmanci, A
   Lochovsky, L
   Min, R
   Mu, XMJ
   Rozowsky, J
   Yan, KK
   Yip, KY
   Birney, E
AF Dunham, Ian
   Kundaje, Anshul
   Aldred, Shelley F.
   Collins, Patrick J.
   Davis, CarrieA.
   Doyle, Francis
   Epstein, Charles B.
   Frietze, Seth
   Harrow, Jennifer
   Kaul, Rajinder
   Khatun, Jainab
   Lajoie, Bryan R.
   Landt, Stephen G.
   Lee, Bum-Kyu
   Pauli, Florencia
   Rosenbloom, Kate R.
   Sabo, Peter
   Safi, Alexias
   Sanyal, Amartya
   Shoresh, Noam
   Simon, Jeremy M.
   Song, Lingyun
   Trinklein, Nathan D.
   Altshuler, Robert C.
   Birney, Ewan
   Brown, James B.
   Cheng, Chao
   Djebali, Sarah
   Dong, Xianjun
   Dunham, Ian
   Ernst, Jason
   Furey, Terrence S.
   Gerstein, Mark
   Giardine, Belinda
   Greven, Melissa
   Hardison, Ross C.
   Harris, Robert S.
   Herrero, Javier
   Hoffman, Michael M.
   Iyer, Sowmya
   Kellis, Manolis
   Khatun, Jainab
   Kheradpour, Pouya
   Kundaje, Anshul
   Lassmann, Timo
   Li, Qunhua
   Lin, Xinying
   Marinov, Georgi K.
   Merkel, Angelika
   Mortazavi, Ali
   Parker, Stephen C. J.
   Reddy, Timothy E.
   Rozowsky, Joel
   Schlesinger, Felix
   Thurman, Robert E.
   Wang, Jie
   Ward, Lucas D.
   Whitfield, Troy W.
   Wilder, Steven P.
   Wu, Weisheng
   Xi, Hualin S.
   Yip, Kevin Y.
   Zhuang, Jiali
   Bernstein, Bradley E.
   Birney, Ewan
   Dunham, Ian
   Green, Eric D.
   Gunter, Chris
   Snyder, Michael
   Pazin, Michael J.
   Lowdon, Rebecca F.
   Dillon, Laura A. L.
   Adams, Leslie B.
   Kelly, Caroline J.
   Zhang, Julia
   Wexler, Judith R.
   Green, Eric D.
   Good, Peter J.
   Feingold, Elise A.
   Bernstein, Bradley E.
   Birney, Ewan
   Crawford, Gregory E.
   Dekker, Job
   Elnitski, Laura
   Farnham, Peggy J.
   Gerstein, Mark
   Giddings, Morgan C.
   Gingeras, Thomas R.
   Green, Eric D.
   Guigo, Roderic
   Hardison, Ross C.
   Hubbard, Timothy J.
   Kellis, Manolis
   Kent, W. James
   Lieb, Jason D.
   Margulies, Elliott H.
   Myers, Richard M.
   Snyder, Michael
   Stamatoyannopoulos, John A.
   Tenenbaum, Scott A.
   Weng, Zhiping
   White, Kevin P.
   Wold, Barbara
   Khatun, Jainab
   Yu, Yanbao
   Wrobel, John
   Risk, Brian A.
   Gunawardena, Harsha P.
   Kuiper, Heather C.
   Maier, Christopher W.
   Xie, Ling
   Chen, Xian
   Giddings, Morgan C.
   Bernstein, Bradley E.
   Epstein, Charles B.
   Shoresh, Noam
   Ernst, Jason
   Kheradpour, Pouya
   Mikkelsen, Tarjei S.
   Gillespie, Shawn
   Goren, Alon
   Ram, Oren
   Zhang, Xiaolan
   Wang, Li
   Issner, Robbyn
   Coyne, Michael J.
   Durham, Timothy
   Ku, Manching
   Truong, Thanh
   Ward, Lucas D.
   Altshuler, Robert C.
   Eaton, Matthew L.
   Kellis, Manolis
   Djebali, Sarah
   Davis, Carrie A.
   Merkel, Angelika
   Dobin, Alex
   Lassmann, Timo
   Mortazavi, Ali
   Tanzer, Andrea
   Lagarde, Julien
   Lin, Wei
   Schlesinger, Felix
   Xue, Chenghai
   Marinov, Georgi K.
   Khatun, Jainab
   Williams, Brian A.
   Zaleski, Chris
   Rozowsky, Joel
   Roeder, Maik
   Kokocinski, Felix
   Abdelhamid, Rehab F.
   Alioto, Tyler
   Antoshechkin, Igor
   Baer, Michael T.
   Batut, Philippe
   Bell, Ian
   Bell, Kimberly
   Chakrabortty, Sudipto
   Chen, Xian
   Chrast, Jacqueline
   Curado, Joao
   Derrien, Thomas
   Drenkow, Jorg
   Dumais, Erica
   Dumais, Jackie
   Duttagupta, Radha
   Fastuca, Megan
   Fejes-Toth, Kata
   Ferreira, Pedro
   Foissac, Sylvain
   Fullwood, Melissa J.
   Gao, Hui
   Gonzalez, David
   Gordon, Assaf
   Gunawardena, Harsha P.
   Howald, Cedric
   Jha, Sonali
   Johnson, Rory
   Kapranov, Philipp
   King, Brandon
   Kingswood, Colin
   Li, Guoliang
   Luo, Oscar J.
   Park, Eddie
   Preall, Jonathan B.
   Presaud, Kimberly
   Ribeca, Paolo
   Risk, Brian A.
   Robyr, Daniel
   Ruan, Xiaoan
   Sammeth, Michael
   Sandhu, Kuljeet Singh
   Schaeffer, Lorain
   See, Lei-Hoon
   Shahab, Atif
   Skancke, Jorgen
   Suzuki, Ana Maria
   Takahashi, Hazuki
   Tilgner, Hagen
   Trout, Diane
   Walters, Nathalie
   Wang, Huaien
   Wrobel, John
   Yu, Yanbao
   Hayashizaki, Yoshihide
   Harrow, Jennifer
   Gerstein, Mark
   Hubbard, Timothy J.
   Reymond, Alexandre
   Antonarakis, Stylianos E.
   Hannon, Gregory J.
   Giddings, Morgan C.
   Ruan, Yijun
   Wold, Barbara
   Carninci, Piero
   Guigo, Roderic
   Gingeras, Thomas R.
   Rosenbloom, Kate R.
   Sloan, Cricket A.
   Learned, Katrina
   Malladi, Venkat S.
   Wong, Matthew C.
   Barber, Galtp.
   Cline, Melissa S.
   Dreszer, Timothy R.
   Heitner, Steven G.
   Karolchik, Donna
   Kent, W. James
   Kirkup, Vanessa M.
   Meyer, Laurence R.
   Long, Jeffrey C.
   Maddren, Morgan
   Raney, Brian J.
   Furey, Terrence S.
   Song, Lingyun
   Grasfeder, Linda L.
   Giresi, Paul G.
   Lee, Bum-Kyu
   Battenhouse, Anna
   Sheffield, Nathan C.
   Simon, Jeremy M.
   Showers, Kimberly A.
   Safi, Alexias
   London, Darin
   Bhinge, Akshay A.
   Shestak, Christopher
   Schaner, Matthew R.
   Kim, Seul Ki
   Zhang, Zhuzhu Z.
   Mieczkowski, Piotr A.
   Mieczkowska, Joanna O.
   Liu, Zheng
   McDaniell, Ryan M.
   Ni, Yunyun
   Rashid, Naim U.
   Kim, Min Jae
   Adar, Sheera
   Zhang, Zhancheng
   Wang, Tianyuan
   Winter, Deborah
   Keefe, Damian
   Birney, Ewan
   Iyer, Vishwanath R.
   Lieb, Jason D.
   Crawford, Gregory E.
   Li, Guoliang
   Sandhu, Kuljeet Singh
   Zheng, Meizhen
   Wang, Ping
   Luo, Oscar J.
   Shahab, Atif
   Fullwood, Melissa J.
   Ruan, Xiaoan
   Ruan, Yijun
   Myers, Richard M.
   Pauli, Florencia
   Williams, Brian A.
   Gertz, Jason
   Marinov, Georgi K.
   Reddy, Timothy E.
   Vielmetter, Jost
   Partridge, E. Christopher
   Trout, Diane
   Varley, Katherine E.
   Gasper, Clarke
   Bansal, Anita
   Pepke, Shirley
   Jain, Preti
   Amrhein, Henry
   Bowling, Kevin M.
   Anaya, Michael
   Cross, Marie K.
   King, Brandon
   Muratet, Michael A.
   Antoshechkin, Igor
   Newberry, Kimberly M.
   Mccue, Kenneth
   Nesmith, Amy S.
   Fisher-Aylor, Katherine I.
   Pusey, Barbara
   DeSalvo, Gilberto
   Parker, Stephanie L.
   Balasubramanian, Sreeram
   Davis, Nicholas S.
   Meadows, Sarah K.
   Eggleston, Tracy
   Gunter, Chris
   Newberry, J. Scott
   Levy, Shawn E.
   Absher, Devin M.
   Mortazavi, Ali
   Wong, Wing H.
   Wold, Barbara
   Blow, Matthew J.
   Visel, Axel
   Pennachio, Len A.
   Elnitski, Laura
   Margulies, Elliott H.
   Parker, Stephen C. J.
   Petrykowska, Hanna M.
   Abyzov, Alexej
   Aken, Bronwen
   Barrell, Daniel
   Barson, Gemma
   Berry, Andrew
   Bignell, Alexandra
   Boychenko, Veronika
   Bussotti, Giovanni
   Chrast, Jacqueline
   Davidson, Claire
   Derrien, Thomas
   Despacio-Reyes, Gloria
   Diekhans, Mark
   Ezkurdia, Iakes
   Frankish, Adam
   Gilbert, James
   Gonzalez, Jose Manuel
   Griffiths, Ed
   Harte, Rachel
   Hendrix, David A.
   Howald, Cedric
   Hunt, Toby
   Jungreis, Irwin
   Kay, Mike
   Khurana, Ekta
   Kokocinski, Felix
   Leng, Jing
   Lin, Michael F.
   Loveland, Jane
   Lu, Zhi
   Manthravadi, Deepa
   Mariotti, Marco
   Mudge, Jonathan
   Mukherjee, Gaurab
   Notredame, Cedric
   Pei, Baikang
   Rodriguez, Jose Manuel
   Saunders, Gary
   Sboner, Andrea
   Searle, Stephen
   Sisu, Cristina
   Snow, Catherine
   Steward, Charlie
   Tanzer, Andrea
   Tapanari, Electra
   Tress, Michael L.
   van Baren, Marijke J.
   Walters, Nathalie
   Washietl, Stefan
   Wilming, Laurens
   Zadissa, Amonida
   Zhang, Zhengdong
   Brent, Michael
   Haussler, David
   Kellis, Manolis
   Valencia, Alfonso
   Gerstein, Mark
   Reymond, Alexandre
   Guigo, Roderic
   Harrow, Jennifer
   Hubbard, Timothy J.
   Landt, Stephen G.
   Frietze, Seth
   Abyzov, Alexej
   Addleman, Nick
   Alexander, Roger P.
   Auerbach, Raymond K.
   Balasubramanian, Suganthi
   Bettinger, Keith
   Bhardwaj, Nitin
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   Cao, Alina R.
   Cayting, Philip
   Charos, Alexandra
   Cheng, Yong
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   Eastman, Catharine
   Euskirchen, Ghia
   Fleming, Joseph D.
   Grubert, Fabian
   Habegger, Lukas
   Hariharan, Manoj
   Harmanci, Arif
   Iyengar, Sushma
   Jin, Victor X.
   Karczewski, Konrad J.
   Kasowski, Maya
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   Lamarre-Vincent, Nathan
   Leng, Jing
   Lian, Jin
   Lindahl-Allen, Marianne
   Min, Renqiang
   Miotto, Benoit
   Monahan, Hannah
   Moqtaderi, Zarmik
   Mu, Xinmeng J.
   O'Geen, Henriette
   Ouyang, Zhengqing
   Patacsil, Dorrelyn
   Pei, Baikang
   Raha, Debasish
   Ramirez, Lucia
   Reed, Brian
   Rozowsky, Joel
   Sboner, Andrea
   Shi, Minyi
   Sisu, Cristina
   Slifer, Teri
   Witt, Heather
   Wu, Linfeng
   Xu, Xiaoqin
   Yan, Koon-Kiu
   Yang, Xinqiong
   Yip, Kevin Y.
   Zhang, Zhengdong
   Struhl, Kevin
   Weissman, Sherman M.
   Gerstein, Mark
   Farnham, Peggy J.
   Snyder, Michael
   Tenenbaum, Scott A.
   Penalva, Luiz O.
   Doyle, Francis
   Karmakar, Subhradip
   Landt, Stephen G.
   Bhanvadia, Raj R.
   Choudhury, Alina
   Domanus, Marc
   Ma, Lijia
   Moran, Jennifer
   Patacsil, Dorrelyn
   Slifer, Teri
   Victorsen, Alec
   Yang, Xinqiong
   Snyder, Michael
   White, Kevin P.
   Auer, Thomas
   Centanin, Lazaro
   Eichenlaub, Michael
   Gruhl, Franziska
   Heermann, Stephan
   Hoeckendorf, Burkhard
   Inoue, Daigo
   Kellner, Tanja
   Kirchmaier, Stephan
   Mueller, Claudia
   Reinhardt, Robert
   Schertel, Lea
   Schneider, Stephanie
   Sinn, Rebecca
   Wittbrodt, Beate
   Wittbrodt, Jochen
   Weng, Zhiping
   Whitfield, Troy W.
   Wang, Jie
   Collins, Patrick J.
   Aldred, Shelley F.
   Trinklein, Nathan D.
   Partridge, E. Christopher
   Myers, Richard M.
   Dekker, Job
   Jain, Gaurav
   Lajoie, Bryan R.
   Sanyal, Amartya
   Balasundaram, Gayathri
   Bates, Daniel L.
   Byron, Rachel
   Canfield, Theresa K.
   Diegel, Morgan J.
   Dunn, Douglas
   Ebersol, Abigail K.
   Frum, Tristan
   Garg, Kavita
   Gist, Erica
   Hansen, R. Scott
   Boatman, Lisa
   Haugen, Eric
   Humbert, Richard
   Jain, Gaurav
   Johnson, Audra K.
   Johnson, Ericka M.
   Kutyavin, Tattyana V.
   Lajoie, Bryan R.
   Lee, Kristen
   Lotakis, Dimitra
   Maurano, Matthew T.
   Neph, Shane J.
   Neri, Fiedencio V.
   Nguyen, Eric D.
   Qu, Hongzhu
   Reynolds, Alex P.
   Roach, Vaughn
   Rynes, Eric
   Sabo, Peter
   Sanchez, Minerva E.
   Sandstrom, Richard S.
   Sanyal, Amartya
   Shafer, Anthony O.
   Stergachis, Andrew B.
   Thomas, Sean
   Thurman, Robert E.
   Vernot, Benjamin
   Vierstra, Jeff
   Vong, Shinny
   Wang, Hao
   Weaver, Molly A.
   Yan, Yongqi
   Zhang, Miaohua
   Akey, Joshua M.
   Bender, Michael
   Dorschner, Michael O.
   Groudine, Mark
   MacCoss, Michael J.
   Navas, Patrick
   Stamatoyannopoulos, George
   Kaul, Rajinder
   Dekker, Job
   Stamatoyannopoulos, John A.
   Dunham, Ian
   Beal, Kathryn
   Brazma, Alvis
   Flicek, Paul
   Herrero, Javier
   Johnson, Nathan
   Keefe, Damian
   Lukk, Margus
   Luscombe, Nicholas M.
   Sobral, Daniel
   Vaquerizas, Juan M.
   Wilder, Steven P.
   Batzoglou, Serafim
   Sidow, Arend
   Hussami, Nadine
   Kyriazopoulou-Panagiotopoulou, Sofia
   Libbrecht, Max W.
   Schaub, Marc A.
   Kundaje, Anshul
   Hardison, Ross C.
   Miller, Webb
   Giardine, Belinda
   Harris, Robert S.
   Wu, Weisheng
   Bickel, Peter J.
   Banfai, Balazs
   Boley, Nathan P.
   Brown, James B.
   Huang, Haiyan
   Li, Qunhua
   Li, Jingyi Jessica
   Noble, William Stafford
   Bilmes, Jeffrey A.
   Buske, Orion J.
   Hoffman, Michael M.
   Sahu, Avinash D.
   Kharchenko, Peter V.
   Park, Peter J.
   Baker, Dannon
   Taylor, James
   Weng, Zhiping
   Iyer, Sowmya
   Dong, Xianjun
   Greven, Melissa
   Lin, Xinying
   Wang, Jie
   Xi, Hualin S.
   Zhuang, Jiali
   Gerstein, Mark
   Alexander, Roger P.
   Balasubramanian, Suganthi
   Cheng, Chao
   Harmanci, Arif
   Lochovsky, Lucas
   Min, Renqiang
   Mu, Xinmeng J.
   Rozowsky, Joel
   Yan, Koon-Kiu
   Yip, Kevin Y.
   Birney, Ewan
TI An integrated encyclopedia of DNA elements in the human genome
SO NATURE
LA English
DT Article
ID transcription factor-binding; chromosome conformation capture; human-cells; in-vivo; chromatin; regions; mouse; maps; wide; determinants
AB The human genome encodes the blueprint of life, but the function of the vast majority of its nearly three billion bases is unknown. The Encyclopedia of DNA Elements (ENCODE) project has systematically mapped regions of transcription, transcription factor association, chromatin structure and histone modification. These data enabled us to assign biochemical functions for 80% of the genome, in particular outside of the well-studied protein-coding regions. Many discovered candidate regulatory elements are physically associated with one another and with expressed genes, providing new insights into the mechanisms of gene regulation. The newly identified elements also show a statistical correspondence to sequence variants linked to human disease, and can thereby guide interpretation of this variation. Overall, the project provides new insights into the organization and regulation of our genes and genome, and is an expansive resource of functional annotations for biomedical research.
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   Duke Univ, Dept Pediat, Div Med Genet, Sch Med, Durham, NC 27710 USA.
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C3 European Molecular Biology Laboratory (EMBL); European Bioinformatics Institute; Stanford University; Cold Spring Harbor Laboratory; State University of New York (SUNY) System; University at Albany, SUNY; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; University of Southern California; University Southern California Hospital; Wellcome Trust Sanger Institute; University of Washington; University of Washington Seattle; Boise State University; University of Massachusetts System; University of Massachusetts Worcester; Stanford University; University of Texas System; University of Texas Austin; HudsonAlpha Institute for Biotechnology; University of California System; University of California Santa Cruz; University of Washington; University of Washington Seattle; Duke University; University of North Carolina; University of North Carolina Chapel Hill; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; University of California System; University of California Berkeley; Yale University; Barcelona Institute of Science & Technology; Pompeu Fabra University; Centre de Regulacio Genomica (CRG); University of Massachusetts System; University of Massachusetts Worcester; University of North Carolina; University of North Carolina Chapel Hill; 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; Boston University; RIKEN; California Institute of Technology; University of California System; University of California Irvine; National Institutes of Health (NIH) - USA; NIH National Human Genome Research Institute (NHGRI); University of Massachusetts System; University of Massachusetts Worcester; Howard Hughes Medical Institute; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard Medical School; 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); Duke University; National Institutes of Health (NIH) - USA; NIH National Human Genome Research Institute (NHGRI); Affymetrix; Pompeu Fabra University; University of Washington; University of Washington Seattle; University of Washington; University of Washington Seattle; University of Chicago; California Institute of Technology; University of North Carolina; University of North Carolina Chapel Hill; University of North Carolina School of Medicine; Affymetrix; University of Lausanne; Agency for Science Technology & Research (A*STAR); A*STAR - Genome Institute of Singapore (GIS); Agency for Science Technology & Research (A*STAR); A*STAR - Genome Institute of Singapore (GIS); University of Geneva; University of Geneva; University of North Carolina; University of North Carolina Chapel Hill; University of North Carolina; University of North Carolina Chapel Hill; California Institute of Technology; Stanford University; United States Department of Energy (DOE); University of California System; University of California Berkeley; United States Department of Energy (DOE); Lawrence Berkeley National Laboratory; Centro Nacional de Investigaciones Oncologicas (CNIO); Tsinghua University; Cornell University; Weill Cornell Medicine; Washington University (WUSTL); Yeshiva University; Montefiore Medical Center; Albert Einstein College of Medicine; Howard Hughes Medical Institute; University of California System; University of California Santa Cruz; University of California System; University of California Davis; Yale University; Harvard University; Harvard Medical School; University of Southern California; University System of Ohio; Ohio State University; Yale University; University of Texas System; University of Texas at San Antonio; Ruprecht Karls University Heidelberg; Fred Hutchinson Cancer Center; University of Washington; University of Washington Seattle; Fred Hutchinson Cancer Center; University of Washington; University of Washington Seattle; European Molecular Biology Laboratory (EMBL); European Bioinformatics Institute; European Molecular Biology Laboratory (EMBL); European Bioinformatics Institute; Stanford University; University of Washington; University of Washington Seattle; Harvard University; Harvard Medical School; Emory University; Emory University
RP Dunham, I (corresponding author), European Bioinformat Inst EMBL EBI, Vertebrate Genom Grp, Hinxton CB10 1SD, Cambs, England.
FU NHGRI [U54HG004570, U01HG004695, U54HG004563, U54HG004557, U54HG004555, U41HG004568, U54HG004576, U54HG004558, U54HG004592]; American Recovery and Reinvestment Act (ARRA) funds from the NHGRI [U54HG004570, U54HG004563, U41HG004568, U54HG004592, R01HG003143, RC2HG005591, U01HG004561, RC2HG005679, R01HG003541, R01HG003988]; Intramural Research Program of the NHGRI [ZIAHG200323, ZIAHG200341]; United States Department of Energy Joint Genome Institute, Department of Energy, University of California [DE-AC02-05CH11231];  [R01HG003700];  [R01HG004456-03];  [U01HG004571]; National Cancer Institute [P30CA016086, P30CA045508] Funding Source: NIH RePORTER; National Human Genome Research Institute [R01HG003988, R01HG003143, ZIAHG200323] Funding Source: NIH RePORTER
NR 75
TC 13151
Z9 15282
U1 42
U2 2027
PU NATURE PUBLISHING 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 6
PY 2012
VL 489
IS 7414
BP 57
EP 74
DI 10.1038/nature11247
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 999WW
UT WOS:000308347000039
PM 22955616
DA 2026-03-09
ER

PT J
AU Cassenaer, S
   Laurent, G
AF Cassenaer, Stijn
   Laurent, Gilles
TI Conditional modulation of spike-timing-dependent plasticity for olfactory learning
SO NATURE
LA English
DT Article
ID drosophila mushroom body; synaptic plasticity; odor representations; neurons; memory; dopamine; locust; body; brain; oscillations
AB Mushroom bodies are a well-known site for associative learning in insects. Yet the precise mechanisms that underlie plasticity there and ensure their specificity remain elusive. In locusts, the synapses between the intrinsic mushroom body neurons and their postsynaptic targets obey a Hebbian spike-timing-dependent plasticity (STDP) rule. Although this property homeostatically regulates the timing of mushroom body output, its potential role in associative learning is unknown. Here we show in vivo that pre-post pairing causing STDP can, when followed by the local delivery of a reinforcement-mediating neuromodulator, specify the synapses that will undergo an associative change. At these synapses, and there only, the change is a transformation of the STDP rule itself. These results illustrate the multiple actions of STDP, including a role in associative learning, despite potential temporal dissociation between the pairings that specify synaptic modification and the delivery of reinforcement-mediating neuromodulator signals.
C1 [Cassenaer, Stijn; Laurent, Gilles] CALTECH, Div Biol, Pasadena, CA 91125 USA.
   [Cassenaer, Stijn] CALTECH, Broad Fellows Program Brain Circuitry, Pasadena, CA 91125 USA.
   [Laurent, Gilles] Max Planck Inst Brain Res, D-60528 Frankfurt, Germany.
C3 California Institute of Technology; California Institute of Technology; Max Planck Society
RP Laurent, G (corresponding author), CALTECH, Div Biol, Pasadena, CA 91125 USA.
EM stijn@caltech.edu; gilles.laurent@brain.mpg.de
FU Lawrence Hanson Chair at Caltech; National Institutes on Deafness and other Communication Disorders; Caltech; Office of Naval Research [N00014-07-1-0741, N00014-10-1-0735]; Max Planck Society
NR 45
TC 164
Z9 181
U1 2
U2 68
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD FEB 2
PY 2012
VL 482
IS 7383
BP 47
EP U62
DI 10.1038/nature10776
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 884RN
UT WOS:000299726000032
PM 22278062
DA 2026-03-09
ER

PT J
AU Maercker, M
   Mohamed, S
   Vlemmings, WHT
   Ramstedt, S
   Groenewegen, MAT
   Humphreys, E
   Kerschbaum, F
   Lindqvist, M
   Olofsson, H
   Paladini, C
   Wittkowski, M
   de Gregorio-Monsalvo, I
   Nyman, LA
AF Maercker, M.
   Mohamed, S.
   Vlemmings, W. H. T.
   Ramstedt, S.
   Groenewegen, M. A. T.
   Humphreys, E.
   Kerschbaum, F.
   Lindqvist, M.
   Olofsson, H.
   Paladini, C.
   Wittkowski, M.
   de Gregorio-Monsalvo, I.
   Nyman, L. -A.
TI Unexpectedly large mass loss during the thermal pulse cycle of the red giant star R Sculptoris
SO NATURE
LA English
DT Article
ID detached shells; circumstellar envelopes; high-resolution; branch stars; agb stars; nebulae; origin
AB The asymptotic-giant-branch star R Sculptoris is surrounded by a detached shell of dust and gas(1,2). The shell originates from a thermal pulse during which the star underwent a brief period of increased mass loss(3,4). It has hitherto been impossible to constrain observationally the timescales and mass-loss properties during and after a thermal pulse-parameters that determine the lifetime of the asymptotic giant branch and the amount of elements returned by the star. Here we report observations of CO emission from the circumstellar envelope and shell around R Sculptoris with an angular resolution of 1.3 ''. What was previously thought to be only a thin, spherical shell with a clumpy structure is revealed to also contain a spiral structure. Spiral structures associated with circumstellar envelopes have been previously seen, leading to the conclusion that the systems must be binaries(5-8). Combining the observational data with hydrodynamic simulations, we conclude that R Sculptoris is a binary system that underwent a thermal pulse about 1,800 years ago, lasting approximately 200 years. About 3 x 10(-3) solar masses of material were ejected at a velocity of 14.3 km s(-1) and at a rate around 30 times higher than the pre-pulse mass-loss rate. This shows that about three times more mass was returned to the interstellar medium during and immediately after the pulse than previously thought.
C1 [Maercker, M.; Humphreys, E.; Wittkowski, M.] European So Observ, D-85748 Garching, Germany.
   [Maercker, M.; Ramstedt, S.] Univ Bonn, Argelander Inst Astron, D-53121 Bonn, Germany.
   [Mohamed, S.] S African Astron Observ, ZA-7935 Cape Town, Western Cape, South Africa.
   [Vlemmings, W. H. T.; Lindqvist, M.; Olofsson, H.] Chalmers Univ Technol, Dept Earth & Space Sci, Onsala Space Observ, SE-43992 Onsala, Sweden.
   [Groenewegen, M. A. T.] Royal Observ Belgium, B-1180 Brussels, Belgium.
   [Kerschbaum, F.; Paladini, C.] Univ Vienna, Dept Astrophys, A-1180 Vienna, Austria.
   [de Gregorio-Monsalvo, I.; Nyman, L. -A.] Joint ALMA Observ, Santiago, Chile.
C3 European Southern Observatory; University of Bonn; National Research Foundation - South Africa; South African Astronomical Observatory; Chalmers University of Technology; University of Vienna
RP Maercker, M (corresponding author), European So Observ, Karl Schwarzschild Str 2, D-85748 Garching, Germany.
EM mmaercke@eso.org
FU ADS/JAO.ALMA [2011.0.00131.S]; Austrian Science Fund FWF [P23586-N16, I163-N16, P23006-N16]; Austrian Science Fund (FWF) [P 23586, P 23006] Funding Source: researchfish; Austrian Science Fund (FWF) [P23006] Funding Source: Austrian Science Fund (FWF)
NR 18
TC 148
Z9 167
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 OCT 11
PY 2012
VL 490
IS 7419
BP 232
EP 234
DI 10.1038/nature11511
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 019IY
UT WOS:000309733300043
PM 23060194
DA 2026-03-09
ER

PT J
AU Bohnet, JG
   Chen, ZL
   Weiner, JM
   Meiser, D
   Holland, MJ
   Thompson, JK
AF Bohnet, Justin G.
   Chen, Zilong
   Weiner, Joshua M.
   Meiser, Dominic
   Holland, Murray J.
   Thompson, James K.
TI A steady-state superradiant laser with less than one intracavity photon
SO NATURE
LA English
DT Article
ID atom laser; quantum; linewidth; dynamics
AB The spectral purity of an oscillator is central to many applications, such as detecting gravity waves(1), defining the second(2,3), ground-state cooling and quantum manipulation of nanomechanical objects(4), and quantum computation(5). Recent proposals(6-9) suggest that laser oscillators which use very narrow optical transitions in atoms can be orders of magnitude more spectrally pure than present lasers. Lasers of this high spectral purity are predicted to operate deep in the 'bad-cavity', or superradiant, regime, where the bare atomic linewidth is much less than the cavity linewidth. Here we demonstrate a Raman superradiant laser source in which spontaneous synchronization of more than one million rubidium-87 atomic dipoles is continuously sustained by less than 0.2 photons on average inside the optical cavity. By operating at low intracavity photon number, we demonstrate isolation of the collective atomic dipole from the environment by a factor of more than ten thousand, as characterized by cavity frequency pulling measurements. The emitted light has a frequency linewidth, measured relative to the Raman dressing laser, that is less than that of single-particle decoherence linewidths and more than ten thousand times less than the quantum linewidth limit typically applied to 'good-cavity' optical lasers(10), for which the cavity linewidth is much less than the atomic linewidth. These results demonstrate several key predictions for future superradiant lasers, which could be used to improve the stability of passive atomic clocks(3) and which may lead to new searches for physics beyond the standard model(11,12).
C1 [Bohnet, Justin G.; Chen, Zilong; Weiner, Joshua M.; Meiser, Dominic; Holland, Murray J.; Thompson, James K.] NIST, JILA, Boulder, CO 80309 USA.
   [Bohnet, Justin G.; Chen, Zilong; Weiner, Joshua M.; Meiser, Dominic; Holland, Murray J.; Thompson, James K.] Univ Colorado, Dept Phys, Boulder, CO 80309 USA.
C3 National Institute of Standards & Technology (NIST) - USA; University of Colorado System; University of Colorado Boulder
RP Thompson, JK (corresponding author), NIST, JILA, 440 UCB, Boulder, CO 80309 USA.
EM jkt@jila.colorado.edu
FU NSF PFC; NIST; ARO; DARPA QuASaR through ARO; NSF; NSF GRF; A*STAR Singapore; Direct For Mathematical & Physical Scien; Division Of Physics [1068560] Funding Source: National Science Foundation; Division Of Physics; Direct For Mathematical & Physical Scien [1125844] Funding Source: National Science Foundation
NR 29
TC 409
Z9 464
U1 1
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 5
PY 2012
VL 484
IS 7392
BP 78
EP 81
DI 10.1038/nature10920
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 919QN
UT WOS:000302343400037
PM 22481360
DA 2026-03-09
ER

PT J
AU Lavzin, M
   Rapoport, S
   Polsky, A
   Garion, L
   Schiller, J
AF Lavzin, Maria
   Rapoport, Sophia
   Polsky, Alon
   Garion, Liora
   Schiller, Jackie
TI Nonlinear dendritic processing determines angular tuning of barrel cortex neurons in vivo
SO NATURE
LA English
DT Article
ID primary visual-cortex; 5 pyramidal neurons; basal dendrites; thalamocortical synapses; direction selectivity; somatosensory cortex; nmda spikes; layer-iv; cells; organization
AB Layer 4 neurons in primary sensory cortices receive direct sensory information from the external world(1,2). A general feature of these neurons is their selectivity to specific features of the sensory stimulation(3-5). Various theories try to explain the manner in which these neurons are driven by their incoming sensory information(6-11). In all of these theories neurons are regarded as simple elements summing small biased inputs to create tuned output through the axosomatic amplification mechanism(12). However, the possible role of active dendritic integration(13-15) in further amplifying the sensory responses and sharpening the tuning curves of neurons(16-19) is disregarded. Our findings show that dendrites of layer 4 spiny stellate neurons in the barrel cortex can generate local and global multi-branch N-methyl-D-aspartate (NMDA) spikes, which are the main regenerative events in these dendrites. In turn, these NMDA receptor (NMDAR) regenerative mechanisms can sum supralinearly the coactivated thalamocortical and corticocortical inputs. Using in vivo whole-cell recordings combined with an intracellular NMDAR blocker and membrane hyperpolarization, we show that dendritic NMDAR-dependent regenerative responses contribute substantially to the angular tuning of layer 4 neurons by preferentially amplifying the preferred angular directions over non-preferred angles. Taken together, these findings indicate that dendritic NMDAR regenerative amplification mechanisms contribute markedly to sensory responses and critically determine the tuning of cortical neurons.
C1 [Lavzin, Maria; Rapoport, Sophia; Garion, Liora; Schiller, Jackie] Technion Israel Inst Technol, Rappaport Fac Med, Dept Physiol, IL-31096 Haifa, Israel.
   [Lavzin, Maria; Rapoport, Sophia; Garion, Liora; Schiller, Jackie] Technion Israel Inst Technol, Res Inst, IL-31096 Haifa, Israel.
   [Polsky, Alon] NINDS, Synapt Physiol Sect, NIH, Bethesda, MD 20892 USA.
C3 Technion Israel Institute of Technology; Rappaport Faculty of Medicine; Technion Israel Institute of Technology; National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS)
RP Schiller, J (corresponding author), Technion Israel Inst Technol, Rappaport Fac Med, Dept Physiol, IL-31096 Haifa, Israel.
EM Jackie@tx.technion.ac.il
FU Israel Science Foundation (ISF); Rappaport Foundation
NR 29
TC 200
Z9 238
U1 0
U2 35
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD OCT 18
PY 2012
VL 490
IS 7420
BP 397
EP 401
DI 10.1038/nature11451
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 021XI
UT WOS:000309918500045
PM 22940864
DA 2026-03-09
ER

PT J
AU Seshagiri, S
   Stawiski, EW
   Durinck, S
   Modrusan, Z
   Storm, EE
   Conboy, CB
   Chaudhuri, S
   Guan, YH
   Janakiraman, V
   Jaiswal, BS
   Guillory, J
   Ha, C
   Dijkgraaf, GJP
   Stinson, J
   Gnad, F
   Huntley, MA
   Degenhardt, JD
   Haverty, PM
   Bourgon, R
   Wang, WR
   Koeppen, H
   Gentleman, R
   Starr, TK
   Zhang, ZM
   Largaespada, DA
   Wu, TD
   de Sauvage, FJ
AF Seshagiri, Somasekar
   Stawiski, Eric W.
   Durinck, Steffen
   Modrusan, Zora
   Storm, Elaine E.
   Conboy, Caitlin B.
   Chaudhuri, Subhra
   Guan, Yinghui
   Janakiraman, Vasantharajan
   Jaiswal, Bijay S.
   Guillory, Joseph
   Ha, Connie
   Dijkgraaf, Gerrit J. P.
   Stinson, Jeremy
   Gnad, Florian
   Huntley, Melanie A.
   Degenhardt, Jeremiah D.
   Haverty, Peter M.
   Bourgon, Richard
   Wang, Weiru
   Koeppen, Hartmut
   Gentleman, Robert
   Starr, Timothy K.
   Zhang, Zemin
   Largaespada, David A.
   Wu, Thomas D.
   de Sauvage, Frederic J.
TI Recurrent R-spondin fusions in colon cancer
SO NATURE
LA English
DT Article
ID circular binary segmentation; wnt/beta-catenin; human breast; receptors; lgr5; mutations; algorithm; discovery; alignment; rna
AB Identifying and understanding changes in cancer genomes is essential for the development of targeted therapeutics(1). Here we analyse systematically more than 70 pairs of primary human colon tumours by applying next-generation sequencing to characterize their exomes, transcriptomes and copy-number alterations. We have identified 36,303 protein-altering somatic changes that include several new recurrent mutations in the Wnt pathway gene TCF7L2, chromatin-remodelling genes such as TET2 and TET3 and receptor tyrosine kinases including ERBB3. Our analysis for significantly mutated cancer genes identified 23 candidates, including the cell cycle checkpoint kinase ATM. Copy-number and RNA-seq data analysis identified amplifications and corresponding overexpression of IGF2 in a subset of colon tumours. Furthermore, using RNA-seq data we identified multiple fusion transcripts including recurrent gene fusions involving R-spondin family members RSPO2 and RSPO3 that together occur in 10% of colon tumours. The RSPO fusions were mutually exclusive with APC mutations, indicating that they probably have a role in the activation of Wnt signalling and tumorigenesis. Consistent with this we show that the RSPO fusion proteins were capable of potentiating Wnt signalling. The R-spondin gene fusions and several other gene mutations identified in this study provide new potential opportunities for therapeutic intervention in colon cancer.
C1 [Seshagiri, Somasekar; Stawiski, Eric W.; Durinck, Steffen; Modrusan, Zora; Storm, Elaine E.; Chaudhuri, Subhra; Guan, Yinghui; Janakiraman, Vasantharajan; Jaiswal, Bijay S.; Guillory, Joseph; Ha, Connie; Dijkgraaf, Gerrit J. P.; Stinson, Jeremy; de Sauvage, Frederic J.] Genentech Inc, Dept Mol Biol, San Francisco, CA 94080 USA.
   [Conboy, Caitlin B.; Largaespada, David A.] Univ Minnesota, Masonic Canc Ctr, Dept Genet Cell Biol & Dev, Minneapolis, MN 55455 USA.
   [Gnad, Florian; Huntley, Melanie A.; Degenhardt, Jeremiah D.; Haverty, Peter M.; Bourgon, Richard; Gentleman, Robert; Zhang, Zemin; Wu, Thomas D.] Genentech Inc, Dept Bioinformat & Computat Biol, San Francisco, CA 94080 USA.
   [Wang, Weiru] Genentech Inc, Dept Biol Struct, San Francisco, CA 94080 USA.
   [Koeppen, Hartmut] Genentech Inc, Dept Pathol, San Francisco, CA 94080 USA.
   [Starr, Timothy K.] Univ Minnesota, Masonic Canc Ctr, Dept Obstet Gynecol & Womens Hlth, Minneapolis, MN 55455 USA.
C3 Roche Holding; Genentech; Roche Holding USA; University of Minnesota System; University of Minnesota Twin Cities; Roche Holding; Genentech; Roche Holding USA; Roche Holding; Genentech; Roche Holding USA; Roche Holding; Genentech; Roche Holding USA; University of Minnesota System; University of Minnesota Twin Cities
RP Seshagiri, S (corresponding author), Genentech Inc, Dept Mol Biol, 1 DNA Way, San Francisco, CA 94080 USA.
EM sekar@gene.com; sauvage@gene.com
FU National Institutes of Health [R01-CA134759]; National Cancer Institute [T32CA009138] Funding Source: NIH RePORTER
NR 38
TC 795
Z9 976
U1 0
U2 105
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 30
PY 2012
VL 488
IS 7413
BP 660
EP +
DI 10.1038/nature11282
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 996NC
UT WOS:000308095100057
PM 22895193
DA 2026-03-09
ER

PT J
AU Edgar, RS
   Green, EW
   Zhao, YW
   van Ooijen, G
   Olmedo, M
   Qin, XM
   Xu, Y
   Pan, M
   Valekunja, UK
   Feeney, KA
   Maywood, ES
   Hastings, MH
   Baliga, NS
   Merrow, M
   Millar, AJ
   Johnson, CH
   Kyriacou, CP
   O'Neill, JS
   Reddy, AB
AF Edgar, Rachel S.
   Green, Edward W.
   Zhao, Yuwei
   van Ooijen, Gerben
   Olmedo, Maria
   Qin, Ximing
   Xu, Yao
   Pan, Min
   Valekunja, Utham K.
   Feeney, Kevin A.
   Maywood, Elizabeth S.
   Hastings, Michael H.
   Baliga, Nitin S.
   Merrow, Martha
   Millar, Andrew J.
   Johnson, Carl H.
   Kyriacou, Charalambos P.
   O'Neill, John S.
   Reddy, Akhilesh B.
TI Peroxiredoxins are conserved markers of circadian rhythms
SO NATURE
LA English
DT Article
ID suprachiasmatic nucleus; 2-cys peroxiredoxin; functional-analysis; crystal-structure; redox state; clock; gene; evolution; time; metabolism
AB Cellular life emerged similar to 3.7 billion years ago. With scant exception, terrestrial organisms have evolved under predictable daily cycles owing to the Earth's rotation. The advantage conferred on organisms that anticipate such environmental cycles has driven the evolution of endogenous circadian rhythms that tune internal physiology to external conditions. The molecular phylogeny of mechanisms driving these rhythms has been difficult to dissect because identified clock genes and proteins are not conserved across the domains of life: Bacteria, Archaea and Eukaryota. Here we show that oxidation-reduction cycles of peroxiredoxin proteins constitute a universal marker for circadian rhythms in all domains of life, by characterizing their oscillations in a variety of model organisms. Furthermore, we explore the interconnectivity between these metabolic cycles and transcription-translation feedback loops of the clockwork in each system. Our results suggest an intimate co-evolution of cellular timekeeping with redox homeostatic mechanisms after the Great Oxidation Event similar to 2.5 billion years ago.
C1 [Edgar, Rachel S.; Valekunja, Utham K.; Feeney, Kevin A.; O'Neill, John S.; Reddy, Akhilesh B.] Univ Cambridge, Addenbrookes Hosp, NIHR Biomed Res Ctr, Inst Metab Sci,Metab Res Labs,Dept Clin Neurosci, Cambridge CB2 0QQ, England.
   [Green, Edward W.; Kyriacou, Charalambos P.] Univ Leicester, Dept Genet, Leicester LE1 7RH, Leics, England.
   [Zhao, Yuwei; Qin, Ximing; Xu, Yao; Johnson, Carl H.] Vanderbilt Univ, Dept Biol Sci, Nashville, TN 37235 USA.
   [van Ooijen, Gerben; Millar, Andrew J.] Synthet & Syst Biol SynthSys, Edinburgh EH9 3JD, Midlothian, Scotland.
   [Olmedo, Maria; Merrow, Martha] Univ Groningen, Ctr Life Sci, Dept Mol Chronobiol, NL-9700 CC Groningen, Netherlands.
   [Pan, Min; Baliga, Nitin S.] Inst Syst Biol, Seattle, WA 98109 USA.
   [Maywood, Elizabeth S.; Hastings, Michael H.] MRC, Mol Biol Lab, Cambridge CB2 2QH, England.
   [Millar, Andrew J.] Univ Edinburgh, Sch Biol Sci, Edinburgh EH9 3JR, Midlothian, Scotland.
C3 University of Cambridge; Cambridge University Hospitals NHS Foundation Trust; Addenbrooke's Hospital; University of Leicester; Vanderbilt University; University of Groningen; Institute for Systems Biology (ISB); MRC Laboratory Molecular Biology; University of Edinburgh
RP Reddy, AB (corresponding author), Univ Cambridge, Addenbrookes Hosp, NIHR Biomed Res Ctr, Inst Metab Sci,Metab Res Labs,Dept Clin Neurosci, Cambridge CB2 0QQ, England.
EM jso22@medschl.cam.ac.uk; areddy@cantab.net
FU Wellcome Trust [083643/Z/07/Z, 093734/Z/10/Z]; European Research Council (ERC) [281348]; EMBO; Medical Research Council Centre for Obesity and Related metabolic Disorders (MRC CORD); National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre; European Commission [018741]; Biotechnology and Biological Sciences Research Council (BBSRC) [BB/C006941/1]; Engineering and Physical Sciences Research Council (EPSRC) [BB/D019621]; ENIGMA; US Department of Energy [DE-AC02-05CH11231]; National Institutes of Health (NIH) [P50GM076547, R01GM088595, R01GM067152, R21HL102492]; Netherlands Organisation for Scientific Research (NWO); Dutch Science Foundation VICI; University of Groningen; BBSRC [BB/D019621/1] Funding Source: UKRI; MRC [MC_UP_1201/4, MC_U105170643] Funding Source: UKRI; Wellcome Trust [083643/Z/07/Z] Funding Source: Wellcome Trust; Biotechnology and Biological Sciences Research Council [BB/D019621/1, BB/C006941/1] Funding Source: researchfish; Medical Research Council [MC_UP_1201/4, G0600717, G0600717B, MC_U105170643] Funding Source: researchfish; National Institute of General Medical Sciences [R37GM067152] Funding Source: NIH RePORTER
NR 67
TC 700
Z9 825
U1 4
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 MAY 24
PY 2012
VL 485
IS 7399
BP 459
EP U65
DI 10.1038/nature11088
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 946IH
UT WOS:000304344500034
PM 22622569
DA 2026-03-09
ER

PT J
AU Warden, MR
   Selimbeyoglu, A
   Mirzabekov, JJ
   Lo, M
   Thompson, KR
   Kim, SY
   Adhikari, A
   Tye, KM
   Frank, LM
   Deisseroth, K
AF Warden, Melissa R.
   Selimbeyoglu, Aslihan
   Mirzabekov, Julie J.
   Lo, Maisie
   Thompson, Kimberly R.
   Kim, Sung-Yon
   Adhikari, Avishek
   Tye, Kay M.
   Frank, Loren M.
   Deisseroth, Karl
TI A prefrontal cortex-brainstem neuronal projection that controls response to behavioural challenge
SO NATURE
LA English
DT Article
ID cognitive control; lateral habenula; depression; rat; disorders; stimulation; mood
AB The prefrontal cortex (PFC) is thought to participate in high-level control of the generation of behaviours (including the decision to execute actions(1)); indeed, imaging and lesion studies in human beings have revealed that PFC dysfunction can lead to either impulsive states with increased tendency to initiate action(2), or to amotivational states characterized by symptoms such as reduced activity, hopelessness and depressed mood(3). Considering the opposite valence of these two phenotypes as well as the broad complexity of other tasks attributed to PFC, we sought to elucidate the PFC circuitry that favours effortful behavioural responses to challenging situations. Here we develop and use a quantitative method for the continuous assessment and control of active response to a behavioural challenge, synchronized with single-unit electrophysiology and optogenetics in freely moving rats. In recording from the medial PFC (mPFC), we observed that many neurons were not simply movement-related in their spike-firing patterns but instead were selectively modulated from moment to moment, according to the animal's decision to act in a challenging situation. Surprisingly, we next found that direct activation of principal neurons in the mPFC had no detectable causal effect on this behaviour. We tested whether this behaviour could be causally mediated by only a subclass of mPFC cells defined by specific downstream wiring. Indeed, by leveraging optogenetic projection-targeting to control cells with specific efferent wiring patterns, we found that selective activation of those mPFC cells projecting to the brainstem dorsal raphe nucleus (DRN), a serotonergic nucleus implicated in major depressive disorder(4), induced a profound, rapid and reversible effect on selection of the active behavioural state. These results may be of importance in understanding the neural circuitry underlying normal and pathological patterns of action selection and motivation in behaviour.
C1 [Warden, Melissa R.; Selimbeyoglu, Aslihan; Mirzabekov, Julie J.; Thompson, Kimberly R.; Kim, Sung-Yon; Adhikari, Avishek; Tye, Kay M.; Deisseroth, Karl] Stanford Univ, Dept Bioengn, Stanford, CA 94305 USA.
   [Selimbeyoglu, Aslihan; Kim, Sung-Yon; Deisseroth, Karl] Stanford Univ, Neurosci Program, Stanford, CA 94305 USA.
   [Lo, Maisie] Stanford Univ, Bio X Program, Stanford, CA 94305 USA.
   [Tye, Kay M.] MIT, Dept Brain & Cognit Sci, Picower Inst Learning & Memory, Cambridge, MA 02139 USA.
   [Frank, Loren M.] Univ Calif San Francisco, Dept Physiol, San Francisco, CA 94143 USA.
   [Frank, Loren M.] Univ Calif San Francisco, WM Keck Ctr Integrat Neurosci, San Francisco, CA 94143 USA.
   [Deisseroth, Karl] Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA.
   [Deisseroth, Karl] Stanford Univ, CNC Program, Stanford, CA 94305 USA.
   [Deisseroth, Karl] Stanford Univ, Howard Hughes Med Inst, Stanford, CA 94305 USA.
C3 Stanford University; Stanford University; Stanford University; Massachusetts Institute of Technology (MIT); University of California System; University of California San Francisco; University of California System; University of California San Francisco; Stanford University; Stanford University; Howard Hughes Medical Institute; Stanford University
RP Warden, MR (corresponding author), Stanford Univ, Dept Bioengn, Stanford, CA 94305 USA.
EM mwarden@stanford.edu; deissero@stanford.edu
FU Wiegers Family Fund; NARSAD; Stanford Graduate Fellowship; Samsung Scholarship; Berry Foundation Fellowship; NIMH [1F32MH088010-01]; NIMH; NIDA; DARPA REPAIR Program; Keck Foundation; McKnight Foundation; Yu Foundation; Snyder Foundation; Tarlton Foundation; Alice Woo Foundation; Gatsby Charitable Foundation
NR 27
TC 505
Z9 624
U1 4
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 DEC 20
PY 2012
VL 492
IS 7429
BP 428
EP 432
DI 10.1038/nature11617
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 056KQ
UT WOS:000312488200056
PM 23160494
DA 2026-03-09
ER

PT J
AU Elsässer, SJ
   Huang, HD
   Lewis, PW
   Chin, JW
   Allis, CD
   Patel, DJ
AF Elsaesser, Simon J.
   Huang, Hongda
   Lewis, Peter W.
   Chin, Jason W.
   Allis, C. David
   Patel, Dinshaw J.
TI DAXX envelops a histone H3.3-H4 dimer for H3.3-specific recognition
SO NATURE
LA English
DT Article
ID structural basis; chaperone; atrx; h3; genes
AB Histone chaperones represent a structurally and functionally diverse family of histone-binding proteins that prevent promiscuous interactions of histones before their assembly into chromatin. DAXX is a metazoan histone chaperone specific to the evolutionarily conserved histone variant H3.3. Here we report the crystal structures of the DAXX histone-binding domain with a histone H3.3-H4 dimer, including mutants within DAXX and H3.3, together with in vitro and in vivo functional studies that elucidate the principles underlying H3.3 recognition specificity. Occupying 40% of the histone surface-accessible area, DAXX wraps around the H3.3-H4 dimer, with complex formation accompanied by structural transitions in the H3.3-H4 histone fold. DAXX uses an extended a-helical conformation to compete with major inter-histone, DNA and ASF1 interaction sites. Our structural studies identify recognition elements that read out H3.3-specific residues, and functional studies address the contributions of Gly 90 in H3.3 and Glu 225 in DAXX to chaperone-mediated H3.3 variant recognition specificity.
C1 [Elsaesser, Simon J.; Lewis, Peter W.; Allis, C. David] Rockefeller Univ, Lab Chromatin Biol & Epigenet, New York, NY 10065 USA.
   [Elsaesser, Simon J.; Chin, Jason W.] MRC, Mol Biol Lab, Cambridge CB2 0QH, England.
   [Huang, Hongda; Patel, Dinshaw J.] Mem Sloan Kettering Canc Ctr, Struct Biol Program, New York, NY 10065 USA.
C3 Rockefeller University; MRC Laboratory Molecular Biology; Memorial Sloan Kettering Cancer Center
RP Allis, CD (corresponding author), Rockefeller Univ, Lab Chromatin Biol & Epigenet, New York, NY 10065 USA.
EM alliscd@mail.rockefeller.edu; pated@mskcc.org
FU Center for Synchrotron Biosciences from the National Institute of Biomedical Imaging and Bioengineering (NIBIB) [P30-EB-009998]; National Center for Research Resources of the NIH [1S10RR022321-01, 1S10RR027037-01]; Abby Rockefeller Mauze Trust; Maloris Foundation; STARR Foundation; Rockefeller University; UK Medical Research Council (MRC) [U105181009, UD99999908]; Boehringer Ingelheim Funds fellowship; David Rockefeller Graduate Program; National Cancer Institute [P30CA008748] Funding Source: NIH RePORTER; MRC [MC_U105181009] Funding Source: UKRI; Medical Research Council [MC_U105181009] Funding Source: researchfish
NR 29
TC 202
Z9 247
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 NOV 22
PY 2012
VL 491
IS 7425
BP 560
EP +
DI 10.1038/nature11608
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 040RE
UT WOS:000311339800044
PM 23075851
DA 2026-03-09
ER

PT J
AU Castets, M
   Broutier, L
   Molin, Y
   Brevet, M
   Chazot, G
   Gadot, N
   Paquet, A
   Mazelin, L
   Jarrosson-Wuilleme, L
   Scoazec, JY
   Bernet, A
   Mehlen, P
AF Castets, Marie
   Broutier, Laura
   Molin, Yann
   Brevet, Marie
   Chazot, Guillaume
   Gadot, Nicolas
   Paquet, Armelle
   Mazelin, Laetitia
   Jarrosson-Wuilleme, Loraine
   Scoazec, Jean-Yves
   Bernet, Agnes
   Mehlen, Patrick
TI DCC constrains tumour progression via its dependence receptor activity
SO NATURE
LA English
DT Article
ID colorectal tumorigenesis; cancer; gene; activation; apoptosis; identification; mechanism; model; gaps; mice
AB The role of deleted in colorectal carcinoma (DCC) as a tumour suppressor has been a matter of debate for the past 15 years. DCC gene expression is lost or markedly reduced in the majority of advanced colorectal cancers(1) and, by functioning as a dependence receptor, DCC has been shown to induce apoptosis unless engaged by its ligand, netrin-1 (ref. 2). However, so far no animal model has supported the view that the DCC loss-of-function is causally implicated as predisposing to aggressive cancer development(3). To investigate the role of DCC-induced apoptosis in the control of tumour progression, here we created a mouse model in which the pro-apoptotic activity of DCC is genetically silenced. Although the loss of DCC-induced apoptosis in this mouse model is not associated with a major disorganization of the intestines, it leads to spontaneous intestinal neoplasia at a relatively low frequency. Loss of DCC-induced apoptosis is also associated with an increase in the number and aggressiveness of intestinal tumours in a predisposing APC mutant context, resulting in the development of highly invasive adenocarcinomas. These results demonstrate that DCC functions as a tumour suppressor via its ability to trigger tumour cell apoptosis.
C1 [Castets, Marie; Broutier, Laura; Molin, Yann; Chazot, Guillaume; Mazelin, Laetitia; Jarrosson-Wuilleme, Loraine; Bernet, Agnes; Mehlen, Patrick] Univ Lyon, Apoptosis Canc & Dev Lab, Ctr Leon Berard,Ctr Cancerol Lyon,INSERM,U1052, Equipe Labellise La Ligue,LabEX DEVweCAN,CNRS,UMR, F-69008 Lyon, France.
   [Brevet, Marie; Gadot, Nicolas; Paquet, Armelle; Scoazec, Jean-Yves] Univ Lyon, Hop Edouard Herriot, Endocrine Differentiat Lab,CNRS,UMR5286, Hosp Civils Lyon,Ctr Cancerol Lyon,INSERM,U1052, F-69437 Lyon, France.
C3 Centre National de la Recherche Scientifique (CNRS); UNICANCER; Centre Leon Berard; Universite Lyon 1; Institut National de la Sante et de la Recherche Medicale (Inserm); Universite Lyon 1; Institut National de la Sante et de la Recherche Medicale (Inserm); Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB); CHU Lyon
RP Mehlen, P (corresponding author), Univ Lyon, Apoptosis Canc & Dev Lab, Ctr Leon Berard,Ctr Cancerol Lyon,INSERM,U1052, Equipe Labellise La Ligue,LabEX DEVweCAN,CNRS,UMR, F-69008 Lyon, France.
EM patrick.mehlen@lyon.unicancer.fr
FU Ligue Contre le Cancer; INCA; ANR; IP ApoSys; LabEX DEVweCAN [ANR-10-LABX-61]
NR 18
TC 85
Z9 95
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 FEB 23
PY 2012
VL 482
IS 7386
BP 534
EP U259
DI 10.1038/nature10708
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 898VM
UT WOS:000300770500052
PM 22158121
DA 2026-03-09
ER

PT J
AU Maehara, H
   Shibayama, T
   Notsu, S
   Notsu, Y
   Nagao, T
   Kusaba, S
   Honda, S
   Nogami, D
   Shibata, K
AF Maehara, Hiroyuki
   Shibayama, Takuya
   Notsu, Shota
   Notsu, Yuta
   Nagao, Takashi
   Kusaba, Satoshi
   Honda, Satoshi
   Nogami, Daisaku
   Shibata, Kazunari
TI Superflares on solar-type stars
SO NATURE
LA English
DT Article
ID x-ray flare; stellar; rotation
AB Solar flares are caused by the sudden release of magnetic energy stored near sunspots. They release 10(29) to 10(32) ergs of energy on a timescale of hours(1). Similar flares have been observed on many stars, with larger 'superflares' seen on a variety of stars(2,3), some of which are rapidly rotating(4,5) and some of which are of ordinary solar type(3,6). The small number of superflares observed on solar-type stars has hitherto precluded a detailed study of them. Here we report observations of 365 superflares, including some from slowly rotating solar-type stars, from about 83,000 stars observed over 120 days. Quasi-periodic brightness modulations observed in the solar-type stars suggest that they have much larger starspots than does the Sun. The maximum energy of the flare is not correlated with the stellar rotation period, but the data suggest that superflares occur more frequently on rapidly rotating stars. It has been proposed that hot Jupiters may be important in the generation of superflares on solar-type stars(7), but none have been discovered around the stars that we have studied, indicating that hot Jupiters associated with superflares are rare.
C1 [Maehara, Hiroyuki; Shibayama, Takuya; Notsu, Shota; Notsu, Yuta; Nagao, Takashi; Kusaba, Satoshi; Honda, Satoshi; Nogami, Daisaku; Shibata, Kazunari] Kyoto Univ, Kwasan Observ, Yamashina Ku, Kyoto 6078471, Japan.
   [Maehara, Hiroyuki; Shibayama, Takuya; Notsu, Shota; Notsu, Yuta; Nagao, Takashi; Kusaba, Satoshi; Honda, Satoshi; Nogami, Daisaku; Shibata, Kazunari] Kyoto Univ, Hida Observ, Yamashina Ku, Kyoto 6078471, Japan.
C3 Kyoto University; Kyoto University
RP Maehara, H (corresponding author), Kyoto Univ, Kwasan Observ, Yamashina Ku, 17 Ohmine Cho Kita Kazan, Kyoto 6078471, Japan.
EM maehara@kwasan.kyoto-u.ac.jp
FU NASA Science Mission Directorate; Ministry of Education, Culture, Sports, Science and Technology of Japan; Grants-in-Aid for Scientific Research [23740150] Funding Source: KAKEN
NR 29
TC 495
Z9 544
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 MAY 24
PY 2012
VL 485
IS 7399
BP 478
EP 481
DI 10.1038/nature11063
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 946IH
UT WOS:000304344500037
PM 22622572
DA 2026-03-09
ER

PT J
AU Chen, LY
   Redon, S
   Lingner, J
AF Chen, Liuh-Yow
   Redon, Sophie
   Lingner, Joachim
TI The human CST complex is a terminator of telomerase activity
SO NATURE
LA English
DT Article
ID dna-polymerase-alpha; single-stranded-dna; chromosome ends; replication; protection; extension; interacts; protein; cells; processivity
AB The lengths of human telomeres, which protect chromosome ends from degradation and end fusions(1,2), are crucial determinants of cell lifespan(3). During embryogenesis and in cancer, the telomerase enzyme counteracts telomeric DNA shortening. As shown in cancer cells, human telomerase binds the shelterin component TPP1 at telomeres(4,5) during the S phase of the cell cycle, and adds similar to 60 nucleotides in a single round of extension(6), after which telomerase is turned off by unknown mechanisms. Here we show that the human CST (CTC1, STN1 and TEN1) complex, previously implicated in telomere protection and DNA metabolism(7-11), inhibits telomerase activity through primer sequestration and physical interaction with the protection of telomeres 1 (POT1)-TPP1 telomerase processivity factor(12,13). CST competes with POT1-TPP1 for telomeric DNA, and CST-telomeric-DNA binding increases during late S/G2 phase only on telomerase action, coinciding with telomerase shut-off. Depletion of CST allows excessive telomerase activity, promoting telomere elongation. We propose that through binding of the telomerase-extended telomere, CST limits telomerase action at individual telomeres to approximately one binding and extension event per cell cycle. Our findings define the sequence of events that occur to first enable and then terminate telomerase-mediated telomere elongation.
C1 [Chen, Liuh-Yow; Redon, Sophie; Lingner, Joachim] Ecole Polytech Fed Lausanne, Frontiers Genet Natl Ctr Competence Res, Sch Life Sci, Swiss Inst Expt Canc Res ISREC,Stn 19, CH-1015 Lausanne, Switzerland.
C3 Swiss Federal Institutes of Technology Domain; Ecole Polytechnique Federale de Lausanne; Swiss Institute Experimental Cancer Research; Swiss School of Public Health (SSPH+)
RP Lingner, J (corresponding author), Ecole Polytech Fed Lausanne, Frontiers Genet Natl Ctr Competence Res, Sch Life Sci, Swiss Inst Expt Canc Res ISREC,Stn 19, CH-1015 Lausanne, Switzerland.
EM joachim.lingner@epfl.ch
FU Swiss National Science Foundation; European Research Council [232812]; Swiss Cancer League; EPFL; European Research Council (ERC) [232812] Funding Source: European Research Council (ERC)
NR 22
TC 278
Z9 336
U1 2
U2 52
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD AUG 23
PY 2012
VL 488
IS 7412
BP 540
EP +
DI 10.1038/nature11269
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 992FS
UT WOS:000307761600043
PM 22763445
DA 2026-03-09
ER

PT J
AU Banerji, S
   Cibulskis, K
   Rangel-Escareno, C
   Brown, KK
   Carter, SL
   Frederick, AM
   Lawrence, MS
   Sivachenko, AY
   Sougnez, C
   Zou, LH
   Cortes, ML
   Fernandez-Lopez, JC
   Peng, SY
   Ardlie, KG
   Auclair, D
   Bautista-Piña, V
   Duke, F
   Francis, J
   Jung, J
   Maffuz-Aziz, A
   Onofrio, RC
   Parkin, M
   Pho, NH
   Quintanar-Jurado, V
   Ramos, AH
   Rebollar-Vega, R
   Rodriguez-Cuevas, S
   Romero-Cordoba, SL
   Schumacher, SE
   Stransky, N
   Thompson, KM
   Uribe-Figueroa, L
   Baselga, J
   Beroukhim, R
   Polyak, K
   Sgroi, DC
   Richardson, AL
   Jimenez-Sanchez, G
   Lander, ES
   Gabriel, SB
   Garraway, LA
   Golub, TR
   Melendez-Zajgla, J
   Toker, A
   Getz, G
   Hidalgo-Miranda, A
   Meyerson, M
AF Banerji, Shantanu
   Cibulskis, Kristian
   Rangel-Escareno, Claudia
   Brown, Kristin K.
   Carter, Scott L.
   Frederick, Abbie M.
   Lawrence, Michael S.
   Sivachenko, Andrey Y.
   Sougnez, Carrie
   Zou, Lihua
   Cortes, Maria L.
   Fernandez-Lopez, Juan C.
   Peng, Shouyong
   Ardlie, Kristin G.
   Auclair, Daniel
   Bautista-Pina, Veronica
   Duke, Fujiko
   Francis, Joshua
   Jung, Joonil
   Maffuz-Aziz, Antonio
   Onofrio, Robert C.
   Parkin, Melissa
   Pho, Nam H.
   Quintanar-Jurado, Valeria
   Ramos, Alex H.
   Rebollar-Vega, Rosa
   Rodriguez-Cuevas, Sergio
   Romero-Cordoba, Sandra L.
   Schumacher, Steven E.
   Stransky, Nicolas
   Thompson, Kristin M.
   Uribe-Figueroa, Laura
   Baselga, Jose
   Beroukhim, Rameen
   Polyak, Kornelia
   Sgroi, Dennis C.
   Richardson, Andrea L.
   Jimenez-Sanchez, Gerardo
   Lander, Eric S.
   Gabriel, Stacey B.
   Garraway, Levi A.
   Golub, Todd R.
   Melendez-Zajgla, Jorge
   Toker, Alex
   Getz, Gad
   Hidalgo-Miranda, Alfredo
   Meyerson, Matthew
TI Sequence analysis of mutations and translocations across breast cancer subtypes
SO NATURE
LA English
DT Article
ID high-frequency; pik3ca gene; genome; landscapes; patterns; fusion; domain; kinase
AB Breast carcinoma is the leading cause of cancer-related mortality in women worldwide, with an estimated 1.38 million new cases and 458,000 deaths in 2008 alone(1). This malignancy represents a heterogeneous group of tumours with characteristic molecular features, prognosis and responses to available therapy(2-4). Recurrent somatic alterations in breast cancer have been described, including mutations and copy number alterations, notably ERBB2 amplifications, the first successful therapy target defined by a genomic aberration(5). Previous DNA sequencing studies of breast cancer genomes have revealed additional candidate mutations and gene rearrangements(6-10). Here we report the whole-exome sequences of DNA from 103 human breast cancers of diverse subtypes from patients in Mexico and Vietnam compared to matched-normal DNA, together with whole-genome sequences of 22 breast cancer/normal pairs. Beyond confirming recurrent somatic mutations in PIK3CA(11), TP53(6), AKT1(12), GATA3(13) and MAP3K1(10), we discovered recurrent mutations in the CBFB transcription factor gene and deletions of its partner RUNX1. Furthermore, we have identified a recurrent MAGI3-AKT3 fusion enriched in triple-negative breast cancer lacking oestrogen and progesterone receptors and ERBB2 expression. The MAGI3-AKT3 fusion leads to constitutive activation of AKT kinase, which is abolished by treatment with an ATP-competitive AKT small-molecule inhibitor.
C1 [Banerji, Shantanu; Cibulskis, Kristian; Carter, Scott L.; Frederick, Abbie M.; Lawrence, Michael S.; Sivachenko, Andrey Y.; Sougnez, Carrie; Zou, Lihua; Cortes, Maria L.; Ardlie, Kristin G.; Auclair, Daniel; Duke, Fujiko; Francis, Joshua; Jung, Joonil; Onofrio, Robert C.; Parkin, Melissa; Pho, Nam H.; Ramos, Alex H.; Schumacher, Steven E.; Stransky, Nicolas; Thompson, Kristin M.; Beroukhim, Rameen; Lander, Eric S.; Gabriel, Stacey B.; Garraway, Levi A.; Golub, Todd R.; Getz, Gad; Meyerson, Matthew] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.
   [Banerji, Shantanu; Peng, Shouyong; Schumacher, Steven E.; Beroukhim, Rameen; Polyak, Kornelia; Richardson, Andrea L.; Garraway, Levi A.; Meyerson, Matthew] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA.
   [Banerji, Shantanu; Baselga, Jose; Beroukhim, Rameen; Polyak, Kornelia; Sgroi, Dennis C.; Richardson, Andrea L.; Lander, Eric S.; Garraway, Levi A.; Golub, Todd R.; Toker, Alex; Meyerson, Matthew] Harvard Univ, Sch Med, Boston, MA 02115 USA.
   [Rangel-Escareno, Claudia; Fernandez-Lopez, Juan C.; Quintanar-Jurado, Valeria; Rebollar-Vega, Rosa; Romero-Cordoba, Sandra L.; Uribe-Figueroa, Laura; Jimenez-Sanchez, Gerardo; Melendez-Zajgla, Jorge; Hidalgo-Miranda, Alfredo] Inst Nacl Med Genom, Mexico City 01900, DF, Mexico.
   [Brown, Kristin K.; Toker, Alex] Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA.
   [Bautista-Pina, Veronica; Maffuz-Aziz, Antonio; Rodriguez-Cuevas, Sergio] FUCAM, Inst Enfermedades Mama, Mexico City 04980, DF, Mexico.
   [Baselga, Jose] Massachusetts Gen Hosp, Div Hematol & Oncol, Boston, MA 02114 USA.
   [Beroukhim, Rameen; Meyerson, Matthew] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA.
   [Polyak, Kornelia] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
   [Sgroi, Dennis C.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
   [Richardson, Andrea L.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
   [Lander, Eric S.] MIT, Cambridge, MA 02139 USA.
   [Golub, Todd R.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02215 USA.
   [Golub, Todd R.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA.
C3 Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard Medical School; Instituto Nacional de Medicina Genomica; Harvard University; Harvard University Medical Affiliates; Beth Israel Deaconess Medical Center; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Massachusetts Institute of Technology (MIT); Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Howard Hughes Medical Institute
RP Meyerson, M (corresponding author), Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.
EM atoker@bidmc.harvard.edu; gadgetz@broadinstitute.org; ahidalgo@inmegen.gob.mx; matthew_meyerson@dfci.harvard.edu
FU Carlos Slim Health Institute in Mexico; CancerCare Manitoba; University of Manitoba; John Gavin Post-doctoral Fellowship; Genesis Oncology Trust of New Zealand; Mexican Council of Science and Technology (CONACyT); NIH [CA122099]; Dana-Farber/Harvard SPORE in breast cancer under NCI grant [CA089393]
NR 29
TC 971
Z9 1135
U1 0
U2 176
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 21
PY 2012
VL 486
IS 7403
BP 405
EP 409
DI 10.1038/nature11154
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 961LV
UT WOS:000305466800044
PM 22722202
DA 2026-03-09
ER

PT J
AU Marazzi, I
   Ho, JSY
   Kim, J
   Manicassamy, B
   Dewell, S
   Albrecht, RA
   Seibert, CW
   Schaefer, U
   Jeffrey, KL
   Prinjha, RK
   Lee, K
   García-Sastre, A
   Roeder, RG
   Tarakhovsky, A
AF Marazzi, Ivan
   Ho, Jessica S. Y.
   Kim, Jaehoon
   Manicassamy, Balaji
   Dewell, Scott
   Albrecht, Randy A.
   Seibert, Chris W.
   Schaefer, Uwe
   Jeffrey, Kate L.
   Prinjha, Rab K.
   Lee, Kevin
   Garcia-Sastre, Adolfo
   Roeder, Robert G.
   Tarakhovsky, Alexander
TI Suppression of the antiviral response by an influenza histone mimic
SO NATURE
LA English
DT Article
ID virus ns1 protein; rna-polymerase; paf1 complex; transcription elongation; chromatin; h3; methylation; lysine-4; binding; acetylation
AB Viral infection is commonly associated with virus-driven hijacking of host proteins. Here we describe a novel mechanism by which influenza virus affects host cells through the interaction of influenza non-structural protein 1 (NS1) with the infected cell epigenome. We show that the NS1 protein of influenza A H3N2 subtype possesses a histone-like sequence (histone mimic) that is used by the virus to target the human PAF1 transcription elongation complex (hPAF1C). We demonstrate that binding of NS1 to hPAF1C depends on the NS1 histone mimic and results in suppression of hPAF1C-mediated transcriptional elongation. Furthermore, human PAF1 has a crucial role in the antiviral response. Loss of hPAF1C binding by NS1 attenuates influenza infection, whereas hPAF1C deficiency reduces antiviral gene expression and renders cells more susceptible to viruses. We propose that the histone mimic in NS1 enables the influenza virus to affect inducible gene expression selectively, thus contributing to suppression of the antiviral response.
C1 [Marazzi, Ivan; Ho, Jessica S. Y.; Schaefer, Uwe; Jeffrey, Kate L.; Tarakhovsky, Alexander] Rockefeller Univ, Lab Immune Cell Epigenet & Signaling, New York, NY 10065 USA.
   [Kim, Jaehoon; Roeder, Robert G.] Rockefeller Univ, Biochem & Mol Biol Lab, New York, NY 10065 USA.
   [Manicassamy, Balaji; Albrecht, Randy A.; Seibert, Chris W.; Garcia-Sastre, Adolfo] Mt Sinai Sch Med, Dept Microbiol, New York, NY 10029 USA.
   [Manicassamy, Balaji; Albrecht, Randy A.; Garcia-Sastre, Adolfo] Mt Sinai Sch Med, Global Hlth & Infect Pathogens Inst, New York, NY 10029 USA.
   [Dewell, Scott] Rockefeller Univ, Genom Resource Ctr, New York, NY 10065 USA.
   [Prinjha, Rab K.; Lee, Kevin] GlaxoSmithKline, Immunoinflammat Ctr Excellence Drug Discovery, Epinova DPU, Med Res Ctr, Stevenage SG1 2NY, Herts, England.
   [Garcia-Sastre, Adolfo] Mt Sinai Sch Med, Div Infect Dis, Dept Med, New York, NY 10029 USA.
C3 Rockefeller University; Rockefeller University; Icahn School of Medicine at Mount Sinai; Icahn School of Medicine at Mount Sinai; Rockefeller University; GlaxoSmithKline; Glaxosmithkline United Kingdom; Icahn School of Medicine at Mount Sinai
RP Marazzi, I (corresponding author), Rockefeller Univ, Lab Immune Cell Epigenet & Signaling, 1230 York Ave, New York, NY 10065 USA.
EM imarazzi@rockefeller.edu; tarakho@rockefeller.edu
FU NIH/NIAID [1K99AI095320-01]; NIAID [R01AI046954, U19AI083025, HHSN266200700010C]; CRIP (Center for Research in Influenza Pathogenesis); NIH [CA129325, R01AI068058]; Charles H. Revson Foundation; American Italian Cancer Foundation; Agency for Science, Technology and Research (A*STAR), Singapore; Starr Cancer Consortium
NR 50
TC 259
Z9 293
U1 1
U2 46
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 22
PY 2012
VL 483
IS 7390
BP 428
EP 433
DI 10.1038/nature10892
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 912CC
UT WOS:000301771200035
PM 22419161
DA 2026-03-09
ER

PT J
AU Nodine, MD
   Bartel, DP
AF Nodine, Michael D.
   Bartel, David P.
TI Maternal and paternal genomes contribute equally to the transcriptome of early plant embryos
SO NATURE
LA English
DT Article
ID to-zygotic transition; seed development; gene-expression; early embryogenesis; pattern-formation; arabidopsis; cells; activation; endosperm; chromatin
AB In animals, maternal gene products deposited into eggs regulate embryonic development before activation of the zygotic genome(1). In plants, an analogous period of prolonged maternal control over embryogenesis is thought to occur based on some gene-expression studies(2-6). However, other gene-expression studies and genetic analyses show that some transcripts must derive from the early zygotic genome(7-14), implying that the prevailing model does not fully explain the nature of zygotic genome activation in plants. To determine the maternal, paternal and zygotic contributions to the early embryonic transcriptome, we sequenced the transcripts of hybrid embryos from crosses between two polymorphic inbred lines of Arabidopsis thaliana and used single-nucleotide polymorphisms diagnostic of each parental line to quantify parental contributions. Although some transcripts seemed to be either inherited from primarily one parent or transcribed from imprinted loci, the vast majority of transcripts were produced in near-equal amounts from both maternal and paternal alleles, even during the initial stages of embryogenesis. Results of reporter experiments and analyses of transcripts from genes that are not expressed in sperm and egg indicate early and widespread zygotic transcription. Thus, in contrast to early animal embryogenesis, early plant embryogenesis is mostly under zygotic control.
C1 [Nodine, Michael D.; Bartel, David P.] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA.
   [Nodine, Michael D.; Bartel, David P.] MIT, Howard Hughes Med Inst, Cambridge, MA 02139 USA.
   [Nodine, Michael D.; Bartel, David P.] MIT, Dept Biol, 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)
RP Bartel, DP (corresponding author), Whitehead Inst Biomed Res, 9 Cambridge Ctr, Cambridge, MA 02142 USA.
EM dbartel@wi.mit.edu
FU NIH [GM067031, GM084656]; Austrian Science Fund (FWF) [W1207] Funding Source: Austrian Science Fund (FWF)
NR 30
TC 161
Z9 185
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 FEB 2
PY 2012
VL 482
IS 7383
BP 94
EP U120
DI 10.1038/nature10756
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 884RN
UT WOS:000299726000042
PM 22266940
DA 2026-03-09
ER

PT J
AU Cooke, J
   Sullivan, M
   Gal-Yam, A
   Barton, EJ
   Carlberg, RG
   Ryan-Weber, EV
   Horst, C
   Omori, Y
   Díaz, CG
AF Cooke, Jeff
   Sullivan, Mark
   Gal-Yam, Avishay
   Barton, Elizabeth J.
   Carlberg, Raymond G.
   Ryan-Weber, Emma V.
   Horst, Chuck
   Omori, Yuuki
   Diaz, C. Gonzalo
TI Superluminous supernovae at redshifts of 2.05 and 3.90
SO NATURE
LA English
DT Article
ID lyman-break galaxy; population-iii; ic supernovae; discovery; evolution; explosions; stars; gas
AB A rare class of 'superluminous' supernovae that are about ten or more times more luminous at their peaks than other types of luminous supernova has recently been found at low to intermediate redshifts(1,2). A small subset of these events have luminosities that evolve slowly and result in radiated energies of up to about 10(51) ergs. Therefore, they are probably examples of 'pair-instability' or 'pulsational pair-instability' supernovae with estimated progenitor masses of 100 to 250 times that of the Sun(3-5). These events are exceedingly rare at low redshift, but are expected to be more common at high redshift because the mass distribution of the earliest stars was probably skewed to high values(6,7). Here we report the detection of two superluminous supernovae, at redshifts of 2.05 and 3.90, that have slowly evolving light curves. We estimate the rate of events at redshifts of 2 and 4 to be approximately ten times higher than the rate at low redshift. The extreme luminosities of superluminous supernovae extend the redshift limit for supernova detection using present technology, previously 2.36 (ref. 8), and provide a way of investigating the deaths of the first generation of stars to form after the Big Bang.
C1 [Cooke, Jeff; Ryan-Weber, Emma V.; Diaz, C. Gonzalo] Swinburne Univ Technol, Ctr Astrophys & Supercomp, Hawthorn, Vic 3122, Australia.
   [Sullivan, Mark] Univ Oxford, Dept Phys, Oxford OX1 3RH, England.
   [Gal-Yam, Avishay] Weizmann Inst Sci, Benoziyo Ctr Astrophys, IL-76100 Rehovot, Israel.
   [Barton, Elizabeth J.] Univ Calif Irvine, Dept Phys & Astron, Ctr Cosmol, Irvine, CA 92697 USA.
   [Carlberg, Raymond G.] Univ Toronto, Dept Astron & Astrophys, Toronto, ON M5S 3H4, Canada.
   [Horst, Chuck] San Diego State Univ, Dept Astron, San Diego, CA 92182 USA.
   [Omori, Yuuki] McGill Univ, Dept Phys, Montreal, PQ H2A 2T8, Canada.
C3 Swinburne University of Technology; University of Oxford; Weizmann Institute of Science; University of California System; University of California Irvine; University of Toronto; California State University System; San Diego State University; McGill University
RP Cooke, J (corresponding author), Swinburne Univ Technol, Ctr Astrophys & Supercomp, POB 218,H30, Hawthorn, Vic 3122, Australia.
EM jcooke@astro.swin.edu.au
FU ARC; NSERC; Royal Society; ISF; GIF; Minerva grants; ARCHES award; Lord Seiff of Brimpton Fund; ANSTO AMRFP; Commonwealth of Australia; W. M. Keck Foundation
NR 29
TC 147
Z9 157
U1 0
U2 3
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD NOV 8
PY 2012
VL 491
IS 7423
BP 228
EP 231
DI 10.1038/nature11521
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 033DP
UT WOS:000310774300038
PM 23123848
DA 2026-03-09
ER

PT J
AU Denning, DP
   Hatch, V
   Horvitz, HR
AF Denning, Daniel P.
   Hatch, Victoria
   Horvitz, H. Robert
TI Programmed elimination of cells by caspase-independent cell extrusion in C. elegans
SO NATURE
LA English
DT Article
ID functional genomic analysis; dna-degradation; death; nematode; mechanisms; engulfment; apoptosis; kinase; epithelium; pathway
AB The elimination of unnecessary or defective cells from metazoans occurs during normal development and tissue homeostasis, as well as in response to infection or cellular damage(1). Although many cells are removed through caspase-mediated apoptosis followed by phagocytosis by engulfing cells(2), other mechanisms of cell elimination occur(3), including the extrusion of cells from epithelia through a poorly understood, possibly caspase-independent, process(4). Here we identify a mechanism of cell extrusion that is caspase independent and that can eliminate a subset of the Caenorhabditis elegans cells programmed to die during embryonic development. In wild-type animals, these cells die soon after their generation through caspase-mediated apoptosis. However, in mutants lacking all four C. elegans caspase genes, these cells are eliminated by being extruded from the developing embryo into the extra-embryonic space of the egg. The shed cells show apoptosis-like cytological and morphological characteristics, indicating that apoptosis can occur in the absence of caspases in C. elegans. We describe a kinase pathway required for cell extrusion involving PAR-4, STRD-1 and MOP-25.1/-25.2, the C. elegans homologues of the mammalian tumour-suppressor kinase LKB1 and its binding partners STRAD alpha and MO25 alpha. The AMPK-related kinase PIG-1, a possible target of the PAR-4-STRD-1-MOP-25 kinase complex, is also required for cell shedding. PIG-1 promotes shed-cell detachment by preventing the cell-surface expression of cell-adhesion molecules. Our findings reveal a mechanism for apoptotic cell elimination that is fundamentally distinct from that of canonical programmed cell death.
C1 [Denning, Daniel P.; Hatch, Victoria; Horvitz, H. Robert] MIT, Howard Hughes Med Inst, Cambridge, MA 02139 USA.
   [Denning, Daniel P.; Hatch, Victoria; Horvitz, H. Robert] MIT, Dept Biol, Cambridge, MA 02139 USA.
C3 Massachusetts Institute of Technology (MIT); Howard Hughes Medical Institute; Massachusetts Institute of Technology (MIT)
RP Horvitz, HR (corresponding author), MIT, Howard Hughes Med Inst, Cambridge, MA 02139 USA.
EM horvitz@mit.edu
FU National Institutes of Health National Center for Research Resources (NCRR); Damon Runyon Cancer Research Foundation; Charles A. King Trust
NR 38
TC 55
Z9 74
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 AUG 9
PY 2012
VL 488
IS 7410
BP 226
EP +
DI 10.1038/nature11240
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 985LE
UT WOS:000307267000037
PM 22801495
DA 2026-03-09
ER

PT J
AU Turcan, S
   Rohle, D
   Goenka, A
   Walsh, LA
   Fang, F
   Yilmaz, E
   Campos, C
   Fabius, AWM
   Lu, C
   Ward, PS
   Thompson, CB
   Kaufman, A
   Guryanova, O
   Levine, R
   Heguy, A
   Viale, A
   Morris, LGT
   Huse, JT
   Mellinghoff, IK
   Chan, TA
AF Turcan, Sevin
   Rohle, Daniel
   Goenka, Anuj
   Walsh, Logan A.
   Fang, Fang
   Yilmaz, Emrullah
   Campos, Carl
   Fabius, Armida W. M.
   Lu, Chao
   Ward, Patrick S.
   Thompson, Craig B.
   Kaufman, Andrew
   Guryanova, Olga
   Levine, Ross
   Heguy, Adriana
   Viale, Agnes
   Morris, Luc G. T.
   Huse, Jason T.
   Mellinghoff, Ingo K.
   Chan, Timothy A.
TI IDH1 mutation is sufficient to establish the glioma hypermethylator phenotype
SO NATURE
LA English
DT Article
ID island methylator phenotype; integrated genomic analysis; dna methylation; glioblastoma-multiforme; anaplastic astrocytoma; colorectal-cancer; gene; pathways; identification; abnormality
AB Both genome-wide genetic and epigenetic alterations are fundamentally important for the development of cancers, but the interdependence of these aberrations is poorly understood. Glioblastomas and other cancers with the CpG island methylator phenotype (CIMP) constitute a subset of tumours with extensive epigenomic aberrations and a distinct biology(1-3). Glioma CIMP (G-CIMP) is a powerful determinant of tumour pathogenicity, but the molecular basis of G-CIMP remains unresolved. Here we show that mutation of a single gene, isocitrate dehydrogenase 1 (IDH1), establishes G-CIMP by remodelling the methylome. This remodelling results in reorganization of the methylome and transcriptome. Examination of the epigenome of a large set of intermediate-grade gliomas demonstrates a distinct G-CIMP phenotype that is highly dependent on the presence of IDH mutation. Introduction of mutant IDH1 into primary human astrocytes alters specific histone marks, induces extensive DNA hypermethylation, and reshapes the methylome in a fashion that mirrors the changes observed in G-CIMP-positive lower-grade gliomas. Furthermore, the epigenomic alterations resulting from mutant IDH1 activate key gene expression programs, characterize G-CIMP-positive proneural glioblastomas but not other glioblastomas, and are predictive of improved survival. Our findings demonstrate that IDH mutation is the molecular basis of CIMP in gliomas, provide a framework for understanding oncogenesis in these gliomas, and highlight the interplay between genomic and epigenomic changes in human cancers.
C1 [Turcan, Sevin; Rohle, Daniel; Goenka, Anuj; Walsh, Logan A.; Fang, Fang; Yilmaz, Emrullah; Campos, Carl; Fabius, Armida W. M.; Kaufman, Andrew; Guryanova, Olga; Levine, Ross; Heguy, Adriana; Morris, Luc G. T.; Huse, Jason T.; Mellinghoff, Ingo K.; Chan, Timothy A.] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10065 USA.
   [Rohle, Daniel; Mellinghoff, Ingo K.; Chan, Timothy A.] Weill Cornell Coll Med, New York, NY 10065 USA.
   [Goenka, Anuj; Chan, Timothy A.] Mem Sloan Kettering Canc Ctr, Dept Radiat Oncol, New York, NY 10065 USA.
   [Lu, Chao; Ward, Patrick S.] Univ Penn, Sch Med, Dept Canc Biol, Philadelphia, PA 19104 USA.
   [Morris, Luc G. T.] Mem Sloan Kettering Canc Ctr, Dept Surg, New York, NY 10065 USA.
   [Huse, Jason T.] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10065 USA.
   [Mellinghoff, Ingo K.] Mem Sloan Kettering Canc Ctr, Dept Neurol, New York, NY 10065 USA.
   [Mellinghoff, Ingo K.; Chan, Timothy A.] Mem Sloan Kettering Canc Ctr, Brain Tumor Ctr, New York, NY 10065 USA.
C3 Memorial Sloan Kettering Cancer Center; Cornell University; Memorial Sloan Kettering Cancer Center; University of Pennsylvania; Memorial Sloan Kettering Cancer Center; Memorial Sloan Kettering Cancer Center; Memorial Sloan Kettering Cancer Center; Memorial Sloan Kettering Cancer Center
RP Chan, TA (corresponding author), Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10065 USA.
EM mellingi@mskcc.org; chant@mskcc.org
FU National Institutes of Health [R01CA154767-01]; National Cancer Institute [U54-CA143798]; American Society of Clinical Oncology; Doris Duke Charitable Fund; National Brain Tumor Society; MSKCC Brain Tumor Center; Louis Gerstner Foundation; STARR Cancer Consortium; Sontag Foundation; National Cancer Institute [T32CA009685, P30CA008748] Funding Source: NIH RePORTER
NR 42
TC 1565
Z9 1812
U1 3
U2 211
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 22
PY 2012
VL 483
IS 7390
BP 479
EP U137
DI 10.1038/nature10866
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 912CC
UT WOS:000301771200046
PM 22343889
DA 2026-03-09
ER

PT J
AU Nakano, M
   Shibuya, K
   Okuyama, D
   Hatano, T
   Ono, S
   Kawasaki, M
   Iwasa, Y
   Tokura, Y
AF Nakano, M.
   Shibuya, K.
   Okuyama, D.
   Hatano, T.
   Ono, S.
   Kawasaki, M.
   Iwasa, Y.
   Tokura, Y.
TI Collective bulk carrier delocalization driven by electrostatic surface charge accumulation
SO NATURE
LA English
DT Article
ID electric-field control; metal-insulator-transition; mott transition; phase-transition; vo2; superconductivity; temperature; peierls; hubbard; cobalt
AB In the classic transistor, the number of electric charge carriers-and thus the electrical conductivity-is precisely controlled by external voltage, providing electrical switching capability. This simple but powerful feature is essential for information processing technology, and also provides a platform for fundamental physics research(1-16). As the number of charges essentially determines the electronic phase of a condensed-matter system, transistor operation enables reversible and isothermal changes in the system's state, as successfully demonstrated in electric-field-induced ferromagnetism(2-4) and superconductivity(5-10). However, this effect of the electric field is limited to a channel thickness of nanometres or less, owing to the presence of Thomas-Fermi screening. Here we show that this conventional picture does not apply to a class of materials characterized by inherent collective interactions between electrons and the crystal lattice. We prepared metal-insulator-semiconductor field-effect transistors based on vanadium dioxide-a strongly correlated-material with a thermally driven, first-order metal-insulator transition well above room temperature(17-23)-and found that electrostatic charging at a surface drives all the previously localized charge carriers in the bulk material into motion, leading to the emergence of a three-dimensional metallic ground state. This non-local switching of the electronic state is achieved by applying a voltage of only about one volt. In a voltage-sweep measurement, the first-order nature of the metal-insulator transition provides a non-volatilememory effect, which is operable at room temperature. Our results demonstrate a conceptually new field-effect device, extending the concept of electric-field control to macroscopic phase control.
C1 [Nakano, M.; Shibuya, K.; Okuyama, D.; Hatano, T.; Ono, S.; Kawasaki, M.; Iwasa, Y.; Tokura, Y.] RIKEN Adv Sci Inst, CERG, Wako, Saitama 3510198, Japan.
   [Nakano, M.; Shibuya, K.; Okuyama, D.; Hatano, T.; Ono, S.; Kawasaki, M.; Iwasa, Y.; Tokura, Y.] RIKEN Adv Sci Inst, Cross Correlated Mat Res Grp CMRG, Wako, Saitama 3510198, Japan.
   [Ono, S.] Cent Res Inst Elect Power Ind, Komae, Tokyo 2018511, Japan.
   [Kawasaki, M.; Iwasa, Y.; Tokura, Y.] Univ Tokyo, Quantum Phase Elect Ctr, Tokyo 1138656, Japan.
   [Kawasaki, M.; Iwasa, Y.; Tokura, Y.] Univ Tokyo, Dept Appl Phys, Tokyo 1138656, Japan.
C3 RIKEN; RIKEN; Central Research Institute of Electric Power Industry - Japan; University of Tokyo; University of Tokyo
RP Nakano, M (corresponding author), RIKEN Adv Sci Inst, CERG, Wako, Saitama 3510198, Japan.
EM mnakano@riken.jp; iwasa@ap.t.u-tokyo.ac.jp
FU Japan Society for the Promotion of Science (JSAP) through 'Funding Program for World-Leading Innovative R&D on Science and Technology (FIRST Program)'; RIKEN through the Incentive Research Grant;  [22760016];  [21224009]; Grants-in-Aid for Scientific Research [23684031, 21224009] Funding Source: KAKEN
NR 30
TC 687
Z9 775
U1 9
U2 627
PU NATURE PUBLISHING 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 26
PY 2012
VL 487
IS 7408
BP 459
EP 462
DI 10.1038/nature11296
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 979KD
UT WOS:000306815300033
PM 22837001
DA 2026-03-09
ER

PT J
AU Zeppenfeld, M
   Englert, BGU
   Glöckner, R
   Prehn, A
   Mielenz, M
   Sommer, C
   van Buuren, LD
   Motsch, M
   Rempe, G
AF Zeppenfeld, Martin
   Englert, Barbara G. U.
   Gloeckner, Rosa
   Prehn, Alexander
   Mielenz, Manuel
   Sommer, Christian
   van Buuren, Laurens D.
   Motsch, Michael
   Rempe, Gerhard
TI Sisyphus cooling of electrically trapped polyatomic molecules
SO NATURE
LA English
DT Article
ID polar-molecules; spectroscopy; atoms; gas
AB Polar molecules have a rich internal structure and long-range dipole-dipole interactions, making them useful for quantum-controlled applications and fundamental investigations. Their potential fully unfolds at ultracold temperatures, where various effects are predicted in many-body physics(1,2), quantum information science(3,4), ultracold chemistry(5,6) and physics beyond the standard model(7,8). Whereas a wide range of methods to produce cold molecular ensembles have been developed(9-13), the cooling of polyatomic molecules (that is, with three or more atoms) to ultracold temperatures has seemed intractable. Here we report the experimental realization of optoelectrical cooling(14), a recently proposed cooling and accumulation method for polar molecules. Its key attribute is the removal of a large fraction of a molecule's kinetic energy in each cycle of the cooling sequence via a Sisyphus effect, allowing cooling with only a few repetitions of the dissipative decay process. We demonstrate the potential of optoelectrical cooling by reducing the temperature of about one million CH3F molecules by a factor of 13.5, with the phase-space density increased by a factor of 29 (or a factor of 70 discounting trap losses). In contrast to other cooling mechanisms, our scheme proceeds in a trap, cools in all three dimensions and should work for a large variety of polar molecules. With no fundamental temperature limit anticipated down to the photon-recoil temperature in the nanokelvin range, we expect our method to be able to produce ultracold polyatomic molecules. The low temperatures, large molecule numbers and long trapping times of up to 27 seconds should allow an interaction-dominated regime to be attained, enabling collision studies and investigation of evaporative cooling towards a Bose-Einstein condensate of polyatomic molecules.
C1 [Zeppenfeld, Martin; Englert, Barbara G. U.; Gloeckner, Rosa; Prehn, Alexander; Mielenz, Manuel; Sommer, Christian; van Buuren, Laurens D.; Motsch, Michael; Rempe, Gerhard] Max Planck Inst Quantum Opt, D-85748 Garching, Germany.
C3 Max Planck Society
RP Zeppenfeld, M (corresponding author), Max Planck Inst Quantum Opt, Hans Kopfermann Str 1, D-85748 Garching, Germany.
EM martin.zeppenfeld@mpq.mpg.de
FU Deutsche Forschungsgemeinschaft via the excellence cluster "Munich Centre for Advanced Photonics"
NR 30
TC 172
Z9 201
U1 2
U2 76
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD NOV 22
PY 2012
VL 491
IS 7425
BP 570
EP 573
DI 10.1038/nature11595
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 040RE
UT WOS:000311339800046
PM 23151480
DA 2026-03-09
ER

PT J
AU Krimpenfort, P
   Song, JY
   Proost, N
   Zevenhoven, J
   Jonkers, J
   Berns, A
AF Krimpenfort, Paul
   Song, Ji-Ying
   Proost, Natalie
   Zevenhoven, John
   Jonkers, Jos
   Berns, Anton
TI Deleted in colorectal carcinoma suppresses metastasis in p53-deficient mammary tumours
SO NATURE
LA English
DT Article
ID dcc gene; breast-cancer; transcriptional target; netrin receptor; nervous-system; cell-death; apoptosis; p53; mice; expression
AB Since its discovery in the early 1990s the deleted in colorectal cancer (DCC) gene, located on chromosome 18q21, has been proposed as a tumour suppressor gene as its loss is implicated in the majority of advanced colorectal and many other cancers(1). DCC belongs to the family of netrin 1 receptors, which function as dependence receptors as they control survival or apoptosis depending on ligand binding. However, the role of DCC as a tumour suppressor remains controversial because of the rarity of DCC-specific mutations and the presence of other tumour suppressor genes in the same chromosomal region. Here we show that in a mouse model of mammary carcinoma based on somatic inactivation of p53, additional loss of DCC promotes metastasis formation without affecting the primary tumour phenotype. Furthermore, we demonstrate that in cell cultures derived from p53-deficient mouse mammary tumours DCC expression controls netrin-1-dependent cell survival, providing a mechanistic basis for the enhanced metastatic capacity of tumour cells lacking DCC. Consistent with this idea, in vivo tumour-cell survival is enhanced by DCC loss. Together, our data support the function of DCC as a context-dependent tumour suppressor that limits survival of disseminated tumour cells.
C1 [Krimpenfort, Paul; Proost, Natalie; Zevenhoven, John; Berns, Anton] Netherlands Canc Inst, Div Mol Genet, NL-1066 CX Amsterdam, Netherlands.
   [Jonkers, Jos] Netherlands Canc Inst, Div Mol Biol, NL-1066 CX Amsterdam, Netherlands.
   [Jonkers, Jos] Netherlands Canc Inst, Ctr Biomed Genet, NL-1066 CX Amsterdam, Netherlands.
   [Song, Ji-Ying] Netherlands Canc Inst, Dept Expt Anim Pathol, NL-1066 CX Amsterdam, Netherlands.
   [Berns, Anton] Netherlands Canc Inst, AMC, NL-1066 CX Amsterdam, Netherlands.
C3 Netherlands Cancer Institute; Netherlands Cancer Institute; Netherlands Cancer Institute; Netherlands Cancer Institute; University of Amsterdam; Academic Medical Center Amsterdam; Netherlands Cancer Institute
RP Berns, A (corresponding author), Netherlands Canc Inst, Div Mol Genet, Plesmanlaan 121, NL-1066 CX Amsterdam, Netherlands.
EM a.berns@nki.nl
NR 28
TC 74
Z9 84
U1 0
U2 30
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 23
PY 2012
VL 482
IS 7386
BP 538
EP U134
DI 10.1038/nature10790
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 898VM
UT WOS:000300770500053
PM 22358843
DA 2026-03-09
ER

PT J
AU Lefebvre, JL
   Kostadinov, D
   Chen, WSV
   Maniatis, T
   Sanes, JR
AF Lefebvre, Julie L.
   Kostadinov, Dimitar
   Chen, Weisheng V.
   Maniatis, Tom
   Sanes, Joshua R.
TI Protocadherins mediate dendritic self-avoidance in the mammalian nervous system
SO NATURE
LA English
DT Article
ID retinal ganglion-cells; bax-deficient mice; mouse retina; gamma-protocadherins; transgenic mice; purkinje-cells; amacrine cells; require dscam; axon guidance; expression
AB Dendritic arborizations of many neurons are patterned by a process called self-avoidance, in which branches arising from a single neuron repel each other(1-7). By minimizing gaps and overlaps within the arborization, self-avoidance facilitates complete coverage of a neuron's territory by its neurites(1-3). Remarkably, some neurons that display self-avoidance interact freely with other neurons of the same subtype, implying that they discriminate self from non-self. Here we demonstrate roles for the clustered protocadherins (Pcdhs) in dendritic self-avoidance and self/non-self discrimination. The Pcdh locus encodes 58 related cadherin-like transmembrane proteins, at least some of which exhibit isoform-specific homophilic adhesion in heterologous cells and are expressed stochastically and combinatorially in single neurons(7-11). Deletion of all 22 Pcdh genes in the mouse gamma-subcluster (Pcdhg genes) disrupts self-avoidance of dendrites in retinal starburst amacrine cells (SACs) and cerebellar Purkinje cells. Further genetic analysis of SACs showed that Pcdhg proteins act cell-autonomously during development, and that replacement of the 22 Pcdhg proteins with a single isoform restores self-avoidance. Moreover, expression of the same single isoform in all SACs decreases interactions among dendrites of neighbouring SACs (heteroneuronal interactions). These results suggest that homophilic Pcdhg interactions between sibling neurites (isoneuronal interactions) generate a repulsive signal that leads to self-avoidance. In this model, heteroneuronal interactions are normally permitted because dendrites seldom encounter a matched set of Pcdhg proteins unless they emanate from the same soma. In many respects, our results mirror those reported for Dscam1 (Down syndrome cell adhesion molecule) in Drosophila: this complex gene encodes thousands of recognition molecules that exhibit stochastic expression and isoform-specific interactions, and mediate both self-avoidance and self/non-self discrimination(4-7,12-15). Thus, although insect Dscam and vertebrate Pcdh proteins share no sequence homology, they seem to underlie similar strategies for endowing neurons with distinct molecular identities and patterning their arborizations.
C1 [Lefebvre, Julie L.; Kostadinov, Dimitar; Sanes, Joshua R.] Harvard Univ, Ctr Brain Sci, Cambridge, MA 02138 USA.
   [Lefebvre, Julie L.; Kostadinov, Dimitar; Sanes, Joshua R.] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA.
   [Chen, Weisheng V.; Maniatis, Tom] Columbia Univ, Med Ctr, Dept Biochem & Mol Biophys, New York, NY 10032 USA.
C3 Harvard University; Harvard University; Columbia University
RP Sanes, JR (corresponding author), Harvard Univ, Ctr Brain Sci, 52 Oxford St, Cambridge, MA 02138 USA.
EM sanesj@mcb.harvard.edu
FU NIH [R01NS029169, R01EY022073, R01NS043915]; NARSAD
NR 50
TC 343
Z9 446
U1 0
U2 58
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD AUG 23
PY 2012
VL 488
IS 7412
BP 517
EP +
DI 10.1038/nature11305
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 992FS
UT WOS:000307761600038
PM 22842903
DA 2026-03-09
ER

PT J
AU Ipsaro, JJ
   Haase, AD
   Knott, SR
   Joshua-Tor, L
   Hannon, GJ
AF Ipsaro, Jonathan J.
   Haase, Astrid D.
   Knott, Simon R.
   Joshua-Tor, Leemor
   Hannon, Gregory J.
TI The structural biochemistry of Zucchini implicates it as a nuclease in piRNA biogenesis
SO NATURE
LA English
DT Article
ID small rnas; nuage formation; messenger-rna; protein; recognition; mechanism; elements; mitopld; pathway
AB PIWI-family proteins and their associated small RNAs (piRNAs) act in an evolutionarily conserved innate immune mechanism to provide essential protection for germ-cell genomes against the activity of mobile genetic elements(1). piRNA populations comprise a molecular definition of transposons, which permits them to distinguish transposons from host genes and selectively silence them. piRNAs can be generated in two distinct ways, forming either primary or secondary piRNAs. Primary piRNAs come from discrete genomic loci, termed piRNA clusters, and seem to be derived from long, single-stranded precursors(2). The biogenesis of primary piRNAs involves at least two nucleolytic steps. An unknown enzyme cleaves piRNA cluster transcripts to generate monophosphorylated piRNA 5' ends. piRNA 3' ends are probably formed by exonucleolytic trimming, after a piRNA precursor is loaded into its PIWI partner(1,3). Secondary piRNAs arise during the adaptive 'ping-pong' cycle, with their 5' termini being formed by the activity of PIWIs themselves(2,4). A number of proteins have been implicated genetically in primary piRNA biogenesis. One of these, Drosophila melanogaster Zucchini, is a member of the phospholipase-D family of phosphodiesterases, which includes both phospholipases and nucleases(5-7). Here we produced a dimeric, soluble fragment of the mouse Zucchini homologue (mZuc; also known as PLD6) and show that it possesses single-strand-specific nuclease activity. A crystal structure of mZuc at 1.75 angstrom resolution indicates greater architectural similarity to phospholipase-D family nucleases than to phospholipases. Together, our data suggest that the Zucchini proteins act in primary piRNA biogenesis as nucleases, perhaps generating the 5' ends of primary piRNAs.
C1 [Ipsaro, Jonathan J.; Haase, Astrid D.; Knott, Simon R.; Joshua-Tor, Leemor; Hannon, Gregory J.] Cold Spring Harbor Lab, Howard Hughes Med Inst, Cold Spring Harbor, NY 11724 USA.
   [Ipsaro, Jonathan J.; Joshua-Tor, Leemor] Cold Spring Harbor Lab, WM Keck Struct Biol Lab, Cold Spring Harbor, NY 11724 USA.
C3 Howard Hughes Medical Institute; Cold Spring Harbor Laboratory; Cold Spring Harbor Laboratory
RP Hannon, GJ (corresponding author), Cold Spring Harbor Lab, Howard Hughes Med Inst, Cold Spring Harbor, NY 11724 USA.
EM leemor@cshl.edu; hannon@cshl.edu
FU National Cancer Institute Cancer Center Support Grant [CA045508]; Department of Energy, Office of Basic Energy Sciences; Harvey L. Karp award; Ruth L. Kirschstein National Research Service Awards National Institutes of Health (NIH) [F32GM97888]; NIH [R01GM062534]; National Cancer Institute [P30CA045508] Funding Source: NIH RePORTER
NR 44
TC 259
Z9 310
U1 0
U2 40
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 8
PY 2012
VL 491
IS 7423
BP 279
EP U151
DI 10.1038/nature11502
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 033DP
UT WOS:000310774300049
PM 23064227
DA 2026-03-09
ER

PT J
AU Kong, A
   Frigge, ML
   Masson, G
   Besenbacher, S
   Sulem, P
   Magnusson, G
   Gudjonsson, SA
   Sigurdsson, A
   Jonasdottir, A
   Jonasdottir, A
   Wong, WSW
   Sigurdsson, G
   Walters, GB
   Steinberg, S
   Helgason, H
   Thorleifsson, G
   Gudbjartsson, DF
   Helgason, A
   Magnusson, OT
   Thorsteinsdottir, U
   Stefansson, K
AF Kong, Augustine
   Frigge, Michael L.
   Masson, Gisli
   Besenbacher, Soren
   Sulem, Patrick
   Magnusson, Gisli
   Gudjonsson, Sigurjon A.
   Sigurdsson, Asgeir
   Jonasdottir, Aslaug
   Jonasdottir, Adalbjorg
   Wong, Wendy S. W.
   Sigurdsson, Gunnar
   Walters, G. Bragi
   Steinberg, Stacy
   Helgason, Hannes
   Thorleifsson, Gudmar
   Gudbjartsson, Daniel F.
   Helgason, Agnar
   Magnusson, Olafur Th.
   Thorsteinsdottir, Unnur
   Stefansson, Kari
TI Rate of de novo mutations and the importance of father's age to disease risk
SO NATURE
LA English
DT Article
ID autism spectrum disorders; schizophrenia; humans; consequences; nucleotide; patterns; nrxn1
AB Mutations generate sequence diversity and provide a substrate for selection. The rate of de novo mutations is therefore of major importance to evolution. Here we conduct a study of genome-wide mutation rates by sequencing the entire genomes of 78 Icelandic parent-offspring trios at high coverage. We show that in our samples, with an average father's age of 29.7, the average de novo mutation rate is 1.20 x 10(-8) per nucleotide per generation. Most notably, the diversity in mutation rate of single nucleotide polymorphisms is dominated by the age of the father at conception of the child. The effect is an increase of about two mutations per year. An exponential model estimates paternal mutations doubling every 16.5 years. After accounting for random Poisson variation, father's age is estimated to explain nearly all of the remaining variation in the de novo mutation counts. These observations shed light on the importance of the father's age on the risk of diseases such as schizophrenia and autism.
C1 [Kong, Augustine; Frigge, Michael L.; Masson, Gisli; Besenbacher, Soren; Sulem, Patrick; Magnusson, Gisli; Gudjonsson, Sigurjon A.; Sigurdsson, Asgeir; Jonasdottir, Aslaug; Jonasdottir, Adalbjorg; Sigurdsson, Gunnar; Walters, G. Bragi; Steinberg, Stacy; Helgason, Hannes; Thorleifsson, Gudmar; Gudbjartsson, Daniel F.; Helgason, Agnar; Magnusson, Olafur Th.; Thorsteinsdottir, Unnur; Stefansson, Kari] deCODE Genet, IS-101 Reykjavik, Iceland.
   [Besenbacher, Soren] Aarhus Univ, Bioinformat Res Ctr, DK-8000 Aarhus, Denmark.
   [Wong, Wendy S. W.] Illumina Cambridge Ltd, Saffron Walden CB10 1XL, Essex, England.
   [Thorsteinsdottir, Unnur; Stefansson, Kari] Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland.
C3 Decode Genetics; Aarhus University; Illumina; University of Iceland
RP Kong, A (corresponding author), deCODE Genet, Sturlugata 8, IS-101 Reykjavik, Iceland.
EM kong@decode.is; kari.stefansson@decode.is
FU National Institutes of Health [MH071425]; European Community [HEALTH-F2-2009-223423, IAPP-MC-251592]; European Community IMI grant EU-AIMS [115300]
NR 27
TC 1518
Z9 1797
U1 3
U2 394
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD AUG 23
PY 2012
VL 488
IS 7412
BP 471
EP 475
DI 10.1038/nature11396
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 992FS
UT WOS:000307761600028
PM 22914163
DA 2026-03-09
ER

PT J
AU Kim, B
   Eggel, A
   Tarchevskaya, SS
   Vogel, M
   Prinz, H
   Jardetzky, TS
AF Kim, Beomkyu
   Eggel, Alexander
   Tarchevskaya, Svetlana S.
   Vogel, Monique
   Prinz, Heino
   Jardetzky, Theodore S.
TI Accelerated disassembly of IgE-receptor complexes by a disruptive macromolecular inhibitor
SO NATURE
LA English
DT Article
ID conformational flexibility; dissociation rate; crystal-structure; fc; reveals; ligands; binding; site
AB IgE antibodies bind the high-affinity IgE Fc receptor (Fc epsilon RI), found primarily on mast cells and basophils, and trigger inflammatory cascades of the allergic response(1,2). Inhibitors of IgE-Fc epsilon RI binding have been identified and an anti-IgE therapeutic antibody (omalizumab) is used to treat severe allergic asthma(3,4). However, preformed IgE-Fc epsilon RI complexes that prime cells before allergen exposure dissociate extremely slowly(5) and cannot be disrupted by strictly competitive inhibitors. IgE-Fc conformational flexibility indicated that inhibition could be mediated by allosteric or other non-classical mechanisms(6-8). Here we demonstrate that an engineered protein inhibitor, DARPin E2_79 (refs 9-11), acts through a non-classical inhibition mechanism, not only blocking IgE-Fc epsilon RI interactions, but actively stimulating the dissociation of preformed ligand-receptor complexes. The structure of the E2_79-IgE-Fc(3-4) complex predicts the presence of two non-equivalent E2_79 sites in the asymmetric IgE-Fc epsilon RI complex, with site 1 distant from the receptor and site 2 exhibiting partial steric overlap. Although the structure is indicative of an allosteric inhibition mechanism, mutational studies and quantitative kinetic modelling indicate that E2_79 acts through a facilitated dissociation mechanism at site 2 alone. These results demonstrate that high-affinity IgE-Fc epsilon RI complexes can be actively dissociated to block the allergic response and suggest that protein-protein complexes may be more generally amenable to active disruption by macromolecular inhibitors.
C1 [Kim, Beomkyu; Tarchevskaya, Svetlana S.; Jardetzky, Theodore S.] Stanford Univ, Sch Med, Dept Biol Struct, Stanford, CA 94305 USA.
   [Eggel, Alexander; Vogel, Monique] Univ Bern, Inst Immunol, CH-3010 Bern, Switzerland.
   [Prinz, Heino] Max Planck Inst Mol Physiol, D-44227 Dortmund, Germany.
C3 Stanford University; University of Bern; Max Planck Society
RP Jardetzky, TS (corresponding author), Stanford Univ, Sch Med, Dept Biol Struct, Stanford, CA 94305 USA.
EM tjardetz@stanford.edu
FU NIH [AI-18939]; American Asthma Foundation; Swiss National Science Foundation [310030_127350]; Swiss National Science Foundation (SNF) [310030_127350] Funding Source: Swiss National Science Foundation (SNF)
NR 34
TC 90
Z9 99
U1 1
U2 53
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 22
PY 2012
VL 491
IS 7425
BP 613
EP +
DI 10.1038/nature11546
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 040RE
UT WOS:000311339800056
PM 23103871
DA 2026-03-09
ER

PT J
AU Andreu-Agullo, C
   Maurin, T
   Thompson, CB
   Lai, EC
AF Andreu-Agullo, Celia
   Maurin, Thomas
   Thompson, Craig B.
   Lai, Eric C.
TI Ars2 maintains neural stem-cell identity through direct transcriptional activation of Sox2
SO NATURE
LA English
DT Article
ID cap-binding complex; self-renewal; rna interference; analysis reveals; transgenic mice; expression; serrate; brain; proliferation; arabidopsis
AB Fundamental questions remain unanswered about the transcriptional networks that control the identity and self-renewal of neural stem cells (NSCs), a specialized subset of astroglial cells that are endowed with stem properties and neurogenic capacity. Here we report that the zinc finger protein Ars2 (arsenite-resistance protein 2; also known as Srrt) is expressed by adult NSCs from the subventricular zone (SVZ) of mice, and that selective knockdown of Ars2 in cells expressing glial fibrillary acidic protein within the adult SVZ depletes the number of NSCs and their neurogenic capacity. These phenotypes are recapitulated in the postnatal SVZ of hGFAP-cre:: Ars2(fl/fl) conditional knockout mice, but are more severe. Ex vivo assays show that Ars2 is necessary and sufficient to promote NSC self-renewal, and that it does so by positively regulating the expression of Sox2. Although plant(1-3) and animal(4,5) orthologues of Ars2 are known for their conserved roles in microRNA biogenesis, we unexpectedly observed that Ars2 retains its capacity to promote self-renewal in Drosha and Dicer1 knockout NSCs. Instead, chromatin immunoprecipitation revealed that Ars2 binds a specific region within the 6-kilobase NSC enhancer of Sox2. This association is RNA-independent, and the region that is bound is required for Ars2-mediated activation of Sox2. We used gel-shift analysis to refine the Sox2 region bound by Ars2 to a specific conserved DNA sequence. The importance of Sox2 as a critical downstream effector is shown by its ability to restore the self-renewal and multipotency defects of Ars2 knockout NSCs. Our findings reveal Ars2 as a new transcription factor that controls the multipotent progenitor state of NSCs through direct activation of the pluripotency factor Sox2.
C1 [Andreu-Agullo, Celia; Maurin, Thomas; Lai, Eric C.] Sloan Kettering Inst, Dept Dev Biol, New York, NY 10065 USA.
   [Thompson, Craig B.] Sloan Kettering Inst, Dept Canc Biol & Genet, New York, NY 10065 USA.
C3 Memorial Sloan Kettering Cancer Center; Memorial Sloan Kettering Cancer Center
RP Andreu-Agullo, C (corresponding author), Sloan Kettering Inst, Dept Dev Biol, 1275 York Ave,Box 252, New York, NY 10065 USA.
EM andreuac@mskcc.org; laie@mskcc.org
FU Burroughs Wellcome Fund; Starr Cancer Consortium [I3-A139]; NIH [R01-GM083300]; EMBO [ALTF 718-2008]; NYSTEM Fellowship; National Institute of General Medical Sciences [R01GM083300] Funding Source: NIH RePORTER
NR 33
TC 72
Z9 84
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 JAN 12
PY 2012
VL 481
IS 7380
BP 195
EP +
DI 10.1038/nature10712
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 874TO
UT WOS:000298981200038
PM 22198669
DA 2026-03-09
ER

PT J
AU Hinke, CB
   Böhmer, M
   Boutachkov, P
   Faestermann, T
   Geissel, H
   Gerl, J
   Gernhäuser, R
   Górska, M
   Gottardo, A
   Grawe, H
   Grebosz, JL
   Krücken, R
   Kurz, N
   Liu, Z
   Maier, L
   Nowacki, F
   Pietri, S
   Podolyák, Z
   Sieja, K
   Steiger, K
   Straub, K
   Weick, H
   Wollersheim, HJ
   Woods, PJ
   Al-Dahan, N
   Alkhomashi, N
   Ataç, A
   Blazhev, A
   Braun, NF
   Celikovic, IT
   Davinson, T
   Dillmann, I
   Domingo-Pardo, C
   Doornenbal, PC
   de France, G
   Farrelly, GF
   Farinon, F
   Goel, N
   Habermann, TC
   Hoischen, R
   Janik, R
   Karny, M
   Kaskas, A
   Kojouharov, IM
   Kröll, T
   Litvinov, Y
   Myalski, S
   Nebel, F
   Nishimura, S
   Nociforo, C
   Nyberg, J
   Parikh, AR
   Procházka, A
   Regan, PH
   Rigollet, C
   Schaffner, H
   Scheidenberger, C
   Schwertel, S
   Söderström, PA
   Steer, SJ
   Stolz, A
   Strmen, P
AF Hinke, C. B.
   Boehmer, M.
   Boutachkov, P.
   Faestermann, T.
   Geissel, H.
   Gerl, J.
   Gernhaeuser, R.
   Gorska, M.
   Gottardo, A.
   Grawe, H.
   Grebosz, J. L.
   Kruecken, R.
   Kurz, N.
   Liu, Z.
   Maier, L.
   Nowacki, F.
   Pietri, S.
   Podolyak, Zs
   Sieja, K.
   Steiger, K.
   Straub, K.
   Weick, H.
   Wollersheim, H. -J.
   Woods, P. J.
   Al-Dahan, N.
   Alkhomashi, N.
   Atac, A.
   Blazhev, A.
   Braun, N. F.
   Celikovic, I. T.
   Davinson, T.
   Dillmann, I.
   Domingo-Pardo, C.
   Doornenbal, P. C.
   de France, G.
   Farrelly, G. F.
   Farinon, F.
   Goel, N.
   Habermann, T. C.
   Hoischen, R.
   Janik, R.
   Karny, M.
   Kaskas, A.
   Kojouharov, I. M.
   Kroell, Th
   Litvinov, Y.
   Myalski, S.
   Nebel, F.
   Nishimura, S.
   Nociforo, C.
   Nyberg, J.
   Parikh, A. R.
   Prochazka, A.
   Regan, P. H.
   Rigollet, C.
   Schaffner, H.
   Scheidenberger, C.
   Schwertel, S.
   Soederstroem, P. -A.
   Steer, S. J.
   Stolz, A.
   Strmen, P.
TI Superallowed Gamow-Teller decay of the doubly magic nucleus 100Sn
SO NATURE
LA English
DT Article
ID shell-model; beta-decay; identification; isomer
AB The shell structure of atomic nuclei is associated with 'magic numbers' and originates in the nearly independent motion of neutrons and protons in a mean potential generated by all nucleons. During beta(+)-decay, a proton transforms into a neutron in a previously not fully occupied orbital, emitting a positron-neutrino pair with either parallel or antiparallel spins, in a Gamow-Teller or Fermi transition, respectively. The transition probability, or strength, of a Gamow-Teller transition depends sensitively on the underlying shell structure and is usually distributed among many states in the neighbouring nucleus. Here we report measurements of the half-life and decay energy for the decay of Sn-100, the heaviest doubly magic nucleus with equal numbers of protons and neutrons. In the beta-decay of Sn-100, a large fraction of the strength is observable because of the large decay energy. We determine the largest Gamow-Teller strength so far measured in allowed nuclear beta-decay, establishing the 'superallowed' nature of this Gamow-Teller transition. The large strength and the low-energy states in the daughter nucleus, In-100, are well reproduced by modern, large-scale shell model calculations.
C1 [Hinke, C. B.; Boehmer, M.; Faestermann, T.; Gernhaeuser, R.; Kruecken, R.; Maier, L.; Steiger, K.; Straub, K.; Nebel, F.; Schwertel, S.] Tech Univ Munich, Phys Dept E12, D-85748 Garching, Germany.
   [Boutachkov, P.; Geissel, H.; Gerl, J.; Gorska, M.; Grawe, H.; Kurz, N.; Pietri, S.; Weick, H.; Wollersheim, H. -J.; Dillmann, I.; Farinon, F.; Goel, N.; Habermann, T. C.; Hoischen, R.; Kojouharov, I. M.; Litvinov, Y.; Nociforo, C.; Prochazka, A.; Schaffner, H.; Scheidenberger, C.] GSI Helmholtzzentrum Schwerionenforsch GmbH, D-64291 Darmstadt, Germany.
   [Gottardo, A.] Ist Nazl Fis Nucl, Lab Nazl Legnaro, I-35020 Legnaro, Italy.
   [Grebosz, J. L.; Myalski, S.] Henryk Niewodniczanski Inst Nucl Phys IFJ PAN, PL-31342 Krakow, Poland.
   [Kruecken, R.] TRIUMF, Vancouver, BC V6T 2A3, Canada.
   [Liu, Z.; Woods, P. J.; Davinson, T.] Univ Edinburgh, Sch Phys & Astron, Edinburgh EH9 3JZ, Midlothian, Scotland.
   [Nowacki, F.; Sieja, K.] Univ Strasbourg, IPHC, F-67037 Strasbourg, France.
   [Podolyak, Zs; Al-Dahan, N.; Alkhomashi, N.; Farrelly, G. F.; Regan, P. H.; Steer, S. J.] Univ Surrey, Dept Phys, Guildford GU2 7XH, Surrey, England.
   [Atac, A.; Kaskas, A.] Ankara Univ, Dept Phys, Fac Sci, TR-06100 Ankara, Turkey.
   [Blazhev, A.; Braun, N. F.] Univ Cologne, Inst Nucl Phys, D-50937 Cologne, Germany.
   [Celikovic, I. T.] Univ Belgrade, Inst Vinca, Belgrade 11000, Serbia.
   [Domingo-Pardo, C.] Univ Valencia, IFIC, CSIC, E-46071 Valencia, Spain.
   [Doornenbal, P. C.; Nishimura, S.; Soederstroem, P. -A.] RIKEN, Nishina Ctr, Wako, Saitama 3510198, Japan.
   [de France, G.] CEA DSM CNRS IN2P3, Grand Accelerateur Natl Ions Lourds, F-14076 Caen, France.
   [Janik, R.; Strmen, P.] Comenius Univ, Bratislava 81806 16, Slovakia.
   [Karny, M.] Univ Warsaw, Inst Expt Phys, PL-00681 Warsaw, Poland.
   [Kroell, Th] Tech Univ Darmstadt, Inst Kernphys, D-64289 Darmstadt, Germany.
   [Nyberg, J.] Uppsala Univ, Dept Phys & Astron, SE-75120 Uppsala, Sweden.
   [Parikh, A. R.] Univ Politecn Catalunya EUETIB, Dept Fis & Engn Nucl, E-08036 Barcelona, Spain.
   [Rigollet, C.] Univ Groningen, KVI, NL-9747 AA Groningen, Netherlands.
   [Stolz, A.] Michigan State Univ, Natl Supercond Cyclotron Lab, E Lansing, MI 48824 USA.
C3 Technical University of Munich; Helmholtz Association; GSI Helmholtz-Center for Heavy Ion Research; Istituto Nazionale di Fisica Nucleare (INFN); Polish Academy of Sciences; Institute of Nuclear Physics - Polish Academy of Sciences; University of British Columbia; University of Edinburgh; Universites de Strasbourg Etablissements Associes; Universite de Strasbourg; University of Surrey; Ankara University; University of Cologne; University of Belgrade; University of Valencia; Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Instituto de Fisica Corpuscular (IFIC); RIKEN; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute of Nuclear and Particle Physics (IN2P3); CEA; Comenius University Bratislava; University of Warsaw; Technical University of Darmstadt; Uppsala University; Universitat Politecnica de Catalunya; University of Groningen; Michigan State University
RP Faestermann, T (corresponding author), Tech Univ Munich, Phys Dept E12, D-85748 Garching, Germany.
EM thomas.faestermann@ph.tum.de
FU BMBF [06MT238, 06MT9156, 06KY205I, 06KY9136I]; GSI; DFG Cluster of Excellence 153 'Origin and Structure of the Universe'; EC within the FP6 through I3-EURONS [RII3-CT-2004-506065]; Swedish Research Council; Grants-in-Aid for Scientific Research [11F01752] Funding Source: KAKEN; STFC [ST/J00006X/1, EP/D003628/1, ST/J000051/1] Funding Source: UKRI; Science and Technology Facilities Council [ST/J000051/1, EP/D003628/1, ST/J00006X/1] Funding Source: researchfish
NR 26
TC 155
Z9 168
U1 7
U2 63
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 21
PY 2012
VL 486
IS 7403
BP 341
EP 345
DI 10.1038/nature11116
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 961LV
UT WOS:000305466800032
PM 22722192
DA 2026-03-09
ER

PT J
AU Yilmaz, ÖH
   Katajisto, P
   Lamming, DW
   Gültekin, Y
   Bauer-Rowe, KE
   Sengupta, S
   Birsoy, K
   Dursun, A
   Yilmaz, VO
   Selig, M
   Nielsen, GP
   Mino-Kenudson, M
   Zukerberg, LR
   Bhan, AK
   Deshpande, V
   Sabatini, DM
AF Yilmaz, Omer H.
   Katajisto, Pekka
   Lamming, Dudley W.
   Gueltekin, Yetis
   Bauer-Rowe, Khristian E.
   Sengupta, Shomit
   Birsoy, Kivanc
   Dursun, Abdulmetin
   Yilmaz, V. Onur
   Selig, Martin
   Nielsen, G. Petur
   Mino-Kenudson, Mari
   Zukerberg, Lawrence R.
   Bhan, Atul K.
   Deshpande, Vikram
   Sabatini, David M.
TI mTORC1 in the Paneth cell niche couples intestinal stem-cell function to calorie intake
SO NATURE
LA English
DT Article
ID restriction; pten; mice; homeostasis; renewal; c57bl/6; impact; size; rat; age
AB How adult tissue stem and niche cells respond to the nutritional state of an organism is not well understood. Here we find that Paneth cells, a key constituent of the mammalian intestinal stem-cell (ISC) niche, augment stem-cell function in response to calorie restriction. Calorie restriction acts by reducing mechanistic target of rapamycin complex 1 (mTORC1) signalling in Paneth cells, and the ISC-enhancing effects of calorie restriction can be mimicked by rapamycin. Calorie intake regulates mTORC1 in Paneth cells, but not ISCs, and forced activation of mTORC1 in Paneth cells during calorie restriction abolishes the ISC-augmenting effects of the niche. Finally, increased expression of bone stromal antigen 1 (Bst1) in Paneth cells-an ectoenzyme that produces the paracrine factor cyclic ADP ribose-mediates the effects of calorie restriction and rapamycin on ISC function. Our findings establish that mTORC1 non-cell-autonomously regulates stem-cell self-renewal, and highlight a significant role of the mammalian intestinal niche in coupling stem-cell function to organismal physiology.
C1 [Yilmaz, Omer H.; Katajisto, Pekka; Lamming, Dudley W.; Gueltekin, Yetis; Bauer-Rowe, Khristian E.; Sengupta, Shomit; Birsoy, Kivanc; Yilmaz, V. Onur; Sabatini, David M.] Whitehead Inst Biomed Res, Boston, MA 02142 USA.
   [Yilmaz, Omer H.; Gueltekin, Yetis; Dursun, Abdulmetin; Selig, Martin; Nielsen, G. Petur; Mino-Kenudson, Mari; Zukerberg, Lawrence R.; Bhan, Atul K.; Deshpande, Vikram] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
   [Yilmaz, Omer H.; Gueltekin, Yetis; Dursun, Abdulmetin; Selig, Martin; Nielsen, G. Petur; Mino-Kenudson, Mari; Zukerberg, Lawrence R.; Bhan, Atul K.; Deshpande, Vikram] Harvard Univ, Sch Med, Boston, MA 02114 USA.
   [Yilmaz, Omer H.; Katajisto, Pekka; Lamming, Dudley W.; Gueltekin, Yetis; Bauer-Rowe, Khristian E.; Sengupta, Shomit; Birsoy, Kivanc; Yilmaz, V. Onur; Sabatini, David M.] MIT, Dept Biol, Cambridge, MA 02139 USA.
   [Yilmaz, Omer H.; Katajisto, Pekka; Lamming, Dudley W.; Gueltekin, Yetis; Bauer-Rowe, Khristian E.; Sengupta, Shomit; Birsoy, Kivanc; Yilmaz, V. Onur; Sabatini, David M.] MIT, Howard Hughes Med Inst, Cambridge, MA 02139 USA.
   [Yilmaz, Omer H.; Katajisto, Pekka; Lamming, Dudley W.; Gueltekin, Yetis; Bauer-Rowe, Khristian E.; Sengupta, Shomit; Birsoy, Kivanc; Yilmaz, V. Onur; Sabatini, David M.] Broad Inst Harvard & MIT, Cambridge Ctr 7, Cambridge, MA 02142 USA.
   [Yilmaz, Omer H.; Katajisto, Pekka; Lamming, Dudley W.; Gueltekin, Yetis; Bauer-Rowe, Khristian E.; Sengupta, Shomit; Birsoy, Kivanc; Yilmaz, V. Onur; Sabatini, David M.] MIT, David H Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA.
C3 Massachusetts Institute of Technology (MIT); Whitehead Institute; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard Medical School; 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, Boston, MA 02142 USA.
EM sabatini@wi.mit.edu; sabatini@wi.mit.edu
FU National Institutes of Health [CA103866, CA129105, 1F32AG032833-01A1]; Koch Institute; Ellison Medical Foundation; Warshaw Institute from the Massachusetts General Hospital; Center for the study of Inflammatory Bowel Disease from the Massachusetts General Hospital; NCI [T32CA09216]; Academy of Finland; Foundations' Post Doc Pool; Jane Coffin Childs Medical Fund; National Cancer Institute [R01CA129105, R01CA103866, T32CA009216] Funding Source: NIH RePORTER; National Institute of Diabetes and Digestive and Kidney Diseases [P30DK043351] Funding Source: NIH RePORTER
NR 31
TC 599
Z9 710
U1 2
U2 84
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 28
PY 2012
VL 486
IS 7404
BP 490
EP +
DI 10.1038/nature11163
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 965IJ
UT WOS:000305760600034
PM 22722868
DA 2026-03-09
ER

PT J
AU Wolkovich, EM
   Cook, BI
   Allen, JM
   Crimmins, TM
   Betancourt, JL
   Travers, SE
   Pau, S
   Regetz, J
   Davies, TJ
   Kraft, NJB
   Ault, TR
   Bolmgren, K
   Mazer, SJ
   McCabe, GJ
   McGill, BJ
   Parmesan, C
   Salamin, N
   Schwartz, MD
   Cleland, EE
AF Wolkovich, E. M.
   Cook, B. I.
   Allen, J. M.
   Crimmins, T. M.
   Betancourt, J. L.
   Travers, S. E.
   Pau, S.
   Regetz, J.
   Davies, T. J.
   Kraft, N. J. B.
   Ault, T. R.
   Bolmgren, K.
   Mazer, S. J.
   McCabe, G. J.
   McGill, B. J.
   Parmesan, C.
   Salamin, N.
   Schwartz, M. D.
   Cleland, E. E.
TI Warming experiments underpredict plant phenological responses to climate change
SO NATURE
LA English
DT Article
ID temperature
AB Warming experiments are increasingly relied on to estimate plant responses to global climate change(1,2). For experiments to provide meaningful predictions of future responses, they should reflect the empirical record of responses to temperature variability and recent warming, including advances in the timing of flowering and leafing(3-5). We compared phenology (the timing of recurring life history events) in observational studies and warming experiments spanning four continents and 1,634 plant species using a common measure of temperature sensitivity (change in days per degree Celsius). We show that warming experiments underpredict advances in the timing of flowering and leafing by 8.5-fold and 4.0-fold, respectively, compared with long-term observations. For species that were common to both study types, the experimental results did not match the observational data in sign or magnitude. The observational data also showed that species that flower earliest in the spring have the highest temperature sensitivities, but this trend was not reflected in the experimental data. These significant mismatches seem to be unrelated to the study length or to the degree of manipulated warming in experiments. The discrepancy between experiments and observations, however, could arise from complex interactions among multiple drivers in the observational data, or it could arise from remediable artefacts in the experiments that result in lower irradiance and drier soils, thus dampening the phenological responses to manipulated warming. Our results introduce uncertainty into ecosystem models that are informed solely by experiments and suggest that responses to climate change that are predicted using such models should be re-evaluated.
C1 [Wolkovich, E. M.; Cleland, E. E.] Univ Calif San Diego, Div Biol Sci, La Jolla, CA 92093 USA.
   [Cook, B. I.] NASA, Goddard Inst Space Studies, New York, NY 10025 USA.
   [Cook, B. I.] Lamont Doherty Earth Observ, Palisades, NY 10964 USA.
   [Allen, J. M.] Univ Connecticut, Dept Ecol & Evolutionary Biol, Storrs, CT 06269 USA.
   [Crimmins, T. M.] USA Natl Phenol Network, Tucson, AZ 85721 USA.
   [Betancourt, J. L.] US Geol Survey, Tucson, AZ 85719 USA.
   [Travers, S. E.] N Dakota State Univ, Dept Biol Sci, Fargo, ND 58108 USA.
   [Pau, S.; Regetz, J.] Natl Ctr Ecol Anal & Synth, Santa Barbara, CA 93101 USA.
   [Davies, T. J.] McGill Univ, Dept Biol, Montreal, PQ H3A 1B1, Canada.
   [Kraft, N. J. B.] Univ British Columbia, Biodivers Res Ctr, Vancouver, BC V6T 1Z4, Canada.
   [Kraft, N. J. B.] Univ Maryland, Dept Biol, College Pk, MD 20742 USA.
   [Ault, T. R.] Natl Ctr Atmospher Res, Boulder, CO 80307 USA.
   [Bolmgren, K.] Swedish Univ Agr Sci, Swedish Natl Phenol Network, Unit Field Based Forest Res, SE-36030 Lammhult, Sweden.
   [Bolmgren, K.] Lund Univ, SE-22362 Lund, Sweden.
   [Mazer, S. J.] Univ Calif Santa Barbara, Dept Ecol Evolut & Marine Biol, Santa Barbara, CA 93106 USA.
   [McCabe, G. J.] US Geol Survey, Denver Fed Ctr, Denver, CO 80225 USA.
   [McGill, B. J.] Univ Maine, Sch Biol & Ecol, Orono, ME 04469 USA.
   [McGill, B. J.] Univ Maine, Sustainabil Solut Initiat, Orono, ME 04469 USA.
   [Parmesan, C.] Univ Texas Austin, Austin, TX 78712 USA.
   [Parmesan, C.] Univ Plymouth, Inst Marine Sci, Plymouth PL4 8AA, Devon, England.
   [Salamin, N.] Univ Lausanne, Dept Ecol & Evolut, CH-1015 Lausanne, Switzerland.
   [Salamin, N.] Swiss Inst Bioinformat, CH-1015 Lausanne, Switzerland.
   [Schwartz, M. D.] Univ Wisconsin, Dept Geog, Milwaukee, WI 53201 USA.
C3 University of California System; University of California San Diego; National Aeronautics & Space Administration (NASA); NASA Goddard Space Flight Center; Goddard Institute for Space Studies; Columbia University; University of Connecticut; United States Department of the Interior; United States Geological Survey; North Dakota State University Fargo; University of California System; University of California Santa Barbara; McGill University; University of British Columbia; University System of Maryland; University of Maryland College Park; National Center Atmospheric Research (NCAR) - USA; Swedish University of Agricultural Sciences; Lund University; University of California System; University of California Santa Barbara; United States Department of the Interior; United States Geological Survey; University of Maine System; University of Maine Orono; University of Maine System; University of Maine Orono; University of Texas System; University of Texas Austin; University of Plymouth; University of Lausanne; Swiss Institute of Bioinformatics; University of Wisconsin System; University of Wisconsin Milwaukee
RP Wolkovich, EM (corresponding author), Univ Calif San Diego, Div Biol Sci, 9500 Gilman Dr 0116, La Jolla, CA 92093 USA.
EM wolkovich@biodiversity.ubc.ca
FU National Center for Ecological Analysis Synthesis [EF-0553768]; National Science Foundation [DBI-0905806, IOS-0639794, DEB-0922080]; Natural Sciences and Engineering Research Council of Canada; Division Of Environmental Biology; Direct For Biological Sciences [1027341] Funding Source: National Science Foundation
NR 28
TC 768
Z9 921
U1 13
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 MAY 24
PY 2012
VL 485
IS 7399
BP 494
EP 497
DI 10.1038/nature11014
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 946IH
UT WOS:000304344500041
PM 22622576
DA 2026-03-09
ER

PT J
AU Smith, CC
   Wang, Q
   Chin, CS
   Salerno, S
   Damon, LE
   Levis, MJ
   Perl, AE
   Travers, KJ
   Wang, S
   Hunt, JP
   Zarrinkar, PP
   Schadt, EE
   Kasarskis, A
   Kuriyan, J
   Shah, NP
AF Smith, Catherine C.
   Wang, Qi
   Chin, Chen-Shan
   Salerno, Sara
   Damon, Lauren E.
   Levis, Mark J.
   Perl, Alexander E.
   Travers, Kevin J.
   Wang, Susana
   Hunt, Jeremy P.
   Zarrinkar, Patrick P.
   Schadt, Eric E.
   Kasarskis, Andrew
   Kuriyan, John
   Shah, Neil P.
TI Validation of ITD mutations in FLT3 as a therapeutic target in human acute myeloid leukaemia
SO NATURE
LA English
DT Article
ID tyrosine kinase domain; myelodysplastic syndrome; crystal-structure; insulin-receptor; structural basis; bcr-abl; resistance; inhibitor; autoinhibition; activation
AB Effective targeted cancer therapeutic development depends upon distinguishing disease-associated 'driver' mutations, which have causative roles in malignancy pathogenesis, from 'passenger' mutations, which are dispensable for cancer initiation and maintenance. Translational studies of clinically active targeted therapeutics can definitively discriminate driver from passenger lesions and provide valuable insights into human cancer biology. Activating internal tandem duplication (ITD) mutations in FLT3 (FLT3-ITD) are detected in approximately 20% of acute myeloid leukaemia (AML) patients and are associated with a poor prognosis(1). Abundant scientific(2) and clinical evidence(1,3), including the lack of convincing clinical activity of early FLT3 inhibitors(4,5), suggests that FLT3-ITD probably represents a passenger lesion. Here we report point mutations at three residues within the kinase domain of FLT3-ITD that confer substantial in vitro resistance to AC220 (quizartinib), an active investigational inhibitor of FLT3, KIT, PDGFRA, PDGFRB and RET6,7; evolution of AC220-resistant substitutions at two of these amino acid positions was observed in eight of eight FLT3-ITD-positive AML patients with acquired resistance to AC220. Our findings demonstrate that FLT3-ITD can represent a driver lesion and valid therapeutic target in human AML. AC220-resistant FLT3 kinase domain mutants represent high-value targets for future FLT3 inhibitor development efforts.
C1 [Smith, Catherine C.; Salerno, Sara; Damon, Lauren E.; Shah, Neil P.] Univ Calif San Francisco, Div Hematol Oncol, San Francisco, CA 94143 USA.
   [Wang, Qi; Kuriyan, John] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA.
   [Chin, Chen-Shan; Travers, Kevin J.; Wang, Susana; Schadt, Eric E.; Kasarskis, Andrew] Pacific Biosci, Menlo Pk, CA 94025 USA.
   [Levis, Mark J.] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Dept Oncol, Baltimore, MD 21231 USA.
   [Perl, Alexander E.] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA.
   [Hunt, Jeremy P.; Zarrinkar, Patrick P.] Ambit Biosci, San Diego, CA 92121 USA.
   [Shah, Neil P.] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94115 USA.
C3 University of California System; University of California San Francisco; University of California System; University of California Berkeley; Johns Hopkins University; Johns Hopkins Medicine; University of Pennsylvania; University of California System; University of California San Francisco; UCSF Medical Center; UCSF Helen Diller Family Comprehensive Cancer Center
RP Shah, NP (corresponding author), Univ Calif San Francisco, Div Hematol Oncol, San Francisco, CA 94143 USA.
EM nshah@medicine.ucsf.edu
FU Leukemia and Lymphoma Society; Doris Duke Charitable Foundation; NCI Leukemia SPORE [P50 CA100632-06]; NCI [R01 CA12886]; NIH; Art and Alison Kern and the Edward S. Ageno family; National Cancer Institute [P50CA100632] Funding Source: NIH RePORTER
NR 33
TC 615
Z9 716
U1 0
U2 133
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD MAY 10
PY 2012
VL 485
IS 7397
BP 260
EP U153
DI 10.1038/nature11016
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 939HJ
UT WOS:000303799800046
PM 22504184
DA 2026-03-09
ER

PT J
AU Bulgarelli, D
   Rott, M
   Schlaeppi, K
   van Themaat, EVL
   Ahmadinejad, N
   Assenza, F
   Rauf, P
   Huettel, B
   Reinhardt, R
   Schmelzer, E
   Peplies, J
   Gloeckner, FO
   Amann, R
   Eickhorst, T
   Schulze-Lefert, P
AF Bulgarelli, Davide
   Rott, Matthias
   Schlaeppi, Klaus
   van Themaat, Emiel Ver Loren
   Ahmadinejad, Nahal
   Assenza, Federica
   Rauf, Philipp
   Huettel, Bruno
   Reinhardt, Richard
   Schmelzer, Elmon
   Peplies, Joerg
   Gloeckner, Frank Oliver
   Amann, Rudolf
   Eickhorst, Thilo
   Schulze-Lefert, Paul
TI Revealing structure and assembly cues for Arabidopsis root-inhabiting bacterial microbiota
SO NATURE
LA English
DT Article
ID catalyzed reporter deposition; in-situ hybridization; diversity; endophytes; patterns
AB The plant root defines the interface between amulticellular eukaryote and soil, one of the richest microbial ecosystems on Earth(1). Notably, soil bacteria are able to multiply inside roots as benign endophytes and modulate plant growth and development(2), with implications ranging from enhanced crop productivity(3) to phytoremediation(4). Endophytic colonization represents an apparent paradox of plant innate immunity because plant cells can detect an array of microbeassociated molecular patterns (also known as MAMPs) to initiate immune responses to terminate microbial multiplication(5). Several studies attempted to describe the structure of bacterial root endophytes(6); however, different sampling protocols and low-resolution profiling methods make it difficult to infer general principles. Here we describemethodology to characterize and compare soil-and rootinhabiting bacterial communities, which reveals not only a function formetabolically active plant cells but also for inert cell-wall features in the selection of soil bacteria for host colonization. We showthat the roots ofArabidopsis thaliana, grown in different natural soils under controlled environmental conditions, are preferentially colonized by Proteobacteria, Bacteroidetes and Actinobacteria, and each bacterial phylum is represented by a dominating class or family. Soil type defines the composition of root-inhabiting bacterial communities and host genotype determines their ribotype profiles to a limited extent. The identification of soil-type-specific members within the root-inhabiting assemblies supports our conclusion that these represent soil-derived root endophytes. Surprisingly, plant cell-wall features of other tested plant species seem to provide a sufficient cue for the assembly of approximately 40% of the Arabidopsis bacterial root-inhabitingmicrobiota, with a bias for Betaproteobacteria. Thus, this root sub-community may not beArabidopsis-specific but saprophytic bacteria that would naturally be found on any plant root or plant debris in the tested soils. By contrast, colonization of Arabidopsis roots by members of the Actinobacteria depends on other cues from metabolically active host cells.
C1 [Bulgarelli, Davide; Rott, Matthias; Schlaeppi, Klaus; van Themaat, Emiel Ver Loren; Ahmadinejad, Nahal; Assenza, Federica; Rauf, Philipp; Schulze-Lefert, Paul] Max Planck Inst Plant Breeding Res, Dept Plant Microbe Interact, D-50829 Cologne, Germany.
   [Huettel, Bruno; Reinhardt, Richard] Max Planck Inst Plant Breeding Res, Max Planck Genome Ctr, D-50829 Cologne, Germany.
   [Peplies, Joerg; Gloeckner, Frank Oliver] Ribocon GmbH, D-28359 Bremen, Germany.
   [Gloeckner, Frank Oliver; Amann, Rudolf] Max Planck Inst Marine Microbiol, Dept Mol Ecol, D-28359 Bremen, Germany.
   [Eickhorst, Thilo] Univ Bremen, Fac Biol & Chem, D-28359 Bremen, Germany.
C3 Max Planck Society; Max Planck Society; Max Planck Society; University of Bremen
RP Schulze-Lefert, P (corresponding author), Max Planck Inst Plant Breeding Res, Dept Plant Microbe Interact, D-50829 Cologne, Germany.
EM schlef@mpipz.mpg.de
FU Max Planck Society [M.IF. A. ZUCH8048]; Swiss National Science Foundation [PBFRP3-133544]; Swiss National Science Foundation (SNF) [PBFRP3-133544] Funding Source: Swiss National Science Foundation (SNF)
NR 21
TC 1835
Z9 2141
U1 25
U2 1568
PU NATURE PUBLISHING 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 2
PY 2012
VL 488
IS 7409
BP 91
EP 95
DI 10.1038/nature11336
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 981ZE
UT WOS:000307010700039
PM 22859207
DA 2026-03-09
ER

PT J
AU Claesson, MJ
   Jeffery, IB
   Conde, S
   Power, SE
   O'Connor, EM
   Cusack, S
   Harris, HMB
   Coakley, M
   Lakshminarayanan, B
   O'Sullivan, O
   Fitzgerald, GF
   Deane, J
   O'Connor, M
   Harnedy, N
   O'Connor, K
   O'Mahony, D
   van Sinderen, D
   Wallace, M
   Brennan, L
   Stanton, C
   Marchesi, JR
   Fitzgerald, AP
   Shanahan, F
   Hill, C
   Ross, RP
   O'Toole, PW
AF Claesson, Marcus J.
   Jeffery, Ian B.
   Conde, Susana
   Power, Susan E.
   O'Connor, Eibhlis M.
   Cusack, Siobhan
   Harris, Hugh M. B.
   Coakley, Mairead
   Lakshminarayanan, Bhuvaneswari
   O'Sullivan, Orla
   Fitzgerald, Gerald F.
   Deane, Jennifer
   O'Connor, Michael
   Harnedy, Norma
   O'Connor, Kieran
   O'Mahony, Denis
   van Sinderen, Douwe
   Wallace, Martina
   Brennan, Lorraine
   Stanton, Catherine
   Marchesi, Julian R.
   Fitzgerald, Anthony P.
   Shanahan, Fergus
   Hill, Colin
   Ross, R. Paul
   O'Toole, Paul W.
TI Gut microbiota composition correlates with diet and health in the elderly
SO NATURE
LA English
DT Article
ID phylogenetic microarray; fecal microbiota; sequences; unifrac; index; age
AB Alterations in intestinal microbiota composition are associated with several chronic conditions, including obesity and inflammatory diseases. The microbiota of older people displays greater inter-individual variation than that of younger adults. Here we show that the faecal microbiota composition from 178 elderly subjects formed groups, correlating with residence location in the community, day-hospital, rehabilitation or in long-term residential care. However, clustering of subjects by diet separated them by the same residence location and microbiota groupings. The separation of microbiota composition significantly correlated with measures of frailty, co-morbidity, nutritional status, markers of inflammation and with metabolites in faecal water. The individual microbiota of people in long-stay care was significantly less diverse than that of community dwellers. Loss of community-associated microbiota correlated with increased frailty. Collectively, the data support a relationship between diet, microbiota and health status, and indicate a role for diet-driven microbiota alterations in varying rates of health decline upon ageing.
C1 [Claesson, Marcus J.; Jeffery, Ian B.; Power, Susan E.; O'Connor, Eibhlis M.; Cusack, Siobhan; Harris, Hugh M. B.; Fitzgerald, Gerald F.; Deane, Jennifer; van Sinderen, Douwe; Hill, Colin; O'Toole, Paul W.] Univ Coll Cork, Dept Microbiol, Cork, Ireland.
   [Claesson, Marcus J.; Jeffery, Ian B.; O'Connor, Eibhlis M.; Fitzgerald, Gerald F.; van Sinderen, Douwe; Stanton, Catherine; Shanahan, Fergus; Hill, Colin; Ross, R. Paul; O'Toole, Paul W.] Univ Coll Cork, Alimentary Pharmabiot Ctr, Cork, Ireland.
   [Conde, Susana; Fitzgerald, Anthony P.] Univ Coll Cork, Dept Stat, Cork, Ireland.
   [Coakley, Mairead; Lakshminarayanan, Bhuvaneswari; O'Sullivan, Orla; Stanton, Catherine; Ross, R. Paul] TEAGASC, Moorepk Food Res Ctr, Fermoy, Cork, Ireland.
   [O'Connor, Michael; Harnedy, Norma; O'Mahony, Denis] Cork Univ Hosp, Cork, Ireland.
   [O'Connor, Michael; Harnedy, Norma; O'Connor, Kieran; O'Mahony, Denis] St Finbarrs Hosp, Cork, Ireland.
   [O'Connor, Kieran] Mercy Univ Hosp, Cork, Ireland.
   [O'Connor, Kieran; O'Mahony, Denis] Victoria Univ Hosp, South Infirm, Cork, Ireland.
   [Wallace, Martina; Brennan, Lorraine] Univ Coll Dublin, Inst Food & Hlth, Dublin, Ireland.
   [Marchesi, Julian R.] Cardiff Univ, Sch Biosci, Cardiff CF10 3AT, S Glam, Wales.
   [Fitzgerald, Anthony P.] Univ Coll Cork, Dept Epidemiol & Publ Hlth, Cork, Ireland.
   [Shanahan, Fergus] Univ Coll Cork, Dept Med, Cork, Ireland.
C3 University College Cork; University College Cork; University College Cork; Teagasc; University College Cork; University College Cork; University College Dublin; Cardiff University; University College Cork; University College Cork
RP O'Toole, PW (corresponding author), Univ Coll Cork, Dept Microbiol, Cork, Ireland.
EM pwotoole@ucc.ie
FU Government of Ireland National Development Plan; Health Research Board FHRI; Science Foundation Ireland; Health Research Board of Ireland
NR 55
TC 2551
Z9 2944
U1 11
U2 819
PU NATURE PUBLISHING 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 9
PY 2012
VL 488
IS 7410
BP 178
EP +
DI 10.1038/nature11319
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 985LE
UT WOS:000307267000026
PM 22797518
DA 2026-03-09
ER

PT J
AU Imai, M
   Watanabe, T
   Hatta, M
   Das, SC
   Ozawa, M
   Shinya, K
   Zhong, GX
   Hanson, A
   Katsura, H
   Watanabe, S
   Li, CJ
   Kawakami, E
   Yamada, S
   Kiso, M
   Suzuki, Y
   Maher, EA
   Neumann, G
   Kawaoka, Y
AF Imai, Masaki
   Watanabe, Tokiko
   Hatta, Masato
   Das, Subash C.
   Ozawa, Makoto
   Shinya, Kyoko
   Zhong, Gongxun
   Hanson, Anthony
   Katsura, Hiroaki
   Watanabe, Shinji
   Li, Chengjun
   Kawakami, Eiryo
   Yamada, Shinya
   Kiso, Maki
   Suzuki, Yasuo
   Maher, Eileen A.
   Neumann, Gabriele
   Kawaoka, Yoshihiro
TI Experimental adaptation of an influenza H5 HA confers respiratory droplet transmission to a reassortant H5 HA/H1N1 virus in ferrets
SO NATURE
LA English
DT Article
ID receptor-binding specificity; swine-origin h1n1; single amino-acid; sialic-acid; avian h5n1; a virus; membrane-fusion; molecular-basis; in-vitro; hemagglutinin
AB Highly pathogenic avian H5N1 influenza A viruses occasionally infect humans, but currently do not transmit efficiently among humans. The viral haemagglutinin (HA) protein is a known host-range determinant as it mediates virus binding to host-specific cellular receptors(1-3). Here we assess the molecular changes in HA that would allow a virus possessing subtype H5 HA to be transmissible among mammals. We identified a reassortant H5 HA/H1N1 virus-comprising H5 HA (from an H5N1 virus) with four mutations and the remaining seven gene segments from a 2009 pandemic H1N1 virus-that was capable of droplet transmission in a ferret model. The transmissible H5 reassortant virus preferentially recognized human-type receptors, replicated efficiently in ferrets, caused lung lesions and weight loss, but was not highly pathogenic and did not cause mortality. These results indicate that H5 HA can convert to an HA that supports efficient viral transmission in mammals; however, we do not know whether the four mutations in the H5 HA identified here would render a wholly avian H5N1 virus transmissible. The genetic origin of the remaining seven viral gene segments may also critically contribute to transmissibility in mammals. Nevertheless, as H5N1 viruses continue to evolve and infect humans, receptor-binding variants of H5N1 viruses with pandemic potential, including avian-human reassortant viruses as tested here, may emerge. Our findings emphasize the need to prepare for potential pandemics caused by influenza viruses possessing H5 HA, and will help individuals conducting surveillance in regions with circulating H5N1 viruses to recognize key residues that predict the pandemic potential of isolates, which will inform the development, production and distribution of effective countermeasures.
C1 [Imai, Masaki; Watanabe, Tokiko; Hatta, Masato; Das, Subash C.; Ozawa, Makoto; Zhong, Gongxun; Hanson, Anthony; Watanabe, Shinji; Li, Chengjun; Maher, Eileen A.; Neumann, Gabriele; Kawaoka, Yoshihiro] Univ Wisconsin, Dept Pathobiol Sci, Madison, WI 53711 USA.
   [Watanabe, Tokiko; Watanabe, Shinji; Kawakami, Eiryo; Kawaoka, Yoshihiro] ERATO Infect Induced Host Responses Project, Kawaguchi, Saitama 3320012, Japan.
   [Ozawa, Makoto; Kawaoka, Yoshihiro] Univ Tokyo, Dept Special Pathogens, Int Res Ctr Infect Dis, Inst Med Sci, Tokyo 1088639, Japan.
   [Shinya, Kyoko] Kobe Univ, Dept Microbiol & Infect Dis, Kobe, Hyogo 6500017, Japan.
   [Katsura, Hiroaki; Yamada, Shinya; Kiso, Maki; Kawaoka, Yoshihiro] Univ Tokyo, Div Virol, Dept Microbiol & Immunol, Inst Med Sci, Tokyo 1088639, Japan.
   [Suzuki, Yasuo] Chubu Univ, Coll Life & Hlth Sci, Kasugai, Aichi 4878501, Japan.
C3 University of Wisconsin System; University of Wisconsin Madison; Japan Science & Technology Agency (JST); University of Tokyo; Kobe University; University of Tokyo; Chubu University
RP Kawaoka, Y (corresponding author), Univ Wisconsin, Dept Pathobiol Sci, Madison, WI 53711 USA.
EM kawaokay@svm.vetmed.wisc.edu
FU Bill & Melinda Gates Foundation [48339, OPPGH5383]; Ministry of Education, Culture, Sports, Science, and Technology of Japan; ERATO (Japan Science and Technology Agency); National Institute of Allergy and Infectious Diseases Public Health Service Research grants; Grants-in-Aid for Scientific Research [24658245, 20390028] Funding Source: KAKEN
NR 46
TC 1211
Z9 1384
U1 1
U2 338
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUN 21
PY 2012
VL 486
IS 7403
BP 420
EP +
DI 10.1038/nature10831
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 961LV
UT WOS:000305466800047
PM 22722205
DA 2026-03-09
ER

PT J
AU Noinaj, N
   Easley, NC
   Oke, M
   Mizuno, N
   Gumbart, J
   Boura, E
   Steere, AN
   Zak, O
   Aisen, P
   Tajkhorshid, E
   Evans, RW
   Gorringe, AR
   Mason, AB
   Steven, AC
   Buchanan, SK
AF Noinaj, Nicholas
   Easley, Nicole C.
   Oke, Muse
   Mizuno, Naoko
   Gumbart, James
   Boura, Evzen
   Steere, Ashley N.
   Zak, Olga
   Aisen, Philip
   Tajkhorshid, Emad
   Evans, Robert W.
   Gorringe, Andrew R.
   Mason, Anne B.
   Steven, Alasdair C.
   Buchanan, Susan K.
TI Structural basis for iron piracy by pathogenic Neisseria
SO NATURE
LA English
DT Article
ID binding protein-b; human serum transferrin; x-ray; molecular-dynamics; c-lobe; meningitidis; receptor; identification; antibody; scattering
AB Neisseria are obligate human pathogens causing bacterial meningitis, septicaemia and gonorrhoea. Neisseria require iron for survival and can extract it directly from human transferrin for transport across the outer membrane. The transport system consists of TbpA, an integral outer membrane protein, and TbpB, a co-receptor attached to the cell surface; both proteins are potentially important vaccine and therapeutic targets. Two key questions driving Neisseria research are how human transferrin is specifically targeted, and how the bacteria liberate iron from transferrin at neutral pH. To address these questions, we solved crystal structures of the TbpA-transferrin complex and of the corresponding co-receptor TbpB. We characterized the TbpB-transferrin complex by small-angle X-ray scattering and the TbpA-TbpB-transferrin complex by electron microscopy. Our studies provide a rational basis for the specificity of TbpA for human transferrin, show how TbpA promotes iron release from transferrin, and elucidate how TbpB facilitates this process.
C1 [Noinaj, Nicholas; Easley, Nicole C.; Oke, Muse; Boura, Evzen; Buchanan, Susan K.] NIDDK, Mol Biol Lab, US Natl Inst Hlth, Bethesda, MD 20892 USA.
   [Mizuno, Naoko; Steven, Alasdair C.] NIAMSD, Struct Biol Lab, US Natl Inst Hlth, Bethesda, MD 20892 USA.
   [Gumbart, James] Argonne Natl Lab, Biosci Div, Argonne, IL 60439 USA.
   [Steere, Ashley N.; Mason, Anne B.] Univ Vermont, Coll Med, Dept Biochem, Burlington, VT 05405 USA.
   [Zak, Olga; Aisen, Philip] Albert Einstein Coll Med, Bronx, NY 10461 USA.
   [Tajkhorshid, Emad] Univ Illinois, Dept Biochem, Urbana, IL 61801 USA.
   [Tajkhorshid, Emad] Univ Illinois, Beckman Inst, Urbana, IL 61801 USA.
   [Evans, Robert W.] Brunel Univ, Sch Hlth Sci & Social Care, Div Biosci, Metalloprot Res Grp, Uxbridge UB8 3PH, Middx, England.
   [Gorringe, Andrew R.] Hlth Protect Agcy, Salisbury SP2 8NY, Wilts, England.
C3 National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK); National Institutes of Health (NIH) - USA; NIH National Institute of Arthritis & Musculoskeletal & Skin Diseases (NIAMS); United States Department of Energy (DOE); Argonne National Laboratory; University of Vermont; Yeshiva University; Montefiore Medical Center; Albert Einstein College of Medicine; University of Illinois System; University of Illinois Urbana-Champaign; University of Illinois System; University of Illinois Urbana-Champaign; Brunel University; Health Protection Agency
RP Buchanan, SK (corresponding author), NIDDK, Mol Biol Lab, US Natl Inst Hlth, Bethesda, MD 20892 USA.
EM skbuchan@helix.nih.gov
FU NIH, National Institute of Diabetes and Digestive and Kidney Diseases; EPSRC Research Committee; NIH, National Institute of Arthritis and Musculoskeletal and Skin Diseases; USPHS [R01-DK21739]; AHA [10PRE4200010]; NIH [R01-GM086749, U54-GM087519, P41-RR05969]; US Department of Energy, Office of Science, Office of Basic Energy Sciences [W-31-109-Eng-38]; US Department of Energy, Basic Energy Sciences, Office of Science [DE-AC02-06CH11357]; Department of Energy, Office of Biological and Environmental Research; National Institutes of Health, National Center for Research Resources; American Heart Association (AHA) [10PRE4200010] Funding Source: American Heart Association (AHA)
NR 52
TC 228
Z9 275
U1 1
U2 59
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 1
PY 2012
VL 483
IS 7387
BP 53
EP U92
DI 10.1038/nature10823
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 900HP
UT WOS:000300877900042
PM 22327295
DA 2026-03-09
ER

PT J
AU Koppikar, P
   Bhagwat, N
   Kilpivaara, O
   Manshouri, T
   Adli, M
   Hricik, T
   Liu, F
   Saunders, LM
   Mullally, A
   Abdel-Wahab, O
   Leung, L
   Weinstein, A
   Marubayashi, S
   Goel, A
   Gönen, M
   Estrov, Z
   Ebert, BL
   Chiosis, G
   Nimer, SD
   Bernstein, BE
   Verstovsek, S
   Levine, RL
AF Koppikar, Priya
   Bhagwat, Neha
   Kilpivaara, Outi
   Manshouri, Taghi
   Adli, Mazhar
   Hricik, Todd
   Liu, Fan
   Saunders, Lindsay M.
   Mullally, Ann
   Abdel-Wahab, Omar
   Leung, Laura
   Weinstein, Abby
   Marubayashi, Sachie
   Goel, Aviva
   Goenen, Mithat
   Estrov, Zeev
   Ebert, Benjamin L.
   Chiosis, Gabriela
   Nimer, Stephen D.
   Bernstein, Bradley E.
   Verstovsek, Srdan
   Levine, Ross L.
TI Heterodimeric JAK-STAT activation as a mechanism of persistence to JAK2 inhibitor therapy
SO NATURE
LA English
DT Article
ID tyrosine kinase; lung adenocarcinomas; resistance; mutation; gefitinib; cancer; efficacy; identification; safety
AB The identification of somatic activating mutations in JAK2 (refs 1-4) and in the thrombopoietin receptor gene (MPL)(5) in most patients with myeloproliferative neoplasm (MPN) led to the clinical development of JAK2 kinase inhibitors(6,7). JAK2 inhibitor therapy improves MPN-associated splenomegaly and systemic symptoms but does not significantly decrease or eliminate the MPN clone in most patients with MPN. We therefore sought to characterize mechanisms by which MPN cells persist despite chronic inhibition of JAK2. Here we show that JAK2 inhibitor persistence is associated with reactivation of JAK-STAT signalling and with heterodimerization between activated JAK2 and JAK1 or TYK2, consistent with activation of JAK2 in trans by other JAK kinases. Further, this phenomenon is reversible: JAK2 inhibitor withdrawal is associated with resensitization to JAK2 kinase inhibitors and with reversible changes in JAK2 expression. We saw increased JAK2 heterodimerization and sustained JAK2 activation in cell lines, in murine models and in patients treated with JAK2 inhibitors. RNA interference and pharmacological studies show that JAK2-inhibitor-persistent cells remain dependent on JAK2 protein expression. Consequently, therapies that result in JAK2 degradation retain efficacy in persistent cells and may provide additional benefit to patients with JAK2-dependent malignancies treated with JAK2 inhibitors.
C1 [Koppikar, Priya; Bhagwat, Neha; Kilpivaara, Outi; Hricik, Todd; Saunders, Lindsay M.; Abdel-Wahab, Omar; Leung, Laura; Weinstein, Abby; Marubayashi, Sachie; Goel, Aviva; Levine, Ross L.] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10065 USA.
   [Bhagwat, Neha; Saunders, Lindsay M.] Mem Sloan Kettering Canc Ctr, Gerstner Sloan Kettering Grad Sch Biomed Sci, New York, NY 10065 USA.
   [Manshouri, Taghi; Estrov, Zeev; Verstovsek, Srdan] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
   [Adli, Mazhar; Bernstein, Bradley E.] Massachusetts Gen Hosp, Dept Pathol, Howard Hughes Med Inst, Boston, MA 02114 USA.
   [Adli, Mazhar; Bernstein, Bradley E.] MIT, Broad Inst Harvard, Boston, MA 02114 USA.
   [Mullally, Ann; Ebert, Benjamin L.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Hematol,Dept Med, Boston, MA 02115 USA.
   [Abdel-Wahab, Omar; Nimer, Stephen D.; Levine, Ross L.] Mem Sloan Kettering Canc Ctr, Leukemia Serv, New York, NY 10065 USA.
   [Goenen, Mithat] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10065 USA.
C3 Memorial Sloan Kettering Cancer Center; Memorial Sloan Kettering Cancer Center; University of Texas System; UTMD Anderson Cancer Center; Howard Hughes Medical Institute; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard Medical School; Memorial Sloan Kettering Cancer Center; Memorial Sloan Kettering Cancer Center
RP Levine, RL (corresponding author), Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10065 USA.
EM leviner@mskcc.org
FU National Cancer Institute [1R01CA151949-01]; Leukemia and Lymphoma Society; Myeloproliferative Neoplasms Foundation; Starr Cancer Consortium; National Cancer Institute [P30CA016672] Funding Source: NIH RePORTER
NR 32
TC 312
Z9 363
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 SEP 6
PY 2012
VL 489
IS 7414
BP 155
EP U222
DI 10.1038/nature11303
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 999WW
UT WOS:000308347000054
PM 22820254
DA 2026-03-09
ER

PT J
AU Steinhauser, ML
   Bailey, AP
   Senyo, SE
   Guillermier, C
   Perlstein, TS
   Gould, AP
   Lee, RT
   Lechene, CP
AF Steinhauser, Matthew L.
   Bailey, Andrew P.
   Senyo, Samuel E.
   Guillermier, Christelle
   Perlstein, Todd S.
   Gould, Alex P.
   Lee, Richard T.
   Lechene, Claude P.
TI Multi-isotope imaging mass spectrometry quantifies stem cell division and metabolism
SO NATURE
LA English
DT Article
ID small-intestine; segregation; telomerase; dna; protect; strands; genome; crypt
AB Mass spectrometry with stable isotope labels has been seminal in discovering the dynamic state of living matter(1,2), but is limited to bulk tissues or cells. We developed multi-isotope imaging mass spectrometry (MIMS) that allowed us to view and measure stable isotope incorporation with submicrometre resolution(3,4). Here we apply MIMS to diverse organisms, including Drosophila, mice and humans. We test the 'immortal strand hypothesis', which predicts that during asymmetric stem cell division chromosomes containing older template DNA are segregated to the daughter destined to remain a stem cell, thus insuring lifetime genetic stability. After labelling mice with N-15-thymidine from gestation until post-natal week 8, we find no N-15 label retention by dividing small intestinal crypt cells after a four-week chase. In adult mice administered N-15-thymidine pulse-chase, we find that proliferating crypt cells dilute the N-15 label, consistent with random strand segregation. We demonstrate the broad utility of MIMS with proof-of-principle studies of lipid turnover in Drosophila and translation to the human haematopoietic system. These studies show that MIMS provides high-resolution quantification of stable isotope labels that cannot be obtained using other techniques and that is broadly applicable to biological and medical research.
C1 [Steinhauser, Matthew L.; Senyo, Samuel E.; Guillermier, Christelle; Perlstein, Todd S.; Lee, Richard T.; Lechene, Claude P.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
   [Steinhauser, Matthew L.; Senyo, Samuel E.; Perlstein, Todd S.; Lee, Richard T.] Brigham & Womens Hosp, Dept Med, Div Cardiovasc Med, Boston, MA 02115 USA.
   [Bailey, Andrew P.; Gould, Alex P.] Natl Inst Med Res, Div Physiol & Metab, MRC, London NW7 1AA, England.
   [Guillermier, Christelle; Lechene, Claude P.] Natl Resource Imaging Mass Spect, Cambridge, MA 02139 USA.
   [Guillermier, Christelle; Lechene, Claude P.] Brigham & Womens Hosp, Dept Med, Div Genet, Boston, MA 02115 USA.
   [Lee, Richard T.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA.
C3 Harvard University; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; MRC National Institute for Medical Research; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard University
RP Lechene, CP (corresponding author), Harvard Univ, Sch Med, Boston, MA 02115 USA.
EM cpl@harvard.edu
FU American Heart Association; Future Leaders in Cardiovascular Medicine; Medical Research Council [U117584237]; National Institutes of Health [AG032977, EB001974, AG034641]; Harvard Stem Cell Institute; Ellison Medical Foundation; Human Frontier Science Program; Medical Research Council [MC_U117584237] Funding Source: researchfish; MRC [MC_U117584237] Funding Source: UKRI
NR 28
TC 255
Z9 294
U1 0
U2 188
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 26
PY 2012
VL 481
IS 7382
BP 516
EP U131
DI 10.1038/nature10734
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 881GY
UT WOS:000299471800042
PM 22246326
DA 2026-03-09
ER

PT J
AU Norris, BRM
   Tuthill, PG
   Ireland, MJ
   Lacour, S
   Zijlstra, AA
   Lykou, F
   Evans, TM
   Stewart, P
   Bedding, TR
AF Norris, Barnaby R. M.
   Tuthill, Peter G.
   Ireland, Michael J.
   Lacour, Sylvestre
   Zijlstra, Albert A.
   Lykou, Foteini
   Evans, Thomas M.
   Stewart, Paul
   Bedding, Timothy R.
TI A close halo of large transparent grains around extreme red giant stars
SO NATURE
LA English
DT Article
ID mass-loss rates; circumstellar envelopes; mira variables; dust formation; winds; atmospheres; mineralogy
AB An intermediate-mass star ends its life by ejecting the bulk of its envelope in a slow, dense wind(1-3). Stellar pulsations are thought to elevate gas to an altitude cool enough for the condensation of dust(1), which is then accelerated by radiation pressure, entraining the gas and driving the wind(2,4,5). Explaining the amount of mass loss, however, has been a problem because of the difficulty of observing tenuous gas and dust only tens of milliarcseconds from the star. For this reason, there is no consensus on the way sufficient momentum is transferred from the light from the star to the outflow. Here we report spatially resolved, multiwavelength observations of circumstellar dust shells of three stars on the asymptotic giant branch of the Hertzsprung-Russell diagram. When imaged in scattered light, dust shells were found at remarkably small radii (less than about two stellar radii) and with unexpectedly large grains (about 300 nanometres in radius). This proximity to the photosphere argues for dust species that are transparent to the light from the star and, therefore, resistant to sublimation by the intense radiation field. Although transparency usually implies insufficient radiative pressure to drive a wind(6,7), the radiation field can accelerate these large grains through photon scattering rather than absorption(8)-a plausible mass loss mechanism for lower-amplitude pulsating stars.
C1 [Norris, Barnaby R. M.; Tuthill, Peter G.; Ireland, Michael J.; Evans, Thomas M.; Stewart, Paul; Bedding, Timothy R.] Univ Sydney, Sch Phys, Sydney Inst Astron, Sydney, NSW 2006, Australia.
   [Ireland, Michael J.] Macquarie Univ, Dept Phys & Astron, N Ryde, NSW 2109, Australia.
   [Ireland, Michael J.] Australian Astron Observ, Epping, NSW 1710, Australia.
   [Lacour, Sylvestre] Univ Paris Diderot, Univ Paris 06, CNRS, LESIA Observ Paris, F-92190 Meudon, France.
   [Zijlstra, Albert A.; Lykou, Foteini] Univ Manchester, Sch Phys & Astron, Jodrell Bank Ctr Astrophys, Manchester M13 9PL, Lancs, England.
   [Evans, Thomas M.] Univ Oxford, Dept Phys, Oxford OX1 3RH, England.
C3 University of Sydney; Macquarie University; Universite Paris Cite; Sorbonne Universite; Centre National de la Recherche Scientifique (CNRS); Universite PSL; Observatoire de Paris; University of Manchester; Jodrell Bank Centre for Astrophysics; University of Oxford
RP Norris, BRM (corresponding author), Univ Sydney, Sch Phys, Sydney Inst Astron, Sydney, NSW 2006, Australia.
EM bnorris@physics.usyd.edu.au
FU STFC [ST/I001425/1] Funding Source: UKRI; Science and Technology Facilities Council [ST/I001425/1] Funding Source: researchfish
NR 25
TC 163
Z9 178
U1 0
U2 10
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 12
PY 2012
VL 484
IS 7393
BP 220
EP 222
DI 10.1038/nature10935
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 930OV
UT WOS:000303149900030
PM 22498626
DA 2026-03-09
ER

PT J
AU Pfau, H
   Hartmann, S
   Stockert, U
   Sun, PJ
   Lausberg, S
   Brando, M
   Friedemann, S
   Krellner, C
   Geibel, C
   Wirth, S
   Kirchner, S
   Abrahams, E
   Si, QM
   Steglich, F
AF Pfau, Heike
   Hartmann, Stefanie
   Stockert, Ulrike
   Sun, Peijie
   Lausberg, Stefan
   Brando, Manuel
   Friedemann, Sven
   Krellner, Cornelius
   Geibel, Christoph
   Wirth, Steffen
   Kirchner, Stefan
   Abrahams, Elihu
   Si, Qimiao
   Steglich, Frank
TI Thermal and electrical transport across a magnetic quantum critical point
SO NATURE
LA English
DT Article
ID wiedemann-franz law; fermi-surface; heavy; phase; temperature; violation
AB A quantum critical point (QCP) arises when a continuous transition between competing phases occurs at zero temperature. Collective excitations at magnetic QCPs give rise to metallic properties that strongly deviate from the expectations of Landau's Fermi-liquid description(1), which is the standard theory of electron correlations in metals. Central to this theory is the notion of quasiparticles, electronic excitations that possess the quantum numbers of the non-interacting electrons. Here we report measurements of thermal and electrical transport across the field-induced magnetic QCP in the heavy-fermion compound YbRh2Si2 (refs 2, 3). We show that the ratio of the thermal to electrical conductivities at the zero-temperature limit obeys the Wiedemann-Franz law for magnetic fields above the critical field at which the QCP is attained. This is also expected for magnetic fields below the critical field, where weak antiferromagnetic order and a Fermi-liquid phase form below 0.07 K (at zero field). At the critical field, however, the low-temperature electrical conductivity exceeds the thermal conductivity by about 10 per cent, suggestive of a non-Fermi-liquid ground state. This apparent violation of the Wiedemann-Franz law provides evidence for an unconventional type of QCP at which the fundamental concept of Landau quasiparticles no longer holds(4-6). These results imply that Landau quasiparticles break up, and that the origin of this disintegration is inelastic scattering associated with electronic quantum critical fluctuations-these insights could be relevant to understanding other deviations from Fermi-liquid behaviour frequently observed in various classes of correlated materials.
C1 [Pfau, Heike; Hartmann, Stefanie; Stockert, Ulrike; Sun, Peijie; Lausberg, Stefan; Brando, Manuel; Friedemann, Sven; Krellner, Cornelius; Geibel, Christoph; Wirth, Steffen; Kirchner, Stefan; Steglich, Frank] Max Planck Inst Chem Phys Solids, D-01187 Dresden, Germany.
   [Kirchner, Stefan] Max Planck Inst Phys Komplexer Syst, D-01187 Dresden, Germany.
   [Abrahams, Elihu] Univ Calif Los Angeles, Dept Phys & Astron, Los Angeles, CA 90095 USA.
   [Si, Qimiao] Rice Univ, Dept Phys & Astron, Houston, TX 77005 USA.
C3 Max Planck Society; Max Planck Society; University of California System; University of California Los Angeles; Rice University
RP Steglich, F (corresponding author), Max Planck Inst Chem Phys Solids, Nothnitzer Str 40, D-01187 Dresden, Germany.
EM steglich@cpfs.mpg.de
FU DFG Research Unit [960]; NSF [DMR-1006985, 1066293]; Robert A. Welch Foundation [C-1411]; Division Of Materials Research; Direct For Mathematical & Physical Scien [1006985] Funding Source: National Science Foundation
NR 30
TC 76
Z9 84
U1 2
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 26
PY 2012
VL 484
IS 7395
BP 493
EP 497
DI 10.1038/nature11072
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 931FF
UT WOS:000303200400046
PM 22538612
DA 2026-03-09
ER

PT J
AU Forget, AL
   Kowalczykowski, SC
AF Forget, Anthony L.
   Kowalczykowski, Stephen C.
TI Single-molecule imaging of DNA pairing by RecA reveals a three-dimensional homology search
SO NATURE
LA English
DT Article
ID double-stranded dna; escherichia-coli; protein; recombination; mechanism; binding; exchange; translocation; biochemistry; filaments
AB DNA breaks can be repaired with high fidelity by homologous recombination. A ubiquitous protein that is essential for this DNA template-directed repair is RecA(1). After resection of broken DNA to produce single-stranded DNA (ssDNA), RecA assembles on this ssDNA into a filament with the unique capacity to search and find DNA sequences in double-stranded DNA (dsDNA) that are homologous to the ssDNA. This homology search is vital to recombinational DNA repair, and results in homologous pairing and exchange of DNA strands. Homologous pairing involves DNA sequence-specific target location by the RecA-ssDNA complex. Despite decades of study, the mechanism of this enigmatic search process remains unknown. RecA is a DNA-dependent ATPase, but ATP hydrolysis is not required for DNA pairing and strand exchange(2,3), eliminating active search processes. Using dual optical trapping to manipulate DNA, and single-molecule fluorescence microscopy to image DNA pairing, we demonstrate that both the three-dimensional conformational state of the dsDNA target and the length of the homologous RecA-ssDNA filament have important roles in the homology search. We discovered that as the end-to-end distance of the target dsDNA molecule is increased, constraining the available three-dimensional (3D) conformations of the molecule, the rate of homologous pairing decreases. Conversely, when the length of the ssDNA in the nucleoprotein filament is increased, homology is found faster. We propose a model for the DNA homology search process termed 'intersegmental contact sampling', in which the intrinsic multivalent nature of the RecA nucleoprotein filament is used to search DNA sequence space within 3D domains of DNA, exploiting multiple weak contacts to rapidly search for homology. Our findings highlight the importance of the 3D conformational dynamics of DNA, reveal a previously unknown facet of the homology search, and provide insight into the mechanism of DNA target location by this member of a universal family of proteins.
C1 [Forget, Anthony L.; Kowalczykowski, Stephen C.] Univ Calif Davis, Dept Microbiol, Davis, CA 95616 USA.
   [Forget, Anthony L.; Kowalczykowski, Stephen C.] Univ Calif Davis, Dept Mol & Cellular Biol, Davis, CA 95616 USA.
C3 University of California System; University of California Davis; University of California System; University of California Davis
RP Kowalczykowski, SC (corresponding author), Univ Calif Davis, Dept Microbiol, Davis, CA 95616 USA.
EM sckowalczykowski@ucdavis.edu
FU American Cancer Society [PF-08-046-01-GMC]; National Institutes of Health [GM-62653, GM-64745]
NR 22
TC 170
Z9 207
U1 3
U2 108
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD FEB 16
PY 2012
VL 482
IS 7385
BP 423
EP U178
DI 10.1038/nature10782
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 892LG
UT WOS:000300287100051
PM 22318518
DA 2026-03-09
ER

PT J
AU Duan, S
   Cermak, L
   Pagan, JK
   Rossi, M
   Martinengo, C
   di Celle, PF
   Chapuy, B
   Shipp, M
   Chiarle, R
   Pagano, M
AF Duan, Shanshan
   Cermak, Lukas
   Pagan, Julia K.
   Rossi, Mario
   Martinengo, Cinzia
   di Celle, Paola Francia
   Chapuy, Bjoern
   Shipp, Margaret
   Chiarle, Roberto
   Pagano, Michele
TI FBXO11 targets BCL6 for degradation and is inactivated in diffuse large B-cell lymphomas
SO NATURE
LA English
DT Article
ID scf ubiquitin ligase; gene-expression; pathogenesis
AB BCL6 is the product of a proto-oncogene implicated in the pathogenesis of human B-cell lymphomas(1,2). By binding specific DNA sequences, BCL6 controls the transcription of a variety of genes involved in B-cell development, differentiation and activation. BCL6 is overexpressed in the majority of patients with aggressive diffuse large B-cell lymphoma (DLBCL), the most common lymphoma in adulthood, and transgenic mice constitutively expressing BCL6 in B cells develop DLBCLs similar to the human disease(3,4). In many DLBCL patients, BCL6 overexpression is achieved through translocation (similar to 40%) or hypermutation of its promoter (similar to 15%). However, many other DLBCLs overexpress BCL6 through an unknown mechanism. Here we show that BCL6 is targeted for ubiquitylation and proteasomal degradation by a SKP1-CUL1-F-box protein (SCF) ubiquitin ligase complex that contains the orphan F-box protein FBXO11 (refs 5, 6). The gene encoding FBXO11 was found to be deleted or mutated in multiple DLBCL cell lines, and this inactivation of FBXO11 correlated with increased levels and stability of BCL6. Similarly, FBXO11 was either deleted or mutated in primary DLBCLs. Notably, tumour-derived FBXO11 mutants displayed an impaired ability to induce BCL6 degradation. Reconstitution of FBXO11 expression in FBXO11-deleted DLBCL cells promoted BCL6 ubiquitylation and degradation, inhibited cell proliferation, and induced cell death. FBXO11-deleted DLBCL cells generated tumours in immunodeficient mice, and the tumorigenicity was suppressed by FBXO11 reconstitution. We reveal a molecular mechanism controlling BCL6 stability and propose that mutations and deletions in FBXO11 contribute to lymphomagenesis through BCL6 stabilization. The deletions/mutations found in DLBCLs are largely monoallelic, indicating that FBXO11 is a haplo-insufficient tumour suppressor gene.
C1 [Duan, Shanshan; Cermak, Lukas; Pagan, Julia K.; Rossi, Mario; Pagano, Michele] NYU, Sch Med, NYU Canc Inst, Dept Pathol, New York, NY 10016 USA.
   [Duan, Shanshan; Cermak, Lukas; Pagan, Julia K.; Pagano, Michele] NYU, Sch Med, Howard Hughes Med Inst, New York, NY 10016 USA.
   [Martinengo, Cinzia; Chiarle, Roberto] Univ Turin, CERMS, Dept Biomed Sci & Human Oncol, I-10126 Turin, Italy.
   [di Celle, Paola Francia] San Giovanni Battista Hosp, I-10126 Turin, Italy.
   [Chapuy, Bjoern; Shipp, Margaret] Dana Farber Canc Inst, Boston, MA 02115 USA.
C3 New York University; New York University; Howard Hughes Medical Institute; University of Turin; A.O.U. Citta della Salute e della Scienza di Torino; AOU San Giovanni Battista-Molinette; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute
RP Pagano, M (corresponding author), NYU, Sch Med, NYU Canc Inst, Dept Pathol, 522 1st Ave,SRB 1107, New York, NY 10016 USA.
EM roberto.chiarle@unito.it; michele.pagano@nyumc.org
FU National Institutes of Health [R01-GM57587, R37-CA76584, R21-CA161108, PO1-CA092625]; Susan G. Komen for the Cure; Lymphoma Research Foundation; AIRC; ERC [ERC-2009-StG-Proposal No242965-LUNELY]
NR 19
TC 244
Z9 281
U1 0
U2 35
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JAN 5
PY 2012
VL 481
IS 7379
BP 90
EP U100
DI 10.1038/nature10688
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 872VD
UT WOS:000298836900035
PM 22113614
DA 2026-03-09
ER

PT J
AU Curtis, BA
   Tanifuji, G
   Burki, F
   Gruber, A
   Irimia, M
   Maruyama, S
   Arias, MC
   Ball, SG
   Gile, GH
   Hirakawa, Y
   Hopkins, JF
   Kuo, A
   Rensing, SA
   Schmutz, J
   Symeonidi, A
   Elias, M
   Eveleigh, RJM
   Herman, EK
   Klute, MJ
   Nakayama, T
   Oborník, M
   Reyes-Prieto, A
   Armbrust, EV
   Aves, SJ
   Beiko, RG
   Coutinho, P
   Dacks, JB
   Durnford, DG
   Fast, NM
   Green, BR
   Grisdale, CJ
   Hempel, F
   Henrissat, B
   Höppner, MP
   Ishida, KI
   Kim, E
   Koreny, LK
   Kroth, PG
   Liu, Y
   Malik, SB
   Maier, UG
   McRose, D
   Mock, T
   Neilson, JAD
   Onodera, NT
   Poole, AM
   Pritham, EJ
   Richards, TA
   Rocap, G
   Roy, SW
   Sarai, C
   Schaack, S
   Shirato, S
   Slamovits, CH
   Spencer, DF
   Suzuki, S
   Worden, AZ
   Zauner, S
   Barry, K
   Bell, C
   Bharti, AK
   Crow, JA
   Grimwood, J
   Kramer, R
   Lindquist, E
   Lucas, S
   Salamov, A
   McFadden, GI
   Lane, CE
   Keeling, PJ
   Gray, MW
   Grigoriev, IV
   Archibald, JM
AF Curtis, Bruce A.
   Tanifuji, Goro
   Burki, Fabien
   Gruber, Ansgar
   Irimia, Manuel
   Maruyama, Shinichiro
   Arias, Maria C.
   Ball, Steven G.
   Gile, Gillian H.
   Hirakawa, Yoshihisa
   Hopkins, Julia F.
   Kuo, Alan
   Rensing, Stefan A.
   Schmutz, Jeremy
   Symeonidi, Aikaterini
   Elias, Marek
   Eveleigh, Robert J. M.
   Herman, Emily K.
   Klute, Mary J.
   Nakayama, Takuro
   Obornik, Miroslav
   Reyes-Prieto, Adrian
   Armbrust, E. Virginia
   Aves, Stephen J.
   Beiko, Robert G.
   Coutinho, Pedro
   Dacks, Joel B.
   Durnford, Dion G.
   Fast, Naomi M.
   Green, Beverley R.
   Grisdale, Cameron J.
   Hempel, Franziska
   Henrissat, Bernard
   Hoeppner, Marc P.
   Ishida, Ken-Ichiro
   Kim, Eunsoo
   Koreny, Lude. K.
   Kroth, Peter G.
   Liu, Yuan
   Malik, Shehre-Banoo
   Maier, Uwe G.
   McRose, Darcy
   Mock, Thomas
   Neilson, Jonathan A. D.
   Onodera, Naoko T.
   Poole, Anthony M.
   Pritham, Ellen J.
   Richards, Thomas A.
   Rocap, Gabrielle
   Roy, Scott W.
   Sarai, Chihiro
   Schaack, Sarah
   Shirato, Shu
   Slamovits, Claudio H.
   Spencer, David F.
   Suzuki, Shigekatsu
   Worden, Alexandra Z.
   Zauner, Stefan
   Barry, Kerrie
   Bell, Callum
   Bharti, Arvind K.
   Crow, John A.
   Grimwood, Jane
   Kramer, Robin
   Lindquist, Erika
   Lucas, Susan
   Salamov, Asaf
   McFadden, Geoffrey I.
   Lane, Christopher E.
   Keeling, Patrick J.
   Gray, Michael W.
   Grigoriev, Igor V.
   Archibald, John M.
TI Algal genomes reveal evolutionary mosaicism and the fate of nucleomorphs
SO NATURE
LA English
DT Article
ID gene-transfer; nucleus; chlorarachniophyte; proteins; sequence; green; red; cryptophytes; eukaryotes; history
AB Cryptophyte and chlorarachniophyte algae are transitional forms in the widespread secondary endosymbiotic acquisition of photosynthesis by engulfment of eukaryotic algae. Unlike most secondary plastid-bearing algae, miniaturized versions of the endosymbiont nuclei (nucleomorphs) persist in cryptophytes and chlorarachniophytes. To determine why, and to address other fundamental questions about eukaryote-eukaryote endosymbiosis, we sequenced the nuclear genomes of the cryptophyte Guillardia theta and the chlorarachniophyte Bigelowiella natans. Both genomes have >21,000 protein genes and are intron rich, and B. natans exhibits unprecedented alternative splicing for a single-celled organism. Phylogenomic analyses and subcellular targeting predictions reveal extensive genetic and biochemical mosaicism, with both host-and endosymbiont-derived genes servicing the mitochondrion, the host cell cytosol, the plastid and the remnant endosymbiont cytosol of both algae. Mitochondrion-to-nucleus gene transfer still occurs in both organisms but plastid-to-nucleus and nucleomorph-to-nucleus transfers do not, which explains why a small residue of essential genes remains locked in each nucleomorph.
C1 [Curtis, Bruce A.; Tanifuji, Goro; Maruyama, Shinichiro; Gile, Gillian H.; Hopkins, Julia F.; Eveleigh, Robert J. M.; Malik, Shehre-Banoo; Onodera, Naoko T.; Slamovits, Claudio H.; Spencer, David F.; Grigoriev, Igor V.] Dalhousie Univ, Dept Biochem & Mol Biol, Halifax, NS B3H 4R2, Canada.
   [Curtis, Bruce A.; Tanifuji, Goro; Maruyama, Shinichiro; Nakayama, Takuro; Onodera, Naoko T.; Spencer, David F.] Dalhousie Univ, Ctr Comparat Genom & Evolutionary Bioinformat, Halifax, NS B3H 4R2, Canada.
   [Curtis, Bruce A.; Tanifuji, Goro; Burki, Fabien; Maruyama, Shinichiro; Nakayama, Takuro; Reyes-Prieto, Adrian] Univ British Columbia, Integrated Microbial Biodivers Program, Canadian Inst Adv Res, Vancouver, BC V6T 1Z4, Canada.
   [Burki, Fabien; Hirakawa, Yoshihisa] Univ British Columbia, Dept Bot, Vancouver, BC V6T 1Z4, Canada.
   [Gruber, Ansgar] Univ Konstanz, Fachbereich Biol, D-78457 Constance, Germany.
   [Irimia, Manuel] Univ Toronto, Dept Med Res, Toronto, ON M5S 3E1, Canada.
   [Arias, Maria C.; Ball, Steven G.] Banting & Best Sci & Technol Lille, F-59655 Villeneuve Dascq, France.
   [Kuo, Alan] US DOE, Joint Genome Inst, Walnut Creek, CA 94598 USA.
   [Rensing, Stefan A.; Schmutz, Jeremy] Univ Freiburg, Fac Biol, D-79085 Freiburg, Germany.
   [Schmutz, Jeremy] HudsonAlpha Genome Sequencing Ctr, Huntsville, AL 35806 USA.
   [Elias, Marek] Univ Ostrava, Fac Sci, Dept Biol & Ecol, Life Sci Res Ctr, Ostrava 71000, Czech Republic.
   [Eveleigh, Robert J. M.] Genome Quebec, Montreal, PQ H3A 1A4, Canada.
   [Herman, Emily K.; Klute, Mary J.] Univ Alberta, Dept Cell Biol, Edmonton, AB T6G 2H7, Canada.
   [Obornik, Miroslav] Univ S Bohemia, Fac Sci, Ceske Budejovice 37005, Czech Republic.
   [Obornik, Miroslav] Univ S Bohemia, Biol Ctr, Ceske Budejovice 37005, Czech Republic.
   [Obornik, Miroslav] Acad Sci Czech Republ, Inst Microbiol, Trebon 37981, Czech Republic.
   [Reyes-Prieto, Adrian] Univ New Brunswick, Dept Biol, Fredericton, NB E3B 5A3, Canada.
   [Armbrust, E. Virginia] Univ Washington, Sch Oceanog, Seattle, WA 98195 USA.
   [Aves, Stephen J.] Univ Exeter, Coll Life & Environm Sci, Exeter EX4 4QD, Devon, England.
   [Beiko, Robert G.] Dalhousie Univ, Fac Comp Sci, Halifax, NS B3H 4R2, Canada.
   [Coutinho, Pedro] Aix Marseille Univ, CNRS UMR 7257, F-13228 Marseille, France.
   [Hempel, Franziska] LOEWE Zentrum Synthet Mikrobiol Synmikro, D-35032 Marburg, Germany.
   [Hoeppner, Marc P.] Uppsala Univ, Dept Med Biochem & Microbiol, SE-75123 Uppsala, Sweden.
   [Ishida, Ken-Ichiro] Univ Tsukuba, Grad Sch Life & Environm Sci, Tsukuba, Ibaraki 3058572, Japan.
   [Kim, Eunsoo] Amer Museum Nat Hist, Div Invertebrate Zool, New York, NY 10024 USA.
   [Liu, Yuan] Nat Hist Museum, London SW7 5BD, England.
   [McRose, Darcy] Monterey Bay Aquarium Res Inst, Moss Landing, CA 95039 USA.
   [Mock, Thomas] Univ E Anglia, Sch Environm Sci, Norwich NR4 7TJ, Norfolk, England.
   [Poole, Anthony M.] Univ Canterbury, Biomol Interact Ctr, Christchurch 8140, New Zealand.
   [Pritham, Ellen J.] Eccles Inst Human Genet, Salt Lake City, UT 84112 USA.
   [Roy, Scott W.] San Francisco State Univ, San Francisco, CA 94132 USA.
   [Schaack, Sarah] Reed Coll, Portland, OR 97202 USA.
   [Kramer, Robin] Natl Ctr Genome Resources, Santa Fe, NM 87505 USA.
   [McFadden, Geoffrey I.] Univ Melbourne, Sch Bot, Melbourne, Vic 3010, Australia.
   [Lane, Christopher E.] Univ Rhode Isl, Kingston, RI 02881 USA.
C3 Dalhousie University; Dalhousie University; University of British Columbia; Canadian Institute for Advanced Research (CIFAR); University of British Columbia; University of Konstanz; University of Toronto; United States Department of Energy (DOE); Joint BioEnergy Institute - JBEI; Joint Genome Institute - JGI; University of Freiburg; HudsonAlpha Institute for Biotechnology; University of Ostrava; University of Alberta; University of South Bohemia Ceske Budejovice; Czech Academy of Sciences; Biology Centre of the Czech Academy of Sciences; University of South Bohemia Ceske Budejovice; Czech Academy of Sciences; Institute of Microbiology of the Czech Academy of Sciences; University of New Brunswick; University of Washington; University of Washington Seattle; University of Exeter; Dalhousie University; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB); Aix-Marseille Universite; Uppsala University; University of Tsukuba; American Museum of Natural History (AMNH); Natural History Museum London; Monterey Bay Aquarium Research Institute; University of East Anglia; University of Canterbury; California State University System; San Francisco State University; Reed College - Portland; National Center for Genome Resources (NCGR); University of Melbourne; University of Rhode Island
RP Archibald, JM (corresponding author), Dalhousie Univ, Dept Biochem & Mol Biol, Halifax, NS B3H 4R2, Canada.
EM john.archibald@dal.ca
FU Office of Science of the US Department of Energy [DE-AC02-05CH11231]; Natural Sciences and Engineering Research Council of Canada; Office Of The Director; Office of Integrative Activities [1004057] Funding Source: National Science Foundation; BBSRC [BB/G00885X/2, BB/G00885X/1] Funding Source: UKRI; Biotechnology and Biological Sciences Research Council [BB/G00885X/1, BB/G00885X/2] Funding Source: researchfish
NR 50
TC 302
Z9 334
U1 1
U2 295
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 6
PY 2012
VL 492
IS 7427
BP 59
EP 65
DI 10.1038/nature11681
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 048EQ
UT WOS:000311893400045
PM 23201678
DA 2026-03-09
ER

PT J
AU Mackay, TFC
   Richards, S
   Stone, EA
   Barbadilla, A
   Ayroles, JF
   Zhu, DH
   Casillas, S
   Han, Y
   Magwire, MM
   Cridland, JM
   Richardson, MF
   Anholt, RRH
   Barrón, M
   Bess, C
   Blankenburg, KP
   Carbone, MA
   Castellano, D
   Chaboub, L
   Duncan, L
   Harris, Z
   Javaid, M
   Jayaseelan, JC
   Jhangiani, SN
   Jordan, KW
   Lara, F
   Lawrence, F
   Lee, SL
   Librado, P
   Linheiro, RS
   Lyman, RF
   Mackey, AJ
   Munidasa, M
   Muzny, DM
   Nazareth, L
   Newsham, I
   Perales, L
   Pu, LL
   Qu, C
   Ràmia, M
   Reid, JG
   Rollmann, SM
   Rozas, J
   Saada, N
   Turlapati, L
   Worley, KC
   Wu, YQ
   Yamamoto, A
   Zhu, YM
   Bergman, CM
   Thornton, KR
   Mittelman, D
   Gibbs, RA
AF Mackay, Trudy F. C.
   Richards, Stephen
   Stone, Eric A.
   Barbadilla, Antonio
   Ayroles, Julien F.
   Zhu, Dianhui
   Casillas, Sonia
   Han, Yi
   Magwire, Michael M.
   Cridland, Julie M.
   Richardson, Mark F.
   Anholt, Robert R. H.
   Barron, Maite
   Bess, Crystal
   Blankenburg, Kerstin Petra
   Carbone, Mary Anna
   Castellano, David
   Chaboub, Lesley
   Duncan, Laura
   Harris, Zeke
   Javaid, Mehwish
   Jayaseelan, Joy Christina
   Jhangiani, Shalini N.
   Jordan, Katherine W.
   Lara, Fremiet
   Lawrence, Faye
   Lee, Sandra L.
   Librado, Pablo
   Linheiro, Raquel S.
   Lyman, Richard F.
   Mackey, Aaron J.
   Munidasa, Mala
   Muzny, Donna Marie
   Nazareth, Lynne
   Newsham, Irene
   Perales, Lora
   Pu, Ling-Ling
   Qu, Carson
   Ramia, Miquel
   Reid, Jeffrey G.
   Rollmann, Stephanie M.
   Rozas, Julio
   Saada, Nehad
   Turlapati, Lavanya
   Worley, Kim C.
   Wu, Yuan-Qing
   Yamamoto, Akihiko
   Zhu, Yiming
   Bergman, Casey M.
   Thornton, Kevin R.
   Mittelman, David
   Gibbs, Richard A.
TI The Drosophila melanogaster Genetic Reference Panel
SO NATURE
LA English
DT Article
ID mcdonald-kreitman test; slightly deleterious mutations; adaptive protein evolution; quantitative traits; molecular evolution; dna polymorphism; population-size; recombination; selection; challenges
AB A major challenge of biology is understanding the relationship between molecular genetic variation and variation in quantitative traits, including fitness. This relationship determines our ability to predict phenotypes from genotypes and to understand how evolutionary forces shape variation within and between species. Previous efforts to dissect the genotype-phenotype map were based on incomplete genotypic information. Here, we describe the Drosophila melanogaster Genetic Reference Panel (DGRP), a community resource for analysis of population genomics and quantitative traits. The DGRP consists of fully sequenced inbred lines derived from a natural population. Population genomic analyses reveal reduced polymorphism in centromeric autosomal regions and the X chromosome, evidence for positive and negative selection, and rapid evolution of the X chromosome. Many variants in novel genes, most at low frequency, are associated with quantitative traits and explain a large fraction of the phenotypic variance. The DGRP facilitates genotype-phenotype mapping using the power of Drosophila genetics.
C1 [Mackay, Trudy F. C.; Stone, Eric A.; Ayroles, Julien F.; Magwire, Michael M.; Carbone, Mary Anna; Duncan, Laura; Harris, Zeke; Jordan, Katherine W.; Lawrence, Faye; Lyman, Richard F.; Rollmann, Stephanie M.; Turlapati, Lavanya; Yamamoto, Akihiko] N Carolina State Univ, Dept Genet, Raleigh, NC 27695 USA.
   [Richards, Stephen; Zhu, Dianhui; Han, Yi; Bess, Crystal; Blankenburg, Kerstin Petra; Chaboub, Lesley; Javaid, Mehwish; Jayaseelan, Joy Christina; Jhangiani, Shalini N.; Lara, Fremiet; Lee, Sandra L.; Munidasa, Mala; Muzny, Donna Marie; Nazareth, Lynne; Newsham, Irene; Perales, Lora; Pu, Ling-Ling; Qu, Carson; Reid, Jeffrey G.; Saada, Nehad; Worley, Kim C.; Wu, Yuan-Qing; Zhu, Yiming; Gibbs, Richard A.] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA.
   [Barbadilla, Antonio; Casillas, Sonia; Barron, Maite; Castellano, David; Ramia, Miquel] Univ Autonoma Barcelona, Genom Bioinformat & Evolut Grp, Inst Biotecnol & Biomed IBB, Dept Genet & Microbiol, Bellaterra 08193, Spain.
   [Ayroles, Julien F.; Thornton, Kevin R.] Univ Calif Irvine, Dept Ecol & Evolutionary Biol, Irvine, CA 92697 USA.
   [Richardson, Mark F.; Linheiro, Raquel S.; Bergman, Casey M.] Univ Manchester, Fac Life Sci, Manchester M13 9PT, Lancs, England.
   [Anholt, Robert R. H.] N Carolina State Univ, Dept Biol, Raleigh, NC 27695 USA.
   [Librado, Pablo; Rozas, Julio] Univ Barcelona, Fac Biol, Mol Evolutionary Genet Grp, Dept Genet, E-08028 Barcelona, Spain.
   [Mackey, Aaron J.] Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA 22908 USA.
   [Mittelman, David] Virginia Tech, Virginia Bioinformat Inst, Blacksburg, VA 24061 USA.
   [Mittelman, David] Virginia Tech, Dept Biol Sci, Blacksburg, VA 24061 USA.
C3 North Carolina State University; Baylor College of Medicine; Autonomous University of Barcelona; University of California System; University of California Irvine; University of Manchester; North Carolina State University; University of Barcelona; University of Virginia; Virginia Polytechnic Institute & State University; Virginia Polytechnic Institute & State University
RP Mackay, TFC (corresponding author), N Carolina State Univ, Dept Genet, Box 7614, Raleigh, NC 27695 USA.
EM trudy_mackay@ncsu.edu
FU National Institutes of Health [GM 45146, R01 GM 059469, MCI BFU 2009-09504, R01 GM 085183, NHGRI U54 HG003273]; NVIDIA Foundation
NR 44
TC 1239
Z9 1499
U1 1
U2 290
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD FEB 9
PY 2012
VL 482
IS 7384
BP 173
EP 178
DI 10.1038/nature10811
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 888HI
UT WOS:000299994100029
PM 22318601
DA 2026-03-09
ER

PT J
AU Takahashi, S
   Brunel, LC
   Edwards, DT
   van Tol, J
   Ramian, G
   Han, S
   Sherwin, MS
AF Takahashi, S.
   Brunel, L. -C.
   Edwards, D. T.
   van Tol, J.
   Ramian, G.
   Han, S.
   Sherwin, M. S.
TI Pulsed electron paramagnetic resonance spectroscopy powered by a free-electron laser
SO NATURE
LA English
DT Article
ID spin-resonance; distance measurements; generation; spectrometer; composites; switches; field; esr
AB Electron paramagnetic resonance (EPR) spectroscopy interrogates unpaired electron spins in solids and liquids to reveal local structure and dynamics; for example, EPR has elucidated parts of the structure of protein complexes that other techniques in structural biology have not been able to reveal(1-4). EPR can also probe the interplay of light and electricity in organic solar cells(5-7) and light-emitting diodes(8), and the origin of decoherence in condensed matter, which is of fundamental importance to the development of quantum information processors(9-13). Like nuclear magnetic resonance, EPR spectroscopy becomes more powerful at high magnetic fields and frequencies, and with excitation by coherent pulses rather than continuous waves. However, the difficulty of generating sequences of powerful pulses at frequencies above 100 gigahertz has, until now, confined high-power pulsed EPR to magnetic fields of 3.5 teslas and below. Here we demonstrate that one-kilowatt pulses from a free-electron laser can power a pulsed EPR spectrometer at 240 gigahertz (8.5 teslas), providing transformative enhancements over the alternative, a state-of-the-art similar to 30-milliwatt solid-state source. Our spectrometer can rotate spin-1/2 electrons through pi/2 in only 6 nanoseconds (compared to 300 nanoseconds with the solid-state source). Fourier-transform EPR on nitrogen impurities in diamond demonstrates excitation and detection of EPR lines separated by about 200 megahertz. We measured decoherence times as short as 63 nanoseconds, in a frozen solution of nitroxide free-radicals at temperatures as high as 190 kelvin. Both free-electron lasers and the quasi-optical technology developed for the spectrometer are scalable to frequencies well in excess of one terahertz, opening the way to high-power pulsed EPR spectroscopy up to the highest static magnetic fields currently available.
C1 [Takahashi, S.; Brunel, L. -C.; Han, S.; Sherwin, M. S.] Univ Calif Santa Barbara, Inst Terahertz Sci & Technol, Santa Barbara, CA 93106 USA.
   [Takahashi, S.] Univ So Calif, Dept Chem, Los Angeles, CA 90089 USA.
   [Edwards, D. T.; Sherwin, M. S.] Univ Calif Santa Barbara, Dept Phys, Santa Barbara, CA 93106 USA.
   [van Tol, J.] Florida State Univ, Natl High Magnet Field Lab, Tallahassee, FL 32310 USA.
   [Han, S.] Univ Calif Santa Barbara, Dept Chem & Biochem, Santa Barbara, CA 93106 USA.
C3 University of California System; University of California Santa Barbara; University of Southern California; University of California System; University of California Santa Barbara; State University System of Florida; Florida State University; University of California System; University of California Santa Barbara
RP Sherwin, MS (corresponding author), Univ Calif Santa Barbara, Inst Terahertz Sci & Technol, Santa Barbara, CA 93106 USA.
EM sherwin@physics.ucsb.edu
FU NSF [CHE-0821589, DMR-0520481, DMR-0703925]; W. M. Keck Foundation; Division Of Chemistry; Direct For Mathematical & Physical Scien [0821589] Funding Source: National Science Foundation
NR 29
TC 75
Z9 88
U1 4
U2 177
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD SEP 20
PY 2012
VL 489
IS 7416
BP 409
EP 413
DI 10.1038/nature11437
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 007AK
UT WOS:000308860900040
PM 22996555
DA 2026-03-09
ER

PT J
AU Eulalio, A
   Mano, M
   Dal Ferro, M
   Zentilin, L
   Sinagra, G
   Zacchigna, S
   Giacca, M
AF Eulalio, Ana
   Mano, Miguel
   Dal Ferro, Matteo
   Zentilin, Lorena
   Sinagra, Gianfranco
   Zacchigna, Serena
   Giacca, Mauro
TI Functional screening identifies miRNAs inducing cardiac regeneration
SO NATURE
LA English
DT Article
ID zebrafish heart regeneration; dna-synthesis; cell-cycle; cardiomyocyte dedifferentiation; mitotic division; gene-expression; hypertrophy; micrornas; proliferation; rna
AB In mammals, enlargement of the heart during embryonic development is primarily dependent on the increase in cardiomyocyte numbers. Shortly after birth, however, cardiomyocytes stop proliferating and further growth of the myocardium occurs through hypertrophic enlargement of the existing myocytes. As a consequence of the minimal renewal of cardiomyocytes during adult life, repair of cardiac damage through myocardial regeneration is very limited. Here we show that the exogenous administration of selected microRNAs (miRNAs) markedly stimulates cardiomyocyte proliferation and promotes cardiac repair. We performed a high-content microscopy, high-throughput functional screening for human miRNAs that promoted neonatal cardiomyocyte proliferation using a whole-genome miRNA library. Forty miRNAs strongly increased both DNA synthesis and cytokinesis in neonatal mouse and rat cardiomyocytes. Two of these miRNAs (hsa-miR-590 and hsa-miR-199a) were further selected for testing and were shown to promote cell cycle re-entry of adult cardiomyocytes ex vivo and to promote cardiomyocyte proliferation in both neonatal and adult animals. After myocardial infarction in mice, these miRNAs stimulated marked cardiac regeneration and almost complete recovery of cardiac functional parameters. The miRNAs identified hold great promise for the treatment of cardiac pathologies consequent to cardiomyocyte loss.
C1 [Eulalio, Ana; Mano, Miguel; Dal Ferro, Matteo; Zentilin, Lorena; Zacchigna, Serena; Giacca, Mauro] ICGEB, Mol Med Lab, I-34149 Trieste, Italy.
   [Dal Ferro, Matteo; Sinagra, Gianfranco] Univ Trieste, Dept Med Surg & Hlth Sci, Trieste, Italy.
   [Dal Ferro, Matteo; Sinagra, Gianfranco] Azienda Osped Univ Osped Riuniti Trieste, Ctr Translat Cardiol, I-34129 Trieste, Italy.
C3 International Center for Genetic Engineering & Biotechnology (ICGEB); University of Trieste; University of Trieste; University Trieste Hospital
RP Giacca, M (corresponding author), ICGEB, Mol Med Lab, I-34149 Trieste, Italy.
EM giacca@icgeb.org
FU FEBS Long Term Fellowship; European Research Council (ERC) [250124]; Project CTC from the Fondazione CRTrieste, Trieste, Italy; European Research Council (ERC) [250124] Funding Source: European Research Council (ERC)
NR 50
TC 856
Z9 993
U1 2
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 DEC 20
PY 2012
VL 492
IS 7429
BP 376
EP +
DI 10.1038/nature11739
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 056KQ
UT WOS:000312488200045
PM 23222520
DA 2026-03-09
ER

PT J
AU Ngaki, MN
   Louie, GV
   Philippe, RN
   Manning, G
   Pojer, F
   Bowman, ME
   Li, L
   Larsen, E
   Wurtele, ES
   Noel, JP
AF Ngaki, Micheline N.
   Louie, Gordon V.
   Philippe, Ryan N.
   Manning, Gerard
   Pojer, Florence
   Bowman, Marianne E.
   Li, Ling
   Larsen, Elise
   Wurtele, Eve Syrkin
   Noel, Joseph P.
TI Evolution of the chalcone-isomerase fold from fatty-acid binding to stereospecific catalysis
SO NATURE
LA English
DT Article
ID reaction-mechanism; functional genomics; diffraction data; arabidopsis; gene; identification; transformation; biosynthesis; alignment; program
AB Specialized metabolic enzymes biosynthesize chemicals of ecological importance, often sharing a pedigree with primary metabolic enzymes(1). However, the lineage of the enzyme chalcone isomerase (CHI) remained unknown. In vascular plants, CHI-catalysed conversion of chalcones to chiral (S)-flavanones is a committed step in the production of plant flavonoids, compounds that contribute to attraction, defence(2) and development(3). CHI operates near the diffusion limit with stereospecific control(4,5). Although associated primarily with plants, the CHI fold occurs in several other eukaryotic lineages and in some bacteria. Here we report crystal structures, ligand-binding properties and in vivo functional characterization of a non-catalytic CHI-fold family from plants. Arabidopsis thaliana contains five actively transcribed genes encoding CHI-fold proteins, three of which additionally encode amino-terminal chloroplast-transit sequences. These three CHI-fold proteins localize to plastids, the site of de novo fatty-acid biosynthesis in plant cells. Furthermore, their expression profiles correlate with those of core fatty-acid biosynthetic enzymes, with maximal expression occurring in seeds and coinciding with increased fatty-acid storage in the developing embryo. In vitro, these proteins are fatty-acid-binding proteins (FAPs). FAP knockout A. thaliana plants show elevated alpha-linolenic acid levels and marked reproductive defects, including aberrant seed formation. Notably, the FAP discovery defines the adaptive evolution of a stereospecific and catalytically 'perfected' enzyme(6) from a non-enzymatic ancestor over a defined period of plant evolution.
C1 [Ngaki, Micheline N.; Li, Ling; Wurtele, Eve Syrkin] Iowa State Univ, Dept Genet Dev & Cell Biol, Ames, IA 50011 USA.
   [Louie, Gordon V.; Philippe, Ryan N.; Pojer, Florence; Bowman, Marianne E.; Larsen, Elise; Noel, Joseph P.] Salk Inst Biol Studies, Howard Hughes Med Inst, Jack H Skirball Ctr Chem Biol & Prote, La Jolla, CA 92037 USA.
   [Manning, Gerard] Salk Inst Biol Studies, Razavi Newman Ctr Bioinformat, La Jolla, CA 92037 USA.
C3 Iowa State University; Howard Hughes Medical Institute; Salk Institute; Salk Institute
RP Wurtele, ES (corresponding author), Iowa State Univ, Dept Genet Dev & Cell Biol, Ames, IA 50011 USA.
EM mash@iastate.edu; noel@salk.edu
FU Fulbright Fellowship; National Science Foundation [MCB-0645794, EEC-0813570, MCB-0951170]; National Cancer Institute [CA14195]; Plant Sciences Institute at Iowa State University; Department of Energy, Office of Biological and Environmental Research; National Institutes of Health, National Institute of General Medical Sciences; National Cancer Institute [P30CA014195] Funding Source: NIH RePORTER; Div Of Molecular and Cellular Bioscience; Direct For Biological Sciences [0951170] Funding Source: National Science Foundation
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NR 56
TC 164
Z9 208
U1 3
U2 137
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 24
PY 2012
VL 485
IS 7399
BP 530
EP U147
DI 10.1038/nature11009
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 946IH
UT WOS:000304344500049
PM 22622584
DA 2026-03-09
ER

PT J
AU Brooks, DWC
   Botter, T
   Schreppler, S
   Purdy, TP
   Brahms, N
   Stamper-Kurn, DM
AF Brooks, Daniel W. C.
   Botter, Thierry
   Schreppler, Sydney
   Purdy, Thomas P.
   Brahms, Nathan
   Stamper-Kurn, Dan M.
TI Non-classical light generated by quantum-noise-driven cavity optomechanics
SO NATURE
LA English
DT Article
ID induced transparency; radiation-pressure; ground-state; reduction
AB Optomechanical systems(1), in which light drives and is affected by the motion of a massive object, will comprise a new framework for nonlinear quantum optics, with applications ranging from the storage(2-4) and transduction(5,6) of quantum information to enhanced detection sensitivity in gravitational wave detectors(7,8). However, quantum optical effects in optomechanical systems have remained obscure, because their detection requires the object's motion to be dominated by vacuum fluctuations in the optical radiation pressure; so far, direct observations have been stymied by technical and thermal noise. Here we report an implementation of cavity optomechanics(9,10) using ultracold atoms in which the collective atomic motion is dominantly driven by quantum fluctuations in radiation pressure. The back-action of this motion onto the cavity light field produces ponderomotive squeezing(11,12). We detect this quantum phenomenon by measuring sub-shot-noise optical squeezing. Furthermore, the system acts as a low-power, high-gain, nonlinear parametric amplifier for optical fluctuations, demonstrating a gain of 20 dB with a pump corresponding to an average of only seven intracavity photons. These findings may pave the way for low-power quantum optical devices, surpassing quantum limits on position and force sensing(13,14), and the control and measurement of motion in quantum gases.
C1 [Brooks, Daniel W. C.; Botter, Thierry; Schreppler, Sydney; Purdy, Thomas P.; Brahms, Nathan; Stamper-Kurn, Dan M.] Univ Calif Berkeley, Dept Phys, Berkeley, CA 94720 USA.
   [Stamper-Kurn, Dan M.] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Div Mat Sci, Berkeley, CA 94720 USA.
C3 University of California System; University of California Berkeley; University of California System; University of California Berkeley; United States Department of Energy (DOE); Lawrence Berkeley National Laboratory
RP Brooks, DWC (corresponding author), Univ Calif Berkeley, Dept Phys, Berkeley, CA 94720 USA.
EM dwb@berkeley.edu
FU AFSOR; NSF; FQRNT; Division Of Physics; Direct For Mathematical & Physical Scien [1105559] Funding Source: National Science Foundation
NR 27
TC 315
Z9 364
U1 2
U2 113
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 23
PY 2012
VL 488
IS 7412
BP 476
EP 480
DI 10.1038/nature11325
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 992FS
UT WOS:000307761600029
PM 22895194
DA 2026-03-09
ER

PT J
AU Britton, JW
   Sawyer, BC
   Keith, AC
   Wang, CCJ
   Freericks, JK
   Uys, H
   Biercuk, MJ
   Bollinger, JJ
AF Britton, Joseph W.
   Sawyer, Brian C.
   Keith, Adam C.
   Wang, C. -C. Joseph
   Freericks, James K.
   Uys, Hermann
   Biercuk, Michael J.
   Bollinger, John J.
TI Engineered two-dimensional Ising interactions in a trapped-ion quantum simulator with hundreds of spins
SO NATURE
LA English
DT Article
ID optical lattices; ultracold atoms; physics; gases
AB The presence of long-range quantum spin correlations underlies a variety of physical phenomena in condensed-matter systems, potentially including high-temperature superconductivity(1,2). However, many properties of exotic, strongly correlated spin systems, such as spin liquids, have proved difficult to study, in part because calculations involving N-body entanglement become intractable for as few as N approximate to 30 particles(3). Feynman predicted that a quantum simulator-a special-purpose 'analogue' processor built using quantum bits (qubits)-would be inherently suited to solving such problems(4,5). In the context of quantum magnetism, a number of experiments have demonstrated the feasibility of this approach(6-14), but simulations allowing controlled, tunable interactions between spins localized on two- or three-dimensional lattices of more than a few tens of qubits have yet to be demonstrated, in part because of the technical challenge of realizing large-scale qubit arrays. Here we demonstrate a variable-range Ising-type spin-spin interaction, J(i,j), on a naturally occurring, two-dimensional triangular crystal lattice of hundreds of spin-half particles (beryllium ions stored in a Penning trap). This is a computationally relevant scale more than an order of magnitude larger than previous experiments. We show that a spin-dependent optical dipole force can produce an antiferromagnetic interaction J(i,j) proportional to d(i,j)(-a), where 0 <= a <= 3 and d(i,j) is the distance between spin pairs. These power laws correspond physically to infinite-range (a = 0), Coulomb-like (a = 1), monopole-dipole (a = 2) and dipole-dipole (a = 3) couplings. Experimentally, we demonstrate excellent agreement with a theory for 0.05 less than or similar to a less than or similar to 1.4. This demonstration, coupled with the high spin count, excellent quantum control and low technical complexity of the Penning trap, brings within reach the simulation of otherwise computationally intractable problems in quantum magnetism.
C1 [Britton, Joseph W.; Sawyer, Brian C.; Bollinger, John J.] US Natl Inst Stand & Technol, Div Time & Frequency, Boulder, CO 80305 USA.
   [Keith, Adam C.; Wang, C. -C. Joseph; Freericks, James K.] Georgetown Univ, Dept Phys, Washington, DC 20057 USA.
   [Keith, Adam C.] N Carolina State Univ, Dept Phys, Raleigh, NC 27695 USA.
   [Uys, Hermann] CSIR, Natl Laser Ctr, ZA-0001 Pretoria, South Africa.
   [Biercuk, Michael J.] Univ Sydney, Sch Phys, Ctr Engn Quantum Syst, Sydney, NSW 2006, Australia.
C3 National Institute of Standards & Technology (NIST) - USA; Georgetown University; North Carolina State University; Council for Scientific & Industrial Research (CSIR) - South Africa; University of Sydney
RP Britton, JW (corresponding author), US Natl Inst Stand & Technol, Div Time & Frequency, Boulder, CO 80305 USA.
EM joe.britton@gmail.com
FU DARPA OLE; NIST; NSF [DMR-1004268]; NRC; Australian Research Council Center of Excellence for Engineered Quantum Systems [CE110001013]; Direct For Mathematical & Physical Scien; Division Of Materials Research [1004268] Funding Source: National Science Foundation
NR 30
TC 791
Z9 891
U1 3
U2 159
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD APR 26
PY 2012
VL 484
IS 7395
BP 489
EP 492
DI 10.1038/nature10981
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 931FF
UT WOS:000303200400045
PM 22538611
DA 2026-03-09
ER

PT J
AU Babu, M
   Vlasblom, J
   Pu, SY
   Guo, XH
   Graham, C
   Bean, BDM
   Burston, HE
   Vizeacoumar, FJ
   Snider, J
   Phanse, S
   Fong, V
   Tam, YYC
   Davey, M
   Hnatshak, O
   Bajaj, N
   Chandran, S
   Punna, T
   Christopolous, C
   Wong, V
   Yu, A
   Zhong, GQ
   Li, J
   Stagljar, I
   Conibear, E
   Wodak, SJ
   Emili, A
   Greenblatt, JF
AF Babu, Mohan
   Vlasblom, James
   Pu, Shuye
   Guo, Xinghua
   Graham, Chris
   Bean, Bjoern D. M.
   Burston, Helen E.
   Vizeacoumar, Franco J.
   Snider, Jamie
   Phanse, Sadhna
   Fong, Vincent
   Tam, Yuen Yi C.
   Davey, Michael
   Hnatshak, Olha
   Bajaj, Navgeet
   Chandran, Shamanta
   Punna, Thanuja
   Christopolous, Constantine
   Wong, Victoria
   Yu, Analyn
   Zhong, Gouqing
   Li, Joyce
   Stagljar, Igor
   Conibear, Elizabeth
   Wodak, Shoshana J.
   Emili, Andrew
   Greenblatt, Jack F.
TI Interaction landscape of membrane-protein complexes in Saccharomyces cerevisiae
SO NATURE
LA English
DT Article
ID physical interactome; er exit; yeast; map; exploration; selection
AB Macromolecular assemblies involving membrane proteins (MPs) serve vital biological roles and are prime drug targets in a variety of diseases(1). Large-scale affinity purification studies of soluble-protein complexes have been accomplished for diverse model organisms, but no global characterization of MP-complex membership has been described so far. Here we report a complete survey of 1,590 putative integral, peripheral and lipid-anchored MPs from Saccharomyces cerevisiae, which were affinity purified in the presence of non-denaturing detergents. The identities of the co-purifying proteins were determined by tandem mass spectrometry and subsequently used to derive a high-confidence physical interaction map encompassing 1,726 membrane protein-protein interactions and 501 putative heteromeric complexes associated with the various cellular membrane systems. Our analysis reveals unexpected physical associations underlying the membrane biology of eukaryotes and delineates the global topological landscape of the membrane interactome.
C1 [Bean, Bjoern D. M.; Burston, Helen E.; Tam, Yuen Yi C.; Davey, Michael; Conibear, Elizabeth] Univ British Columbia, Child & Family Res Inst, Ctr Mol Med & Therapeut, Vancouver, BC V5Z 4H4, Canada.
   [Babu, Mohan; Guo, Xinghua; Graham, Chris; Vizeacoumar, Franco J.; Snider, Jamie; Phanse, Sadhna; Fong, Vincent; Hnatshak, Olha; Bajaj, Navgeet; Chandran, Shamanta; Punna, Thanuja; Christopolous, Constantine; Wong, Victoria; Yu, Analyn; Zhong, Gouqing; Li, Joyce; Stagljar, Igor; Emili, Andrew; Greenblatt, Jack F.] Univ Toronto, Donnelly Ctr, Banting & Best Dept Med Res, Toronto, ON M5S 3E1, Canada.
   [Babu, Mohan] Univ Regina, Res & Innovat Ctr, Dept Biochem, Regina, SK S4S 0A2, Canada.
   [Vlasblom, James; Pu, Shuye; Wodak, Shoshana J.] Hosp Sick Children, Toronto, ON M5G 1X8, Canada.
   [Vlasblom, James; Stagljar, Igor; Wodak, Shoshana J.] Univ Toronto, Dept Biochem, Toronto, ON M5S 1A8, Canada.
   [Stagljar, Igor; Wodak, Shoshana J.; Emili, Andrew; Greenblatt, Jack F.] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A8, Canada.
C3 University of British Columbia; Child & Family Research Institute; University of Toronto; University of Regina; University of Toronto; Hospital for Sick Children (SickKids); University of Toronto; University of Toronto
RP Conibear, E (corresponding author), Univ British Columbia, Child & Family Res Inst, Ctr Mol Med & Therapeut, 950 W 28th Ave, Vancouver, BC V5Z 4H4, Canada.
EM conibear@cmmt.ubc.ca; shoshana@sickkids.ca; andrew.emili@utoronto.ca; jack.greenblatt@utoronto.ca
FU Canadian Foundation for Innovation; Canadian Institutes of Health Research (CIHR MOP) [81156, 64394, 82940]; Canadian Cancer Society Research Institute; Heart and Stroke Foundation; Cystic Fibrosis Foundation; Novartis; Ontario Genomics Institute; Genome Canada; SickKids Foundation
NR 37
TC 185
Z9 209
U1 0
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 SEP 27
PY 2012
VL 489
IS 7417
BP 585
EP +
DI 10.1038/nature11354
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 046RG
UT WOS:000311781500008
PM 22940862
DA 2026-03-09
ER

PT J
AU Eisenhoffer, GT
   Loftus, PD
   Yoshigi, M
   Otsuna, H
   Chien, CB
   Morcos, PA
   Rosenblatt, J
AF Eisenhoffer, George T.
   Loftus, Patrick D.
   Yoshigi, Masaaki
   Otsuna, Hideo
   Chien, Chi-Bin
   Morcos, Paul A.
   Rosenblatt, Jody
TI Crowding induces live cell extrusion to maintain homeostatic cell numbers in epithelia
SO NATURE
LA English
DT Article
ID apoptotic cells; proliferation; extrude; jnk
AB For an epithelium to provide a protective barrier, it must maintain homeostatic cell numbers by matching the number of dividing cells with the number of dying cells. Although compensatory cell division can be triggered by dying cells(1-3), it is unknown how cell death might relieve overcrowding due to proliferation. When we trigger apoptosis in epithelia, dying cells are extruded to preserve a functional barrier(4). Extrusion occurs by cells destined to die signalling to surrounding epithelial cells to contract an actomyosin ring that squeezes the dying cell out(4-6). However, it is not clear what drives cell death during normal homeostasis. Here we show in human, canine and zebrafish cells that overcrowding due to proliferation and migration induces extrusion of live cells to control epithelial cell numbers. Extrusion of live cells occurs at sites where the highest crowding occurs in vivo and can be induced by experimentally overcrowding monolayers in vitro. Like apoptotic cell extrusion, live cell extrusion resulting from overcrowding also requires sphingosine 1-phosphate signalling and Rho-kinase-dependent myosin contraction, but is distinguished by signalling through stretch-activated channels. Moreover, disruption of a stretch-activated channel, Piezo1, in zebrafish prevents extrusion and leads to the formation of epithelial cell masses. Our findings reveal that during homeostatic turnover, growth and division of epithelial cells on a confined substratum cause overcrowding that leads to their extrusion and consequent death owing to the loss of survival factors. These results suggest that live cell extrusion could be a tumour-suppressive mechanism that prevents the accumulation of excess epithelial cells.
C1 [Eisenhoffer, George T.; Loftus, Patrick D.; Rosenblatt, Jody] Univ Utah, Huntsman Canc Inst, Dept Oncol Sci, Salt Lake City, UT 84112 USA.
   [Yoshigi, Masaaki] Univ Utah, Dept Pediat, Salt Lake City, UT 84108 USA.
   [Otsuna, Hideo; Chien, Chi-Bin] Univ Utah, Dept Neurobiol & Anat, Salt Lake City, UT 84132 USA.
   [Morcos, Paul A.] Gene Tools LLC, Philomath, OR 97370 USA.
C3 Utah System of Higher Education; University of Utah; Huntsman Cancer Institute; Utah System of Higher Education; University of Utah; Utah System of Higher Education; University of Utah
RP Rosenblatt, J (corresponding author), Univ Utah, Huntsman Canc Inst, Dept Oncol Sci, 2000 Circle Hope Dr, Salt Lake City, UT 84112 USA.
EM jody.rosenblatt@hci.utah.edu
FU National Institute of Biomedical Imaging and Bioengineering [EB-4443]; NIH-NIGMS NIH [1 DP2OD002056-01]; Laura and Arthur Colwin Endowed Marine Biology Laboratories Summer Research Fellowship Fund; NIH [5T32 CA03247-8, MH092256]; American Cancer Society [120464-PF-11-095-01 CSM]; University of Utah;  [P30 CA042014]; National Cancer Institute [P30CA042014] Funding Source: NIH RePORTER
NR 27
TC 670
Z9 789
U1 4
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 APR 26
PY 2012
VL 484
IS 7395
BP 546
EP U183
DI 10.1038/nature10999
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 931FF
UT WOS:000303200400058
PM 22504183
DA 2026-03-09
ER

PT J
AU Hoppa, MB
   Lana, B
   Margas, W
   Dolphin, AC
   Ryan, TA
AF Hoppa, Michael B.
   Lana, Beatrice
   Margas, Wojciech
   Dolphin, Annette C.
   Ryan, Timothy A.
TI α2δ expression sets presynaptic calcium channel abundance and release probability
SO NATURE
LA English
DT Article
ID gated ca2+ channels; factor-a domain; synaptic-transmission; neurotransmitter release; alpha(2)delta subunits; functional-property; fluorescent proteins; plasma-membrane; trafficking; ca(v)2.1
AB Synaptic neurotransmitter release is driven by Ca2+ influx through active zone voltage-gated calcium channels (VGCCs)(1,2). Control of active zone VGCC abundance and function remains poorly understood. Here we show that a trafficking step probably sets synaptic VGCC levels in rats, because overexpression of the pore-forming alpha 1(A) VGCC subunit fails to change synaptic VGCC abundance or function. alpha 2 delta s are a family of glycosylphosphatidylinositol (GPI)-anchored VGCC-associated subunits(3) that, in addition to being the target of the potent neuropathic analgesics gabapentin and pregabalin (alpha 2 delta-1 and alpha 2 delta-2)(4,5), were also identified in a forward genetic screen for pain genes (alpha 2 delta-3)(6). We show that these proteins confer powerful modulation of presynaptic function through two distinct molecular mechanisms. First, alpha 2 delta subunits set synaptic VGCC abundance, as predicted from their chaperone-like function when expressed in non-neuronal cells(3,7). Second, alpha 2 delta s configure synaptic VGCCs to drive exocytosis through an extracellular metal ion-dependent adhesion site (MIDAS), a conserved set of amino acids within the predicted von Willebrand A domain of alpha 2 delta. Expression of alpha 2 delta with an intact MIDAS motif leads to an 80% increase in release probability, while simultaneously protecting exocytosis from blockade by an intracellular Ca2+ chelator. alpha 2 delta s harbouring MIDAS site mutations still drive synaptic accumulation of VGCCs; however, they no longer change release probability or sensitivity to intracellular Ca2+ chelators. Our data reveal dual functionality of these clinically important VGCC subunits, allowing synapses to make more efficient use of Ca2+ entry to drive neurotransmitter release.
C1 [Hoppa, Michael B.; Ryan, Timothy A.] Weill Cornell Med Coll, Dept Biochem, New York, NY 10023 USA.
   [Lana, Beatrice; Margas, Wojciech; Dolphin, Annette C.] UCL, Dept Neurosci Physiol & Pharmacol, Lab Cellular & Mol Neurosci, London WC1E 6BT, England.
C3 Cornell University; Weill Cornell Medicine; University of London; University College London
RP Ryan, TA (corresponding author), Weill Cornell Med Coll, Dept Biochem, New York, NY 10023 USA.
EM taryan@med.cornell.edu
FU Medical Research Council [G0901758, G0801756, G0700368] Funding Source: researchfish; MRC [G0801756, G0901758, G0700368] Funding Source: UKRI; Medical Research Council [G0801756, G0901758, G0700368] Funding Source: Medline; NIMH NIH HHS [R01 MH085783] Funding Source: Medline
NR 34
TC 294
Z9 343
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 7
PY 2012
VL 486
IS 7401
BP 122
EP U149
DI 10.1038/nature11033
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 953GD
UT WOS:000304854000040
PM 22678293
DA 2026-03-09
ER

PT J
AU Veraart, AJ
   Faassen, EJ
   Dakos, V
   van Nes, EH
   Lürling, M
   Scheffer, M
AF Veraart, Annelies J.
   Faassen, Elisabeth J.
   Dakos, Vasilis
   van Nes, Egbert H.
   Lurling, Miquel
   Scheffer, Marten
TI Recovery rates reflect distance to a tipping point in a living system
SO NATURE
LA English
DT Article
ID slowing-down; light; community; competition; ecosystems; shifts
AB Tipping points, at which complex systems can shift abruptly from one state to another, are notoriously difficult to predict(1). Theory proposes that early warning signals may be based on the phenomenon that recovery rates from small perturbations should tend to zero when approaching a tipping point(2,3); however, evidence that this happens in living systems is lacking. Here we test such 'critical slowing down' using a microcosmin which photo-inhibition drives a cyanobacterial population to a classical tipping point when a critical light level is exceeded. We show that over a large range of conditions, recovery from small perturbations becomes slower as the system comes closer to the critical point. In addition, autocorrelation in the subtle fluctuations of the system's state rose towards the tipping point, supporting the idea that this metric can be used as an indirect indicator of slowing down(4,5). Although stochasticity prohibits prediction of the timing of critical transitions, our results suggest that indicators of slowing down may be used to rank complex systems on a broad scale from resilient to fragile.
C1 [Veraart, Annelies J.; Faassen, Elisabeth J.; Dakos, Vasilis; van Nes, Egbert H.; Lurling, Miquel; Scheffer, Marten] Wageningen Univ, Dept Aquat Ecol & Water Qual Management, NL-6700 AA Wageningen, Netherlands.
   [Lurling, Miquel] Royal Netherlands Acad Arts & Sci, Netherlands Inst Ecol, Dept Aquat Ecol, NL-6700 AB Wageningen, Netherlands.
C3 Wageningen University & Research; Royal Netherlands Academy of Arts & Sciences; Netherlands Institute of Ecology (NIOO-KNAW)
RP van Nes, EH (corresponding author), Wageningen Univ, Dept Aquat Ecol & Water Qual Management, POB 47, NL-6700 AA Wageningen, Netherlands.
EM egbert.vannes@wur.nl
FU European Research Council; Spinoza award
NR 21
TC 337
Z9 381
U1 6
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 JAN 19
PY 2012
VL 481
IS 7381
BP 357
EP U137
DI 10.1038/nature10723
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 877VK
UT WOS:000299210600041
PM 22198671
DA 2026-03-09
ER

PT J
AU Fan, HC
   Gu, W
   Wang, JB
   Blumenfeld, YJ
   El-Sayed, YY
   Quake, SR
AF Fan, H. Christina
   Gu, Wei
   Wang, Jianbin
   Blumenfeld, Yair J.
   El-Sayed, Yasser Y.
   Quake, Stephen R.
TI Non-invasive prenatal measurement of the fetal genome
SO NATURE
LA English
DT Article
ID maternal plasma; dna; aneuploidy
AB The vast majority of prenatal genetic testing requires invasive sampling. However, this poses a risk to the fetus, so one must make a decision that weighs the desire for genetic information against the risk of an adverse outcome due to hazards of the testing process. These issues are not required to be coupled, and it would be desirable to discover genetic information about the fetus without incurring a health risk. Here we demonstrate that it is possible to non-invasively sequence the entire prenatal genome. Our results show that molecular counting of parental haplotypes in maternal plasma by shotgun sequencing of maternal plasma DNA allows the inherited fetal genome to be deciphered non-invasively. We also applied the counting principle directly to each allele in the fetal exome by performing exome capture on maternal plasma DNA before shotgun sequencing. This approach enables non-invasive exome screening of clinically relevant and deleterious alleles that were paternally inherited or had arisen as de novo germline mutations, and complements the haplotype counting approach to provide a comprehensive view of the fetal genome. Non-invasive determination of the fetal genome may ultimately facilitate the diagnosis of all inherited and de novo genetic disease.
C1 [Fan, H. Christina; Gu, Wei; Wang, Jianbin; Quake, Stephen R.] Stanford Univ, Dept Bioengn, Stanford, CA 94305 USA.
   [Blumenfeld, Yair J.; El-Sayed, Yasser Y.] Stanford Univ, Sch Med, Dept Obstet & Gynecol, Div Maternal Fetal Med, Stanford, CA 94305 USA.
   [Quake, Stephen R.] Stanford Univ, Dept Appl Phys, Stanford, CA 94305 USA.
   [Quake, Stephen R.] Stanford Univ, Howard Hughes Med Inst, Stanford, CA 94305 USA.
C3 Stanford University; Stanford University; Stanford University; Stanford University; Howard Hughes Medical Institute
RP Quake, SR (corresponding author), Stanford Univ, Dept Bioengn, Clark Ctr Rm E300,318 Campus Dr, Stanford, CA 94305 USA.
EM quake@stanford.edu
FU NCI NIH HHS [U54 CA151459] Funding Source: Medline; NIH HHS [DP1 OD000251] Funding Source: Medline
CR Altshuler D, 2010, NATURE, V467, P1061, DOI 10.1038/nature09534
   Bellis MA, 2005, J EPIDEMIOL COMMUN H, V59, P749, DOI 10.1136/jech.2005.036517
   Bianchi DW, 2012, OBSTET GYNECOL, V119, P890, DOI 10.1097/AOG.0b013e31824fb482
   Bodurtha J, 2012, NEW ENGL J MED, V366, P64, DOI 10.1056/NEJMra1105043
   Chiu Rossa W K, 2011, BMJ, V342, Pc7401, DOI 10.1136/bmj.c7401
   Clark MJ, 2011, NAT BIOTECHNOL, V29, P908, DOI 10.1038/nbt.1975
   Ehrich M, 2011, AM J OBSTET GYNECOL, V204, P0, DOI 10.1016/j.ajog.2010.12.060
   Fan HC, 2010, PREPRINT, V0, P0
   Fan HC, 2008, P NATL ACAD SCI USA, V105, P16266, DOI 10.1073/pnas.0808319105
   Fan HC, 2011, NAT BIOTECHNOL, V29, P51, DOI 10.1038/nbt.1739
   Kinde I, 2011, P NATL ACAD SCI USA, V108, P9530, DOI 10.1073/pnas.1105422108
   Lo YMD, 2010, SCI TRANSL MED, V2, P0, DOI 10.1126/scitranslmed.3001720
   Lo YMD, 1998, AM J HUM GENET, V62, P768, DOI 10.1086/301800
   MACINTYRE S, 1991, LANCET, V338, P869, DOI 10.1016/0140-6736(91)91513-T
   MANDEL P, 1948, CR SOC BIOL, V142, P241
   Marchini J, 2006, AM J HUM GENET, V78, P437, DOI 10.1086/500808
   Palomaki GE, 2012, GENET MED, V14, P296, DOI 10.1038/gim.2011.73
   Palomaki GE, 2011, GENET MED, V13, P913, DOI 10.1097/GIM.0b013e3182368a0e
   Sehnert AJ, 2011, CLIN CHEM, V57, P1042, DOI 10.1373/clinchem.2011.165910
   White RA, 2009, BMC GENOMICS, V10, P0, DOI 10.1186/1471-2164-10-116
NR 20
TC 301
Z9 518
U1 4
U2 105
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 19
PY 2012
VL 487
IS 7407
BP 320
EP +
DI 10.1038/nature11251
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 975JB
UT WOS:000306506500033
PM 22763444
DA 2026-03-09
ER

PT J
AU Nandi, D
   Finck, ADK
   Eisenstein, JP
   Pfeiffer, LN
   West, KW
AF Nandi, D.
   Finck, A. D. K.
   Eisenstein, J. P.
   Pfeiffer, L. N.
   West, K. W.
TI Exciton condensation and perfect Coulomb drag
SO NATURE
LA English
DT Article
ID bose-einstein condensation; coupled quantum-wells; electron-systems; coherence; polaritons
AB Coulomb drag is a process whereby the repulsive interactions between electrons in spatially separated conductors enable a current flowing in one of the conductors to induce a voltage drop in the other(1-3). If the second conductor is part of a closed circuit, a net current will flow in that circuit. The drag current is typically much smaller than the drive current owing to the heavy screening of the Coulomb interaction. There are, however, rare situations in which strong electronic correlations exist between the two conductors. For example, double quantum well systems can support exciton condensates, which consist of electrons in one well tightly bound to holes in the other(4-6). 'Perfect' drag is therefore expected; a steady transport current of electrons driven through one quantum well should be accompanied by an equal current of holes in the other(7). Here we demonstrate this effect, taking care to ensure that the electron-hole pairs dominate the transport and that tunnelling of charge between the quantum wells, which can readily compromise drag measurements, is negligible. We note that, from an electrical engineering perspective, perfect Coulomb drag is analogous to an electrical transformer that functions at zero frequency.
C1 [Nandi, D.; Finck, A. D. K.; Eisenstein, J. P.] CALTECH, Pasadena, CA 91125 USA.
   [Pfeiffer, L. N.; West, K. W.] Princeton Univ, Dept Elect Engn, Princeton, NJ 08544 USA.
C3 California Institute of Technology; Princeton University
RP Eisenstein, JP (corresponding author), CALTECH, Pasadena, CA 91125 USA.
EM jpe@caltech.edu
FU NSF [DMR-1003080]
NR 27
TC 184
Z9 208
U1 0
U2 76
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD AUG 23
PY 2012
VL 488
IS 7412
BP 481
EP 484
DI 10.1038/nature11302
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 992FS
UT WOS:000307761600030
PM 22914164
DA 2026-03-09
ER

PT J
AU Wei, B
   Dai, MJ
   Yin, P
AF Wei, Bryan
   Dai, Mingjie
   Yin, Peng
TI Complex shapes self-assembled from single-stranded DNA tiles
SO NATURE
LA English
DT Article
ID nanoscale shapes; folding dna; origami; design; crystals; lattices; arrays; rna
AB Programmed self-assembly of strands of nucleic acid has proved highly effective for creating a wide range of structures with desired shapes(1-25). A particularly successful implementation is DNA origami, in which a long scaffold strand is folded by hundreds of short auxiliary strands into a complex shape(9,14-16,18-21,25). Modular strategies are in principle simpler and more versatile and have been used to assemble DNA(2-5,8,10-13,17,23) or RNA(7,22) tiles into periodic(3,4,7,22) and algorithmic(5) two-dimensional lattices, extended ribbons(10,12) and tubes(4,12,13), three-dimensional crystals(17), polyhedra(11) and simple finite two-dimensional shapes(7,8). But creating finite yet complex shapes from a large number of uniquely addressable tiles remains challenging. Here we solve this problem with the simplest tile form, a 'single-stranded tile' (SST) that consists of a 42-base strand of DNA composed entirely of concatenated sticky ends and that binds to four local neighbours during self-assembly(12). Although ribbons and tubes with controlled circumferences(12) have been created using the SST approach, we extend it to assemble complex two-dimensional shapes and tubes from hundreds (in some cases more than one thousand) distinct tiles. Our main design feature is a self-assembled rectangle that serves as a molecular canvas, with each of its constituent SST strands-folded into a 3 nm-by-7 nm tile and attached to four neighbouring tiles-acting as a pixel. A desired shape, drawn on the canvas, is then produced by one-pot annealing of all those strands that correspond to pixels covered by the target shape; the remaining strands are excluded. We implement the strategy with a master strand collection that corresponds to a 310-pixel canvas, and then use appropriate strand subsets to construct 107 distinct and complex two-dimensional shapes, thereby establishing SST assembly as a simple, modular and robust framework for constructing nanostructures with prescribed shapes from short synthetic DNA strands.
C1 [Wei, Bryan; Yin, Peng] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA.
   [Wei, Bryan; Dai, Mingjie; Yin, Peng] Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA.
   [Dai, Mingjie] Harvard Univ, Program Biophys, Boston, MA 02115 USA.
C3 Harvard University; Harvard Medical School; Harvard University; Harvard University
RP Yin, P (corresponding author), Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA.
EM py@hms.harvard.edu
FU Office of Naval Research [N000141110914, N000141010827]; NSF [CCF1054898]; NIH [1DP2OD007292]; Wyss Institute for Biologically Inspired Engineering; Division of Computing and Communication Foundations; Direct For Computer & Info Scie & Enginr [1054898] Funding Source: National Science Foundation
NR 32
TC 826
Z9 1064
U1 10
U2 708
PU NATURE PUBLISHING 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 31
PY 2012
VL 485
IS 7400
BP 623
EP +
DI 10.1038/nature11075
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 949WP
UT WOS:000304608000044
PM 22660323
DA 2026-03-09
ER

PT J
AU Moser, AL
   Bellan, PM
AF Moser, Auna L.
   Bellan, Paul M.
TI Magnetic reconnection from a multiscale instability cascade
SO NATURE
LA English
DT Article
ID kink
AB Magnetic reconnection, the process whereby magnetic field lines break and then reconnect to form a different topology, underlies critical dynamics of magnetically confined plasmas in both nature(1-4) and the laboratory(5-9). Magnetic reconnection involves localized diffusion of the magnetic field across plasma, yet observed reconnection rates are typically much higher than can be accounted for using classical electrical resistivity(10). It is generally proposed(10) that the field diffusion underlying fast reconnection results instead from some combination of non-magnetohydrodynamic processes that become important on the 'microscopic' scale of the ion Larmor radius or the ion skin depth. A recent laboratory experiment(11) demonstrated a transition from slow to fast magnetic reconnection when a current channel narrowed to a microscopic scale, but did not address how a macroscopic magnetohydrodynamic system accesses the microscale. Recent theoretical models(12) and numerical simulations(13,14) suggest that a macroscopic, two-dimensional magnetohydrodynamic current sheet might do this through a sequence of repetitive tearing and thinning into two-dimensional magnetized plasma structures having successively finer scales. Here we report observations demonstrating a cascade of instabilities from a distinct, macroscopic-scale magnetohydrodynamic instability to a distinct, microscopic-scale (ion skin depth) instability associated with fast magnetic reconnection. These observations resolve the full three-dimensional dynamics and give insight into the frequently impulsive nature of reconnection in space and laboratory plasmas.
C1 [Moser, Auna L.; Bellan, Paul M.] CALTECH, Pasadena, CA 91125 USA.
C3 California Institute of Technology
RP Moser, AL (corresponding author), CALTECH, Pasadena, CA 91125 USA.
EM auna@caltech.edu
FU US DOE; NSF; AFOSR; Directorate For Geosciences; Div Atmospheric & Geospace Sciences [0837910] Funding Source: National Science Foundation
NR 24
TC 75
Z9 92
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 FEB 16
PY 2012
VL 482
IS 7385
BP 379
EP 381
DI 10.1038/nature10827
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 892LG
UT WOS:000300287100041
PM 22337058
DA 2026-03-09
ER

PT J
AU Chen, W
   Jongkamonwiwat, N
   Abbas, L
   Eshtan, SJ
   Johnson, SL
   Kuhn, S
   Milo, M
   Thurlow, JK
   Andrews, PW
   Marcotti, W
   Moore, HD
   Rivolta, MN
AF Chen, Wei
   Jongkamonwiwat, Nopporn
   Abbas, Leila
   Eshtan, Sarah Jacob
   Johnson, Stuart L.
   Kuhn, Stephanie
   Milo, Marta
   Thurlow, Johanna K.
   Andrews, Peter W.
   Marcotti, Walter
   Moore, Harry D.
   Rivolta, Marcelo N.
TI Restoration of auditory evoked responses by human ES-cell-derived otic progenitors
SO NATURE
LA English
DT Article
ID embryonic stem-cells; inner-ear; spiral ganglion; in-vitro; placode induction; hair-cells; differentiation; neurons; nerve; transplantation
AB Deafness is a condition with a high prevalence worldwide, produced primarily by the loss of the sensory hair cells and their associated spiral ganglion neurons (SGNs). Of all the forms of deafness, auditory neuropathy is of particular concern. This condition, defined primarily by damage to the SGNs with relative preservation of the hair cells(1), is responsible for a substantial proportion of patients with hearing impairment(2). Although the loss of hair cells can be circumvented partially by a cochlear implant, no routine treatment is available for sensory neuron loss, as poor innervation limits the prospective performance of an implant(3). Using stem cells to recover the damaged sensory circuitry is a potential therapeutic strategy. Here we present a protocol to induce differentiation from human embryonic stem cells (hESCs) using signals involved in the initial specification of the otic placode. We obtained two types of otic progenitors able to differentiate in vitro into hair-cell-like cells and auditory neurons that display expected electrophysiological properties. Moreover, when transplanted into an auditory neuropathy model, otic neuroprogenitors engraft, differentiate and significantly improve auditory-evoked response thresholds. These results should stimulate further research into the development of a cell-based therapy for deafness.
C1 [Chen, Wei; Jongkamonwiwat, Nopporn; Abbas, Leila; Eshtan, Sarah Jacob; Thurlow, Johanna K.; Andrews, Peter W.; Moore, Harry D.; Rivolta, Marcelo N.] Univ Sheffield, Ctr Stem Cell Biol, Sheffield S10 2TN, S Yorkshire, England.
   [Chen, Wei; Jongkamonwiwat, Nopporn; Abbas, Leila; Eshtan, Sarah Jacob; Johnson, Stuart L.; Kuhn, Stephanie; Milo, Marta; Thurlow, Johanna K.; Andrews, Peter W.; Marcotti, Walter; Moore, Harry D.; Rivolta, Marcelo N.] Univ Sheffield, Dept Biomed Sci, Sheffield S10 2TN, S Yorkshire, England.
   [Jongkamonwiwat, Nopporn] Srinakharinwirot Univ, Fac Hlth Sci, Ongkharak 26120, Nakhonnayok, Thailand.
C3 University of Sheffield; University of Sheffield; Srinakharinwirot University
RP Rivolta, MN (corresponding author), Univ Sheffield, Ctr Stem Cell Biol, Sheffield S10 2TN, S Yorkshire, England.
EM m.n.rivolta@sheffield.ac.uk
FU Action on Hearing Loss (RNID); Deafness Research UK; Wellcome Trust [088719]; Medical Research Council; ESTOOLS; Wellcome Trust VIP award; RNID; MRC [G0900919, G0801059, G0700785] Funding Source: UKRI; Medical Research Council [G0700785, G0900919, G0801059] Funding Source: researchfish; RNID [G44, 515:SHE:MR] Funding Source: researchfish
NR 29
TC 303
Z9 347
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 OCT 11
PY 2012
VL 490
IS 7419
BP 278
EP +
DI 10.1038/nature11415
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 019IY
UT WOS:000309733300053
PM 22972191
DA 2026-03-09
ER

PT J
AU Spracklen, DV
   Arnold, SR
   Taylor, CM
AF Spracklen, D. V.
   Arnold, S. R.
   Taylor, C. M.
TI Observations of increased tropical rainfall preceded by air passage over forests
SO NATURE
LA English
DT Article
ID amazon deforestation; climate-change; leaf-area; impact; clouds; basin
AB Vegetation affects precipitation patterns by mediating moisture, energy and trace-gas fluxes between the surface and atmosphere(1). When forests are replaced by pasture or crops, evapotranspiration of moisture from soil and vegetation is often diminished, leading to reduced atmospheric humidity and potentially suppressing precipitation(2,3). Climate models predict that large-scale tropical deforestation causes reduced regional precipitation(4-10), although the magnitude of the effect is model(9,11) and resolution(8) dependent. In contrast, observational studies have linked deforestation to increased precipitation locally(12-14) but have been unable to explore the impact of large-scale deforestation. Here we use satellite remote-sensing data of tropical precipitation and vegetation, combined with simulated atmospheric transport patterns, to assess the pan-tropical effect of forests on tropical rainfall. We find that for more than 60 per cent of the tropical land surface (latitudes 30 degrees south to 30 degrees north), air that has passed over extensive vegetation in the preceding few days produces at least twice as much rain as air that has passed over little vegetation. We demonstrate that this empirical correlation is consistent with evapotranspiration maintaining atmospheric moisture in air that passes over extensive vegetation. We combine these empirical relationships with current trends of Amazonian deforestation to estimate reductions of 12 and 21 per cent in wet-season and dry-season precipitation respectively across the Amazon basin by 2050, due to less-efficient moisture recycling. Our observation-based results complement similar estimates from climate models(4-10), in which the physical mechanisms and feedbacks at work could be explored in more detail.
C1 [Spracklen, D. V.; Arnold, S. R.] Univ Leeds, Sch Earth & Environm, Leeds LS2 9JT, W Yorkshire, England.
   [Taylor, C. M.] Ctr Ecol & Hydrol, Oxford OX10 8BB, England.
C3 University of Leeds; UK Centre for Ecology & Hydrology (UKCEH)
RP Spracklen, DV (corresponding author), Univ Leeds, Sch Earth & Environm, Leeds LS2 9JT, W Yorkshire, England.
EM d.v.spracklen@leeds.ac.uk
FU Natural Environment Research Council [NE/G015015/1]; Natural Environment Research Council [earth010002, NE/G018499/1, NE/G015015/1, NE/F00060X/1, NE/B505538/1] Funding Source: researchfish; NERC [NE/F00060X/1, earth010002, NE/G018499/1, NE/G015015/1] Funding Source: UKRI
NR 32
TC 505
Z9 566
U1 6
U2 308
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 13
PY 2012
VL 489
IS 7415
BP 282
EP U127
DI 10.1038/nature11390
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 003UC
UT WOS:000308635900039
PM 22951966
DA 2026-03-09
ER

PT J
AU Jäger, S
   Kim, DY
   Hultquist, JF
   Shindo, K
   LaRue, RS
   Kwon, E
   Li, M
   Anderson, BD
   Yen, L
   Stanley, D
   Mahon, C
   Kane, J
   Franks-Skiba, K
   Cimermancic, P
   Burlingame, A
   Sali, A
   Craik, CS
   Harris, RS
   Gross, JD
   Krogan, NJ
AF Jaeger, Stefanie
   Kim, Dong Young
   Hultquist, Judd F.
   Shindo, Keisuke
   LaRue, Rebecca S.
   Kwon, Eunju
   Li, Ming
   Anderson, Brett D.
   Yen, Linda
   Stanley, David
   Mahon, Cathal
   Kane, Joshua
   Franks-Skiba, Kathy
   Cimermancic, Peter
   Burlingame, Alma
   Sali, Andrej
   Craik, Charles S.
   Harris, Reuben S.
   Gross, John D.
   Krogan, Nevan J.
TI Vif hijacks CBF-β to degrade APOBEC3G and promote HIV-1 infection
SO NATURE
LA English
DT Article
ID ubiquitin-ligase complex; socs-box; restriction factors; antiviral activity; protein; specificity; proteasome; mechanism; targets; tissue
AB Restriction factors, such as the retroviral complementary DNA deaminase APOBEC3G, are cellular proteins that dominantly block virus replication(1-3). The AIDS virus, human immuno deficiency virus type 1 (HIV-1), produces the accessory factor Vif, which counteracts the host's antiviral defence by hijacking a ubiquitin ligase complex, containing CUL5, ELOC, ELOB and a RING-box protein, and targeting APOBEC3G for degradation(4-10). Here we reveal, using an affinity tag/purification mass spectrometry approach, that Vif additionally recruits the transcription cofactor CBF-beta to this ubiquitin ligase complex. CBF-beta, which normally functions in concert with RUNX DNA binding proteins, allows the reconstitution of a recombinant six-protein assembly that elicits specific polyubiquitination activity with APOBEC3G, but not the related deaminase APOBEC3A. Using RNA knockdown and genetic complementation studies, we also demonstrate that CBF-beta is required for Vif-mediated degradation of APOBEC3G and therefore for preserving HIV-1 infectivity. Finally, simian immunodeficiency virus (SIV) Vif also binds to and requires CBF-beta to degrade rhesus macaque APOBEC3G, indicating functional conservation. Methods of disrupting the CBF-beta-Vif interaction might enable HIV-1 restriction and provide a supplement to current antiviral therapies that primarily target viral proteins.
C1 [Hultquist, Judd F.; Shindo, Keisuke; LaRue, Rebecca S.; Li, Ming; Anderson, Brett D.; Harris, Reuben S.] Univ Minnesota, Inst Mol Virol, Dept Biochem Mol Biol & Biophys, Ctr Genome Engn, Minneapolis, MN 55455 USA.
   [Jaeger, Stefanie; Mahon, Cathal; Kane, Joshua; Franks-Skiba, Kathy; Krogan, Nevan J.] Univ Calif San Francisco, Dept Cellular & Mol Pharmacol, San Francisco, CA 94158 USA.
   [Jaeger, Stefanie; Mahon, Cathal; Kane, Joshua; Franks-Skiba, Kathy; Cimermancic, Peter; Burlingame, Alma; Sali, Andrej; Craik, Charles S.; Gross, John D.; Krogan, Nevan J.] QB3, Calif Inst Quantitat Biosci, San Francisco, CA 94158 USA.
   [Kim, Dong Young; Kwon, Eunju; Yen, Linda; Stanley, David; Mahon, Cathal; Burlingame, Alma; Sali, Andrej; Craik, Charles S.; Gross, John D.] Univ Calif San Francisco, Dept Pharmaceut Chem, San Francisco, CA 94158 USA.
   [Cimermancic, Peter; Sali, Andrej] Univ Calif San Francisco, Dept Bioengn & Therapeut Sci, San Francisco, CA 94158 USA.
   [Sali, Andrej; Gross, John D.; Krogan, Nevan J.] Univ Calif San Francisco, HPC Host Pathogen Circuitry Grp, San Francisco, CA 94158 USA.
   [Krogan, Nevan J.] J David Gladstone Inst, San Francisco, CA 94158 USA.
C3 University of Minnesota System; University of Minnesota Twin Cities; 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; The J David Gladstone Institutes
RP Harris, RS (corresponding author), Univ Minnesota, Inst Mol Virol, Dept Biochem Mol Biol & Biophys, Ctr Genome Engn, Minneapolis, MN 55455 USA.
EM rsh@umn.edu; jdgross@cgl.ucsf.edu; krogan@cmp.ucsf.edu
FU QB3 at University of California, San Francisco; National Institutes of Health [P50 GM082250, P01 AI090935, P50 GM081879, U54 RR022220, R01 AI064046, P01 GM091743, P41RR001614, P50GM081879]; National Institute of Allergy and Infectious Diseases [T32AI083196] Funding Source: NIH RePORTER
NR 27
TC 311
Z9 384
U1 0
U2 31
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JAN 19
PY 2012
VL 481
IS 7381
BP 371
EP 375
DI 10.1038/nature10693
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 877VK
UT WOS:000299210600044
PM 22190037
DA 2026-03-09
ER

PT J
AU Jeyaraj, D
   Haldar, SM
   Wan, XP
   McCauley, MD
   Ripperger, JA
   Hu, K
   Lu, Y
   Eapen, BL
   Sharma, N
   Ficker, E
   Cutler, MJ
   Gulick, J
   Sanbe, A
   Robbins, J
   Demolombe, S
   Kondratov, RV
   Shea, SA
   Albrecht, U
   Wehrens, XHT
   Rosenbaum, DS
   Jain, MK
AF Jeyaraj, Darwin
   Haldar, Saptarsi M.
   Wan, Xiaoping
   McCauley, Mark D.
   Ripperger, Juergen A.
   Hu, Kun
   Lu, Yuan
   Eapen, Betty L.
   Sharma, Nikunj
   Ficker, Eckhard
   Cutler, Michael J.
   Gulick, James
   Sanbe, Atsushi
   Robbins, Jeffrey
   Demolombe, Sophie
   Kondratov, Roman V.
   Shea, Steven A.
   Albrecht, Urs
   Wehrens, Xander H. T.
   Rosenbaum, David S.
   Jain, Mukesh K.
TI Circadian rhythms govern cardiac repolarization and arrhythmogenesis
SO NATURE
LA English
DT Article
ID qt syndrome; i-to; hypertrophy; expression; interval; mammals; disease; death
AB Sudden cardiac death exhibits diurnal variation in both acquired and hereditary forms of heart disease(1,2), but the molecular basis of this variation is unknown. A common mechanism that underlies susceptibility to ventricular arrhythmias is abnormalities in the duration (for example, short or long QT syndromes and heart failure)(3-5) or pattern (for example, Brugada's syndrome)(6) of myocardial repolarization. Here we provide molecular evidence that links circadian rhythms to vulnerability in ventricular arrhythmias in mice. Specifically, we show that cardiac ion-channel expression and QT-interval duration (an index of myocardial repolarization) exhibit endogenous circadian rhythmicity under the control of a clock-dependent oscillator, kruppel-like factor 15 (Klf15). Klf15 transcriptionally controls rhythmic expression of Kv channel-interacting protein 2 (KChIP2), a critical subunit required for generating the transient outward potassium current(7). Deficiency or excess of Klf15 causes loss of rhythmic QT variation, abnormal repolarization and enhanced susceptibility to ventricular arrhythmias. These findings identify circadian transcription of ion channels as a mechanism for cardiac arrhythmogenesis.
C1 [Jeyaraj, Darwin; Haldar, Saptarsi M.; Lu, Yuan; Eapen, Betty L.; Sharma, Nikunj; Jain, Mukesh K.] Case Western Reserve Univ, Case Cardiovasc Res Inst, Harrington Heart & Vasc Inst, Dept Med,Sch Med, Cleveland, OH 44106 USA.
   [Jeyaraj, Darwin; Wan, Xiaoping; Ficker, Eckhard; Cutler, Michael J.; Rosenbaum, David S.] Case Western Reserve Univ, Heart & Vasc Res Ctr, Cleveland, OH 44109 USA.
   [McCauley, Mark D.; Wehrens, Xander H. T.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA.
   [McCauley, Mark D.; Wehrens, Xander H. T.] Baylor Coll Med, Dept Mol Physiol & Biophys, Houston, TX 77030 USA.
   [Ripperger, Juergen A.; Albrecht, Urs] Univ Fribourg, Div Biochem, Dept Med, CH-1700 Fribourg, Switzerland.
   [Hu, Kun; Shea, Steven A.] Brigham & Womens Hosp, Div Sleep Med, Boston, MA 02115 USA.
   [Hu, Kun; Shea, Steven A.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
   [Gulick, James; Sanbe, Atsushi; Robbins, Jeffrey] Cincinnati Childrens Hosp, Med Ctr, Dept Pediat, Div Mol Cardiovasc Biol, Cincinnati, OH 45229 USA.
   [Demolombe, Sophie] Univ Nice Sophia Antipolis, UMR CNRS 6097, Inst Pharmacol Mol & Cellulaire, F-06560 Valbonne, France.
   [Kondratov, Roman V.] Cleveland State Univ, Dept Biol Geol & Environm Sci, Cleveland, OH 44115 USA.
   [Kondratov, Roman V.] Cleveland State Univ, Ctr Gene Regulat Hlth & Dis, Cleveland, OH 44115 USA.
C3 University System of Ohio; Case Western Reserve University; University System of Ohio; Case Western Reserve University; Baylor College of Medicine; Baylor College of Medicine; University of Fribourg; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard University; Harvard Medical School; Cincinnati Children's Hospital Medical Center; Universite Cote d'Azur; Centre National de la Recherche Scientifique (CNRS); University System of Ohio; Cleveland State University; University System of Ohio; Cleveland State University
RP Jeyaraj, D (corresponding author), Case Western Reserve Univ, Case Cardiovasc Res Inst, Harrington Heart & Vasc Inst, Dept Med,Sch Med, Cleveland, OH 44106 USA.
EM darwinjeyaraj@gmail.com; mukesh.jain2@case.edu
FU Heart RhythmSociety Fellowship; National Institutes of Health [HL094660, HL066991, HL086614]; American Heart Association [HL089598, HL091947, HL76446, HL102241, HL054807, HL075427, HL076754, HL084154, HL086548, HL097595]; Swiss National Science Foundation [31003A/131086, M01-RR02635]; Leducq Foundation of the ENAFRA Network [07CVD03]; Centre National de la Recherche Scientifique; National Heart Lung and Blood Institute [R01HL089598] Funding Source: NIH RePORTER; National Institute on Aging [R01AG039547] Funding Source: NIH RePORTER
CR Antzelevitch C, 2007, AM J PHYSIOL-HEART C, V293, PH2024, DOI 10.1152/ajpheart.00355.2007
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   BEXTON RS, 1986, BRIT HEART J, V55, P253
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   Fisch S, 2007, P NATL ACAD SCI USA, V104, P13851, DOI 10.1073/pnas.0706717104
   Fisch S, 2007, P NATL ACAD SCI USA, V104, P7074, DOI 10.1073/pnas.0701981104
   Goldenberg I, 2008, J AM COLL CARDIOL, V51, P2291, DOI 10.1016/j.jacc.2008.02.068
   Haldar SM, 2010, SCI TRANSL MED, V2, P0, DOI 10.1126/scitranslmed.3000502
   Hu K, 2011, CIRCULATION, V123, P961, DOI 10.1161/CIRCULATIONAHA.110.943019
   Kong TQ, 1995, CIRCULATION, V92, P1507
   Kuo HC, 2001, CELL, V107, P801, DOI 10.1016/S0092-8674(01)00588-8
   Libbus I, 2004, AM J PHYSIOL-HEART C, V286, PH1901, DOI 10.1152/ajpheart.00581.2003
   Martino TA, 2009, CIRC RES, V105, P1047, DOI 10.1161/CIRCRESAHA.109.206201
   Matsuo K, 1999, EUR HEART J, V20, P465, DOI 10.1053/euhj.1998.1332
   Mitchell GF, 1998, AM J PHYSIOL-HEART C, V274, PH747, DOI 10.1152/ajpheart.1998.274.3.H747
   MULLER JE, 1987, CIRCULATION, V75, P131, DOI 10.1161/01.CIR.75.1.131
   NELSON W, 1979, CHRONOBIOLOGIA, V6, P305
   Paschos GK, 2010, CIRC RES, V106, P833, DOI 10.1161/CIRCRESAHA.109.211706
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   Reppert SM, 2002, NATURE, V418, P935, DOI 10.1038/nature00965
   Ripperger JRA, 2006, NAT GENET, V38, P369, DOI 10.1038/ng1738
   Sanbe A, 2003, CIRC RES, V92, P609, DOI 10.1161/01.RES.0000065442.64694.9F
   Tomaselli GF, 1999, CARDIOVASC RES, V42, P270, DOI 10.1016/S0008-6363(99)00017-6
   Tuteja G, 2008, NUCLEIC ACIDS RES, V36, P4149, DOI 10.1093/nar/gkn366
   van Oort RJ, 2010, CIRCULATION, V122, P2669, DOI 10.1161/CIRCULATIONAHA.110.982298
   Wagner S, 2009, CIRC-ARRHYTHMIA ELEC, V2, P285, DOI 10.1161/CIRCEP.108.842799
   Wang B, 2008, J MOL CELL CARDIOL, V45, P193, DOI 10.1016/j.yjmcc.2008.05.005
   Yamashita T, 2003, CIRCULATION, V107, P1917, DOI 10.1161/01.CIR.0000058752.79734.F0
NR 29
TC 278
Z9 325
U1 2
U2 62
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD MAR 1
PY 2012
VL 483
IS 7387
BP 96
EP U141
DI 10.1038/nature10852
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 900HP
UT WOS:000300877900052
PM 22367544
DA 2026-03-09
ER

PT J
AU Liu, LD
   Ulbrich, J
   Müller, J
   Wüstefeld, T
   Aeberhard, L
   Kress, TR
   Muthalagu, N
   Rycak, L
   Rudalska, R
   Moll, R
   Kempa, S
   Zender, L
   Eilers, M
   Murphy, DJ
AF Liu, Lidan
   Ulbrich, Jannes
   Mueller, Judith
   Wuestefeld, Torsten
   Aeberhard, Lukas
   Kress, Theresia R.
   Muthalagu, Nathiya
   Rycak, Lukas
   Rudalska, Ramona
   Moll, Roland
   Kempa, Stefan
   Zender, Lars
   Eilers, Martin
   Murphy, Daniel J.
TI Deregulated MYC expression induces dependence upon AMPK-related kinase 5
SO NATURE
LA English
DT Article
ID synthetic lethal interaction; c-myc; mitochondrial biogenesis; cancer-cells; b kinase; metabolism; suppression; glutamine; addiction; growth
AB Deregulated expression of the MYC oncoprotein contributes to the genesis of many human tumours, yet strategies to exploit this for a rational tumour therapy are scarce. MYC promotes cell growth and proliferation, andalters cellularmetabolismto enhance the provision of precursors for phospholipids and cellularmacromolecules(1,2). Here we showinhuman andmurine cell lines thatoncogenic levels ofMYC establish a dependence on AMPK-related kinase 5 (ARK5; also known as NUAK1) for maintaining metabolic homeostasis and for cell survival. ARK5 is an upstream regulator of AMPK and limits protein synthesis via inhibition of the mammalian target of rapamycin 1 (mTORC1) signalling pathway. ARK5 also maintains expression of mitochondrial respiratory chain complexes and respiratory capacity, which is required for efficient glutamine metabolism. Inhibition of ARK5 leads to a collapse of cellular ATP levels in cells expressing deregulated MYC, inducing multiple pro-apoptotic responses as a secondary consequence. Depletion of ARK5 prolongs survival in MYC-driven mouse models of hepatocellular carcinoma, demonstrating that targeting cellular energy homeostasis is a valid therapeutic strategy to eliminate tumour cells that express deregulated MYC.
C1 [Liu, Lidan; Ulbrich, Jannes; Mueller, Judith; Kress, Theresia R.; Muthalagu, Nathiya; Eilers, Martin; Murphy, Daniel J.] Univ Wurzburg, Bioctr, Theodor Boveri Inst, D-97074 Wurzburg, Germany.
   [Wuestefeld, Torsten; Rudalska, Ramona; Zender, Lars] Helmholtz Ctr Infect Res, D-38124 Braunschweig, Germany.
   [Wuestefeld, Torsten; Zender, Lars] Hannover Med Sch, Dept Gastroenterol Hepatol & Endocrinol, D-30625 Hannover, Germany.
   [Aeberhard, Lukas; Kempa, Stefan] Berlin Inst Med Syst Biol, Max Delbruck Ctr Mol Med, D-13125 Berlin, Germany.
   [Rycak, Lukas] Inst Mol Biol & Tumor Res, D-35037 Marburg, Germany.
   [Moll, Roland] Univ Marburg, Inst Pathol, D-35033 Marburg, Germany.
C3 University of Wurzburg; Helmholtz Association; Helmholtz-Center for Infection Research; Hannover Medical School; Helmholtz Association; Max Delbruck Center for Molecular Medicine; Philipps University Marburg
RP Eilers, M (corresponding author), Univ Wurzburg, Bioctr, Theodor Boveri Inst, Hubland, D-97074 Wurzburg, Germany.
EM martin.eilers@biozentrum.uni-wuerzburg.de; daniel.murphy@biozentrum.uni-wuerzburg.de
FU GROWTHSTOP consortium of the European Union; Deutsche Forschungsgemeinschaft [Transregio 17, Transregio 77]; Emmy Noether Programme [ZE 545/2-1]; Bundesministerium fur Bildung und Forschung; Senate of Berlin; University of Wuerzburg Graduate School of Life Sciences and the "Rebirth" Cluster of Excellence
NR 33
TC 232
Z9 284
U1 1
U2 52
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD MAR 29
PY 2012
VL 483
IS 7391
BP 608
EP U131
DI 10.1038/nature10927
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 915EF
UT WOS:000302006100041
PM 22460906
DA 2026-03-09
ER

PT J
AU Liu, N
   Landreh, M
   Cao, KJ
   Abe, M
   Hendriks, GJ
   Kennerdell, JR
   Zhu, YQ
   Wang, LS
   Bonini, NM
AF Liu, Nan
   Landreh, Michael
   Cao, Kajia
   Abe, Masashi
   Hendriks, Gert-Jan
   Kennerdell, Jason R.
   Zhu, Yongqing
   Wang, Li-San
   Bonini, Nancy M.
TI The microRNA miR-34 modulates ageing and neurodegeneration in Drosophila
SO NATURE
LA English
DT Article
ID down-regulation; life-span; degeneration; brain; transcription; melanogaster; expression; disease; target; gene
AB Human neurodegenerative diseases have the temporal hallmark of afflicting the elderly population. Ageing is one of the most prominent factors to influence disease onset and progression(1), yet little is known about the molecular pathways that connect these processes. To understand this connection it is necessary to identify the pathways that functionally integrate ageing, chronic maintenance of the brain and modulation of neurodegenerative disease. MicroRNAs (miRNA) are emerging as critical factors in gene regulation during development; however, their role in adult-onset, age-associated processes is only beginning to be revealed. Here we report that the conserved miRNA miR-34 regulates age-associated events and long-term brain integrity in Drosophila, providing a molecular link between ageing and neurodegeneration. Fly mir-34 expression exhibits adult-onset, brain-enriched and age-modulated characteristics. Whereas mir-34 loss triggers a gene profile of accelerated brain ageing, late-onset brain degeneration and a catastrophic decline in survival, mir-34 upregulation extends median lifespan and mitigates neurodegeneration induced by human pathogenic polyglutamine disease protein. Some of the age-associated effects of miR-34 require adult-onset translational repression of Eip74EF, an essential ETS domain transcription factor involved in steroid hormone pathways. Our studies indicate that miRNA-dependent pathways may have an impact on adult-onset, age-associated events by silencing developmental genes that later have a deleterious influence on adult life cycle and disease, and highlight fly miR-34 as a key miRNA with a role in this process.
C1 [Liu, Nan; Landreh, Michael; Abe, Masashi; Hendriks, Gert-Jan; Kennerdell, Jason R.; Zhu, Yongqing; Bonini, Nancy M.] Univ Penn, Dept Biol, Philadelphia, PA 19104 USA.
   [Cao, Kajia; Wang, Li-San] Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA.
   [Wang, Li-San] Univ Penn, Inst Aging, Philadelphia, PA 19104 USA.
   [Wang, Li-San] Univ Penn, Penn Ctr Bioinformat, Philadelphia, PA 19104 USA.
   [Bonini, Nancy M.] Univ Penn, Howard Hughes Med Inst, Philadelphia, PA 19104 USA.
C3 University of Pennsylvania; University of Pennsylvania; University of Pennsylvania; University of Pennsylvania; University of Pennsylvania; Howard Hughes Medical Institute
RP Bonini, NM (corresponding author), Univ Penn, Dept Biol, Philadelphia, PA 19104 USA.
EM nbonini@sas.upenn.edu
FU NINDS [R01-NS043578]; Ellison Foundation; Penn Genome Frontiers Institute; NIA [U01-AG-032984-02, RC2-AG036528-01]; Penn Institute on Aging [AG010124]; NIH [T32 AG00255]; National Institute on Aging [T32AG000255, U01AG032984] Funding Source: NIH RePORTER
NR 33
TC 323
Z9 387
U1 0
U2 101
PU NATURE PUBLISHING 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 23
PY 2012
VL 482
IS 7386
BP 519
EP U240
DI 10.1038/nature10810
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 898VM
UT WOS:000300770500049
PM 22343898
DA 2026-03-09
ER

PT J
AU Wiener, R
   Zhang, XB
   Wang, T
   Wolberger, C
AF Wiener, Reuven
   Zhang, Xiangbin
   Wang, Tao
   Wolberger, Cynthia
TI The mechanism of OTUB1-mediated inhibition of ubiquitination
SO NATURE
LA English
DT Article
ID conjugating enzyme complex; structural basis; polyubiquitin chains; crystal-structure; recognition; specificity; system; model
AB Histones are ubiquitinated in response toDNAdouble-strand breaks (DSB), promoting recruitment of repair proteins to chromatin(1). UBC13 (also known as UBE2N) is a ubiquitin-conjugating enzyme (E2) that heterodimerizes withUEV1A(2) (also knownasUBE2V1) and synthesizes K63-linked polyubiquitin (K63Ub) chains at DSB sites in concert with the ubiquitin ligase (E3), RNF168 (ref. 3). K63Ub synthesis is regulated in a non-canonicalmanner by the deubiquitinating enzyme, OTUB1 (OTU domain-containing ubiquitin aldehydebinding protein 1), which binds preferentially to the UBC13 similar to Ub thiolester(4). Residues amino-terminal to the OTU domain, which had been implicated in ubiquitin binding(4), are required for binding to UBC13 similar to Ub and inhibition of K63Ub synthesis(5). Here we describe structural and biochemical studies elucidating how OTUB1 inhibits UBC13 and other E2 enzymes. We unexpectedly find that OTUB1 binding to UBC13 Ub is allosterically regulated by free ubiquitin, which binds to a second site in OTUB1 and increases its affinity for UBC13 similar to Ub, while at the same time disrupting interactions with UEV1A in a manner that depends on the OTUB1 N terminus. Crystal structures of an OTUB1-UBC13 complex and of OTUB1 bound to ubiquitin aldehyde and a chemical UBC13 similar to Ub conjugate show that binding of free ubiquitin to OTUB1 triggers conformational changes in the OTU domain and formation of a ubiquitinbinding helix in the N terminus, thus promoting binding of the conjugated donor ubiquitin in UBC13 similar to Ub to OTUB1. The donor ubiquitin thus cannot interact with the E2 enzyme, which has been shown to be important for ubiquitin transfer(6,7). The N-terminal helix of OTUB1 is positioned to interfere with UEV1A binding to UBC13, as well as with attack on the thiolester by an acceptor ubiquitin, thereby inhibiting K63Ub synthesis. OTUB1 binding also occludes the RING E3 binding site on UBC13, thus providing a further component of inhibition. The general features of the inhibition mechanism explain how OTUB1 inhibits other E2 enzymes4 in a non-catalytic manner.
C1 [Wiener, Reuven; Zhang, Xiangbin; Wang, Tao; Wolberger, Cynthia] Johns Hopkins Univ, Sch Med, Dept Biophys & Biophys Chem, Baltimore, MD 21205 USA.
   [Wiener, Reuven; Zhang, Xiangbin; Wang, Tao; Wolberger, Cynthia] Johns Hopkins Univ, Sch Med, Howard Hughes Med Inst, Baltimore, MD 21205 USA.
C3 Johns Hopkins University; Johns Hopkins University; Howard Hughes Medical Institute
RP Wolberger, C (corresponding author), Johns Hopkins Univ, Sch Med, Dept Biophys & Biophys Chem, Baltimore, MD 21205 USA.
EM cwolberg@jhmi.edu
FU US Department of Energy, Basic Energy Sciences, Office of Science [DE-AC02-06CH11357]; National Cancer Institute [Y1-CO-1020]; National Institute of General Medical Science [Y1-GM-1104]
NR 30
TC 214
Z9 247
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 MAR 29
PY 2012
VL 483
IS 7391
BP 618
EP U143
DI 10.1038/nature10911
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 915EF
UT WOS:000302006100043
PM 22367539
DA 2026-03-09
ER

PT J
AU Allesina, S
   Tang, S
AF Allesina, Stefano
   Tang, Si
TI Stability criteria for complex ecosystems
SO NATURE
LA English
DT Article
ID food webs; ecological community; mutualistic networks; interaction strength; biodiversity; architecture; diversity; matrices; models
AB Forty years ago, May proved(1,2) that sufficiently large or complex ecological networks have a probability of persisting that is close to zero, contrary to previous expectations(3-5). May analysed large networks in which species interact at random(1,2,6). However, in natural systems pairs of species have well-defined interactions (for example predator-prey, mutualistic or competitive). Here we extend May's results to these relationships and find remarkable differences between predator-prey interactions, which are stabilizing, and mutualistic and competitive interactions, which are destabilizing. We provide analytic stability criteria for all cases. We use the criteria to prove that, counterintuitively, the probability of stability for predator-prey networks decreases when a realistic food web structure is imposed(7,8) or if there is a large preponderance of weak interactions(9,10). Similarly, stability is negatively affected by nestedness(11-14) in bipartite mutualistic networks. These results are found by separating the contribution of network structure and interaction strengths to stability. Stable predator-prey networks can be arbitrarily large and complex, provided that predator-prey pairs are tightly coupled. The stability criteria are widely applicable, because they hold for any system of differential equations.
C1 [Allesina, Stefano; Tang, Si] Univ Chicago, Dept Ecol & Evolut, Chicago, IL 60637 USA.
   [Allesina, Stefano] Univ Chicago, Computat Inst, Chicago, IL 60637 USA.
C3 University of Chicago; University of Chicago
RP Allesina, S (corresponding author), Univ Chicago, Dept Ecol & Evolut, 1101 E 57th St, Chicago, IL 60637 USA.
EM sallesina@uchicago.edu
FU National Science Foundation [EF0827493]; Direct For Biological Sciences [0827493] Funding Source: National Science Foundation; Emerging Frontiers [0827493] Funding Source: National Science Foundation
NR 24
TC 977
Z9 1080
U1 10
U2 694
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD MAR 8
PY 2012
VL 483
IS 7388
BP 205
EP 208
DI 10.1038/nature10832
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 904DT
UT WOS:000301174900037
PM 22343894
DA 2026-03-09
ER

PT J
AU Minko, Y
   Pasco, M
   Lercher, L
   Botoshansky, M
   Marek, I
AF Minko, Yury
   Pasco, Morgane
   Lercher, Lukas
   Botoshansky, Mark
   Marek, Ilan
TI Forming all-carbon quaternary stereogenic centres in acyclic systems from alkynes
SO NATURE
LA English
DT Article
ID ireland-claisen rearrangement; diastereoselective preparation; stereoselective construction; stereocenters; generation; products; reagents; creation; esters
AB The formation of all-carbon quaternary stereocentres in acyclic systems is one of the most difficult contemporary challenges in modern synthetic organic chemistry(1,2). Particularly challenging is the preparation of all-carbon quaternary stereocentres in aldol adducts(3); this difficulty is problematic because the aldol reaction represents one of the most valuable chemical transformations in organic synthesis(4). The main problem that limits the formation of these stereocentres is the absence of an efficient method of preparing stereodefined trisubstituted enolates in acyclic systems(5-8). Here we describe a different approach that involves the formation of two new stereogenic centres-including the all-carbon quaternary one-via a combined carbometalation-oxidation reaction of an organocuprate to give a stereodefined trisubstituted enolate. We use this method to generate a series of aldol and Mannich products from ynamides with excellent diastereomeric and enantiomeric ratios and moderate yields.
C1 [Minko, Yury; Pasco, Morgane; Lercher, Lukas; Marek, Ilan] Technion Israel Inst Technol, Schulich Fac Chem, Mallat Family Lab Organ Chem, IL-32000 Haifa, Israel.
   [Minko, Yury; Pasco, Morgane; Lercher, Lukas; Marek, Ilan] Technion Israel Inst Technol, Lise Meitner Minerva Ctr Computat Quantum Chem, IL-32000 Haifa, Israel.
   [Botoshansky, Mark] Technion Israel Inst Technol, Xray Anal Lab, IL-32000 Haifa, Israel.
C3 Technion Israel Institute of Technology; Technion Israel Institute of Technology; Technion Israel Institute of Technology
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 Israel Science Foundation [140/12]; Fund for Promotion of Research at the Technion; Bayer-Stiftung
NR 30
TC 181
Z9 192
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 OCT 25
PY 2012
VL 490
IS 7421
BP 522
EP 526
DI 10.1038/nature11569
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 025NK
UT WOS:000310196200038
PM 23099407
DA 2026-03-09
ER

PT J
AU Beck, PG
   Montalban, J
   Kallinger, T
   De Ridder, J
   Aerts, C
   Garcia, RA
   Hekker, S
   Dupret, MA
   Mosser, B
   Eggenberger, P
   Stello, D
   Elsworth, Y
   Frandsen, S
   Carrier, F
   Hillen, M
   Gruberbauer, M
   Christensen-Dalsgaard, J
   Miglio, A
   Valentini, M
   Bedding, TR
   Kjeldsen, H
   Girouard, FR
   Hall, JR
   Ibrahim, KA
AF Beck, Paul G.
   Montalban, Josefina
   Kallinger, Thomas
   De Ridder, Joris
   Aerts, Conny
   Garcia, Rafael A.
   Hekker, Saskia
   Dupret, Marc-Antoine
   Mosser, Benoit
   Eggenberger, Patrick
   Stello, Dennis
   Elsworth, Yvonne
   Frandsen, Soren
   Carrier, Fabien
   Hillen, Michel
   Gruberbauer, Michael
   Christensen-Dalsgaard, Jorgen
   Miglio, Andrea
   Valentini, Marica
   Bedding, Timothy R.
   Kjeldsen, Hans
   Girouard, Forrest R.
   Hall, Jennifer R.
   Ibrahim, Khadeejah A.
TI Fast core rotation in red-giant stars as revealed by gravity-dominated mixed modes
SO NATURE
LA English
DT Article
ID asteroseismology; oscillations; circulation
AB When the core hydrogen is exhausted during stellar evolution, the central region of a star contracts and the outer envelope expands and cools, giving rise to a red giant. Convection takes place overmuch of the star's radius. Conservation of angular momentum requires that the cores of these stars rotate faster than their envelopes; indirect evidence supports this(1,2). Information about the angular-momentum distribution is inaccessible to direct observations, but it can be extracted from the effect of rotation on oscillation modes that probe the stellar interior. Here we report an increasing rotation rate from the surface of the star to the stellar core in the interiors of red giants, obtained using the rotational frequency splitting of recently detected 'mixed modes'(3,4). By comparison with theoretical stellar models, we conclude that the core must rotate at least ten times faster than the surface. This observational result confirms the theoretical prediction of a steep gradient in the rotation profile towards the deep stellar interior(1,5,6).
C1 [Beck, Paul G.; Kallinger, Thomas; De Ridder, Joris; Aerts, Conny; Carrier, Fabien; Hillen, Michel] Katholieke Univ Leuven, Inst Sterrenkunde, B-3001 Louvain, Belgium.
   [Montalban, Josefina; Dupret, Marc-Antoine; Valentini, Marica] Univ Liege, Inst Astrophys Geophys, B-4000 Liege, Belgium.
   [Kallinger, Thomas] Univ Vienna, Inst Astron, A-1180 Vienna, Austria.
   [Aerts, Conny] Radboud Univ Nijmegen, IMAPP, NL-6500 GL Nijmegen, Netherlands.
   [Garcia, Rafael A.] Univ Paris Diderot, CNRS, IRFU Sap, Ctr Saclay,CEA DSM,Lab Astrophys Instrumentat & M, F-91191 Gif Sur Yvette, France.
   [Hekker, Saskia] Univ Amsterdam, Astron Inst Anton Pannekoek, NL-1098 XH Amsterdam, Netherlands.
   [Hekker, Saskia; Elsworth, Yvonne; Miglio, Andrea] Univ Birmingham, Sch Phys & Astron, Birmingham B15 2TT, W Midlands, England.
   [Mosser, Benoit] Univ Paris 07, Univ Paris 06, CNRS, Observ Paris,Lab Etudes Spatiales & Instrumentat, F-92195 Meudon, France.
   [Eggenberger, Patrick] Univ Geneva, Observ Geneve, CH-1290 Sauverny, Switzerland.
   [Stello, Dennis; Bedding, Timothy R.] Univ Sydney, Sch Phys, Sydney Inst Astron SIfA, Sydney, NSW 2006, Australia.
   [Frandsen, Soren; Christensen-Dalsgaard, Jorgen; Kjeldsen, Hans] Aarhus Univ, Dept Phys & Astron, DK-8000 Aarhus C, Denmark.
   [Gruberbauer, Michael] St Marys Univ, Dept Phys & Astron, Halifax, NS B3H 3C3, Canada.
   [Girouard, Forrest R.; Hall, Jennifer R.; Ibrahim, Khadeejah A.] NASA, Ames Res Ctr, Orbital Sci Corp, Moffett Field, CA 94035 USA.
C3 KU Leuven; University of Liege; University of Vienna; Radboud University Nijmegen; Centre National de la Recherche Scientifique (CNRS); CEA; Universite Paris Cite; Universite Paris Saclay; University of Amsterdam; University of Birmingham; Centre National de la Recherche Scientifique (CNRS); Sorbonne Universite; Universite Paris Cite; Universite PSL; Observatoire de Paris; University of Geneva; University of Sydney; Aarhus University; Saint Marys University - Canada; Orbital Sciences Corporation; National Aeronautics & Space Administration (NASA); NASA Ames Research Center
RP Beck, PG (corresponding author), Katholieke Univ Leuven, Inst Sterrenkunde, B-3001 Louvain, Belgium.
EM paul.beck@ster.kuleuven.be
FU NASA's Science Mission Directorate; European Community; Fund for Scientific Research, Flanders; Netherlands Organisation for Scientific Research; Belgian Science Policy Office
NR 24
TC 412
Z9 433
U1 0
U2 297
PU NATURE PUBLISHING 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 5
PY 2012
VL 481
IS 7379
BP 55
EP 57
DI 10.1038/nature10612
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 872VD
UT WOS:000298836900027
PM 22158105
DA 2026-03-09
ER

PT J
AU Sun, LL
   Chen, XJ
   Guo, J
   Gao, PW
   Huang, QZ
   Wang, HD
   Fang, MH
   Chen, XL
   Chen, GF
   Wu, Q
   Zhang, C
   Gu, DC
   Dong, XL
   Wang, L
   Yang, K
   Li, AG
   Dai, X
   Mao, HK
   Zhao, ZX
AF Sun, Liling
   Chen, Xiao-Jia
   Guo, Jing
   Gao, Peiwen
   Huang, Qing-Zhen
   Wang, Hangdong
   Fang, Minghu
   Chen, Xiaolong
   Chen, Genfu
   Wu, Qi
   Zhang, Chao
   Gu, Dachun
   Dong, Xiaoli
   Wang, Lin
   Yang, Ke
   Li, Aiguo
   Dai, Xi
   Mao, Ho-kwang
   Zhao, Zhongxian
TI Re-emerging superconductivity at 48 kelvin in iron chalcogenides
SO NATURE
LA English
DT Article
ID 43 k; pressure
AB Pressure has an essential role in the production(1) and control(2,3) of superconductivity in iron-based superconductors. Substitution of a large cation by a smaller rare-earth ion to simulate the pressure effect has raised the superconducting transition temperature T-c to a record high of 55 K in these materials(4,5). In the same way as T-c exhibits a bell-shaped curve of dependence on chemical doping, pressure-tuned T-c typically drops monotonically after passing the optimal pressure(1-3). Here we report that in the superconducting iron chalcogenides, a second superconducting phase suddenly re-emerges above 11.5 GPa, after the T-c drops from the first maximum of 32 K at 1 GPa. The T-c of the re-emerging superconducting phase is considerably higher than the first maximum, reaching 48.0-48.7 K for Tl0.6Rb0.4Fe1.67Se2, K0.8Fe1.7Se2 and K0.8Fe1.78Se2.
C1 [Sun, Liling; Guo, Jing; Gao, Peiwen; Chen, Xiaolong; Chen, Genfu; Wu, Qi; Zhang, Chao; Gu, Dachun; Dong, Xiaoli; Dai, Xi; Zhao, Zhongxian] Chinese Acad Sci, Inst Phys, Beijing 100190, Peoples R China.
   [Sun, Liling; Guo, Jing; Gao, Peiwen; Chen, Xiaolong; Chen, Genfu; Wu, Qi; Zhang, Chao; Gu, Dachun; Dong, Xiaoli; Dai, Xi; Zhao, Zhongxian] Chinese Acad Sci, Beijing Natl Lab Condensed Matter Phys, Beijing 100190, Peoples R China.
   [Chen, Xiao-Jia; Mao, Ho-kwang] Carnegie Inst Sci, Geophys Lab, Washington, DC 20015 USA.
   [Chen, Xiao-Jia] S China Univ Technol, Dept Phys, Guangzhou 510640, Guangdong, Peoples R China.
   [Huang, Qing-Zhen] Natl Inst Stand & Technol, NIST Ctr Neutron Res, Gaithersburg, MD 20899 USA.
   [Wang, Hangdong; Fang, Minghu] Zhejiang Univ, Dept Phys, Hangzhou 310027, Zhejiang, Peoples R China.
   [Wang, Lin] Carnegie Inst Sci, Geophys Lab, HPSynC, Argonne, IL 60439 USA.
   [Yang, Ke; Li, Aiguo] Chinese Acad Sci, Shanghai Inst Appl Phys, Shanghai Synchrotron Radiat Facil, Shanghai 201204, Peoples R China.
C3 Chinese Academy of Sciences; Institute of Physics, CAS; Chinese Academy of Sciences; Carnegie Institution for Science; South China University of Technology; National Institute of Standards & Technology (NIST) - USA; Zhejiang University; Carnegie Institution for Science; Chinese Academy of Sciences; Shanghai Institute of Applied Physics, CAS
RP Zhao, ZX (corresponding author), Chinese Acad Sci, Inst Phys, Beijing 100190, Peoples R China.
EM hmao@gl.ciw.edu; zhxzhao@iphy.ac.cn
FU NSCF; 973 projects; Chinese Academy of Sciences; EFree, an Energy Frontier Research Center; US Department of Energy, Office of Science, Office of Basic Energy Sciences (DOE-BES); CIW; CDAC; UNLV; LLNL through DOE-NNSA; NSF
NR 21
TC 302
Z9 334
U1 1
U2 369
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 1
PY 2012
VL 483
IS 7387
BP 67
EP 69
DI 10.1038/nature10813
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 900HP
UT WOS:000300877900045
PM 22367543
DA 2026-03-09
ER

PT J
AU Qin, JJ
   Li, YR
   Cai, ZM
   Li, SH
   Zhu, JF
   Zhang, F
   Liang, SS
   Zhang, WW
   Guan, YL
   Shen, DQ
   Peng, YQ
   Zhang, DY
   Jie, ZY
   Wu, WX
   Qin, YW
   Xue, WB
   Li, JH
   Han, LC
   Lu, DH
   Wu, PX
   Dai, YL
   Sun, XJ
   Li, ZS
   Tang, AF
   Zhong, SL
   Li, XP
   Chen, WN
   Xu, R
   Wang, MB
   Feng, Q
   Gong, MH
   Yu, J
   Zhang, YY
   Zhang, M
   Hansen, T
   Sanchez, G
   Raes, J
   Falony, G
   Okuda, S
   Almeida, M
   LeChatelier, E
   Renault, P
   Pons, N
   Batto, JM
   Zhang, ZX
   Chen, H
   Yang, RF
   Zheng, WM
   Li, SG
   Yang, HM
   Wang, J
   Ehrlich, SD
   Nielsen, R
   Pedersen, O
   Kristiansen, K
   Wang, J
AF Qin, Junjie
   Li, Yingrui
   Cai, Zhiming
   Li, Shenghui
   Zhu, Jianfeng
   Zhang, Fan
   Liang, Suisha
   Zhang, Wenwei
   Guan, Yuanlin
   Shen, Dongqian
   Peng, Yangqing
   Zhang, Dongya
   Jie, Zhuye
   Wu, Wenxian
   Qin, Youwen
   Xue, Wenbin
   Li, Junhua
   Han, Lingchuan
   Lu, Donghui
   Wu, Peixian
   Dai, Yali
   Sun, Xiaojuan
   Li, Zesong
   Tang, Aifa
   Zhong, Shilong
   Li, Xiaoping
   Chen, Weineng
   Xu, Ran
   Wang, Mingbang
   Feng, Qiang
   Gong, Meihua
   Yu, Jing
   Zhang, Yanyan
   Zhang, Ming
   Hansen, Torben
   Sanchez, Gaston
   Raes, Jeroen
   Falony, Gwen
   Okuda, Shujiro
   Almeida, Mathieu
   LeChatelier, Emmanuelle
   Renault, Pierre
   Pons, Nicolas
   Batto, Jean-Michel
   Zhang, Zhaoxi
   Chen, Hua
   Yang, Ruifu
   Zheng, Weimou
   Li, Songgang
   Yang, Huanming
   Wang, Jian
   Ehrlich, S. Dusko
   Nielsen, Rasmus
   Pedersen, Oluf
   Kristiansen, Karsten
   Wang, Jun
TI A metagenome-wide association study of gut microbiota in type 2 diabetes
SO NATURE
LA English
DT Article
ID obesity; diversity; bacteremia; infection; stress
AB Assessment and characterization of gut microbiota has become a major research area in human disease, including type 2 diabetes, the most prevalent endocrine disease worldwide. To carry out analysis on gut microbial content in patients with type 2 diabetes, we developed a protocol for a metagenome-wide association study (MGWAS) and undertook a two-stage MGWAS based on deep shotgun sequencing of the gut microbial DNA from 345 Chinese individuals. We identified and validated approximately 60,000 type-2-diabetes-associated markers and established the concept of a metagenomic linkage group, enabling taxonomic species-level analyses. MGWAS analysis showed that patients with type 2 diabetes were characterized by a moderate degree of gut microbial dysbiosis, a decrease in the abundance of some universal butyrate-producing bacteria and an increase in various opportunistic pathogens, as well as an enrichment of other microbial functions conferring sulphate reduction and oxidative stress resistance. An analysis of 23 additional individuals demonstrated that these gut microbial markers might be useful for classifying type 2 diabetes.
C1 [Qin, Junjie; Li, Yingrui; Li, Shenghui; Zhu, Jianfeng; Liang, Suisha; Zhang, Wenwei; Guan, Yuanlin; Shen, Dongqian; Peng, Yangqing; Zhang, Dongya; Jie, Zhuye; Wu, Wenxian; Qin, Youwen; Xue, Wenbin; Li, Junhua; Chen, Weineng; Xu, Ran; Wang, Mingbang; Feng, Qiang; Gong, Meihua; Yu, Jing; Zhang, Yanyan; Zhang, Ming; Zhang, Zhaoxi; Chen, Hua; Yang, Ruifu; Zheng, Weimou; Li, Songgang; Yang, Huanming; Wang, Jian; Kristiansen, Karsten; Wang, Jun] BGI Shenzhen, Shenzhen 518083, Peoples R China.
   [Cai, Zhiming; Li, Zesong; Tang, Aifa; Zhong, Shilong] Shenzhen Univ, Affiliated Hosp 1, Shenzhen Peoples Hosp 2, Shenzhen 518035, Peoples R China.
   [Zhang, Fan; Han, Lingchuan; Lu, Donghui; Wu, Peixian; Dai, Yali; Sun, Xiaojuan] Peking Univ, Shenzhen Hosp, Shenzhen 518036, Peoples R China.
   [Li, Xiaoping] Guangdong Acad Med Sci, Guangdong Gen Hosp, Med Res Ctr, Guangzhou 510080, Peoples R China.
   [Hansen, Torben; Pedersen, Oluf; Wang, Jun] Univ Copenhagen, Fac Hlth Sci, Novo Nordisk Fdn Ctr Basic Metab Res, DK-2100 Copenhagen, Denmark.
   [Sanchez, Gaston; Nielsen, Rasmus] Univ Calif Berkeley, Dept Integrat Biol, Berkeley, CA 94820 USA.
   [Sanchez, Gaston; Nielsen, Rasmus] Univ Calif Berkeley, Dept Stat, Berkeley, CA 94820 USA.
   [Raes, Jeroen; Falony, Gwen; Okuda, Shujiro] VIB, Dept Biol Struct, B-1050 Brussels, Belgium.
   [Raes, Jeroen; Falony, Gwen; Okuda, Shujiro] Vrije Univ Brussel, Dept Appl Biol Sci DBIT, B-1050 Brussels, Belgium.
   [Almeida, Mathieu; LeChatelier, Emmanuelle; Renault, Pierre; Pons, Nicolas; Batto, Jean-Michel; Ehrlich, S. Dusko] INRA, F-78350 Jouy En Josas, France.
   [Yang, Ruifu] Beijing Inst Microbiol & Epidemiol, State Key Lab Pathogen & Biosecur, Beijing 100071, Peoples R China.
   [Pedersen, Oluf] Univ Copenhagen, Inst Biomed Sci, DK-8000 Aarhus, Denmark.
   [Pedersen, Oluf] Univ Aarhus, Fac Hlth Sci, DK-8000 Aarhus, Denmark.
   [Pedersen, Oluf] Hagedorn Res Inst, DK-2820 Gentofte, Denmark.
   [Pedersen, Oluf] Hagedorn Res Inst, DK-2820 Gentofte, Denmark.
   [Kristiansen, Karsten; Wang, Jun] Univ Copenhagen, Dept Biol, DK-2200 Copenhagen, Denmark.
C3 Beijing Genomics Institute (BGI); Shenzhen University; Peking University; Guangdong Academy of Medical Sciences & Guangdong General Hospital; Southern Medical University - China; University of Copenhagen; Novo Nordisk Foundation; University of California System; University of California Berkeley; University of California System; University of California Berkeley; Flanders Institute for Biotechnology (VIB); Vrije Universiteit Brussel; Universite Paris Saclay; INRAE; Beijing Institute of Microbiology & Epidemiology; University of Copenhagen; Aarhus University; Novo Nordisk; Hagedorn Research Institute; Novo Nordisk; Hagedorn Research Institute; University of Copenhagen
RP Wang, J (corresponding author), BGI Shenzhen, Shenzhen 518083, Peoples R China.
EM wangj@genomics.org.cn
FU Ministry of Science and Technology of China [2012AA02A201]; National Natural Science Foundation of China [30890032, 30725008, 30811130531, 31161130357]; Shenzhen Municipal Government of China [ZYC200903240080A, BGI20100001, CXB201108250096A, CXB201108250098A]; Danish Strategic Research Council [2106-07-0021]; Danish Natural Science Research Council; Solexa project [272-07-0196]; European Commission [HEALTH-F4-2007-201052]; Novo Nordisk Foundation; Ministry of Science and Technology of China [2012AA02A201]; National Natural Science Foundation of China [30890032, 30725008, 30811130531, 31161130357]; Shenzhen Municipal Government of China [ZYC200903240080A, BGI20100001, CXB201108250096A, CXB201108250098A]; Danish Strategic Research Council [2106-07-0021]; Danish Natural Science Research Council; Solexa project [272-07-0196]; European Commission [HEALTH-F4-2007-201052]; Novo Nordisk Foundation
NR 36
TC 5241
Z9 6251
U1 50
U2 1917
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 4
PY 2012
VL 490
IS 7418
BP 55
EP 60
DI 10.1038/nature11450
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 015LG
UT WOS:000309446800031
PM 23023125
DA 2026-03-09
ER

PT J
AU Bedell, VM
   Wang, Y
   Campbell, JM
   Poshusta, TL
   Starker, CG
   Krug, RG
   Tan, WF
   Penheiter, SG
   Ma, AC
   Leung, AYH
   Fahrenkrug, SC
   Carlson, DF
   Voytas, DF
   Clark, KJ
   Essner, JJ
   Ekker, SC
AF Bedell, Victoria M.
   Wang, Ying
   Campbell, Jarryd M.
   Poshusta, Tanya L.
   Starker, Colby G.
   Krug, Randall G., II
   Tan, Wenfang
   Penheiter, Sumedha G.
   Ma, Alvin C.
   Leung, Anskar Y. H.
   Fahrenkrug, Scott C.
   Carlson, Daniel F.
   Voytas, Daniel F.
   Clark, Karl J.
   Essner, Jeffrey J.
   Ekker, Stephen C.
TI In vivo genome editing using a high-efficiency TALEN system
SO NATURE
LA English
DT Article
ID targeted gene disruption; dna-binding specificity; zebrafish; nuclease; cells
AB The zebrafish (Danio rerio) is increasingly being used to study basic vertebrate biology and human disease with a rich array of in vivo genetic and molecular tools. However, the inability to readily modify the genome in a targeted fashion has been a bottleneck in the field. Here we show that improvements in artificial transcription activator-like effector nucleases (TALENs) provide a powerful new approach for targeted zebrafish genome editing and functional genomic applications(1-5). Using the GoldyTALEN modified scaffold and zebrafish delivery system, we show that this enhanced TALEN toolkit has a high efficiency in inducing locus-specific DNA breaks in somatic and germline tissues. At some loci, this efficacy approaches 100%, including biallelic conversion in somatic tissues that mimics phenotypes seen using morpholino-based targeted gene knockdowns(6). With this updated TALEN system, we successfully used single-stranded DNA oligonucleotides to precisely modify sequences at predefined locations in the zebrafish genome through homology-directed repair, including the introduction of a custom-designed EcoRV site and a modified loxP (mloxP) sequence into somatic tissue in vivo. We further show successful germline transmission of both EcoRV and mloxP engineered chromosomes. This combined approach offers the potential to model genetic variation as well as to generate targeted conditional alleles.
C1 [Bedell, Victoria M.; Campbell, Jarryd M.; Poshusta, Tanya L.; Krug, Randall G., II; Penheiter, Sumedha G.; Ma, Alvin C.; Clark, Karl J.; Ekker, Stephen C.] Mayo Clin, Dept Biochem & Mol Biol, Rochester, MN 55905 USA.
   [Wang, Ying; Essner, Jeffrey J.] Iowa State Univ, Dept Genet Dev & Cell Biol, Ames, IA 50011 USA.
   [Starker, Colby G.; Tan, Wenfang; Fahrenkrug, Scott C.; Carlson, Daniel F.; Voytas, Daniel F.] Univ Minnesota, Ctr Genome Engn, Dept Genet Cell Biol & Dev, Minneapolis, MN 55455 USA.
   [Starker, Colby G.; Tan, Wenfang; Fahrenkrug, Scott C.; Carlson, Daniel F.; Voytas, Daniel F.] Univ Minnesota, Dept Anim Sci, Minneapolis, MN 55455 USA.
   [Ma, Alvin C.; Leung, Anskar Y. H.] Univ Hong Kong, LKS Fac Med, Dept Med, Hong Kong, Hong Kong, Peoples R China.
   [Fahrenkrug, Scott C.; Carlson, Daniel F.] Recombinetics Inc, St Paul, MN 55114 USA.
C3 Mayo Clinic; Iowa State University; University of Minnesota System; University of Minnesota Twin Cities; University of Minnesota System; University of Minnesota Twin Cities; University of Hong Kong
RP Ekker, SC (corresponding author), Mayo Clin, Dept Biochem & Mol Biol, Rochester, MN 55905 USA.
EM ekker.stephen@mayo.edu
FU State of Minnesota [H001274506]; NIH [GM63904, P30DK084567, DK083219, DA032194, R41HL108440, GM088424]; Mayo Foundation; NSF [DBI0923827]; Research Grant Council, The University of Hong Kong [HKU771611, HKU771110, HKU769809M]; Tang King Yin Research Fund; Direct For Biological Sciences; Division Of Integrative Organismal Systems [0923827] Funding Source: National Science Foundation; National Institute of Diabetes and Digestive and Kidney Diseases [P30DK084567] Funding Source: NIH RePORTER; National Institute of General Medical Sciences [R01GM063904] Funding Source: NIH RePORTER
NR 27
TC 743
Z9 1037
U1 2
U2 509
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 1
PY 2012
VL 491
IS 7422
BP 114
EP U133
DI 10.1038/nature11537
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 028PM
UT WOS:000310434500041
PM 23000899
DA 2026-03-09
ER

PT J
AU Treiber, CD
   Salzer, MC
   Riegler, J
   Edelman, N
   Sugar, C
   Breuss, M
   Pichler, P
   Cadiou, H
   Saunders, M
   Lythgoe, M
   Shaw, J
   Keays, DA
AF Treiber, Christoph Daniel
   Salzer, Marion Claudia
   Riegler, Johannes
   Edelman, Nathaniel
   Sugar, Cristina
   Breuss, Martin
   Pichler, Paul
   Cadiou, Herve
   Saunders, Martin
   Lythgoe, Mark
   Shaw, Jeremy
   Keays, David Anthony
TI Clusters of iron-rich cells in the upper beak of pigeons are macrophages not magnetosensitive neurons
SO NATURE
LA English
DT Article
ID magnetite-based magnetoreception; homing pigeons; putative magnetoreceptor; trigeminal mediation; migratory bird; orientation; mechanism; ferritin; compass; tissue
AB Understanding the molecular and cellular mechanisms that mediate magnetosensation in vertebrates is a formidable scientific problem(1,2). One hypothesis is that magnetic information is transduced into neuronal impulses by using a magnetite-based magnetoreceptor(3,4). Previous studies claim to have identified a magnetic sense system in the pigeon, common to avian species, which consists of magnetite-containing trigeminal afferents located at six specific loci in the rostral subepidermis of the beak(5-8). These studies have been widely accepted in the field and heavily relied upon by both behavioural biologists and physicists(9-11). Here we show that clusters of iron-rich cells in the rostro-medial upper beak of the pigeon Columbia livia are macrophages, not magnetosensitive neurons. Our systematic characterization of the pigeon upper beak identified iron-rich cells in the stratum laxum of the subepidermis, the basal region of the respiratory epithelium and the apex of feather follicles. Using a three-dimensional blueprint of the pigeon beak created by magnetic resonance imaging and computed tomography, we mapped the location of iron-rich cells, revealing unexpected variation in their distribution and number-an observation that is inconsistent with a role in magnetic sensation. Ultrastructure analysis of these cells, which are not unique to the beak, showed that their subcellular architecture includes ferritin-like granules, siderosomes, haemosiderin and filopodia, characteristics of iron-rich macrophages. Our conclusion that these cells are macrophages and not magnetosensitive neurons is supported by immunohistological studies showing co-localization with the antigen-presenting molecule major histocompatibility complex class II. Our work necessitates a renewed search for the true magnetite-dependent magnetoreceptor in birds.
C1 [Treiber, Christoph Daniel; Salzer, Marion Claudia; Edelman, Nathaniel; Sugar, Cristina; Breuss, Martin; Pichler, Paul; Keays, David Anthony] Inst Mol Pathol, A-1030 Vienna, Austria.
   [Riegler, Johannes; Lythgoe, Mark] UCL, Ctr Adv Biomed Imaging, Dept Med, London WC1E 6DD, England.
   [Riegler, Johannes; Lythgoe, Mark] UCL, Inst Child Hlth, London WC1E 6DD, England.
   [Cadiou, Herve] Univ Strasbourg, INCI, CNRS, UPR 3212, F-67084 Strasbourg, France.
   [Breuss, Martin; Shaw, Jeremy] Univ Western Australia, Ctr Microscopy Characterisat & Anal, Crawley 6009, Australia.
C3 Vienna Biocenter (VBC); Research Institute of Molecular Pathology (IMP); University of London; University College London; University of London; University College London; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB); Universites de Strasbourg Etablissements Associes; Universite de Strasbourg; University of Western Australia
RP Keays, DA (corresponding author), Inst Mol Pathol, A-1030 Vienna, Austria.
EM keays@imp.ac.at
FU Boehringer Ingelheim; EPSRC [EP/I014667/1] Funding Source: UKRI; Engineering and Physical Sciences Research Council [EP/I014667/1] Funding Source: researchfish
NR 31
TC 142
Z9 172
U1 1
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 APR 19
PY 2012
VL 484
IS 7394
BP 367
EP U102
DI 10.1038/nature11046
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 927YM
UT WOS:000302946500031
PM 22495303
DA 2026-03-09
ER

PT J
AU Blaga, CI
   Xu, JL
   DiChiara, AD
   Sistrunk, E
   Zhang, KK
   Agostini, P
   Miller, TA
   DiMauro, LF
   Lin, CD
AF Blaga, Cosmin I.
   Xu, Junliang
   DiChiara, Anthony D.
   Sistrunk, Emily
   Zhang, Kaikai
   Agostini, Pierre
   Miller, Terry A.
   DiMauro, Louis F.
   Lin, C. D.
TI Imaging ultrafast molecular dynamics with laser-induced electron diffraction
SO NATURE
LA English
DT Article
AB Establishing the structure of molecules and solids has always had an essential role in physics, chemistry and biology. The methods of choice are X-ray and electron diffraction, which are routinely used to determine atomic positions with sub-a ngstrom spatial resolution. Although both methods are currently limited to probing dynamics on timescales longer than a picosecond, the recent development of femtosecond sources of X-ray pulses and electron beams suggests that they might soon be capable of taking ultrafast snapshots of biological molecules(1,2) and condensed-phase systems(3-6) undergoing structural changes. The past decade has also witnessed the emergence of an alternative imaging approach based on laser-ionized bursts of coherent electron wave packets that self-interrogate the parent molecular structure(7-11). Here we show that this phenomenon can indeed be exploited for laser-induced electron diffraction(10) (LIED), to image molecular structures with subangstrom precision and exposure times of a few femtoseconds. We apply the method to oxygen and nitrogen molecules, which on strong-field ionization at three mid-infrared wavelengths (1.7, 2.0 and 2.3 mu m) emit photoelectrons with a momentum distribution from which we extract diffraction patterns. The long wavelength is essential for achieving atomic-scale spatial resolution, and the wavelength variation is equivalent to taking snapshots at different times. We show that the method has the sensitivity to measure a 0.1 angstrom displacement in the oxygen bond length occurring in a time interval of similar to 5 fs, which establishes LIED as a promising approach for the imaging of gas-phase molecules with unprecedented spatio-temporal resolution.
C1 [Blaga, Cosmin I.; DiChiara, Anthony D.; Sistrunk, Emily; Zhang, Kaikai; Agostini, Pierre; DiMauro, Louis F.] Ohio State Univ, Dept Phys, Columbus, OH 43210 USA.
   [Xu, Junliang; Lin, C. D.] Kansas State Univ, Dept Phys, Manhattan, KS 66506 USA.
   [Miller, Terry A.] Ohio State Univ, Dept Chem, Columbus, OH 43210 USA.
C3 University System of Ohio; Ohio State University; Kansas State University; University System of Ohio; Ohio State University
RP Blaga, CI (corresponding author), Ohio State Univ, Dept Phys, 174 W 18th Ave, Columbus, OH 43210 USA.
EM cblaga@mps.ohio-state.edu
FU DOE/BES [DE-FG02-06ER15833, DE-FG02-06ER15832]; Hagenlocker chair; U.S. Department of Energy (DOE) [DE-FG02-06ER15833, DE-FG02-06ER15832] Funding Source: U.S. Department of Energy (DOE)
NR 29
TC 540
Z9 598
U1 3
U2 333
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 8
PY 2012
VL 483
IS 7388
BP 194
EP 197
DI 10.1038/nature10820
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 904DT
UT WOS:000301174900034
PM 22398558
DA 2026-03-09
ER

PT J
AU Qian, L
   Huang, Y
   Spencer, CI
   Foley, A
   Vedantham, V
   Liu, L
   Conway, SJ
   Fu, JD
   Srivastava, D
AF Qian, Li
   Huang, Yu
   Spencer, C. Ian
   Foley, Amy
   Vedantham, Vasanth
   Liu, Lei
   Conway, Simon J.
   Fu, Ji-dong
   Srivastava, Deepak
TI In vivo reprogramming of murine cardiac fibroblasts into induced cardiomyocytes
SO NATURE
LA English
DT Article
ID defined factors; stem-cells; direct conversion; gene-transfer; adult; heart; injury; repair; differentiation; expression
AB The reprogramming of adult cells into pluripotent cells or directly into alternative adult cell types holds great promise for regenerative medicine. We reported previously that cardiac fibroblasts, which represent 50% of the cells in the mammalian heart, can be directly reprogrammed to adult cardiomyocyte-like cells in vitro by the addition of Gata4, Mef2c and Tbx5 (GMT). Here we use genetic lineage tracing to show that resident non-myocytes in the murine heart can be reprogrammed into cardiomyocyte-like cells in vivo by local delivery of GMT after coronary ligation. Induced cardiomyocytes became binucleate, assembled sarcomeres and had cardiomyocyte-like gene expression. Analysis of single cells revealed ventricular cardiomyocyte-like action potentials, beating upon electrical stimulation, and evidence of electrical coupling. In vivo delivery of GMT decreased infarct size and modestly attenuated cardiac dysfunction up to 3 months after coronary ligation. Delivery of the pro-angiogenic and fibroblast-activating peptide, thymosin beta 4, along with GMT, resulted in further improvements in scar area and cardiac function. These findings demonstrate that cardiac fibroblasts can be reprogrammed into cardiomyocyte-like cells in their native environment for potential regenerative purposes.
C1 [Qian, Li; Huang, Yu; Spencer, C. Ian; Foley, Amy; Vedantham, Vasanth; Liu, Lei; Fu, Ji-dong; Srivastava, Deepak] Gladstone Inst Cardiovasc Dis, San Francisco, CA 94158 USA.
   [Qian, Li; Huang, Yu; Spencer, C. Ian; Foley, Amy; Liu, Lei; Fu, Ji-dong; Srivastava, Deepak] Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94158 USA.
   [Qian, Li; Huang, Yu; Spencer, C. Ian; Foley, Amy; Liu, Lei; Fu, Ji-dong; Srivastava, Deepak] Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94158 USA.
   [Vedantham, Vasanth] Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94158 USA.
   [Vedantham, Vasanth] Univ Calif San Francisco, Dept Med, San Francisco, CA 94158 USA.
   [Conway, Simon J.] Indiana Univ Sch Med, Dev Biol & Neonatal Med Res Program, Indianapolis, IN 46202 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; Indiana University System; Indiana University Bloomington
RP Srivastava, D (corresponding author), Gladstone Inst Cardiovasc Dis, San Francisco, CA 94158 USA.
EM dsrivastava@gladstone.ucsf.edu
FU GlaxoSmithKline Research and Education Foundation; NIH/NHLBI [K08HL101989, R01 HL060714]; American Heart Association; CIRM; Younger Family Foundation; Roddenberry Foundation; L.K. Whittier Foundation; NIH/NCRR [C06 RR018928]
NR 40
TC 1067
Z9 1294
U1 2
U2 291
PU NATURE PUBLISHING 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 31
PY 2012
VL 485
IS 7400
BP 593
EP +
DI 10.1038/nature11044
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 949WP
UT WOS:000304608000038
PM 22522929
DA 2026-03-09
ER

PT J
AU Zheng, JK
   Umikawa, M
   Cui, CH
   Li, JY
   Chen, XL
   Zhang, CZ
   Hyunh, HD
   Kang, XL
   Silvany, R
   Wan, X
   Ye, JX
   Cantó, AP
   Chen, SH
   Wang, HY
   Ward, ES
   Zhang, CC
AF Zheng, Junke
   Umikawa, Masato
   Cui, Changhao
   Li, Jiyuan
   Chen, Xiaoli
   Zhang, Chaozheng
   Hyunh, HoangDinh
   Kang, Xunlei
   Silvany, Robert
   Wan, Xuan
   Ye, Jingxiao
   Canto, Alberto Puig
   Chen, Shu-Hsia
   Wang, Huan-You
   Ward, E. Sally
   Zhang, Cheng Cheng
TI Inhibitory receptors bind ANGPTLs and support blood stem cells and leukaemia development
SO NATURE
LA English
DT Article
ID ex-vivo expansion; transformation; proteins; pirb
AB How environmental cues regulate adult stem cell and cancer cell activity through surface receptors is poorly understood. Angiopoietin-like proteins (ANGPTLs), a family of seven secreted glycoproteins, are known to support the activity of haematopoietic stem cells (HSCs) in vitro and in vivo(1-10). ANGPTLs also have important roles in lipid metabolism, angiogenesis and inflammation, but were considered 'orphan ligands' because no receptors were identified(3,11,12). Here we show that the immune-inhibitory receptor human leukocyte immunoglobulin-like receptor B2 (LILRB2) and its mouse orthologue paired immunoglobulin-like receptor (PIRB) are receptors for several ANGPTLs. LILRB2 and PIRB are expressed on human and mouse HSCs, respectively, and the binding of ANGPTLs to these receptors supported ex vivo expansion of HSCs. In mouse transplantation acute myeloid leukaemia models, a deficiency in intracellular signalling of PIRB resulted in increased differentiation of leukaemia cells, revealing that PIRB supports leukaemia development. Our study indicates an unexpected functional significance of classical immune-inhibitory receptors in maintenance of stemness of normal adult stem cells and in support of cancer development.
C1 [Zheng, Junke; Umikawa, Masato; Cui, Changhao; Li, Jiyuan; Chen, Xiaoli; Zhang, Chaozheng; Hyunh, HoangDinh; Kang, Xunlei; Silvany, Robert; Wan, Xuan; Ye, Jingxiao; Zhang, Cheng Cheng] Univ Texas SW Med Ctr Dallas, Dept Physiol, Dallas, TX 75390 USA.
   [Zheng, Junke; Umikawa, Masato; Cui, Changhao; Li, Jiyuan; Chen, Xiaoli; Zhang, Chaozheng; Hyunh, HoangDinh; Kang, Xunlei; Silvany, Robert; Wan, Xuan; Ye, Jingxiao; Zhang, Cheng Cheng] Univ Texas SW Med Ctr Dallas, Dept Dev Biol, Dallas, TX 75390 USA.
   [Zheng, Junke] Shanghai Jiao Tong Univ, Sch Med, Key Lab Cell Differentiat & Apoptosis Chinese Min, Shanghai 200025, Peoples R China.
   [Umikawa, Masato] Univ Ryukyus, Dept Med Biochem, Okinawa 9030215, Japan.
   [Canto, Alberto Puig; Ward, E. Sally] Univ Texas SW Med Ctr Dallas, Dept Immunol, Dallas, TX 75390 USA.
   [Chen, Shu-Hsia] Mt Sinai Sch Med, Dept Oncol Sci, New York, NY 10029 USA.
   [Wang, Huan-You] Univ Calif San Diego, Dept Pathol, La Jolla, CA 92093 USA.
C3 University of Texas System; University of Texas Southwestern Medical Center; University of Texas System; University of Texas Southwestern Medical Center; Shanghai Jiao Tong University; University of the Ryukyus; University of Texas System; University of Texas Southwestern Medical Center; Icahn School of Medicine at Mount Sinai; University of California System; University of California San Diego
RP Zhang, CC (corresponding author), Univ Texas SW Med Ctr Dallas, Dept Physiol, Dallas, TX 75390 USA.
EM Alec.Zhang@UTsouthwestern.edu
FU NIH [K01 CA 120099]; American Society of Hematology; March of Dimes; DOD [PR093256]; CPRIT [RP100402]; Gabrielle's Angel Foundation
NR 37
TC 228
Z9 268
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 MAY 31
PY 2012
VL 485
IS 7400
BP 656
EP +
DI 10.1038/nature11095
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 949WP
UT WOS:000304608000051
PM 22660330
DA 2026-03-09
ER

PT J
AU Koivunen, P
   Lee, S
   Duncan, CG
   Lopez, G
   Lu, G
   Ramkissoon, S
   Losman, JA
   Joensuu, P
   Bergmann, U
   Gross, S
   Travins, J
   Weiss, S
   Looper, R
   Ligon, KL
   Verhaak, RGW
   Yan, H
   Kaelin, WG
AF Koivunen, Peppi
   Lee, Sungwoo
   Duncan, Christopher G.
   Lopez, Giselle
   Lu, Gang
   Ramkissoon, Shakti
   Losman, Julie A.
   Joensuu, Paivi
   Bergmann, Ulrich
   Gross, Stefan
   Travins, Jeremy
   Weiss, Samuel
   Looper, Ryan
   Ligon, Keith L.
   Verhaak, Roel G. W.
   Yan, Hai
   Kaelin, William G., Jr.
TI Transformation by the (R)-enantiomer of 2-hydroxyglutarate linked to EGLN activation
SO NATURE
LA English
DT Article
ID hypoxia-inducible factor; oncometabolite 2-hydroxyglutarate; prolyl 4-hydroxylase; active-site; mutations; tumors; idh1; hydroxylases; knockouts; cells
AB The identification of succinate dehydrogenase (SDH), fumarate hydratase (FH) and isocitrate dehydrogenase (IDH) mutations in human cancers has rekindled the idea that altered cellular metabolism can transform cells. Inactivating SDH and FH mutations cause the accumulation of succinate and fumarate, respectively, which can inhibit 2-oxoglutarate (2-OG)-dependent enzymes, including the EGLN prolyl 4-hydroxylases that mark the hypoxia inducible factor (HIF) transcription factor for polyubiquitylation and proteasomal degradation(1). Inappropriate HIF activation is suspected of contributing to the pathogenesis of SDH-defective and FH-defective tumours but can suppress tumour growth in some other contexts. IDH1 and IDH2, which catalyse the interconversion of isocitrate and 2-OG, are frequently mutated in human brain tumours and leukaemias. The resulting mutants have the neomorphic ability to convert 2-OG to the (R)-enantiomer of 2-hydroxyglutarate ((R)-2HG)(2,3). Here we show that (R)-2HG, but not (S)-2HG, stimulates EGLN activity, leading to diminished HIF levels, which enhances the proliferation and soft agar growth of human astrocytes. These findings define an enantiomer-specific mechanism by which the (R)-2HG that accumulates in IDH mutant brain tumours promotes transformation and provide a justification for exploring EGLN inhibition as a potential treatment strategy.
C1 [Lee, Sungwoo; Lu, Gang; Ramkissoon, Shakti; Losman, Julie A.; Ligon, Keith L.; Kaelin, William G., Jr.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA.
   [Lee, Sungwoo; Lu, Gang; Ramkissoon, Shakti; Losman, Julie A.; Ligon, Keith L.; Kaelin, William G., Jr.] Brigham & Womens Hosp, Boston, MA 02215 USA.
   [Koivunen, Peppi] Univ Oulu, Oulu Ctr Cell Matrix Res, Dept Med Biochem & Mol Biol, Bioctr Oulu, FIN-90014 Oulu, Finland.
   [Duncan, Christopher G.; Lopez, Giselle; Yan, Hai] Pediat Brain Tumor Fdn Inst, Preston Robert Tisch Brain Tumor Ctr Duke, Durham, NC 27710 USA.
   [Duncan, Christopher G.; Lopez, Giselle; Yan, Hai] Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA.
   [Ramkissoon, Shakti; Ligon, Keith L.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
   [Ramkissoon, Shakti; Ligon, Keith L.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
   [Joensuu, Paivi] Univ Oulu, Dept Chem, FIN-90014 Oulu, Finland.
   [Bergmann, Ulrich] Univ Oulu, Dept Biochem, Mass Spectrometry Core Facil, Bioctr Oulu, FIN-90014 Oulu, Finland.
   [Gross, Stefan; Travins, Jeremy] Agios Pharmaceut, Cambridge, MA 02139 USA.
   [Weiss, Samuel] Univ Calgary, Fac Med, Dept Cell Biol, Hotchkiss Brain Inst, Calgary, AB T2N 4N1, Canada.
   [Weiss, Samuel] Univ Calgary, Fac Med, Dept Anat, Hotchkiss Brain Inst, Calgary, AB T2N 4N1, Canada.
   [Looper, Ryan] Univ Utah, Dept Chem, Salt Lake City, UT 84112 USA.
   [Ligon, Keith L.] Childrens Hosp Boston, Dept Pathol, Boston, MA 02115 USA.
   [Verhaak, Roel G. W.] Univ Texas MD Anderson Canc Ctr, Dept Bioinformat & Computat Biol, Houston, TX 77030 USA.
   [Kaelin, William G., Jr.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA.
C3 Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; University of Oulu; Duke University; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard University; Harvard Medical School; University of Oulu; Finland National Institute for Health & Welfare; University of Oulu; Agios Pharmaceuticals; University of Calgary; University of Calgary; Utah System of Higher Education; University of Utah; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; University of Texas System; UTMD Anderson Cancer Center; Howard Hughes Medical Institute
RP Kaelin, WG (corresponding author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA.
EM william_kaelin@dfci.harvard.edu
FU National Institutes of Health; HHMI; Doris Duke Foundation; Academy of Finland [120156, 140765, 218129]; S. Juselius Foundation; Academy of Finland (AKA) [218129, 140765, 120156] Funding Source: Academy of Finland (AKA)
NR 41
TC 623
Z9 733
U1 0
U2 124
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 22
PY 2012
VL 483
IS 7390
BP 485
EP U144
DI 10.1038/nature10898
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 912CC
UT WOS:000301771200047
PM 22343896
DA 2026-03-09
ER

PT J
AU Gezari, S
   Chornock, R
   Rest, A
   Huber, ME
   Forster, K
   Berger, E
   Challis, PJ
   Neill, JD
   Martin, DC
   Heckman, T
   Lawrence, A
   Norman, C
   Narayan, G
   Foley, RJ
   Marion, GH
   Scolnic, D
   Chomiuk, L
   Soderberg, A
   Smith, K
   Kirshner, RP
   Riess, AG
   Smartt, SJ
   Stubbs, CW
   Tonry, JL
   Wood-Vasey, WM
   Burgett, WS
   Chambers, KC
   Grav, T
   Heasley, JN
   Kaiser, N
   Kudritzki, RP
   Magnier, EA
   Morgan, JS
   Price, PA
AF Gezari, S.
   Chornock, R.
   Rest, A.
   Huber, M. E.
   Forster, K.
   Berger, E.
   Challis, P. J.
   Neill, J. D.
   Martin, D. C.
   Heckman, T.
   Lawrence, A.
   Norman, C.
   Narayan, G.
   Foley, R. J.
   Marion, G. H.
   Scolnic, D.
   Chomiuk, L.
   Soderberg, A.
   Smith, K.
   Kirshner, R. P.
   Riess, A. G.
   Smartt, S. J.
   Stubbs, C. W.
   Tonry, J. L.
   Wood-Vasey, W. M.
   Burgett, W. S.
   Chambers, K. C.
   Grav, T.
   Heasley, J. N.
   Kaiser, N.
   Kudritzki, R. -P.
   Magnier, E. A.
   Morgan, J. S.
   Price, P. A.
TI An ultraviolet-optical flare from the tidal disruption of a helium-rich stellar core
SO NATURE
LA English
DT Article
ID massive black-hole; star; luminosity; evolution; outburst; galaxy
AB The flare of radiation from the tidal disruption and accretion of a star can be used as a marker for supermassive black holes that otherwise lie dormant and undetected in the centres of distant galaxies(1). Previous candidate flares(2-6) have had declining light curves in good agreement with expectations, but with poor constraints on the time of disruption and the type of star disrupted, because the rising emission was not observed. Recently, two 'relativistic' candidate tidal disruption events were discovered, each of whose extreme X-ray luminosity and synchrotron radio emission were interpreted as the onset of emission from a relativistic jet(7-10). Here we report a luminous ultraviolet-optical flare from the nuclear region of an inactive galaxy at a redshift of 0.1696. The observed continuum is cooler than expected for a simple accreting debris disk, but the well-sampled rise and decay of the light curve follow the predicted mass accretion rate and can be modelled to determine the time of disruption to an accuracy of two days. The black hole has a mass of about two million solar masses, modulo a factor dependent on the mass and radius of the star disrupted. On the basis of the spectroscopic signature of ionized helium from the unbound debris, we determine that the disrupted star was a helium-rich stellar core.
C1 [Gezari, S.; Heckman, T.; Norman, C.; Scolnic, D.; Riess, A. G.] Johns Hopkins Univ, Dept Phys & Astron, Baltimore, MD 21218 USA.
   [Chornock, R.; Berger, E.; Challis, P. J.; Narayan, G.; Foley, R. J.; Marion, G. H.; Chomiuk, L.; Soderberg, A.; Kirshner, R. P.; Stubbs, C. W.] Harvard Smithsonian Ctr Astrophys, Cambridge, MA 02138 USA.
   [Rest, A.] Space Telescope Sci Inst, Baltimore, MD 21218 USA.
   [Huber, M. E.; Tonry, J. L.; Burgett, W. S.; Chambers, K. C.; Heasley, J. N.; Kaiser, N.; Kudritzki, R. -P.; Magnier, E. A.; Morgan, J. S.] Univ Hawaii, Inst Astron, Honolulu, HI 96822 USA.
   [Forster, K.; Neill, J. D.; Martin, D. C.] CALTECH, Pasadena, CA 91125 USA.
   [Lawrence, A.] Univ Edinburgh, Royal Observ, Scottish Univ Phys Alliance, Inst Astron, Edinburgh EH9 3HJ, Midlothian, Scotland.
   [Smith, K.; Smartt, S. J.] Queens Univ Belfast, Sch Math & Phys, Astrophys Res Ctr, Belfast BT7 1NN, Antrim, North Ireland.
   [Wood-Vasey, W. M.] Univ Pittsburgh, Dept Phys & Astron, Pittsburgh Particle Phys Astrophys & Cosmol Ctr, Pittsburgh, PA 15260 USA.
   [Grav, T.] Planetary Sci Inst, Tucson, AZ 85719 USA.
   [Price, P. A.] Princeton Univ, Dept Astrophys Sci, Princeton, NJ 08544 USA.
C3 Johns Hopkins University; Smithsonian Astrophysical Observatory; Smithsonian Institution; Harvard University; Space Telescope Science Institute; University of Hawaii System; California Institute of Technology; University of Edinburgh; Queens University Belfast; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh; Princeton University
RP Gezari, S (corresponding author), Johns Hopkins Univ, Dept Phys & Astron, 3400 N Charles St, Baltimore, MD 21218 USA.
EM suvi@pha.jhu.edu
FU NASA; National Science Foundation; UK Science and Technology Facilities Council; Space Telescope Science Institute; Planetary Science Division of the NASA Science Mission Directorate; STFC [ST/I001123/1, ST/G009465/1] Funding Source: UKRI; Science and Technology Facilities Council [ST/I001123/1, ST/G009465/1] Funding Source: researchfish; Direct For Mathematical & Physical Scien; Division Of Astronomical Sciences [1009749] Funding Source: National Science Foundation
NR 29
TC 418
Z9 456
U1 2
U2 15
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD MAY 10
PY 2012
VL 485
IS 7397
BP 217
EP 220
DI 10.1038/nature10990
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 939HJ
UT WOS:000303799800036
PM 22575962
DA 2026-03-09
ER

PT J
AU Venkatesh, S
   Smolle, M
   Li, H
   Gogol, MM
   Saint, M
   Kumar, S
   Natarajan, K
   Workman, JL
AF Venkatesh, Swaminathan
   Smolle, Michaela
   Li, Hua
   Gogol, Madelaine M.
   Saint, Malika
   Kumar, Shambhu
   Natarajan, Krishnamurthy
   Workman, Jerry L.
TI Set2 methylation of histone H3 lysine 36 suppresses histone exchange on transcribed genes
SO NATURE
LA English
DT Article
ID rna-polymerase-ii; chromatin; acetylation; regions; complex; deacetylation; elongation; history; recruits; directs
AB Set2-mediated methylation of histone H3 at Lys 36 (H3K36me) is a co-transcriptional event that is necessary for the activation of the Rpd3S histone deacetylase complex, thereby maintaining the coding region of genes in a hypoacetylated state(1,2). In the absence of Set2, H3K36 or Rpd3S acetylated histones accumulate on open reading frames (ORFs), leading to transcription initiation from cryptic promoters within ORFs(1,3). Although the co-transcriptional deacetylation pathway is well characterized, the factors responsible for acetylation are as yet unknown. Here we show that, in yeast, co-transcriptional acetylation is achieved in part by histone exchange over ORFs. In addition to its function of targeting and activating the Rpd3S complex, H3K36 methylation suppresses the interaction of H3 with histone chaperones, histone exchange over coding regions and the incorporation of new acetylated histones. Thus, Set2 functions both to suppress the incorporation of acetylated histones and to signal for the deacetylation of these histones in transcribed genes. By suppressing spurious cryptic transcripts from initiating within ORFs, this pathway is essential to maintain the accuracy of transcription by RNA polymerase II.
C1 [Venkatesh, Swaminathan; Smolle, Michaela; Li, Hua; Gogol, Madelaine M.; Workman, Jerry L.] Stowers Inst Med Res, Kansas City, MO 64110 USA.
   [Saint, Malika; Kumar, Shambhu; Natarajan, Krishnamurthy] Jawarharlal Nehru Univ, Sch Life Sci, New Delhi 110067, India.
C3 Stowers Institute for Medical Research; Jawaharlal Nehru University, New Delhi
RP Workman, JL (corresponding author), Stowers Inst Med Res, 1000 E 50th St, Kansas City, MO 64110 USA.
EM jlw@stowers.org
FU National Institutes of Health [R01GM04867]; Stowers Institute for Medical Research
NR 35
TC 238
Z9 308
U1 0
U2 38
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD SEP 20
PY 2012
VL 489
IS 7416
BP 452
EP U145
DI 10.1038/nature11326
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 007AK
UT WOS:000308860900050
PM 22914091
DA 2026-03-09
ER

PT J
AU Dietrich, JP
   Werner, N
   Clowe, D
   Finoguenov, A
   Kitching, T
   Miller, L
   Simionescu, A
AF Dietrich, Joerg P.
   Werner, Norbert
   Clowe, Douglas
   Finoguenov, Alexis
   Kitching, Tom
   Miller, Lance
   Simionescu, Aurora
TI A filament of dark matter between two clusters of galaxies
SO NATURE
LA English
DT Article
ID hot intergalactic medium; weak lensing surveys; x-ray-absorption; cosmic web; shape measurement; sculptor wall; supercluster; abell-222; universe; baryons
AB It is a firm prediction of the concordance cold-dark-matter cosmological model that galaxy clusters occur at the intersection of large-scale structure filaments(1). The thread-like structure of this 'cosmic web' has been traced by galaxy redshift surveys for decades(2,3). More recently, the warm-hot intergalactic medium (a sparse plasma with temperatures of 10(5) kelvin to 10(7) kelvin) residing in low-redshift filaments has been observed in emission(4) and absorption(5,6). However, a reliable direct detection of the underlying dark-matter skeleton, which should contain more than half of all matter(7), has remained elusive, because earlier candidates for such detections(8-10) were either falsified(11,12) or suffered from low signal-to-noise ratios(8,10) and unphysical misalignments of dark and luminous matter(9,10). Here we report the detection of a dark-matter filament connecting the two main components of the Abell 222/223 supercluster system from its weak gravitational lensing signal, both in a non-parametric mass reconstruction and in parametric model fits. This filament is coincident with an overdensity of galaxies(10,13) and diffuse, soft-X-ray emission(4), and contributes a mass comparable to that of an additional galaxy cluster to the total mass of the supercluster. By combining this result with X-ray observations(4), we can place an upper limit of 0.09 on the hot gas fraction (the mass of X-ray-emitting gas divided by the total mass) in the filament.
C1 [Dietrich, Joerg P.] Univ Michigan, Dept Phys, Ann Arbor, MI 48109 USA.
   [Dietrich, Joerg P.] Univ Michigan, Michigan Ctr Theoret Phys, Ann Arbor, MI 48109 USA.
   [Werner, Norbert; Simionescu, Aurora] Stanford Univ, Kavli Inst Particle Astrophys & Cosmol, Stanford, CA 94305 USA.
   [Clowe, Douglas] Ohio Univ, Dept Phys & Astron, Clippinger Lab 251B, Athens, OH 45701 USA.
   [Finoguenov, Alexis] Max Planck Inst Extraterr Phys, D-85748 Garching, Germany.
   [Kitching, Tom] Univ Edinburgh, Royal Observ, Inst Astron, Edinburgh EH9 3HJ, Midlothian, Scotland.
   [Miller, Lance] Univ Oxford, Dept Phys, Oxford OX1 3RH, England.
C3 University of Michigan System; University of Michigan; University of Michigan System; University of Michigan; Stanford University; University System of Ohio; Ohio University; Max Planck Society; University of Edinburgh; University of Oxford
RP Dietrich, JP (corresponding author), Univ Michigan, Dept Phys, 450 Church St, Ann Arbor, MI 48109 USA.
EM jorgd@umich.edu
FU NSF [AST 0807304]; National Aeronautics and Space Administration [PF9-00070]; STFC [ST/H002456/1] Funding Source: UKRI; Science and Technology Facilities Council [ST/H002456/1] Funding Source: researchfish; Direct For Mathematical & Physical Scien [0807304] Funding Source: National Science Foundation; Division Of Astronomical Sciences [0807304] Funding Source: National Science Foundation
NR 26
TC 106
Z9 128
U1 1
U2 19
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUL 12
PY 2012
VL 487
IS 7406
BP 202
EP 204
DI 10.1038/nature11224
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 972LP
UT WOS:000306278900032
PM 22763438
DA 2026-03-09
ER

PT J
AU Nakamura, T
   Liu, YJ
   Nakashima, H
   Umehara, H
   Inoue, K
   Matoba, S
   Tachibana, M
   Ogura, A
   Shinkai, Y
   Nakano, T
AF Nakamura, Toshinobu
   Liu, Yu-Jung
   Nakashima, Hiroyuki
   Umehara, Hiroki
   Inoue, Kimiko
   Matoba, Shogo
   Tachibana, Makoto
   Ogura, Atsuo
   Shinkai, Yoichi
   Nakano, Toru
TI PGC7 binds histone H3K9me2 to protect against conversion of 5mC to 5hmC in early embryos
SO NATURE
LA English
DT Article
ID dna methyltransferases; 5-hydroxymethylcytosine; methylation; chromatin; 5-methylcytosine; transcription; excision; genome; cells; tet1
AB The modification of DNA by 5-methylcytosine (5mC) has essential roles in cell differentiation and development through epigenetic gene regulation(1). 5mC can be converted to another modified base, 5-hydroxymethylcytosine (5hmC), by the tet methylcytosine dioxygenase (Tet) family of enzymes(2,3). Notably, the balance between 5hmC and 5mC in the genome is linked with cell-differentiation processes such as pluripotency and lineage commitment(4-7). We have previously reported that the maternal factor PGC7 (also known as Dppa3, Stella) is required for the maintenance of DNA methylation in early embryogenesis, and protects 5mC from conversion to 5hmC in the maternal genome(8,9). Here we show that PGC7 protects 5mC from Tet3-mediated conversion to 5hmC by binding to maternal chromatin containing dimethylated histone H3 lysine 9 (H3K9me2) in mice. In addition, imprinted loci that are marked with H3K9me2 in mature sperm are protected by PGC7 binding in early embryogenesis. This type of regulatory mechanism could be involved in DNA modifications in somatic cells as well as in early embryos.
C1 [Liu, Yu-Jung; Nakashima, Hiroyuki; Umehara, Hiroki] Osaka Univ, Grad Sch Frontier Biosci, Suita, Osaka 5650871, Japan.
   [Nakamura, Toshinobu; Nakano, Toru] Osaka Univ, Dept Pathol, Grad Sch Med, Suita, Osaka 5650871, Japan.
   [Inoue, Kimiko; Matoba, Shogo; Ogura, Atsuo] RIKEN BioResouce Ctr, Tsukuba, Ibaraki 3050074, Japan.
   [Tachibana, Makoto; Shinkai, Yoichi] Kyoto Univ, Expt Res Ctr Infect Dis, Inst Virus Res, Kyoto 6068507, Japan.
C3 University of Osaka; University of Osaka; RIKEN; Kyoto University
RP Nakamura, T (corresponding author), Nagahama Inst Biosci & Technol, Shiga 5260829, Japan.
EM tnakamura@nagahama-i-bio.ac.jp; tnakano@patho.med.osaka-u.ac.jp
FU Ministry of Education, Science, Sports, Culture and Technology of Japan; Grants-in-Aid for Scientific Research [23220011, 24659135, 19061001, 23013016, 20062007, 23770224, 20062005] Funding Source: KAKEN
NR 25
TC 373
Z9 441
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 JUN 21
PY 2012
VL 486
IS 7403
BP 415
EP +
DI 10.1038/nature11093
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 961LV
UT WOS:000305466800046
PM 22722204
DA 2026-03-09
ER

PT J
AU Cassan, A
   Kubas, D
   Beaulieu, JP
   Dominik, M
   Horne, K
   Greenhill, J
   Wambsganss, J
   Menzies, J
   Williams, A
   Jorgensen, UG
   Udalski, A
   Bennett, DP
   Albrow, MD
   Batista, V
   Brillant, S
   Caldwell, JAR
   Cole, A
   Coutures, C
   Cook, KH
   Dieters, S
   Prester, DD
   Donatowicz, J
   Fouqué, P
   Hill, K
   Kains, N
   Kane, S
   Marquette, JB
   Martin, R
   Pollard, KR
   Sahu, KC
   Vinter, C
   Warren, D
   Watson, B
   Zub, M
   Sumi, T
   Szymanski, MK
   Kubiak, M
   Poleski, R
   Soszynski, I
   Ulaczyk, K
   Pietrzynski, G
   Wyrzykowski, L
AF Cassan, A.
   Kubas, D.
   Beaulieu, J. -P.
   Dominik, M.
   Horne, K.
   Greenhill, J.
   Wambsganss, J.
   Menzies, J.
   Williams, A.
   Jorgensen, U. G.
   Udalski, A.
   Bennett, D. P.
   Albrow, M. D.
   Batista, V.
   Brillant, S.
   Caldwell, J. A. R.
   Cole, A.
   Coutures, Ch.
   Cook, K. H.
   Dieters, S.
   Prester, D. Dominis
   Donatowicz, J.
   Fouque, P.
   Hill, K.
   Kains, N.
   Kane, S.
   Marquette, J. -B.
   Martin, R.
   Pollard, K. R.
   Sahu, K. C.
   Vinter, C.
   Warren, D.
   Watson, B.
   Zub, M.
   Sumi, T.
   Szymanski, M. K.
   Kubiak, M.
   Poleski, R.
   Soszynski, I.
   Ulaczyk, K.
   Pietrzynski, G.
   Wyrzykowski, L.
TI One or more bound planets per Milky Way star from microlensing observations
SO NATURE
LA English
DT Article
ID extrasolar planets; galactic planets; mass planet; systems; events; companion; discovery; frequency; neptunes; common
AB Most known extrasolar planets (exoplanets) have been discovered using the radial velocity(1,2) or transit(3) methods. Both are biased towards planets that are relatively close to their parent stars, and studies find that around 17-30% (refs 4, 5) of solar-like stars host a planet. Gravitational microlensing(6-9), on the other hand, probes planets that are further away from their stars. Recently, a population of planets that are unbound or very far from their stars was discovered by microlensing(10). These planets are at least as numerous as the stars in the Milky Way(10). Here we report a statistical analysis of microlensing data (gathered in 2002-07) that reveals the fraction of bound planets 0.5-10 AU (Sun-Earth distance) from their stars. We find that 17(-9)(+6)% of stars host Jupiter-mass planets (0.3-10M(J), where M-J = 318 M-circle plus and M-circle plus is Earth's mass). Cool Neptunes (10-30 M-circle plus) and super-Earths (5-10 M-circle plus) are even more common: their respective abundances per star are 52(-29)(+22)% and 62(-37)(+35)%. We conclude that stars are orbited by planets as a rule, rather than the exception.
C1 [Cassan, A.; Kubas, D.; Beaulieu, J. -P.; Dominik, M.; Horne, K.; Greenhill, J.; Wambsganss, J.; Menzies, J.; Williams, A.; Jorgensen, U. G.; Bennett, D. P.; Albrow, M. D.; Batista, V.; Brillant, S.; Caldwell, J. A. R.; Cole, A.; Coutures, Ch.; Cook, K. H.; Dieters, S.; Prester, D. Dominis; Donatowicz, J.; Fouque, P.; Hill, K.; Kains, N.; Kane, S.; Marquette, J. -B.; Martin, R.; Pollard, K. R.; Sahu, K. C.; Vinter, C.; Warren, D.; Watson, B.] Univ Paris 06, Probing Lensing Anomalies Network PLANET Collabro, Inst Astrophys Paris, UPMC CNRS,UMR7095, F-75014 Paris, France.
   [Cassan, A.; Wambsganss, J.] Heidelberg Univ, ARI, Zentrum Astron, D-69120 Heidelberg, Germany.
   [Kubas, D.; Brillant, S.] European So Observ, Santiago 19001, Chile.
   [Horne, K.] Univ St Andrews, SUPA, Sch Phys & Astron, St Andrews KY16 9SS, Fife, Scotland.
   [Greenhill, J.; Dieters, S.] Univ Tasmania, Sch Maths & Phys, Hobart, Tas 7001, Australia.
   [Menzies, J.] S African Astron Observ, ZA-7935 Observatory, South Africa.
   [Williams, A.; Martin, R.] Perth Observ, Perth, WA 6076, Australia.
   [Jorgensen, U. G.] Niels Bohr Inst, DK-2100 Copenhagen, Denmark.
   [Udalski, A.; Szymanski, M. K.; Kubiak, M.; Poleski, R.; Soszynski, I.; Ulaczyk, K.; Pietrzynski, G.; Wyrzykowski, L.] Univ Warsaw Observ, OGLE Collaborat, PL-00478 Warsaw, Poland.
   [Bennett, D. P.] Univ Notre Dame, Dept Phys, Baltimore, MD 21218 USA.
   [Albrow, M. D.] Univ Canterbury, Dept Phys & Astron, Christchurch 8140, New Zealand.
   [Cook, K. H.] Lawrence Livermore Natl Lab, Inst Geophys & Planetary Phys, Livermore, CA 94550 USA.
   [Prester, D. Dominis] Univ Rijeka, Dept Phys, Rijeka 51000, Croatia.
   [Donatowicz, J.] Vienna Univ Technol, Dept Comp, A-1040 Vienna, Austria.
   [Kane, S.] CALTECH, NASA Exoplanet Sci Inst, Pasadena, CA 91125 USA.
   [Sumi, T.] Osaka Univ, Dept Earth & Space Sci, MOA Collaborat, Osaka 5600043, Japan.
   [Sumi, T.] Osaka Univ, Dept Earth & Space Sci, Osaka 5600043, Japan.
   [Wyrzykowski, L.] Univ Cambridge, Inst Astron, Cambridge CB3 0HA, England.
   [Wyrzykowski, L.] UCL, Dept Phys & Astron, London WC1E 6BT, England.
C3 Sorbonne Universite; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Earth Sciences & Astronomy (INSU); Ruprecht Karls University Heidelberg; European Southern Observatory; University of St Andrews; University of Tasmania; National Research Foundation - South Africa; South African Astronomical Observatory; Perth Observatory; University of Copenhagen; Niels Bohr Institute; University of Warsaw; Warsaw University Observatory; University of Canterbury; United States Department of Energy (DOE); Lawrence Livermore National Laboratory; University of Rijeka; Technische Universitat Wien; California Institute of Technology; National Aeronautics & Space Administration (NASA); University of Osaka; University of Osaka; University of Cambridge; University of London; University College London
RP Cassan, A (corresponding author), Univ Paris 06, Probing Lensing Anomalies Network PLANET Collabro, Inst Astrophys Paris, UPMC CNRS,UMR7095, 98 Bis Blvd Arago, F-75014 Paris, France.
EM cassan@iap.fr
FU French Agence Nationale de la Recherche (ANR); French National Centre for Scientific Research (CNRS); NASA; US National Science Foundation; Lawrence Livermore National Laboratory/National Nuclear Security Administration/Department of Energy; French National Programme of Planetology; Program of International Cooperation in Science France-Australia; German Research Foundation; Instrument Center for Danish Astronomy; Danish Natural Science Research Council; European Research Council; Qatar National Research Fund; Grants-in-Aid for Scientific Research [23103002, 23340044] Funding Source: KAKEN; STFC [ST/G001987/1] Funding Source: UKRI; Science and Technology Facilities Council [ST/G001987/1] Funding Source: researchfish; Division Of Astronomical Sciences; Direct For Mathematical & Physical Scien [1009621] Funding Source: National Science Foundation
NR 30
TC 449
Z9 516
U1 0
U2 44
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JAN 12
PY 2012
VL 481
IS 7380
BP 167
EP 169
DI 10.1038/nature10684
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 874TO
UT WOS:000298981200031
PM 22237108
DA 2026-03-09
ER

PT J
AU Ren, AM
   Rajashankar, KR
   Patel, DJ
AF Ren, Aiming
   Rajashankar, Kanagalaghatta R.
   Patel, Dinshaw J.
TI Fluoride ion encapsulation by Mg2+ ions and phosphates in a fluoride riboswitch
SO NATURE
LA English
DT Article
ID thiamine pyrophosphate riboswitch; bacterial gene-expression; structural basis; glycine riboswitch; messenger-rnas; ligand; recognition; domain; molecules; mechanism
AB Significant advances in our understanding of RNA architecture, folding and recognition have emerged from structure-function studies on riboswitches, non-coding RNAs whose sensing domains bind small ligands and whose adjacent expression platforms contain RNA elements involved in the control of gene regulation. We now report on the ligand-bound structure of the Thermotoga petrophila fluoride riboswitch, which adopts a higher-order RNA architecture stabilized by pseudoknot and long-range reversed Watson-Crick and Hoogsteen A.U pair formation. The bound fluoride ion is encapsulated within the junctional architecture, anchored in place through direct coordination to three Mg2+ ions, which in turn are octahedrally coordinated to water molecules and five inwardly pointing backbone phosphates. Our structure of the fluoride riboswitch in the bound state shows how RNA can form a binding pocket selective for fluoride, while discriminating against larger halide ions. The T. petrophila fluoride riboswitch probably functions in gene regulation through a transcription termination mechanism.
C1 [Ren, Aiming; Patel, Dinshaw J.] Mem Sloan Kettering Ctr, Struct Biol Program, New York, NY 10065 USA.
   [Rajashankar, Kanagalaghatta R.] Argonne Natl Lab, Adv Photon Source, NE CAT, Chicago, IL 60439 USA.
   [Rajashankar, Kanagalaghatta R.] Cornell Univ, Dept Chem & Chem Biol, Ithaca, NY 14853 USA.
C3 Memorial Sloan Kettering Cancer Center; United States Department of Energy (DOE); Argonne National Laboratory; Cornell University
RP Patel, DJ (corresponding author), Mem Sloan Kettering Ctr, Struct Biol Program, New York, NY 10065 USA.
EM pateld@mskcc.org
FU NIH [GM34504]; National Cancer Institute [P30CA008748] Funding Source: NIH RePORTER
NR 31
TC 149
Z9 217
U1 1
U2 79
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUN 7
PY 2012
VL 486
IS 7401
BP 85
EP U1501
DI 10.1038/nature11152
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 953GD
UT WOS:000304854000031
PM 22678284
DA 2026-03-09
ER

PT J
AU Garrouste, R
   Clément, G
   Nel, P
   Engel, MS
   Grandcolas, P
   D'Haese, C
   Lagebro, L
   Denayer, J
   Gueriau, P
   Lafaite, P
   Olive, S
   Prestianni, C
   Nel, A
AF Garrouste, Romain
   Clement, Gael
   Nel, Patricia
   Engel, Michael S.
   Grandcolas, Philippe
   D'Haese, Cyrille
   Lagebro, Linda
   Denayer, Julien
   Gueriau, Pierre
   Lafaite, Patrick
   Olive, Sebastien
   Prestianni, Cyrille
   Nel, Andre
TI A complete insect from the Late Devonian period
SO NATURE
LA English
DT Article
ID arthropod; morphology; tetrapod; synapomorphy; ephemeroptera; odonatoptera; plant
AB After terrestrialization, the diversification of arthropods and vertebrates is thought to have occurred in two distinct phases(1), the first between the Silurian and the Frasnian stages (Late Devonian period) (425-385 million years (Myr) ago), and the second characterized by the emergence of numerous new major taxa, during the Late Carboniferous period (after 345 Myr ago). These two diversification periods bracket the depauperate vertebrate Romer's gap (360-345 Myr ago) and arthropod gap (385-325 Myr ago)(1), which could be due to preservational artefact(2,3). Although a recent molecular dating has given an age of 390 Myr for the Holometabola(4), the record of hexapods during the Early-Middle Devonian (411.5-391 Myr ago, Pragian to Givetian stages) is exceptionally sparse and based on fragmentary remains, which hinders the timing of this diversification. Indeed, although Devonian Archaeognatha are problematic(5,6), the Pragian of Scotland has given some Collembola and the incomplete insect Rhyniognatha, with its diagnostic dicondylic, metapterygotan mandibles(5,7). The oldest, definitively winged insects are from the Serpukhovian stage (latest Early Carboniferous period)(8). Here we report the first complete Late Devonian insect, which was probably a terrestrial species. Its 'orthopteroid' mandibles are of an omnivorous type, clearly not modified for a solely carnivorous diet. This discovery narrows the 45-Myr gap in the fossil record of Hexapoda, and demonstrates [GRAPHICS] further a first Devonian phase of diversification for the Hexapoda, as in vertebrates, and suggests that the Pterygota diversified before and during Romer's gap.
C1 [Garrouste, Romain; Nel, Patricia; Grandcolas, Philippe; D'Haese, Cyrille; Nel, Andre] Museum Natl Hist Nat, CNRS, UMR 7205, CP 50, F-75005 Paris, France.
   [Clement, Gael; Gueriau, Pierre] Museum Natl Hist Nat, CNRS, UMR 7207, F-75005 Paris, France.
   [Engel, Michael S.] Univ Kansas, Nat Hist Museum, Div Entomol, Lawrence, KS 66045 USA.
   [Engel, Michael S.] Univ Kansas, Dept Ecol & Evolutionary Biol, Lawrence, KS 66045 USA.
   [Lagebro, Linda] Uppsala Univ, Dept Earth Sci, SE-75236 Uppsala, Sweden.
   [Denayer, Julien; Olive, Sebastien] Univ Liege, Dept Geol, Serv Paleontol Anim & Humaine, B-4000 Liege, Belgium.
   [Gueriau, Pierre] Minist Culture & Commun, CNRS, USR 3461, IPANEMA, F-91190 Saint Aubin, France.
   [Lafaite, Patrick] CNRS MNHN DICAP, Serv Multimedia, CP 27, F-75005 Paris, France.
   [Olive, Sebastien; Prestianni, Cyrille] Royal Belgian Inst Nat Sci, Dept Palaeontol, B-1000 Brussels, Belgium.
C3 Sorbonne Universite; Museum National d'Histoire Naturelle (MNHN); Centre National de la Recherche Scientifique (CNRS); CNRS - Institute of Ecology & Environment (INEE); Museum National d'Histoire Naturelle (MNHN); Centre National de la Recherche Scientifique (CNRS); CNRS - Institute of Ecology & Environment (INEE); Sorbonne Universite; University of Kansas; University of Kansas; Uppsala University; University of Liege; Centre National de la Recherche Scientifique (CNRS); Centre National de la Recherche Scientifique (CNRS); Royal Belgian Institute of Natural Sciences
RP Garrouste, R (corresponding author), Museum Natl Hist Nat, CNRS, UMR 7205, CP 50, 45 Rue Buffon, F-75005 Paris, France.
EM garroust@mnhn.fr; anel@mnhn.fr
FU French National Agency under the TERRES project [ANR-2010-BLAN-607]; US National Science Foundation [DEB-0542909]
NR 30
TC 58
Z9 66
U1 0
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 AUG 2
PY 2012
VL 488
IS 7409
BP 82
EP 85
DI 10.1038/nature11281
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 981ZE
UT WOS:000307010700037
PM 22859205
DA 2026-03-09
ER

PT J
AU Deardorff, MA
   Bando, M
   Nakato, R
   Watrin, E
   Itoh, T
   Minamino, M
   Saitoh, K
   Komata, M
   Katou, Y
   Clark, D
   Cole, KE
   De Baere, E
   Decroos, C
   Di Donato, N
   Ernst, S
   Francey, LJ
   Gyftodimou, Y
   Hirashima, K
   Hullings, M
   Ishikawa, Y
   Jaulin, C
   Kaur, M
   Kiyono, T
   Lombardi, PM
   Magnaghi-Jaulin, L
   Mortier, GR
   Nozaki, N
   Petersen, MB
   Seimiya, H
   Siu, VM
   Suzuki, Y
   Takagaki, K
   Wilde, JJ
   Willems, PJ
   Prigent, C
   Gillessen-Kaesbach, G
   Christianson, DW
   Kaiser, FJ
   Jackson, LG
   Hirota, T
   Krantz, ID
   Shirahige, K
AF Deardorff, Matthew A.
   Bando, Masashige
   Nakato, Ryuichiro
   Watrin, Erwan
   Itoh, Takehiko
   Minamino, Masashi
   Saitoh, Katsuya
   Komata, Makiko
   Katou, Yuki
   Clark, Dinah
   Cole, Kathryn E.
   De Baere, Elfride
   Decroos, Christophe
   Di Donato, Nataliya
   Ernst, Sarah
   Francey, Lauren J.
   Gyftodimou, Yolanda
   Hirashima, Kyotaro
   Hullings, Melanie
   Ishikawa, Yuuichi
   Jaulin, Christian
   Kaur, Maninder
   Kiyono, Tohru
   Lombardi, Patrick M.
   Magnaghi-Jaulin, Laura
   Mortier, Geert R.
   Nozaki, Naohito
   Petersen, Michael B.
   Seimiya, Hiroyuki
   Siu, Victoria M.
   Suzuki, Yutaka
   Takagaki, Kentaro
   Wilde, Jonathan J.
   Willems, Patrick J.
   Prigent, Claude
   Gillessen-Kaesbach, Gabriele
   Christianson, David W.
   Kaiser, Frank J.
   Jackson, Laird G.
   Hirota, Toru
   Krantz, Ian D.
   Shirahige, Katsuhiko
TI HDAC8 mutations in Cornelia de Lange syndrome affect the cohesin acetylation cycle
SO NATURE
LA English
DT Article
ID sister-chromatid cohesion; x-chromosome-inactivation; s-phase; human genome; nipped-b; rna-seq; binding; complex; proteins; nipbl
AB Cornelia de Lange syndrome (CdLS) is a dominantly inherited congenital malformation disorder, caused by mutations in the cohesin-loading protein NIPBL1,2 for nearly 60% of individuals with classical CdLS3-5, and by mutations in the core cohesin components SMC1A (similar to 5%) and SMC3 (<1%) for a smaller fraction of probands(6,7). In humans, the multisubunit complex cohesin is made up of SMC1, SMC3, RAD21 and a STAG protein. These form a ring structure that is proposed to encircle sister chromatids to mediate sister chromatid cohesion(8) and also has key roles in gene regulation(9). SMC3 is acetylated during S-phase to establish cohesiveness of chromatin-loaded cohesin(10-13), and in yeast, the class I histone deacetylase Hos1 deacetylates SMC3 during anaphase(14-16). Here we identify HDAC8 as the vertebrate SMC3 deacetylase, as well as loss-of-function HDAC8 mutations in six CdLS probands. Loss of HDAC8 activity results in increased SMC3 acetylation and inefficient dissolution of the 'used' cohesin complex released from chromatin in both prophase and anaphase. SMC3 with retained acetylation is loaded onto chromatin, and chromatin immunoprecipitation sequencing analysis demonstrates decreased occupancy of cohesin localization sites that results in a consistent pattern of altered transcription seen in CdLS cell lines with either NIPBL or HDAC8 mutations.
C1 [Deardorff, Matthew A.; Clark, Dinah; Ernst, Sarah; Francey, Lauren J.; Hullings, Melanie; Kaur, Maninder; Wilde, Jonathan J.; Jackson, Laird G.; Krantz, Ian D.] Childrens Hosp Philadelphia, Div Human Genet & Mol Biol, Philadelphia, PA 19104 USA.
   [Deardorff, Matthew A.; Krantz, Ian D.] Univ Penn, Perelman Sch Med, Dept Pediat, Philadelphia, PA 19104 USA.
   [Bando, Masashige; Nakato, Ryuichiro; Minamino, Masashi; Saitoh, Katsuya; Komata, Makiko; Katou, Yuki; Shirahige, Katsuhiko] Univ Tokyo, Inst Mol & Cellular Biosci, Res Ctr Epigenet Dis, Tokyo 1130032, Japan.
   [Watrin, Erwan; Jaulin, Christian; Magnaghi-Jaulin, Laura; Prigent, Claude] Fac Med, Ctr Natl Rech Sci CNRS, Res Inst Genet & Dev IGDR, F-35043 Rennes, France.
   [Itoh, Takehiko] Tokyo Inst Technol, Sch & Grad Sch Biosci & Biotechnol, Yokohama, Kanagawa 2268503, Japan.
   [Cole, Kathryn E.; Decroos, Christophe; Lombardi, Patrick M.; Christianson, David W.] Univ Penn, Dept Chem, Philadelphia, PA 19104 USA.
   [De Baere, Elfride] Ghent Univ Hosp, Ctr Med Genet, B-9000 Ghent, Belgium.
   [Di Donato, Nataliya] Tech Univ Dresden, Inst Klin Genet, D-01307 Dresden, Germany.
   [Gyftodimou, Yolanda; Petersen, Michael B.] Inst Child Hlth, Dept Genet, Athens 11527, Greece.
   [Hirashima, Kyotaro; Seimiya, Hiroyuki] Japanese Fdn Canc Res, Div Mol Biotherapy, Tokyo 1358550, Japan.
   [Ishikawa, Yuuichi] Japanese Fdn Canc Res, Dept Pathol, Tokyo 1358550, Japan.
   [Kiyono, Tohru] Natl Canc Ctr, Res Inst, Div Virol, Tokyo 1040045, Japan.
   [Mortier, Geert R.] Univ Antwerp Hosp, Dept Med Genet, B-2650 Antwerp, Belgium.
   [Mortier, Geert R.] Univ Antwerp, B-2650 Antwerp, Belgium.
   [Nozaki, Naohito] Tokyo Inst Technol, Biofrontier Res Ctr, Yokohama, Kanagawa 2268503, Japan.
   [Petersen, Michael B.] Aarhus Univ Hosp, Aalborg Hosp, Dept Clin Genet, DK-9100 Aalborg, Denmark.
   [Siu, Victoria M.] Univ Western Ontario, London, ON N6A 5W9, Canada.
   [Suzuki, Yutaka; Hirota, Toru] Univ Tokyo, Grad Sch Frontier Sci, Tokyo 2778561, Japan.
   [Willems, Patrick J.] GENDIA, B-2020 Antwerp, Belgium.
   [Gillessen-Kaesbach, Gabriele; Kaiser, Frank J.] Med Univ Lubeck, Inst Humangenet Lubeck, D-23538 Lubeck, Germany.
   [Jackson, Laird G.] Drexel Univ, Sch Med, Dept Obstet & Gynecol, Philadelphia, PA 19102 USA.
   [Shirahige, Katsuhiko] JST, CREST, Chiyoda Ku, Tokyo 1020076, Japan.
C3 University of Pennsylvania; Pennsylvania Medicine; Childrens Hospital of Philadelphia; University of Pennsylvania; University of Tokyo; Universite de Rennes; Centre National de la Recherche Scientifique (CNRS); Institute of Science Tokyo; Tokyo Institute of Technology; University of Pennsylvania; Ghent University; Ghent University Hospital; Technische Universitat Dresden; Japanese Foundation for Cancer Research; Japanese Foundation for Cancer Research; National Cancer Center - Japan; University of Antwerp; University of Antwerp; Institute of Science Tokyo; Tokyo Institute of Technology; Aalborg University; Aalborg University Hospital; Aarhus University; Western University (University of Western Ontario); University of Tokyo; University of Lubeck; Drexel University; Japan Science & Technology Agency (JST)
RP Deardorff, MA (corresponding author), Childrens Hosp Philadelphia, Div Human Genet & Mol Biol, Philadelphia, PA 19104 USA.
EM deardorff@email.chop.edu; ian2@mail.med.upenn.edu; kshirahi@iam.u-tokyo.ac.jp
FU US and International Cornelia de Lange Syndrome Foundations; National Institutes of Health [K08HD055488, GM49758, P01 HD052860]; US CdLS Foundation; Children's Hospital of Philadelphia; University of Lubeck (Schwerpunktprogramm, Medizinische Genetik: Von seltenen Varianten zur Krankheitsentstehung); Research Program of Innovative Cell Biology by Innovative Technology; MEXT; National Institute of General Medical Sciences [R01GM049758] Funding Source: NIH RePORTER; Grants-in-Aid for Scientific Research [24650639, 21681025, 22300341] Funding Source: KAKEN
NR 44
TC 464
Z9 558
U1 1
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 SEP 13
PY 2012
VL 489
IS 7415
BP 313
EP +
DI 10.1038/nature11316
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 003UC
UT WOS:000308635900046
PM 22885700
DA 2026-03-09
ER

PT J
AU Lu, C
   Ward, PS
   Kapoor, GS
   Rohle, D
   Turcan, S
   Abdel-Wahab, O
   Edwards, CR
   Khanin, R
   Figueroa, ME
   Melnick, A
   Wellen, KE
   O'Rourke, DM
   Berger, SL
   Chan, TA
   Levine, RL
   Mellinghoff, IK
   Thompson, CB
AF Lu, Chao
   Ward, Patrick S.
   Kapoor, Gurpreet S.
   Rohle, Dan
   Turcan, Sevin
   Abdel-Wahab, Omar
   Edwards, Christopher R.
   Khanin, Raya
   Figueroa, Maria E.
   Melnick, Ari
   Wellen, Kathryn E.
   O'Rourke, Donald M.
   Berger, Shelley L.
   Chan, Timothy A.
   Levine, Ross L.
   Mellinghoff, Ingo K.
   Thompson, Craig B.
TI IDH mutation impairs histone demethylation and results in a block to cell differentiation
SO NATURE
LA English
DT Article
ID integrated genomic analysis; oncometabolite 2-hydroxyglutarate; leukemia; gene; dna; transcription; setdb1; tumors; brain
AB Recurrent mutations in isocitrate dehydrogenase 1 (IDH1) and IDH2 have been identified in gliomas, acute myeloid leukaemias (AML) and chondrosarcomas, and share a novel enzymatic property of producing 2-hydroxyglutarate (2HG) from alpha-ketoglutarate(1-6). Here we report that 2HG-producing IDH mutants can prevent the histone demethylation that is required for lineage-specific progenitor cells to differentiate into terminally differentiated cells. In tumour samples from glioma patients, IDH mutations were associated with a distinct gene expression profile enriched for genes expressed in neural progenitor cells, and this was associated with increased histone methylation. To test whether the ability of IDH mutants to promote histone methylation contributes to a block in cell differentiation in non-transformed cells, we tested the effect of neomorphic IDH mutants on adipocyte differentiation in vitro. Introduction of either mutant IDH or cell-permeable 2HG was associated with repression of the inducible expression of lineage-specific differentiation genes and a block to differentiation. This correlated with a significant increase in repressive histone methylation marks without observable changes in promoter DNA methylation. Gliomas were found to have elevated levels of similar histone repressive marks. Stable transfection of a 2HG-producing mutant IDH into immortalized astrocytes resulted in progressive accumulation of histone methylation. Of the marks examined, increased H3K9 methylation reproducibly preceded a rise in DNA methylation as cells were passaged in culture. Furthermore, we found that the 2HG-inhibitable H3K9 demethylase KDM4C was induced during adipocyte differentiation, and that RNA-interference suppression of KDM4C was sufficient to block differentiation. Together these data demonstrate that 2HG can inhibit histone demethylation and that inhibition of histone demethylation can be sufficient to block the differentiation of non-transformed cells.
C1 [Lu, Chao; Ward, Patrick S.; Thompson, Craig B.] Mem Sloan Kettering Canc Ctr, Canc Biol & Genet Program, New York, NY 10065 USA.
   [Lu, Chao; Ward, Patrick S.; Wellen, Kathryn E.] Univ Penn, Perelman Sch Med, Dept Canc Biol, Philadelphia, PA 19104 USA.
   [Kapoor, Gurpreet S.] Univ Penn, Perelman Sch Med, Dept Neurosurg, Philadelphia, PA 19104 USA.
   [Rohle, Dan; Turcan, Sevin; Abdel-Wahab, Omar; Chan, Timothy A.; Levine, Ross L.; Mellinghoff, Ingo K.] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10065 USA.
   [Rohle, Dan; Mellinghoff, Ingo K.] Weill Cornell Med Coll, Dept Pharmacol, New York, NY 10065 USA.
   [Abdel-Wahab, Omar; Levine, Ross L.] Mem Sloan Kettering Canc Ctr, Dept Med, Leukemia Serv, New York, NY 10065 USA.
   [Edwards, Christopher R.; Berger, Shelley L.] Univ Penn, Perelman Sch Med, Dept Cell & Dev Biol, Philadelphia, PA 19104 USA.
   [Figueroa, Maria E.; Melnick, Ari] Weill Cornell Med Coll, Div Hematol Oncol, New York, NY 10065 USA.
   [O'Rourke, Donald M.] Univ Penn, Perelman Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA.
   [Mellinghoff, Ingo K.] Mem Sloan Kettering Canc Ctr, Dept Neurol, New York, NY 10065 USA.
C3 Memorial Sloan Kettering Cancer Center; University of Pennsylvania; University of Pennsylvania; Memorial Sloan Kettering Cancer Center; Cornell University; Weill Cornell Medicine; Memorial Sloan Kettering Cancer Center; University of Pennsylvania; Cornell University; Weill Cornell Medicine; University of Pennsylvania; Memorial Sloan Kettering Cancer Center
RP Thompson, CB (corresponding author), Mem Sloan Kettering Canc Ctr, Canc Biol & Genet Program, New York, NY 10065 USA.
EM thompsonc@mskcc.org
FU National Cancer Institute; National Institutes of Health; Howard Hughes Medical Institute; MSKCC; Abramson Cancer Center at University of Pennsylvania; Doris Duke Charitable Foundation; American Society of Clinical Oncology;  [NCI-U54CA143798]; National Cancer Institute [R01CA078831] Funding Source: NIH RePORTER
NR 30
TC 1623
Z9 1906
U1 3
U2 258
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 22
PY 2012
VL 483
IS 7390
BP 474
EP U130
DI 10.1038/nature10860
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 912CC
UT WOS:000301771200045
PM 22343901
DA 2026-03-09
ER

PT J
AU Ince, DC
   Hatton, L
   Graham-Cumming, J
AF Ince, Darrel C.
   Hatton, Leslie
   Graham-Cumming, John
TI The case for open computer programs
SO NATURE
LA English
DT Article
ID reproducible research; errors; code
AB Scientific communication relies on evidence that cannot be entirely included in publications, but the rise of computational science has added a new layer of inaccessibility. Although it is now accepted that data should be made available on request, the current regulations regarding the availability of software are inconsistent. We argue that, with some exceptions, anything less than the release of source programs is intolerable for results that depend on computation. The vagaries of hardware, software and natural language will always ensure that exact reproducibility remains uncertain, but withholding code increases the chances that efforts to reproduce results will fail.
C1 [Ince, Darrel C.] Open Univ, Dept Comp, Walton Hall, Milton Keynes MK7 6AA, Bucks, England.
   [Hatton, Leslie] Kingston Univ, Sch Comp & Informat Syst, Kingston KT1 2EE, England.
C3 Open University - UK; Kingston University
RP Ince, DC (corresponding author), Open Univ, Dept Comp, Walton Hall, Milton Keynes MK7 6AA, Bucks, England.
EM d.c.ince@open.ac.uk
NR 37
TC 360
Z9 423
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 FEB 23
PY 2012
VL 482
IS 7386
BP 485
EP 488
DI 10.1038/nature10836
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 898VM
UT WOS:000300770500042
PM 22358837
DA 2026-03-09
ER

PT J
AU James, JR
   Vale, RD
AF James, John R.
   Vale, Ronald D.
TI Biophysical mechanism of T-cell receptor triggering in a reconstituted system
SO NATURE
LA English
DT Article
ID pattern-formation; activation; cd45; segregation; antigen; microclusters; thresholds; clusters; adhesion; kinases
AB A T-cell-mediated immune response is initiated by the T-cell receptor (TCR) interacting with peptide-bound major histocompatibility complex (pMHC) on an infected cell. The mechanism by which this interaction triggers intracellular phosphorylation of the TCR, which lacks a kinase domain, remains poorly understood. Here, we have introduced the TCR and associated signalling molecules into a non-immune cell and reconstituted ligand-specific signalling when these cells are conjugated with antigen-presenting cells. We show that signalling requires the differential segregation of a phosphatase and kinase in the plasma membrane. An artificial, chemically controlled receptor system generates the same effect as TCR-pMHC, demonstrating that the binding energy of an extracellular protein-protein interaction can drive the spatial segregation of membrane proteins without a transmembrane conformational change. This general mechanism may extend to other receptors that rely on extrinsic kinases, including, as we demonstrate, chimaeric antigen receptors being developed for cancer immunotherapy.
C1 [James, John R.; Vale, Ronald D.] Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94158 USA.
   [James, John R.; Vale, Ronald D.] Univ Calif San Francisco, Dept Cellular & Mol Pharmacol, San Francisco, CA 94158 USA.
C3 Howard Hughes Medical Institute; University of California System; University of California San Francisco; University of California System; University of California San Francisco
RP Vale, RD (corresponding author), Univ Calif San Francisco, Howard Hughes Med Inst, 600 16th St, San Francisco, CA 94158 USA.
EM vale@cmp.ucsf.edu
FU Howard Hughes Medical Institute Funding Source: Medline
NR 38
TC 271
Z9 352
U1 3
U2 72
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUL 5
PY 2012
VL 487
IS 7405
BP 64
EP 69
DI 10.1038/nature11220
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 968LM
UT WOS:000305982900050
PM 22763440
DA 2026-03-09
ER

PT J
AU Muller, FL
   Colla, S
   Aquilanti, E
   Manzo, VE
   Genovese, G
   Lee, J
   Eisenson, D
   Narurkar, R
   Deng, PN
   Nezi, L
   Lee, MA
   Hu, BL
   Hu, J
   Sahin, E
   Ong, D
   Fletcher-Sananikone, E
   Ho, D
   Kwong, L
   Brennan, C
   Wang, YA
   Chin, L
   DePinho, RA
AF Muller, Florian L.
   Colla, Simona
   Aquilanti, Elisa
   Manzo, Veronica E.
   Genovese, Giannicola
   Lee, Jaclyn
   Eisenson, Daniel
   Narurkar, Rujuta
   Deng, Pingna
   Nezi, Luigi
   Lee, Michelle A.
   Hu, Baoli
   Hu, Jian
   Sahin, Ergun
   Ong, Derrick
   Fletcher-Sananikone, Eliot
   Ho, Dennis
   Kwong, Lawrence
   Brennan, Cameron
   Wang, Y. Alan
   Chin, Lynda
   DePinho, Ronald A.
TI Passenger deletions generate therapeutic vulnerabilities in cancer
SO NATURE
LA English
DT Article
ID enolase deficiency; inhibition; regions; cells
AB Inactivation of tumour-suppressor genes by homozygous deletion is a prototypic event in the cancer genome, yet such deletions often encompass neighbouring genes. We propose that homozygous deletions in such passenger genes can expose cancer-specific therapeutic vulnerabilities when the collaterally deleted gene is a member of a functionally redundant family of genes carrying out an essential function. The glycolytic gene enolase 1 (ENO1) in the 1p36 locus is deleted in glioblastoma (GBM), which is tolerated by the expression of ENO2. Here we show that short-hairpin-RNA-mediated silencing of ENO2 selectively inhibits growth, survival and the tumorigenic potential of ENO1-deleted GBM cells, and that the enolase inhibitor phosphonoacetohydroxamate is selectively toxic to ENO1-deleted GBM cells relative to ENO1-intact GBM cells or normal astrocytes. The principle of collateral vulnerability should be applicable to other passenger-deleted genes encoding functionally redundant essential activities and provide an effective treatment strategy for cancers containing such genomic events.
C1 [Muller, Florian L.; Colla, Simona; Aquilanti, Elisa; Manzo, Veronica E.; Genovese, Giannicola; Lee, Jaclyn; Eisenson, Daniel; Narurkar, Rujuta; Deng, Pingna; Nezi, Luigi; Lee, Michelle A.; Hu, Baoli; Hu, Jian; Sahin, Ergun; Ong, Derrick; Fletcher-Sananikone, Eliot; Ho, Dennis; Kwong, Lawrence; Wang, Y. Alan; Chin, Lynda; DePinho, Ronald A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
   [Muller, Florian L.; Colla, Simona; Genovese, Giannicola; Deng, Pingna; Nezi, Luigi; Hu, Baoli; Hu, Jian; Ong, Derrick; Fletcher-Sananikone, Eliot; Kwong, Lawrence; Wang, Y. Alan; Chin, Lynda] Univ Texas MD Anderson Canc Ctr, Dept Genom Med, Houston, TX 77030 USA.
   [Muller, Florian L.; Colla, Simona; Hu, Jian; Sahin, Ergun; Ong, Derrick; Ho, Dennis; DePinho, Ronald A.] Harvard Univ, Sch Med, Dept Genet & Med, Boston, MA 02115 USA.
   [Lee, Michelle A.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
   [Hu, Baoli; Wang, Y. Alan; Chin, Lynda; DePinho, Ronald A.] Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, Boston, MA 02115 USA.
   [Brennan, Cameron] Mem Sloan Kettering Canc Ctr, Dept Neurosurg, New York, NY 10065 USA.
   [DePinho, Ronald A.] Univ Texas MD Anderson Canc Ctr, Dept Canc Biol, Houston, TX 77030 USA.
C3 Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; University of Texas System; UTMD Anderson Cancer Center; Harvard University; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Memorial Sloan Kettering Cancer Center; University of Texas System; UTMD Anderson Cancer Center
RP DePinho, RA (corresponding author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
EM rdepinho@mdanderson.org
FU National Institutes of Health (NIH) [T32-CA009361, P01CA95616]; American Cancer Society [115992-PF-08-261-01-TBE]; Dana-Farber Cancer Institute/Harvard Cancer Center Myeloma SPORE career development grant; Howard Hughes Medical Institute Medical Research Fellowship [57006984]; Harvard PRISE fellowship; Diversity in Health-Related research award [3 P01 CA095616-08S1]; Ben and Catherine Ivy Foundation
NR 37
TC 279
Z9 330
U1 1
U2 53
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 16
PY 2012
VL 488
IS 7411
BP 337
EP +
DI 10.1038/nature11331
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 988OS
UT WOS:000307501000033
PM 22895339
DA 2026-03-09
ER

PT J
AU Ma, D
   Lu, PL
   Yan, CY
   Fan, C
   Yin, P
   Wang, JW
   Shi, YG
AF Ma, Dan
   Lu, Peilong
   Yan, Chuangye
   Fan, Chao
   Yin, Ping
   Wang, Jiawei
   Shi, Yigong
TI Structure and mechanism of a glutamate-GABA antiporter
SO NATURE
LA English
DT Article
ID dependent acid resistance; crystal-structure; escherichia-coli; molecular-basis; substrate recognition; agmatine antiporter; binding-site; transport; arginine; protein
AB Food-borne hemorrhagic Escherichia coli, exemplified by the strains O157:H7 and O104:H4 (refs 1, 2), require elaborate acid-resistance systems (ARs)(3) to survive the extremely acidic environment such as the stomach (pH approximate to 2). AR2 expels intracellular protons through the decarboxylation of L-glutamate (Glu) in the cytoplasm and exchange of the reaction product c-aminobutyric acid (GABA) with extracellular Glu. The latter process is mediated by the Glu-GABA antiporter GadC(4,5), a representative member of theamino-acid-polyamine-organocation superfamily of membrane transporters. The functional mechanism of GadC remains largely unknown. Here we show, with the use of anin vitro proteoliposome-based assay, that GadC transports GABA/Glu only under acidic conditions, with no detectable activity at pH values higher than 6.5. We determined the crystal structure of E. coli GadC at 3.1 angstrom resolution under basic conditions. GadC, comprising 12 transmembrane segments (TMs), exists in a closed state, with its carboxy-terminal domain serving as a plug to block an otherwise inward-open conformation. Structural and biochemical analyses reveal the essential transport residues, identify the transport path and suggest a conserved transport mechanism involving the rigid-body rotation of a helical bundle for GadC and other amino acid antiporters.
C1 [Ma, Dan; Lu, Peilong; Fan, Chao; Shi, Yigong] Tsinghua Univ, Sch Life Sci, Struct Biol Ctr, Prot Sci Lab,Minist Educ, Beijing 100084, Peoples R China.
   [Ma, Dan; Lu, Peilong; Yan, Chuangye; Fan, Chao; Yin, Ping; Wang, Jiawei; Shi, Yigong] Tsinghua Univ, Sch Med, Beijing 100084, Peoples R China.
   [Yan, Chuangye; Yin, Ping; Wang, Jiawei] Tsinghua Univ, Sch Life Sci, Struct Biol Ctr, State Key Lab Biomembrane & Membrane Biotechnol, Beijing 100084, Peoples R China.
   [Ma, Dan; Lu, Peilong; Yan, Chuangye; Shi, Yigong] Tsinghua Univ, Sch Life Sci, Struct Biol Ctr, Tsinghua Peking Joint Ctr Life Sci, Beijing 100084, Peoples R China.
C3 Tsinghua University; Tsinghua University; Tsinghua University; Tsinghua University
RP Shi, YG (corresponding author), Tsinghua Univ, Sch Life Sci, Struct Biol Ctr, Prot Sci Lab,Minist Educ, Beijing 100084, Peoples R China.
EM shi-lab@tsinghua.edu.cn
FU Ministry of Science and Technology [2009CB918801]; National Natural Science Foundation; Beijing Municipal Commissions of Education and Science and Technology
NR 35
TC 170
Z9 201
U1 1
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 MAR 29
PY 2012
VL 483
IS 7391
BP 632
EP U161
DI 10.1038/nature10917
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 915EF
UT WOS:000302006100046
PM 22407317
DA 2026-03-09
ER

PT J
AU Schuster-Böckler, B
   Lehner, B
AF Schuster-Boeckler, Benjamin
   Lehner, Ben
TI Chromatin organization is a major influence on regional mutation rates in human cancer cells
SO NATURE
LA English
DT Article
ID human genome; somatic mutations; mammalian genome; map; recombination; methylations; leukemia; repair
AB Cancer genome sequencing provides the first direct information on how mutation rates vary across the human genome in somatic cells(1-7). Testing diverse genetic and epigenetic features, here we show that mutation rates in cancer genomes are strikingly related to chromatin organization. Indeed, at the megabase scale, a single feature-levels of the heterochromatin-associated histone modification H3K9me3-can account for more than 40% of mutation-rate variation, and a combination of features can account for more than 55%. The strong association between mutation rates and chromatin organization is upheld in samples from different tissues and for different mutation types. This suggests that the arrangement of the genome into heterochromatin- and euchromatin-like domains is a dominant influence on regional mutation-rate variation in human somatic cells.
C1 [Schuster-Boeckler, Benjamin; Lehner, Ben] CRG, EMBL CRG Syst Biol Unit, Barcelona 08003, Spain.
   [Schuster-Boeckler, Benjamin; Lehner, Ben] UPF, Barcelona 08003, Spain.
   [Schuster-Boeckler, Benjamin] Pear Comp LLP, London W5 1SH, England.
   [Lehner, Ben] Passeig Lluis Co 23, ICREA, Barcelona 08010, Spain.
C3 Barcelona Institute of Science & Technology; Pompeu Fabra University; Centre de Regulacio Genomica (CRG); Pompeu Fabra University; ICREA
RP Lehner, B (corresponding author), CRG, EMBL CRG Syst Biol Unit, Barcelona 08003, Spain.
EM ben.lehner@crg.es
FU European Research Council (ERC); European Union [277899 4DCellFate]; ERASysBioPLUS; Ministerio de Ciencia e Innovacion (MICINN) [BFU2008-00365, BFU2011-26206]; Agencia de Gestio d'Ajuts Universitaris i de Recerca (AGAUR); European Molecular Biology Organization (EMBO); EMBL-CRG Systems Biology Program; Juan de la Cierva postdoctoral fellowship; ICREA Funding Source: Custom
NR 30
TC 493
Z9 590
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 AUG 23
PY 2012
VL 488
IS 7412
BP 504
EP +
DI 10.1038/nature11273
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 992FS
UT WOS:000307761600035
PM 22820252
DA 2026-03-09
ER

PT J
AU Johnson, JE
   Reyes, FE
   Polaski, JT
   Batey, RT
AF Johnson, James E., Jr.
   Reyes, Francis E.
   Polaski, Jacob T.
   Batey, Robert T.
TI B12 cofactors directly stabilize an mRNA regulatory switch
SO NATURE
LA English
DT Article
ID vitamin-b-12 metabolism; comparative genomics; genetic-control; folding motif; riboswitches; recognition; mechanisms; expression; bacteria; elements
AB Structures of riboswitch receptor domains bound to their effector have shown how messenger RNAs recognize diverse small molecules, but mechanistic details linking the structures to the regulation of gene expression remain elusive(1,2). To address this, here we solve crystal structures of two different classes of cobalamin (vitamin B-12)-binding riboswitches that include the structural switch of the downstream regulatory domain. These classes share a common cobalamin-binding core, but use distinct peripheral extensions to recognize different B12 derivatives. In each case, recognition is accomplished through shape complementarity between the RNA and cobalamin, with relatively few hydrogen bonding interactions that typically govern RNA-small molecule recognition. We show that a composite cobalamin-RNA scaffold stabilizes an unusual long-range intramolecular kissing-loop interaction that controls mRNA expression. This is the first, to our knowledge, riboswitch crystal structure detailing how the receptor and regulatory domains communicate in a ligand-dependent fashion to regulate mRNA expression.
C1 [Johnson, James E., Jr.; Reyes, Francis E.; Polaski, Jacob T.; Batey, Robert T.] Univ Colorado, Dept Chem & Biochem, Boulder, CO 80309 USA.
C3 University of Colorado System; University of Colorado Boulder
RP Batey, RT (corresponding author), Univ Colorado, Dept Chem & Biochem, UCB 596, Boulder, CO 80309 USA.
EM francis.reyes@colorado.edu; robert.batey@colorado.edu
FU National Institutes of Health [GM073850, 1S10RR026516]; Colorado Diversity Initiative Fellowship; NIH Ruth L. Kirschstein fellowship [F32GM095121]; Office of Science, Office of Basic Energy Sciences, of the US Department of Energy [DE-AC02-05CH11231]; National Institute of General Medical Sciences [R01GM073850] Funding Source: NIH RePORTER
NR 40
TC 163
Z9 211
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 DEC 6
PY 2012
VL 492
IS 7427
BP 133
EP +
DI 10.1038/nature11607
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 048EQ
UT WOS:000311893400060
PM 23064232
DA 2026-03-09
ER

PT J
AU Basler, M
   Pilhofer, M
   Henderson, GP
   Jensen, GJ
   Mekalanos, JJ
AF Basler, M.
   Pilhofer, M.
   Henderson, G. P.
   Jensen, G. J.
   Mekalanos, J. J.
TI Type VI secretion requires a dynamic contractile phage tail-like structure
SO NATURE
LA English
DT Article
ID enteroaggregative escherichia-coli; pseudomonas-aeruginosa; protein secretion; target-cells; system; tomography; apparatus; alignment; bacteria; actin
AB Type VI secretion systems are bacterial virulence-associated nanomachines composed of proteins that are evolutionarily related to components of bacteriophage tails. Here we show that protein secretion by the type VI secretion system of Vibrio cholerae requires the action of a dynamic intracellular tubular structure that is structurally and functionally homologous to contractile phage tail sheath. Time-lapse fluorescence light microscopy reveals that sheaths of the type VI secretion system cycle between assembly, quick contraction, disassembly and re-assembly. Whole-cell electron cryotomography further shows that the sheaths appear as long tubular structures in either extended or contracted conformations that are connected to the inner membrane by a distinct basal structure. These data support a model in which the contraction of the type VI secretion system sheath provides the energy needed to translocate proteins out of effector cells and into adjacent target cells.
C1 [Pilhofer, M.; Henderson, G. P.; Jensen, G. J.] CALTECH, Div Biol, Pasadena, CA 91125 USA.
   [Basler, M.; Mekalanos, J. J.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA 02115 USA.
   [Pilhofer, M.; Jensen, G. J.] CALTECH, Howard Hughes Med Inst, Pasadena, CA 91125 USA.
C3 California Institute of Technology; Harvard University; Harvard Medical School; Howard Hughes Medical Institute; California Institute of Technology
RP Jensen, GJ (corresponding author), CALTECH, Div Biol, 1200 E Calif Blvd, Pasadena, CA 91125 USA.
EM Jensen@caltech.edu; john_mekalanos@hms.harvard.edu
FU National Institute of Allergy and Infectious Diseases [AI-018045, AI-26289]; National Institute of General Medical Sciences [GM094800B]; National Institute of Allergy and Infectious Diseases [R37AI018045] Funding Source: NIH RePORTER
NR 36
TC 543
Z9 662
U1 4
U2 212
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD MAR 8
PY 2012
VL 483
IS 7388
BP 182
EP U78
DI 10.1038/nature10846
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 904DT
UT WOS:000301174900031
PM 22367545
DA 2026-03-09
ER

PT J
AU Gibaud, T
   Barry, E
   Zakhary, MJ
   Henglin, M
   Ward, A
   Yang, YS
   Berciu, C
   Oldenbourg, R
   Hagan, MF
   Nicastro, D
   Meyer, RB
   Dogic, Z
AF Gibaud, Thomas
   Barry, Edward
   Zakhary, Mark J.
   Henglin, Mir
   Ward, Andrew
   Yang, Yasheng
   Berciu, Cristina
   Oldenbourg, Rudolf
   Hagan, Michael F.
   Nicastro, Daniela
   Meyer, Robert B.
   Dogic, Zvonimir
TI Reconfigurable self-assembly through chiral control of interfacial tension
SO NATURE
LA English
DT Article
ID twist penetration; microscope; length; model; layer
AB From determining the optical properties of simple molecular crystals to establishing the preferred handedness in highly complex vertebrates, molecular chirality profoundly influences the structural, mechanical and optical properties of both synthetic and biological matter on macroscopic length scales(1,2). In soft materials such as amphiphilic lipids and liquid crystals, the competition between local chiral interactions and global constraints imposed by the geometry of the self-assembled structures leads to frustration and the assembly of unique materials(3-6). An example of particular interest is smectic liquid crystals, where the two-dimensional layered geometry cannot support twist and chirality is consequently expelled to the edges in a manner analogous to the expulsion of a magnetic field from superconductors(7-10). Here we demonstrate a consequence of this geometric frustration that leads to a new design principle for the assembly of chiral molecules. Using a model system of colloidal membranes(11), we show that molecular chirality can control the interfacial tension, an important property of multi-component mixtures. This suggests an analogy between chiral twist, which is expelled to the edges of two-dimensional membranes, and amphiphilic surfactants, which are expelled to oil-water interfaces(12). As with surfactants, chiral control of interfacial tension drives the formation of many polymorphic assemblages such as twisted ribbons with linear and circular topologies, starfish membranes, and double and triple helices. Tuning molecular chirality in situ allows dynamical control of line tension, which powers polymorphic transitions between various chiral structures. These findings outline a general strategy for the assembly of reconfigurable chiral materials that can easily be moved, stretched, attached to one another and transformed between multiple conformational states, thus allowing precise assembly and nanosculpting of highly dynamical and designable materials with complex topologies.
C1 [Gibaud, Thomas; Barry, Edward; Zakhary, Mark J.; Henglin, Mir; Ward, Andrew; Yang, Yasheng; Hagan, Michael F.; Meyer, Robert B.; Dogic, Zvonimir] Brandeis Univ, Martin Fisher Sch Phys, 415 South St, Waltham, MA 02454 USA.
   [Berciu, Cristina; Nicastro, Daniela] Brandeis Univ, Dept Biol, Waltham, MA 02454 USA.
   [Oldenbourg, Rudolf] Marine Biol Lab, Woods Hole, MA 02543 USA.
C3 Brandeis University; Brandeis University; Marine Biological Laboratory - Woods Hole
RP Dogic, Z (corresponding author), Brandeis Univ, Martin Fisher Sch 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, NSF-CMMI-1068566]; Petroleum Research Fund [ACS-PRF 50558-DNI7]; Direct For Mathematical & Physical Scien; Division Of Materials Research [0820492, 0923054] Funding Source: National Science Foundation; Direct For Mathematical & Physical Scien; Division Of Materials Research [0955776, 0923057] Funding Source: National Science Foundation
NR 38
TC 214
Z9 238
U1 2
U2 406
PU NATURE PUBLISHING 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 19
PY 2012
VL 481
IS 7381
BP 348
EP +
DI 10.1038/nature10769
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 877VK
UT WOS:000299210600039
PM 22217941
DA 2026-03-09
ER

PT J
AU Kanfi, Y
   Naiman, S
   Amir, G
   Peshti, V
   Zinman, G
   Nahum, L
   Bar-Joseph, Z
   Cohen, HY
AF Kanfi, Yariv
   Naiman, Shoshana
   Amir, Gail
   Peshti, Victoria
   Zinman, Guy
   Nahum, Liat
   Bar-Joseph, Ziv
   Cohen, Haim Y.
TI The sirtuin SIRT6 regulates lifespan in male mice
SO NATURE
LA English
DT Article
ID gene-expression; caloric restriction; metabolic syndrome; protects; receptor; elegans; absence; tissue; mouse; igf1
AB The significant increase in human lifespan during the past century confronts us with great medical challenges. To meet these challenges, the mechanisms that determine healthy ageing must be understood and controlled. Sirtuins are highly conserved deacetylases that have been shown to regulate lifespan in yeast, nematodes and fruitflies(1). However, the role of sirtuins in regulating worm and fly lifespan has recently become controversial(2). Moreover, the role of the seven mammalian sirtuins, SIRT1 to SIRT7 (homologues of the yeast sirtuin Sir2), in regulating lifespan is unclear(3). Here we show that male, but not female, transgenic mice overexpressing Sirt6 (ref. 4) have a significantly longer lifespan than wild-type mice. Gene expression analysis revealed significant differences between male Sirt6-transgenic mice and male wild-type mice: transgenic males displayed lower serum levels of insulin-like growth factor 1 (IGF1), higher levels of IGF-binding protein 1 and altered phosphorylation levels of major components of IGF1 signalling, a key pathway in the regulation of lifespan(5). This study shows the regulation of mammalian lifespan by a sirtuin family member and has important therapeutic implications for age-related diseases.
C1 [Kanfi, Yariv; Naiman, Shoshana; Peshti, Victoria; Nahum, Liat; Cohen, Haim Y.] Bar Ilan Univ, Mina & Everard Goodman Fac Life Sci, IL-52900 Ramat Gan, Israel.
   [Amir, Gail] Hadassah Med Ctr, Dept Pathol, IL-91120 Jerusalem, Israel.
   [Amir, Gail] Hebrew Univ Jerusalem, IL-91120 Jerusalem, Israel.
   [Zinman, Guy; Bar-Joseph, Ziv] Carnegie Mellon Univ, Sch Comp Sci, Lane Ctr Computat Biol, Pittsburgh, PA 15217 USA.
C3 Bar Ilan University; Hebrew University of Jerusalem; Hadassah University Hospital; Hadassah University Medical Center; Hebrew University of Jerusalem; Carnegie Mellon University
RP Cohen, HY (corresponding author), Bar Ilan Univ, Mina & Everard Goodman Fac Life Sci, IL-52900 Ramat Gan, Israel.
EM Haim.Cohen@biu.ac.il
FU National Institutes of Health [1RO1 GM085022]; Israeli Academy of Sciences; United States - Israel Binational Science Foundation; Israel Cancer Association; Koret Foundation; Israel Cancer Research Fund; Israel Health Ministry [41/1]; Israel Science Foundation; European Research Council
NR 26
TC 838
Z9 996
U1 3
U2 189
PU NATURE PUBLISHING 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 8
PY 2012
VL 483
IS 7388
BP 218
EP 221
DI 10.1038/nature10815
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 904DT
UT WOS:000301174900040
PM 22367546
DA 2026-03-09
ER

PT J
AU Zhang, X
   Ren, WL
   DeCaen, P
   Yan, CY
   Tao, X
   Tang, L
   Wang, JJ
   Hasegawa, K
   Kumasaka, T
   He, JH
   Wang, JW
   Clapham, DE
   Yan, N
AF Zhang, Xu
   Ren, Wenlin
   DeCaen, Paul
   Yan, Chuangye
   Tao, Xiao
   Tang, Lin
   Wang, Jingjing
   Hasegawa, Kazuya
   Kumasaka, Takashi
   He, Jianhua
   Wang, Jiawei
   Clapham, David E.
   Yan, Nieng
TI Crystal structure of an orthologue of the NaChBac voltage-gated sodium channel
SO NATURE
LA English
DT Article
ID swiss-model; gating charge; k+ channel; inactivation; crystallography; environment; activation; movement; software; motions
AB Voltage-gated sodium (Na-v) channels are essential for the rapid depolarization of nerve and muscle(1), and are important drug targets(2). Determination of the structures of Na-v channels will shed light on ion channel mechanisms and facilitate potential clinical applications. A family of bacterial Na-v channels, exemplified by the Na+-selective channel of bacteria (NaChBac)(3), provides a useful model system for structure-function analysis. Here we report the crystal structure of NavRh, a NaChBac orthologue from the marine alphaproteobacterium HIMB114 (Rickettsiales sp. HIMB114; denoted Rh), at 3.05 angstrom resolution. The channel comprises an asymmetric tetramer. The carbonyl oxygen atoms of Thr 178 and Leu 179 constitute an inner site within the selectivity filter where a hydrated Ca2+ resides in the crystal structure. The outer mouth of the Na+ selectivity filter, defined by Ser 181 and Glu 183, is closed, as is the activation gate at the intracellular side of the pore. The voltage sensors adopt a depolarized conformation in which all the gating charges are exposed to the extracellular environment. We propose that NavRh is in an 'inactivated' conformation. Comparison of NavRh with Na(v)Ab(4) reveals considerable conformational rearrangements that may underlie the electromechanical coupling mechanism of voltage-gated channels.
C1 [Zhang, Xu; Ren, Wenlin; Yan, Chuangye; Wang, Jiawei; Yan, Nieng] Tsinghua Univ, Sch Life Sci, Struct Biol Ctr, State Key Lab Biomembrane & Membrane Biotechnol, Beijing 100084, Peoples R China.
   [Zhang, Xu; Ren, Wenlin; Yan, Chuangye; Wang, Jiawei; Yan, Nieng] Tsinghua Univ, Sch Med, Beijing 100084, Peoples R China.
   [Zhang, Xu; Ren, Wenlin; Yan, Chuangye; Yan, Nieng] Tsinghua Univ, Tsinghua Peking Ctr Life Sci, Beijing 100084, Peoples R China.
   [DeCaen, Paul; Clapham, David E.] Childrens Hosp Boston, Dept Cardiol, Howard Hughes Med Inst, Boston, MA 02115 USA.
   [DeCaen, Paul; Clapham, David E.] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA.
   [Tao, Xiao] Rockefeller Univ, Howard Hughes Med Inst, Lab Mol Neurobiol & Biophys, New York, NY 10065 USA.
   [Tang, Lin; He, Jianhua] Chinese Acad Sci, Shanghai Inst Appl Phys, Shanghai 201204, Peoples R China.
   [Wang, Jingjing] Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China.
   [Hasegawa, Kazuya; Kumasaka, Takashi] SPring 8, Japan Synchrotron Radiat Res Inst, Sayo, Hyogo 6795198, Japan.
C3 Tsinghua University; Tsinghua University; Tsinghua University; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Howard Hughes Medical Institute; Harvard University; Harvard Medical School; Rockefeller University; Howard Hughes Medical Institute; Chinese Academy of Sciences; Shanghai Institute of Applied Physics, CAS; Chinese Academy of Sciences; Shanghai Institute of Materia Medica, CAS; Japan Synchrotron Radiation Research Institute
RP Yan, N (corresponding author), Tsinghua Univ, Sch Life Sci, Struct Biol Ctr, State Key Lab Biomembrane & Membrane Biotechnol, Beijing 100084, Peoples R China.
EM nyan@tsinghua.edu.cn
FU Ministry of Science and Technology [2009CB918802, 2011CB910501, 2011CB911102]; National Natural Science Foundation of China [31125009, 91017011]; Tsinghua University; National Heart Lung and Blood Institute [T32HL007572] Funding Source: NIH RePORTER
NR 47
TC 410
Z9 463
U1 8
U2 327
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 7
PY 2012
VL 486
IS 7401
BP 130
EP U160
DI 10.1038/nature11054
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 953GD
UT WOS:000304854000042
PM 22678295
DA 2026-03-09
ER

PT J
AU Chao, WCH
   Kulkarni, K
   Zhang, ZG
   Kong, EH
   Barford, D
AF Chao, William C. H.
   Kulkarni, Kiran
   Zhang, Ziguo
   Kong, Eric H.
   Barford, David
TI Structure of the mitotic checkpoint complex
SO NATURE
LA English
DT Article
ID anaphase-promoting complex; spindle-assembly checkpoint; ken box; pseudosubstrate inhibition; mad2 activation; protein mad2; cdc20; binding; bubr1; apc/c
AB In mitosis, the spindle assembly checkpoint (SAC) ensures genome stability by delaying chromosome segregation until all sister chromatids have achieved bipolar attachment to the mitotic spindle. The SAC is imposed by the mitotic checkpoint complex (MCC), whose assembly is catalysed by unattached chromosomes and which binds and inhibits the anaphase-promoting complex/cyclosome (APC/C), the E3 ubiquitin ligase that initiates chromosome segregation. Here, using the crystal structure of Schizosaccharomyces pombe MCC(a complex of mitotic spindle assembly checkpoint proteins Mad2, Mad3 and APC/C co-activator protein Cdc20), we reveal the molecular basis of MCC-mediated APC/C inhibition and the regulation of MCC assembly. The MCC inhibits the APC/C by obstructing degron recognition sites on Cdc20 (the substrate recruitment subunit of the APC/C) and displacing Cdc20 to disrupt formation of a bipartite D-box receptor with the APC/C subunit Apc10. Mad2, in the closed conformation (C-Mad2), stabilizes the complex by optimally positioning the Mad3 KEN-box degron to bind Cdc20. Mad3 and p31(comet) (also known as MAD2L1-binding protein) compete for the same C-Mad2 interface, which explains how p31(comet) disrupts MCC assembly to antagonize the SAC. This study shows how APC/C inhibition is coupled to degron recognition by co-activators.
C1 [Chao, William C. H.; Kulkarni, Kiran; Zhang, Ziguo; Kong, Eric H.; Barford, David] Inst Canc Res, Chester Beatty Labs, Div Struct Biol, London SW3 6JB, England.
C3 University of London; Institute of Cancer Research - UK; Royal Marsden NHS Foundation Trust
RP Barford, D (corresponding author), Inst Canc Res, Chester Beatty Labs, Div Struct Biol, 237 Fulham Rd, London SW3 6JB, England.
EM david.barford@icr.ac.uk
FU Cancer Research UK; ICR; Cancer Research UK [14109] Funding Source: researchfish
NR 61
TC 250
Z9 306
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 APR 12
PY 2012
VL 484
IS 7393
BP 208
EP U89
DI 10.1038/nature10896
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 930OV
UT WOS:000303149900028
PM 22437499
DA 2026-03-09
ER

PT J
AU Reinhardt, C
   Bergentall, M
   Greiner, TU
   Schaffner, F
   Östergren-Lundén, G
   Petersen, LC
   Ruf, W
   Bäckhed, F
AF Reinhardt, Christoph
   Bergentall, Mattias
   Greiner, Thomas U.
   Schaffner, Florence
   Ostergren-Lunden, Gunnel
   Petersen, Lars C.
   Ruf, Wolfram
   Backhed, Fredrik
TI Tissue factor and PAR1 promote microbiota-induced intestinal vascular remodelling
SO NATURE
LA English
DT Article
ID factor cytoplasmic domain; endothelial-cells; thrombin receptor; factor expression; angiogenesis; hemostasis; mice
AB The gut microbiota is a complex ecosystem that has coevolved with host physiology. Colonization of germ-free (GF) mice with a microbiota promotes increased vessel density in the small intestine(1), but little is known about the mechanisms involved. Tissue factor (TF) is themembrane receptor that initiates the extrinsic coagulation pathway(2), and it promotes developmental and tumour angiogenesis(3,4). Here we show that the gut microbiota promotes TF glycosylation associated with localization of TF on the cell surface, the activation of coagulation proteases, and phosphorylation of theTFcytoplasmic domain in the small intestine. Anti-TF treatment of colonized GF mice decreased microbiota-induced vascular remodelling and expression of the proangiogenic factor angiopoietin-1 (Ang-1) in the small intestine. Mice with a genetic deletion of theTFcytoplasmic domain or with hypomorphic TF (F3) alleles had a decreased intestinal vessel density. Coagulation proteases downstream of TF activate protease-activated receptor (PAR) signalling implicated in angiogenesis(5). Vesseldensity and phosphorylation of the cytoplasmic domain of TF were decreased in small intestine fromPAR1-deficient (F2r(-/-)) but not PAR2-deficient (F2rl1(-/-)) mice, and inhibition of thrombin showed that thrombin-PAR1 signalling was upstream of TF phosphorylation. Thus, the microbiota-induced extravascular TF-PAR1 signalling loop is a novel pathway thatmay bemodulated to influence vascular remodelling in the small intestine.
C1 [Reinhardt, Christoph; Bergentall, Mattias; Greiner, Thomas U.; Ostergren-Lunden, Gunnel; Backhed, Fredrik] Univ Gothenburg, Sahlgrenska Ctr Cardiovasc & Metab Res, Wallenberg Lab, S-41345 Gothenburg, Sweden.
   [Reinhardt, Christoph; Bergentall, Mattias; Greiner, Thomas U.; Ostergren-Lunden, Gunnel; Backhed, Fredrik] Univ Gothenburg, Dept Mol & Clin Med, S-41345 Gothenburg, Sweden.
   [Reinhardt, Christoph] Univ Med Ctr Mainz, CTH, D-55131 Mainz, Germany.
   [Schaffner, Florence; Ruf, Wolfram] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA.
   [Petersen, Lars C.] Novo Nordisk AS, Haemostasis Biol, DK-2760 Malov, Denmark.
   [Backhed, Fredrik] Univ Copenhagen, Fac Hlth Sci, Sect Metab Receptol & Enteroendocrinol, Novo Nordisk Fdn Ctr Basic Metab Res, DK-2200 Copenhagen, Denmark.
C3 University of Gothenburg; University of Gothenburg; Johannes Gutenberg University of Mainz; Scripps Research Institute; Novo Nordisk; University of Copenhagen; Novo Nordisk Foundation
RP Bäckhed, F (corresponding author), Univ Gothenburg, Sahlgrenska Ctr Cardiovasc & Metab Res, Wallenberg Lab, S-41345 Gothenburg, Sweden.
EM fredrik.backhed@wlab.gu.se
FU Swedish Foundation for Strategic Research; Swedish Research Council; Torsten and Ragnar Soderberg's foundation; Petrus and Augusta Hedlund's foundation; Swedish federal government under LUA/ALF; National Institutes of Health [HL-60742, HL-77753]; European Union; German Federal Ministry of Education and Research [BMBF 01EO1003]
NR 34
TC 223
Z9 263
U1 1
U2 61
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 29
PY 2012
VL 483
IS 7391
BP 627
EP U155
DI 10.1038/nature10893
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 915EF
UT WOS:000302006100045
PM 22407318
DA 2026-03-09
ER

PT J
AU Vijay, R
   Macklin, C
   Slichter, DH
   Weber, SJ
   Murch, KW
   Naik, R
   Korotkov, AN
   Siddiqi, I
AF Vijay, R.
   Macklin, C.
   Slichter, D. H.
   Weber, S. J.
   Murch, K. W.
   Naik, R.
   Korotkov, A. N.
   Siddiqi, I.
TI Stabilizing Rabi oscillations in a superconducting qubit using quantum feedback
SO NATURE
LA English
DT Article
ID homodyne detection; time
AB The act of measurement bridges the quantum and classical worlds by projecting a superposition of possible states into a single (probabilistic) outcome. The timescale of this 'instantaneous' process can be stretched using weak measurements(1,2), such that it takes the form of a gradual random walk towards a final state. Remarkably, the interim measurement record is sufficient to continuously track and steer the quantum state using feedback(3-8). Here we implement quantum feedback control in a solid-state system, namely a superconducting quantum bit (qubit) coupled to a microwave cavity(9). A weak measurement of the qubit is implemented by probing the cavity with microwave photons, maintaining its average occupation at less than one photon. These photons are then directed to a high-bandwidth, quantum-noise-limited amplifier(10,11), which allows real-time monitoring of the state of the cavity (and, hence, that of the qubit) with high fidelity. We demonstrate quantum feedback control by inhibiting the decay of Rabi oscillations, allowing them to persist indefinitely(12). Such an ability permits the active suppression of decoherence and enables a method of quantum error correction based on weak continuous measurements(13,14). Other applications include quantum state stabilization(4,7,15), entanglement generation using measurement(16), state purification(17) and adaptive measurements(18,19).
C1 [Vijay, R.; Macklin, C.; Slichter, D. H.; Weber, S. J.; Murch, K. W.; Naik, R.; Siddiqi, I.] Univ Calif Berkeley, Dept Phys, Quantum Nanoelect Lab, Berkeley, CA 94720 USA.
   [Korotkov, A. N.] Univ Calif Riverside, Dept Elect Engn, Riverside, CA 92521 USA.
C3 University of California System; University of California Berkeley; University of California System; University of California Riverside
RP Vijay, R (corresponding author), Univ Calif Berkeley, Dept Phys, Quantum Nanoelect Lab, Berkeley, CA 94720 USA.
EM rvijay@berkeley.edu; irfan@berkeley.edu
FU US Army Research Office [W911NF-11-1-0029]; Office of the Director of National Intelligence (ODNI), Intelligence Advanced Research Projects Activity (IARPA), through the Army Research Office; Hertz Foundation; ARO MURI
NR 29
TC 411
Z9 480
U1 0
U2 135
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD OCT 4
PY 2012
VL 490
IS 7418
BP 77
EP 80
DI 10.1038/nature11505
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 015LG
UT WOS:000309446800035
PM 23038468
DA 2026-03-09
ER

PT J
AU Jonsson, T
   Atwal, JK
   Steinberg, S
   Snaedal, J
   Jonsson, PV
   Bjornsson, S
   Stefansson, H
   Sulem, P
   Gudbjartsson, D
   Maloney, J
   Hoyte, K
   Gustafson, A
   Liu, YC
   Lu, YM
   Bhangale, T
   Graham, RR
   Huttenlocher, J
   Bjornsdottir, G
   Andreassen, OA
   Jönsson, EG
   Palotie, A
   Behrens, TW
   Magnusson, OT
   Kong, A
   Thorsteinsdottir, U
   Watts, RJ
   Stefansson, K
AF Jonsson, Thorlakur
   Atwal, Jasvinder K.
   Steinberg, Stacy
   Snaedal, Jon
   Jonsson, Palmi V.
   Bjornsson, Sigurbjorn
   Stefansson, Hreinn
   Sulem, Patrick
   Gudbjartsson, Daniel
   Maloney, Janice
   Hoyte, Kwame
   Gustafson, Amy
   Liu, Yichin
   Lu, Yanmei
   Bhangale, Tushar
   Graham, Robert R.
   Huttenlocher, Johanna
   Bjornsdottir, Gyda
   Andreassen, Ole A.
   Jonsson, Erik G.
   Palotie, Aarno
   Behrens, Timothy W.
   Magnusson, Olafur T.
   Kong, Augustine
   Thorsteinsdottir, Unnur
   Watts, Ryan J.
   Stefansson, Kari
TI A mutation in APP protects against Alzheimer's disease and age-related cognitive decline
SO NATURE
LA English
DT Article
ID amyloid precursor protein; beta-secretase; identification; purification; prevalence; imputation; dementia; cleavage; gene; bace
AB The prevalence of dementia in the Western world in people over the age of 60 has been estimated to be greater than 5%, about two-thirds of which are due to Alzheimer's disease(1-4). The age-specific prevalence of Alzheimer's disease nearly doubles every 5 years after age 65, leading to a prevalence of greater than 25% in those over the age of 90 (ref. 3). Here, to search for low-frequency variants in the amyloid-beta precursor protein (APP) gene with a significant effect on the risk of Alzheimer's disease, we studied coding variants in APP in a set of whole-genome sequence data from 1,795 Icelanders. We found a coding mutation (A673T) in the APP gene that protects against Alzheimer's disease and cognitive decline in the elderly without Alzheimer's disease. This substitution is adjacent to the aspartyl protease beta-site in APP, and results in an approximately 40% reduction in the formation of amyloidogenic peptides in vitro. The strong protective effect of the A673T substitution against Alzheimer's disease provides proof of principle for the hypothesis that reducing the beta-cleavage of APP may protect against the disease. Furthermore, as the A673T allele also protects against cognitive decline in the elderly without Alzheimer's disease, the two may be mediated through the same or similar mechanisms.
C1 [Jonsson, Thorlakur; Steinberg, Stacy; Stefansson, Hreinn; Sulem, Patrick; Gudbjartsson, Daniel; Huttenlocher, Johanna; Bjornsdottir, Gyda; Magnusson, Olafur T.; Kong, Augustine; Thorsteinsdottir, Unnur; Stefansson, Kari] deCODE Genet, IS-101 Reykjavik, Iceland.
   [Atwal, Jasvinder K.; Maloney, Janice; Hoyte, Kwame; Gustafson, Amy; Liu, Yichin; Lu, Yanmei; Bhangale, Tushar; Graham, Robert R.; Behrens, Timothy W.; Watts, Ryan J.] Genentech Inc, San Francisco, CA 94080 USA.
   [Snaedal, Jon; Jonsson, Palmi V.; Bjornsson, Sigurbjorn] Landspitali Univ Hosp, Dept Geriatr, IS-101 Reykjavik, Iceland.
   [Huttenlocher, Johanna] Inst Human Genet, Dept Med Genet, D-72026 Tubingen, Germany.
   [Andreassen, Ole A.] Univ Oslo, Ulleval Univ Hosp, Dept Psychiat, N-0407 Oslo, Norway.
   [Andreassen, Ole A.] Univ Oslo, Inst Psychiat, N-0407 Oslo, Norway.
   [Jonsson, Erik G.] Karolinska Hosp & Inst, HUBIN Project, Dept Clin Neurosci, SE-17176 Stockholm, Sweden.
   [Palotie, Aarno] Univ Helsinki, Dept Med Genet, FIN-00014 Helsinki, Finland.
   [Jonsson, Palmi V.; Thorsteinsdottir, Unnur; Stefansson, Kari] Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland.
C3 Decode Genetics; Roche Holding; Roche Holding USA; Genentech; Landspitali National University Hospital; Eberhard Karls University of Tubingen; University of Oslo; University of Oslo; Karolinska Institutet; Karolinska University Hospital; University of Helsinki; University of Iceland
RP Stefansson, K (corresponding author), deCODE Genet, Sturlugata 8, IS-101 Reykjavik, Iceland.
EM kstefans@decode.is
FU Lung GO Sequencing Project [HL-102923]; WHI Sequencing Project [HL-102924]; Broad GO Sequencing Project [HL-102925]; Seattle GO Sequencing Project [HL-102926]; Heart GO Sequencing Project [HL-103010]
NR 28
TC 1340
Z9 1631
U1 2
U2 343
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD AUG 2
PY 2012
VL 488
IS 7409
BP 96
EP 99
DI 10.1038/nature11283
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 981ZE
UT WOS:000307010700040
PM 22801501
DA 2026-03-09
ER

PT J
AU Yoon, H
   Yeung, KYM
   Umansky, V
   Ham, D
AF Yoon, Hosang
   Yeung, Kitty Y. M.
   Umansky, Vladimir
   Ham, Donhee
TI A Newtonian approach to extraordinarily strong negative refraction
SO NATURE
LA English
DT Article
ID 2-dimensional electron-gas; visible frequency; index metamaterial; circuits
AB Metamaterials with negative refractive indices can manipulate electromagnetic waves in unusual ways, and can be used to achieve, for example, sub-diffraction-limit focusing(1), the bending of light in the 'wrong' direction(2), and reversed Doppler and Cerenkov effects(2). These counterintuitive and technologically useful behaviours have spurred considerable efforts to synthesize a broad array of negative-index metamaterials with engineered electric, magnetic or optical properties(1-10). Here we demonstrate another route to negative refraction by exploiting the inertia of electrons in semiconductor two-dimensional electron gases, collectively accelerated by electromagnetic waves according to Newton's second law of motion, where this acceleration effect manifests as kinetic inductance(11,12). Using kinetic inductance to attain negative refraction was theoretically proposed for three-dimensional metallic nanoparticles(13) and seen experimentally with surface plasmons on the surface of a three-dimensional metal(14). The two-dimensional electron gas that we use at cryogenic temperatures has a larger kinetic inductance than three-dimensional metals, leading to extraordinarily strong negative refraction at gigahertz frequencies, with an index as large as -700. This pronounced negative refractive index and the corresponding reduction in the effective wavelength opens a path to miniaturization in the science and technology of negative refraction.
C1 [Yoon, Hosang; Yeung, Kitty Y. M.; Ham, Donhee] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA.
   [Umansky, Vladimir] Weizmann Inst Sci, Dept Condensed Matter Phys, IL-76100 Rehovot, Israel.
C3 Harvard University; Weizmann Institute of Science
RP Ham, D (corresponding author), Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA.
EM donhee@seas.harvard.edu
FU Air Force Office of Scientific Research [FA 9550-09-1-0369, FA 9550-08-1-0254]
NR 30
TC 35
Z9 40
U1 1
U2 102
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD AUG 2
PY 2012
VL 488
IS 7409
BP 65
EP 69
DI 10.1038/nature11297
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 981ZE
UT WOS:000307010700033
PM 22859202
DA 2026-03-09
ER

PT J
AU Tsai, PT
   Hull, C
   Chu, YX
   Greene-Colozzi, E
   Sadowski, AR
   Leech, JM
   Steinberg, J
   Crawley, JN
   Regehr, WG
   Sahin, M
AF Tsai, Peter T.
   Hull, Court
   Chu, YunXiang
   Greene-Colozzi, Emily
   Sadowski, Abbey R.
   Leech, Jarrett M.
   Steinberg, Jason
   Crawley, Jacqueline N.
   Regehr, Wade G.
   Sahin, Mustafa
TI Autistic-like behaviour and cerebellar dysfunction in Purkinje cell Tsc1 mutant mice
SO NATURE
LA English
DT Article
ID tuberous sclerosis complex; mouse model; ultrasonic vocalizations; brain; children; mtorc1
AB Autism spectrum disorders (ASDs) are highly prevalent neurodevelopmental disorders(1), but the underlying pathogenesis remains poorly understood. Recent studies have implicated the cerebellum in these disorders, with post-mortem studies in ASD patients showing cerebellar Purkinje cell (PC) loss(2,3), and isolated cerebellar injury has been associated with a higher incidence of ASDs(4). However, the extent of cerebellar contribution to the pathogenesis of ASDs remains unclear. Tuberous sclerosis complex (TSC) is a genetic disorder with high rates of comorbid ASDs(5) that result from mutation of either TSC1 or TSC2, whose protein products dimerize and negatively regulate mammalian target of rapamycin (mTOR) signalling. TSC is an intriguing model to investigate the cerebellar contribution to the underlying pathogenesis of ASDs, as recent studies in TSC patients demonstrate cerebellar pathology(6) and correlate cerebellar pathology with increased ASD symptomatology(7,8). Functional imaging also shows that TSC patients with ASDs display hypermetabolism in deep cerebellar structures, compared to TSC patients without ASDs(9). However, the roles of Tsc1 and the sequelae of Tsc1 dysfunction in the cerebellum have not been investigated so far. Here we show that both heterozygous and homozygous loss of Tsc1 in mouse cerebellar PCs results in autistic-like behaviours, including abnormal social interaction, repetitive behaviour and vocalizations, in addition to decreased PC excitability. Treatment of mutant mice with the mTOR inhibitor, rapamycin, prevented the pathological and behavioural deficits. These findings demonstrate new roles for Tsc1 in PC function and define a molecular basis for a cerebellar contribution to cognitive disorders such as autism.
C1 [Tsai, Peter T.; Greene-Colozzi, Emily; Sadowski, Abbey R.; Leech, Jarrett M.; Steinberg, Jason; Sahin, Mustafa] Harvard Univ, Sch Med, Boston Childrens Hosp, FM Kirby Neurobiol Ctr,Dept Neurol, Boston, MA 02115 USA.
   [Hull, Court; Chu, YunXiang; Regehr, Wade G.] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA.
   [Crawley, Jacqueline N.] NIMH, Lab Behav Neurosci, Intramural Res Program, Bethesda, MD 20892 USA.
C3 Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Boston Children's Hospital; Harvard University; Harvard Medical School; National Institutes of Health (NIH) - USA; NIH National Institute of Mental Health (NIMH)
RP Sahin, M (corresponding author), Harvard Univ, Sch Med, Boston Childrens Hosp, FM Kirby Neurobiol Ctr,Dept Neurol, Boston, MA 02115 USA.
EM peter.tsai@childrens.harvard.edu; mustafa.sahin@childrens.harvard.edu
FU Developmental Neurology Training grant [T32 NS007473]; American Academy of Neurology; Nancy Lurie Marks Family Foundation; National Institutes of Health (NIH) [R01 NS58956]; John Merck Scholars Fund; Autism Speaks; Boston Children's Hospital Translational Research Program; Manton Center for Orphan Disease Research; Boston Children's Hospital Intellectual and Developmental Disabilities Research Center [P30 HD18655]; Intramural Research Program, National Institute of Mental Health; NIH [R01NS032405]; Simons Foundation [SFARI 232304]; Howard Hughes Medical Institute Medical Research Fellowship; National Institute of Mental Health [T32MH020017] Funding Source: NIH RePORTER; National Institute of Neurological Disorders and Stroke [T32NS007473] Funding Source: NIH RePORTER; National Institute of Neurological Disorders and Stroke; National Institute on Alcohol Abuse and Alcoholism [T32MH020017] Funding Source: NIH RePORTER
NR 38
TC 688
Z9 809
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 AUG 30
PY 2012
VL 488
IS 7413
BP 647
EP +
DI 10.1038/nature11310
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 996NC
UT WOS:000308095100054
PM 22763451
DA 2026-03-09
ER

PT J
AU Elias, M
   Wellner, A
   Goldin-Azulay, K
   Chabriere, E
   Vorholt, JA
   Erb, TJ
   Tawfik, DS
AF Elias, Mikael
   Wellner, Alon
   Goldin-Azulay, Korina
   Chabriere, Eric
   Vorholt, Julia A.
   Erb, Tobias J.
   Tawfik, Dan S.
TI The molecular basis of phosphate discrimination in arsenate-rich environments
SO NATURE
LA English
DT Article
ID beta-semialdehyde dehydrogenase; hydrogen-bonds; escherichia-coli; transport-systems; active-transport; protein; specificity; bacteria; receptor; gfaj-1
AB Arsenate and phosphate are abundant on Earth and have striking similarities: nearly identical pK(a) values(1,2), similarly charged oxygen atoms, and thermochemical radii that differ by only 4% (ref. 3). Phosphate is indispensable and arsenate is toxic, but this extensive similarity raises the question whether arsenate may substitute for phosphate in certain niches(4,5). However, whether it is used or excluded, discriminating phosphate from arsenate is a paramount challenge. Enzymes that utilize phosphate, for example, have the same binding mode and kinetic parameters as arsenate, and the latter's presence therefore decouples metabolism(6,7). Can proteins discriminate between these two anions, and how would they do so? In particular, cellular phosphate uptake systems face a challenge in arsenate-rich environments. Here we describe a molecular mechanism for this process. We examined the periplasmic phosphate-binding proteins (PBPs) of the ABC-type transport system that mediates phosphate uptake into bacterial cells, including two PBPs from the arsenate-rich Mono Lake Halomonas strain GFAJ-1. All PBPs tested are capable of discriminating phosphate over arsenate at least 500-fold. The exception is one of the PBPs of GFAJ-1 that shows roughly 4,500-fold discrimination and its gene is highly expressed under phosphate-limiting conditions. Sub-angstrom-resolution structures of Pseudomonas fluorescens PBP with both arsenate and phosphate show a unique mode of binding that mediates discrimination. An extensive network of dipole-anion interactions(8,9), and of repulsive interactions, results in the 4% larger arsenate distorting a unique low-barrier hydrogen bond. These features enable the phosphate transport system to bind phosphate selectively over arsenate (at least 10(3) excess) even in highly arsenate-rich environments.
C1 [Elias, Mikael; Wellner, Alon; Goldin-Azulay, Korina; Tawfik, Dan S.] Weizmann Inst Sci, Dept Biol Chem, IL-76100 Rehovot, Israel.
   [Chabriere, Eric] Univ Aix Marseille 2, CNRS, Fac Med & Pharm, Unite Rech Malad Infect & Trop Emergentes, F-13385 Marseille, France.
   [Vorholt, Julia A.; Erb, Tobias J.] ETH, Inst Microbiol, CH-8093 Zurich, Switzerland.
C3 Weizmann Institute of Science; Aix-Marseille Universite; Centre National de la Recherche Scientifique (CNRS); Institut National de la Sante et de la Recherche Medicale (Inserm); Institut de Recherche pour le Developpement (IRD); Swiss Federal Institutes of Technology Domain; ETH Zurich
RP Tawfik, DS (corresponding author), Weizmann Inst Sci, Dept Biol Chem, IL-76100 Rehovot, Israel.
EM mikael.elias@weizmann.ac.il; tawfik@weizmann.ac.il
FU Israel Science Foundation; Intra-European Fellowships Marie Curie program [252836]; Eidgenossische Technische Hochschule fellowship
NR 30
TC 171
Z9 203
U1 1
U2 191
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD NOV 1
PY 2012
VL 491
IS 7422
BP 134
EP 137
DI 10.1038/nature11517
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 028PM
UT WOS:000310434500045
PM 23034649
DA 2026-03-09
ER

PT J
AU Close, P
   East, P
   Dirac-Svejstrup, AB
   Hartmann, H
   Heron, M
   Maslen, S
   Chariot, A
   Söding, J
   Skehel, M
   Svejstrup, JQ
AF Close, Pierre
   East, Philip
   Dirac-Svejstrup, A. Barbara
   Hartmann, Holger
   Heron, Mark
   Maslen, Sarah
   Chariot, Alain
   Soeding, Johannes
   Skehel, Mark
   Svejstrup, Jesper Q.
TI DBIRD complex integrates alternative mRNA splicing with RNA polymerase II transcript elongation
SO NATURE
LA English
DT Article
ID proteomic analysis; binding-proteins; in-vivo; cleavage; cells
AB Alternative messenger RNA splicing is the main reason that vast mammalian proteomic complexity can be achieved with a limited number of genes. Splicing is physically and functionally coupled to transcription, and is greatly affected by the rate of transcript elongation(1-3). As the nascent pre-mRNA emerges from transcribing RNA polymerase II (RNAPII), it is assembled into a messenger ribonucleoprotein (mRNP) particle; this is the functional form of the nascent pre-mRNA and determines the fate of the mature transcript(4). However, factors that connect the transcribing polymerase with the mRNP particle and help to integrate transcript elongation with mRNA splicing remain unclear. Here we characterize the human interactome of chromatin-associated mRNP particles. This led us to identify deleted in breast cancer 1 (DBC1) and ZNF326 (which we call ZNF-protein interacting with nuclear mRNPs and DBC1 (ZIRD)) as subunits of a novel protein complex-named DBIRD-that binds directly to RNAPII. DBIRD regulates alternative splicing of a large set of exons embedded in (A + T)-rich DNA, and is present at the affected exons. RNA-interference-mediated DBIRD depletion results in region-specific decreases in transcript elongation, particularly across areas encompassing affected exons. Together, these data indicate that the DBIRD complex acts at the interface between mRNP particles and RNAPII, integrating transcript elongation with the regulation of alternative splicing.
C1 [Close, Pierre; Dirac-Svejstrup, A. Barbara; Svejstrup, Jesper Q.] Canc Res UK London Res Inst, Mech Transcript Lab, Clare Hall Labs, S Mimms EN6 3LD, Herts, England.
   [Close, Pierre; Chariot, Alain] Univ Liege, Unit Med Chem, GIGA Signal Transduct, GIGA R,CHU, B-4000 Liege, Belgium.
   [East, Philip] Canc Res UK London Res Inst, Bioinformat & Biostat Grp, London WC2A 3LY, England.
   [Hartmann, Holger; Heron, Mark; Soeding, Johannes] Univ Munich, Gene Ctr, D-81377 Munich, Germany.
   [Hartmann, Holger; Heron, Mark; Soeding, Johannes] Univ Munich, Ctr Integrated Prot Sci Munich, D-81377 Munich, Germany.
   [Maslen, Sarah; Skehel, Mark] Canc Res UK London Res Inst, London Res Inst, Prot Anal & Prote Lab, Clare Hall Labs, S Mimms EN6 3LD, Herts, England.
C3 Cancer Research UK; University of Liege; Cancer Research UK; University of Munich; University of Munich; Cancer Research UK
RP Svejstrup, JQ (corresponding author), Canc Res UK London Res Inst, Mech Transcript Lab, Clare Hall Labs, S Mimms EN6 3LD, Herts, England.
EM j.svejstrup@cancer.org.uk
FU Cancer Research UK; European Research council (ERC); European Molecular Biology Organization (EMBO); Fonds Leon Fredericq foundation; Cancer Research UK [11567] Funding Source: researchfish
NR 24
TC 103
Z9 133
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 APR 19
PY 2012
VL 484
IS 7394
BP 386
EP 389
DI 10.1038/nature10925
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 927YM
UT WOS:000302946500035
PM 22446626
DA 2026-03-09
ER

PT J
AU Ebran, JP
   Khan, E
   Niksic, T
   Vretenar, D
AF Ebran, J. -P.
   Khan, E.
   Niksic, T.
   Vretenar, D.
TI How atomic nuclei cluster
SO NATURE
LA English
DT Article
ID radii
AB Nucleonic matter displays a quantum-liquid structure, but in some cases finite nuclei behave like molecules composed of clusters of protons and neutrons. Clustering is a recurrent feature in light nuclei, from beryllium to nickel(1-3). Cluster structures are typically observed as excited states close to the corresponding decay threshold; the origin of this phenomenon lies in the effective nuclear interaction, but the detailed mechanism of clustering in nuclei has not yet been fully understood. Here we use the theoretical framework of energy-density functionals(4,5), encompassing both cluster and quantum liquid-drop aspects of nuclei, to show that conditions for cluster formation can in part be traced back to the depth of the confining nuclear potential. For the illustrative example of neon-20, we show that the depth of the potential determines the energy spacings between single-nucleon orbitals in deformed nuclei, the localization of the corresponding wavefunctions and, therefore, the degree of nucleonic density clustering. Relativistic functionals, in particular, are characterized by deep single-nucleon potentials. When compared to non-relativistic functionals that yield similar ground-state properties (binding energy, deformation, radii), they predict the occurrence of much more pronounced cluster structures. More generally, clustering is considered as a transitional phenomenon between crystalline and quantum-liquid phases of fermionic systems.
C1 [Khan, E.] Univ Paris 11, CNRS, IN2P3, Inst Phys Nucl, F-91406 Orsay, France.
   [Ebran, J. -P.] CEA DAM DIF, F-91297 Arpajon, France.
   [Niksic, T.; Vretenar, D.] Univ Zagreb, Fac Sci, Dept Phys, Zagreb 10000, Croatia.
C3 Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute of Nuclear and Particle Physics (IN2P3); Universite Paris Saclay; CEA; University of Zagreb
RP Khan, E (corresponding author), Univ Paris 11, CNRS, IN2P3, Inst Phys Nucl, F-91406 Orsay, France.
EM khan@ipno.in2p3.fr
FU Institut Universitaire de France; Croatian Ministry of Science, Education and Sport [1191005-1010]
NR 30
TC 154
Z9 176
U1 0
U2 58
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUL 19
PY 2012
VL 487
IS 7407
BP 341
EP 344
DI 10.1038/nature11246
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 975JB
UT WOS:000306506500037
PM 22810698
DA 2026-03-09
ER

PT J
AU Hsieh, AC
   Liu, Y
   Edlind, MP
   Ingolia, NT
   Janes, MR
   Sher, A
   Shi, EY
   Stumpf, CR
   Christensen, C
   Bonham, MJ
   Wang, SY
   Ren, PD
   Martin, M
   Jessen, K
   Feldman, ME
   Weissman, JS
   Shokat, KM
   Rommel, C
   Ruggero, D
AF Hsieh, Andrew C.
   Liu, Yi
   Edlind, Merritt P.
   Ingolia, Nicholas T.
   Janes, Matthew R.
   Sher, Annie
   Shi, Evan Y.
   Stumpf, Craig R.
   Christensen, Carly
   Bonham, Michael J.
   Wang, Shunyou
   Ren, Pingda
   Martin, Michael
   Jessen, Katti
   Feldman, Morris E.
   Weissman, Jonathan S.
   Shokat, Kevan M.
   Rommel, Christian
   Ruggero, Davide
TI The translational landscape of mTOR signalling steers cancer initiation and metastasis
SO NATURE
LA English
DT Article
ID top messenger-rnas; prostate-cancer; stem-cells; in-vivo; protein-synthesis; phosphorylation; rapamycin; promotes; pathway; complex
AB The mammalian target of rapamycin (mTOR) kinase is a master regulator of protein synthesis that couples nutrient sensing to cell growth and cancer. However, the downstream translationally regulated nodes of gene expression that may direct cancer development are poorly characterized. Using ribosome profiling, we uncover specialized translation of the prostate cancer genome by oncogenic mTOR signalling, revealing a remarkably specific repertoire of genes involved in cell proliferation, metabolism and invasion. We extend these findings by functionally characterizing a class of translationally controlled pro-invasion messenger RNAs that we show direct prostate cancer invasion and metastasis downstream of oncogenic mTOR signalling. Furthermore, we develop a clinically relevant ATP site inhibitor of mTOR, INK128, which reprograms this gene expression signature with therapeutic benefit for prostate cancer metastasis, for which there is presently no cure. Together, these findings extend our understanding of how the 'cancerous' translation machinery steers specific cancer cell behaviours, including metastasis, and may be therapeutically targeted.
C1 [Hsieh, Andrew C.; Edlind, Merritt P.; Sher, Annie; Shi, Evan Y.; Stumpf, Craig R.; Christensen, Carly; Ruggero, Davide] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, Sch Med, San Francisco, CA 94158 USA.
   [Hsieh, Andrew C.; Edlind, Merritt P.; Sher, Annie; Shi, Evan Y.; Stumpf, Craig R.; Christensen, Carly; Ruggero, Davide] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, Dept Urol, San Francisco, CA 94158 USA.
   [Hsieh, Andrew C.] Univ Calif San Francisco, Dept Internal Med, San Francisco, CA 94143 USA.
   [Hsieh, Andrew C.] Univ Calif San Francisco, Div Hematol Oncol, San Francisco, CA 94143 USA.
   [Liu, Yi; Janes, Matthew R.; Wang, Shunyou; Ren, Pingda; Martin, Michael; Jessen, Katti; Rommel, Christian] Intellikine Inc, La Jolla, CA 92037 USA.
   [Ingolia, Nicholas T.] Carnegie Inst Sci, Baltimore, MD 21218 USA.
   [Bonham, Michael J.] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94143 USA.
   [Feldman, Morris E.; Weissman, Jonathan S.; Shokat, Kevan M.] Univ Calif San Francisco, Dept Cellular & Mol Pharmacol, Howard Hughes Med Inst, San Francisco, CA 94158 USA.
C3 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; 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; Carnegie Institution for Science; University of California System; University of California San Francisco; University of California System; University of California San Francisco; Howard Hughes Medical Institute
RP Ruggero, D (corresponding author), Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, Sch Med, San Francisco, CA 94158 USA.
EM christian@intellikine.com; davide.ruggero@ucsf.edu
FU American Cancer Society [119084-PF-10-233-01-TBE]; DOD; NIH [R01 CA154916, R01 CA140456]; Phi Beta Psi Sorority
NR 41
TC 1058
Z9 1266
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 MAY 3
PY 2012
VL 485
IS 7396
BP 55
EP U196
DI 10.1038/nature10912
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 934NV
UT WOS:000303451900033
PM 22367541
DA 2026-03-09
ER

PT J
AU Cipolletta, D
   Feuerer, M
   Li, A
   Kamei, N
   Lee, J
   Shoelson, SE
   Benoist, C
   Mathis, D
AF Cipolletta, Daniela
   Feuerer, Markus
   Li, Amy
   Kamei, Nozomu
   Lee, Jongsoon
   Shoelson, Steven E.
   Benoist, Christophe
   Mathis, Diane
TI PPAR-γ is a major driver of the accumulation and phenotype of adipose tissue Treg cells
SO NATURE
LA English
DT Article
ID insulin-resistance; system; mice; thiazolidinediones; differentiation; retrovirus; inflammation; sensitivity; activation; expression
AB Obesity and type-2 diabetes have increased markedly over the past few decades, in parallel. One of the major links between these two disorders is chronic, low-grade inflammation(1). Prolonged nutrient excess promotes the accumulation and activation of leukocytes in visceral adipose tissue (VAT) and ultimately other tissues, leading to metabolic abnormalities such as insulin resistance, type-2 diabetes and fatty-liver disease. Although invasion of VAT by pro-inflammatory macrophages is considered to be a key event driving adipose-tissue inflammation and insulin resistance, little is known about the roles of other immune system cell types in these processes. A unique population of VAT-resident regulatory T (T-reg) cells was recently implicated in control of the inflammatory state of adipose tissue and, thereby, insulin sensitivity(2). Here we identify peroxisome proliferator-activated receptor (PPAR)-gamma, the 'master regulator' of adipocyte differentiation, as a crucial molecular orchestrator of VAT T-reg cell accumulation, phenotype and function. Unexpectedly, PPAR-gamma expression by VAT T-reg cells was necessary for complete restoration of insulin sensitivity in obese mice by the thiazolidinedione drug pioglitazone. These findings suggest a previously unknown cellular mechanism for this important class of thiazolidinedione drugs, and provide proof-of-principle that discrete populations of T-reg cells with unique functions can be precisely targeted to therapeutic ends.
C1 [Cipolletta, Daniela; Feuerer, Markus; Li, Amy; Benoist, Christophe; Mathis, Diane] Harvard Univ, Sch Med, Dept Microbiol & Immunol, Div Immunol, Boston, MA 02115 USA.
   [Kamei, Nozomu; Lee, Jongsoon; Shoelson, Steven E.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA.
   [Kamei, Nozomu; Lee, Jongsoon; Shoelson, Steven E.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA.
C3 Harvard University; Harvard Medical School; Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Joslin Diabetes Center, Inc.; Harvard University; Harvard Medical School
RP Mathis, D (corresponding author), Harvard Univ, Sch Med, Dept Microbiol & Immunol, Div Immunol, Boston, MA 02115 USA.
EM cbdm@hms.harvard.edu
FU National Institutes of Health (NIH) [DK092541, DK51729]; Ellison Foundation (Boston); Dana Foundation; American Diabetes Association [RA 110BS97]; Joslin Diabetes Center [P30DK36836]; King Trust; National Institute of Diabetes and Digestive and Kidney Diseases [P30DK036836, R01DK092541] Funding Source: NIH RePORTER; National Institute of General Medical Sciences [T32GM007753] Funding Source: NIH RePORTER
NR 23
TC 980
Z9 1133
U1 2
U2 93
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUN 28
PY 2012
VL 486
IS 7404
BP 549
EP U151
DI 10.1038/nature11132
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 965IJ
UT WOS:000305760600047
PM 22722857
DA 2026-03-09
ER

PT J
AU Libby, T
   Moore, TY
   Chang-Siu, E
   Li, D
   Cohen, DJ
   Jusufi, A
   Full, RJ
AF Libby, Thomas
   Moore, Talia Y.
   Chang-Siu, Evan
   Li, Deborah
   Cohen, Daniel J.
   Jusufi, Ardian
   Full, Robert J.
TI Tail-assisted pitch control in lizards, robots and dinosaurs
SO NATURE
LA English
DT Article
ID body; balance
AB In 1969, a palaeontologist proposed(1) that theropod dinosaurs used their tails as dynamic stabilizers during rapid or irregular movements, contributing to their depiction as active and agile predators. Since then the inertia of swinging appendages has been implicated in stabilizing human walking(2,3), aiding acrobatic manoeuvres by primates(4-8) and rodents(9), and enabling cats to balance on branches(10). Recent studies on geckos(11-13) suggest that active tail stabilization occurs during climbing, righting and gliding. By contrast, studies on the effect of lizard tail loss show evidence of a decrease, an increase or no change in performance(14,15). Application of a control-theoretic framework could advance our general understanding of inertial appendage use in locomotion. Here we report that lizards control the swing of their tails in a measured manner to redirect angular momentum from their bodies to their tails, stabilizing body attitude in the sagittal plane. We video-recorded Red-Headed Agama lizards (Agama agama) leaping towards a vertical surface by first vaulting onto an obstacle with variable traction to induce a range of perturbations in body angular momentum. To examine a known controlled tail response, we built a lizard-sized robot with an active tail that used sensory feedback to stabilize pitch as it drove off a ramp. Our dynamics model revealed that a body swinging its tail experienced less rotation than a body with a rigid tail, a passively compliant tail or no tail. To compare a range of tails, we calculated tail effectiveness as the amount of tailless body rotation a tail could stabilize. A model Velociraptor mongoliensis supported the initial tail stabilization hypothesis(1), showing as it did a greater tail effectiveness than the Agama lizards. Leaping lizards show that inertial control of body attitude can advance our understanding of appendage evolution and provide biological inspiration for the next generation of manoeuvrable search-and-rescue robots.
C1 [Moore, Talia Y.; Li, Deborah; Jusufi, Ardian; Full, Robert J.] Univ Calif Berkeley, Dept Integrat Biol, Berkeley, CA 94720 USA.
   [Libby, Thomas] Univ Calif Berkeley, Ctr Interdisciplinary Bioinspirat Educ & Res, Berkeley, CA 94720 USA.
   [Chang-Siu, Evan] Univ Calif Berkeley, Dept Mech Engn, Berkeley, CA 94720 USA.
   [Cohen, Daniel J.] Univ Calif Berkeley, Dept Bioengn, Berkeley, CA 94720 USA.
C3 University of California System; University of California Berkeley; University of California System; University of California Berkeley; University of California System; University of California Berkeley; University of California System; University of California Berkeley
RP Full, RJ (corresponding author), Univ Calif Berkeley, Dept Integrat Biol, Berkeley, CA 94720 USA.
EM rjfull@berkeley.edu
FU US NSF FIBR; MAST CTA; NSF IGERT [DGE-0903711]; Swiss NSF
NR 27
TC 249
Z9 298
U1 2
U2 180
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 12
PY 2012
VL 481
IS 7380
BP 181
EP +
DI 10.1038/nature10710
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 874TO
UT WOS:000298981200035
PM 22217942
DA 2026-03-09
ER

PT J
AU Metzger, T
   Gache, V
   Xu, M
   Cadot, B
   Folker, ES
   Richardson, BE
   Gomes, ER
   Baylies, MK
AF Metzger, Thomas
   Gache, Vincent
   Xu, Mu
   Cadot, Bruno
   Folker, Eric S.
   Richardson, Brian E.
   Gomes, Edgar R.
   Baylies, Mary K.
TI MAP and kinesin-dependent nuclear positioning is required for skeletal muscle function
SO NATURE
LA English
DT Article
ID drosophila-melanogaster; neuromuscular-junction; myoblast fusion; protein; identification; cells; localization; microtubules; mice; differentiation
AB The basic unit of skeletal muscle in all metazoans is the multinucleate myofibre, within which individual nuclei are regularly positioned(1). The molecular machinery responsible for myonuclear positioning is not known. Improperly positioned nuclei are a hallmark of numerous diseases of muscle(2), including centronuclear myopathies(3), but it is unclear whether correct nuclear positioning is necessary for muscle function. Here we identify the microtubule-associated protein ensconsin (Ens)/microtubule-associated protein 7 (MAP7) and kinesin heavy chain (Khc)/Kif5b as essential, evolutionarily conserved regulators of myonuclear positioning in Drosophila and cultured mammalian myotubes. We find that these proteins interact physically and that expression of the Kif5b motor domain fused to the MAP7 microtubule-binding domain rescues nuclear positioning defects in MAP7-depleted cells. This suggests that MAP7 links Kif5b to the microtubule cytoskeleton to promote nuclear positioning. Finally, we show that myonuclear positioning is physiologically important. Drosophila ens mutant larvae have decreased locomotion and incorrect myonuclear positioning, and these phenotypes are rescued by muscle-specific expression of Ens. We conclude that improper nuclear positioning contributes to muscle dysfunction in a cell-autonomous fashion.
C1 [Gache, Vincent; Cadot, Bruno; Gomes, Edgar R.] Univ Paris 06, INSERM, UMR S 787, F-75634 Paris, France.
   [Metzger, Thomas; Xu, Mu; Folker, Eric S.; Richardson, Brian E.; Baylies, Mary K.] Sloan Kettering Inst, Program Dev Biol, New York, NY 10065 USA.
   [Metzger, Thomas; Baylies, Mary K.] Cornell Univ, Weill Grad Sch Med Sci, New York, NY 10065 USA.
   [Gomes, Edgar R.] Grp Hosp Pitie Salpetriere, Inst Myol, F-75013 Paris, France.
C3 Sorbonne Universite; Institut National de la Sante et de la Recherche Medicale (Inserm); Memorial Sloan Kettering Cancer Center; Cornell University; Assistance Publique Hopitaux Paris (APHP); Hopital Universitaire Pitie-Salpetriere - APHP; Sorbonne Universite
RP Gomes, ER (corresponding author), Univ Paris 06, INSERM, UMR S 787, F-75634 Paris, France.
EM edgar.gomes@upmc.fr; m-baylies@ski.mskcc.org
FU National Institutes of Health (NIH) [GM056989, GM0781318]; Muscular Dystrophy Association (MDA); NIH [T32 BM008539]; Fondation pour la Recherche Medicale (FRM); Region Ile-de-France; INSERM Avenir; Agence Nationale de la Recherche (ANR)
NR 39
TC 217
Z9 269
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 APR 5
PY 2012
VL 484
IS 7392
BP 120
EP +
DI 10.1038/nature10914
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 919QN
UT WOS:000302343400046
PM 22425998
DA 2026-03-09
ER

PT J
AU Rasmussen, B
   Fletcher, IR
   Bekker, A
   Muhling, JR
   Gregory, CJ
   Thorne, AM
AF Rasmussen, Birger
   Fletcher, Ian R.
   Bekker, Andrey
   Muhling, Janet R.
   Gregory, Courtney J.
   Thorne, Alan M.
TI Deposition of 1.88-billion-year-old iron formations as a consequence of rapid crustal growth
SO NATURE
LA English
DT Article
ID billion years ago; continental growth; western-australia; mantle; ocean; zircon; transition; isotopes; province; events
AB Iron formations are chemical sedimentary rocks comprising layers of iron-rich and silica-rich minerals whose deposition requires anoxic and iron-rich (ferruginous) sea water. Their demise after the rise in atmospheric oxygen by 2.32 billion years (Gyr) ago(1) has been attributed to the removal of dissolved iron through progressive oxidation(2) or sulphidation(3,4) of the deep ocean. Therefore, a sudden return of voluminous iron formations nearly 500 million years later poses an apparent conundrum(3,5). Most late Palaeoproterozoic iron formations are about 1.88 Gyr old(6-8) and occur in the Superior region of North America(5,9,10). Major iron formations are also preserved in Australia, but these were apparently deposited(11) after the transition to a sulphidic ocean at 1.84 Gyr ago that should have terminated iron formation deposition(4), implying that they reflect local marine conditions(5,12). Here we date zircons in tuff layers to show that iron formations in the Frere Formation of Western Australia are about 1.88 Gyr old, indicating that the deposition of iron formations from two disparate cratons was coeval and probably reflects global ocean chemistry. The sudden reappearance of major iron formations at 1.88 Gyr ago-contemporaneous with peaks in global mafic-ultramafic magmatism(13,14), juvenile continental and oceanic crust formation(15,16), mantle depletion(17,18) and volcanogenic massive sulphide formation(5,19)-suggests deposition of iron formations as a consequence of major mantle activity and rapid crustal growth(5,10,15,20). Our findings support the idea that enhanced submarine volcanism and hydrothermal activity linked to a peak in mantle melting released large volumes of ferrous iron and other reductants that overwhelmed the sulphate and oxygen reservoirs of the ocean, decoupling atmospheric and seawater redox states, and causing the return of widespread ferruginous conditions. Iron formations formed on clastic-starved coastal shelves where dissolved iron upwelled and mixed with oxygenated surface water. The disappearance of iron formations after this event may reflect waning mafic-ultramafic magmatism and a diminished flux of hydrothermal iron relative to seawater oxidants.
C1 [Rasmussen, Birger; Fletcher, Ian R.; Gregory, Courtney J.] Curtin Univ Technol, Dept Appl Geol, Bentley, WA 6102, Australia.
   [Bekker, Andrey] Univ Manitoba, Dept Geol Sci, Winnipeg, MB R3T 2N2, Canada.
   [Muhling, Janet R.] Univ Western Australia, Ctr Microscopy Characterisat & Anal, Crawley, WA 6009, Australia.
   [Thorne, Alan M.] Geol Survey Western Australia, Dept Mines & Petr, Perth, WA 6004, Australia.
C3 Curtin University; University of Manitoba; University of Western Australia; Geological Survey of Western Australia
RP Rasmussen, B (corresponding author), Curtin Univ Technol, Dept Appl Geol, Kent St, Bentley, WA 6102, Australia.
EM b.rasmussen@curtin.edu.au
FU ARC; Western Australian government; NSERC
NR 30
TC 111
Z9 129
U1 0
U2 89
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD APR 26
PY 2012
VL 484
IS 7395
BP 498
EP 501
DI 10.1038/nature11021
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 931FF
UT WOS:000303200400047
PM 22538613
DA 2026-03-09
ER

PT J
AU Pyenson, ND
   Goldbogen, JA
   Vogl, AW
   Szathmary, G
   Drake, RL
   Shadwick, RE
AF Pyenson, Nicholas D.
   Goldbogen, Jeremy A.
   Vogl, A. Wayne
   Szathmary, Gabor
   Drake, Richard L.
   Shadwick, Robert E.
TI Discovery of a sensory organ that coordinates lunge feeding in rorqual whales
SO NATURE
LA English
DT Article
ID fin whales; mysticete; mechanics; cetacea; baleen
AB Top ocean predators have evolved multiple solutions to the challenges of feeding in the water(1-3). At the largest scale, rorqual whales (Balaenopteridae) engulf and filter prey-laden water by lunge feeding(4), a strategy that is unique among vertebrates(1). Lunge feeding is facilitated by several morphological specializations, including bilaterally separate jaws that loosely articulate with the skull(5,6), hyper-expandable throat pleats, or ventral groove blubber(7), and a rigid y-shaped fibrocartilage structure branching from the chin into the ventral groove blubber(8). The linkages and functional coordination among these features, however, remain poorly understood. Here we report the discovery of a sensory organ embedded within the fibrous symphysis between the unfused jaws that is present in several rorqual species, at both fetal and adult stages. Vascular and nervous tissue derived from the ancestral, anterior-most tooth socket insert into this organ, which contains connective tissue and papillae suspended in a gel-like matrix. These papillae show the hallmarks of a mechanoreceptor, containing nerves and encapsulated nerve termini. Histological, anatomical and kinematic evidence indicate that this sensory organ responds to both the dynamic rotation of the jaws during mouth opening and closure, and ventral groove blubber(7) expansion through direct mechanical linkage with the y-shaped fibrocartilage structure. Along with vibrissae on the chin(9), providing tactile prey sensation, this organ provides the necessary input to the brain for coordinating the initiation, modulation and end stages of engulfment, a paradigm that is consistent with unsteady hydrodynamic models and tag data from lunge-feeding rorquals(10-13). Despite the antiquity of unfused jaws in baleen whales since the late Oligocene(14) (similar to 23-28 million years ago), this organ represents an evolutionary novelty for rorquals, based on its absence in all other lineages of extant baleen whales. This innovation has a fundamental role in one of the most extreme feeding methods in aquatic vertebrates, which facilitated the evolution of the largest vertebrates ever.
C1 [Pyenson, Nicholas D.] Smithsonian Inst, Natl Museum Nat Hist, Dept Paleobiol, Washington, DC 20013 USA.
   [Pyenson, Nicholas D.] Burke Museum Nat Hist & Culture, Dept Mammal, Seattle, WA 98195 USA.
   [Pyenson, Nicholas D.] Burke Museum Nat Hist & Culture, Dept Paleontol, Seattle, WA 98195 USA.
   [Goldbogen, Jeremy A.] Cascadia Res Collect, Olympia, WA 98501 USA.
   [Vogl, A. Wayne] Univ British Columbia, Dept Cellular & Physiol Sci, Vancouver, BC V6T 1Z3, Canada.
   [Szathmary, Gabor] FPInnovations, Vancouver, BC V6T 1W5, Canada.
   [Drake, Richard L.] Case Western Reserve Univ, Cleveland Clin, Lerner Coll Med, Cleveland, OH 44195 USA.
   [Shadwick, Robert E.] Univ British Columbia, Dept Zool, Vancouver, BC V6T 1Z4, Canada.
C3 Smithsonian Institution; Smithsonian National Museum of Natural History; University of British Columbia; University System of Ohio; Case Western Reserve University; Cleveland Clinic Foundation; University of British Columbia
RP Pyenson, ND (corresponding author), Smithsonian Inst, Natl Museum Nat Hist, Dept Paleobiol, POB 37012, Washington, DC 20013 USA.
EM pyensonn@si.edu
FU Natural Sciences and Engineering Research Council of Canada; Smithsonian Institution; Remington Kellogg Fund; University of British Columbia; Scripps Postdoctoral Research Fellowship; NSERC
CR BEST RC, 1981, CAN J ZOOL, V59, P2386, DOI 10.1139/z81-319
   Brodie Paul F, 2001, P345, V0, P0
   BRODIE PF, 1993, CAN J ZOOL, V71, P2546, DOI 10.1139/z93-348
   Canning C, 2011, ANIM BEHAV, V82, P901, DOI 10.1016/j.anbehav.2011.07.031
   Catania KC, 2008, P NATL ACAD SCI USA, V105, P571, DOI 10.1073/pnas.0709534104
   Currey J, 2002, BONES STRUCTURE MECH, V0, P0, DOI DOI 10.1515/9781400849505
   Czech-Damal NU, 2012, P ROY SOC B-BIOL SCI, V279, P663, DOI 10.1098/rspb.2011.1127
   Deméré TA, 2008, SYST BIOL, V57, P15, DOI 10.1080/10635150701884632
   Fitzgerald EMG, 2012, BIOL LETTERS, V8, P94, DOI 10.1098/rsbl.2011.0690
   Fitzgerald EMG, 2010, ZOOL J LINN SOC-LOND, V158, P367, DOI 10.1111/j.1096-3642.2009.00572.x
   Friedman M, 2010, SCIENCE, V327, P990, DOI 10.1126/science.1184743
   Goldbogen JA, 2011, J EXP BIOL, V214, P131, DOI 10.1242/jeb.048157
   Goldbogen JA, 2007, MAR ECOL PROG SER, V349, P289, DOI 10.3354/meps07066
   Goldbogen JA, 2012, FUNCT ECOL, V26, P216, DOI 10.1111/j.1365-2435.2011.01905.x
   Goldbogen JA, 2010, AM SCI, V98, P124, DOI 10.1511/2010.83.124
   Johnston C, 2010, MAR MAMMAL SCI, V26, P186, DOI 10.1111/j.1748-7692.2009.00305.x
   LAMBERTSEN R, 1995, J MAMMAL, V76, P877, DOI 10.2307/1382758
   Lambertsen RH, 1983, J MAMMAL, V64, P76
   Ling JK, 1977, P387, V0, P0
   ORTON LS, 1987, CAN J ZOOL, V65, P2898, DOI 10.1139/z87-440
   PIVORUNAS A, 1977, J MORPHOL, V151, P299, DOI 10.1002/jmor.1051510207
   Potvin J, 2010, J THEOR BIOL, V267, P437, DOI 10.1016/j.jtbi.2010.08.026
   Potvin J, 2009, J R SOC INTERFACE, V6, P1005, DOI 10.1098/rsif.2008.0492
   Reeves RR, 2006, WHALES, V0, P0
   SANDERSON SL, 1993, SKULL, V3, P37
   SCAPINO R, 1981, J MORPHOL, V167, P339, DOI 10.1002/jmor.1051670308
   TERSHY BR, 1992, MAR MAMMAL SCI, V8, P315, DOI 10.1111/j.1748-7692.1992.tb00416.x
   Thewissen JGM, 2008, SENSORY EVOLUTION ON THE THRESHOLD: ADAPTATIONS IN SECONDARILY AQUATIC VERTEBRATES, V0, P1
   Werth AJ, 2000, FEEDING MARINE MAMMA, V0, PP487, DOI 10.1016/B978-012632590-4/50017-4
NR 30
TC 91
Z9 98
U1 2
U2 81
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD MAY 24
PY 2012
VL 485
IS 7399
BP 498
EP 501
DI 10.1038/nature11135
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 946IH
UT WOS:000304344500042
PM 22622577
DA 2026-03-09
ER

PT J
AU Anand, PK
   Malireddi, RKS
   Lukens, JR
   Vogel, P
   Bertin, J
   Lamkanfi, M
   Kanneganti, TD
AF Anand, Paras K.
   Malireddi, R. K. Subbarao
   Lukens, John R.
   Vogel, Peter
   Bertin, John
   Lamkanfi, Mohamed
   Kanneganti, Thirumala-Devi
TI NLRP6 negatively regulates innate immunity and host defence against bacterial pathogens
SO NATURE
LA English
DT Article
ID listeria-monocytogenes; inflammasome; salmonella; caspase-1; infection; activation; receptors; kinase; roles
AB Members of the intracellular nucleotide-binding and oligomerization domain (NOD)-like receptor (NLR) family contribute to immune responses through activation of nuclear factor-kappa B (NF-kappa B), type I interferon and inflammasome signalling(1). Mice lacking the NLR family member NLRP6 were recently shown to be susceptible to colitis and colorectal tumorigenesis(2-4), but the role of NLRP6 in microbial infections and the nature of the inflammatory signalling pathways regulated by NLRP6 remain unclear. Here we show that Nlrp6-deficient mice are highly resistant to infection with the bacterial pathogens Listeria monocytogenes, Salmonella typhimurium and Escherichia coli. Infected Nlrp6-deficient mice had increased numbers of monocytes and neutrophils in circulation, and NLRP6 signalling in both haematopoietic and radioresistant cells contributed to increased susceptibility. Nlrp6 deficiency enhanced activation of mitogen-activated protein kinase (MAPK) and the canonical NF-kappa B pathway after Toll-like receptor ligation, but not cytosolic NOD1/2 ligation, in vitro. Consequently, infected Nlrp6-deficient cells produced increased levels of NF-kappa B-and MAPK-dependent cytokines and chemokines. Thus, our results reveal NLRP6 as a negative regulator of inflammatory signalling, and demonstrate a role for this NLR in impeding clearance of both Gram-positive and -negative bacterial pathogens.
C1 [Anand, Paras K.; Malireddi, R. K. Subbarao; Lukens, John R.; 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.
   [Bertin, John] GlaxoSmithKline, Immunoinflammat TA, Pattern Recognit Receptor DPU, Collegeville, PA 19426 USA.
   [Lamkanfi, Mohamed] Univ Ghent, Dept Biochem, B-9000 Ghent, Belgium.
   [Lamkanfi, Mohamed] VIB, Dept Med Prot Res, B-9000 Ghent, Belgium.
C3 St Jude Children's Research Hospital; St Jude Children's Research Hospital; St Jude Children's Research Hospital; GlaxoSmithKline; Glaxosmithkline USA; Ghent University; Flanders Institute for Biotechnology (VIB)
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 European Union [256432]; European Research Council [281600]; Fund for Scientific Research Flanders [G030212N, 1.2.201.10.N.00, 1.5.122.11.N.00]; National Institute of Health [AR056296, AI101935]; American Lebanese Syrian Associated Charities (ALSAC); 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; European Research Council (ERC) [281600] Funding Source: European Research Council (ERC)
NR 25
TC 347
Z9 413
U1 5
U2 62
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 16
PY 2012
VL 488
IS 7411
BP 389
EP +
DI 10.1038/nature11250
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 988OS
UT WOS:000307501000044
PM 22763455
DA 2026-03-09
ER

PT J
AU Rosenstiel, TN
   Shortlidge, EE
   Melnychenko, AN
   Pankow, JF
   Eppley, SM
AF Rosenstiel, Todd N.
   Shortlidge, Erin E.
   Melnychenko, Andrea N.
   Pankow, James F.
   Eppley, Sarah M.
TI Sex-specific volatile compounds influence microarthropod-mediated fertilization of moss
SO NATURE
LA English
DT Article
ID folsomia-candida collembola; floral scent; land plants; evolution; sperm; preferences; bryophytes; dimorphism; diversity; patterns
AB Sexual reproduction in non-vascular plants requires unicellular free-motile sperm to travel from male to female reproductive structures across the terrestrial landscape(1). Recent data suggest that microarthropods can disperse sperm in mosses(2). However, little is known about the chemical communication, if any, that is involved in this interaction or the relative importance of microarthropod dispersal compared to abiotic dispersal agents in mosses. Here we show that tissues of the cosmopolitan moss Ceratodon purpureus emit complex volatile scents, similar in chemical diversity to those described in pollination mutualisms between flowering plants and insects, that the chemical composition of C. purpureus volatiles are sex-specific, and that moss-dwelling microarthropods are differentially attracted to these sex-specific moss volatile cues. Furthermore, using experimental microcosms, we show that microarthropods significantly increase moss fertilization rates, even in the presence of water spray, highlighting the important role of microarthropod dispersal in contributing to moss mating success. Taken together, our results indicate the presence of a scent-based 'plant-pollinator-like' relationship that has evolved between two of Earth's most ancient terrestrial lineages, mosses and microarthropods.
C1 [Rosenstiel, Todd N.; Shortlidge, Erin E.; Melnychenko, Andrea N.; Eppley, Sarah M.] Portland State Univ, Dept Biol, Portland, OR 97201 USA.
   [Rosenstiel, Todd N.; Shortlidge, Erin E.; Melnychenko, Andrea N.; Eppley, Sarah M.] Portland State Univ, Ctr Life Extreme Environm, Portland, OR 97201 USA.
   [Pankow, James F.] Portland State Univ, Dept Chem, Portland, OR 97201 USA.
   [Pankow, James F.] Portland State Univ, Dept Civil & Environm Engn, Portland, OR 97201 USA.
C3 Portland State University; Portland State University; Portland State University; Portland State University
RP Eppley, SM (corresponding author), Portland State Univ, Dept Biol, 1719 SW 10th Ave, Portland, OR 97201 USA.
EM eppley@pdx.edu
FU 3M Corporation; National Science Foundation [DEB-0743461, IOS-0719570]; Direct For Biological Sciences; Division Of Environmental Biology [0743461] Funding Source: National Science Foundation; Direct For Biological Sciences; Div Of Biological Infrastructure [0963548] Funding Source: National Science Foundation
NR 36
TC 59
Z9 72
U1 3
U2 157
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD SEP 20
PY 2012
VL 489
IS 7416
BP 431
EP U118
DI 10.1038/nature11330
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 007AK
UT WOS:000308860900045
PM 22810584
DA 2026-03-09
ER

PT J
AU Ross-Innes, CS
   Stark, R
   Teschendorff, AE
   Holmes, KA
   Ali, HR
   Dunning, MJ
   Brown, GD
   Gojis, O
   Ellis, IO
   Green, AR
   Ali, S
   Chin, SF
   Palmieri, C
   Caldas, C
   Carroll, JS
AF Ross-Innes, Caryn S.
   Stark, Rory
   Teschendorff, Andrew E.
   Holmes, Kelly A.
   Ali, H. Raza
   Dunning, Mark J.
   Brown, Gordon D.
   Gojis, Ondrej
   Ellis, Ian O.
   Green, Andrew R.
   Ali, Simak
   Chin, Suet-Feung
   Palmieri, Carlo
   Caldas, Carlos
   Carroll, Jason S.
TI Differential oestrogen receptor binding is associated with clinical outcome in breast cancer
SO NATURE
LA English
DT Article
ID gene-expression signature; er-alpha; survival; reveals; foxa1; rna
AB Oestrogen receptor-alpha (ER) is the defining and driving transcription factor in the majority of breast cancers and its target genes dictate cell growth and endocrine response, yet genomic understanding of ER function has been restricted to model systems(1-3). Here we map genome-wide ER-binding events, by chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq), in primary breast cancers from patients with different clinical outcomes and in distant ER-positive metastases. We find that drug-resistant cancers still recruit ER to the chromatin, but that ER binding is a dynamic process, with the acquisition of unique ER-binding regions in tumours from patients that are likely to relapse. The acquired ER regulatory regions associated with poor clinical outcome observed in primary tumours reveal gene signatures that predict clinical outcome in ER-positive disease exclusively. We find that the differential ER-binding programme observed in tumours from patients with poor outcome is not due to the selection of a rare subpopulation of cells, but is due to the FOXA1-mediated reprogramming of ER binding on a rapid time-scale. The parallel redistribution of ER and FOXA1 binding events in drug-resistant cellular contexts is supported by histological co-expression of ER and FOXA1 in metastatic samples. By establishing transcription-factor mapping in primary tumour material, we show that there is plasticity in ER-binding capacity, with distinct combinations of cis-regulatory elements linked with the different clinical outcomes.
C1 [Ross-Innes, Caryn S.; Stark, Rory; Holmes, Kelly A.; Ali, H. Raza; Dunning, Mark J.; Brown, Gordon D.; Chin, Suet-Feung; Caldas, Carlos; Carroll, Jason S.] Li Ka Shing Ctr, Cambridge Res Inst, Canc Res UK, Cambridge CB2 0RE, England.
   [Teschendorff, Andrew E.] UCL, UCL Canc Inst, London WC1E 6BT, England.
   [Gojis, Ondrej; Ali, Simak; Palmieri, Carlo] Univ London Imperial Coll Sci Technol & Med, London W12 0NN, England.
   [Gojis, Ondrej] Charles Univ Prague, Fac Med 3, Dept Obstet & Gynaecol, Prague 10000 10, Czech Republic.
   [Gojis, Ondrej] Charles Univ Prague, Fac Med 3, Dept Pathol, Prague 10000 10, Czech Republic.
   [Ellis, Ian O.; Green, Andrew R.] Nottingham Univ Hosp NHS Trust, City Hosp Nottingham, Dept Histopathol, Nottingham NG5 1PB, England.
   [Caldas, Carlos; Carroll, Jason S.] Univ Cambridge, Dept Oncol, Cambridge CB2 0XZ, England.
   [Ali, H. Raza; Caldas, Carlos] Cambridge Univ Hosp NHS Fdn Trust, Addenbrookes Hosp, Cambridge Breast Unit, Cambridge CB2 2QQ, England.
   [Ali, H. Raza; Caldas, Carlos] NIHR Cambridge Biomed Res Ctr, Cambridge CB2 2QQ, England.
   [Caldas, Carlos] Cambridge Expt Canc Med Ctr ECMC, Cambridge CB2 0RE, England.
C3 Cancer Research UK; University of Cambridge; CRUK Cambridge Institute; University of London; University College London; Imperial College London; Charles University Prague; Charles University Prague; Nottingham University Hospital NHS Trust; Nottingham City Hospital; University of Cambridge; Cambridge University Hospitals NHS Foundation Trust; Addenbrooke's Hospital; University of Cambridge; University of Cambridge
RP Carroll, JS (corresponding author), Li Ka Shing Ctr, Cambridge Res Inst, Canc Res UK, Robinson Way, Cambridge CB2 0RE, England.
EM carlos.caldas@cancer.org.uk; jason.carroll@cancer.org.uk
FU University of Cambridge; Cancer Research UK; Hutchison Whampoa Limited; NIHR Biomedical Research Centre; Experimental Cancer Medicine Centre; Commonwealth Scholarship; Ministry of Education of the Czech Republic [MSM0021620808]; European Society of Medical Oncology; ERC; EMBO; Cancer Research UK [12011, 15602] Funding Source: researchfish; National Institute for Health Research [NF-SI-0611-10154] Funding Source: researchfish
NR 30
TC 1573
Z9 1827
U1 1
U2 133
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 19
PY 2012
VL 481
IS 7381
BP 389
EP U177
DI 10.1038/nature10730
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 877VK
UT WOS:000299210600048
PM 22217937
DA 2026-03-09
ER

PT J
AU de Vries, BL
   Acke, B
   Blommaert, JADL
   Waelkens, C
   Waters, LBFM
   Vandenbussche, B
   Min, M
   Olofsson, G
   Dominik, C
   Decin, L
   Barlow, MJ
   Brandeker, A
   Di Francesco, J
   Glauser, AM
   Greaves, J
   Harvey, PM
   Holland, WS
   Ivison, RJ
   Liseau, R
   Pantin, EE
   Pilbratt, GL
   Royer, P
   Sibthorpe, B
AF de Vries, B. L.
   Acke, B.
   Blommaert, J. A. D. L.
   Waelkens, C.
   Waters, L. B. F. M.
   Vandenbussche, B.
   Min, M.
   Olofsson, G.
   Dominik, C.
   Decin, L.
   Barlow, M. J.
   Brandeker, A.
   Di Francesco, J.
   Glauser, A. M.
   Greaves, J.
   Harvey, P. M.
   Holland, W. S.
   Ivison, R. J.
   Liseau, R.
   Pantin, E. E.
   Pilbratt, G. L.
   Royer, P.
   Sibthorpe, B.
TI Comet-like mineralogy of olivine crystals in an extrasolar proto-Kuiper belt
SO NATURE
LA English
DT Article
ID beta-pictoris; protoplanetary disks; debris disks; hd 100546; dust; silicates; spectra; spectroscopy; chondrites; forsterite
AB Some planetary systems harbour debris disks containing planetesimals such as asteroids and comets(1). Collisions between such bodies produce small dust particles(2), the spectral features of which reveal their composition and, hence, that of their parent bodies. A measurement of the composition of olivine crystals (Mg2-2xFe2xSiO4) has been done for the protoplanetary disk HD 100546 (refs 3, 4) and for olivine crystals in the warm inner parts of planetary systems. The latter compares well with the iron-rich olivine in asteroids(5,6) (x approximate to 0.29). In the cold outskirts of the beta Pictoris system, an analogue to the young Solar System, olivine crystals were detected(7) but their composition remained undetermined, leaving unknown how the composition of the bulk of Solar System cometary olivine grains compares with that of extrasolar comets(8,9). Here we report the detection of the 69-micrometre-wavelength band of olivine crystals in the spectrum of beta Pictoris. Because the disk is optically thin, we can associate the crystals with an extrasolar proto-Kuiper belt a distance of 15-45 astronomical units from the star (one astronomical unit is the Sun-Earth distance), determine their magnesium-rich composition (x = 0.01 +/- 0.001) and show that they make up 3.6 +/- 1.0 per cent of the total dust mass. These values are strikingly similar to those for the dust emitted by the most primitive comets in the Solar System(8-10), even though beta Pictoris is more massive and more luminous and has a different planetary system architecture.
C1 [de Vries, B. L.; Acke, B.; Blommaert, J. A. D. L.; Waelkens, C.; Vandenbussche, B.; Decin, L.; Royer, P.] Katholieke Univ Leuven, Sterrekundig Inst, B-3001 Louvain, Belgium.
   [Waters, L. B. F. M.] SRON, NL-3584 CA Utrecht, Netherlands.
   [Waters, L. B. F. M.; Min, M.; Dominik, C.; Decin, L.] Univ Amsterdam, Astron Inst Anton Pannekoek, NL-1090 GE Amsterdam, Netherlands.
   [Olofsson, G.; Brandeker, A.] Stockholm Univ, AlbaNova Univ Ctr, Dept Astron, S-10691 Stockholm, Sweden.
   [Dominik, C.] Radboud Univ Nijmegen, Dept Astrophys IMAPP, NL-6500 GL Nijmegen, Netherlands.
   [Barlow, M. J.] UCL, Dept Phys & Astron, London WC1E 6BT, England.
   [Di Francesco, J.] Natl Res Council Canada, Victoria, BC V9E 2E7, Canada.
   [Glauser, A. M.] Swiss Fed Inst Technol, Inst Astron, CH-8093 Zurich, Switzerland.
   [Glauser, A. M.; Holland, W. S.; Ivison, R. J.; Sibthorpe, B.] Royal Observ Edinburgh, UK Astron Technol Ctr, Edinburgh EH9 3HJ, Midlothian, Scotland.
   [Greaves, J.] SUPA, St Andrews KY16 9SS, Fife, Scotland.
   [Harvey, P. M.] Univ Texas Austin, Dept Astron, Austin, TX 78712 USA.
   [Holland, W. S.] Univ Edinburgh, Inst Astron, Royal Observ, Edinburgh EH9 3HJ, Midlothian, Scotland.
   [Liseau, R.] Chalmers, Onsala Space Observ, S-43992 Onsala, Sweden.
   [Pantin, E. E.] Univ Paris Diderot, IRFU Serv Astrophys, CEA Saclay, Lab AIM,CEA,DSM,CNRS, F-91191 Gif Sur Yvette, France.
   [Pilbratt, G. L.] ESTEC SRE SA, ESA Res & Sci Support Dept, NL-2201 AZ Noordwijk, Netherlands.
C3 KU Leuven; University of Amsterdam; Stockholm University; Radboud University Nijmegen; University of London; University College London; National Research Council Canada; Swiss Federal Institutes of Technology Domain; ETH Zurich; University of Edinburgh; University of St Andrews; University of Texas System; University of Texas Austin; University of Edinburgh; Chalmers University of Technology; Universite Paris Saclay; CEA; Centre National de la Recherche Scientifique (CNRS); Universite Paris Cite; European Space Agency; European Space Research & Technology Centre
RP de Vries, BL (corresponding author), Katholieke Univ Leuven, Sterrekundig Inst, Celestijnenlaan 200D, B-3001 Louvain, Belgium.
EM bldevries.science@gmail.com
FU BMVIT (Austria); ESA-PRODEX (Belgium); CEA/CNES (France); DLR (Germany); ASI (Italy); CICT/MCT (Spain); STFC [ST/J001511/1, ST/G001987/1, ST/J001651/1] Funding Source: UKRI; Science and Technology Facilities Council [ST/J001651/1, ST/J001511/1, ST/G001987/1] Funding Source: researchfish
NR 30
TC 45
Z9 50
U1 0
U2 13
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD OCT 4
PY 2012
VL 490
IS 7418
BP 74
EP 76
DI 10.1038/nature11469
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 015LG
UT WOS:000309446800034
PM 23038467
DA 2026-03-09
ER

PT J
AU Manske, M
   Miotto, O
   Campino, S
   Auburn, S
   Almagro-Garcia, J
   Maslen, G
   O'Brien, J
   Djimde, A
   Doumbo, O
   Zongo, I
   Ouedraogo, JB
   Michon, P
   Mueller, I
   Siba, P
   Nzila, A
   Borrmann, S
   Kiara, SM
   Marsh, K
   Jiang, H
   Su, XZ
   Amaratunga, C
   Fairhurst, R
   Socheat, D
   Nosten, F
   Imwong, M
   White, NJ
   Sanders, M
   Anastasi, E
   Alcock, D
   Drury, E
   Oyola, S
   Quail, MA
   Turner, DJ
   Ruano-Rubio, V
   Jyothi, D
   Amenga-Etego, L
   Hubbart, C
   Jeffreys, A
   Rowlands, K
   Sutherland, C
   Roper, C
   Mangano, V
   Modiano, D
   Tan, JC
   Ferdig, MT
   Amambua-Ngwa, A
   Conway, DJ
   Takala-Harrison, S
   Plowe, CV
   Rayner, JC
   Rockett, KA
   Clark, TG
   Newbold, CI
   Berriman, M
   MacInnis, B
   Kwiatkowski, DP
AF Manske, Magnus
   Miotto, Olivo
   Campino, Susana
   Auburn, Sarah
   Almagro-Garcia, Jacob
   Maslen, Gareth
   O'Brien, Jack
   Djimde, Abdoulaye
   Doumbo, Ogobara
   Zongo, Issaka
   Ouedraogo, Jean-Bosco
   Michon, Pascal
   Mueller, Ivo
   Siba, Peter
   Nzila, Alexis
   Borrmann, Steffen
   Kiara, Steven M.
   Marsh, Kevin
   Jiang, Hongying
   Su, Xin-Zhuan
   Amaratunga, Chanaki
   Fairhurst, Rick
   Socheat, Duong
   Nosten, Francois
   Imwong, Mallika
   White, Nicholas J.
   Sanders, Mandy
   Anastasi, Elisa
   Alcock, Dan
   Drury, Eleanor
   Oyola, Samuel
   Quail, Michael A.
   Turner, Daniel J.
   Ruano-Rubio, Valentin
   Jyothi, Dushyanth
   Amenga-Etego, Lucas
   Hubbart, Christina
   Jeffreys, Anna
   Rowlands, Kate
   Sutherland, Colin
   Roper, Cally
   Mangano, Valentina
   Modiano, David
   Tan, John C.
   Ferdig, Michael T.
   Amambua-Ngwa, Alfred
   Conway, David J.
   Takala-Harrison, Shannon
   Plowe, Christopher V.
   Rayner, Julian C.
   Rockett, Kirk A.
   Clark, Taane G.
   Newbold, Chris I.
   Berriman, Matthew
   MacInnis, Bronwyn
   Kwiatkowski, Dominic P.
TI Analysis of Plasmodium falciparum diversity in natural infections by deep sequencing
SO NATURE
LA English
DT Article
ID papua-new-guinea; malaria parasite; library preparation; genome; resistance; transmission; polymorphism; evolution; selection; patterns
AB Malaria elimination strategies require surveillance of the parasite population for genetic changes that demand a public health response, such as new forms of drug resistance(1,2). Here we describe methods for the large-scale analysis of genetic variation in Plasmodium falciparum by deep sequencing of parasite DNA obtained from the blood of patients with malaria, either directly or after short-term culture. Analysis of 86,158 exonic single nucleotide polymorphisms that passed genotyping quality control in 227 samples from Africa, Asia and Oceania provides genome-wide estimates of allele frequency distribution, population structure and linkage disequilibrium. By comparing the genetic diversity of individual infections with that of the local parasite population, we derive a metric of within-host diversity that is related to the level of inbreeding in the population. An open-access web application has been established for the exploration of regional differences in allele frequency and of highly differentiated loci in the P. falciparum genome.
C1 [Manske, Magnus; Campino, Susana; Auburn, Sarah; Almagro-Garcia, Jacob; Maslen, Gareth; Sanders, Mandy; Anastasi, Elisa; Alcock, Dan; Drury, Eleanor; Oyola, Samuel; Quail, Michael A.; Turner, Daniel J.; Ruano-Rubio, Valentin; Jyothi, Dushyanth; Rayner, Julian C.; Rockett, Kirk A.; Clark, Taane G.; Newbold, Chris I.; Berriman, Matthew; MacInnis, Bronwyn; Kwiatkowski, Dominic P.] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England.
   [Manske, Magnus; Miotto, Olivo; Campino, Susana; Auburn, Sarah; Almagro-Garcia, Jacob; Maslen, Gareth; O'Brien, Jack; Ruano-Rubio, Valentin; Jyothi, Dushyanth; Amenga-Etego, Lucas; Rockett, Kirk A.; Clark, Taane G.; Newbold, Chris I.; MacInnis, Bronwyn; Kwiatkowski, Dominic P.] Univ Oxford, MRC Ctr Genom & Global Hlth, Oxford OX3 7BN, England.
   [Miotto, Olivo; Nosten, Francois; White, Nicholas J.] Mahidol Univ, Mahidol Oxford Trop Med Res Unit, Bangkok 10400, Thailand.
   [Auburn, Sarah] Charles Darwin Univ, Menzies Sch Hlth Res, Darwin, NT 0811, Australia.
   [Almagro-Garcia, Jacob; O'Brien, Jack; Ruano-Rubio, Valentin; Amenga-Etego, Lucas; Hubbart, Christina; Jeffreys, Anna; Rowlands, Kate; Rockett, Kirk A.; Kwiatkowski, Dominic P.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.
   [Djimde, Abdoulaye; Doumbo, Ogobara] Univ Bamako, Fac Med, Malaria Res & Training Ctr, Bamako, Mali.
   [Zongo, Issaka; Ouedraogo, Jean-Bosco] Inst Rech Sci Sante, Direct Reg Ouest, Bobo Dioulasso, Burkina Faso.
   [Michon, Pascal; Mueller, Ivo; Siba, Peter] Papua New Guinea Inst Med Res, Madang 511, Papua N Guinea.
   [Nzila, Alexis; Borrmann, Steffen; Kiara, Steven M.; Marsh, Kevin] KEMRI Wellcome Trust Res Program, Kilifi, Kenya.
   [Jiang, Hongying; Su, Xin-Zhuan; Amaratunga, Chanaki; Fairhurst, Rick] Nat Inst Allergy & Infect Dis, NIH, Rockville, MD 20892 USA.
   [Socheat, Duong] Cambodia Natl Malaria Ctr, Phnom Penh, Cambodia.
   [Nosten, Francois] Shoklo Malaria Res Unit, Mae Sot 63110, Tak, Thailand.
   [Nosten, Francois; White, Nicholas J.] Univ Oxford, Ctr Trop Med, Oxford OX3 7LJ, England.
   [Imwong, Mallika] Mahidol Univ, Fac Trop Med, Dept Mol Trop Med & Genet, Bangkok 10400, Thailand.
   [Amenga-Etego, Lucas] Navrongo Hlth Ctr, Navrongo, Ghana.
   [Sutherland, Colin; Roper, Cally; Conway, David J.; Clark, Taane G.] London Sch Hyg & Trop Med, London WC1E 7HT, England.
   [Mangano, Valentina; Modiano, David] Univ Roma La Sapienza, Dept Publ Hlth Sci, I-00185 Rome, Italy.
   [Tan, John C.; Ferdig, Michael T.] Univ Notre Dame, Eck Inst Global Hlth, Dept Biol Sci, Notre Dame, IN 46556 USA.
   [Amambua-Ngwa, Alfred; Conway, David J.] MRC Labs, Fajara, Gambia.
   [Takala-Harrison, Shannon; Plowe, Christopher V.] Univ Maryland, Ctr Vaccine Dev, Baltimore, MD 21201 USA.
   [Newbold, Chris I.] Univ Oxford, Weatherall Inst Mol Med, Oxford OX3 9DS, England.
C3 Wellcome Trust Sanger Institute; University of Oxford; Mahidol University; Mahidol Oxford Tropical Medicine Research Unit (MORU); Charles Darwin University; Menzies School of Health Research; University of Oxford; Wellcome Centre for Human Genetics; University of Bamako; PNG Institute Of Medical Research; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID); Mahidol University; University of Oxford; Mahidol University; University of London; London School of Hygiene & Tropical Medicine; Sapienza University Rome; University of Notre Dame; MRC Laboratory Molecular Biology; University System of Maryland; University of Maryland Baltimore; University of Oxford
RP Kwiatkowski, DP (corresponding author), Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England.
EM dominic@sanger.ac.uk
FU Wellcome Trust through Sanger Institute [077012/Z/05/Z, 098051, 090770/Z/09/Z]; Medical Research Council (MRC) through the MRC Centre for Genomics and Global Health [G0600718]; MRC [G19/9]; Wellcome Trust [075491/Z/04, 090532/Z/09/Z]; Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health; Howard Hughes Medical Institute [55005502]; National Institute of Allergy and Infectious Diseases [ZIAAI001066] Funding Source: NIH RePORTER; Medical Research Council [G19/9, G0600718, G0600230] Funding Source: researchfish; MRC [G19/9, G0600718] Funding Source: UKRI; Wellcome Trust [090770/Z/09/Z] Funding Source: Wellcome Trust
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NR 30
TC 387
Z9 436
U1 0
U2 73
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUL 19
PY 2012
VL 487
IS 7407
BP 375
EP 379
DI 10.1038/nature11174
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 975JB
UT WOS:000306506500045
PM 22722859
DA 2026-03-09
ER

PT J
AU High, AA
   Leonard, JR
   Hammack, AT
   Fogler, MM
   Butov, LV
   Kavokin, AV
   Campman, KL
   Gossard, AC
AF High, A. A.
   Leonard, J. R.
   Hammack, A. T.
   Fogler, M. M.
   Butov, L. V.
   Kavokin, A. V.
   Campman, K. L.
   Gossard, A. C.
TI Spontaneous coherence in a cold exciton gas
SO NATURE
LA English
DT Article
ID bose-einstein condensation; coupled quantum-wells; nobel lecture; semiconductors; transport; vortices; liquid
AB If bosonic particles are cooled down below the temperature of quantum degeneracy, they can spontaneously form a coherent state in which individual matter waves synchronize and combine. Spontaneous coherence of matter waves forms the basis of a number of fundamental phenomena in physics, including superconductivity, superfluidity and Bose-Einstein condensation(1,2). Spontaneous coherence is the key characteristic of condensation in momentum space(3). Excitons-bound pairs of electrons and holes-form amodel system to explore the quantum physics of cold bosons in solids(4,5). Cold exciton gases can be realized in a system of indirect excitons, which can cool down below the temperature of quantum degeneracy owing to their long lifetimes(6). Here we report measurements of spontaneous coherence in a gas of indirect excitons. We found that spontaneous coherence of excitons emerges in the region of the macroscopically ordered exciton state(7) and in the region of vortices of linear polarization. The coherence length in these regions is much larger than in a classical gas, indicating a coherent state with a much narrower than classical exciton distribution in momentum space, characteristic of a condensate. A pattern of extended spontaneous coherence is correlated with a pattern of spontaneous polarization, revealing the properties of a multicomponent coherent state. We also observed phase singularities in the coherent exciton gas. All these phenomena emerge when the exciton gas is cooled below a few kelvin.
C1 [High, A. A.; Leonard, J. R.; Hammack, A. T.; Fogler, M. M.; Butov, L. V.] Univ Calif San Diego, Dept Phys, La Jolla, CA 92093 USA.
   [Kavokin, A. V.] Univ Southampton, Sch Phys & Astron, Southampton SO17 1BJ, Hants, England.
   [Kavokin, A. V.] St Petersburg State Univ, Spin Opt Lab, St Petersburg 198504, Russia.
   [Campman, K. L.; Gossard, A. C.] Univ Calif Santa Barbara, Dept Mat, Santa Barbara, CA 93106 USA.
C3 University of California System; University of California San Diego; University of Southampton; Saint Petersburg State University; University of California System; University of California Santa Barbara
RP High, AA (corresponding author), Univ Calif San Diego, Dept Phys, La Jolla, CA 92093 USA.
EM alex.high@gmail.com
FU DOE Office of Basic Energy Sciences [DE-FG02-07ER46449]; UCOP; Royal Society (UK); Division Of Materials Research; Direct For Mathematical & Physical Scien [0907349] Funding Source: National Science Foundation; U.S. Department of Energy (DOE) [DE-FG02-07ER46449] Funding Source: U.S. Department of Energy (DOE)
NR 30
TC 278
Z9 310
U1 0
U2 109
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD MAR 29
PY 2012
VL 483
IS 7391
BP 584
EP 588
DI 10.1038/nature10903
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 915EF
UT WOS:000302006100036
PM 22437498
DA 2026-03-09
ER

PT J
AU Scally, A
   Dutheil, JY
   Hillier, LW
   Jordan, GE
   Goodhead, I
   Herrero, J
   Hobolth, A
   Lappalainen, T
   Mailund, T
   Marques-Bonet, T
   McCarthy, S
   Montgomery, SH
   Schwalie, PC
   Tang, YA
   Ward, MC
   Xue, YL
   Yngvadottir, B
   Alkan, C
   Andersen, LN
   Ayub, Q
   Ball, EV
   Beal, K
   Bradley, BJ
   Chen, Y
   Clee, CM
   Fitzgerald, S
   Graves, TA
   Gu, Y
   Heath, P
   Heger, A
   Karakoc, E
   Kolb-Kokocinski, A
   Laird, GK
   Lunter, G
   Meader, S
   Mort, M
   Mullikin, JC
   Munch, K
   O'Connor, TD
   Phillips, AD
   Prado-Martinez, J
   Rogers, AS
   Sajjadian, S
   Schmidt, D
   Shaw, K
   Simpson, JT
   Stenson, PD
   Turner, DJ
   Vigilant, L
   Vilella, AJ
   Whitener, W
   Zhu, BL
   Cooper, DN
   de Jong, P
   Dermitzakis, ET
   Eichler, EE
   Flicek, P
   Goldman, N
   Mundy, NI
   Ning, ZM
   Odom, DT
   Ponting, CP
   Quail, MA
   Ryder, OA
   Searle, SM
   Warren, WC
   Wilson, RK
   Schierup, MH
   Rogers, J
   Tyler-Smith, C
   Durbin, R
AF Scally, Aylwyn
   Dutheil, Julien Y.
   Hillier, LaDeana W.
   Jordan, Gregory E.
   Goodhead, Ian
   Herrero, Javier
   Hobolth, Asger
   Lappalainen, Tuuli
   Mailund, Thomas
   Marques-Bonet, Tomas
   McCarthy, Shane
   Montgomery, Stephen H.
   Schwalie, Petra C.
   Tang, Y. Amy
   Ward, Michelle C.
   Xue, Yali
   Yngvadottir, Bryndis
   Alkan, Can
   Andersen, Lars N.
   Ayub, Qasim
   Ball, Edward V.
   Beal, Kathryn
   Bradley, Brenda J.
   Chen, Yuan
   Clee, Chris M.
   Fitzgerald, Stephen
   Graves, Tina A.
   Gu, Yong
   Heath, Paul
   Heger, Andreas
   Karakoc, Emre
   Kolb-Kokocinski, Anja
   Laird, Gavin K.
   Lunter, Gerton
   Meader, Stephen
   Mort, Matthew
   Mullikin, James C.
   Munch, Kasper
   O'Connor, Timothy D.
   Phillips, Andrew D.
   Prado-Martinez, Javier
   Rogers, Anthony S.
   Sajjadian, Saba
   Schmidt, Dominic
   Shaw, Katy
   Simpson, Jared T.
   Stenson, Peter D.
   Turner, Daniel J.
   Vigilant, Linda
   Vilella, Albert J.
   Whitener, Weldon
   Zhu, Baoli
   Cooper, David N.
   de Jong, Pieter
   Dermitzakis, Emmanouil T.
   Eichler, Evan E.
   Flicek, Paul
   Goldman, Nick
   Mundy, Nicholas I.
   Ning, Zemin
   Odom, Duncan T.
   Ponting, Chris P.
   Quail, Michael A.
   Ryder, Oliver A.
   Searle, Stephen M.
   Warren, Wesley C.
   Wilson, Richard K.
   Schierup, Mikkel H.
   Rogers, Jane
   Tyler-Smith, Chris
   Durbin, Richard
TI Insights into hominid evolution from the gorilla genome sequence
SO NATURE
LA English
DT Article
ID copy number; consequences; patterns; primates; reveals; humans; family; genes
AB Gorillas are humans' closest living relatives after chimpanzees, and are of comparable importance for the study of human origins and evolution. Here we present the assembly and analysis of a genome sequence for the western lowland gorilla, and compare the whole genomes of all extant great ape genera. We propose a synthesis of genetic and fossil evidence consistent with placing the human-chimpanzee and human-chimpanzee-gorilla speciation events at approximately 6 and 10 million years ago. In 30% of the genome, gorilla is closer to human or chimpanzee than the latter are to each other; this is rarer around coding genes, indicating pervasive selection throughout great ape evolution, and has functional consequences in gene expression. A comparison of protein coding genes reveals approximately 500 genes showing accelerated evolution on each of the gorilla, human and chimpanzee lineages, and evidence for parallel acceleration, particularly of genes involved in hearing. We also compare the western and eastern gorilla species, estimating an average sequence divergence time 1.75 million years ago, but with evidence for more recent genetic exchange and a population bottleneck in the eastern species. The use of the genome sequence in these and future analyses will promote a deeper understanding of great ape biology and evolution.
C1 [Scally, Aylwyn; Goodhead, Ian; McCarthy, Shane; Tang, Y. Amy; Xue, Yali; Yngvadottir, Bryndis; Ayub, Qasim; Chen, Yuan; Clee, Chris M.; Gu, Yong; Heath, Paul; Kolb-Kokocinski, Anja; Laird, Gavin K.; Rogers, Anthony S.; Simpson, Jared T.; Turner, Daniel J.; Whitener, Weldon; Ning, Zemin; Odom, Duncan T.; Quail, Michael A.; Searle, Stephen M.; Rogers, Jane; Tyler-Smith, Chris; Durbin, Richard] Wellcome Trust Sanger Inst, Hinxton CB10 1SA, England.
   [Dutheil, Julien Y.; Hobolth, Asger; Mailund, Thomas; Andersen, Lars N.; Munch, Kasper; Schierup, Mikkel H.] Aarhus Univ, Bioinformat Res Ctr, DK-8000 Aarhus C, Denmark.
   [Hillier, LaDeana W.; Marques-Bonet, Tomas; Alkan, Can; Karakoc, Emre; Sajjadian, Saba; Eichler, Evan E.] Univ Washington, Sch Med, Dept Genome Sci, Seattle, WA 98195 USA.
   [Jordan, Gregory E.; Herrero, Javier; Schwalie, Petra C.; Beal, Kathryn; Fitzgerald, Stephen; Vilella, Albert J.; Flicek, Paul; Goldman, Nick] European Bioinformat Inst, Hinxton CB10 1SD, England.
   [Lappalainen, Tuuli; Dermitzakis, Emmanouil T.] Univ Geneva, Sch Med, Dept Genet Med & Dev, CH-1211 Geneva 4, Switzerland.
   [Marques-Bonet, Tomas; Prado-Martinez, Javier] Inst Biol Evolut UPF CSIC, Barcelona 08003, Catalonia, Spain.
   [Marques-Bonet, Tomas] ICREA, Barcelona 08010, Spain.
   [Montgomery, Stephen H.; Bradley, Brenda J.; O'Connor, Timothy D.; Mundy, Nicholas I.] Univ Cambridge, Dept Zool, Cambridge CB2 3EJ, England.
   [Ward, Michelle C.; Schmidt, Dominic; Odom, Duncan T.] Univ Cambridge, Dept Oncol, Hutchison MRC Res Ctr, Cambridge CB2 0XZ, England.
   [Ward, Michelle C.; Schmidt, Dominic; Odom, Duncan T.] Cambridge Res Inst, Canc Res UK, Li Ka Shing Ctr, Cambridge CB2 0RE, England.
   [Alkan, Can; Eichler, Evan E.] Univ Washington, Howard Hughes Med Inst, Seattle, WA USA.
   [Ball, Edward V.; Mort, Matthew; Phillips, Andrew D.; Shaw, Katy; Stenson, Peter D.; Cooper, David N.] Cardiff Univ, Inst Med Genet, Cardiff CF14 4XN, S Glam, Wales.
   [Bradley, Brenda J.] Yale Univ, Dept Anthropol, New Haven, CT 06511 USA.
   [Graves, Tina A.; Warren, Wesley C.; Wilson, Richard K.] Washington Univ, Sch Med, Genome Inst, St Louis, MO 63108 USA.
   [Heger, Andreas; Meader, Stephen; Ponting, Chris P.] Univ Oxford, Dept Physiol Anat & Genet, MRC Funct Genom Unit, Oxford OX1 3QX, England.
   [Lunter, Gerton] Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.
   [Mullikin, James C.] NHGRI, Comparat Genom Unit, Genome Technol Branch, NIH, Bethesda, MD 20892 USA.
   [Vigilant, Linda] Max Planck Inst Evolutionary Anthropol, Primatol Dept, D-04103 Leipzig, Germany.
   [Zhu, Baoli; de Jong, Pieter] Childrens Hosp Oakland, Res Inst, Oakland, CA 94609 USA.
   [Ryder, Oliver A.] San Diego Zoos Inst Conservat Res, Escondido, CA 92027 USA.
C3 Wellcome Trust Sanger Institute; Aarhus University; University of Washington; University of Washington Seattle; European Molecular Biology Laboratory (EMBL); European Bioinformatics Institute; University of Geneva; Consejo Superior de Investigaciones Cientificas (CSIC); CSIC-UPF - Institut de Biologia Evolutiva (IBE); ICREA; University of Cambridge; University of Cambridge; CRUK Cambridge Institute; University of Cambridge; Cancer Research UK; University of Washington; University of Washington Seattle; Howard Hughes Medical Institute; Cardiff University; Yale University; Washington University (WUSTL); University of Oxford; University of Oxford; Wellcome Centre for Human Genetics; National Institutes of Health (NIH) - USA; NIH National Human Genome Research Institute (NHGRI); Max Planck Society; University of California System; University of California San Francisco; UCSF Medical Center; UCSF Benioff Children's Hospital Oakland; Children's Hospital Oakland Research Institute; Zoological Society of San Diego
RP Durbin, R (corresponding author), Wellcome Trust Sanger Inst, Wellcome Trust Genome Campus, Hinxton CB10 1SA, England.
EM rd@sanger.ac.uk
FU Wellcome Trust [WT062023, WT089066, WT077192, WT077009, WT077198, 075491/Z/04]; EMBL; Gates Cambridge Trust; MRC; Lundbeck Foundation; Academy of Finlandand the Emil Aaltonen Foundation; Marie Curie fellowship; European Community [StG_20091118]; Spanish Ministry of Education [BES-2010-032251]; BBSRC; UK Medical Research Council; National Human Genome Research Institute, National Institutes of Health; Danish Council for Independent Research, Natural Sciences [09-062535]; Commonwealth Scholarship; Swiss National Science Foundation; Louis Jeantet Foundation; ERC; EMBO; Hutchinson Whampoa; NHGRI; BIOBASE GmbH; US National Science Foundation [DGE-0739133]; NHGRI [U54 HG003079]; NIH [HG002385]; National Human Genome Research Institute [R01HG002385, ZIAHG200330] Funding Source: NIH RePORTER; Cancer Research UK [15603] Funding Source: researchfish; Medical Research Council [G0701805, G0501331] Funding Source: researchfish; MRC [G0701805, G0501331] Funding Source: UKRI; ICREA Funding Source: Custom
NR 51
TC 519
Z9 609
U1 0
U2 218
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 8
PY 2012
VL 483
IS 7388
BP 169
EP 175
DI 10.1038/nature10842
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 904DT
UT WOS:000301174900029
PM 22398555
DA 2026-03-09
ER

PT J
AU Carrieri, C
   Cimatti, L
   Biagioli, M
   Beugnet, A
   Zucchelli, S
   Fedele, S
   Pesce, E
   Ferrer, I
   Collavin, L
   Santoro, C
   Forrest, ARR
   Carninci, P
   Biffo, S
   Stupka, E
   Gustincich, S
AF Carrieri, Claudia
   Cimatti, Laura
   Biagioli, Marta
   Beugnet, Anne
   Zucchelli, Silvia
   Fedele, Stefania
   Pesce, Elisa
   Ferrer, Isidre
   Collavin, Licio
   Santoro, Claudio
   Forrest, Alistair R. R.
   Carninci, Piero
   Biffo, Stefano
   Stupka, Elia
   Gustincich, Stefano
TI Long non-coding antisense RNA controls Uchl1 translation through an embedded SINEB2 repeat
SO NATURE
LA English
DT Article
ID parkinsons-disease; mammalian genome; gene-expression; lewy body; transcription; sequences; dementia; uch-l1
AB Most of the mammalian genome is transcribed(1-3). This generates a vast repertoire of transcripts that includes protein-coding messenger RNAs, long non-coding RNAs (lncRNAs) and repetitive sequences, such as SINEs (short interspersed nuclear elements). A large percentage of ncRNAs are nuclear-enriched with unknown function(4). Antisense lncRNAs may form sense-antisense pairs by pairing with a protein-coding gene on the opposite strand to regulate epigenetic silencing, transcription and mRNA stability(5-10). Here we identify a nuclear-enriched lncRNA antisense to mouse ubiquitin carboxyterminal hydrolase L1 (Uchl1), a gene involved in brain function and neurodegenerative diseases(11). Antisense Uchl1 increases UCHL1 protein synthesis at a post-transcriptional level, hereby identifying a new functional class of lncRNAs. Antisense Uchl1 activity depends on the presence of a 59 overlapping sequence and an embedded inverted SINEB2 element. These features are shared by other natural antisense transcripts and can confer regulatory activity to an artificial antisense to green fluorescent protein. Antisense Uchl1 function is under the control of stress signalling pathways, as mTORC1 inhibition by rapamycin causes an increase in UCHL1 protein that is associated to the shuttling of antisense Uchl1 RNA from the nucleus to the cytoplasm. Antisense Uchl1 RNA is then required for the association of the overlapping sense protein-coding mRNA to active polysomes for translation. These data reveal another layer of gene expression control at the post-transcriptional level.
C1 [Carrieri, Claudia; Cimatti, Laura; Biagioli, Marta; Zucchelli, Silvia; Fedele, Stefania; Gustincich, Stefano] Int Sch Adv Studies SISSA, Area Neurosci, I-34136 Trieste, Italy.
   [Biagioli, Marta; Zucchelli, Silvia; Gustincich, Stefano] Giovanni Armenise Harvard Fdn Lab, I-34136 Trieste, Italy.
   [Beugnet, Anne; Pesce, Elisa; Biffo, Stefano] Ist Sci San Raffaele, DIBIT, Lab Mol Histol & Cell Growth, I-20132 Milan, Italy.
   [Ferrer, Isidre] Univ Hosp Bellvitge, IDIBELL, Inst Neuropathol, Lhospitalet De Llobregat 08907, Spain.
   [Collavin, Licio] LNCIB, I-34149 Trieste, Italy.
   [Collavin, Licio] Univ Trieste, Dept Life Sci DSV, I-34129 Trieste, Italy.
   [Santoro, Claudio] Univ Piemonte Orientale, Dept Hlth Sci, I-28100 Novara, Italy.
   [Forrest, Alistair R. R.; Carninci, Piero] RIKEN Yokohama Inst, Om Sci Ctr, Tsurumi Ku, Yokohama, Kanagawa 2300045, Japan.
   [Biffo, Stefano] Univ Piemonte Orientale, Dept Environm & Life Sci, I-15121 Alessandria, Italy.
   [Stupka, Elia] Ist Sci San Raffaele, Ctr Translat Genom & Bioinformat, I-20132 Milan, Italy.
C3 International School for Advanced Studies (SISSA); Vita-Salute San Raffaele University; IRCCS Ospedale San Raffaele; Institut d'Investigacio Biomedica de Bellvitge (IDIBELL); Bellvitge University Hospital; University of Trieste; University of Eastern Piedmont Amedeo Avogadro; RIKEN; University of Eastern Piedmont Amedeo Avogadro; Vita-Salute San Raffaele University; IRCCS Ospedale San Raffaele
RP Gustincich, S (corresponding author), Int Sch Adv Studies SISSA, Area Neurosci, Via Bonomea 265, I-34136 Trieste, Italy.
EM gustinci@sissa.it
FU FP7 Dopaminet; Giovanni Armenise-Harvard Foundation; Compagnia di San Paolo
NR 32
TC 807
Z9 943
U1 2
U2 193
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD NOV 15
PY 2012
VL 491
IS 7424
BP 454
EP +
DI 10.1038/nature11508
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 036MY
UT WOS:000311031600048
PM 23064229
DA 2026-03-09
ER

PT J
AU Thoreen, CC
   Chantranupong, L
   Keys, HR
   Wang, T
   Gray, NS
   Sabatini, DM
AF Thoreen, Carson C.
   Chantranupong, Lynne
   Keys, Heather R.
   Wang, Tim
   Gray, Nathanael S.
   Sabatini, David M.
TI A unifying model for mTORC1-mediated regulation of mRNA translation
SO NATURE
LA English
DT Article
ID ribosome entry sites; large gene lists; cell-proliferation; independent manner; mammalian target; mtor pathway; akt activity; cyclin d1; rapamycin; inhibition
AB The mTOR complex 1 (mTORC1) kinase nucleates a pathway that promotes cell growth and proliferation and is the target of rapamycin, a drug with many clinical uses(1). mTORC1 regulates messenger RNA translation, but the overall translational program is poorly defined and no unifying model exists to explain how mTORC1 differentially controls the translation of specific mRNAs. Here we use high-resolution transcriptome-scale ribosome profiling to monitor translation in mouse cells acutely treated with the mTOR inhibitor Torin 1, which, unlike rapamycin, fully inhibits mTORC1 (ref. 2). Our data reveal a surprisingly simple model of the mRNA features and mechanisms that confer mTORC1-dependent translation control. The subset of mRNAs that are specifically regulated by mTORC1 consists almost entirely of transcripts with established 5' terminal oligopyrimidine (TOP) motifs, or, like Hsp90ab1 and Ybx1, with previously unrecognized TOP or related TOP-like motifs that we identified. We find no evidence to support proposals that mTORC1 preferentially regulates mRNAs with increased 5' untranslated region length or complexity(3). mTORC1 phosphorylates a myriad of translational regulators, but how it controls TOP mRNA translation is unknown(4). Remarkably, loss of just the 4E-BP family of translational repressors, arguably the best characterized mTORC1 substrates, is sufficient to render TOP and TOP-like mRNA translation resistant to Torin 1. The 4E-BPs inhibit translation initiation by interfering with the interaction between the cap-binding protein eIF4E and eIF4G1. Loss of this interaction diminishes the capacity of eIF4E to bind TOP and TOP-like mRNAs much more than other mRNAs, explaining why mTOR inhibition selectively suppresses their translation. Our results clarify the translational program controlled by mTORC1 and identify 4E-BPs and eIF4G1 as its master effectors.
C1 [Thoreen, Carson C.; Gray, Nathanael S.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
   [Thoreen, Carson C.; Gray, Nathanael S.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
   [Thoreen, Carson C.; Chantranupong, Lynne; Keys, Heather R.; Wang, Tim; Sabatini, David M.] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA.
   [Chantranupong, Lynne; Keys, Heather R.; Wang, Tim; Sabatini, David M.] MIT, Howard Hughes Med Inst, Cambridge, MA 02139 USA.
   [Chantranupong, Lynne; Keys, Heather R.; Wang, Tim; Sabatini, David M.] MIT, Dept Biol, Cambridge, MA 02139 USA.
   [Chantranupong, Lynne; Keys, Heather R.; Sabatini, David M.] Broad Inst Harvard & MIT, Cambridge, MA 02142 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); Howard Hughes Medical Institute; Massachusetts Institute of Technology (MIT); Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute
RP Gray, NS (corresponding author), Dana Farber Canc Inst, Dept Canc Biol, 250 Longwood Ave, Boston, MA 02115 USA.
EM nathanael_gray@dfci.harvard.edu; sabatini@wi.mit.edu
FU National Institutes of Health [CA103866, CA129105]; Department of Defense [W81XWH-07-0448]; W.M. Keck Foundation; LAM Foundation; Dana Farber Cancer Institute; American Cancer Society; National Science Foundation; National Cancer Institute [R01CA129105, R01CA103866] Funding Source: NIH RePORTER
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NR 39
TC 1171
Z9 1442
U1 2
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 MAY 3
PY 2012
VL 485
IS 7396
BP 109
EP U142
DI 10.1038/nature11083
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 934NV
UT WOS:000303451900044
PM 22552098
DA 2026-03-09
ER

PT J
AU Paterson, AH
   Wendel, JF
   Gundlach, H
   Guo, H
   Jenkins, J
   Jin, DC
   Llewellyn, D
   Showmaker, KC
   Shu, SQ
   Udall, J
   Yoo, MJ
   Byers, R
   Chen, W
   Doron-Faigenboim, A
   Duke, MV
   Gong, L
   Grimwood, J
   Grover, C
   Grupp, K
   Hu, GJ
   Lee, TH
   Li, JP
   Lin, LF
   Liu, T
   Marler, BS
   Page, JT
   Roberts, AW
   Romanel, E
   Sanders, WS
   Szadkowski, E
   Tan, X
   Tang, HB
   Xu, CM
   Wang, JP
   Wang, ZN
   Zhang, D
   Zhang, L
   Ashrafi, H
   Bedon, F
   Bowers, JE
   Brubaker, CL
   Chee, PW
   Das, S
   Gingle, AR
   Haigler, CH
   Harker, D
   Hoffmann, LV
   Hovav, R
   Jones, DC
   Lemke, C
   Mansoor, S
   Rahman, MU
   Rainville, LN
   Rambani, A
   Reddy, UK
   Rong, JK
   Saranga, Y
   Scheffler, BE
   Scheffler, JA
   Stelly, DM
   Triplett, BA
   Van Deynze, A
   Vaslin, MFS
   Waghmare, VN
   Walford, SA
   Wright, RJ
   Zaki, EA
   Zhang, TZ
   Dennis, ES
   Mayer, KFX
   Peterson, DG
   Rokhsar, DS
   Wang, XY
   Schmutz, J
AF Paterson, Andrew H.
   Wendel, Jonathan F.
   Gundlach, Heidrun
   Guo, Hui
   Jenkins, Jerry
   Jin, Dianchuan
   Llewellyn, Danny
   Showmaker, Kurtis C.
   Shu, Shengqiang
   Udall, Joshua
   Yoo, Mi-jeong
   Byers, Robert
   Chen, Wei
   Doron-Faigenboim, Adi
   Duke, Mary V.
   Gong, Lei
   Grimwood, Jane
   Grover, Corrinne
   Grupp, Kara
   Hu, Guanjing
   Lee, Tae-ho
   Li, Jingping
   Lin, Lifeng
   Liu, Tao
   Marler, Barry S.
   Page, Justin T.
   Roberts, Alison W.
   Romanel, Elisson
   Sanders, William S.
   Szadkowski, Emmanuel
   Tan, Xu
   Tang, Haibao
   Xu, Chunming
   Wang, Jinpeng
   Wang, Zining
   Zhang, Dong
   Zhang, Lan
   Ashrafi, Hamid
   Bedon, Frank
   Bowers, John E.
   Brubaker, Curt L.
   Chee, Peng W.
   Das, Sayan
   Gingle, Alan R.
   Haigler, Candace H.
   Harker, David
   Hoffmann, Lucia V.
   Hovav, Ran
   Jones, Donald C.
   Lemke, Cornelia
   Mansoor, Shahid
   Rahman, Mehboob Ur
   Rainville, Lisa N.
   Rambani, Aditi
   Reddy, Umesh K.
   Rong, Jun-kang
   Saranga, Yehoshua
   Scheffler, Brian E.
   Scheffler, Jodi A.
   Stelly, David M.
   Triplett, Barbara A.
   Van Deynze, Allen
   Vaslin, Maite F. S.
   Waghmare, Vijay N.
   Walford, Sally A.
   Wright, Robert J.
   Zaki, Essam A.
   Zhang, Tianzhen
   Dennis, Elizabeth S.
   Mayer, Klaus F. X.
   Peterson, Daniel G.
   Rokhsar, Daniel S.
   Wang, Xiyin
   Schmutz, Jeremy
TI Repeated polyploidization of Gossypium genomes and the evolution of spinnable cotton fibres
SO NATURE
LA English
DT Article
ID dna; sequence; recombination; arabidopsis; plants; organization; barbadense; pathways; ancient; protein
AB Polyploidy often confers emergent properties, such as the higher fibre productivity and quality of tetraploid cottons than diploid cottons bred for the same environments(1). Here we show that an abrupt five-to sixfold ploidy increase approximately 60 million years (Myr) ago, and allopolyploidy reuniting divergent Gossypium genomes approximately 1-2 Myr ago(2), conferred about 30-36-fold duplication of ancestral angiosperm (flowering plant) genes in elite cottons (Gossypium hirsutum and Gossypium barbadense), genetic complexity equalled only by Brassica(3) among sequenced angiosperms. Nascent fibre evolution, before allopolyploidy, is elucidated by comparison of spinnable-fibred Gossypium herbaceum A and non-spinnable Gossypium longicalyx F genomes to one another and the outgroup D genome of non-spinnable Gossypium raimondii. The sequence of a G. hirsutum A(t)D(t) (in which 't' indicates tetraploid) cultivar reveals many non-reciprocal DNA exchanges between subgenomes that may have contributed to phenotypic innovation and/or other emergent properties such as ecological adaptation by polyploids. Most DNA-level novelty in G. hirsutum recombines alleles from the D-genome progenitor native to its New World habitat and the Old World A-genome progenitor in which spinnable fibre evolved. Coordinated expression changes in proximal groups of functionally distinct genes, including a nuclear mitochondrial DNA block, may account for clusters of cotton-fibre quantitative trait loci affecting diverse traits. Opportunities abound for dissecting emergent properties of other polyploids, particularly angiosperms, by comparison to diploid progenitors and outgroups.
C1 [Paterson, Andrew H.; Guo, Hui; Lee, Tae-ho; Li, Jingping; Lin, Lifeng; Marler, Barry S.; Tan, Xu; Tang, Haibao; Wang, Zining; Zhang, Dong; Bowers, John E.; Das, Sayan; Gingle, Alan R.; Lemke, Cornelia; Mansoor, Shahid; Rainville, Lisa N.; Rong, Jun-kang; Wang, Xiyin] Univ Georgia, Plant Genome Mapping Lab, Athens, GA 30602 USA.
   [Wendel, Jonathan F.; Yoo, Mi-jeong; Gong, Lei; Grover, Corrinne; Grupp, Kara; Hu, Guanjing; Szadkowski, Emmanuel; Xu, Chunming] Iowa State Univ, Dept Ecol Evolut & Organismal Biol, Ames, IA 50011 USA.
   [Gundlach, Heidrun; Mayer, Klaus F. X.] German Res Ctr Environm Hlth GmbH, MIPS IBIS Inst Bioinformat & Syst Biol, D-85764 Neuherberg, Germany.
   [Jenkins, Jerry; Shu, Shengqiang; Grimwood, Jane; Rokhsar, Daniel S.; Schmutz, Jeremy] Joint Genome Inst, Dept Energy, Walnut Creek, CA 94595 USA.
   [Jenkins, Jerry; Grimwood, Jane; Schmutz, Jeremy] HudsonAlpha Inst Biotechnol, Huntsville, AL 35806 USA.
   [Jin, Dianchuan; Chen, Wei; Liu, Tao; Wang, Jinpeng; Zhang, Lan; Wang, Xiyin] Hebei United Univ, Sch Life Sci, Ctr Genom & Computat Biol, Tangshan 063000, Hebei, Peoples R China.
   [Jin, Dianchuan; Chen, Wei; Liu, Tao; Wang, Jinpeng; Zhang, Lan; Wang, Xiyin] Hebei United Univ, Sch Sci, Tangshan 063000, Hebei, Peoples R China.
   [Llewellyn, Danny; Bedon, Frank; Brubaker, Curt L.; Walford, Sally A.; Dennis, Elizabeth S.] CSIRO Plant Ind, Canberra, ACT 2601, Australia.
   [Showmaker, Kurtis C.; Sanders, William S.; Peterson, Daniel G.] Mississippi State Univ, Inst Genom Biocomp & Biotechnol, Mississippi State, MS 39762 USA.
   [Udall, Joshua; Byers, Robert; Page, Justin T.; Harker, David; Rambani, Aditi] Brigham Young Univ, Plant & Wildlife Sci Dept, Provo, UT 84602 USA.
   [Doron-Faigenboim, Adi; Hovav, Ran] Agr Res Org, Inst Plant Sci, Dept Field Crops, IL-50250 Bet Dagan, Israel.
   [Duke, Mary V.; Scheffler, Brian E.; Scheffler, Jodi A.] USDA ARS, Jamie Whitten Delta States Res Ctr, Stoneville, MS 38776 USA.
   [Roberts, Alison W.] Univ Rhode Isl, Dept Biol Sci, Kingston, RI 02881 USA.
   [Romanel, Elisson] Univ Fed Rio de Janeiro, Dept Genet, BR-21941901 Rio De Janeiro, Brazil.
   [Tang, Haibao] J Craig Venter Inst, Rockville, MD 20850 USA.
   [Xu, Chunming] NE Normal Univ, Inst Cytol & Genet, Unit Plant Epigenet, Key Lab Mol Epigenet MOE, Changchun 5268, Peoples R China.
   [Ashrafi, Hamid; Van Deynze, Allen] Univ Calif Davis, Plant Reprod Biol Extens Ctr, Davis, CA 95616 USA.
   [Brubaker, Curt L.] Bayer CropSci, B-9052 Ghent, Belgium.
   [Chee, Peng W.] Univ Georgia, Coastal Plain Expt Stn, Tifton, GA 31793 USA.
   [Haigler, Candace H.] N Carolina State Univ, Dept Crop Sci, Raleigh, NC 27695 USA.
   [Haigler, Candace H.] N Carolina State Univ, Dept Plant Biol, Raleigh, NC 27695 USA.
   [Hoffmann, Lucia V.] EMBRAPA, Ctr Nacl Pesquisa Algodao, BR-75375000 Santo Antonio De Goias, Go, Brazil.
   [Jones, Donald C.] Cotton Inc, Cary, NC 27513 USA.
   [Mansoor, Shahid; Rahman, Mehboob Ur] Natl Inst Biotechnol & Genet Engn, Faisalabad 38000, Pakistan.
   [Reddy, Umesh K.] W Virginia State Univ, Dept Biol, Institute, WV 25112 USA.
   [Saranga, Yehoshua] Hebrew Univ Jerusalem, Robert H Smith Inst Plant Sci & Genet Agr, IL-76100 Rehovot, Israel.
   [Stelly, David M.] Texas A&M Univ, Dept Soil & Crop Sci, College Stn, TX 77843 USA.
   [Triplett, Barbara A.] USDA ARS, New Orleans, LA 70124 USA.
   [Vaslin, Maite F. S.] Univ Fed Rio de Janeiro, Dept Microbiol, BR-21941971 Rio De Janeiro, Brazil.
   [Waghmare, Vijay N.] Cent Inst Cotton Res, Nagpur 440010, Maharashtra, India.
   [Wright, Robert J.] Texas Tech Univ, Dept Plant Sci, Lubbock, TX 79415 USA.
   [Zaki, Essam A.] Genet Engn & Biotechnol Res Inst, Nucle Acids Dept, Alexandria 21934, Egypt.
   [Zhang, Tianzhen] Nanjing Agr Univ, Key Lab Crop Genet & Germplasm Enhancement, Nanjing 210095, Jiangsu, Peoples R China.
C3 University System of Georgia; University of Georgia; Iowa State University; Helmholtz Association; Helmholtz-Center Munich - German Research Center for Environmental Health; United States Department of Energy (DOE); Joint Genome Institute - JGI; Joint BioEnergy Institute - JBEI; HudsonAlpha Institute for Biotechnology; North China University of Science & Technology; North China University of Science & Technology; Commonwealth Scientific & Industrial Research Organisation (CSIRO); Plant Industry; Mississippi State University; Brigham Young University; Volcani Institute of Agricultural Research; United States Department of Agriculture (USDA); University of Rhode Island; Universidade Federal do Rio de Janeiro; J. Craig Venter Institute; Northeast Normal University - China; University of California System; University of California Davis; Bayer AG; Bayer CropScience; University System of Georgia; University of Georgia; North Carolina State University; North Carolina State University; Empresa Brasileira de Pesquisa Agropecuaria (EMBRAPA); Cotton Incorporated; Pakistan Institute of Engineering & Applied Science; West Virginia State University; Hebrew University of Jerusalem; Texas A&M University System; Texas A&M University College Station; United States Department of Agriculture (USDA); Universidade Federal do Rio de Janeiro; Indian Council of Agricultural Research (ICAR); ICAR - Central Institute of Cotton Research; Texas Tech University System; Texas Tech University; Nanjing Agricultural University
RP Paterson, AH (corresponding author), Univ Georgia, Plant Genome Mapping Lab, Athens, GA 30602 USA.
EM paterson@plantbio.uga.edu; jschmutz@hudsonalpha.org
FU Office of Science of the US Department of Energy [DE-AC02-05CH11231]; US National Science Foundation [DBI 98-72630, DBI 02-11700, DBI 02-08311, IIP-0917856, IIP-1127755, IOS 1025947]; USDA [ARS-58-6402-7-241, 58-6402-1-644, 58-6402-1-645, ARS 6402-21310-003-00, NRI 00-52100-9685, 02-35301-12045]; Bayer CropScience; Consortium for Plant Biotechnology Research; Cotton, Inc.; Georgia State Support Committee; Texas State Support Committee; Pakistan-US Science and Technology Cooperation Program; US-Egypt Science and Technology Cooperation Program; Fulbright Scholar Program; Conselho Nacional de Desenvolvimento Cientifico e Tecnologico [PDJ150690/2012-6]; Fundacao de Amparo a Pesquisa Pensa Rio [E-26/110.324/2010]; Texas AgriLife; Brigham Young University (BYU); Direct For Biological Sciences; Division Of Integrative Organismal Systems [1025947] Funding Source: National Science Foundation; Direct For Biological Sciences; Div Of Molecular and Cellular Bioscience [0841821, 1021718] Funding Source: National Science Foundation; Directorate For Engineering; Div Of Industrial Innovation & Partnersh [0917856, 1127755] Funding Source: National Science Foundation; Div Of Biological Infrastructure; Direct For Biological Sciences [0849896] Funding Source: National Science Foundation; Div Of Molecular and Cellular Bioscience; Direct For Biological Sciences [1118646] Funding Source: National Science Foundation
NR 42
TC 1021
Z9 1161
U1 11
U2 439
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 20
PY 2012
VL 492
IS 7429
BP 423
EP +
DI 10.1038/nature11798
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 056KQ
UT WOS:000312488200055
PM 23257886
DA 2026-03-09
ER

PT J
AU D'Hont, A
   Denoeud, F
   Aury, JM
   Baurens, FC
   Carreel, F
   Garsmeur, O
   Noel, B
   Bocs, S
   Droc, G
   Rouard, M
   Da Silva, C
   Jabbari, K
   Cardi, C
   Poulain, J
   Souquet, M
   Labadie, K
   Jourda, C
   Lengellé, J
   Rodier-Goud, M
   Alberti, A
   Bernard, M
   Correa, M
   Ayyampalayam, S
   Mckain, MR
   Leebens-Mack, J
   Burgess, D
   Freeling, M
   Mbéguié-A-Mbéguié, D
   Chabannes, M
   Wicker, T
   Panaud, O
   Barbosa, J
   Hribova, E
   Heslop-Harrison, P
   Habas, R
   Rivallan, R
   Francois, P
   Poiron, C
   Kilian, A
   Burthia, D
   Jenny, C
   Bakry, F
   Brown, S
   Guignon, V
   Kema, G
   Dita, M
   Waalwijk, C
   Joseph, S
   Dievart, A
   Jaillon, O
   Leclercq, J
   Argout, X
   Lyons, E
   Almeida, A
   Jeridi, M
   Dolezel, J
   Roux, N
   Risterucci, AM
   Weissenbach, J
   Ruiz, M
   Glaszmann, JC
   Quétier, F
   Yahiaoui, N
   Wincker, P
AF D'Hont, Angelique
   Denoeud, France
   Aury, Jean-Marc
   Baurens, Franc-Christophe
   Carreel, Francoise
   Garsmeur, Olivier
   Noel, Benjamin
   Bocs, Stephanie
   Droc, Gaetan
   Rouard, Mathieu
   Da Silva, Corinne
   Jabbari, Kamel
   Cardi, Celine
   Poulain, Julie
   Souquet, Marlene
   Labadie, Karine
   Jourda, Cyril
   Lengelle, Juliette
   Rodier-Goud, Marguerite
   Alberti, Adriana
   Bernard, Maria
   Correa, Margot
   Ayyampalayam, Saravanaraj
   Mckain, Michael R.
   Leebens-Mack, Jim
   Burgess, Diane
   Freeling, Mike
   Mbeguie-A-Mbeguie, Didier
   Chabannes, Matthieu
   Wicker, Thomas
   Panaud, Olivier
   Barbosa, Jose
   Hribova, Eva
   Heslop-Harrison, Pat
   Habas, Remy
   Rivallan, Ronan
   Francois, Philippe
   Poiron, Claire
   Kilian, Andrzej
   Burthia, Dheema
   Jenny, Christophe
   Bakry, Frederic
   Brown, Spencer
   Guignon, Valentin
   Kema, Gert
   Dita, Miguel
   Waalwijk, Cees
   Joseph, Steeve
   Dievart, Anne
   Jaillon, Olivier
   Leclercq, Julie
   Argout, Xavier
   Lyons, Eric
   Almeida, Ana
   Jeridi, Mouna
   Dolezel, Jaroslav
   Roux, Nicolas
   Risterucci, Ange-Marie
   Weissenbach, Jean
   Ruiz, Manuel
   Glaszmann, Jean-Christophe
   Quetier, Francis
   Yahiaoui, Nabila
   Wincker, Patrick
TI The banana (Musa acuminata) genome and the evolution of monocotyledonous plants
SO NATURE
LA English
DT Article
ID differential expression; dna-sequences; gene; diversification; identification; resource; rice; polyploidy; alignment; blast
AB Bananas (Musa spp.), including dessert and cooking types, are giant perennial monocotyledonous herbs of the order Zingiberales, a sister group to the well-studied Poales, which include cereals. Bananas are vital for food security in many tropical and subtropical countries and the most popular fruit in industrialized countries(1). The Musa domestication process started some 7,000 years ago in Southeast Asia. It involved hybridizations between diverse species and subspecies, fostered by human migrations(2), and selection of diploid and triploid seedless, parthenocarpic hybrids thereafter widely dispersed by vegetative propagation. Half of the current production relies on somaclones derived from a single triploid genotype (Cavendish)(1). Pests and diseases have gradually become adapted, representing an imminent danger for global banana production(3,4). Here we describe the draft sequence of the 523-megabase genome of a Musa acuminata doubled-haploid genotype, providing a crucial stepping-stone for genetic improvement of banana. We detected three rounds of whole-genome duplications in the Musa lineage, independently of those previously described in the Poales lineage and the one we detected in the Arecales lineage. This first monocotyledon high-continuity whole-genome sequence reported outside Poales represents an essential bridge for comparative genome analysis in plants. As such, it clarifies commelinid-monocotyledon phylogenetic relationships, reveals Poaceae-specific features and has led to the discovery of conserved noncoding sequences predating monocotyledon-eudicotyledon divergence.
C1 [D'Hont, Angelique; Baurens, Franc-Christophe; Carreel, Francoise; Garsmeur, Olivier; Bocs, Stephanie; Droc, Gaetan; Cardi, Celine; Souquet, Marlene; Jourda, Cyril; Lengelle, Juliette; Rodier-Goud, Marguerite; Rivallan, Ronan; Francois, Philippe; Poiron, Claire; Burthia, Dheema; Jenny, Christophe; Bakry, Frederic; Guignon, Valentin; Joseph, Steeve; Dievart, Anne; Leclercq, Julie; Argout, Xavier; Jeridi, Mouna; Risterucci, Ange-Marie; Ruiz, Manuel; Glaszmann, Jean-Christophe; Yahiaoui, Nabila] Ctr Cooperat Int Rech Agron Dev CIRAD, UMR AGAP, F-34398 Montpellier, France.
   [Denoeud, France; Aury, Jean-Marc; Noel, Benjamin; Da Silva, Corinne; Jabbari, Kamel; Poulain, Julie; Labadie, Karine; Alberti, Adriana; Bernard, Maria; Correa, Margot; Jaillon, Olivier; Weissenbach, Jean; Wincker, Patrick] CEA, IG, F-91057 Evry, France.
   [Denoeud, France; Jabbari, Kamel; Jaillon, Olivier; Weissenbach, Jean; Wincker, Patrick] CNRS, UMR 8030, Evry, France.
   [Denoeud, France; Jabbari, Kamel; Jaillon, Olivier; Weissenbach, Jean; Wincker, Patrick] Univ Evry, UMR 8030, Evry, France.
   [Carreel, Francoise; Chabannes, Matthieu; Habas, Remy] CIRAD, UMR BGPI, F-34398 Montpellier, France.
   [Rouard, Mathieu; Guignon, Valentin; Roux, Nicolas] Biovers Int, F-34397 Montpellier 5, France.
   [Ayyampalayam, Saravanaraj; Mckain, Michael R.; Leebens-Mack, Jim] Univ Georgia, Dept Plant Biol, Athens, GA 30602 USA.
   [Burgess, Diane; Freeling, Mike; Almeida, Ana] Univ Calif Berkeley, Dept Plant & Microbial Biol, Berkeley, CA 94720 USA.
   [Mbeguie-A-Mbeguie, Didier] CIRAD, UMR QUALISUD Stn Neufchateau, F-97130 Capesterre Belle Eau, France.
   [Wicker, Thomas] Univ Zurich, Inst Plant Biol, CH-8008 Zurich, Switzerland.
   [Panaud, Olivier; Barbosa, Jose] UMR 5096 CNRS UPVD, Lab Genome & Dev Plantes, F-66000 Perpignan, France.
   [Hribova, Eva] Ctr Reg Hana Biotechnol & Agr Res, Inst Expt Bot, CZ-77200 Olomouc, Czech Republic.
   [Heslop-Harrison, Pat] Univ Leicester, Dept Biol, Leicester LE1 7RH, Leics, England.
   [Kilian, Andrzej] Divers Arrays Technol, Yarralumla, ACT 2600, Australia.
   [Brown, Spencer] CNRS, UPR 2355, Inst Sci Vegetal, F-91198 Gif Sur Yvette, France.
   [Brown, Spencer] FRC3115, F-91198 Gif Sur Yvette, France.
   [Guignon, Valentin; Kema, Gert; Waalwijk, Cees] Univ Wageningen, Plant Res Int, NL-6700 AA Wageningen, Netherlands.
   [Lyons, Eric] Univ Arizona, Dept Plant Sci, Tucson, AZ 85721 USA.
   [Quetier, Francis] Univ Evry Val dEssonne, Dept Biol, Evry, France.
   [Dita, Miguel] Brazilian Agr Res Corp EMBRAPA, Embrapa Cassava & Fruits, BR-44380000 Salvador, BA, Brazil.
C3 CIRAD; Universite de Montpellier; CEA; CEA; Centre National de la Recherche Scientifique (CNRS); Universite Paris Saclay; CNRS - National Institute for Biology (INSB); CEA; Centre National de la Recherche Scientifique (CNRS); Universite Paris Saclay; CNRS - National Institute for Biology (INSB); CIRAD; Alliance; Bioversity International; University System of Georgia; University of Georgia; University of California System; University of California Berkeley; CIRAD; University of Zurich; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB); Universite Perpignan Via Domitia; Czech Academy of Sciences; Institute of Experimental Botany of the Czech Academy of Sciences; University of Leicester; Universite Paris Saclay; Centre National de la Recherche Scientifique (CNRS); Wageningen University & Research; University of Arizona; Universite Paris Saclay; Empresa Brasileira de Pesquisa Agropecuaria (EMBRAPA)
RP D'Hont, A (corresponding author), Ctr Cooperat Int Rech Agron Dev CIRAD, UMR AGAP, F-34398 Montpellier, France.
EM angelique.d'hont@cirad.fr; pwincker@genoscope.cns.fr
FU French National Research Agency; Commissariat a l'Energie Atomique; Centre de cooperation Internationale en Recherche Agronomique pour le Developpement; Direct For Biological Sciences; Division Of Environmental Biology [1010905] Funding Source: National Science Foundation; Direct For Biological Sciences; Division Of Integrative Organismal Systems [0922742] Funding Source: National Science Foundation; Division Of Environmental Biology; Direct For Biological Sciences [0830009, 0841988] Funding Source: National Science Foundation; Div Of Molecular and Cellular Bioscience; Direct For Biological Sciences [0820821] Funding Source: National Science Foundation
NR 61
TC 886
Z9 988
U1 6
U2 450
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 9
PY 2012
VL 488
IS 7410
BP 213
EP +
DI 10.1038/nature11241
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 985LE
UT WOS:000307267000034
PM 22801500
DA 2026-03-09
ER

PT J
AU Nakamura, T
   Zhao, Y
   Yamagata, Y
   Hua, YJ
   Yang, W
AF Nakamura, Teruya
   Zhao, Ye
   Yamagata, Yuriko
   Hua, Yue-Jin
   Yang, Wei
TI Watching DNA polymerase η make a phosphodiester bond
SO NATURE
LA English
DT Article
ID crystal-structures; 2-metal-ion mechanism; ternary complexes; transition-state; structural basis; active-site; substrate; fidelity; metal; binding
AB DNA synthesis has been extensively studied, but the chemical reaction itself has not been visualized. Here we follow the course of phosphodiester bond formation using time-resolved X-ray crystallography. Native human DNA polymerase eta, DNA and dATP were co-crystallized at pH 6.0 without Mg2+. The polymerization reaction was initiated by exposing crystals to 1 mM Mg2+ at pH 7.0, and stopped by freezing at desired time points for structural analysis. The substrates and two Mg2+ ions are aligned within 40 s, but the bond formation is not evident until 80 s. From 80 to 300 s structures show a mixture of decreasing substrate and increasing product of the nucleotidyl-transfer reaction. Transient electron densities indicate that deprotonation and an accompanying C2'-endo to C3'-endo conversion of the nucleophile 3'-OH are rate limiting. A third Mg2+ ion, which arrives with the new bond and stabilizes the intermediate state, may be an unappreciated feature of the two-metal-ion mechanism.
C1 [Nakamura, Teruya; Zhao, Ye; Yang, Wei] NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
   [Nakamura, Teruya; Yamagata, Yuriko] Kumamoto Univ, Grad Sch Pharmaceut Sci, Kumamoto 8620973, Japan.
   [Zhao, Ye; Hua, Yue-Jin] Zhejiang Univ, Inst Nucl Agr Sci, Hangzhou 310029, Zhejiang, Peoples R China.
C3 National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK); Kumamoto University; Zhejiang University
RP Yang, W (corresponding author), NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
EM wei.yang@nih.gov
FU National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health; Japan Society for the Promotion of Science; Kumamoto University; Kumayaku Alumni Research Fund; Chinese Ministry of Education; National Natural Science Foundation of China; Ministry of Education, Culture, Sports, Science, and Technology of Japan; Grants-in-Aid for Scientific Research [23790052, 24113719, 22131007] Funding Source: KAKEN; National Institute of Diabetes and Digestive and Kidney Diseases [ZIADK036146] Funding Source: NIH RePORTER
NR 55
TC 240
Z9 279
U1 1
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 JUL 12
PY 2012
VL 487
IS 7406
BP 196
EP U77
DI 10.1038/nature11181
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 972LP
UT WOS:000306278900031
PM 22785315
DA 2026-03-09
ER

PT J
AU Tokinaga, H
   Xie, SP
   Deser, C
   Kosaka, Y
   Okumura, YM
AF Tokinaga, Hiroki
   Xie, Shang-Ping
   Deser, Clara
   Kosaka, Yu
   Okumura, Yuko M.
TI Slowdown of the Walker circulation driven by tropical Indo-Pacific warming
SO NATURE
LA English
DT Article
ID asian climate; precipitation; sensitivity; simulation; shift
AB Global mean sea surface temperature (SST) has risen steadily over the past century(1,2), but the overall pattern contains extensive and often uncertain spatial variations, with potentially important effects on regional precipitation(3,4). Observations suggest a slowdown of the zonal atmospheric overturning circulation above the tropical Pacific Ocean (the Walker circulation) over the twentieth century(1,5). Although this change has been attributed to a muted hydrological cycle forced by global warming(5,6), the effect of SST warming patterns has not been explored and quantified(1,7,8). Here we perform experiments using an atmospheric model, and find that SST warming patterns are the main cause of the weakened Walker circulation over the past six decades (1950-2009). The SST trend reconstructed from bucket-sampled SST and night-time marine surface air temperature features a reduced zonal gradient in the tropical Indo-Pacific Ocean, a change consistent with subsurface temperature observations(8). Model experiments with this trend pattern robustly simulate the observed changes, including the Walker circulation slowdown and the eastward shift of atmospheric convection from the Indonesian maritime continent to the central tropical Pacific. Our results cannot establish whether the observed changes are due to natural variability or anthropogenic global warming, but they do show that the observed slowdown in the Walker circulation is presumably driven by oceanic rather than atmospheric processes.
C1 [Tokinaga, Hiroki; Xie, Shang-Ping] Univ Hawaii Manoa, SOEST, Dept Meteorol, Int Pacific Res Ctr, 1680 EW Rd, Honolulu, HI 96822 USA.
   [Xie, Shang-Ping] Ocean Univ China, Phys Oceanog Lab, Qingdao 266003, Peoples R China.
   [Deser, Clara] Natl Ctr Atmospher Res, Boulder, CO 80307 USA.
   [Okumura, Yuko M.] Univ Texas Austin, Inst Geophys, Austin, TX 78758 USA.
C3 University of Hawaii System; University of Hawaii Manoa; Ocean University of China; National Center Atmospheric Research (NCAR) - USA; University of Texas System; University of Texas Austin
RP Tokinaga, H (corresponding author), Univ Hawaii Manoa, SOEST, Dept Meteorol, Int Pacific Res Ctr, 1680 EW Rd, Honolulu, HI 96822 USA.
EM tokinaga@hawaii.edu; xie@hawaii.edu
FU JAMSTEC; National Basic Research Program of China [2012CB955600]; NASA; NSF; NOAA; Div Atmospheric & Geospace Sciences; Directorate For Geosciences [1305719] Funding Source: National Science Foundation
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   Meng QJ, 2012, CLIM DYNAM, V38, P1757, DOI 10.1007/s00382-011-1047-8
   Power SB, 2011, J CLIMATE, V24, P6501, DOI 10.1175/2011JCLI4101.1
   Ramanathan V, 2005, P NATL ACAD SCI USA, V102, P5326, DOI 10.1073/pnas.0500656102
   Rayner NA, 2003, J GEOPHYS RES-ATMOS, V108, P0, DOI 10.1029/2002JD002670
   Schneider U, 2008, GLOBAL PRECIPITATION, V0, P0
   SEN PK, 1968, J AM STAT ASSOC, V63, P1379
   Shin SI, 2011, CLIM DYNAM, V36, P1577, DOI 10.1007/s00382-009-0732-3
   Smith TM, 2008, J CLIMATE, V21, P2283, DOI 10.1175/2007JCLI2100.1
   Solomon S, 2007, AR4 CLIMATE CHANGE 2007: THE PHYSICAL SCIENCE BASIS, V0, P1
   Tokinaga H, 2012, J CLIMATE, V25, P1689, DOI 10.1175/JCLI-D-11-00263.1
   Tokinaga H, 2011, J CLIMATE, V24, P267, DOI 10.1175/2010JCLI3789.1
   Uppala SM, 2005, Q J ROY METEOR SOC, V131, P2961, DOI 10.1256/qj.04.176
   Vecchi GA, 2006, NATURE, V441, P73, DOI 10.1038/nature04744
   Vecchi GA, 2007, J CLIMATE, V20, P4316, DOI 10.1175/JCLI4258.1
   WILLMOTT CJ, 1995, INT J CLIMATOL, V15, P221, DOI 10.1002/joc.3370150207
   Woodruff SD, 2011, INT J CLIMATOL, V31, P951, DOI 10.1002/joc.2103
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   Xie SP, 2010, J CLIMATE, V23, P966, DOI 10.1175/2009JCLI3329.1
NR 38
TC 297
Z9 330
U1 3
U2 214
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 15
PY 2012
VL 491
IS 7424
BP 439
EP 443
DI 10.1038/nature11576
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 036MY
UT WOS:000311031600045
PM 23151588
DA 2026-03-09
ER

PT J
AU Li, P
   Spolski, R
   Liao, W
   Wang, L
   Murphy, TL
   Murphy, KM
   Leonard, WJ
AF Li, Peng
   Spolski, Rosanne
   Liao, Wei
   Wang, Lu
   Murphy, Theresa L.
   Murphy, Kenneth M.
   Leonard, Warren J.
TI BATF-JUN is critical for IRF4-mediated transcription in T cells
SO NATURE
LA English
DT Article
ID b-atf; il-21; gene; differentiation; modulation; activation; expression; responses; irf-4; stat3
AB Interferon regulatory factor 4 (IRF4) is an IRF family transcription factor with critical roles in lymphoid development and in regulating the immune response(1,2). IRF4 binds DNA weakly owing to a carboxy-terminal auto-inhibitory domain, but cooperative binding with factors such as PU.1 or SPIB in B cells increases binding affinity(3), allowing IRF4 to regulate genes containing ETS-IRF composite elements (EICEs; 5'-GGAAnnGAAA-3')(1). Here we show that in mouse CD4(+) T cells, where PU.1/SPIB expression is low, and in B cells, where PU.1 is well expressed, IRF4 unexpectedly can cooperate with activator protein-1 (AP1) complexes to bind to AP1-IRF4 composite (5'-TGAnTCA/GAAA-3') motifs that we denote as AP1-IRF composite elements (AICEs). Moreover, BATF-JUN family protein complexes cooperate with IRF4 in binding to AICEs in pre-activated CD4(+) T cells stimulated with IL-21 and in T(H)17 differentiated cells. Importantly, BATF binding was diminished in Irf4(-/-) T cells and IRF4 binding was diminished in Batf(-/-) T cells, consistent with functional cooperation between these factors. Moreover, we show that AP1 and IRF complexes cooperatively promote transcription of the Il10 gene, which is expressed in T(H)17 cells and potently regulated by IL-21. These findings reveal that IRF4 can signal via complexes containing ETS or AP1 motifs depending on the cellular context, thus indicating new approaches for modulating IRF4-dependent transcription.
C1 [Li, Peng; Spolski, Rosanne; Liao, Wei; Wang, Lu; Leonard, Warren J.] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA.
   [Li, Peng; Spolski, Rosanne; Liao, Wei; Wang, Lu; Leonard, Warren J.] NHLBI, Ctr Immunol, NIH, Bethesda, MD 20892 USA.
   [Murphy, Theresa L.; Murphy, Kenneth M.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA.
   [Murphy, Kenneth M.] Washington Univ, Sch Med, Howard Hughes Med Inst, St Louis, MO 63110 USA.
C3 National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI); National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI); Washington University (WUSTL); Washington University (WUSTL); Howard Hughes Medical Institute
RP Li, P (corresponding author), NHLBI, Lab Mol Immunol, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM lip3@nhlbi.nih.gov; wjl@helix.nih.gov
FU Division of Intramural Research, National Heart, Lung, and Blood Institute, NIH; Howard Hughes Medical Institute; National Heart Lung and Blood Institute [ZIAHL005408, ZIGHL006020, ZIAHL005402] Funding Source: NIH RePORTER; National Institute of Diabetes and Digestive and Kidney Diseases [P30DK020579] Funding Source: NIH RePORTER
NR 33
TC 359
Z9 425
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 OCT 25
PY 2012
VL 490
IS 7421
BP 543
EP +
DI 10.1038/nature11530
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 025NK
UT WOS:000310196200043
PM 22992523
DA 2026-03-09
ER

PT J
AU Xiao, CH
   Fujita, N
   Miyasaka, K
   Sakamoto, Y
   Terasaki, O
AF Xiao, Changhong
   Fujita, Nobuhisa
   Miyasaka, Keiichi
   Sakamoto, Yasuhiro
   Terasaki, Osamu
TI Dodecagonal tiling in mesoporous silica
SO NATURE
LA English
DT Article
ID square-triangle tilings; quasi-crystals; order; 12-fold; phase
AB Recent advances in the fabrication of quasicrystals in soft matter systems have increased the length scales for quasicrystals(1) into the mesoscale range (20 to 500 angstroms). Thus far, dendritic liquid crystals(2), ABC-star polymers(3), colloids(4) and inorganic nanoparticles(5) have been reported to yield quasicrystals. These quasicrystals offer larger length scales than intermetallic quasicrystals (a few angstroms)(1,6), thus potentially leading to optical applications through the realization of a complete photonic bandgap induced via multiple scattering of light waves in virtually all directions(7-9). However, the materials remain far from structurally ideal, in contrast to their intermetallic counterparts, and fine control over the structure through a self-organization process has yet to be attained. Here we use the well-established self-assembly of surfactant micelles to produce a new class of mesoporous silicas, which exhibit 12-fold (dodecagonal) symmetry in both electron diffraction and morphology. Each particle reveals, in the 12-fold cross-section, an analogue of dodecagonal quasicrystals in the centre surrounded by 12 fans of crystalline domains in the peripheral part. The quasicrystallinity has been verified by selected-area electron diffraction and quantitative phason strain analyses on transmission electron microscope images obtained from the central region. We argue that the structure forms through a non-equilibrium growth process, wherein the competition between different micellar configurations has a central role in tuning the structure. A simple theoretical model successfully reproduces the observed features and thus establishes a link between the formation process and the resulting structure.
C1 [Xiao, Changhong; Miyasaka, Keiichi; Sakamoto, Yasuhiro; Terasaki, Osamu] Stockholm Univ, Bezelii Ctr EXSELENT Porous Mat, Dept Mat & Environm Chem, S-10691 Stockholm, Sweden.
   [Fujita, Nobuhisa] Tohoku Univ, Inst Multidisciplinary Res Adv Mat, Sendai, Miyagi 9808577, Japan.
   [Miyasaka, Keiichi; Terasaki, Osamu] Korea Adv Inst Sci & Technol, Grad Sch EEWS WCU, Taejon 305701, South Korea.
   [Sakamoto, Yasuhiro] Osaka Prefecture Univ, Nanosci & Nanotechnol Res Ctr, Sakai, Osaka 5998570, Japan.
C3 Stockholm University; Tohoku University; Korea Advanced Institute of Science & Technology (KAIST); Osaka Metropolitan University
RP Terasaki, O (corresponding author), Stockholm Univ, Bezelii Ctr EXSELENT Porous Mat, Dept Mat & Environm Chem, S-10691 Stockholm, Sweden.
EM terasaki@mmk.su.se
FU Swedish Research Council (VR); Japan Science and Technology Agency (JST); Berzelii EXSELENT; Knut and Alice Wallenberg Foundation; WCU programme, Korea [R-31-2008-000-10055-0]; JSPS [23710132]; MEXT, Japan; Grants-in-Aid for Scientific Research [23710132] Funding Source: KAKEN
NR 30
TC 143
Z9 167
U1 1
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 JUL 19
PY 2012
VL 487
IS 7407
BP 349
EP 353
DI 10.1038/nature11230
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 975JB
UT WOS:000306506500039
PM 22810699
DA 2026-03-09
ER

PT J
AU Churchland, MM
   Cunningham, JP
   Kaufman, MT
   Foster, JD
   Nuyujukian, P
   Ryu, SI
   Shenoy, KV
AF Churchland, Mark M.
   Cunningham, John P.
   Kaufman, Matthew T.
   Foster, Justin D.
   Nuyujukian, Paul
   Ryu, Stephen I.
   Shenoy, Krishna V.
TI Neural population dynamics during reaching
SO NATURE
LA English
DT Article
ID optimal feedback-control; motor cortex reflects; preparatory activity; output kinematics; isometric-force; arm movements; premotor; muscle; direction; neurons
AB Most theories of motor cortex have assumed that neural activity represents movement parameters. This view derives from what is known about primary visual cortex, where neural activity represents patterns of light. Yet it is unclear how well the analogy between motor and visual cortex holds. Single-neuron responses in motor cortex are complex, and there is marked disagreement regarding which movement parameters are represented. A better analogy might be with other motor systems, where a common principle is rhythmic neural activity. Here we find that motor cortex responses during reaching contain a brief but strong oscillatory component, something quite unexpected for a non-periodic behaviour. Oscillation amplitude and phase followed naturally from the preparatory state, suggesting a mechanistic role for preparatory neural activity. These results demonstrate an unexpected yet surprisingly simple structure in the population response. This underlying structure explains many of the confusing features of individual neural responses.
C1 [Churchland, Mark M.] Columbia Univ, Med Ctr, David Mahoney Ctr, Dept Neurosci,Kavli Inst Brain Sci, New York, NY 10032 USA.
   [Churchland, Mark M.; Kaufman, Matthew T.; Foster, Justin D.; Ryu, Stephen I.; Shenoy, Krishna V.] Stanford Univ, Dept Elect Engn, Stanford, CA 94305 USA.
   [Churchland, Mark M.; Kaufman, Matthew T.; Shenoy, Krishna V.] Stanford Univ, Neurosci Program, Stanford, CA 94305 USA.
   [Cunningham, John P.] Washington Univ St Louis, Dept Biomed Engn, St Louis, MO 63130 USA.
   [Cunningham, John P.] Univ Cambridge, Dept Engn, Cambridge CB2 1PZ, England.
   [Nuyujukian, Paul; Shenoy, Krishna V.] Stanford Univ, Dept Bioengn, Stanford, CA 94705 USA.
   [Nuyujukian, Paul] Stanford Univ, Sch Med, Stanford, CA 94305 USA.
   [Ryu, Stephen I.] Palo Alto Med Fdn, Dept Neurosurg, Palo Alto, CA 94301 USA.
   [Shenoy, Krishna V.] Stanford Univ, Sch Med, Dept Neurobiol, Stanford, CA 94305 USA.
C3 Columbia University; Stanford University; Stanford University; Washington University (WUSTL); University of Cambridge; Stanford University; Stanford University; Palo Alto Medical Foundation Research Institute; Stanford University
RP Churchland, MM (corresponding author), Columbia Univ, Med Ctr, David Mahoney Ctr, Dept Neurosci,Kavli Inst Brain Sci, New York, NY 10032 USA.
EM mc3502@columbia.edu
FU Helen Hay Whitney postdoctoral fellowship; National Institutes of Health (NIH); Burroughs Wellcome Fund Career Awards in the Biomedical Sciences; Engineering and Physical Sciences Research Council [EP/H019472/1]; McDonnell Center; National Science Foundation; Texas Instruments Stanford Graduate Fellowship; Paul and Daisy Soros Fellowship; Stanford Medical Scientist Training Program; NIH [1DP1OD006409]; NIH NINDS EUREKA [R01-NS066311]; NIH NINDS BRP [R01-NS064318]; NIH NINDS CRCNS [R01-NS054283]; DARPA-DSO REPAIR [N66001-10-C-2010]; Stanford Center for Integrated Systems; NSF Center for Neuromorphic Systems Engineering at Caltech; Office of Naval Research; Whitaker Foundation; McKnight Foundation; Sloan Foundation; Weston Havens Foundation; EPSRC [EP/H019472/1] Funding Source: UKRI; Engineering and Physical Sciences Research Council [EP/H019472/1] Funding Source: researchfish
NR 42
TC 1019
Z9 1308
U1 2
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 JUL 5
PY 2012
VL 487
IS 7405
BP 51
EP +
DI 10.1038/nature11129
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 968LM
UT WOS:000305982900048
PM 22722855
DA 2026-03-09
ER

PT J
AU Glover, TE
   Fritz, DM
   Cammarata, M
   Allison, TK
   Coh, S
   Feldkamp, JM
   Lemke, H
   Zhu, D
   Feng, Y
   Coffee, RN
   Fuchs, M
   Ghimire, S
   Chen, J
   Shwartz, S
   Reis, DA
   Harris, SE
   Hastings, JB
AF Glover, T. E.
   Fritz, D. M.
   Cammarata, M.
   Allison, T. K.
   Coh, Sinisa
   Feldkamp, J. M.
   Lemke, H.
   Zhu, D.
   Feng, Y.
   Coffee, R. N.
   Fuchs, M.
   Ghimire, S.
   Chen, J.
   Shwartz, S.
   Reis, D. A.
   Harris, S. E.
   Hastings, J. B.
TI X-ray and optical wave mixing
SO NATURE
LA English
DT Article
ID scattering; diffraction; conversion; diamond; field; bond
AB Light-matter interactions are ubiquitous, and underpin a wide range of basic research fields and applied technologies. Although optical interactions have been intensively studied, their microscopic details are often poorly understood and have so far not been directly measurable. X-ray and optical wave mixing was proposed nearly half a century ago as an atomic-scale probe of optical interactions but has not yet been observed owing to a lack of sufficiently intense X-ray sources. Here we use an X-ray laser to demonstrate X-ray and optical sum-frequency generation. The underlying nonlinearity is a reciprocal-space probe of the optically induced charges and associated microscopic fields that arise in an illuminated material. To within the experimental errors, the measured efficiency is consistent with first-principles calculations of microscopic optical polarization in diamond. The ability to probe optical interactions on the atomic scale offers new opportunities in both basic and applied areas of science.
C1 [Glover, T. E.] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Adv Light Source Div, Berkeley, CA 94720 USA.
   [Fritz, D. M.; Feldkamp, J. M.; Lemke, H.; Zhu, D.; Feng, Y.; Coffee, R. N.; Hastings, J. B.] SLAC Natl Accelerator Lab, Linac Coherent Light Source, Menlo Pk, CA 94025 USA.
   [Cammarata, M.] Univ Rennes 1, Inst Phys Rennes, CNRS UR1, UMR 6251, F-35042 Rennes, France.
   [Allison, T. K.] NIST, JILA, Boulder, CO 80309 USA.
   [Allison, T. K.] Univ Colorado, Boulder, CO 80309 USA.
   [Coh, Sinisa] Univ Calif Berkeley, Dept Phys, Berkeley, CA 94720 USA.
   [Coh, Sinisa] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Div Mat Sci, Berkeley, CA 94720 USA.
   [Fuchs, M.; Ghimire, S.; Chen, J.; Reis, D. A.] SLAC Natl Accelerator Lab, PULSE Inst, Menlo Pk, CA 94025 USA.
   [Chen, J.; Shwartz, S.; Reis, D. A.; Harris, S. E.] Stanford Univ, Dept Appl Phys, Stanford, CA 94305 USA.
   [Reis, D. A.] Stanford Univ, Dept Photon Sci, Stanford, CA 94305 USA.
   [Harris, S. E.] Stanford Univ, Dept Elect Engn, Stanford, CA 94305 USA.
C3 United States Department of Energy (DOE); Lawrence Berkeley National Laboratory; University of California System; University of California Berkeley; Stanford University; United States Department of Energy (DOE); SLAC National Accelerator Laboratory; Universite de Rennes; Centre National de la Recherche Scientifique (CNRS); CNRS - Institute of Physics (INP); National Institute of Standards & Technology (NIST) - USA; University of Colorado System; University of Colorado Boulder; University of California System; University of California Berkeley; United States Department of Energy (DOE); Lawrence Berkeley National Laboratory; University of California System; University of California Berkeley; Stanford University; United States Department of Energy (DOE); SLAC National Accelerator Laboratory; Stanford University; Stanford University; Stanford University
RP Glover, TE (corresponding author), Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Adv Light Source Div, Berkeley, CA 94720 USA.
EM teglover@lbl.gov
FU Office of Science, Office of Basic Energy Sciences, of the US Department of Energy [DE-AC02-05CH11231]; US Air Force Office of Scientific Research; US Army Research Office; AMOS programme within the Chemical Sciences, Geosciences, and Biosciences Division, Office of Basic Energy Sciences, US Department of Energy
NR 40
TC 195
Z9 223
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 AUG 30
PY 2012
VL 488
IS 7413
BP 603
EP +
DI 10.1038/nature11340
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 996NC
UT WOS:000308095100046
PM 22932384
DA 2026-03-09
ER

PT J
AU Rand, DG
   Greene, JD
   Nowak, MA
AF Rand, David G.
   Greene, Joshua D.
   Nowak, Martin A.
TI Spontaneous giving and calculated greed
SO NATURE
LA English
DT Article
ID evolution; cooperation; systems
AB Cooperation is central to human social behaviour(1-9). However, choosing to cooperate requires individuals to incur a personal cost to benefit others. Here we explore the cognitive basis of cooperative decision-making in humans using a dual-process framework(10-18). We ask whether people are predisposed towards selfishness, behaving cooperatively only through active self-control; or whether they are intuitively cooperative, with reflection and prospective reasoning favouring 'rational' self-interest. To investigate this issue, we perform ten studies using economic games. We find that across a range of experimental designs, subjects who reach their decisions more quickly are more cooperative. Furthermore, forcing subjects to decide quickly increases contributions, whereas instructing them to reflect and forcing them to decide slowly decreases contributions. Finally, an induction that primes subjects to trust their intuitions increases contributions compared with an induction that promotes greater reflection. To explain these results, we propose that cooperation is intuitive because cooperative heuristics are developed in daily life where cooperation is typically advantageous. We then validate predictions generated by this proposed mechanism. Our results provide convergent evidence that intuition supports cooperation in social dilemmas, and that reflection can undermine these cooperative impulses.
C1 [Rand, David G.; Nowak, Martin A.] Harvard Univ, Program Evolutionary Dynam, Cambridge, MA 02138 USA.
   [Rand, David G.; Greene, Joshua D.] Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA.
   [Rand, David G.] Yale Univ, Dept Psychol, New Haven, CT 06520 USA.
   [Nowak, Martin A.] Harvard Univ, Dept Math, Cambridge, MA 02138 USA.
   [Nowak, Martin A.] Harvard Univ, Dept Organism & Evolutionary Biol, Cambridge, MA 02138 USA.
C3 Harvard University; Harvard University; Yale University; Harvard University; Harvard University
RP Rand, DG (corresponding author), Harvard Univ, Program Evolutionary Dynam, Cambridge, MA 02138 USA.
EM drand@fas.harvard.edu
FU National Science Foundation [SES-0821978]; John Templeton Foundation; Direct For Social, Behav & Economic Scie; Divn Of Social and Economic Sciences [0821978] Funding Source: National Science Foundation
NR 30
TC 904
Z9 1086
U1 13
U2 520
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 20
PY 2012
VL 489
IS 7416
BP 427
EP 430
DI 10.1038/nature11467
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 007AK
UT WOS:000308860900044
PM 22996558
DA 2026-03-09
ER

PT J
AU Li, MQ
   Kao, E
   Gao, X
   Sandig, H
   Limmer, K
   Pavon-Eternod, M
   Jones, TE
   Landry, S
   Pan, T
   Weitzman, MD
   David, M
AF Li, Manqing
   Kao, Elaine
   Gao, Xia
   Sandig, Hilary
   Limmer, Kirsten
   Pavon-Eternod, Mariana
   Jones, Thomas E.
   Landry, Sebastien
   Pan, Tao
   Weitzman, Matthew D.
   David, Michael
TI Codon-usage-based inhibition of HIV protein synthesis by human schlafen 11
SO NATURE
LA English
DT Article
ID influenza-a virus; export pathway; nuclear export; messenger-rna; gene; bias; immunodeficiency; activation; expression; selection
AB In mammals, one of the most pronounced consequences of viral infection is the induction of type I interferons, cytokines with potent antiviral activity. Schlafen (Slfn) genes are a subset of interferon-stimulated early response genes (ISGs) that are also induced directly by pathogens via the interferon regulatory factor 3 (IRF3) pathway(1). However, many ISGs are of unknown or incompletely understood function. Here we show that human SLFN11 potently and specifically abrogates the production of retroviruses such as human immunodeficiency virus 1 (HIV-1). Our study revealed that SLFN11 has no effect on the early steps of the retroviral infection cycle, including reverse transcription, integration and transcription. Rather, SLFN11 acts at the late stage of virus production by selectively inhibiting the expression of viral proteins in a codon-usage-dependent manner. We further find that SLFN11 binds transfer RNA, and counteracts changes in the tRNA pool elicited by the presence of HIV. Our studies identified a novel antiviral mechanism within the innate immune response, in which SLFN11 selectively inhibits viral protein synthesis in HIV-infected cells by means of codon-bias discrimination.
C1 [Li, Manqing; Kao, Elaine; Gao, Xia; Sandig, Hilary; Limmer, Kirsten; David, Michael] Univ Calif San Diego, Mol Biol Sect, Div Biol Sci, La Jolla, CA 92093 USA.
   [Pavon-Eternod, Mariana; Jones, Thomas E.; Pan, Tao] Univ Chicago, Dept Biochem & Mol Biol, Chicago, IL 60637 USA.
   [Landry, Sebastien; Weitzman, Matthew D.] Salk Inst Biol Studies, Genet Lab, La Jolla, CA 92037 USA.
   [David, Michael] Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA 92093 USA.
C3 University of California System; University of California San Diego; University of Chicago; Salk Institute; University of California System; University of California San Diego
RP David, M (corresponding author), Univ Calif San Diego, Mol Biol Sect, Div Biol Sci, La Jolla, CA 92093 USA.
EM midavid@ucsd.edu
FU NIH [AI81019, AI074967, P01AI090935, R01GM101982, R21AI088490, P30AI36214]; HINT Program [NIH P01AI090935]; National Institute of Nursing Research; National Heart Lung and Blood Institute; National Institute on Minority Health and Health Disparities; National Institute on Aging; National Cancer Institute; Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Institute on Drug Abuse; National Institute of Diabetes and Digestive and Kidney Diseases; National Institute of Allergy and Infectious Diseases; National Institute of Dental and Craniofacial Research [P30AI036214] Funding Source: NIH RePORTER
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NR 28
TC 302
Z9 381
U1 0
U2 45
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 1
PY 2012
VL 491
IS 7422
BP 125
EP U145
DI 10.1038/nature11433
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 028PM
UT WOS:000310434500043
PM 23000900
DA 2026-03-09
ER

PT J
AU Lingwood, D
   McTamney, PM
   Yassine, HM
   Whittle, JRR
   Guo, XT
   Boyington, JC
   Wei, CJ
   Nabel, GJ
AF Lingwood, Daniel
   McTamney, Patrick M.
   Yassine, Hadi M.
   Whittle, James R. R.
   Guo, Xiaoti
   Boyington, Jeffrey C.
   Wei, Chih-Jen
   Nabel, Gary J.
TI Structural and genetic basis for development of broadly neutralizing influenza antibodies
SO NATURE
LA English
DT Article
ID cell antigen receptor; virus; specificity; vaccination; activation; induction; lymphomas; immunity; density; hiv-1
AB Influenza viruses take a yearly toll on human life despite efforts to contain them with seasonal vaccines. These viruses evade human immunity through the evolution of variants that resist neutralization. The identification of antibodies that recognize invariant structures on the influenza haemagglutinin (HA) protein have invigorated efforts to develop universal influenza vaccines. Specifically, antibodies to the highly conserved stem region of HA neutralize diverse viral subtypes. These antibodies largely derive from a specific antibody gene, heavy-chain variable region IGHV1-69, after limited affinity maturation from their germline ancestors(1,2), but how HA stimulates naive B cells to mature and induce protective immunity is unknown. To address this question, we analysed the structural and genetic basis for their engagement and maturation into broadly neutralizing antibodies. Here we show that the germline-encoded precursors of these antibodies act as functional B-cell antigen receptors (BCRs) that initiate subsequent affinity maturation. Neither the germline precursor of a prototypic antibody, CR6261 (ref. 3), nor those of two other natural human IGHV1-69 antibodies, bound HA as soluble immunoglobulin-G(IgG). However, all three IGHV1-69 precursors engaged HA when the antibody was expressed as cell surface IgM. HA triggered BCR-associated tyrosine kinase signalling by germline transmembrane IgM. Recognition and virus neutralization was dependent solely on the heavy chain, and affinity maturation of CR6261 required only seven amino acids in the complementarity-determining region (CDR) H1 and framework region 3 (FR3) to restore full activity. These findings provide insight into the initial events that lead to the generation of broadly neutralizing antibodies to influenza, informing the rational design of vaccines to elicit such antibodies and providing a model relevant to other infectious diseases, including human immunodeficiency virus/AIDS. The data further suggest that selected immunoglobulin genes recognize specific protein structural 'patterns' that provide a substrate for further affinity maturation.
C1 [Lingwood, Daniel; McTamney, Patrick M.; Yassine, Hadi M.; Whittle, James R. R.; Guo, Xiaoti; Boyington, Jeffrey C.; Wei, Chih-Jen; Nabel, Gary J.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
C3 National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID)
RP Nabel, GJ (corresponding author), NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM gnabel@nih.gov
FU US Department of Energy, Office of Science, Office of Basic Energy Sciences [W-31-109-Eng-38]; Intramural Research Program of the Vaccine Research Center, NIAID, National Institutes of Health
NR 31
TC 223
Z9 257
U1 0
U2 58
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD SEP 27
PY 2012
VL 489
IS 7417
BP 566
EP +
DI 10.1038/nature11371
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 046RG
UT WOS:000311781500004
PM 22932267
DA 2026-03-09
ER

PT J
AU Park, SH
   Das, BB
   Casagrande, F
   Tian, Y
   Nothnagel, HJ
   Chu, MN
   Kiefer, H
   Maier, K
   De Angelis, AA
   Marassi, FM
   Opella, SJ
AF Park, Sang Ho
   Das, Bibhuti B.
   Casagrande, Fabio
   Tian, Ye
   Nothnagel, Henry J.
   Chu, Mignon
   Kiefer, Hans
   Maier, Klaus
   De Angelis, Anna A.
   Marassi, Francesca M.
   Opella, Stanley J.
TI Structure of the chemokine receptor CXCR1 in phospholipid bilayers
SO NATURE
LA English
DT Article
ID protein-coupled receptor; human interleukin-8 receptor; nmr chemical-shifts; solid-state nmr; membrane-proteins; crystal-structure; spectroscopy; gpcr; proteoliposm; refinement
AB CXCR1 is one of two high-affinity receptors for the CXC chemokine interleukin-8 (IL-8), a major mediator of immune and inflammatory responses implicated in many disorders, including tumour growth(1-3). IL-8, released in response to inflammatory stimuli, binds to the extracellular side of CXCR1. The ligand-activated intracellular signalling pathways result in neutrophil migration to the site of inflammation(2). CXCR1 is a class A, rhodopsin-like G-protein-coupled receptor (GPCR), the largest class of integral membrane proteins responsible for cellular signal transduction and targeted as drug receptors(4-7). Despite its importance, the molecular mechanism of CXCR1 signal transduction is poorly understood owing to the limited structural information available. Recent structural determination of GPCRs has advanced by modifying the receptors with stabilizing mutations, insertion of the protein T4 lysozyme and truncations of their amino acid sequences(8), as well as addition of stabilizing antibodies and small molecules(9) that facilitate crystallization in cubic phase monoolein mixtures(10). The intracellular loops of GPCRs are crucial for G-protein interactions(11), and activation of CXCR1 involves both amino-terminal residues and extracellular loops(2,12,13). Our previous nuclear magnetic resonance studies indicate that IL-8 binding to the N-terminal residues is mediated by the membrane, underscoring the importance of the phospholipid bilayer for physiological activity(14). Here we report the three-dimensional structure of human CXCR1 determined by NMR spectroscopy. The receptor is in liquid crystalline phospholipid bilayers, without modification of its amino acid sequence and under physiological conditions. Features important for intracellular G-protein activation and signal transduction are revealed. The structure of human CXCR1 in a lipid bilayer should help to facilitate the discovery of new compounds that interact with GPCRs and combat diseases such as breast cancer.
C1 [Park, Sang Ho; Das, Bibhuti B.; Casagrande, Fabio; Tian, Ye; Nothnagel, Henry J.; Chu, Mignon; Opella, Stanley J.] Univ Calif San Diego, Dept Chem & Biochem, La Jolla, CA 92093 USA.
   [Tian, Ye; Marassi, Francesca M.] Sanford Burnham Med Res Inst, La Jolla, CA 92037 USA.
   [Kiefer, Hans] HBC Hsch Biberach, D-88400 Biberach, Germany.
   [Maier, Klaus; De Angelis, Anna A.] Membrane Receptor Technol, San Diego, CA 92121 USA.
C3 University of California System; University of California San Diego; Sanford Burnham Prebys Medical Discovery Institute
RP Opella, SJ (corresponding author), Univ Calif San Diego, Dept Chem & Biochem, 9500 Gilman Dr, La Jolla, CA 92093 USA.
EM sopella@ucsd.edu
FU National Institutes of Health (NIH) [R01EB005161, R01GM075877, R21GM94727, R21GM075917, P01AI074805, P41EB002031]; Swiss National Science Foundation [PBBSP3-123151]; Novartis Foundation; Swiss National Science Foundation (SNF) [PBBSP3-123151] Funding Source: Swiss National Science Foundation (SNF)
NR 46
TC 393
Z9 472
U1 1
U2 322
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 29
PY 2012
VL 491
IS 7426
BP 779
EP +
DI 10.1038/nature11580
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 044FY
UT WOS:000311606000050
PM 23086146
DA 2026-03-09
ER

PT J
AU Cho, H
   Zhao, X
   Hatori, M
   Yu, RT
   Barish, GD
   Lam, MT
   Chong, LW
   DiTacchio, L
   Atkins, AR
   Glass, CK
   Liddle, C
   Auwerx, J
   Downes, M
   Panda, S
   Evans, RM
AF Cho, Han
   Zhao, Xuan
   Hatori, Megumi
   Yu, Ruth T.
   Barish, Grant D.
   Lam, Michael T.
   Chong, Ling-Wa
   DiTacchio, Luciano
   Atkins, Annette R.
   Glass, Christopher K.
   Liddle, Christopher
   Auwerx, Johan
   Downes, Michael
   Panda, Satchidananda
   Evans, Ronald M.
TI Regulation of circadian behaviour and metabolism by REV-ERB-α and REV-ERB-β
SO NATURE
LA English
DT Article
ID clock; receptor; transcription; rhythms; genes; roles; oscillator; mouse; liver; mice
AB The circadian clock acts at the genomic level to coordinate internal behavioural and physiological rhythms via the CLOCK-BMAL1 transcriptional heterodimer. Although the nuclear receptors REV-ERB-alpha and REV-ERB-beta have been proposed to form an accessory feedback loop that contributes to clock function(1,2), their precise roles and importance remain unresolved. To establish their regulatory potential, we determined the genome-wide cis-acting targets (cistromes) of both REV-ERB isoforms in murine liver, which revealed shared recognition at over 50% of their total DNA binding sites and extensive overlap with the master circadian regulator BMAL1. Although REV-ERB-alpha has been shown to regulate Bmal1 expression directly(1,2), our cistromic analysis reveals a more profound connection between BMAL1 and the REV-ERB-alpha and REV-ERB-beta genomic regulatory circuits than was previously suspected. Genes within the intersection of the BMAL1, REV-ERB-alpha and REV-ERB-beta cistromes are highly enriched for both clock and metabolic functions. As predicted by the cistromic analysis, dual depletion of Rev-erb-alpha and Rev-erb-beta function by creating double-knockout mice profoundly disrupted circadian expression of core circadian clock and lipid homeostatic gene networks. As a result, double-knockout mice show markedly altered circadian wheel-running behaviour and deregulated lipid metabolism. These data now unite REV-ERB-alpha and REV-ERB-beta with PER, CRY and other components of the principal feedback loop that drives circadian expression and indicate a more integral mechanism for the coordination of circadian rhythm and metabolism.
C1 [Cho, Han; Zhao, Xuan; Yu, Ruth T.; Barish, Grant D.; Chong, Ling-Wa; Atkins, Annette R.; Downes, Michael; Evans, Ronald M.] Salk Inst Biol Studies, Gene Express Lab, La Jolla, CA 92037 USA.
   [Hatori, Megumi; DiTacchio, Luciano; Panda, Satchidananda] Salk Inst Biol Studies, Regulatory Biol Lab, La Jolla, CA 92037 USA.
   [Lam, Michael T.; Glass, Christopher K.] Univ Calif San Diego, Sch Med, Dept Cellular & Mol Med, La Jolla, CA 92093 USA.
   [Liddle, Christopher] Westmead Millennium Inst, Storr Liver Unit, Westmead, NSW 2145, Australia.
   [Liddle, Christopher] Univ Sydney, Westmead Hosp, Westmead, NSW 2145, Australia.
   [Auwerx, Johan] Ecole Polytech Fed Lausanne, CH-1015 Lausanne, Switzerland.
   [Evans, Ronald M.] Salk Inst Biol Studies, Howard Hughes Med Inst, La Jolla, CA 92037 USA.
C3 Salk Institute; Salk Institute; University of California System; University of California San Diego; University of Sydney; Westmead Institute for Medical Research; University of Sydney; NSW Health; Westmead Hospital; Swiss Federal Institutes of Technology Domain; Ecole Polytechnique Federale de Lausanne; Howard Hughes Medical Institute; Salk Institute
RP Evans, RM (corresponding author), Salk Inst Biol Studies, Gene Express Lab, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA.
EM evans@salk.edu
FU National Research Service Award [T32-HL007770]; National Institutes of Health [DK062434, DK057978, DK090962, DK091618, HL105278]; National Health and Medical Research Council of Australia [NHMRC 512354, 632886]; Helmsley Charitable Trust; Glenn Foundation; Howard Hughes Medical Institute; National Health and Medical Research Council (NHMRC) [632886] Funding Source: National Health and Medical Research Council (NHMRC); National Cancer Institute [P30CA014195] Funding Source: NIH RePORTER; National Institute of Diabetes and Digestive and Kidney Diseases [R01DK057978] Funding Source: NIH RePORTER
NR 29
TC 858
Z9 1024
U1 1
U2 180
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 3
PY 2012
VL 485
IS 7396
BP 123
EP 127
DI 10.1038/nature11048
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 934NV
UT WOS:000303451900047
PM 22460952
DA 2026-03-09
ER

PT J
AU Booth, BBB
   Dunstone, NJ
   Halloran, PR
   Andrews, T
   Bellouin, N
AF Booth, Ben B. B.
   Dunstone, Nick J.
   Halloran, Paul R.
   Andrews, Timothy
   Bellouin, Nicolas
TI Aerosols implicated as a prime driver of twentieth-century North Atlantic climate variability
SO NATURE
LA English
DT Article
ID multidecadal oscillation; rainfall; temperatures
AB Systematic climate shifts have been linked to multidecadal variability in observed sea surface temperatures in the North Atlantic Ocean(1). These links are extensive, influencing a range of climate processes such as hurricane activity(2) and African Sahel(3-5) and Amazonian(5) droughts. The variability is distinct from historical global-mean temperature changes and is commonly attributed to natural ocean oscillations(6-10). A number of studies have provided evidence that aerosols can influence long-term changes in sea surface temperatures(11,12), but climate models have so far failed to reproduce these interactions(6,9) and the role of aerosols in decadal variability remains unclear. Here we use a state-of-the-art Earth system climate model to show that aerosol emissions and periods of volcanic activity explain 76 per cent of the simulated multidecadal variance in detrended 1860-2005 North Atlantic sea surface temperatures. After 1950, simulated variability is within observational estimates; our estimates for 1910-1940 capture twice the warming of previous generation models but do not explain the entire observed trend. Other processes, such as ocean circulation, may also have contributed to variability in the early twentieth century. Mechanistically, we find that inclusion of aerosol-cloud microphysical effects, which were included in few previous multimodel ensembles, dominates the magnitude (80 per cent) and the spatial pattern of the total surface aerosol forcing in the North Atlantic. Our findings suggest that anthropogenic aerosol emissions influenced a range of societally important historical climate events such as peaks in hurricane activity and Sahel drought. Decadal-scale model predictions of regional Atlantic climate will probably be improved by incorporating aerosol-cloud microphysical interactions and estimates of future concentrations of aerosols, emissions of which are directly addressable by policy actions.
C1 [Booth, Ben B. B.; Dunstone, Nick J.; Halloran, Paul R.; Andrews, Timothy; Bellouin, Nicolas] Met Off Hadley Ctr, Exeter EX1 3PB, Devon, England.
C3 Met Office - UK; Hadley Centre
RP Booth, BBB (corresponding author), Met Off Hadley Ctr, FitzRoy Rd, Exeter EX1 3PB, Devon, England.
EM ben.booth@metoffice.gov.uk
FU Office of Science, US Department of Energy; DECC/Defra Met Office Hadley Centre [GA01101]; EU
NR 30
TC 806
Z9 893
U1 5
U2 319
PU NATURE PUBLISHING 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 12
PY 2012
VL 484
IS 7393
BP 228
EP U110
DI 10.1038/nature10946
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 930OV
UT WOS:000303149900032
PM 22498628
DA 2026-03-09
ER

PT J
AU Ballantyne, AP
   Alden, CB
   Miller, JB
   Tans, PP
   White, JWC
AF Ballantyne, A. P.
   Alden, C. B.
   Miller, J. B.
   Tans, P. P.
   White, J. W. C.
TI Increase in observed net carbon dioxide uptake by land and oceans during the past 50 years
SO NATURE
LA English
DT Article
ID co2; trends; sink
AB One of the greatest sources of uncertainty for future climate predictions is the response of the global carbon cycle to climate change(1). Although approximately one-half of total CO2 emissions is at present taken up by combined land and ocean carbon reservoirs(2), models predict a decline in future carbon uptake by these reservoirs, resulting in a positive carbon-climate feedback(3). Several recent studies suggest that rates of carbon uptake by the land(4-6) and ocean(7-10) have remained constant or declined in recent decades. Other work, however, has called into question the reported decline(11-13). Here we use global-scale atmospheric CO2 measurements, CO2 emission inventories and their full range of uncertainties to calculate changes in global CO2 sources and sinks during the past 50 years. Our mass balance analysis shows that net global carbon uptake has increased significantly by about 0.05 billion tonnes of carbon per year and that global carbon uptake doubled, from 2.4 +/- 0.8 to 5.0 +/- 0.9 billion tonnes per year, between 1960 and 2010. Therefore, it is very unlikely that both land and ocean carbon sinks have decreased on a global scale. Since 1959, approximately 350 billion tonnes of carbon have been emitted by humans to the atmosphere, of which about 55 per cent has moved into the land and oceans. Thus, identifying the mechanisms and locations responsible for increasing global carbon uptake remains a critical challenge in constraining the modern global carbon budget and predicting future carbon-climate interactions.
C1 [Ballantyne, A. P.; White, J. W. C.] Univ Colorado, Dept Geol, Boulder, CO 80309 USA.
   [Alden, C. B.; White, J. W. C.] Univ Colorado, Inst Arctic & Alpine Res, Boulder, CO 80309 USA.
   [Miller, J. B.] Univ Colorado, Cooperat Inst Res Environm Sci, Boulder, CO 80309 USA.
   [Miller, J. B.; Tans, P. P.] Natl Oceanog & Atmospher Adm, Earth Syst Res Lab, Boulder, CO 80305 USA.
C3 University of Colorado System; University of Colorado Boulder; University of Colorado System; University of Colorado Boulder; University of Colorado System; University of Colorado Boulder; National Oceanic Atmospheric Admin (NOAA) - USA
RP Ballantyne, AP (corresponding author), Univ Montana, Dept Ecosyst & Conservat Sci, Missoula, MT 59812 USA.
EM apballantyne@gmail.com
FU US National Research Council; US National Science Foundation
NR 27
TC 577
Z9 681
U1 6
U2 617
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 2
PY 2012
VL 488
IS 7409
BP 70
EP +
DI 10.1038/nature11299
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 981ZE
UT WOS:000307010700034
PM 22859203
DA 2026-03-09
ER

PT J
AU Rowe, JH
   Ertelt, JM
   Xin, LJ
   Way, SS
AF Rowe, Jared H.
   Ertelt, James M.
   Xin, Lijun
   Way, Sing Sing
TI Pregnancy imprints regulatory memory that sustains anergy to fetal antigen
SO NATURE
LA English
DT Article
ID t-cells; foxp3(+); preeclampsia; expression; tolerance; expansion; selection; system
AB Pregnancy is an intricately orchestrated process where immune effector cells with fetal specificity are selectively silenced. This requires the sustained expansion of immune-suppressive maternal FOXP3(+) regulatory T cells (T-reg cells), because even transient partial ablation triggers fetal-specific effector T-cell activation and pregnancy loss(1,2). In turn, many idiopathic pregnancy complications proposed to originate from disrupted fetal tolerance are associated with blunted maternal T-reg expansion(3-5). Importantly, however, the antigen specificity and cellular origin of maternal Treg cells that accumulate during gestation remain incompletely defined. Here we show that pregnancy selectively stimulates the accumulation of maternal FOXP3(+) CD4 cells with fetal specificity using tetramer-based enrichment that allows the identification of rare endogenous T cells(6). Interestingly, after delivery, fetal-specific T-reg cells persist at elevated levels, maintain tolerance to pre-existing fetal antigen, and rapidly re-accumulate during subsequent pregnancy. The accelerated expansion of T-reg cells during secondary pregnancy was driven almost exclusively by proliferation of fetal-specific FOXP3(+) cells retained from prior pregnancy, whereas induced FOXP3 expression and proliferation of pre-existing FOXP3(+) cells each contribute to T-reg expansion during primary pregnancy. Furthermore, fetal resorption in secondary compared with primary pregnancy becomes more resilient to partial maternal FOXP3(+) cell ablation. Thus, pregnancy imprints FOXP3(+) CD4 cells that sustain protective regulatory memory to fetal antigen. We anticipate that these findings will spark further investigation on maternal regulatory T-cell specificity that unlocks new strategies for improving pregnancy outcomes and novel approaches for therapeutically exploiting T-reg cell memory.
C1 [Rowe, Jared H.; Ertelt, James M.; Xin, Lijun; Way, Sing Sing] Univ Minnesota, Sch Med, Ctr Infect Dis & Microbiol Translat Res, Ctr Immunol,Dept Pediat, Minneapolis, MN 55455 USA.
   [Rowe, Jared H.; Ertelt, James M.; Xin, Lijun; Way, Sing Sing] Univ Minnesota, Sch Med, Ctr Infect Dis & Microbiol Translat Res, Ctr Immunol,Dept Microbiol, Minneapolis, MN 55455 USA.
C3 University of Minnesota System; University of Minnesota Twin Cities; University of Minnesota System; University of Minnesota Twin Cities
RP Way, SS (corresponding author), Cincinnati Childrens Hosp Med Ctr, Div Infect Dis, Cincinnati, OH 45229 USA.
EM singsing.way@cchmc.org
FU NIH-NIAID [R01AI087830, R01AI100934]; NIH-NIDDK [F30DK084674]; Burroughs Wellcome Fund
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NR 34
TC 427
Z9 492
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 OCT 4
PY 2012
VL 490
IS 7418
BP 102
EP U119
DI 10.1038/nature11462
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 015LG
UT WOS:000309446800041
PM 23023128
DA 2026-03-09
ER

PT J
AU Khajavikhan, M
   Simic, A
   Katz, M
   Lee, JH
   Slutsky, B
   Mizrahi, A
   Lomakin, V
   Fainman, Y
AF Khajavikhan, M.
   Simic, A.
   Katz, M.
   Lee, J. H.
   Slutsky, B.
   Mizrahi, A.
   Lomakin, V.
   Fainman, Y.
TI Thresholdless nanoscale coaxial lasers
SO NATURE
LA English
DT Article
ID optical microcavity; spontaneous emission; linewidth; nanolaser; quantum
AB The effects of cavity quantum electrodynamics (QED), caused by the interaction of matter and the electromagnetic field in subwavelength resonant structures, have been the subject of intense research in recent years(1). The generation of coherent radiation by subwavelength resonant structures has attracted considerable interest, not only as a means of exploring the QED effects that emerge at small volume, but also for its potential in applications ranging from on-chip optical communication to ultrahigh-resolution and high-throughput imaging, sensing and spectroscopy. One such strand of research is aimed at developing the 'ultimate' nanolaser: a scalable, low-threshold, efficient source of radiation that operates at room temperature and occupies a small volume on a chip(2). Different resonators have been proposed for the realization of such a nanolaser-microdisk(3) and photonic bandgap(4) resonators, and, more recently, metallic(5,6), metallodielectric(7-10) and plasmonic(11,12) resonators. But progress towards realizing the ultimate nanolaser has been hindered by the lack of a systematic approach to scaling down the size of the laser cavity without significantly increasing the threshold power required for lasing. Here we describe a family of coaxial nanostructured cavities that potentially solve the resonator scalability challenge by means of their geometry and metal composition. Using these coaxial nanocavities, we demonstrate the smallest room-temperature, continuous-wave telecommunications-frequency laser to date. In addition, by further modifying the design of these coaxial nanocavities, we achieve thresholdless lasing with a broadband gain medium. In addition to enabling laser applications, these nanoscale resonators should provide a powerful platform for the development of other QED devices and metamaterials in which atom-field interactions generate new functionalities(13,14).
C1 [Khajavikhan, M.; Simic, A.; Katz, M.; Lee, J. H.; Slutsky, B.; Mizrahi, A.; Lomakin, V.; Fainman, Y.] Univ Calif San Diego, Dept Elect & Comp Engn, La Jolla, CA 92093 USA.
C3 University of California System; University of California San Diego
RP Khajavikhan, M (corresponding author), Univ Calif San Diego, Dept Elect & Comp Engn, 9500 Gilman Dr, La Jolla, CA 92093 USA.
EM mercedeh@umn.edu
FU Defense Advanced Research Projects Agency (DARPA); National Science Foundation (NSF); NSF Center for Integrated Access Networks (CIAN); Cymer Corporation; US Army Research Office; UCSD; Division Of Computer and Network Systems; Direct For Computer & Info Scie & Enginr [0923523] Funding Source: National Science Foundation
NR 30
TC 494
Z9 572
U1 3
U2 323
PU NATURE PUBLISHING 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 9
PY 2012
VL 482
IS 7384
BP 204
EP 207
DI 10.1038/nature10840
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 888HI
UT WOS:000299994100035
PM 22318604
DA 2026-03-09
ER

PT J
AU Senn, MS
   Wright, JP
   Attfield, JP
AF Senn, Mark S.
   Wright, Jon P.
   Attfield, J. Paul
TI Charge order and three-site distortions in the Verwey structure of magnetite
SO NATURE
LA English
DT Article
ID x-ray-diffraction; transition; fe3o4; temperature; oxides
AB The mineral magnetite (Fe(3)O(4)) undergoes a complex structural distortion and becomes electrically insulating at temperatures less than 125 kelvin. Verwey proposed in 1939 that this transition is driven by a charge ordering of Fe(2+) and Fe(3+) ions(1), but the ground state of the low-temperature phase has remained contentious(2,3) because twinning of crystal domains hampers diffraction studies of the structure(4). Recent powder diffraction refinements(5-7) and resonant X-ray studies(8-12) have led to proposals of a variety of charge-ordered and bond-dimerized ground-state models(13-19). Here we report the full low-temperature superstructure of magnetite, determined by high-energy X-ray diffraction from an almost single-domain, 40-micrometre grain, and identify the emergent order. The acentric structure is described by a superposition of 168 atomic displacement waves (frozen phonon modes), all with amplitudes of less than 0.24 angstroms. Distortions of the FeO(6) octahedra show that Verwey's hypothesis is correct to a first approximation and that the charge and Fe(2+) orbital order are consistent with a recent prediction(17). However, anomalous shortening of some Fe-Fe distances suggests that the localized electrons are distributed over linear three-Fe-site units, which we call 'trimerons'. The charge order and three-site distortions induce substantial off-centre atomic displacements and couple the resulting large electrical polarization to the magnetization. Trimerons may be important quasiparticles in magnetite above the Verwey transition and in other transition metal oxides.
C1 [Senn, Mark S.; Attfield, J. Paul] Univ Edinburgh, Ctr Sci Extreme Condit, Edinburgh EH9 3JZ, Midlothian, Scotland.
   [Senn, Mark S.; Attfield, J. Paul] Univ Edinburgh, Sch Chem, Edinburgh EH9 3JZ, Midlothian, Scotland.
   [Wright, Jon P.] European Synchrotron Radiat Facil, F-38043 Grenoble 9, France.
C3 University of Edinburgh; University of Edinburgh; European Synchrotron Radiation Facility (ESRF)
RP Attfield, JP (corresponding author), Univ Edinburgh, Ctr Sci Extreme Condit, W Mains Rd, Edinburgh EH9 3JZ, Midlothian, Scotland.
EM wright@esrf.fr; j.p.attfield@ed.ac.uk
FU Leverhulme Trust; EPSRC; STFC; EPSRC [EP/F02083X/1] Funding Source: UKRI; Engineering and Physical Sciences Research Council [EP/F02083X/1] Funding Source: researchfish
NR 29
TC 440
Z9 475
U1 4
U2 373
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JAN 12
PY 2012
VL 481
IS 7380
BP 173
EP 176
DI 10.1038/nature10704
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 874TO
UT WOS:000298981200033
PM 22190035
DA 2026-03-09
ER

PT J
AU Brogi, M
   Snellen, IAG
   de Kok, RJ
   Albrecht, S
   Birkby, J
   de Mooij, EJW
AF Brogi, Matteo
   Snellen, Ignas A. G.
   de Kok, Remco J.
   Albrecht, Simon
   Birkby, Jayne
   de Mooij, Ernst J. W.
TI The signature of orbital motion from the dayside of the planet τ Bootis b
SO NATURE
LA English
DT Article
ID reflected starlight; hot jupiters; upper limit; exoplanets; spectrum; catalog; stars; light
AB The giant planet orbiting tau Bootis (named tau Bootis b) was amongst the first extrasolar planets to be discovered(1). It is one of the brightest exoplanets and one of the nearest to us, with an orbital period of just a few days. Over the course of more than a decade, measurements of its orbital inclination have been announced(2) and refuted(3), and have hitherto remained elusive(4-8). Here we report the detection of carbon monoxide absorption in the thermal dayside spectrum of tau Bootis b. At a spectral resolution of similar to 100,000, we trace the change in the radial velocity of the planet over a large range in phase, determining an orbital inclination of 44.5 degrees +/- 1.5 degrees and a mass 5.95 +/- 0.28 times that of Jupiter, demonstrating that atmospheric characterization is possible for non-transiting planets. The strong absorption signal points to an atmosphere with a temperature that is decreasing towards higher altitudes, in contrast to the temperature inversion inferred for other highly irradiated planets(9,10). This supports the hypothesis that the absorbing compounds believed to cause such atmospheric inversions are destroyed in tau Bootis b by the ultraviolet emission from the active host star(11).
C1 [Brogi, Matteo; Snellen, Ignas A. G.; Birkby, Jayne; de Mooij, Ernst J. W.] Leiden Univ, Leiden Observ, NL-2300 RA Leiden, Netherlands.
   [de Kok, Remco J.] SRON, NL-3584 CA Utrecht, Netherlands.
   [Albrecht, Simon] MIT, Dept Phys, Cambridge, MA 02139 USA.
   [Albrecht, Simon] MIT, Kavli Inst Astrophys & Space Res, Cambridge, MA 02139 USA.
   [de Mooij, Ernst J. W.] Univ Toronto, Dept Astron & Astrophys, Toronto, ON M5S 3H4, Canada.
C3 Leiden University; Leiden University - Excl LUMC; Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); University of Toronto
RP Brogi, M (corresponding author), Leiden Univ, Leiden Observ, Postbus 9513, NL-2300 RA Leiden, Netherlands.
EM brogi@strw.leidenuniv.nl
FU Netherlands Organisation for Scientific Research (NWO); NSF [1108595]; Division Of Astronomical Sciences; Direct For Mathematical & Physical Scien [1108595] Funding Source: National Science Foundation; National Health and Medical Research Council (NHMRC) [1108595] Funding Source: National Health and Medical Research Council (NHMRC)
NR 22
TC 316
Z9 356
U1 2
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 JUN 28
PY 2012
VL 486
IS 7404
BP 502
EP 504
DI 10.1038/nature11161
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 965IJ
UT WOS:000305760600036
PM 22739313
DA 2026-03-09
ER

PT J
AU Hong, WZ
   Mosca, TJ
   Luo, LQ
AF Hong, Weizhe
   Mosca, Timothy J.
   Luo, Liqun
TI Teneurins instruct synaptic partner matching in an olfactory map
SO NATURE
LA English
DT Article
ID rich repeat proteins; transmembrane proteins; pair-rule; receptor neurons; drosophila; gene; expression; system; chemoaffinity; transgenesis
AB Neurons are interconnected with extraordinary precision to assemble a functional nervous system. Compared to axon guidance, far less is understood about how individual pre- and postsynaptic partners are matched. To ensure the proper relay of olfactory information in the fruitfly Drosophila, axons of similar to 50 classes of olfactory receptor neurons (ORNs) form one-to-one connections with dendrites of similar to 50 classes of projection neurons (PNs). Here, using genetic screens, we identified two evolutionarily conserved, epidermal growth factor (EGF)-repeat containing transmembrane Teneurin proteins, Ten-m and Ten-a, as synaptic-partner-matching molecules between PN dendrites and ORN axons. Ten-m and Ten-a are highly expressed in select PN-ORN matching pairs. Teneurin loss- and gain-of-function cause specific mismatching of select ORNs and PNs. Finally, Teneurins promote homophilic interactions in vitro, and Ten-m co-expression in non-partner PNs and ORNs promotes their ectopic connections in vivo. We propose that Teneurins instruct matching specificity between synaptic partners through homophilic attraction.
C1 [Hong, Weizhe; Mosca, Timothy J.; Luo, Liqun] Stanford Univ, Howard Hughes Med Inst, Dept Biol, Stanford, CA 94305 USA.
C3 Stanford University; Howard Hughes Medical Institute
RP Luo, LQ (corresponding author), Stanford Univ, Howard Hughes Med Inst, Dept Biol, Stanford, CA 94305 USA.
EM lluo@stanford.edu
FU National Institutes of Health (NIH) [R01 DC-005982, 5T32 NS007280, HD007249]; National Institute on Deafness and Other Communication Disorders [R01DC005982] Funding Source: NIH RePORTER
NR 63
TC 182
Z9 236
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 APR 12
PY 2012
VL 484
IS 7393
BP 201
EP +
DI 10.1038/nature10926
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 930OV
UT WOS:000303149900027
PM 22425994
DA 2026-03-09
ER

PT J
AU Straussman, R
   Morikawa, T
   Shee, K
   Barzily-Rokni, M
   Qian, ZR
   Du, JY
   Davis, A
   Mongare, MM
   Gould, J
   Frederick, DT
   Cooper, ZA
   Chapman, PB
   Solit, DB
   Ribas, A
   Lo, RS
   Flaherty, KT
   Ogino, S
   Wargo, JA
   Golub, TR
AF Straussman, Ravid
   Morikawa, Teppei
   Shee, Kevin
   Barzily-Rokni, Michal
   Qian, Zhi Rong
   Du, Jinyan
   Davis, Ashli
   Mongare, Margaret M.
   Gould, Joshua
   Frederick, Dennie T.
   Cooper, Zachary A.
   Chapman, Paul B.
   Solit, David B.
   Ribas, Antoni
   Lo, Roger S.
   Flaherty, Keith T.
   Ogino, Shuji
   Wargo, Jennifer A.
   Golub, Todd R.
TI Tumour micro-environment elicits innate resistance to RAF inhibitors through HGF secretion
SO NATURE
LA English
DT Article
ID c-met; acquired-resistance; colorectal-cancer; v600e mutation; growth-factor; colon-cancer; melanoma; braf; vemurafenib; overexpression
AB Drug resistance presents a challenge to the treatment of cancer patients. Many studies have focused on cell-autonomous mechanisms of drug resistance. By contrast, we proposed that the tumour micro-environment confers innate resistance to therapy. Here we developed a co-culture system to systematically assay the ability of 23 stromal cell types to influence the innate resistance of 45 cancer cell lines to 35 anticancer drugs. We found that stroma-mediated resistance is common, particularly to targeted agents. We characterized further the stroma-mediated resistance of BRAF-mutant melanoma to RAF inhibitors because most patients with this type of cancer show some degree of innate resistance(1-4). Proteomic analysis showed that stromal cell secretion of hepatocyte growth factor (HGF) resulted in activation of the HGF receptor MET, reactivation of the mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3-OH kinase (PI(3)K)-AKT signalling pathways, and immediate resistance to RAF inhibition. Immunohistochemistry experiments confirmed stromal cell expression of HGF in patients with BRAF-mutant melanoma and showed a significant correlation between HGF expression by stromal cells and innate resistance to RAF inhibitor treatment. Dual inhibition of RAF and either HGF or MET resulted in reversal of drug resistance, suggesting RAF plus HGF or MET inhibitory combination therapy as a potential therapeutic strategy for BRAF-mutant melanoma. A similar resistance mechanism was uncovered in a subset of BRAF-mutant colorectal and glioblastoma cell lines. More generally, this study indicates that the systematic dissection of interactions between tumours and their micro-environment can uncover important mechanisms underlying drug resistance.
C1 [Straussman, Ravid; Shee, Kevin; Barzily-Rokni, Michal; Du, Jinyan; Davis, Ashli; Mongare, Margaret M.; Gould, Joshua; Golub, Todd R.] Eli & Edythe L Broad Inst, Cambridge, MA 02142 USA.
   [Morikawa, Teppei; Qian, Zhi Rong; Ogino, Shuji] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
   [Frederick, Dennie T.; Cooper, Zachary A.; Flaherty, Keith T.; Wargo, Jennifer A.] Massachusetts Gen Hosp, Div Surg Oncol Med Oncol & Dermatol, Boston, MA 02114 USA.
   [Chapman, Paul B.; Solit, David B.] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10065 USA.
   [Solit, David B.] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10065 USA.
   [Ribas, Antoni] Univ Calif Los Angeles, Div Hematol & Oncol, Dept Med, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA.
   [Ribas, Antoni; Lo, Roger S.] Univ Calif Los Angeles, Dept Mol & Med Pharmacol, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA.
   [Lo, Roger S.] Univ Calif Los Angeles, Div Dermatol, Dept Med, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA.
   [Ogino, Shuji] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
   [Ogino, Shuji; Golub, Todd R.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
   [Golub, Todd R.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
   [Golub, Todd R.] Howard Hughes Med Inst, Chevy Chase, MD 20815 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; Memorial Sloan Kettering Cancer Center; Memorial Sloan Kettering Cancer Center; UCLA Jonsson Comprehensive Cancer Center; University of California System; University of California Los Angeles; UCLA Jonsson Comprehensive Cancer Center; University of California System; University of California Los Angeles; UCLA Jonsson Comprehensive Cancer Center; University of California System; University of California Los Angeles; 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; Howard Hughes Medical Institute
RP Golub, TR (corresponding author), Eli & Edythe L Broad Inst, 7 Cambridge Ctr, Cambridge, MA 02142 USA.
EM golub@broadinstitute.org
FU Howard Hughes Medical Institute; National Cancer Institute [P50CA093683, U54CA112962]; Melanoma Research Alliance Team Science Award; National Cancer Institute [R01CA166480] Funding Source: NIH RePORTER
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NR 30
TC 1492
Z9 1752
U1 1
U2 349
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUL 26
PY 2012
VL 487
IS 7408
BP 500
EP U118
DI 10.1038/nature11183
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 979KD
UT WOS:000306815300042
PM 22763439
DA 2026-03-09
ER

PT J
AU Song, J
   Zhong, C
   Bonaguidi, MA
   Sun, GJ
   Hsu, D
   Gu, Y
   Meletis, K
   Huang, ZJ
   Ge, SY
   Enikolopov, G
   Deisseroth, K
   Luscher, B
   Christian, KM
   Ming, GL
   Song, HJ
AF Song, Juan
   Zhong, Chun
   Bonaguidi, Michael A.
   Sun, Gerald J.
   Hsu, Derek
   Gu, Yan
   Meletis, Konstantinos
   Huang, Z. Josh
   Ge, Shaoyu
   Enikolopov, Grigori
   Deisseroth, Karl
   Luscher, Bernhard
   Christian, Kimberly M.
   Ming, Guo-li
   Song, Hongjun
TI Neuronal circuitry mechanism regulating adult quiescent neural stem-cell fate decision
SO NATURE
LA English
DT Article
ID newly generated neurons; immunoreactive neurons; neurogenesis; brain; receptors; system
AB Adult neurogenesis arises from neural stem cells within specialized niches(1-3). Neuronal activity and experience, presumably acting on this local niche, regulate multiple stages of adult neurogenesis, from neural progenitor proliferation to new neuron maturation, synaptic integration and survival(1,3). It is unknown whether local neuronal circuitry has a direct impact on adult neural stem cells. Here we show that, in the adult mouse hippocampus, nestin-expressing radial glia-like quiescent neural stem cells(4-9) (RGLs) respond tonically to the neurotransmitter gamma-aminobutyric acid (GABA) by means of gamma(2)-subunit-containing GABA(A) receptors. Clonal analysis(9) of individual RGLs revealed a rapid exit from quiescence and enhanced symmetrical self-renewal after conditional deletion of gamma(2). RGLs are in close proximity to terminals expressing 67-kDa glutamic acid decarboxylase (GAD67) of parvalbumin-expressing (PV+) interneurons and respond tonically to GABA released from these neurons. Functionally, optogenetic control of the activity of dentate PV+ interneurons, but not that of somatostatin-expressing or vasoactive intestinal polypeptide (VIP)-expressing interneurons, can dictate the RGL choice between quiescence and activation. Furthermore, PV+ interneuron activation restores RGL quiescence after social isolation, an experience that induces RGL activation and symmetrical division(8). Our study identifies a niche cell-signal-receptor trio and a local circuitry mechanism that control the activation and self-renewal mode of quiescent adult neural stem cells in response to neuronal activity and experience.
C1 [Song, Juan; Zhong, Chun; Bonaguidi, Michael A.; Sun, Gerald J.; Hsu, Derek; Christian, Kimberly M.; Ming, Guo-li; Song, Hongjun] Johns Hopkins Univ, Sch Med, Inst Cell Engn, Baltimore, MD 21205 USA.
   [Song, Juan; Zhong, Chun; Bonaguidi, Michael A.; Christian, Kimberly M.; Ming, Guo-li; Song, Hongjun] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA.
   [Sun, Gerald J.; Ming, Guo-li; Song, Hongjun] Johns Hopkins Univ, Sch Med, Solomon H Snyder Dept Neurosci, Baltimore, MD 21205 USA.
   [Gu, Yan; Ge, Shaoyu] SUNY Stony Brook, Dept Neurobiol & Behav, Stony Brook, NY 11794 USA.
   [Meletis, Konstantinos] Karolinska Inst, Dept Neurosci, S-17177 Stockholm, Sweden.
   [Huang, Z. Josh; Enikolopov, Grigori] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA.
   [Deisseroth, Karl] Stanford Univ, Dept Bioengn, Stanford, CA 94305 USA.
   [Luscher, Bernhard] Penn State Univ, Dept Biol, University Pk, PA 16802 USA.
C3 Johns Hopkins University; Johns Hopkins University; Johns Hopkins University; State University of New York (SUNY) System; Stony Brook University; Karolinska Institutet; Cold Spring Harbor Laboratory; Stanford University; Pennsylvania Commonwealth System of Higher Education (PCSHE); Pennsylvania State University; Pennsylvania State University - University Park
RP Song, HJ (corresponding author), Johns Hopkins Univ, Sch Med, Inst Cell Engn, Baltimore, MD 21205 USA.
EM gming1@jhmi.edu; shongju1@jhmi.edu
FU National Institutes of Health (NIH) [NS047344, NS048271, HD069184, MH089111, AG040209]; National Alliance for Research on Schizophrenia and Depression; Adelson Medical Research Foundation; New York State Stem Cell Science; Ellison Medical Foundation; Life Sciences Research Foundation; Maryland Stem Cell Research Fund
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   Seri B, 2001, J NEUROSCI, V21, P7153, DOI 10.1523/JNEUROSCI.21-18-07153.2001
   Taniguchi H, 2011, NEURON, V71, P995, DOI 10.1016/j.neuron.2011.07.026
   Zhao CM, 2008, CELL, V132, P645, DOI 10.1016/j.cell.2008.01.033
NR 30
TC 408
Z9 492
U1 6
U2 101
PU NATURE PUBLISHING 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 6
PY 2012
VL 489
IS 7414
BP 150
EP U216
DI 10.1038/nature11306
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 999WW
UT WOS:000308347000053
PM 22842902
DA 2026-03-09
ER

PT J
AU Shui, JW
   Larange, A
   Kim, G
   Vela, JL
   Zahner, S
   Cheroutre, H
   Kronenberg, M
AF Shui, Jr-Wen
   Larange, Alexandre
   Kim, Gisen
   Vela, Jose Luis
   Zahner, Sonja
   Cheroutre, Hilde
   Kronenberg, Mitchell
TI HVEM signalling at mucosal barriers provides host defence against pathogenic bacteria
SO NATURE
LA English
DT Article
ID nf-kappa-b; herpesvirus entry mediator; citrobacter-rodentium; protects mice; nk cells; receptor; il-22; innate; expression; infection
AB The herpes virus entry mediator (HVEM), a member of the tumour-necrosis factor receptor family, has diverse functions, augmenting or inhibiting the immune response(1). HVEM was recently reported as a colitis risk locus in patients(2), and in a mouse model of colitis we demonstrated an anti-inflammatory role for HVEM3, but its mechanism of action in the mucosal immune system was unknown. Here we report an important role for epithelial HVEM in innate mucosal defence against pathogenic bacteria. HVEM enhances immune responses by NF-kappa B-inducing kinase-dependent Stat3 activation, which promotes the epithelial expression of genes important for immunity. During intestinal Citrobacter rodentium infection(4-6), a mouse model for enteropathogenic Escherichia coli infection, Hvem(-/-) mice showed decreased Stat3 activation, impaired responses in the colon, higher bacterial burdens and increased mortality. We identified the immunoglobulin superfamily molecule CD160 (refs 7 and 8), expressed predominantly by innate-like intraepithelial lymphocytes, as the ligand engaging epithelial HVEM for host protection. Likewise, in pulmonary Streptococcus pneumoniae infection(9), HVEM is also required for host defence. Our results pinpoint HVEM as an important orchestrator of mucosal immunity, integrating signals from innate lymphocytes to induce optimal epithelial Stat3 activation, which indicates that targeting HVEM with agonists could improve host defence.
C1 [Shui, Jr-Wen; Larange, Alexandre; Kim, Gisen; Vela, Jose Luis; Zahner, Sonja; Cheroutre, Hilde; Kronenberg, Mitchell] La Jolla Inst Allergy & Immunol, Div Dev Immunol, La Jolla, CA 92037 USA.
C3 La Jolla Institute for Immunology
RP Kronenberg, M (corresponding author), La Jolla Inst Allergy & Immunol, Div Dev Immunol, 9420 Athena Circle, La Jolla, CA 92037 USA.
EM mitch@liai.org
FU National Institutes of Health [RO1-AI061516, PO1 DK46763, F32-DK082249, F32-AI083029]; La Jolla Institute for Allergy and Immunology; Center for Infectious Disease [LIAI-JAN-2011-CID]
NR 33
TC 117
Z9 140
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 AUG 9
PY 2012
VL 488
IS 7410
BP 222
EP +
DI 10.1038/nature11242
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 985LE
UT WOS:000307267000036
PM 22801499
DA 2026-03-09
ER

PT J
AU Dumusque, X
   Pepe, F
   Lovis, C
   Ségransan, D
   Sahlmann, J
   Benz, W
   Bouchy, F
   Mayor, M
   Queloz, D
   Santos, N
   Udry, S
AF Dumusque, Xavier
   Pepe, Francesco
   Lovis, Christophe
   Segransan, Damien
   Sahlmann, Johannes
   Benz, Willy
   Bouchy, Francois
   Mayor, Michel
   Queloz, Didier
   Santos, Nuno
   Udry, Stephane
TI An Earth-mass planet orbiting α Centauri B
SO NATURE
LA English
DT Article
ID solar-like oscillations; line asymmetry; habitable zone; stars; rotation; search; dwarf; i.
AB Exoplanets down to the size of Earth have been found, but not in the habitable zone-that is, at a distance from the parent star at which water, if present, would be liquid. There are planets in the habitable zone of stars cooler than our Sun, but for reasons such as tidal locking and strong stellar activity, they are unlikely to harbour water-carbon life as we know it. The detection of a habitable Earth-mass planet orbiting a star similar to our Sun is extremely difficult, because such a signal is overwhelmed by stellar perturbations. Here we report the detection of an Earth-mass planet orbiting our neighbour star alpha Centauri B, a member of the closest stellar system to the Sun. The planet has an orbital period of 3.236 days and is about 0.04 astronomical units from the star (one astronomical unit is the Earth-Sun distance).
C1 [Dumusque, Xavier; Pepe, Francesco; Lovis, Christophe; Segransan, Damien; Sahlmann, Johannes; Bouchy, Francois; Mayor, Michel; Queloz, Didier; Udry, Stephane] Univ Geneva, Observ Geneve, CH-1290 Sauverny, Switzerland.
   [Dumusque, Xavier; Santos, Nuno] Univ Porto, Ctr Astrofis, P-4150762 Oporto, Portugal.
   [Benz, Willy] Univ Bern, Inst Phys, CH-3012 Bern, Switzerland.
   [Bouchy, Francois] Univ Paris 06, CNRS, Inst Astrophys Paris, UMR7095, F-75014 Paris, France.
   [Santos, Nuno] Univ Porto, Fac Ciencias, Dept Fis & Astron, P-4169007 Oporto, Portugal.
C3 University of Geneva; Universidade do Porto; University of Bern; Sorbonne Universite; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Earth Sciences & Astronomy (INSU); Universidade do Porto
RP Dumusque, X (corresponding author), Univ Geneva, Observ Geneve, 51 Chemin Maillettes, CH-1290 Sauverny, Switzerland.
EM xavier.dumusque@unige.ch; francesco.pepe@unige.ch
FU European Research Council/European Community [239953]; Fundacao para a Ciencia e a Tecnologia (FCT); FCT/MCTES (Portugal); POPH/FSE (EC);  [PTDC/CTE-AST/098528/2008];  [PTDC/CTE-AST/098604/2008]; Fundação para a Ciência e a Tecnologia [PTDC/CTE-AST/098604/2008] Funding Source: FCT
NR 41
TC 320
Z9 371
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 NOV 8
PY 2012
VL 491
IS 7423
BP 207
EP 211
DI 10.1038/nature11572
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 033DP
UT WOS:000310774300034
PM 23075844
DA 2026-03-09
ER

PT J
AU Litvak, V
   Ratushny, AV
   Lampano, AE
   Schmitz, F
   Huang, AC
   Raman, A
   Rust, AG
   Bergthaler, A
   Aitchison, JD
   Aderem, A
AF Litvak, Vladimir
   Ratushny, Alexander V.
   Lampano, Aaron E.
   Schmitz, Frank
   Huang, Albert C.
   Raman, Ayush
   Rust, Alistair G.
   Bergthaler, Andreas
   Aitchison, John D.
   Aderem, Alan
TI A FOXO3-IRF7 gene regulatory circuit limits inflammatory sequelae of antiviral responses
SO NATURE
LA English
DT Article
ID forkhead transcription factors; histone acetylation; expression; activation; database; cells
AB Antiviral responses must be tightly regulated to defend rapidly against infection while minimizing inflammatory damage. Type 1 interferons (IFN-I) are crucial mediators of antiviral responses(1) and their transcription is regulated by a variety of transcription factors(2); principal among these is the family of interferon regulatory factors (IRFs)(3). The IRF gene regulatory networks are complex and contain multiple feedback loops. The tools of systems biology are well suited to elucidate the complex interactions that give rise to precise coordination of the interferon response. Here we have used an unbiased systems approach to predict that a member of the forkhead family of transcription factors, FOXO3, is a negative regulator of a subset of antiviral genes. This prediction was validated using macrophages isolated from Foxo3-null mice. Genome-wide location analysis combined with gene deletion studies identified the Irf7 gene as a critical target of FOXO3. FOXO3 was identified as a negative regulator of Irf7 transcription and we have further demonstrated that FOXO3, IRF7 and IFN-I forma coherent feed-forward regulatory circuit. Our data suggest that the FOXO3-IRF7 regulatory circuit represents a novel mechanism for establishing the requisite set points in the interferon pathway that balances the beneficial effects and deleterious sequelae of the antiviral response.
C1 [Litvak, Vladimir; Ratushny, Alexander V.; Lampano, Aaron E.; Schmitz, Frank; Aitchison, John D.; Aderem, Alan] Seattle Biomed Res Inst, Seattle, WA 98109 USA.
   [Ratushny, Alexander V.; Huang, Albert C.; Raman, Ayush; Aitchison, John D.] Inst Syst Biol, Seattle, WA 98109 USA.
   [Rust, Alistair G.] Welcome Trust Sanger Inst, Cambridge CB10 1HH, England.
   [Bergthaler, Andreas] Austrian Acad Sci, Res Ctr Mol Med, A-1090 Vienna, Austria.
C3 Center for Infectious Disease Research; Institute for Systems Biology (ISB); Wellcome Trust Sanger Institute; Austrian Academy of Sciences
RP Aderem, A (corresponding author), Seattle Biomed Res Inst, 4 Nickerson St, Seattle, WA 98109 USA.
EM alan.aderem@seattlebiomed.org
FU National Institutes of Health [R01AI025032, R01AI032972, HHSN272200700038C, HHSN272200800058C, U54GM103511]; National Institute of Allergy and Infectious Diseases [U19AI100627] Funding Source: NIH RePORTER
NR 37
TC 125
Z9 141
U1 0
U2 24
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 18
PY 2012
VL 490
IS 7420
BP 421
EP +
DI 10.1038/nature11428
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 021XI
UT WOS:000309918500050
PM 22982991
DA 2026-03-09
ER

PT J
AU Kirwan, ML
   Mudd, SM
AF Kirwan, Matthew L.
   Mudd, Simon M.
TI Response of salt-marsh carbon accumulation to climate change
SO NATURE
LA English
DT Article
ID coastal wetlands; spartina-alterniflora; decomposition; productivity; feedback; dioxide; drag
AB About half of annual marine carbon burial takes place in shallow water ecosystems where geomorphic and ecological stability is driven by interactions between the flow of water, vegetation growth and sediment transport(1). Although the sensitivity of terrestrial and deep marine carbon pools to climate change has been studied for decades, there is little understanding of how coastal carbon accumulation rates will change and potentially feed back on climate(2,3). Here we develop a numerical model of salt marsh evolution, informed by recent measurements of productivity and decomposition, and demonstrate that competition between mineral sediment deposition and organic-matter accumulation determines the net impact of climate change on carbon accumulation in intertidal wetlands. We find that the direct impact of warming on soil carbon accumulation rates is more subtle than the impact of warming-driven sea level rise, although the impact of warming increases with increasing rates of sea level rise. Our simulations suggest that the net impact of climate change will be to increase carbon burial rates in the first half of the twenty-first century, but that carbon-climate feedbacks are likely to diminish over time.
C1 [Kirwan, Matthew L.] Univ Virginia, Dept Environm Sci, Charlottesville, VA 24151 USA.
   [Mudd, Simon M.] Univ Edinburgh, Sch GeoSci, Edinburgh EH8 9XP, Midlothian, Scotland.
   [Mudd, Simon M.] Univ Calif Santa Barbara, Earth Res Inst, Santa Barbara, CA 93106 USA.
C3 University of Virginia; University of Edinburgh; University of California System; University of California Santa Barbara
RP Kirwan, ML (corresponding author), Univ Virginia, Dept Environm Sci, POB 400123, Charlottesville, VA 24151 USA.
EM mlk4n@virginia.edu
FU USGS Global Change Research Program
NR 32
TC 285
Z9 365
U1 17
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 SEP 27
PY 2012
VL 489
IS 7417
BP 550
EP +
DI 10.1038/nature11440
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 011LT
UT WOS:000309167100047
PM 23018965
DA 2026-03-09
ER

PT J
AU Yatsunenko, T
   Rey, FE
   Manary, MJ
   Trehan, I
   Dominguez-Bello, MG
   Contreras, M
   Magris, M
   Hidalgo, G
   Baldassano, RN
   Anokhin, AP
   Heath, AC
   Warner, B
   Reeder, J
   Kuczynski, J
   Caporaso, JG
   Lozupone, CA
   Lauber, C
   Clemente, JC
   Knights, D
   Knight, R
   Gordon, JI
AF Yatsunenko, Tanya
   Rey, Federico E.
   Manary, Mark J.
   Trehan, Indi
   Dominguez-Bello, Maria Gloria
   Contreras, Monica
   Magris, Magda
   Hidalgo, Glida
   Baldassano, Robert N.
   Anokhin, Andrey P.
   Heath, Andrew C.
   Warner, Barbara
   Reeder, Jens
   Kuczynski, Justin
   Caporaso, J. Gregory
   Lozupone, Catherine A.
   Lauber, Christian
   Clemente, Jose Carlos
   Knights, Dan
   Knight, Rob
   Gordon, Jeffrey I.
TI Human gut microbiome viewed across age and geography
SO NATURE
LA English
DT Article
ID free amino-acids; bacterial community; normal men; urea; nitrogen; cluster; diet; validation; succession; patterns
AB Gut microbial communities represent one source of human genetic and metabolic diversity. To examine how gut microbiomes differ among human populations, here we characterize bacterial species in fecal samples from 531 individuals, plus the gene content of 110 of them. The cohort encompassed healthy children and adults from the Amazonas of Venezuela, rural Malawi and US metropolitan areas and included mono-and dizygotic twins. Shared features of the functional maturation of the gut microbiome were identified during the first three years of life in all three populations, including age-associated changes in the genes involved in vitamin biosynthesis and metabolism. Pronounced differences in bacterial assemblages and functional gene repertoires were noted between US residents and those in the other two countries. These distinctive features are evident in early infancy as well as adulthood. Our findings underscore the need to consider the microbiome when evaluating human development, nutritional needs, physiological variations and the impact of westernization.
C1 [Yatsunenko, Tanya; Rey, Federico E.; Gordon, Jeffrey I.] Washington Univ, Sch Med, Ctr Genome Sci & Syst Biol, St Louis, MO 63108 USA.
   [Manary, Mark J.; Trehan, Indi; Warner, Barbara] Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA.
   [Manary, Mark J.] Univ Malawi, Dept Community Hlth, Coll Med, Blantyre, Malawi.
   [Trehan, Indi] Univ Malawi, Dept Paediat & Child Hlth, Coll Med, Blantyre, Malawi.
   [Dominguez-Bello, Maria Gloria] Univ Puerto Rico, Dept Biol, Rio Piedras, PR 00931 USA.
   [Contreras, Monica] Venezuelan Inst Sci Res IVIC, Altos De Pipe, Venezuela.
   [Magris, Magda; Hidalgo, Glida] Amazon Ctr Res & Control Trop Dis CAICET, Amazonas, Venezuela.
   [Baldassano, Robert N.] Childrens Hosp Philadelphia, Div Gastroenterol & Nutr, Philadelphia, PA 19104 USA.
   [Anokhin, Andrey P.; Heath, Andrew C.] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA.
   [Reeder, Jens; Kuczynski, Justin; Lozupone, Catherine A.; Lauber, Christian; Clemente, Jose Carlos; Knights, Dan; Knight, Rob] Univ Colorado, Dept Chem & Biochem, Boulder, CO 80309 USA.
   [Caporaso, J. Gregory] No Arizona Univ, Dept Comp Sci, Flagstaff, AZ 86001 USA.
   [Knight, Rob] Univ Colorado, Howard Hughes Med Inst, Boulder, CO 80309 USA.
C3 Washington University (WUSTL); Washington University (WUSTL); University of Malawi; University of Malawi; University of Puerto Rico; University of Puerto Rico Medical Sciences Campus; University of Puerto Rico Rio Piedras; Venezuelan Institute Science Research; University of Pennsylvania; Pennsylvania Medicine; Childrens Hospital of Philadelphia; Washington University (WUSTL); University of Colorado System; University of Colorado Boulder; Northern Arizona University; University of Colorado System; University of Colorado Boulder; Howard Hughes Medical Institute
RP Gordon, JI (corresponding author), Washington Univ, Sch Med, Ctr Genome Sci & Syst Biol, St Louis, MO 63108 USA.
EM jgordon@wustl.edu
FU National Institutes of Health [DK078669, T32-HD049338]; St. Louis Children's Discovery Institute [MD112009-201]; Howard Hughes Medical Institute; Crohn's and Colitis Foundation of America; Bill and Melinda Gates Foundation; National Science Foundation [CNS-0821794]; University of Colorado, Boulder; University of Colorado, Denver; National Center for Atmospheric Research; Div Of Biological Infrastructure; Direct For Biological Sciences [0959864] Funding Source: National Science Foundation; Action Medical Research; Crohn&apos;s & Colitis Foundation [2158] Funding Source: researchfish
NR 39
TC 5824
Z9 7075
U1 21
U2 1863
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 14
PY 2012
VL 486
IS 7402
BP 222
EP +
DI 10.1038/nature11053
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 957UH
UT WOS:000305189000027
PM 22699611
DA 2026-03-09
ER

PT J
AU Golzio, C
   Willer, J
   Talkowski, ME
   Oh, EC
   Taniguchi, Y
   Jacquemont, S
   Reymond, A
   Sun, M
   Sawa, A
   Gusella, JF
   Kamiya, A
   Beckmann, JS
   Katsanis, N
AF Golzio, Christelle
   Willer, Jason
   Talkowski, Michael E.
   Oh, Edwin C.
   Taniguchi, Yu
   Jacquemont, Sebastien
   Reymond, Alexandre
   Sun, Mei
   Sawa, Akira
   Gusella, James F.
   Kamiya, Atsushi
   Beckmann, Jacques S.
   Katsanis, Nicholas
TI KCTD13 is a major driver of mirrored neuroanatomical phenotypes of the 16p11.2 copy number variant
SO NATURE
LA English
DT Article
ID tooth disease type-1a; microdeletion syndrome; chromosome 16p11.2; syndrome region; autism; gene; schizophrenia; duplications; association; deletions
AB Copy number variants (CNVs) are major contributors to genetic disorders(1). We have dissected a region of the 16p11.2 chromosome-which encompasses 29 genes-that confers susceptibility to neurocognitive defects when deleted or duplicated(2,3). Overexpression of each human transcript in zebrafish embryos identified KCTD13 as the sole message capable of inducing the microcephaly phenotype associated with the 16p11.2 duplication(2-5), whereas suppression of the same locus yielded the macrocephalic phenotype associated with the 16p11.2 deletion(5,6), capturing the mirror phenotypes of humans. Analyses of zebrafish and mouse embryos suggest that microcephaly is caused by decreased proliferation of neuronal progenitors with concomitant increase in apoptosis in the developing brain, whereas macrocephaly arises by increased proliferation and no changes in apoptosis. A role for KCTD13 dosage changes is consistent with autism in both a recently reported family with a reduced 16p11.2 deletion and a subject reported here with a complex 16p11.2 rearrangement involving de novo structural alteration of KCTD13. Our data suggest that KCTD13 is a major driver for the neurodevelopmental phenotypes associated with the 16p11.2 CNV, reinforce the idea that one or a small number of transcripts within a CNV can underpin clinical phenotypes, and offer an efficient route to identifying dosage-sensitive loci.
C1 [Golzio, Christelle; Willer, Jason; Oh, Edwin C.; Katsanis, Nicholas] Duke Univ, Ctr Human Dis Modeling, Durham, NC 27710 USA.
   [Golzio, Christelle; Willer, Jason; Oh, Edwin C.; Katsanis, Nicholas] Duke Univ, Dept Cell Biol, Durham, NC 27710 USA.
   [Talkowski, Michael E.; Sun, Mei; Gusella, James F.] Massachusetts Gen Hosp, Ctr Human Genet Res, Mol Neurogenet Unit, Boston, MA 02114 USA.
   [Talkowski, Michael E.; Gusella, James F.] Harvard Univ, Sch Med, Dept Neurol & Genet, Boston, MA 02115 USA.
   [Taniguchi, Yu; Sawa, Akira; Kamiya, Atsushi] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21287 USA.
   [Jacquemont, Sebastien; Beckmann, Jacques S.] CHU Vaudois, Serv Med Genet, CH-1011 Lausanne, Switzerland.
   [Reymond, Alexandre] Univ Lausanne, Ctr Integrat Gen, CH-1015 Lausanne, Switzerland.
   [Beckmann, Jacques S.] Univ Lausanne, Dept Med Genet, CH-1005 Lausanne, Switzerland.
   [Katsanis, Nicholas] Duke Univ, Dept Pediat, Durham, NC 27710 USA.
C3 Duke University; Duke University; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard Medical School; Johns Hopkins University; University of Lausanne; Centre Hospitalier Universitaire Vaudois (CHUV); University of Lausanne; University of Lausanne; Duke University
RP Katsanis, N (corresponding author), Duke Univ, Ctr Human Dis Modeling, Durham, NC 27710 USA.
EM katsanis@cellbio.duke.edu
FU Silvo O. Conte center from the National Institute of Mental Health (NIMH), National Institutes of Health [MH-094268, MH-084018, MH-091230, HD06286]; Simon's Foundation; Autism Consortium of Boston; Leenaards Foundation; Swiss National Science Foundation; Swiss National Science Foundation Sinergia; NIMH National Research Service [F32MH087123]; bourse de releve academique de la Faculte de Biologie et Medecine de l'Universite de Lausanne
NR 31
TC 325
Z9 375
U1 0
U2 47
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD MAY 17
PY 2012
VL 485
IS 7398
BP 363
EP U111
DI 10.1038/nature11091
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 943CW
UT WOS:000304099100041
PM 22596160
DA 2026-03-09
ER

PT J
AU Archin, NM
   Liberty, AL
   Kashuba, AD
   Choudhary, SK
   Kuruc, JD
   Crooks, AM
   Parker, DC
   Anderson, EM
   Kearney, MF
   Strain, MC
   Richman, DD
   Hudgens, MG
   Bosch, RJ
   Coffin, JM
   Eron, JJ
   Hazuda, DJ
   Margolis, DM
AF Archin, N. M.
   Liberty, A. L.
   Kashuba, A. D.
   Choudhary, S. K.
   Kuruc, J. D.
   Crooks, A. M.
   Parker, D. C.
   Anderson, E. M.
   Kearney, M. F.
   Strain, M. C.
   Richman, D. D.
   Hudgens, M. G.
   Bosch, R. J.
   Coffin, J. M.
   Eron, J. J.
   Hazuda, D. J.
   Margolis, D. M.
TI Administration of vorinostat disrupts HIV-1 latency in patients on antiretroviral therapy
SO NATURE
LA English
DT Article
ID histone deacetylase inhibitors; suberoylanilide hydroxamic acid; valproic acid; in-vivo; type-1; expression; infection; cells; pcr; activation
AB Despite antiretroviral therapy, proviral latency of human immunodeficiency virus type 1 (HIV-1) remains a principal obstacle to curing the infection(1). Inducing the expression of latent genomes within resting CD4(+) T cells is the primary strategy to clear this reservoir(2,3). Although histone deacetylase inhibitors such as suberoylanilide hydroxamic acid (also known as vorinostat, VOR) can disrupt HIV-1 latency in vitro(4-6), the utility of this approach has never been directly proven in a translational clinical study of HIV-infected patients. Here we isolated the circulating resting CD4(+) T cells of patients in whom viraemia was fully suppressed by antiretroviral therapy, and directly studied the effect of VOR on this latent reservoir. In each of eight patients, a single dose of VOR increased both biomarkers of cellular acetylation, and simultaneously induced an increase in HIV RNA expression in resting CD4(+) cells (mean increase, 4.8-fold). This demonstrates that a molecular mechanism known to enforce HIV latency can be therapeutically targeted in humans, provides proof-of-concept for histone deacetylase inhibitors as a therapeutic class, and defines a precise approach to test novel strategies to attack and eradicate latent HIV infection directly.
C1 [Archin, N. M.; Liberty, A. L.; Kashuba, A. D.; Choudhary, S. K.; Kuruc, J. D.; Crooks, A. M.; Parker, D. C.; Hudgens, M. G.; Eron, J. J.; Margolis, D. M.] Univ N Carolina, Chapel Hill, NC 27599 USA.
   [Anderson, E. M.; Kearney, M. F.; Coffin, J. M.] NCI, HIV Drug Resistance Program, NIH, Frederick, MD 21702 USA.
   [Strain, M. C.; Richman, D. D.] VA San Diego Healthcare Syst, San Diego, CA 92093 USA.
   [Strain, M. C.; Richman, D. D.] Univ Calif San Diego, San Diego, CA 92093 USA.
   [Bosch, R. J.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
   [Hazuda, D. J.] Merck Res Labs, White Horse Junction, PA USA.
C3 University of North Carolina; University of North Carolina Chapel Hill; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); US Department of Veterans Affairs; Veterans Health Administration (VHA); VA San Diego Healthcare System; University of California System; University of California San Diego; Harvard University; Harvard T.H. Chan School of Public Health; Merck & Company
RP Margolis, DM (corresponding author), Univ N Carolina, Chapel Hill, NC 27599 USA.
EM dmargo@med.unc.edu
FU National Institutes of Health [AI084553, AI095052, AI096113, RR024383, AI50410]; Merck Co; James B. Pendleton Charitable Trust; Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Institute of Allergy and Infectious Diseases; National Institute of Nursing Research; National Institute on Aging; National Institute of Dental and Craniofacial Research; National Institute on Minority Health and Health Disparities; National Cancer Institute; National Institute on Drug Abuse; National Heart Lung and Blood Institute; National Institute of Diabetes and Digestive and Kidney Diseases [P30AI050410] Funding Source: NIH RePORTER
NR 25
TC 972
Z9 1164
U1 1
U2 107
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUL 26
PY 2012
VL 487
IS 7408
BP 482
EP U1650
DI 10.1038/nature11286
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 979KD
UT WOS:000306815300038
PM 22837004
DA 2026-03-09
ER

PT J
AU Png, KJ
   Halberg, N
   Yoshida, M
   Tavazoie, SF
AF Png, Kim J.
   Halberg, Nils
   Yoshida, Mitsukuni
   Tavazoie, Sohail F.
TI A microRNA regulon that mediates endothelial recruitment and metastasis by cancer cells
SO NATURE
LA English
DT Article
ID growth
AB Metastatic progression of cancer is a complex and clinically daunting process(1-4). We previously identified a set of human microRNAs ( miRNAs) that robustly suppress breast cancer metastasis to lung and bone(5,6) and which display expression levels that predict human metastasis. Although these findings revealed miRNAs as suppressors of cell-autonomous metastatic phenotypes, the roles of noncoding RNAs in non-cell-autonomous cancer progression processes remain unknown. Here we reveal that endogenous miR-126, an miRNA silenced in a variety of common human cancers(7,8), non-cell-autonomously regulates endothelial cell recruitment to metastatic breast cancer cells, in vitro and in vivo. It suppresses metastatic endothelial recruitment, metastatic angiogenesis and metastatic colonization through coordinate targeting of IGFBP2, PITPNC1 and MERTK-novel pro-angiogenic genes and biomarkers of human metastasis. Insulin-like growth factor binding protein 2 ( IGFBP2) secreted by metastatic cells recruits endothelia by modulating IGF1-mediated activation of the IGF type-I receptor on endothelial cells; whereas c-Mer tyrosine kinase (MERTK) receptor cleaved from metastatic cells promotes endothelial recruitment by competitively antagonizing the binding of its ligand GAS6 to endothelial MERTK receptors. Co-injection of endothelial cells with breast cancer cells non-cell-autonomously rescues their miR-126-induced metastatic defect, revealing a novel and important role for endothelial interactions in metastatic initiation. Through loss-of-function and epistasis experiments, we delineate an miRNA regulatory network's individual components as novel and cell-extrinsic regulators of endothelial recruitment, angiogenesis and metastatic colonization. We also identify the IGFBP2/IGF1/IGF1R and GAS6/MERTK signalling pathways as regulators of cancer-mediated endothelial recruitment. Our work further reveals endothelial recruitment and endothelial interactions in the tumour microenvironment to be critical features of metastatic breast cancer.
C1 [Png, Kim J.; Halberg, Nils; Yoshida, Mitsukuni; Tavazoie, Sohail F.] Rockefeller Univ, Lab Syst Canc Biol, New York, NY 10065 USA.
C3 Rockefeller University
RP Tavazoie, SF (corresponding author), Rockefeller Univ, Lab Syst Canc Biol, 1230 York Ave, New York, NY 10065 USA.
EM stavazoie@mail.rockefeller.edu
NR 18
TC 453
Z9 526
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 JAN 12
PY 2012
VL 481
IS 7380
BP 190
EP +
DI 10.1038/nature10661
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 874TO
UT WOS:000298981200037
PM 22170610
DA 2026-03-09
ER

PT J
AU Shah, SP
   Roth, A
   Goya, R
   Oloumi, A
   Ha, G
   Zhao, YJ
   Turashvili, G
   Ding, JR
   Tse, K
   Haffari, G
   Bashashati, A
   Prentice, LM
   Khattra, J
   Burleigh, A
   Yap, D
   Bernard, V
   McPherson, A
   Shumansky, K
   Crisan, A
   Giuliany, R
   Heravi-Moussavi, A
   Rosner, J
   Lai, D
   Birol, I
   Varhol, R
   Tam, A
   Dhalla, N
   Zeng, T
   Ma, K
   Chan, SK
   Griffith, M
   Moradian, A
   Cheng, SWG
   Morin, GB
   Watson, P
   Gelmon, K
   Chia, S
   Chin, SF
   Curtis, C
   Rueda, OM
   Pharoah, PD
   Damaraju, S
   Mackey, J
   Hoon, K
   Harkins, T
   Tadigotla, V
   Sigaroudinia, M
   Gascard, P
   Tlsty, T
   Costello, JF
   Meyer, IM
   Eaves, CJ
   Wasserman, WW
   Jones, S
   Huntsman, D
   Hirst, M
   Caldas, C
   Marra, MA
   Aparicio, S
AF Shah, Sohrab P.
   Roth, Andrew
   Goya, Rodrigo
   Oloumi, Arusha
   Ha, Gavin
   Zhao, Yongjun
   Turashvili, Gulisa
   Ding, Jiarui
   Tse, Kane
   Haffari, Gholamreza
   Bashashati, Ali
   Prentice, Leah M.
   Khattra, Jaswinder
   Burleigh, Angela
   Yap, Damian
   Bernard, Virginie
   McPherson, Andrew
   Shumansky, Karey
   Crisan, Anamaria
   Giuliany, Ryan
   Heravi-Moussavi, Alireza
   Rosner, Jamie
   Lai, Daniel
   Birol, Inanc
   Varhol, Richard
   Tam, Angela
   Dhalla, Noreen
   Zeng, Thomas
   Ma, Kevin
   Chan, Simon K.
   Griffith, Malachi
   Moradian, Annie
   Cheng, S. -W. Grace
   Morin, Gregg B.
   Watson, Peter
   Gelmon, Karen
   Chia, Stephen
   Chin, Suet-Feung
   Curtis, Christina
   Rueda, Oscar M.
   Pharoah, Paul D.
   Damaraju, Sambasivarao
   Mackey, John
   Hoon, Kelly
   Harkins, Timothy
   Tadigotla, Vasisht
   Sigaroudinia, Mahvash
   Gascard, Philippe
   Tlsty, Thea
   Costello, Joseph F.
   Meyer, Irmtraud M.
   Eaves, Connie J.
   Wasserman, Wyeth W.
   Jones, Steven
   Huntsman, David
   Hirst, Martin
   Caldas, Carlos
   Marra, Marco A.
   Aparicio, Samuel
TI The clonal and mutational evolution spectrum of primary triple-negative breast cancers
SO NATURE
LA English
DT Article
ID retinoblastoma tumor-suppressor; squamous-cell carcinoma; basal-like; genome; genes; tp53; head
AB Primary triple-negative breast cancers (TNBCs), a tumour type defined by lack of oestrogen receptor, progesterone receptor and ERBB2 gene amplification, represent approximately 16% of all breast cancers(1). Here we show in 104 TNBC cases that at the time of diagnosis these cancers exhibit a wide and continuous spectrum of genomic evolution, with some having only a handful of coding somatic aberrations in a few pathways, whereas others contain hundreds of coding somatic mutations. High-throughput RNA sequencing (RNA-seq) revealed that only approximately 36% of mutations are expressed. Using deep re-sequencing measurements of allelic abundance for 2,414 somatic mutations, we determine for the first time-to our knowledge-in an epithelial tumour subtype, the relative abundance of clonal frequencies among cases representative of the population. We show that TNBCs vary widely in their clonal frequencies at the time of diagnosis, with the basal subtype of TNBC2,3 showing more variation than non-basal TNBC. Although p53 (also known as TP53), PIK3CA and PTEN somatic mutations seem to be clonally dominant compared to other genes, in some tumours their clonal frequencies are incompatible with founder status. Mutations in cytoskeletal, cell shape and motility proteins occurred at lower clonal frequencies, suggesting that they occurred later during tumour progression. Taken together, our results show that understanding the biology and therapeutic responses of patients with TNBC will require the determination of individual tumour clonal genotypes.
C1 [Shah, Sohrab P.; Roth, Andrew; Oloumi, Arusha; Ha, Gavin; Turashvili, Gulisa; Ding, Jiarui; Haffari, Gholamreza; Bashashati, Ali; Prentice, Leah M.; Khattra, Jaswinder; Burleigh, Angela; Yap, Damian; McPherson, Andrew; Shumansky, Karey; Crisan, Anamaria; Giuliany, Ryan; Heravi-Moussavi, Alireza; Rosner, Jamie; Lai, Daniel; Watson, Peter; Huntsman, David; Aparicio, Samuel] Univ British Columbia, Dept Pathol & Lab Med, Vancouver, BC V6T 2B5, Canada.
   [Shah, Sohrab P.; Roth, Andrew; Oloumi, Arusha; Ha, Gavin; Turashvili, Gulisa; Ding, Jiarui; Haffari, Gholamreza; Bashashati, Ali; Prentice, Leah M.; Khattra, Jaswinder; Burleigh, Angela; Yap, Damian; McPherson, Andrew; Shumansky, Karey; Crisan, Anamaria; Giuliany, Ryan; Heravi-Moussavi, Alireza; Rosner, Jamie; Lai, Daniel; Huntsman, David; Aparicio, Samuel] British Columbia Canc Res Ctr, Vancouver, BC V5Z 1L3, Canada.
   [Goya, Rodrigo; Zhao, Yongjun; Tse, Kane; Birol, Inanc; Varhol, Richard; Tam, Angela; Dhalla, Noreen; Zeng, Thomas; Ma, Kevin; Chan, Simon K.; Griffith, Malachi; Moradian, Annie; Cheng, S. -W. Grace; Morin, Gregg B.; Jones, Steven; Hirst, Martin; Marra, Marco A.] Canadas Michael Smith Genome Sci Ctr, Vancouver, BC V5Z 1L3, Canada.
   [Bernard, Virginie; Wasserman, Wyeth W.] Ctr Mol Med & Therapeut, Vancouver, BC V5Z 4H4, Canada.
   [Morin, Gregg B.; Meyer, Irmtraud M.; Wasserman, Wyeth W.; Jones, Steven; Marra, Marco A.] Univ British Columbia, Dept Med Genet, Vancouver, BC V6T 1Z3, Canada.
   [Chin, Suet-Feung; Curtis, Christina; Rueda, Oscar M.; Pharoah, Paul D.; Caldas, Carlos] Cancer Res UK, Cambridge Res Inst, Li Ka Shing Ctr, Cambridge CB2 0RE, England.
   [Chin, Suet-Feung; Curtis, Christina; Rueda, Oscar M.; Caldas, Carlos] Univ Cambridge, Dept Oncol, Cambridge CB2 2XZ, England.
   [Curtis, Christina] Univ So Calif, Dept Prevent Med, Keck Sch Med, Los Angeles, CA 90033 USA.
   [Damaraju, Sambasivarao; Mackey, John] Univ Alberta, Dept Oncol, Cross Canc Inst, Edmonton, AB T6G 1Z2, Canada.
   [Damaraju, Sambasivarao; Mackey, John] Univ Alberta, Dept Lab Med & Pathol, Cross Canc Inst, Edmonton, AB T6G 1Z2, Canada.
   [Hoon, Kelly; Harkins, Timothy; Tadigotla, Vasisht] Life Technol, Foster City, CA 94404 USA.
   [Sigaroudinia, Mahvash; Gascard, Philippe; Tlsty, Thea] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94143 USA.
   [Costello, Joseph F.] Univ Calif San Francisco, Brain Tumor Res Ctr, Dept Neurosurg, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA.
   [Meyer, Irmtraud M.] Univ British Columbia, Dept Comp Sci, Vancouver, BC V6T 1Z4, Canada.
   [Meyer, Irmtraud M.; Hirst, Martin] Univ British Columbia, Ctr High Throughput Biol, Vancouver, BC V6T 1Z4, Canada.
   [Eaves, Connie J.] British Columbia Canc Agcy, Terry Fox Lab, Vancouver, BC V5Z 1L3, Canada.
   [Jones, Steven] Simon Fraser Univ, Dept Mol Biol & Biochem, Burnaby, BC V5A 1S6, Canada.
   [Huntsman, David] British Columbia Canc Agcy, Ctr Translat & Appl Gen, Vancouver, BC V5Z 4E6, Canada.
   [Hirst, Martin] Univ British Columbia, Dept Microbiol & Immunol, Vancouver, BC V6T 1Z3, Canada.
   [Caldas, Carlos] Cambridge Univ Hosp NHS Fdn Trust, Cambridge Breast Unit, Addenbrookes Hosp, Cambridge CB2 2QQ, England.
   [Caldas, Carlos] NIHR Cambridge Biomed Res Ctr, Cambridge CB2 2QQ, England.
   [Caldas, Carlos] Cambridge Expt Canc Med Ctr ECMC, Cambridge CB2 0RE, England.
C3 University of British Columbia; British Columbia Cancer Agency; University of British Columbia; University of Cambridge; Cancer Research UK; CRUK Cambridge Institute; University of Cambridge; University of Southern California; University of Alberta; University of Alberta; Thermo Fisher Scientific; University of California System; University of California San Francisco; University of California System; University of California San Francisco; UCSF Medical Center; UCSF Helen Diller Family Comprehensive Cancer Center; University of British Columbia; University of British Columbia; British Columbia Cancer Agency; Simon Fraser University; British Columbia Cancer Agency; University of British Columbia; Cambridge University Hospitals NHS Foundation Trust; Addenbrooke's Hospital; University of Cambridge; University of Cambridge
RP Aparicio, S (corresponding author), Univ British Columbia, Dept Pathol & Lab Med, Vancouver, BC V6T 2B5, Canada.
EM carlos.caldas@cancer.org.uk; mmarra@bcgsc.ca; saparicio@bccrc.ca
FU BC Cancer Agency Tumour Bank; CBCF Breast Tumour Bank Alberta; Addenbrookes Tumour bank supported by NIHR; Addenbrookes Tumour bank supported by ECMC; BC Cancer Foundation; US Department of Defense CDMRP program; Canadian Breast Cancer Foundation; Michael Smith Foundation for Health Research; US National Institutes of Health (NIH) Roadmap Epigenomics Program; NIH [5U01ES017154-02]; Cancer Research UK; National Institute of General Medical Sciences [R01GM084875]; Canadian Breast Cancer Research Alliance; Canadian Cancer Society; National Institute for Health Research [NF-SI-0611-10154] Funding Source: researchfish
NR 22
TC 1550
Z9 1783
U1 1
U2 303
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUN 21
PY 2012
VL 486
IS 7403
BP 395
EP 399
DI 10.1038/nature10933
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 961LV
UT WOS:000305466800042
PM 22495314
DA 2026-03-09
ER

PT J
AU Ascano, M
   Mukherjee, N
   Bandaru, P
   Miller, JB
   Nusbaum, JD
   Corcoran, DL
   Langlois, C
   Munschauer, M
   Dewell, S
   Hafner, M
   Williams, Z
   Ohler, U
   Tuschl, T
AF Ascano, Manuel, Jr.
   Mukherjee, Neelanjan
   Bandaru, Pradeep
   Miller, Jason B.
   Nusbaum, Jeffrey D.
   Corcoran, David L.
   Langlois, Christine
   Munschauer, Mathias
   Dewell, Scott
   Hafner, Markus
   Williams, Zev
   Ohler, Uwe
   Tuschl, Thomas
TI FMRP targets distinct mRNA sequence elements to regulate protein expression
SO NATURE
LA English
DT Article
ID fragile-x-syndrome; mental-retardation protein; par-clip; synaptic function; binding protein; cgg-repeat; gene; identification; mutation; autism
AB Fragile X syndrome (FXS) is a multi-organ disease that leads to mental retardation, macro-orchidism in males and premature ovarian insufficiency in female carriers. FXS is also a prominent monogenic disease associated with autism spectrum disorders (ASDs). FXS is typically caused by the loss of fragile X mental retardation 1 (FMR1) expression, which codes for the RNA-binding protein FMRP. Here we report the discovery of distinct RNA-recognition elements that correspond to the two independent RNA-binding domains of FMRP, in addition to the binding sites within the messenger RNA targets for wild-type and I304N mutant FMRP isoforms and the FMRP paralogues FXR1P and FXR2P (also known as FXR1 and FXR2). RNA-recognition-element frequency, ratio and distribution determine target mRNA association with FMRP. Among highly enriched targets, we identify many genes involved in ASD and show that FMRP affects their protein levels in human cell culture, mouse ovaries and human brain. Notably, we discovered that these targets are also dysregulated in Fmr1(-/-) mouse ovaries showing signs of premature follicular overdevelopment. These results indicate that FMRP targets share signalling pathways across different cellular contexts. As the importance of signalling pathways in both FXS and ASD is becoming increasingly apparent, our results provide a ranked list of genes as basis for the pursuit of new therapeutic targets for these neurological disorders.
C1 [Ascano, Manuel, Jr.; Bandaru, Pradeep; Miller, Jason B.; Nusbaum, Jeffrey D.; Munschauer, Mathias; Hafner, Markus; Williams, Zev; Tuschl, Thomas] Rockefeller Univ, Howard Hughes Med Inst, Lab RNA Mol Biol, New York, NY 10065 USA.
   [Mukherjee, Neelanjan; Corcoran, David L.; Ohler, Uwe] Duke Univ, Inst Genome Sci & Policy, Durham, NC 27708 USA.
   [Langlois, Christine; Williams, Zev] Albert Einstein Coll Med, Dept Obstet & Gynecol & Womens Hlth, Program Early & Recurrent Pregnancy Loss, Bronx, NY 10461 USA.
   [Dewell, Scott] Rockefeller Univ, Genom Resource Ctr, New York, NY 10065 USA.
C3 Howard Hughes Medical Institute; Rockefeller University; Duke University; Yeshiva University; Montefiore Medical Center; Albert Einstein College of Medicine; Rockefeller University
RP Tuschl, T (corresponding author), Rockefeller Univ, Howard Hughes Med Inst, Lab RNA Mol Biol, New York, NY 10065 USA.
EM uwe.ohler@duke.edu; ttuschl@rockefeller.edu
FU NIH/NCRR/RU CCTS [UL1RR024143]; NSF [MCB-0822033]; Simons Foundation Autism Research Initiative [CEN5300891]; NIH [R01 MH080442, K08 HD068546]
NR 50
TC 556
Z9 680
U1 1
U2 111
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD DEC 20
PY 2012
VL 492
IS 7429
BP 382
EP +
DI 10.1038/nature11737
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 056KQ
UT WOS:000312488200046
PM 23235829
DA 2026-03-09
ER

PT J
AU Everitt, AR
   Clare, S
   Pertel, T
   John, SP
   Wash, RS
   Smith, SE
   Chin, CR
   Feeley, EM
   Sims, JS
   Adams, DJ
   Wise, HM
   Kane, L
   Goulding, D
   Digard, P
   Anttila, V
   Baillie, JK
   Walsh, TS
   Hume, DA
   Palotie, A
   Xue, YL
   Colonna, V
   Tyler-Smith, C
   Dunning, J
   Gordon, SB
   Smyth, RL
   Openshaw, PJ
   Dougan, G
   Brass, AL
   Kellam, P
AF Everitt, Aaron R.
   Clare, Simon
   Pertel, Thomas
   John, Sinu P.
   Wash, Rachael S.
   Smith, Sarah E.
   Chin, Christopher R.
   Feeley, Eric M.
   Sims, Jennifer S.
   Adams, David J.
   Wise, Helen M.
   Kane, Leanne
   Goulding, David
   Digard, Paul
   Anttila, Verneri
   Baillie, J. Kenneth
   Walsh, Tim S.
   Hume, David A.
   Palotie, Aarno
   Xue, Yali
   Colonna, Vincenza
   Tyler-Smith, Chris
   Dunning, Jake
   Gordon, Stephen B.
   Smyth, Rosalind L.
   Openshaw, Peter J.
   Dougan, Gordon
   Brass, Abraham L.
   Kellam, Paul
TI IFITM3 restricts the morbidity and mortality associated with influenza
SO NATURE
LA English
DT Article
ID west nile virus; proteins; pathogenesis; infection
AB The 2009 H1N1 influenza pandemic showed the speed with which a novel respiratory virus can spread and the ability of a generally mild infection to induce severe morbidity and mortality in a subset of the population. Recent in vitro studies show that the interferon-inducible transmembrane (IFITM) protein family members potently restrict the replication of multiple pathogenic viruses(1-7). Both the magnitude and breadth of the IFITM proteins' in vitro effects suggest that they are critical for intrinsic resistance to such viruses, including influenza viruses. Using a knockout mouse model(8), we now test this hypothesis directly and find that IFITM3 is essential for defending the host against influenza A virus in vivo. Mice lacking Ifitm3 display fulminant viral pneumonia when challenged with a normally low-pathogenicity influenza virus, mirroring the destruction inflicted by the highly pathogenic 1918 'Spanish' influenza(9,10). Similar increased viral replication is seen in vitro, with protection rescued by the re-introduction of Ifitm3. To test the role of IFITM3 in human influenza virus infection, we assessed the IFITM3 alleles of individuals hospitalized with seasonal or pandemic influenza H1N1/09 viruses. We find that a statistically significant number of hospitalized subjects show enrichment for a minor IFITM3 allele (SNP rs12252-C) that alters a splice acceptor site, and functional assays show the minor CC genotype IFITM3 has reduced influenza virus restriction in vitro. Together these data reveal that the action of a single intrinsic immune effector, IFITM3, profoundly alters the course of influenza virus infection in mouse and humans.
C1 [Everitt, Aaron R.; Clare, Simon; Wash, Rachael S.; Smith, Sarah E.; Adams, David J.; Kane, Leanne; Goulding, David; Anttila, Verneri; Palotie, Aarno; Xue, Yali; Colonna, Vincenza; Tyler-Smith, Chris; Dougan, Gordon; Kellam, Paul] Wellcome Trust Sanger Inst, Hinxton CB10 1SA, England.
   [Pertel, Thomas; John, Sinu P.; Chin, Christopher R.; Feeley, Eric M.; Sims, Jennifer S.; Brass, Abraham L.] MIT, Ragon Inst Massachusetts, Gen Hosp, Charlestown, MA 02129 USA.
   [Pertel, Thomas; John, Sinu P.; Chin, Christopher R.; Feeley, Eric M.; Sims, Jennifer S.; Brass, Abraham L.] Harvard Univ, Charlestown, MA 02129 USA.
   [Wise, Helen M.; Digard, Paul] Univ Cambridge, Dept Pathol, Div Virol, Cambridge CB2 1QP, England.
   [Baillie, J. Kenneth; Hume, David A.] Univ Edinburgh, Div Genet & Genom, Roslin Inst, Roslin EH25 9RG, Midlothian, Scotland.
   [Baillie, J. Kenneth; Walsh, Tim S.] Univ Edinburgh, Dept Crit Care Med, Edinburgh EH16 4TJ, Midlothian, Scotland.
   [Colonna, Vincenza] Natl Res Council CNR, Inst Genet & Biophys A Buzzati Traverso, Naples, Italy.
   [Dunning, Jake; Openshaw, Peter J.] Univ London Imperial Coll Sci Technol & Med, Ctr Resp Infect, Natl Heart & Lung Inst, London W2 1PG, England.
   [Gordon, Stephen B.] Univ Liverpool, Liverpool Sch Trop Med, Liverpool L3 5QA, Merseyside, England.
   [Smyth, Rosalind L.] Univ Liverpool, Inst Translat Med, Alder Hey Childrens Hosp, Liverpool L12 2AP, Merseyside, England.
   [Brass, Abraham L.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02117 USA.
   [Kellam, Paul] UCL, UCL MRC Ctr Med Mol Virol, Dept Infect, London W1T 4JF, England.
C3 Wellcome Trust Sanger Institute; Harvard University; Massachusetts Institute of Technology (MIT); Ragon Institute; Harvard University; University of Cambridge; UK Research & Innovation (UKRI); Biotechnology and Biological Sciences Research Council (BBSRC); Roslin Institute; University of Edinburgh; University of Edinburgh; Consiglio Nazionale delle Ricerche (CNR); Istituto di Genetica e Biofisica Adriano Buzzati-Traverso (IGB-CNR); Imperial College London; Liverpool School of Tropical Medicine; University of Liverpool; University of Liverpool; Alder Hey Children's NHS Foundation Trust; Alder Hey Children's Hospital; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; University of London; University College London
RP Kellam, P (corresponding author), Wellcome Trust Sanger Inst, Wellcome Trust Genome Campus, Hinxton CB10 1SA, England.
EM abrass@partners.org; pk5@sanger.ac.uk
FU Wellcome Trust [090382/Z/09/Z]; Imperial's Comprehensive Biomedical Research Centre (cBRC); Medical Research Council UK; Chief Scientist Office (Scotland); Charles H. Hood Foundation; Phillip T. and Susan M. Ragon Institute Foundation; Bill and Melinda Gates Foundation; National Institute of Allergy and Infectious Diseases [R01AI091786]; Wellcome Trust through the Edinburgh Clinical Academic Track (ECAT) [090385/Z/09/Z]; Comprehensive Local Research Networks (CLRNs); National Institute for Health Research (NIHR), UK; Biomedical Research Centre (BRC); Unit (BRU); Biotechnology and Biological Sciences Research Council [BBS/E/D/20251969, BBS/E/D/20241866, BBS/E/D/20241864, BBS/E/D/20241863] Funding Source: researchfish; Cancer Research UK [13031] Funding Source: researchfish; Medical Research Council [G0800767, G0802752, G0600511, MC_U122785833, G1000758, G0901697, G0800777, G0600371, MC_G1001212, G1000758B, 975284] Funding Source: researchfish; National Institute for Health Research [CL-2007-21-012, NF-SI-0508-10212, DHCS/04/G121/68] Funding Source: researchfish; Wellcome Trust [096964/Z/11/Z] Funding Source: researchfish; BBSRC [BBS/E/D/20251969, BBS/E/D/20241866, BBS/E/D/20241864, BBS/E/D/20241863] Funding Source: UKRI; MRC [MC_U122785833, G0600511, G0800767, G0800777, G0600371, MC_G1001212, G0802752, G0901697] Funding Source: UKRI; Wellcome Trust [090382/Z/09/Z, 090385/Z/09/Z] Funding Source: Wellcome Trust; National Institute of Diabetes and Digestive and Kidney Diseases [P30DK043351] Funding Source: NIH RePORTER
NR 33
TC 618
Z9 730
U1 0
U2 99
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 26
PY 2012
VL 484
IS 7395
BP 519
EP U146
DI 10.1038/nature10921
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 931FF
UT WOS:000303200400052
PM 22446628
DA 2026-03-09
ER

PT J
AU Ramrath, DJF
   Yamamoto, H
   Rother, K
   Wittek, D
   Pech, M
   Mielke, T
   Loerke, J
   Scheerer, P
   Ivanov, P
   Teraoka, Y
   Shpanchenko, O
   Nierhaus, KH
   Spahn, CMT
AF Ramrath, David J. F.
   Yamamoto, Hiroshi
   Rother, Kristian
   Wittek, Daniela
   Pech, Markus
   Mielke, Thorsten
   Loerke, Justus
   Scheerer, Patrick
   Ivanov, Pavel
   Teraoka, Yoshika
   Shpanchenko, Olga
   Nierhaus, Knud H.
   Spahn, Christian M. T.
TI The complex of tmRNA-SmpB and EF-G on translocating ribosomes
SO NATURE
LA English
DT Article
ID transfer-messenger-rna; bacterial ribosome; hybrid-state; cryo-em; electron-microscopy; crystal-structure; stalled ribosome; structural basis; 70s ribosome; system
AB Bacterial ribosomes stalled at the 3' end of malfunctioning messenger RNAs can be rescued by transfer-messenger RNA (tmRNA)-mediated trans-translation(1,2). The SmpB protein forms a complex with the tmRNA, and the transfer-RNA-like domain (TLD) of the tmRNA then enters the A site of the ribosome. Subsequently, the TLD-SmpB module is translocated to the P site, a process that is facilitated by the elongation factor EF-G, and translation is switched to the mRNA-like domain (MLD) of the tmRNA. Accurate loading of the MLD into the mRNA path is an unusual initiation mechanism. Despite various snapshots of different ribosome-tmRNA complexes at low to intermediate resolution(3-7), it is unclear how the large, highly structured tmRNA is translocated and how the MLD is loaded. Here we present a cryo-electron microscopy reconstruction of a fusidic-acid-stalled ribosomal 70S-tmRNA-SmpB-EF-G complex (carrying both of the large ligands, that is, EF-G and tmRNA) at 8.3 angstrom resolution. This post-translocational intermediate (TIPOST) presents the TLD-SmpB module in an intrasubunit ap/P hybrid site and a tRNA(fMet) in an intrasubunit pe/E hybrid site. Conformational changes in the ribosome and tmRNA occur in the intersubunit space and on the solvent side. The key underlying event is a unique extra-large swivel movement of the 30S head, which is crucial for both tmRNA-SmpB translocation and MLD loading, thereby coupling translocation to MLD loading. This mechanism exemplifies the versatile, dynamic nature of the ribosome, and it shows that the conformational modes of the ribosome that normally drive canonical translation can also be used in a modified form to facilitate more complex tasks in specialized non-canonical pathways.
C1 [Ramrath, David J. F.; Yamamoto, Hiroshi; Pech, Markus; Mielke, Thorsten; Loerke, Justus; Scheerer, Patrick; Nierhaus, Knud H.; Spahn, Christian M. T.] Charite, Inst Med Phys & Biophys, D-10117 Berlin, Germany.
   [Yamamoto, Hiroshi; Wittek, Daniela; Pech, Markus; Ivanov, Pavel; Teraoka, Yoshika; Shpanchenko, Olga; Nierhaus, Knud H.] Max Planck Inst Mol Genet, Abt Vingron, AG Ribosomen, D-14195 Berlin, Germany.
   [Rother, Kristian] Adam Mickiewicz Univ, Coll Biol, Inst Biol & Mol Biotechnol, PL-61614 Poznan, Poland.
   [Mielke, Thorsten] Max Planck Inst Mol Genet, UltraStrukturNetzwerk, D-14195 Berlin, Germany.
   [Ivanov, Pavel; Shpanchenko, Olga] Moscow MV Lomonosov State Univ, Dept Chem, Moscow 119899, Russia.
C3 Free University of Berlin; Humboldt University of Berlin; Charite Universitatsmedizin Berlin; Max Planck Society; Adam Mickiewicz University; Max Planck Society; Lomonosov Moscow State University
RP Spahn, CMT (corresponding author), Charite, Inst Med Phys & Biophys, Ziegelstr 5-9, D-10117 Berlin, Germany.
EM christian.spahn@charite.de
FU Deutsche Forschungsgemeinschaft DFG [SP 1130/2-1, SFB740]; German Academic Exchange Service [D/09/42768]; European Union; Senatsverwaltung fur Wissenschaft, Forschung und Kultur Berlin (UltraStructureNetwork, Anwenderzentrum); Alexander-von-Humboldt grant [GAN 1127366 STP-2]
NR 42
TC 72
Z9 90
U1 0
U2 28
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD MAY 24
PY 2012
VL 485
IS 7399
BP 526
EP U140
DI 10.1038/nature11006
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 946IH
UT WOS:000304344500048
PM 22622583
DA 2026-03-09
ER

PT J
AU Brick, K
   Smagulova, F
   Khil, P
   Camerini-Otero, RD
   Petukhova, GV
AF Brick, Kevin
   Smagulova, Fatima
   Khil, Pavel
   Camerini-Otero, R. Daniel
   Petukhova, Galina V.
TI Genetic recombination is directed away from functional genomic elements in mice
SO NATURE
LA English
DT Article
ID meiotic recombination; prdm9; initiation; identification; landscape; hotspots; sites; marks
AB Genetic recombination occurs during meiosis, the key developmental programme of gametogenesis. Recombination in mammals has been recently linked to the activity of a histone H3 methyltransferase, PR domain containing 9 (PRDM9)(1-6), the product of the only known speciation-associated gene in mammals(7). PRDM9 is thought to determine the preferred recombination sites-recombination hotspots-through sequence-specific binding of its highly polymorphic multi-Zn-finger domain(8). Nevertheless, Prdm9 knockout mice are proficient at initiating recombination(9). Here we map and analyse the genome-wide distribution of recombination initiation sites in Prdm9 knockout mice and in two mouse strains with different Prdm9 alleles and their F-1 hybrid. We show that PRDM9 determines the positions of practically all hotspots in the mouse genome, with the exception of the pseudo-autosomal region (PAR)-the only area of the genome that undergoes recombination in 100% of cells(10). Surprisingly, hotspots are still observed in Prdm9 knockout mice, and as in wild type, these hotspots are found at H3 lysine 4 (H3K4) trimethylation marks. However, in the absence of PRDM9, most recombination is initiated at promoters and at other sites of PRDM9-independent H3K4 trimethylation. Such sites are rarely targeted in wild-type mice, indicating an unexpected role of the PRDM9 protein in sequestering the recombination machinery away from gene-promoter regions and other functional genomic elements.
C1 [Smagulova, Fatima; Petukhova, Galina V.] Uniformed Serv Univ Hlth Sci, Dept Biochem & Mol Biol, Bethesda, MD 20814 USA.
   [Brick, Kevin; Khil, Pavel; Camerini-Otero, R. Daniel] Natl Inst Diabet Digest & Kidney Dis, NIH, Bethesda, MD 20892 USA.
C3 Uniformed Services University of the Health Sciences - USA; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK)
RP Petukhova, GV (corresponding author), Uniformed Serv Univ Hlth Sci, Dept Biochem & Mol Biol, Bethesda, MD 20814 USA.
EM rdcamerini@mail.nih.gov; gpetukhova@usuhs.mil
FU NIDDK; March of Dimes Foundation [5-FY07-667]; NIH from NIGMS [1R01GM084104-01A1]; USUHS [FS71HU, R071HU, CS71HU]; National Institute of Diabetes and Digestive and Kidney Diseases [ZIADK052034] Funding Source: NIH RePORTER
NR 30
TC 315
Z9 374
U1 2
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 31
PY 2012
VL 485
IS 7400
BP 642
EP 645
DI 10.1038/nature11089
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 949WP
UT WOS:000304608000048
PM 22660327
DA 2026-03-09
ER

PT J
AU Ma, XS
   Herbst, T
   Scheidl, T
   Wang, DQ
   Kropatschek, S
   Naylor, W
   Wittmann, B
   Mech, A
   Kofler, J
   Anisimova, E
   Makarov, V
   Jennewein, T
   Ursin, R
   Zeilinger, A
AF Ma, Xiao-Song
   Herbst, Thomas
   Scheidl, Thomas
   Wang, Daqing
   Kropatschek, Sebastian
   Naylor, William
   Wittmann, Bernhard
   Mech, Alexandra
   Kofler, Johannes
   Anisimova, Elena
   Makarov, Vadim
   Jennewein, Thomas
   Ursin, Rupert
   Zeilinger, Anton
TI Quantum teleportation over 143 kilometres using active feed-forward
SO NATURE
LA English
DT Article
ID entanglement; state; communication
AB The quantum internet(1) is predicted to be the next-generation information processing platform, promising secure communication(2,3) and an exponential speed-up in distributed computation(2,4). The distribution of single qubits over large distances via quantum teleportation(5) is a key ingredient for realizing such a global platform. By using quantum teleportation, unknown quantum states can be transferred over arbitrary distances to a party whose location is unknown. Since the first experimental demonstrations of quantum teleportation of independent external qubits(6), an internal qubit(7) and squeezed states(8), researchers have progressively extended the communication distance. Usually this occurs without active feed-forward of the classical Bell-state measurement result, which is an essential ingredient in future applications such as communication between quantum computers. The benchmark for a global quantum internet is quantum teleportation of independent qubits over a free-space link whose attenuation corresponds to the path between a satellite and a ground station. Here we report such an experiment, using active feed-forward in real time. The experiment uses two free-space optical links, quantum and classical, over 143 kilometres between the two Canary Islands of La Palma and Tenerife. To achieve this, we combine advanced techniques involving a frequency-uncorrelated polarization-entangled photon pair source, ultra-low-noise single-photon detectors and entanglement-assisted clock synchronization. The average teleported state fidelity is well beyond the classical limit(9) of two-thirds. Furthermore, we confirm the quality of the quantum teleportation procedure without feed-forward by complete quantum process tomography. Our experiment verifies the maturity and applicability of such technologies in real-world scenarios, in particular for future satellite-based quantum teleportation.
C1 [Ma, Xiao-Song; Herbst, Thomas; Scheidl, Thomas; Wang, Daqing; Kropatschek, Sebastian; Naylor, William; Wittmann, Bernhard; Mech, Alexandra; Kofler, Johannes; Jennewein, Thomas; Ursin, Rupert; Zeilinger, Anton] Austrian Acad Sci, Inst Quantum Opt & Quantum Informat IQOQI, A-1090 Vienna, Austria.
   [Ma, Xiao-Song; Herbst, Thomas; Wittmann, Bernhard; Mech, Alexandra; Zeilinger, Anton] Univ Vienna, Fac Phys, Vienna Ctr Quantum Sci & Technol, A-1090 Vienna, Austria.
   [Kofler, Johannes] Max Planck Inst Quantum Opt, D-85748 Garching, Germany.
   [Anisimova, Elena; Makarov, Vadim; Jennewein, Thomas] Univ Waterloo, Inst Quantum Comp, Waterloo, ON N2L 3G1, Canada.
   [Anisimova, Elena; Makarov, Vadim; Jennewein, Thomas] Univ Waterloo, Dept Phys & Astron, Waterloo, ON N2L 3G1, Canada.
C3 Austrian Academy of Sciences; University of Vienna; Max Planck Society; University of Waterloo; University of Waterloo
RP Ma, XS (corresponding author), Yale Univ, Dept Elect Engn, New Haven, CT 06520 USA.
EM Xiaosong.Ma@Univie.ac.at; Anton.Zeilinger@Univie.ac.at
FU EU project MALICIA; Research Council of Norway [180439/V30]; Industry Canada; European Space Agency [4000104180/11/NL/AF]; Austrian Science Foundation (FWF) [SFB F4008]; CoQuS; FFG for the QTS project within the ASAP 7 program [828316]; European Commission; Q-ESSENCE [248095]; John Templeton Foundation; Austrian Science Fund (FWF) [W1210] Funding Source: Austrian Science Fund (FWF)
NR 33
TC 507
Z9 579
U1 5
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 13
PY 2012
VL 489
IS 7415
BP 269
EP 273
DI 10.1038/nature11472
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 003UC
UT WOS:000308635900036
PM 22951967
DA 2026-03-09
ER

PT J
AU Joiner, MLA
   Koval, OM
   Li, JD
   He, BJ
   Allamargot, C
   Gao, Z
   Luczak, ED
   Hall, DD
   Fink, BD
   Chen, BY
   Yang, JY
   Moore, SA
   Scholz, TD
   Strack, S
   Mohler, PJ
   Sivitz, WI
   Song, LS
   Anderson, ME
AF Joiner, Mei-ling A.
   Koval, Olha M.
   Li, Jingdong
   He, B. Julie
   Allamargot, Chantal
   Gao, Zhan
   Luczak, Elizabeth D.
   Hall, Duane D.
   Fink, Brian D.
   Chen, Biyi
   Yang, Jinying
   Moore, Steven A.
   Scholz, Thomas D.
   Strack, Stefan
   Mohler, Peter J.
   Sivitz, William I.
   Song, Long-Sheng
   Anderson, Mark E.
TI CaMKII determines mitochondrial stress responses in heart
SO NATURE
LA English
DT Article
ID ii inhibition protects; kinase-ii; calmodulin kinase; calcium uniporter; in-vivo; inner membrane; failure; hypertrophy; apoptosis; oxidation
AB Myocardial cell death is initiated by excessive mitochondrial Ca2+ entry causing Ca2+ overload, mitochondrial permeability transition pore (mPTP) opening and dissipation of the mitochondrial inner membrane potential (Delta Psi m)(1,2). However, the signalling pathways that control mitochondrial Ca2+ entry through the inner membrane mitochondrial Ca2+ uniporter (MCU)(3-5) are not known. The multifunctional Ca2+/calmodulin-dependent protein kinase II (CaMKII) is activated in ischaemia reperfusion, myocardial infarction and neurohumoral injury, common causes of myocardial death and heart failure; these findings suggest that CaMKII could couple disease stress to mitochondrial injury. Here we show that CaMKII promotes mPTP opening and myocardial death by increasing MCU current (I-MCU). Mitochondrial-targeted CaMKII inhibitory protein or cyclosporin A, an mPTP antagonist with clinical efficacy in ischaemia reperfusion injury(6), equivalently prevent mPTP opening, Delta Psi m deterioration and diminish mitochondrial disruption and programmed cell death in response to ischaemia reperfusion injury. Mice with myocardial and mitochondrial-targeted CaMKII inhibition have reduced I-MCU and are resistant to ischaemia reperfusion injury, myocardial infarction and neurohumoral injury, suggesting that pathological actions of CaMKII are substantially mediated by increasing I-MCU. Our findings identify CaMKII activity as a central mechanism for mitochondrial Ca2+ entry in myocardial cell death, and indicate that mitochondrial-targeted CaMKII inhibition could prevent or reduce myocardial death and heart failure in response to common experimental forms of pathophysiological stress.
C1 [Joiner, Mei-ling A.; Koval, Olha M.; Li, Jingdong; He, B. Julie; Gao, Zhan; Luczak, Elizabeth D.; Hall, Duane D.; Chen, Biyi; Yang, Jinying; Mohler, Peter J.; Sivitz, William I.; Song, Long-Sheng; Anderson, Mark E.] Univ Iowa, Dept Internal Med, Iowa City, IA 52242 USA.
   [Joiner, Mei-ling A.; Koval, Olha M.; Li, Jingdong; He, B. Julie; Gao, Zhan; Luczak, Elizabeth D.; Hall, Duane D.; Chen, Biyi; Yang, Jinying; Mohler, Peter J.; Sivitz, William I.; Song, Long-Sheng; Anderson, Mark E.] Univ Iowa, Ctr Cardiovasc, Carver Coll Med, Iowa City, IA 52242 USA.
   [He, B. Julie; Moore, Steven A.; Anderson, Mark E.] Univ Iowa, Carver Coll Med, Dept Mol Physiol & Biophys, Iowa City, IA 52242 USA.
   [Allamargot, Chantal] Univ Iowa, Carver Coll Med, Cent Microscopy Res Facil, Iowa City, IA 52242 USA.
   [Fink, Brian D.; Sivitz, William I.] Iowa City Vet Affairs Med Ctr, Iowa City, IA 52246 USA.
   [Moore, Steven A.] Univ Iowa, Dept Pathol, Carver Coll Med, Iowa City, IA 52242 USA.
   [Scholz, Thomas D.] Univ Iowa, Dept Pediat, Carver Coll Med, Iowa City, IA 52242 USA.
   [Strack, Stefan] Univ Iowa, Dept Pharmacol, Carver Coll Med, Iowa City, IA 52242 USA.
C3 University of Iowa; University of Iowa; University of Iowa; University of Iowa; US Department of Veterans Affairs; Veterans Health Administration (VHA); Iowa City VA Health Care System; University of Iowa; University of Iowa; University of Iowa
RP Joiner, MLA (corresponding author), Univ Iowa, Dept Internal Med, Iowa City, IA 52242 USA.
EM mei-ling-joiner@uiowa.edu; mark-e-anderson@uiowa.edu
FU AHA [0635357N]; NIH [R01 HL090905, R01 HL079031, R01 HL62494, R01 HL70250, R01 HL113001, R01 HL084583, R01 HL083422]; Fondation Leducq for the Alliance for CaMKII Signaling; Pew Scholars Trust; American Heart Association (AHA) [0635357N] Funding Source: American Heart Association (AHA)
NR 31
TC 351
Z9 394
U1 1
U2 66
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD NOV 8
PY 2012
VL 491
IS 7423
BP 269
EP +
DI 10.1038/nature11444
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 033DP
UT WOS:000310774300047
PM 23051746
DA 2026-03-09
ER

PT J
AU Hao, QZ
   Wang, L
   Oldfield, F
   Peng, SZ
   Qin, L
   Song, Y
   Xu, B
   Qiao, YS
   Bloemendal, J
   Guo, ZT
AF Hao, Qingzhen
   Wang, Luo
   Oldfield, Frank
   Peng, Shuzhen
   Qin, Li
   Song, Yang
   Xu, Bing
   Qiao, Yansong
   Bloemendal, Jan
   Guo, Zhengtang
TI Delayed build-up of Arctic ice sheets during 400,000-year minima in insolation variability
SO NATURE
LA English
DT Article
ID chinese loess; climate variability; antarctic climate; grain-size; volume; temperature; greenland; record
AB Knowledge of the past variability of climate at high northern latitudes during astronomical analogues of the present interglacial(1) may help to inform our understanding of future climate change. Unfortunately, long-term continuous records of ice-sheet variability in the Northern Hemisphere only are scarce because records of benthic O-18 content represent an integrated signal of changes in ice volume in both polar regions(2). However, variations in Northern Hemisphere ice sheets influence the Siberian High(3) (an atmospheric pressure system), so variations in the East Asian winter monsoon (EAWM)-as recorded in the aeolian dust deposits on the Chinese Loess Plateau-can serve as a useful proxy of Arctic climate variability before the ice-core record begins. Here we present an EAWM proxy record using grain-size variations in two parallel loess sections representative of sequences across the whole of the Chinese Loess Plateau over the past 900,000 years. The results show that during periods of low eccentricity and precessional variability at approximately 400,000-year intervals, the grain-size-inferred intensity of the EAWM remains weak for up to 20,000 years after the end of the interglacial episode of high summer monsoon activity and strong pedogenesis. In contrast, there is a rapid increase in the EAWM after the end of most other interglacials. We conclude that, for both the 400,000-year interglacials, the weak EAWM winds maintain a mild, non-glacial climate at high northern latitudes for much longer than expected from the conventional loess and marine oxygen isotope records. During these times, the less-severe summer insolation minima at 65 degrees N (ref. 4) would have suppressed ice and snow accumulation, leading to a weak Siberian High and, consequently, weak EAWM winds.
C1 [Hao, Qingzhen; Wang, Luo; Song, Yang; Xu, Bing; Guo, Zhengtang] Chinese Acad Sci, Inst Geol & Geophys, Key Lab Cenozo Geol & Environm, Beijing 100029, Peoples R China.
   [Oldfield, Frank; Bloemendal, Jan] Univ Liverpool, Sch Environm Sci, Liverpool L69 7ZT, Merseyside, England.
   [Peng, Shuzhen] Taishan Univ, Key Lab Tourism & Resources Environm Univ Shandon, Tai An 271021, Shandong, Peoples R China.
   [Qin, Li] China Three Gorges Museum, Chongqing Three Gorges Inst Paleoanthropol, Chongqing 400015, Peoples R China.
   [Song, Yang] Chinese Acad Sci, Grad Univ, Beijing 100049, Peoples R China.
   [Qiao, Yansong] Chinese Acad Geol Sci, Inst Geomech, Beijing 100081, Peoples R China.
C3 Chinese Academy of Sciences; Institute of Geology & Geophysics, CAS; University of Liverpool; Taishan University; Chongqing Three Gorges University; Chinese Academy of Sciences; University of Chinese Academy of Sciences, CAS; China Geological Survey; Institute of Geomechanics, Chinese Academy of Geological Sciences; Chinese Academy of Geological Sciences
RP Hao, QZ (corresponding author), Chinese Acad Sci, Inst Geol & Geophys, Key Lab Cenozo Geol & Environm, POB 9825, Beijing 100029, Peoples R China.
EM haoqz@mail.iggcas.ac.cn; oldfield.f@gmail.com
FU National Natural Science Foundation of China [41172323]; Ministry of Science and Technology [2010CB950204]; Ministry of Land and Resources [201211077]; Chinese Academy of Sciences
NR 30
TC 342
Z9 428
U1 7
U2 251
PU NATURE PUBLISHING 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 18
PY 2012
VL 490
IS 7420
BP 393
EP 396
DI 10.1038/nature11493
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 021XI
UT WOS:000309918500044
PM 23034648
DA 2026-03-09
ER

PT J
AU Sutton, MD
   Briggs, DEG
   Siveter, DJ
   Siveter, DJ
   Sigwart, JD
AF Sutton, Mark D.
   Briggs, Derek E. G.
   Siveter, David J.
   Siveter, Derek J.
   Sigwart, Julia D.
TI A Silurian armoured aplacophoran and implications for molluscan phylogeny
SO NATURE
LA English
DT Article
ID invertebrate evolution; vermiform mollusk; acaenoplax; polychaete; fossils; origin; chiton
AB The Mollusca is one of the most diverse, important and well-studied invertebrate phyla; however, relationships among major molluscan taxa have long been a subject of controversy(1-9). In particular, the position of the shell-less vermiform Aplacophora and its relationship to the better-known Polyplacophora (chitons) have been problematic: Aplacophora has been treated as a paraphyletic or monophyletic group at the base of the Mollusca(3,6,8), proximate to other derived clades such as Cephalopoda(2,3,10), or as sister group to the Polyplacophora, forming the clade Aculifera(1,5,7,11,12). Resolution of this debate is required to allow the evolutionary origins of Mollusca to be reconstructed with confidence. Recent fossil finds(13-16) support the Aculifera hypothesis, demonstrating that the Palaeozoic-era palaeoloricate 'chitons' included taxa combining certain polyplacophoran and aplacophoran characteristics(5). However, fossils combining an unambiguously aplacophoran-like body with chiton-like valves have remained elusive. Here we describe such a fossil, Kulindroplax perissokomos gen. et sp. nov., from the Herefordshire Lagerstatte(17,18) (about 425 million years BP), a Silurian deposit preserving a marine biota(18) in unusual three-dimensional detail. The specimen is reconstructed three-dimensionally through physical-optical tomography(19). Phylogenetic analysis indicates that this and many other palaeoloricate chitons are crown-group aplacophorans.
C1 [Sutton, Mark D.] Univ London Imperial Coll Sci Technol & Med, Dept Earth Sci & Engn, London SW7 2BP, England.
   [Briggs, Derek E. G.] Yale Univ, Dept Geol & Geophys, New Haven, CT 06520 USA.
   [Briggs, Derek E. G.] Yale Univ, Yale Peabody Museum Nat Hist, New Haven, CT 06520 USA.
   [Siveter, David J.] Univ Leicester, Dept Geol, Leicester LE1 7RH, Leics, England.
   [Siveter, Derek J.] Univ Oxford, Dept Earth Sci, Oxford OX1 3AN, England.
   [Siveter, Derek J.] Univ Museum Nat Hist, Oxford OX1 3PW, England.
   [Sigwart, Julia D.] Queens Univ Belfast, Sch Biol Sci, Marine Lab, Portaferry BT22 1PF, North Ireland.
C3 Imperial College London; Yale University; Yale University; University of Leicester; University of Oxford; University of Oxford; Queens University Belfast
RP Sutton, MD (corresponding author), Univ London Imperial Coll Sci Technol & Med, Dept Earth Sci & Engn, London SW7 2BP, England.
EM m.sutton@imperial.ac.uk
FU Natural Environmental Research Council (NERC) [NE/F018037/1]; NERC [NE/F018037/1, NE/F01693X/1] Funding Source: UKRI; Natural Environment Research Council [NE/F01693X/1, NE/F018037/1] Funding Source: researchfish
NR 29
TC 63
Z9 67
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 OCT 4
PY 2012
VL 490
IS 7418
BP 94
EP 97
DI 10.1038/nature11328
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 015LG
UT WOS:000309446800039
PM 23038472
DA 2026-03-09
ER

PT J
AU Sanchez, T
   Chen, DTN
   DeCamp, SJ
   Heymann, M
   Dogic, Z
AF Sanchez, Tim
   Chen, Daniel T. N.
   DeCamp, Stephen J.
   Heymann, Michael
   Dogic, Zvonimir
TI Spontaneous motion in hierarchically assembled active matter
SO NATURE
LA English
DT Article
ID self-organization; microtubules; filaments; bundles; motors; driven; cells; purification; networks
AB With remarkable precision and reproducibility, cells orchestrate the cooperative action of thousands of nanometre-sized molecular motors to carry out mechanical tasks at much larger length scales, such as cell motility, division and replication(1). Besides their biological importance, such inherently non-equilibrium processes suggest approaches for developing biomimetic active materials from microscopic components that consume energy to generate continuous motion(2-4). Being actively driven, these materials are not constrained by the laws of equilibrium statistical mechanics and can thus exhibit sought-after properties such as autonomous motility, internally generated flows and self-organized beating(5-7). Here, starting from extensile microtubule bundles, we hierarchically assemble far-from-equilibrium analogues of conventional polymer gels, liquid crystals and emulsions. At high enough concentration, the microtubules form a percolating active network characterized by internally driven chaotic flows, hydrodynamic instabilities, enhanced transport and fluid mixing. When confined to emulsion droplets, three-dimensional networks spontaneously adsorb onto the droplet surfaces to produce highly active two-dimensional nematic liquid crystals whose streaming flows are controlled by internally generated fractures and self-healing, as well as unbinding and annihilation of oppositely charged disclination defects. The resulting active emulsions exhibit unexpected properties, such as autonomous motility, which are not observed in their passive analogues. Taken together, these observations exemplify how assemblages of animate microscopic objects exhibit collective biomimetic properties that are very different from those found in materials assembled from inanimate building blocks, challenging us to develop a theoretical framework that would allow for a systematic engineering of their far-from-equilibrium material properties.
C1 [Sanchez, Tim; Chen, Daniel T. N.; DeCamp, Stephen J.; Heymann, Michael; Dogic, Zvonimir] Brandeis Univ, Martin Fisher Sch Phys, Waltham, MA 02454 USA.
   [Heymann, Michael] Brandeis Univ, Grad Program Biophys & Struct Biol, Waltham, MA 02454 USA.
C3 Brandeis University; Brandeis University
RP Dogic, Z (corresponding author), Brandeis Univ, Martin Fisher Sch Phys, 415 South St, Waltham, MA 02454 USA.
EM zdogic@brandeis.edu
FU W. M. Keck Foundation; National Institute of Health [5K25GM85613]; National Science Foundation [NSF-MRSEC-0820492, NSF-MRI 0923057]; Pioneer Research Center Program through the National Research Foundation of Korea [2012-0001255]; Division Of Materials Research; Direct For Mathematical & Physical Scien [0923054, 0923057] Funding Source: National Science Foundation
NR 41
TC 1191
Z9 1367
U1 11
U2 827
PU NATURE PUBLISHING 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 15
PY 2012
VL 491
IS 7424
BP 431
EP +
DI 10.1038/nature11591
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 036MY
UT WOS:000311031600043
PM 23135402
DA 2026-03-09
ER

PT J
AU Buckley, BA
   Burkhart, KB
   Gu, SG
   Spracklin, G
   Kershner, A
   Fritz, H
   Kimble, J
   Fire, A
   Kennedy, S
AF Buckley, Bethany A.
   Burkhart, Kirk B.
   Gu, Sam Guoping
   Spracklin, George
   Kershner, Aaron
   Fritz, Heidi
   Kimble, Judith
   Fire, Andrew
   Kennedy, Scott
TI A nuclear Argonaute promotes multigenerational epigenetic inheritance and germline immortality
SO NATURE
LA English
DT Article
ID double-stranded-rna; c-elegans; caenorhabditis-elegans; gene; interference; protein; memory; pirnas; rde-1
AB Epigenetic information is frequently erased near the start of each new generation(1). In some cases, however, epigenetic information can be transmitted from parent to progeny (multigenerational epigenetic inheritance)(2). A particularly notable example of this type of epigenetic inheritance is double-stranded RNA-mediated gene silencing in Caenorhabditis elegans. This RNA-mediated interference (RNAi) can be inherited for more than five generations(3-8). To understand this process, here we conduct a genetic screen for nematodes defective in transmitting RNAi silencing signals to future generations. This screen identified the heritable RNAi defective 1 (hrde-1) gene. hrde-1 encodes an Argonaute protein that associates with small interfering RNAs in the germ cells of progeny of animals exposed to double-stranded RNA. In the nuclei of these germ cells, HRDE-1 engages the nuclear RNAi defective pathway to direct the trimethylation of histone H3 at Lys 9 (H3K9me3) at RNAi-targeted genomic loci and promote RNAi inheritance. Under normal growth conditions, HRDE-1 associates with endogenously expressed short interfering RNAs, which direct nuclear gene silencing in germ cells. In hrde-1- or nuclear RNAi-deficient animals, germline silencing is lost over generational time. Concurrently, these animals exhibit steadily worsening defects in gamete formation and function that ultimately lead to sterility. These results establish that the Argonaute protein HRDE-1 directs gene-silencing events in germ-cell nuclei that drive multigenerational RNAi inheritance and promote immortality of the germ-cell lineage. We propose that C. elegans use the RNAi inheritance machinery to transmit epigenetic information, accrued by past generations, into future generations to regulate important biological processes.
C1 [Buckley, Bethany A.; Burkhart, Kirk B.; Spracklin, George; Fritz, Heidi; Kimble, Judith; Kennedy, Scott] Univ Wisconsin, Lab Genet, Madison, WI 53706 USA.
   [Gu, Sam Guoping; Fire, Andrew] Stanford Univ, Dept Pathol, Stanford, CA 94305 USA.
   [Gu, Sam Guoping; Fire, Andrew] Stanford Univ, Dept Genet, Stanford, CA 94305 USA.
   [Kershner, Aaron; Fritz, Heidi] Univ Wisconsin, Howard Hughes Med Inst, Madison, WI 53706 USA.
   [Kershner, Aaron; Kimble, Judith] Univ Wisconsin, Dept Biochem, Madison, WI 53706 USA.
C3 University of Wisconsin System; University of Wisconsin Madison; Stanford University; Stanford University; Howard Hughes Medical Institute; University of Wisconsin System; University of Wisconsin Madison; University of Wisconsin System; University of Wisconsin Madison
RP Kennedy, S (corresponding author), Univ Wisconsin, Lab Genet, Madison, WI 53706 USA.
EM sgkennedy@wisc.edu
FU Pew scholar's program; Shaw scholar's program; National Institutes of Health [GM88289, GM37706, GM069454]; National Institute of General Medical Sciences [R01GM088289] Funding Source: NIH RePORTER
NR 21
TC 373
Z9 470
U1 1
U2 91
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD SEP 20
PY 2012
VL 489
IS 7416
BP 447
EP 451
DI 10.1038/nature11352
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 007AK
UT WOS:000308860900049
PM 22810588
DA 2026-03-09
ER

PT J
AU van den Bosch, RCE
   Gebhardt, K
   Gueltekin, K
   van de Ven, G
   van der Wel, A
   Walsh, JL
AF van den Bosch, Remco C. E.
   Gebhardt, Karl
   Gueltekin, Kayhan
   van de Ven, Glenn
   van der Wel, Arjen
   Walsh, Jonelle L.
TI An over-massive black hole in the compact lenticular galaxy NGC 1277
SO NATURE
LA English
DT Article
ID active galactic nuclei; elliptic galaxy; scaling relations; masses; luminosity; centers; model; disks
AB Most massive galaxies have supermassive black holes at their centres, and the masses of the black holes are believed to correlate with properties of the host-galaxy bulge component(1). Several explanations have been proposed for the existence of these locally established empirical relationships, including the non-causal, statistical process of galaxy-galaxy merging(2), direct feedback between the black hole and its host galaxy(3), and galaxy-galaxy merging and the subsequent violent relaxation and dissipation(4). The empirical scaling relations are therefore important for distinguishing between various theoretical models of galaxy evolution(5,6), and they furthermore form the basis for all black-hole mass measurements at large distances. Observations have shown that the mass of the black hole is typically 0.1 per cent of the mass of the stellar bulge of the galaxy(7,8). Until now, the galaxy with the largest known fraction of its mass in its central black hole (11 per cent) was the small galaxy NGC 4486B(1,9). Here we report observations of the stellar kinematics of NGC 1277, which is a compact, lenticular galaxy with a mass of 1.2 x 10(11) solar masses. From the data, we determine that the mass of the central black hole is 1.7 x 10(10) solar masses, or 59 per cent of its bulge mass. We also show observations of five other compact galaxies that have properties similar to NGC 1277 and therefore may also contain over-massive black holes. It is not yet known if these galaxies represent a tail of a distribution, or if disk-dominated galaxies fail to follow the usual black-hole mass scaling relations(4,10).
C1 [van den Bosch, Remco C. E.; van de Ven, Glenn; van der Wel, Arjen] Max Planck Inst Astron, D-69117 Heidelberg, Germany.
   [van den Bosch, Remco C. E.; Gebhardt, Karl; Walsh, Jonelle L.] Univ Texas Austin, Dept Astron, Austin, TX 78712 USA.
   [Gueltekin, Kayhan] Univ Michigan, Dept Astron, Ann Arbor, MI 48109 USA.
C3 Max Planck Society; University of Texas System; University of Texas Austin; University of Michigan System; University of Michigan
RP van den Bosch, RCE (corresponding author), Max Planck Inst Astron, Konigstuhl 17, D-69117 Heidelberg, Germany.
EM bosch@mpia.de
FU US National Science Foundation [NSF-0908639, AST-1102845]; US National Aeronautics Space Administration [GO0-11151X, G02-13111X]; Space Telescope Science Institute [HST-GO-12557.01-A]; Division Of Astronomical Sciences; Direct For Mathematical & Physical Scien [0908639, 1102845] Funding Source: National Science Foundation
NR 28
TC 180
Z9 192
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 NOV 29
PY 2012
VL 491
IS 7426
BP 729
EP 731
DI 10.1038/nature11592
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 044FY
UT WOS:000311606000038
PM 23192149
DA 2026-03-09
ER

PT J
AU Levin, AM
   Bates, DL
   Ring, AM
   Krieg, C
   Lin, JT
   Su, L
   Moraga, I
   Raeber, ME
   Bowman, GR
   Novick, P
   Pande, VS
   Fathman, CG
   Boyman, O
   Garcia, KC
AF Levin, Aron M.
   Bates, Darren L.
   Ring, Aaron M.
   Krieg, Carsten
   Lin, Jack T.
   Su, Leon
   Moraga, Ignacio
   Raeber, Miro E.
   Bowman, Gregory R.
   Novick, Paul
   Pande, Vijay S.
   Fathman, C. Garrison
   Boyman, Onur
   Garcia, K. Christopher
TI Exploiting a natural conformational switch to engineer an interleukin-2 'superkine'
SO NATURE
LA English
DT Article
ID selective stimulation; molecular-cloning; alpha-receptor; expression; complexes; proteins; dynamics; kinetics; chain
AB The immunostimulatory cytokine interleukin-2 (IL-2) is a growth factor for a wide range of leukocytes, including T cells and natural killer (NK) cells(1-3). Considerable effort has been invested in using IL-2 as a therapeutic agent for a variety of immune disorders ranging from AIDS to cancer. However, adverse effects have limited its use in the clinic. On activated T cells, IL-2 signals through a quaternary 'high affinity' receptor complex consisting of IL-2, IL-2R alpha (termed CD25), IL-2R beta and IL-2R gamma(4-8). Naive T cells express only a low density of IL-2R beta and IL-2R gamma, and are therefore relatively insensitive to IL-2, but acquire sensitivity after CD25 expression, which captures the cytokine and presents it to IL-2R beta and IL-2R gamma. Here, using in vitro evolution, we eliminated the functional requirement of IL-2 for CD25 expression by engineering an IL-2 'superkine' (also called super-2) with increased binding affinity for IL-2R beta. Crystal structures of the IL-2 superkine in free and receptor-bound forms showed that the evolved mutations are principally in the core of the cytokine, and molecular dynamics simulations indicated that the evolved mutations stabilized IL-2, reducing the flexibility of a helix in the IL-2R beta binding site, into an optimized receptor-binding conformation resembling that when bound to CD25. The evolved mutations in the IL-2 superkine recapitulated the functional role of CD25 by eliciting potent phosphorylation of STAT5 and vigorous proliferation of T cells irrespective of CD25 expression. Compared to IL-2, the IL-2 superkine induced superior expansion of cytotoxic T cells, leading to improved antitumour responses in vivo, and elicited proportionally less expansion of T regulatory cells and reduced pulmonary oedema. Collectively, we show that in vitro evolution has mimicked the functional role of CD25 in enhancing IL-2 potency and regulating target cell specificity, which has implications for immunotherapy.
C1 [Levin, Aron M.; Garcia, K. Christopher] Stanford Univ, Howard Hughes Med Inst, Sch Med, Stanford, CA 94305 USA.
   [Bates, Darren L.; Ring, Aaron M.; Moraga, Ignacio; Garcia, K. Christopher] Stanford Univ, Dept Mol & Cellular Physiol, Sch Med, Stanford, CA 94305 USA.
   [Bates, Darren L.; Ring, Aaron M.; Moraga, Ignacio; Garcia, K. Christopher] Stanford Univ, Dept Biol Struct, Sch Med, Stanford, CA 94305 USA.
   [Krieg, Carsten; Raeber, Miro E.; Boyman, Onur] Univ Zurich, Lab Appl Immunobiol, CH-8006 Zurich, Switzerland.
   [Krieg, Carsten; Raeber, Miro E.; Boyman, Onur] Univ Zurich Hosp, Allergy Unit, Dept Dermatol, CH-8091 Zurich, Switzerland.
   [Lin, Jack T.; Su, Leon; Fathman, C. Garrison] Stanford Univ, Sch Med, Dept Med, Div Rheumatol & Immunol, Stanford, CA 94305 USA.
   [Bowman, Gregory R.; Novick, Paul; Pande, Vijay S.] Stanford Univ, Dept Chem, Stanford, CA 94305 USA.
C3 Stanford University; Howard Hughes Medical Institute; Stanford University; Stanford University; University of Zurich; University of Zurich; University Zurich Hospital; Stanford University; Stanford University
RP Garcia, KC (corresponding author), Stanford Univ, Howard Hughes Med Inst, Sch Med, Stanford, CA 94305 USA.
EM onur.boyman@uzh.ch; kcgarcia@stanford.edu
FU Swiss National Science Foundation [NIH-RO1AI51321, PP00P3-128421]; Swiss Cancer League [KFS-02672-08-2010]; NIH [R01-GM062868, U01 DK078123, U19 AI 082719]; MRI-R2; American Recovery and Reinvestment Act [NIH-AR050942]; Stanford Medical Scientist Training Program [NIH-GM07365]; Swiss National Science Foundation (SNF) [PP00P3_128421] Funding Source: Swiss National Science Foundation (SNF); National Institute of Allergy and Infectious Diseases [R01AI051321, R37AI051321] Funding Source: NIH RePORTER; National Institute of Arthritis and Musculoskeletal and Skin Diseases [T32AR050942] Funding Source: NIH RePORTER; National Institute of General Medical Sciences [T32GM007365] Funding Source: NIH RePORTER
NR 39
TC 452
Z9 611
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 26
PY 2012
VL 484
IS 7395
BP 529
EP U159
DI 10.1038/nature10975
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 931FF
UT WOS:000303200400054
PM 22446627
DA 2026-03-09
ER

PT J
AU Li, GW
   Oh, E
   Weissman, JS
AF Li, Gene-Wei
   Oh, Eugene
   Weissman, Jonathan S.
TI The anti-Shine-Dalgarno sequence drives translational pausing and codon choice in bacteria
SO NATURE
LA English
DT Article
ID escherichia-coli; messenger-rna; ribosomal-rna; in-vivo; elongation; genes; usage; transcription; abundance; reveals
AB Protein synthesis by ribosomes takes place on a linear substrate but at non-uniform speeds. Transient pausing of ribosomes can affect a variety of co-translational processes, including protein targeting and folding(1). These pauses are influenced by the sequence of the messenger RNA(2). Thus, redundancy in the genetic code allows the same protein to be translated at different rates. However, our knowledge of both the position and the mechanism of translational pausing in vivo is highly limited. Here we present a genome-wide analysis of translational pausing in bacteria by ribosome profiling-deep sequencing of ribosome-protected mRNA fragments(3-5). This approach enables the high-resolution measurement of ribosome density profiles along most transcripts at unperturbed, endogenous expression levels. Unexpectedly, we found that codons decoded by rare transfer RNAs do not lead to slow translation under nutrient-rich conditions. Instead, Shine-Dalgarno-(SD) 6-like features within coding sequences cause pervasive translational pausing. Using an orthogonal ribosome(7,8) possessing an altered anti-SD sequence, we show that pausing is due to hybridization between the mRNA and 16S ribosomal RNA of the translating ribosome. In protein-coding sequences, internal SD sequences are disfavoured, which leads to biased usage, avoiding codons and codon pairs that resemble canonical SD sites. Our results indicate that internal SD-like sequences are a major determinant of translation rates and a global driving force for the coding of bacterial genomes.
C1 [Li, Gene-Wei; Oh, Eugene; Weissman, Jonathan S.] Univ Calif San Francisco, Howard Hughes Med Inst, Dept Cellular & Mol Pharmacol, San Francisco, CA 94158 USA.
C3 Howard Hughes Medical Institute; University of California System; University of California San Francisco
RP Weissman, JS (corresponding author), Univ Calif San Francisco, Howard Hughes Med Inst, Dept Cellular & Mol Pharmacol, San Francisco, CA 94158 USA.
EM weissman@cmp.ucsf.edu
FU Helen Hay Whitney Foundation; Howard Hughes Medical Institute
NR 37
TC 485
Z9 618
U1 1
U2 136
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD APR 26
PY 2012
VL 484
IS 7395
BP 538
EP U172
DI 10.1038/nature10965
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 931FF
UT WOS:000303200400056
PM 22456704
DA 2026-03-09
ER

PT J
AU Vonlanthen, P
   Bittner, D
   Hudson, AG
   Young, KA
   Müller, R
   Lundsgaard-Hansen, B
   Roy, D
   Di Piazza, S
   Largiader, CR
   Seehausen, O
AF Vonlanthen, P.
   Bittner, D.
   Hudson, A. G.
   Young, K. A.
   Mueller, R.
   Lundsgaard-Hansen, B.
   Roy, D.
   Di Piazza, S.
   Largiader, C. R.
   Seehausen, O.
TI Eutrophication causes speciation reversal in whitefish adaptive radiations
SO NATURE
LA English
DT Article
ID ecological speciation; lake; hybridization; fish; requirements; conservation; biodiversity; gasterosteus; evolution; patterns
AB Species diversity can be lost through two different but potentially interacting extinction processes: demographic decline and speciation reversal through introgressive hybridization. To investigate the relative contribution of these processes, we analysed historical and contemporary data of replicate whitefish radiations from 17 pre-alpine European lakes and reconstructed changes in genetic species differentiation through time using historical samples. Here we provide evidence that species diversity evolved in response to ecological opportunity, and that eutrophication, by diminishing this opportunity, has driven extinctions through speciation reversal and demographic decline. Across the radiations, the magnitude of eutrophication explains the pattern of species loss and levels of genetic and functional distinctiveness among remaining species. We argue that extinction by speciation reversal may be more widespread than currently appreciated. Preventing such extinctions will require that conservation efforts not only target existing species but identify and protect the ecological and evolutionary processes that generate and maintain species.
C1 [Vonlanthen, P.; Hudson, A. G.; Lundsgaard-Hansen, B.; Di Piazza, S.; Seehausen, O.] Univ Bern, Inst Ecol & Evolut, Div Aquat Ecol & Evolut, CH-3012 Bern, Switzerland.
   [Vonlanthen, P.; Bittner, D.; Hudson, A. G.; Young, K. A.; Mueller, R.; Lundsgaard-Hansen, B.; Roy, D.; Di Piazza, S.; Seehausen, O.] EAWAG Swiss Fed Inst Aquat Sci & Technol, Ctr Ecol Evolut & Biogeochem, Dept Fish Ecol & Evolut, CH-6047 Kastanienbaum, Switzerland.
   [Bittner, D.] Univ Bern, Inst Ecol & Evolut, Computat & Mol Populat Genet CMPG Lab, CH-3012 Bern, Switzerland.
   [Young, K. A.] Environm Agcy, Cardiff CF24 0TP, S Glam, Wales.
   [Roy, D.] Dalhousie Univ, Dept Biol, Halifax, NS B3H 4R2, Canada.
   [Largiader, C. R.] Univ Hosp Bern, Inselspital, Inst Clin Chem, CH-3010 Bern, Switzerland.
   [Largiader, C. R.] Univ Bern, Inselspital, CH-3010 Bern, Switzerland.
C3 University of Bern; Swiss Federal Institutes of Technology Domain; Swiss Federal Institute of Aquatic Science & Technology (EAWAG); University of Bern; Dalhousie University; University of Bern; University Hospital of Bern; University of Bern
RP Seehausen, O (corresponding author), Univ Bern, Inst Ecol & Evolut, Div Aquat Ecol & Evolut, Baltzerstr 6, CH-3012 Bern, Switzerland.
EM ole.seehausen@eawag.ch
FU Eawag Action Field Grant 'AquaDiverse-understanding and predicting changes in aquatic biodiversity'
NR 47
TC 384
Z9 439
U1 2
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 FEB 16
PY 2012
VL 482
IS 7385
BP 357
EP U1500
DI 10.1038/nature10824
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 892LG
UT WOS:000300287100037
PM 22337055
DA 2026-03-09
ER

PT J
AU Cheneau, M
   Barmettler, P
   Poletti, D
   Endres, M
   Schauss, P
   Fukuhara, T
   Gross, C
   Bloch, I
   Kollath, C
   Kuhr, S
AF Cheneau, Marc
   Barmettler, Peter
   Poletti, Dario
   Endres, Manuel
   Schauss, Peter
   Fukuhara, Takeshi
   Gross, Christian
   Bloch, Immanuel
   Kollath, Corinna
   Kuhr, Stefan
TI Light-cone-like spreading of correlations in a quantum many-body system
SO NATURE
LA English
DT Article
ID matrix renormalization-group; lieb-robinson bounds; dynamics; atoms
AB In relativistic quantum field theory, information propagation is bounded by the speed of light. No such limit exists in the non-relativistic case, although in real physical systems, short-range interactions may be expected to restrict the propagation of information to finite velocities. The question of how fast correlations can spread in quantum many-body systems has been long studied(1). The existence of a maximal velocity, known as the Lieb-Robinson bound, has been shown theoretically to exist in several interacting many-body systems (for example, spins on a lattice(2-5))-such systems can be regarded as exhibiting an effective light cone that bounds the propagation speed of correlations. The existence of such a 'speed of light' has profound implications for condensed matter physics and quantum information, but has not been observed experimentally. Here we report the time-resolved detection of propagating correlations in an interacting quantum many-body system. By quenching a one-dimensional quantum gas in an optical lattice, we reveal how quasiparticle pairs transport correlations with a finite velocity across the system, resulting in an effective light cone for the quantum dynamics. Our results open perspectives for understanding the relaxation of closed quantum systems far from equilibrium(6), and for engineering the efficient quantum channels necessary for fast quantum computations(7).
C1 [Cheneau, Marc; Endres, Manuel; Schauss, Peter; Fukuhara, Takeshi; Gross, Christian; Bloch, Immanuel; Kuhr, Stefan] Max Planck Inst Quantum Opt, D-85748 Garching, Germany.
   [Barmettler, Peter; Poletti, Dario; Kollath, Corinna] Univ Geneva, Dept Phys Theor, CH-1211 Geneva, Switzerland.
   [Bloch, Immanuel] Univ Munich, D-80799 Munich, Germany.
   [Kollath, Corinna] Ecole Polytech, CNRS, Ctr Phys Theor, F-91128 Palaiseau, France.
   [Kuhr, Stefan] Univ Strathclyde, SUPA, Glasgow G4 0NG, Lanark, Scotland.
C3 Max Planck Society; University of Geneva; University of Munich; Institut Polytechnique de Paris; Ecole Polytechnique; Centre National de la Recherche Scientifique (CNRS); University of Strathclyde
RP Cheneau, M (corresponding author), Max Planck Inst Quantum Opt, D-85748 Garching, Germany.
EM marc.cheneau@mpq.mpg
FU MPG; DFG; EU; JSPS; 'Triangle de la physique'; ANR; SNSF; Fondation Ernst et Lucie Schmidheiny
NR 30
TC 672
Z9 721
U1 2
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 JAN 26
PY 2012
VL 481
IS 7382
BP 484
EP 487
DI 10.1038/nature10748
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 881GY
UT WOS:000299471800035
PM 22281597
DA 2026-03-09
ER

PT J
AU Fritz, JH
   Rojas, OL
   Simard, N
   McCarthy, DD
   Hapfelmeier, S
   Rubino, S
   Robertson, SJ
   Larijani, M
   Gosselin, J
   Ivanov, II
   Martin, A
   Casellas, R
   Philpott, DJ
   Girardin, SE
   McCoy, KD
   Macpherson, AJ
   Paige, CJ
   Gommerman, JL
AF Fritz, Joerg H.
   Rojas, Olga Lucia
   Simard, Nathalie
   McCarthy, Douglas D.
   Hapfelmeier, Siegfried
   Rubino, Stephen
   Robertson, Susan J.
   Larijani, Mani
   Gosselin, Jean
   Ivanov, Ivaylo I.
   Martin, Alberto
   Casellas, Rafael
   Philpott, Dana J.
   Girardin, Stephen E.
   McCoy, Kathy D.
   Macpherson, Andrew J.
   Paige, Christopher J.
   Gommerman, Jennifer L.
TI Acquisition of a multifunctional IgA+ plasma cell phenotype in the gut
SO NATURE
LA English
DT Article
ID b-cells; dendritic cells; bacterial-infection; aid expression; stromal cells; bone-marrow; homeostasis; microbiota; progenitors; maturation
AB The largest mucosal surface in the body is in the gastrointestinal tract, a location that is heavily colonized by microbes that are normally harmless. A key mechanism required for maintaining a homeostatic balance between this microbial burden and the lymphocytes that densely populate the gastrointestinal tract is the production and transepithelial transport of poly-reactive IgA (ref. 1). Within the mucosal tissues, B cells respond to cytokines, sometimes in the absence of T-cell help, undergo class switch recombination of their immunoglobulin receptor to IgA, and differentiate to become plasma cells(2). However, IgA-secreting plasma cells probably have additional attributes that are needed for coping with the tremendous bacterial load in the gastrointestinal tract. Here we report that mouse IgA(+) plasma cells also produce the antimicrobial mediators tumour-necrosis factor-alpha (TNF-alpha) and inducible nitric oxide synthase (iNOS), and expressmany molecules that are commonly associated with monocyte/granulocytic cell types. The development of iNOS-producing IgA(+) plasma cells can be recapitulated in vitro in the presence of gut stroma, and the acquisition of this multifunctional phenotype in vivo and in vitro relies on microbial co-stimulation. Deletion of TNF-a and iNOS in B-lineage cells resulted in a reduction in IgA production, altered diversification of the gut microbiota and poor clearance of a gut-tropic pathogen. These findings reveal a novel adaptation to maintaining homeostasis in the gut, and extend the repertoire of protective responses exhibited by some B-lineage cells.
C1 [Fritz, Joerg H.; Rojas, Olga Lucia; Simard, Nathalie; McCarthy, Douglas D.; Robertson, Susan J.; Larijani, Mani; Martin, Alberto; Philpott, Dana J.; Paige, Christopher J.; Gommerman, Jennifer L.] Univ Toronto, Dept Immunol, Toronto, ON M5S 1A8, Canada.
   [Simard, Nathalie; Paige, Christopher J.] Princess Margaret Hosp, Univ Hlth Network, Ontario Canc Inst, Toronto, ON M5G 2M9, Canada.
   [Hapfelmeier, Siegfried; McCoy, Kathy D.; Macpherson, Andrew J.] Univ Bern, Dept Klin Forsch Gastroenterol, CH-3010 Bern, Switzerland.
   [Rubino, Stephen; Girardin, Stephen E.] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON M5S 1A8, Canada.
   [Gosselin, Jean] Univ Laval, Dept Mol Med, Quebec City, PQ G1V 4G2, Canada.
   [Ivanov, Ivaylo I.] Columbia Univ, Coll Phys & Surg, Dept Microbiol & Immunol, Med Ctr, New York, NY 10032 USA.
   [Casellas, Rafael] NIAMSD, NIH, Bethesda, MD 20892 USA.
C3 University of Toronto; University of Toronto; University Health Network Toronto; Princess Margaret Cancer Centre; University of Bern; University of Toronto; Laval University; Columbia University; National Institutes of Health (NIH) - USA; NIH National Institute of Arthritis & Musculoskeletal & Skin Diseases (NIAMS)
RP Gommerman, JL (corresponding author), Univ Toronto, Dept Immunol, Toronto, ON M5S 1A8, Canada.
EM jen.gommerman@utoronto.ca
FU CIHR [9862, 89783, 114972, 67157]; National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health; NIH [R00 DK085329-02]; CCFA [2388]; National Institute of Arthritis and Musculoskeletal and Skin Diseases [ZIAAR041148] Funding Source: NIH RePORTER; Academy of Finland (AKA) [114972] Funding Source: Academy of Finland (AKA)
NR 29
TC 151
Z9 193
U1 0
U2 36
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JAN 12
PY 2012
VL 481
IS 7380
BP 199
EP +
DI 10.1038/nature10698
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 874TO
UT WOS:000298981200039
PM 22158124
DA 2026-03-09
ER

PT J
AU Henao-Mejia, J
   Elinav, E
   Jin, CC
   Hao, LM
   Mehal, WZ
   Strowig, T
   Thaiss, CA
   Kau, AL
   Eisenbarth, SC
   Jurczak, MJ
   Camporez, JP
   Shulman, GI
   Gordon, JI
   Hoffman, HM
   Flavell, RA
AF Henao-Mejia, Jorge
   Elinav, Eran
   Jin, Chengcheng
   Hao, Liming
   Mehal, Wajahat Z.
   Strowig, Till
   Thaiss, Christoph A.
   Kau, Andrew L.
   Eisenbarth, Stephanie C.
   Jurczak, Michael J.
   Camporez, Joao-Paulo
   Shulman, Gerald I.
   Gordon, Jeffrey I.
   Hoffman, Hal M.
   Flavell, Richard A.
TI Inflammasome-mediated dysbiosis regulates progression of NAFLD and obesity
SO NATURE
LA English
DT Article
ID nonalcoholic fatty liver; nlrp3 inflammasome; animal-models; steatohepatitis; activation; mechanism; cirrhosis
AB Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome and the leading cause of chronic liver disease in the Western world. Twenty per cent of NAFLD individuals develop chronic hepatic inflammation (non-alcoholic steatohepatitis, NASH) associated with cirrhosis, portal hypertension and hepatocellular carcinoma, yet the causes of progression from NAFLD to NASH remain obscure. Here, we show that the NLRP6 and NLRP3 inflammasomes and the effector protein IL-18 negatively regulate NAFLD/NASH progression, as well as multiple aspects of metabolic syndrome via modulation of the gut microbiota. Different mouse models reveal that inflammasome-deficiency-associated changes in the configuration of the gut microbiota are associated with exacerbated hepatic steatosis and inflammation through influx of TLR4 and TLR9 agonists into the portal circulation, leading to enhanced hepatic tumour-necrosis factor (TNF)-alpha expression that drives NASH progression. Furthermore, co-housing of inflammasome-deficient mice with wild-type mice results in exacerbation of hepatic steatosis and obesity. Thus, altered interactions between the gut microbiota and the host, produced by defective NLRP3 and NLRP6 inflammasome sensing, may govern the rate of progression of multiple metabolic syndrome-associated abnormalities, highlighting the central role of the microbiota in the pathogenesis of heretofore seemingly unrelated systemic auto-inflammatory and metabolic disorders.
C1 [Henao-Mejia, Jorge; Elinav, Eran; Jin, Chengcheng; Strowig, Till; Thaiss, Christoph A.; Flavell, Richard A.] Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT 06520 USA.
   [Jin, Chengcheng] Yale Univ, Sch Med, Dept Cell Biol, New Haven, CT 06520 USA.
   [Hao, Liming] Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06520 USA.
   [Mehal, Wajahat Z.; Jurczak, Michael J.; Camporez, Joao-Paulo; Shulman, Gerald I.] Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06520 USA.
   [Kau, Andrew L.; Gordon, Jeffrey I.] Washington Univ, Sch Med, Ctr Genome Sci & Syst Biol, St Louis, MO 63108 USA.
   [Kau, Andrew L.] Washington Univ, Sch Med, Dept Internal Med, Div Allergy & Immunol, St Louis, MO 63108 USA.
   [Eisenbarth, Stephanie C.] Yale Univ, Sch Med, Dept Lab Med, New Haven, CT 06520 USA.
   [Shulman, Gerald I.; Flavell, Richard A.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA.
   [Hoffman, Hal M.] Univ Calif San Diego, Dept Pediat, Rady Childrens Hosp San Diego, La Jolla, CA 92093 USA.
C3 Yale University; Yale University; Yale University; Yale University; Washington University (WUSTL); Washington University (WUSTL); Yale University; Howard Hughes Medical Institute; Rady Childrens Hospital San Diego; University of California System; University of California San Diego
RP Flavell, RA (corresponding author), Yale Univ, Sch Med, Dept Immunobiol, 333 Cedar St, New Haven, CT 06520 USA.
EM richard.flavell@yale.edu
FU Cancer Research Institute; Israel-US educational foundation; American Physicians for Medicine in Israel Foundation; Leukemia and Lymphoma Society; VA Merit award; Howard Hughes Medical Institute; United States-Israel binational Foundation; Crohn's and Colitis Foundation of America;  [T32HL007974];  [K08A1085038];  [R01DK076674-01];  [R01 DK-40936];  [R24 DK-085638];  [P30 DK-45735];  [U24 DK-059635]; National Heart Lung and Blood Institute [T32HL007974] Funding Source: NIH RePORTER; National Institute of Diabetes and Digestive and Kidney Diseases [P30DK045735] Funding Source: NIH RePORTER; Action Medical Research; Crohn&apos;s & Colitis Foundation [2158] Funding Source: researchfish
NR 41
TC 1942
Z9 2286
U1 9
U2 808
PU NATURE PUBLISHING 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 9
PY 2012
VL 482
IS 7384
BP 179
EP U67
DI 10.1038/nature10809
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 888HI
UT WOS:000299994100030
PM 22297845
DA 2026-03-09
ER

PT J
AU Otsuka, K
   Karato, S
AF Otsuka, Kazuhiko
   Karato, Shun-ichiro
TI Deep penetration of molten iron into the mantle caused by a morphological instability
SO NATURE
LA English
DT Article
ID fe-mg interdiffusion; high-pressures; earths core; constraints; conductivity; temperatures; entrainment; mechanisms; diffusion; boundary
AB The core-mantle boundary of Earth is a region where iron-rich liquids interact with oxides and silicates in the mantle(1). Iron enrichment may occur at the bottom of the mantle, leading to low seismic-wave velocities and high electrical conductivity(2-5), but plausible physical processes of iron enrichment have not been suggested. Diffusion-controlled iron enrichment is inefficient because it is too slow(6), although the diffusion can be fast enough along grain boundaries for some elements(7). More fundamentally, experimental studies and geophysical observations show that the core is under-saturated with oxygen, implying that the mantle next to the core should be depleted in FeO. Here we show that (Mg,Fe)O in contact with iron-rich liquids leads to a morphological instability, causing blobs of iron-rich liquid to penetrate the oxide. This morphological instability is generated by the chemical potential gradient between two materials when they are not in bulk chemical equilibrium, and should be a common process in Earth's interior. Iron-rich melt could be transported 50 to 100 kilometres away from the core-mantle boundary by this mechanism, providing an explanation for the iron-rich regions in the mantle.
C1 [Otsuka, Kazuhiko; Karato, Shun-ichiro] Yale Univ, Dept Geol & Geophys, New Haven, CT 06511 USA.
C3 Yale University
RP Karato, S (corresponding author), Yale Univ, Dept Geol & Geophys, 210 Whitney Ave, New Haven, CT 06511 USA.
EM shun-ichiro.karato@yale.edu
FU National Science Foundation [EAR-0809330]; Division Of Earth Sciences; Directorate For Geosciences [0809330] Funding Source: National Science Foundation
NR 34
TC 81
Z9 94
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 DEC 13
PY 2012
VL 492
IS 7428
BP 243
EP +
DI 10.1038/nature11663
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 053GM
UT WOS:000312259300040
PM 23235879
DA 2026-03-09
ER

PT J
AU Paniello, RC
   Day, JMD
   Moynier, F
AF Paniello, Randal C.
   Day, James M. D.
   Moynier, Frederic
TI Zinc isotopic evidence for the origin of the Moon
SO NATURE
LA English
DT Article
ID giant impact; lunar-samples; mare basalts; meteorites; copper; differentiation; geochemistry; abundances; accretion; petrology
AB Volatile elements have a fundamental role in the evolution of planets. But how budgets of volatiles were set in planets, and the nature and extent of volatile-depletion of planetary bodies during the earliest stages of Solar System formation remain poorly understood(1,2). The Moon is considered to be volatile-depleted and so it has been predicted that volatile loss should have fractionated stable isotopes of moderately volatile elements(3). One such element, zinc, exhibits strong isotopic fractionation during volatilization in planetary rocks(4,5), but is hardly fractionated during terrestrial igneous processes(6), making it a powerful tracer of the volatile histories of planets. Here we present high-precision zinc isotopic and abundance data which show that lunar magmatic rocks are enriched in the heavy isotopes of zinc and have lower zinc concentrations than terrestrial or Martian igneous rocks. Conversely, Earth and Mars have broadly chondritic zinc isotopic compositions. We show that these variations represent large-scale evaporation of zinc, most probably in the aftermath of the Moon-forming event, rather than small-scale evaporation processes during volcanism. Our results therefore represent evidence for volatile depletion of the Moon through evaporation, and are consistent with a giant impact origin for the Earth and Moon.
C1 [Paniello, Randal C.; Moynier, Frederic] Washington Univ, Dept Earth & Planetary Sci, St Louis, MO 63130 USA.
   [Paniello, Randal C.; Moynier, Frederic] Washington Univ, McDonnell Ctr Space Sci, St Louis, MO 63130 USA.
   [Day, James M. D.] Univ Calif San Diego, Scripps Inst Oceanog, Geosci Res Div, La Jolla, CA 92093 USA.
C3 Washington University (WUSTL); Washington University (WUSTL); University of California System; University of California San Diego; Scripps Institution of Oceanography
RP Moynier, F (corresponding author), Washington Univ, Dept Earth & Planetary Sci, St Louis, MO 63130 USA.
EM moynier@levee.wustl.edu
FU NASA LASER; Cosmochemistry programmes [NNX09AM64G, NNX12AH70G, NNX11AG34G, NNX12AH75G]; Exobiology programme [NNX12AD88G]
NR 33
TC 251
Z9 293
U1 0
U2 172
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD OCT 18
PY 2012
VL 490
IS 7420
BP 376
EP +
DI 10.1038/nature11507
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 021XI
UT WOS:000309918500040
PM 23075987
DA 2026-03-09
ER

PT J
AU Chen, T
   Heller, E
   Beronja, S
   Oshimori, N
   Stokes, N
   Fuchs, E
AF Chen, Ting
   Heller, Evan
   Beronja, Slobodan
   Oshimori, Naoki
   Stokes, Nicole
   Fuchs, Elaine
TI An RNA interference screen uncovers a new molecule in stem cell self-renewal and long-term regeneration
SO NATURE
LA English
DT Article
ID differentiation; niche; tbx1; proliferation; induction; quiescent; distinct; mice
AB Adult stem cells sustain tissue maintenance and regeneration throughout the lifetime of an animal(1,2). These cells often reside in specific signalling niches that orchestrate the stem cell's balancing act between quiescence and cell-cycle re-entry based on the demand for tissue regeneration(2-4). How stem cells maintain their capacity to replenish themselves after tissue regeneration is poorly understood. Here we use RNA-interference-based loss-of-function screening as a powerful approach to uncover transcriptional regulators that govern the self-renewal capacity and regenerative potential of stem cells. Hair follicle stem cells provide an ideal model. These cells have been purified and characterized from their native niche in vivo and, in contrast to their rapidly dividing progeny, they can be maintained and passaged long-term in vitro(5-7). Focusing on the nuclear proteins and/or transcription factors that are enriched in stem cells compared with their progeny(5,6), we screened similar to 2,000 short hairpin RNAs for their effect on long-term, but not short-term, stem cell self-renewal in vitro. To address the physiological relevance of our findings, we selected one candidate that was uncovered in the screen: TBX1. This transcription factor is expressed in many tissues but has not been studied in the context of stem cell biology. By conditionally ablating Tbx1 in vivo, we showed that during homeostasis, tissue regeneration occurs normally but is markedly delayed. We then devised an in vivo assay for stem cell replenishment and found that when challenged with repetitive rounds of regeneration, the Tbx1-deficient stem cell niche becomes progressively depleted. Addressing the mechanism of TBX1 action, we discovered that TBX1 acts as an intrinsic rheostat of BMP signalling: it is a gatekeeper that governs the transition between stem cell quiescence and proliferation in hair follicles. Our results validate the RNA interference screen and underscore its power in unearthing new molecules that govern stem cell self-renewal and tissue-regenerative potential.
C1 [Chen, Ting; Heller, Evan; Beronja, Slobodan; Oshimori, Naoki; Stokes, Nicole; Fuchs, Elaine] Rockefeller Univ, Howard Hughes Med Inst, New York, NY 10065 USA.
C3 Howard Hughes Medical Institute; Rockefeller University
RP Fuchs, E (corresponding author), Rockefeller Univ, Howard Hughes Med Inst, New York, NY 10065 USA.
EM fuchs@rockefeller.edu
FU NYSTEM [C026722]; NYSDOH [C023046]; National Institutes of Health [R01-AR050452]; Empire State Stem Cell [NYSTEM N09G074]; New York Stem Cell Foundation; National Institute of Arthritis and Musculoskeletal and Skin Diseases [R01AR050452] Funding Source: NIH RePORTER
NR 31
TC 83
Z9 105
U1 1
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 MAY 3
PY 2012
VL 485
IS 7396
BP 104
EP U134
DI 10.1038/nature10940
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 934NV
UT WOS:000303451900043
PM 22495305
DA 2026-03-09
ER

PT J
AU Steinmetz, PRH
   Kraus, JEM
   Larroux, C
   Hammel, JU
   Amon-Hassenzahl, A
   Houliston, E
   Wörheide, G
   Nickel, M
   Degnan, BM
   Technau, U
AF Steinmetz, Patrick R. H.
   Kraus, Johanna E. M.
   Larroux, Claire
   Hammel, Joerg U.
   Amon-Hassenzahl, Annette
   Houliston, Evelyn
   Woerheide, Gert
   Nickel, Michael
   Degnan, Bernard M.
   Technau, Ulrich
TI Independent evolution of striated muscles in cnidarians and bilaterians
SO NATURE
LA English
DT Article
ID multiple sequence alignment; tethya-wilhelma; sea-anemone; invertebrate muscles; molecular evolution; genome reveals; expression; protein; chain; demosponge
AB Striated muscles are present in bilaterian animals (for example, vertebrates, insects and annelids) and some non-bilaterian eumetazoans (that is, cnidarians and ctenophores). The considerable ultrastructural similarity of striated muscles between these animal groups is thought to reflect a common evolutionary origin(1,2). Here we show that a muscle protein core set, including a type II myosin heavy chain (MyHC) motor protein characteristic of striated muscles in vertebrates, was already present in unicellular organisms before the origin of multicellular animals. Furthermore, 'striated muscle' and 'non-muscle' myhc orthologues are expressed differentially in two sponges, compatible with a functional diversification before the origin of true muscles and the subsequent use of striated muscle MyHC in fast-contracting smooth and striated muscle. Cnidarians and ctenophores possess striated muscle myhc orthologues but lack crucial components of bilaterian striated muscles, such as genes that code for titin and the troponin complex, suggesting the convergent evolution of striated muscles. Consistently, jellyfish orthologues of a shared set of bilaterian Z-disc proteins are not associated with striated muscles, but are instead expressed elsewhere or ubiquitously. The independent evolution of eumetazoan striated muscles through the addition of new proteins to a pre-existing, ancestral contractile apparatus may serve as a model for the evolution of complex animal cell types.
C1 [Steinmetz, Patrick R. H.; Kraus, Johanna E. M.; Technau, Ulrich] Univ Vienna, Dept Mol Evolut & Dev, Ctr Organismal Syst Biol, A-1090 Vienna, Austria.
   [Larroux, Claire; Degnan, Bernard M.] Univ Queensland, Sch Biol Sci, Ctr Marine Sci, Brisbane, Qld 4072, Australia.
   [Larroux, Claire; Woerheide, Gert] Univ Munich, Dept Earth & Environm Sci Palaeontol & Geobiol, D-80333 Munich, Germany.
   [Hammel, Joerg U.; Nickel, Michael] Univ Jena, Inst Spezielle Zool & Evolut biol, Phyletischem Museum, D-07743 Jena, Germany.
   [Amon-Hassenzahl, Annette] Tech Univ Darmstadt, Inst Zool, D-64287 Darmstadt, Germany.
   [Houliston, Evelyn] CNRS, Biol Dev UMR 7009, F-06230 Villefranche Sur Mer, France.
   [Houliston, Evelyn] Univ Paris 06, F-06230 Villefranche Sur Mer, France.
   [Woerheide, Gert; Nickel, Michael] Univ Munich, GeoBio Ctr, D-80333 Munich, Germany.
   [Woerheide, Gert] Bayer Staatssammlung Palaontol & Geol, D-80333 Munich, Germany.
C3 University of Vienna; University of Queensland; University of Munich; Friedrich Schiller University of Jena; Technical University of Darmstadt; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB); Sorbonne Universite; University of Munich
RP Technau, U (corresponding author), Univ Vienna, Dept Mol Evolut & Dev, Ctr Organismal Syst Biol, Althanstr 14, A-1090 Vienna, Austria.
EM ulrich.technau@univie.ac.at
FU Austrian Science Fund [P21108-B17]; ITN EVONET [215781]; Australian Research Council; Alexander von Humboldt Foundation; ANR; German Science Foundation [1174, Wo896/6]; Academy of Finland (AKA) [215781] Funding Source: Academy of Finland (AKA); Austrian Science Fund (FWF) [P21108] Funding Source: Austrian Science Fund (FWF); Austrian Science Fund (FWF) [P 21108] Funding Source: researchfish
NR 67
TC 187
Z9 223
U1 0
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 JUL 12
PY 2012
VL 487
IS 7406
BP 231
EP U1508
DI 10.1038/nature11180
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 972LP
UT WOS:000306278900039
PM 22763458
DA 2026-03-09
ER

PT J
AU Li, W
   Shuai, L
   Wan, HF
   Dong, MZ
   Wang, M
   Sang, LS
   Feng, CJ
   Luo, GZ
   Li, TD
   Li, X
   Wang, LB
   Zheng, QY
   Sheng, C
   Wu, HJ
   Liu, ZH
   Liu, L
   Wang, L
   Wang, XJ
   Zhao, XY
   Zhou, Q
AF Li, Wei
   Shuai, Ling
   Wan, Haifeng
   Dong, Mingzhu
   Wang, Meng
   Sang, Lisi
   Feng, Chunjing
   Luo, Guan-Zheng
   Li, Tianda
   Li, Xin
   Wang, Libin
   Zheng, Qin-Yuan
   Sheng, Chao
   Wu, Hua-Jun
   Liu, Zhonghua
   Liu, Lei
   Wang, Liu
   Wang, Xiu-Jie
   Zhao, Xiao-Yang
   Zhou, Qi
TI Androgenetic haploid embryonic stem cells produce live transgenic mice
SO NATURE
LA English
DT Article
ID mouse embryos; generation; embryogenesis; pluripotent; derivation; oocytes; genome; expression; injection; develop
AB Haploids and double haploids are important resources for studying recessive traits and have large impacts on crop breeding(1), but natural haploids are rare in animals. Mammalian haploids are restricted to germline cells and are occasionally found in tumours with massive chromosome loss(2,3). Recent success in establishing haploid embryonic stem (ES) cells in medaka fish(4) and mice(5,6) raised the possibility of using engineered mammalian haploid cells in genetic studies. However, the availability and functional characterization of mammalian haploid ES cells are still limited. Here we show that mouse androgenetic haploid ES (ahES) cell lines can be established by transferring sperm into an enucleated oocyte. The ahES cells maintain haploidy and stable growth over 30 passages, express pluripotent markers, possess the ability to differentiate into all three germ layers in vitro and in vivo, and contribute to germlines of chimaeras when injected into blastocysts. Although epigenetically distinct from sperm cells, the ahES cells can produce viable and fertile progenies after intracytoplasmic injection into mature oocytes. The oocyte-injection procedure can also produce viable transgenic mice from genetically engineered ahES cells. Our findings show the developmental pluripotency of androgenentic haploids and provide a new tool to quickly produce genetic models for recessive traits. They may also shed new light on assisted reproduction.
C1 [Li, Wei; Shuai, Ling; Wan, Haifeng; Dong, Mingzhu; Sang, Lisi; Feng, Chunjing; Li, Tianda; Li, Xin; Wang, Libin; Zheng, Qin-Yuan; Sheng, Chao; Liu, Lei; Wang, Liu; Zhao, Xiao-Yang; Zhou, Qi] Chinese Acad Sci, Inst Zool, State Key Lab Reprod Biol, Beijing 100101, Peoples R China.
   [Li, Wei; Wan, Haifeng; Dong, Mingzhu; Sang, Lisi; Feng, Chunjing; Wang, Libin; Zheng, Qin-Yuan; Wu, Hua-Jun] Chinese Acad Sci, Grad Univ, Beijing 100049, Peoples R China.
   [Shuai, Ling; Li, Tianda; Li, Xin; Sheng, Chao; Liu, Zhonghua] NE Agr Univ China, Coll Life Sci, Harbin 150030, Peoples R China.
   [Wang, Meng; Luo, Guan-Zheng; Wu, Hua-Jun; Wang, Xiu-Jie] Chinese Acad Sci, Inst Genet & Dev Biol, Ctr Mol Syst Biol, Beijing 100101, Peoples R China.
C3 Chinese Academy of Sciences; Institute of Zoology, CAS; Chinese Academy of Sciences; University of Chinese Academy of Sciences, CAS; Northeast Agricultural University - China; Chinese Academy of Sciences; Institute of Genetics & Developmental Biology, CAS
RP Zhou, Q (corresponding author), Chinese Acad Sci, Inst Zool, State Key Lab Reprod Biol, Beijing 100101, Peoples R China.
EM xyzhao@ioz.ac.cn; qzhou@ioz.ac.cn
FU National Science Foundation of China [90919060]; China National Basic Research Program [2012CBA01300]; Chinese Academy of Sciences [XDA01020100]
NR 31
TC 146
Z9 194
U1 3
U2 163
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD OCT 18
PY 2012
VL 490
IS 7420
BP 407
EP +
DI 10.1038/nature11435
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 021XI
UT WOS:000309918500047
PM 23023130
DA 2026-03-09
ER

PT J
AU Shah, DI
   Takahashi-Makise, N
   Cooney, JD
   Li, LT
   Schultz, IJ
   Pierce, EL
   Narla, A
   Seguin, A
   Hattangadi, SM
   Medlock, AE
   Langer, NB
   Dailey, TA
   Hurst, SN
   Faccenda, D
   Wiwczar, JM
   Heggers, SK
   Vogin, G
   Chen, W
   Chen, CY
   Campagna, DR
   Brugnara, C
   Zhou, Y
   Ebert, BL
   Danial, NN
   Fleming, MD
   Ward, DM
   Campanella, M
   Dailey, HA
   Kaplan, J
   Paw, BH
AF Shah, Dhvanit I.
   Takahashi-Makise, Naoko
   Cooney, Jeffrey D.
   Li, Liangtao
   Schultz, Iman J.
   Pierce, Eric L.
   Narla, Anupama
   Seguin, Alexandra
   Hattangadi, Shilpa M.
   Medlock, Amy E.
   Langer, Nathaniel B.
   Dailey, Tamara A.
   Hurst, Slater N.
   Faccenda, Danilo
   Wiwczar, Jessica M.
   Heggers, Spencer K.
   Vogin, Guillaume
   Chen, Wen
   Chen, Caiyong
   Campagna, Dean R.
   Brugnara, Carlo
   Zhou, Yi
   Ebert, Benjamin L.
   Danial, Nika N.
   Fleming, Mark D.
   Ward, Diane M.
   Campanella, Michelangelo
   Dailey, Harry A.
   Kaplan, Jerry
   Paw, Barry H.
TI Mitochondrial Atpif1 regulates haem synthesis in developing erythroblasts
SO NATURE
LA English
DT Article
ID iron-metabolism; zebrafish; yeast; ferrochelatase; inhibitor; transport; defects; protein; cytosol; anemia
AB Defects in the availability of haem substrates or the catalytic activity of the terminal enzyme in haem biosynthesis, ferrochelatase (Fech), impair haem synthesis and thus cause human congenital anaemias(1,2). The interdependent functions of regulators of mitochondrial homeostasis and enzymes responsible for haem synthesis are largely unknown. To investigate this we used zebrafish genetic screens and cloned mitochondrial ATPase inhibitory factor 1 (atpif1) from a zebrafish mutant with profound anaemia, pinotage (pnt (tq209)). Here we describe a direct mechanism establishing that Atpif1 regulates the catalytic efficiency of vertebrate Fech to synthesize haem. The loss of Atpif1 impairs haemoglobin synthesis in zebrafish, mouse and human haematopoietic models as a consequence of diminished Fech activity and elevated mitochondrial pH. To understand the relationship between mitochondrial pH, redox potential, [2Fe-2S] clusters and Fech activity, we used genetic complementation studies of Fech constructs with or without [2Fe-2S] clusters in pnt, as well as pharmacological agents modulating mitochondrial pH and redox potential. The presence of [2Fe-2S] cluster renders vertebrate Fech vulnerable to perturbations in Atpif1-regulated mitochondrial pH and redox potential. Therefore, Atpif1 deficiency reduces the efficiency of vertebrate Fech to synthesize haem, resulting in anaemia. The identification of mitochondrial Atpif1 as a regulator of haem synthesis advances our understanding of the mechanisms regulating mitochondrial haem homeostasis and red blood cell development. An ATPIF1 deficiency may contribute to important human diseases, such as congenital sideroblastic anaemias and mitochondriopathies.
C1 [Shah, Dhvanit I.; Cooney, Jeffrey D.; Schultz, Iman J.; Pierce, Eric L.; Narla, Anupama; Langer, Nathaniel B.; Hurst, Slater N.; Heggers, Spencer K.; Vogin, Guillaume; Chen, Wen; Chen, Caiyong; Ebert, Benjamin L.; Paw, Barry H.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Div Hematol, Boston, MA 02115 USA.
   [Takahashi-Makise, Naoko; Li, Liangtao; Seguin, Alexandra; Ward, Diane M.; Kaplan, Jerry] Univ Utah, Sch Med, Dept Pathol, Salt Lake City, UT 84312 USA.
   [Narla, Anupama; Hattangadi, Shilpa M.; Paw, Barry H.] Harvard Univ, Sch Med, Boston Childrens Hosp, Dept Med,Div Hematol Oncol, Boston, MA 02115 USA.
   [Hattangadi, Shilpa M.] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA.
   [Hattangadi, Shilpa M.] MIT, Cambridge, MA 02142 USA.
   [Medlock, Amy E.; Dailey, Tamara A.; Dailey, Harry A.] Univ Georgia, Dept Microbiol, Biomed & Hlth Sci Inst, Athens, GA 30602 USA.
   [Medlock, Amy E.; Dailey, Tamara A.; Dailey, Harry A.] Univ Georgia, Dept Biochem, Biomed & Hlth Sci Inst, Athens, GA 30602 USA.
   [Medlock, Amy E.; Dailey, Tamara A.; Dailey, Harry A.] Univ Georgia, Dept Mol Biol, Biomed & Hlth Sci Inst, Athens, GA 30602 USA.
   [Faccenda, Danilo; Campanella, Michelangelo] Univ London Royal Vet Coll, London NW1 0TU, England.
   [Faccenda, Danilo; Campanella, Michelangelo] UCL, Consortium Mitochondrial Res, London NW1 0TU, England.
   [Wiwczar, Jessica M.; Danial, Nika N.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
   [Campagna, Dean R.; Fleming, Mark D.] Harvard Univ, Sch Med, Boston Childrens Hosp, Dept Pathol, Boston, MA 02115 USA.
   [Brugnara, Carlo] Harvard Univ, Sch Med, Boston Childrens Hosp, Dept Lab Med, Boston, MA 02115 USA.
C3 Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard Medical School; Utah System of Higher Education; University of Utah; Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Boston Children's Hospital; Massachusetts Institute of Technology (MIT); Whitehead Institute; Massachusetts Institute of Technology (MIT); University System of Georgia; University of Georgia; University System of Georgia; University of Georgia; University System of Georgia; University of Georgia; University of London; University of London Royal Veterinary College; University of London; University College London; Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Harvard Medical School
RP Paw, BH (corresponding author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Div Hematol, Boston, MA 02115 USA.
EM hdailey@uga.edu; jerry.kaplan@path.utah.edu; bpaw@rics.bwh.harvard.edu
FU Cooley's Anemia Foundation; March of Dimes Foundation; American Heart Association; Dutch National Science Fund; Fondation Soldati pour la Recherche en Cancerologie; Burroughs Welcome Fund; NIDDK; NHLBI; BBSRC [BB/I013695/1] Funding Source: UKRI; Biotechnology and Biological Sciences Research Council [BB/I013695/1] Funding Source: researchfish; National Heart Lung and Blood Institute [R01HL082945, P01HL032262] Funding Source: NIH RePORTER
NR 30
TC 83
Z9 100
U1 0
U2 33
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD NOV 22
PY 2012
VL 491
IS 7425
BP 608
EP 612
DI 10.1038/nature11536
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 040RE
UT WOS:000311339800055
PM 23135403
DA 2026-03-09
ER

PT J
AU Whyte, WA
   Bilodeau, S
   Orlando, DA
   Hoke, HA
   Frampton, GM
   Foster, CT
   Cowley, SM
   Young, RA
AF Whyte, Warren A.
   Bilodeau, Steve
   Orlando, David A.
   Hoke, Heather A.
   Frampton, Garrett M.
   Foster, Charles T.
   Cowley, Shaun M.
   Young, Richard A.
TI Enhancer decommissioning by LSD1 during embryonic stem cell differentiation
SO NATURE
LA English
DT Article
ID histone demethylase; interaction network; gene; transcription; chromatin; expression; complexes; programs; oct-3/4; sox2
AB Transcription factors and chromatin modifiers are important in the programming and reprogramming of cellular states during development(1,2). Transcription factors bind to enhancer elements and recruit coactivators and chromatin-modifying enzymes to facilitate transcription initiation(3,4). During differentiation a subset of these enhancers must be silenced, but the mechanisms underlying enhancer silencing are poorly understood. Here we show that the histone demethylase lysine-specific demethylase 1 (LSD1; ref. 5), which demethylates histone H3 on Lys 4 or Lys 9 (H3K4/K9), is essential in decommissioning enhancers during the differentiation of mouse embryonic stem cells (ESCs). LSD1 occupies enhancers of active genes that are critical for control of the state of ESCs. However, LSD1 is not essential for the maintenance of ESC identity. Instead, ESCs lacking LSD1 activity fail to differentiate fully, and ESC-specific enhancers fail to undergo the histone demethylation events associated with differentiation. At active enhancers, LSD1 is a component of the NuRD (nucleosome remodelling and histone deacetylase) complex, which contains additional subunits that are necessary for ESC differentiation. We propose that the LSD1-NuRD complex decommissions enhancers of the pluripotency program during differentiation, which is essential for the complete shutdown of the ESC gene expression program and the transition to new cell states.
C1 [Whyte, Warren A.; Bilodeau, Steve; Orlando, David A.; Hoke, Heather A.; Frampton, Garrett M.; Young, Richard A.] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA.
   [Whyte, Warren A.; Hoke, Heather A.; Frampton, Garrett M.; Young, Richard A.] MIT, Dept Biol, Cambridge, MA 02139 USA.
   [Foster, Charles T.] Univ Munich, Adolf Butenandt Inst, Dept Mol Biol, D-80336 Munich, Germany.
   [Foster, Charles T.; Cowley, Shaun M.] Univ Leicester, Dept Biochem, Leicester LE1 9HN, Leics, England.
C3 Massachusetts Institute of Technology (MIT); Whitehead Institute; Massachusetts Institute of Technology (MIT); University of Munich; University of Leicester
RP Young, RA (corresponding author), Whitehead Inst Biomed Res, 9 Cambridge Ctr, Cambridge, MA 02142 USA.
EM young@wi.mit.edu
FU Canadian Institutes of Health Research; Medical Research Council; National Institutes of Health [HG002668, NS055923]; MRC [MR/J009202/1, G0600135] Funding Source: UKRI; Medical Research Council [G0600135, MR/J009202/1] Funding Source: researchfish
NR 30
TC 481
Z9 592
U1 0
U2 67
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD FEB 9
PY 2012
VL 482
IS 7384
BP 221
EP 225
DI 10.1038/nature10805
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 888HI
UT WOS:000299994100039
PM 22297846
DA 2026-03-09
ER

PT J
AU Sanyal, A
   Lajoie, BR
   Jain, G
   Dekker, J
AF Sanyal, Amartya
   Lajoie, Bryan R.
   Jain, Gaurav
   Dekker, Job
TI The long-range interaction landscape of gene promoters
SO NATURE
LA English
DT Article
ID chromosomal interactions; chromatin conformation; elements; binding; domain; 5c
AB The vast non-coding portion of the human genome is full of functional elements and disease-causing regulatory variants. The principles defining the relationships between these elements and distal target genes remain unknown. Promoters and distal elements can engage in looping interactions that have been implicated in gene regulation(1). Here we have applied chromosome conformation capture carbon copy (5C(2)) to interrogate comprehensively interactions between transcription start sites (TSSs) and distal elements in 1% of the human genome representing the ENCODE pilot project regions(3). 5C maps were generated for GM12878, K562 and HeLa-S3 cells and results were integrated with data from the ENCODE consortium(4). In each cell line we discovered >1,000 long-range interactions between promoters and distal sites that include elements resembling enhancers, promoters and CTCF-bound sites. We observed significant correlations between gene expression, promoter-enhancer interactions and the presence of enhancer RNAs. Long-range interactions show marked asymmetry with a bias for interactions with elements located similar to 120 kilobases upstream of the TSS. Long-range interactions are often not blocked by sites bound by CTCF and cohesin, indicating that many of these sites do not demarcate physically insulated gene domains. Furthermore, only similar to 7% of looping interactions are with the nearest gene, indicating that genomic proximity is not a simple predictor for long-range interactions. Finally, promoters and distal elements are engaged in multiple long-range interactions to form complex networks. Our results start to place genes and regulatory elements in three-dimensional context, revealing their functional relationships.
C1 [Sanyal, Amartya; Lajoie, Bryan R.; Jain, Gaurav; Dekker, Job] Univ Massachusetts, Sch Med, Dept Biochem & Mol Pharmacol, Program Syst Biol,Program Gene Funct & Express, Worcester, MA 01605 USA.
C3 University of Massachusetts System; University of Massachusetts Worcester
RP Dekker, J (corresponding author), Univ Massachusetts, Sch Med, Dept Biochem & Mol Pharmacol, Program Syst Biol,Program Gene Funct & Express, 364 Plantat St, Worcester, MA 01605 USA.
EM job.dekker@umassmed.edu
FU National Institutes of Health, National Human Genome Research Institute [HG003143, HG003143-06S1]; W.M Keck Foundation; National Human Genome Research Institute [R01HG003143] Funding Source: NIH RePORTER
NR 26
TC 1117
Z9 1430
U1 0
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 SEP 6
PY 2012
VL 489
IS 7414
BP 109
EP U127
DI 10.1038/nature11279
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 999WW
UT WOS:000308347000044
PM 22955621
DA 2026-03-09
ER

PT J
AU Rozenblatt-Rosen, O
   Deo, RC
   Padi, M
   Adelmant, G
   Calderwood, MA
   Rolland, T
   Grace, M
   Dricot, A
   Askenazi, M
   Tavares, M
   Pevzner, SJ
   Abderazzaq, F
   Byrdsong, D
   Carvunis, AR
   Chen, AA
   Cheng, JW
   Correll, M
   Duarte, M
   Fan, CY
   Feltkamp, MC
   Ficarro, SB
   Franchi, R
   Garg, BK
   Gulbahce, N
   Hao, T
   Holthaus, AM
   James, R
   Korkhin, A
   Litovchick, L
   Mar, JC
   Pak, TR
   Rabello, S
   Rubio, R
   Shen, Y
   Singh, S
   Spangle, JM
   Tasan, M
   Wanamaker, S
   Webber, JT
   Roecklein-Canfield, J
   Johannsen, E
   Barabási, AL
   Beroukhim, R
   Kieff, E
   Cusick, ME
   Hill, DE
   Münger, K
   Marto, JA
   Quackenbush, J
   Roth, FP
   DeCaprio, JA
   Vidal, M
AF Rozenblatt-Rosen, Orit
   Deo, Rahul C.
   Padi, Megha
   Adelmant, Guillaume
   Calderwood, Michael A.
   Rolland, Thomas
   Grace, Miranda
   Dricot, Amelie
   Askenazi, Manor
   Tavares, Maria
   Pevzner, Samuel J.
   Abderazzaq, Fieda
   Byrdsong, Danielle
   Carvunis, Anne-Ruxandra
   Chen, Alyce A.
   Cheng, Jingwei
   Correll, Mick
   Duarte, Melissa
   Fan, Changyu
   Feltkamp, Mariet C.
   Ficarro, Scott B.
   Franchi, Rachel
   Garg, Brijesh K.
   Gulbahce, Natali
   Hao, Tong
   Holthaus, Amy M.
   James, Robert
   Korkhin, Anna
   Litovchick, Larisa
   Mar, Jessica C.
   Pak, Theodore R.
   Rabello, Sabrina
   Rubio, Renee
   Shen, Yun
   Singh, Saurav
   Spangle, Jennifer M.
   Tasan, Murat
   Wanamaker, Shelly
   Webber, James T.
   Roecklein-Canfield, Jennifer
   Johannsen, Eric
   Barabasi, Albert-Laszlo
   Beroukhim, Rameen
   Kieff, Elliott
   Cusick, Michael E.
   Hill, David E.
   Muenger, Karl
   Marto, Jarrod A.
   Quackenbush, John
   Roth, Frederick P.
   DeCaprio, James A.
   Vidal, Marc
TI Interpreting cancer genomes using systematic host network perturbations by tumour virus proteins
SO NATURE
LA English
DT Article
ID epstein-barr-virus; association; complex
AB Genotypic differences greatly influence susceptibility and resistance to disease. Understanding genotype-phenotype relationships requires that phenotypes be viewed as manifestations of network properties, rather than simply as the result of individual genomic variations(1). Genome sequencing efforts have identified numerous germline mutations, and large numbers of somatic genomic alterations, associated with a predisposition to cancer(2). However, it remains difficult to distinguish background, or 'passenger', cancer mutations from causal, or 'driver', mutations in these data sets. Human viruses intrinsically depend on their host cell during the course of infection and can elicit pathological phenotypes similar to those arising from mutations(3). Here we test the hypothesis that genomic variations and tumour viruses may cause cancer through related mechanisms, by systematically examining host interactome and transcriptome network perturbations caused by DNA tumour virus proteins. The resulting integrated viral perturbation data reflects rewiring of the host cell networks, and highlights pathways, such as Notch signalling and apoptosis, that go awry in cancer. We show that systematic analyses of host targets of viral proteins can identify cancer genes with a success rate on a par with their identification through functional genomics and large-scale cataloguing of tumour mutations. Together, these complementary approaches increase the specificity of cancer gene identification. Combining systems-level studies of pathogen-encoded gene products with genomic approaches will facilitate the prioritization of cancer-causing driver genes to advance the understanding of the genetic basis of human cancer.
C1 [Rozenblatt-Rosen, Orit; Deo, Rahul C.; Padi, Megha; Adelmant, Guillaume; Calderwood, Michael A.; Rolland, Thomas; Dricot, Amelie; Askenazi, Manor; Tavares, Maria; Abderazzaq, Fieda; Byrdsong, Danielle; Chen, Alyce A.; Duarte, Melissa; Fan, Changyu; Ficarro, Scott B.; Franchi, Rachel; Garg, Brijesh K.; Gulbahce, Natali; Hao, Tong; Holthaus, Amy M.; James, Robert; Korkhin, Anna; Litovchick, Larisa; Mar, Jessica C.; Rabello, Sabrina; Rubio, Renee; Shen, Yun; Spangle, Jennifer M.; Tasan, Murat; Johannsen, Eric; Barabasi, Albert-Laszlo; Kieff, Elliott; Cusick, Michael E.; Hill, David E.; Muenger, Karl; Marto, Jarrod A.; Quackenbush, John; Roth, Frederick P.; DeCaprio, James A.; Vidal, Marc] Dana Farber Canc Inst, CCSB, Genom Anal Network Perturbat Ctr Excellence Genom, Boston, MA 02215 USA.
   [Rozenblatt-Rosen, Orit; Tavares, Maria; Cheng, Jingwei; Korkhin, Anna; Litovchick, Larisa; Beroukhim, Rameen; DeCaprio, James A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA.
   [Rozenblatt-Rosen, Orit; Tavares, Maria; Cheng, Jingwei; Korkhin, Anna; Litovchick, Larisa; Rabello, Sabrina; Barabasi, Albert-Laszlo; Beroukhim, Rameen; DeCaprio, James A.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
   [Deo, Rahul C.; Adelmant, Guillaume; Askenazi, Manor; Ficarro, Scott B.; Garg, Brijesh K.; Singh, Saurav; Tasan, Murat; Webber, James T.; Marto, Jarrod A.; Roth, Frederick P.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
   [Deo, Rahul C.] Univ Calif San Francisco, Dept Med, Cardiovasc Res Inst, San Francisco, CA 94143 USA.
   [Deo, Rahul C.] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA.
   [Padi, Megha; Abderazzaq, Fieda; Correll, Mick; Mar, Jessica C.; Rubio, Renee; Quackenbush, John] Dana Farber Canc Inst, CCCB, Dept Biostat & Computat Biol, Boston, MA 02215 USA.
   [Padi, Megha; Adelmant, Guillaume; Calderwood, Michael A.; Rolland, Thomas; Dricot, Amelie; Askenazi, Manor; Tavares, Maria; Pevzner, Samuel J.; Abderazzaq, Fieda; Byrdsong, Danielle; Carvunis, Anne-Ruxandra; Correll, Mick; Duarte, Melissa; Fan, Changyu; Ficarro, Scott B.; Franchi, Rachel; Garg, Brijesh K.; Gulbahce, Natali; Hao, Tong; James, Robert; Mar, Jessica C.; Rabello, Sabrina; Rubio, Renee; Shen, Yun; Singh, Saurav; Wanamaker, Shelly; Webber, James T.; Roecklein-Canfield, Jennifer; Barabasi, Albert-Laszlo; Beroukhim, Rameen; Cusick, Michael E.; Hill, David E.; Marto, Jarrod A.; Quackenbush, John; Roth, Frederick P.; Vidal, Marc] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA.
   [Padi, Megha; Mar, Jessica C.; Quackenbush, John] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
   [Adelmant, Guillaume; Askenazi, Manor; Tavares, Maria; Ficarro, Scott B.; Garg, Brijesh K.; Singh, Saurav; Webber, James T.; Marto, Jarrod A.] Dana Farber Canc Inst, Blais Prote Ctr, Boston, MA 02215 USA.
   [Calderwood, Michael A.; Rolland, Thomas; Dricot, Amelie; Pevzner, Samuel J.; Byrdsong, Danielle; Carvunis, Anne-Ruxandra; Fan, Changyu; Hao, Tong; James, Robert; Shen, Yun; Wanamaker, Shelly; Cusick, Michael E.; Hill, David E.; Vidal, Marc] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
   [Calderwood, Michael A.; Duarte, Melissa; Holthaus, Amy M.; Johannsen, Eric; Kieff, Elliott] Brigham & Womens Hosp, Channing Lab, Div Infect Dis, Boston, MA 02115 USA.
   [Calderwood, Michael A.; Grace, Miranda; Chen, Alyce A.; Duarte, Melissa; Holthaus, Amy M.; Spangle, Jennifer M.; Johannsen, Eric; Kieff, Elliott; Muenger, Karl] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.
   [Calderwood, Michael A.; Duarte, Melissa; Holthaus, Amy M.; Johannsen, Eric; Kieff, Elliott] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA 02115 USA.
   [Pevzner, Samuel J.] Boston Univ, Dept Biomed Engn, Boston, MA 02118 USA.
   [Pevzner, Samuel J.] Boston Univ, Sch Med, Boston, MA 02118 USA.
   [Feltkamp, Mariet C.] Leiden Univ, Med Ctr, Dept Med Microbiol, NL-2300 RC Leiden, Netherlands.
   [Franchi, Rachel; Wanamaker, Shelly; Roecklein-Canfield, Jennifer] Simmons Coll, Dept Chem, Boston, MA 02115 USA.
   [Gulbahce, Natali; Rabello, Sabrina; Barabasi, Albert-Laszlo] Northeastern Univ, CCNR, Boston, MA 02115 USA.
   [Gulbahce, Natali; Rabello, Sabrina; Barabasi, Albert-Laszlo] Northeastern Univ, Dept Phys, Boston, MA 02115 USA.
   [Gulbahce, Natali] Univ Calif San Francisco, Dept Cellular & Mol Pharmacol, San Francisco, CA 94158 USA.
   [Pak, Theodore R.; Tasan, Murat; Roth, Frederick P.] Univ Toronto, Donnelly Ctr, Toronto, ON M5G 1X5, Canada.
   [Pak, Theodore R.; Tasan, Murat; Roth, Frederick P.] Univ Toronto, Dept Mol Genet, Toronto, ON M5G 1X5, Canada.
   [Pak, Theodore R.; Tasan, Murat; Roth, Frederick P.] Univ Toronto, Dept Comp Sci, Toronto, ON M5G 1X5, Canada.
   [Pak, Theodore R.; Tasan, Murat; Roth, Frederick P.] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada.
   [Beroukhim, Rameen] Broad Inst, Cambridge, MA 02142 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 Medical School; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard University; Harvard Medical School; University of California System; University of California San Francisco; University of California System; University of California San Francisco; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard T.H. Chan School of Public Health; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard University; Harvard Medical School; Harvard University; Harvard Medical School; Boston University; Boston University; Leiden University - Excl LUMC; Leiden University; Leiden University Medical Center (LUMC); Simmons University; Northeastern University; Northeastern University; University of California System; University of California San Francisco; University of Toronto; University of Toronto; University of Toronto; University of Toronto; Sinai Health System Toronto; Lunenfeld Tanenbaum Research Institute; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute
RP Marto, JA (corresponding author), Dana Farber Canc Inst, CCSB, Genom Anal Network Perturbat Ctr Excellence Genom, Boston, MA 02215 USA.
EM jarrod_marto@dfci.harvard.edu; johnq@jimmy.harvard.edu; fritz.roth@utoronto.ca; james_decaprio@dfci.harvard.edu; marc_vidal@dfci.harvard.edu
FU Center of Excellence in Genomic Science (CEGS) from the National Human Genome Research Institute (NHGRI) of the National Institutes of Health (NIH) [P50HG004233]; Institute Sponsored Research funds from the Dana-Farber Cancer Institute Strategic Initiative; NIH [R01HG001715, R01CA093804, R01CA063113, P01CA050661, R01CA081135, R01CA066980, U01CA141583, R01CA131354, R01CA047006, R01CA085180, T32HL007208, K08HL098361, K08CA122833, F32GM095284, K25HG006031]; Canada Excellence Research Chairs (CERC) Program, Canadian Institute for Advanced Research Fellowship and Ontario Research Fund; James S. McDonnell Foundation [220020084]; National Cancer Institute [R01CA047006] Funding Source: NIH RePORTER; National Heart Lung and Blood Institute [T32HL007208] Funding Source: NIH RePORTER
NR 29
TC 313
Z9 376
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 JUL 26
PY 2012
VL 487
IS 7408
BP 491
EP 495
DI 10.1038/nature11288
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 979KD
UT WOS:000306815300040
PM 22810586
DA 2026-03-09
ER

PT J
AU Neale, BM
   Kou, Y
   Liu, L
   Ma'ayan, A
   Samocha, KE
   Sabo, A
   Lin, CF
   Stevens, C
   Wang, LS
   Makarov, V
   Polak, P
   Yoon, S
   Maguire, J
   Crawford, EL
   Campbell, NG
   Geller, ET
   Valladares, O
   Schafer, C
   Liu, H
   Zhao, T
   Cai, GQ
   Lihm, J
   Dannenfelser, R
   Jabado, O
   Peralta, Z
   Nagaswamy, U
   Muzny, D
   Reid, JG
   Newsham, I
   Wu, YQ
   Lewis, L
   Han, Y
   Voight, BF
   Lim, E
   Rossin, E
   Kirby, A
   Flannick, J
   Fromer, M
   Shakir, K
   Fennell, T
   Garimella, K
   Banks, E
   Poplin, R
   Gabriel, S
   DePristo, M
   Wimbish, JR
   Boone, BE
   Levy, SE
   Betancur, C
   Sunyaev, S
   Boerwinkle, E
   Buxbaum, JD
   Cook, EH
   Devlin, B
   Gibbs, RA
   Roeder, K
   Schellenberg, GD
   Sutcliffe, JS
   Daly, MJ
AF Neale, Benjamin M.
   Kou, Yan
   Liu, Li
   Ma'ayan, Avi
   Samocha, Kaitlin E.
   Sabo, Aniko
   Lin, Chiao-Feng
   Stevens, Christine
   Wang, Li-San
   Makarov, Vladimir
   Polak, Paz
   Yoon, Seungtai
   Maguire, Jared
   Crawford, Emily L.
   Campbell, Nicholas G.
   Geller, Evan T.
   Valladares, Otto
   Schafer, Chad
   Liu, Han
   Zhao, Tuo
   Cai, Guiqing
   Lihm, Jayon
   Dannenfelser, Ruth
   Jabado, Omar
   Peralta, Zuleyma
   Nagaswamy, Uma
   Muzny, Donna
   Reid, Jeffrey G.
   Newsham, Irene
   Wu, Yuanqing
   Lewis, Lora
   Han, Yi
   Voight, Benjamin F.
   Lim, Elaine
   Rossin, Elizabeth
   Kirby, Andrew
   Flannick, Jason
   Fromer, Menachem
   Shakir, Khalid
   Fennell, Tim
   Garimella, Kiran
   Banks, Eric
   Poplin, Ryan
   Gabriel, Stacey
   DePristo, Mark
   Wimbish, Jack R.
   Boone, Braden E.
   Levy, Shawn E.
   Betancur, Catalina
   Sunyaev, Shamil
   Boerwinkle, Eric
   Buxbaum, Joseph D.
   Cook, Edwin H., Jr.
   Devlin, Bernie
   Gibbs, Richard A.
   Roeder, Kathryn
   Schellenberg, Gerard D.
   Sutcliffe, James S.
   Daly, Mark J.
TI Patterns and rates of exonic de novo mutations in autism spectrum disorders
SO NATURE
LA English
DT Article
ID dna-sequencing data; association; framework; disease
AB Autism spectrum disorders (ASD) are believed to have genetic and environmental origins, yet in only a modest fraction of individuals can specific causes be identified(1,2). To identify further genetic risk factors, here we assess the role of de novo mutations in ASD by sequencing the exomes of ASD cases and their parents (n = 175 trios). Fewer than half of the cases (46.3%) carry a missense or nonsense de novo variant, and the overall rate of mutation is only modestly higher than the expected rate. In contrast, the proteins encoded by genes that harboured de novo missense or nonsense mutations showed a higher degree of connectivityamong themselves and to previous ASD genes(3) as indexed by protein-protein interaction screens. The small increase in the rate of de novo events, when taken together with the protein interaction results, are consistent with an important but limited role for de novo point mutations in ASD, similar to that documented for de novo copy number variants. Genetic models incorporating these data indicate that most of the observed de novo events are unconnected to ASD; those that do confer risk are distributed across many genes and are incompletely penetrant (that is, not necessarily sufficient for disease). Our results support polygenic models in which spontaneous coding mutations in any of a large number of genes increases risk by 5- to 20-fold. Despite the challenge posed by such models, results from de novo events and a large parallel case-control study provide strong evidence in favour of CHD8 and KATNAL2 as genuine autism risk factors.
C1 [Neale, Benjamin M.; Samocha, Kaitlin E.; Lim, Elaine; Rossin, Elizabeth; Kirby, Andrew; Fromer, Menachem; Daly, Mark J.] Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA.
   [Neale, Benjamin M.; Samocha, Kaitlin E.; Lim, Elaine; Rossin, Elizabeth; Kirby, Andrew; Fromer, Menachem; Daly, Mark J.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
   [Neale, Benjamin M.; Samocha, Kaitlin E.; Stevens, Christine; Polak, Paz; Maguire, Jared; Voight, Benjamin F.; Lim, Elaine; Rossin, Elizabeth; Kirby, Andrew; Flannick, Jason; Fromer, Menachem; Shakir, Khalid; Fennell, Tim; Garimella, Kiran; Banks, Eric; Poplin, Ryan; Gabriel, Stacey; DePristo, Mark; Sunyaev, Shamil; Daly, Mark J.] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA 02142 USA.
   [Kou, Yan; Ma'ayan, Avi; Dannenfelser, Ruth] Mt Sinai Sch Med, Dept Pharmacol & Syst Therapeut, New York, NY 10029 USA.
   [Kou, Yan; Makarov, Vladimir; Yoon, Seungtai; Cai, Guiqing; Lihm, Jayon; Buxbaum, Joseph D.] Mt Sinai Sch Med, Seaver Autism Ctr Res & Treatment, New York, NY 10029 USA.
   [Liu, Li; Schafer, Chad; Roeder, Kathryn] Carnegie Mellon Univ, Dept Stat, Pittsburgh, PA 15232 USA.
   [Sabo, Aniko; Nagaswamy, Uma; Muzny, Donna; Reid, Jeffrey G.; Newsham, Irene; Wu, Yuanqing; Lewis, Lora; Han, Yi; Boerwinkle, Eric; Gibbs, Richard A.] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA.
   [Makarov, Vladimir; Yoon, Seungtai; Cai, Guiqing; Lihm, Jayon; Buxbaum, Joseph D.] Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA.
   [Polak, Paz; Sunyaev, Shamil] Brigham & Womens Hosp, Dept Med, Div Genet, Boston, MA 02115 USA.
   [Polak, Paz; Sunyaev, Shamil] Harvard Univ, Sch Med, Boston, MA 02115 USA.
   [Crawford, Emily L.; Campbell, Nicholas G.; Sutcliffe, James S.] Vanderbilt Univ, Vanderbilt Brain Inst, Dept Mol Physiol & Biophys, Nashville, TN 37232 USA.
   [Crawford, Emily L.; Campbell, Nicholas G.; Sutcliffe, James S.] Vanderbilt Univ, Vanderbilt Brain Inst, Dept Psychiat, Nashville, TN 37232 USA.
   [Liu, Han; Zhao, Tuo] Johns Hopkins Univ, Dept Biostat, Baltimore, MD 21205 USA.
   [Liu, Han; Zhao, Tuo] Johns Hopkins Univ, Dept Comp Sci, Baltimore, MD 21205 USA.
   [Jabado, Omar; Peralta, Zuleyma; Buxbaum, Joseph D.] Mt Sinai Sch Med, Dept Genet & Genom Sci, New York, NY 10029 USA.
   [Voight, Benjamin F.] Univ Penn, Perelman Sch Med, Dept Pharmacol, Philadelphia, PA 19104 USA.
   [Wimbish, Jack R.; Boone, Braden E.; Levy, Shawn E.] HudsonAlpha Inst Biotechnol, Huntsville, AL 35806 USA.
   [Betancur, Catalina] INSERM, U952, F-75005 Paris, France.
   [Betancur, Catalina] CNRS, UMR 7224, F-75005 Paris, France.
   [Betancur, Catalina] Univ Paris 06, F-75005 Paris, France.
   [Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Human Genet Ctr, Houston, TX 77030 USA.
   [Buxbaum, Joseph D.] Mt Sinai Sch Med, Friedman Brain Inst, New York, NY 10029 USA.
   [Cook, Edwin H., Jr.] Univ Illinois, Dept Psychiat, Chicago, IL 60608 USA.
   [Devlin, Bernie] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15213 USA.
C3 Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard Medical School; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Icahn School of Medicine at Mount Sinai; Icahn School of Medicine at Mount Sinai; Carnegie Mellon University; Baylor College of Medicine; Icahn School of Medicine at Mount Sinai; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard University; Harvard Medical School; Vanderbilt University; Vanderbilt University; Johns Hopkins University; Johns Hopkins University; Icahn School of Medicine at Mount Sinai; University of Pennsylvania; HudsonAlpha Institute for Biotechnology; Institut National de la Sante et de la Recherche Medicale (Inserm); Centre National de la Recherche Scientifique (CNRS); Sorbonne Universite; University of Texas System; University of Texas Health Science Center Houston; Icahn School of Medicine at Mount Sinai; University of Illinois System; University of Illinois Chicago; University of Illinois Chicago Hospital; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh
RP Daly, MJ (corresponding author), Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA.
EM joseph.buxbaum@mssm.edu; kathryn.roeder@gmail.com; mjdaly@atgu.mgh.harvard.edu
FU NIH [R01MH089208, R01 MH089025, R01 MH089004, R01MH089175, R01 MH089482, P50 HD055751, RO1 MH057881, R01 MH061009]; Seaver Foundation; NIH NCRR [UL1 RR024975]; Vanderbilt Kennedy Center for Research on Human Development [P30 HD015052];  [R01MH084676];  [U54 HG003273];  [U54 HG003067]; National Institute of General Medical Sciences [T32GM007753] Funding Source: NIH RePORTER; Direct For Computer & Info Scie & Enginr; Div Of Information & Intelligent Systems [1332109, 1116730] Funding Source: National Science Foundation
NR 18
TC 1354
Z9 1636
U1 0
U2 171
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD MAY 10
PY 2012
VL 485
IS 7397
BP 242
EP U129
DI 10.1038/nature11011
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 939HJ
UT WOS:000303799800042
PM 22495311
DA 2026-03-09
ER

PT J
AU Czyzewski, BK
   Wang, DN
AF Czyzewski, Bryan K.
   Wang, Da-Neng
TI Identification and characterization of a bacterial hydrosulphide ion channel
SO NATURE
LA English
DT Article
ID escherichia-coli; sulfide acquisition; chloride channel; membrane; transporter; purification; biochemistry; binding; protein; nirc
AB The hydrosulphide ion (HS-) and its undissociated form, hydrogen sulphide (H2S), which are believed to have been critical to the origin of life on Earth(1), remain important in physiology and cellular signalling(2). As a major metabolite in anaerobic bacterial growth, hydrogen sulphide is a product of both assimilatory and dissimilatory sulphate reduction(2-4). These pathways can reduce various oxidized sulphur compounds including sulphate, sulphite and thiosulphate. The dissimilatory sulphate reduction pathway uses this molecule as the terminal electron acceptor for anaerobic respiration, in which process it produces excess amounts of H2S (ref. 4). The reduction of sulphite is a key intermediate step in all sulphate reduction pathways. In Clostridium and Salmonella, an inducible sulphite reductase is directly linked to the regeneration of NAD(+), which has been suggested to have a role in energy production and growth, as well as in the detoxification of sulphite(3). Above a certain concentration threshold, both H2S and HS- inhibit cell growth by binding the metal centres of enzymes and cytochrome oxidase(5), necessitating a release mechanism for the export of this toxic metabolite from the cell(5-9). Here we report the identification of a hydrosulphide ion channel in the pathogen Clostridium difficile through a combination of genetic, biochemical and functional approaches. The HS- channel is a member of the formate/nitrite transport family, in which about 50 hydrosulphide ion channels form a third subfamily alongside those for formate(10,11) (FocA) and for nitrite(12) (NirC). The hydrosulphide ion channel is permeable to formate and nitrite as well as to HS- ions. Such polyspecificity can be explained by the conserved ion selectivity filter observed in the channel's crystal structure. The channel has a low open probability and is tightly regulated, to avoid decoupling of the membrane proton gradient.
C1 [Czyzewski, Bryan K.; Wang, Da-Neng] NYU, Sch Med, Skirball Inst Biomol Med, Helen L & Martin S Kimmel Ctr Biol & Med, New York, NY 10016 USA.
   [Czyzewski, Bryan K.] NYU, Sch Med, Mol Biophys Grad Program, New York, NY 10016 USA.
   [Wang, Da-Neng] NYU, Sch Med, Dept Cell Biol, New York, NY 10016 USA.
C3 New York University; New York University; New York University
RP Wang, DN (corresponding author), NYU, Sch Med, Skirball Inst Biomol Med, Helen L & Martin S Kimmel Ctr Biol & Med, 540 1st Ave, New York, NY 10016 USA.
EM wang@saturn.med.nyu.edu
FU NIH [R01-GM093825, R01-DK073973, R01-MH083840, U54-GM075026, R01-DK053973-08A1S1, F31-AI086072]
NR 43
TC 121
Z9 139
U1 0
U2 91
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 22
PY 2012
VL 483
IS 7390
BP 494
EP U155
DI 10.1038/nature10881
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 912CC
UT WOS:000301771200049
PM 22407320
DA 2026-03-09
ER

PT J
AU Seufert, V
   Ramankutty, N
   Foley, JA
AF Seufert, Verena
   Ramankutty, Navin
   Foley, Jonathan A.
TI Comparing the yields of organic and conventional agriculture
SO NATURE
LA English
DT Article
ID productivity; metaanalyses; availability; challenge; quality; legume; feed
AB Numerous reports have emphasized the need for major changes in the global food system: agriculture must meet the twin challenge of feeding a growing population, with rising demand for meat and high-calorie diets, while simultaneously minimizing its global environmental impacts(1,2). Organic farming-a system aimed at producing food with minimal harm to ecosystems, animals or humans-is often proposed as a solution(3,4). However, critics argue that organic agriculture may have lower yields and would therefore need more land to produce the same amount of food as conventional farms, resulting in more widespread deforestation and bio-diversity loss, and thus undermining the environmental benefits of organic practices(5). Here we use a comprehensive meta-analysis to examine the relative yield performance of organic and conventional farming systems globally. Our analysis of available data shows that, overall, organic yields are typically lower than conventional yields. But these yield differences are highly contextual, depending on system and site characteristics, and range from 5% lower organic yields (rain-fed legumes and perennials on weak-acidic to weak-alkaline soils), 13% lower yields (when best organic practices are used), to 34% lower yields (when the conventional and organic systems are most comparable). Under certain conditions-that is, with good management practices, particular crop types and growing conditions-organic systems can thus nearly match conventional yields, whereas under others it at present cannot. To establish organic agriculture as an important tool in sustainable food production, the factors limiting organic yields need to be more fully understood, alongside assessments of the many social, environmental and economic benefits of organic farming systems.
C1 [Seufert, Verena; Ramankutty, Navin] McGill Univ, Dept Geog, Montreal, PQ H2T 3A3, Canada.
   [Seufert, Verena; Ramankutty, Navin] McGill Univ, Global Environm & Climate Change Ctr, Montreal, PQ H2T 3A3, Canada.
   [Foley, Jonathan A.] Univ Minnesota, Inst Environm IonE, St Paul, MN 55108 USA.
C3 McGill University; McGill University; University of Minnesota System; University of Minnesota Twin Cities
RP Seufert, V (corresponding author), McGill Univ, Dept Geog, Montreal, PQ H2T 3A3, Canada.
EM verena.seufert@mail.mcgill.ca
FU Natural Science and Engineering Research Council of Canada
NR 40
TC 1467
Z9 1802
U1 19
U2 1787
PU NATURE PUBLISHING 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 10
PY 2012
VL 485
IS 7397
BP 229
EP U113
DI 10.1038/nature11069
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 939HJ
UT WOS:000303799800039
PM 22535250
DA 2026-03-09
ER

PT J
AU Hoye, TR
   Baire, B
   Niu, DW
   Willoughby, PH
   Woods, BP
AF Hoye, Thomas R.
   Baire, Beeraiah
   Niu, Dawen
   Willoughby, Patrick H.
   Woods, Brian P.
TI The hexadehydro-Diels-Alder reaction
SO NATURE
LA English
DT Article
ID organic-synthesis; aryne chemistry; generation; benzyne; cycloaromatization; cyclohexyne; system
AB Arynes (aromatic systems containing, formally, a carbon-carbon triple bond) are among the most versatile of all reactive intermediates in organic chemistry. They can be 'trapped' to give products that are used as pharmaceuticals, agrochemicals, dyes, polymers and other fine chemicals. Here we explore a strategy that unites the de novo generation of benzynes-through a hexadehydro-Diels-Alder reaction-with their in situ elaboration into structurally complex benzenoid products. In the hexadehydro-Diels-Alder reaction, a 1,3-diyne is engaged in a [4+2] cycloisomerization with a 'diynophile' to produce the highly reactive benzyne intermediate. The reaction conditions for this simple, thermal transformation are notable for being free of metals and reagents. The subsequent and highly efficient trapping reactions increase the power of the overall process. Finally, we provide examples of how this de novo benzyne generation approach allows new modes of intrinsic reactivity to be revealed.
C1 [Hoye, Thomas R.; Baire, Beeraiah; Niu, Dawen; Willoughby, Patrick H.; Woods, Brian P.] Univ Minnesota, Dept Chem, Minneapolis, MN 55455 USA.
C3 University of Minnesota System; University of Minnesota Twin Cities
RP Hoye, TR (corresponding author), Univ Minnesota, Dept Chem, 207 Pleasant St SE, Minneapolis, MN 55455 USA.
EM hoye@umn.edu
FU National Science Foundation; National Institutes of Health [GM65597, CA76497]
NR 28
TC 388
Z9 467
U1 5
U2 285
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD OCT 11
PY 2012
VL 490
IS 7419
BP 208
EP 212
DI 10.1038/nature11518
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 019IY
UT WOS:000309733300039
PM 23060191
DA 2026-03-09
ER

PT J
AU Chen, ZH
   Schaap, P
AF Chen, Zhi-hui
   Schaap, Pauline
TI The prokaryote messenger c-di-GMP triggers stalk cell differentiation in Dictyostelium
SO NATURE
LA English
DT Article
ID gene-expression; phylogeny; phosphodiesterase; evolution; pattern
AB Cyclic di-(3':5')-guanosine monophosphate (c-di-GMP) is a major prokaryote signalling intermediate that is synthesized by diguanylate cyclases and triggers sessility and biofilm formation(1,2). We detected the first eukaryote diguanylate cyclases in all major groups of Dictyostelia. On food depletion, Dictyostelium discoideum amoebas collect into aggregates, which first transform into migrating slugs and then into sessile fruiting structures(3). These structures consist of a spherical spore mass that is supported by a column of stalk cells and a basal disk. Apolyketide, DIF-1, which induces stalklike cells in vitro, was isolated earlier(4). However, its role in vivo proved recently to be restricted to basal disk formation(5). Here we show that the Dictyostelium diguanylate cyclase, DgcA, produces c-di-GMP as the morphogen responsible for stalk cell differentiation. Dictyostelium discoideum DgcA synthesized c-di-GMP in a GTP-dependent manner and was expressed at the slug tip, which is the site of stalk cell differentiation. Disruption of the DgcA gene blocked the transition from slug migration to fructification and the expression of stalk genes. Fructification and stalk formation were restored by exposing DgcA-null slugs to wild-type secretion products or to c-di-GMP. Moreover, c-di-GMP, but not cyclic di-(3':5')-adenosine monophosphate, induced stalk gene expression in dilute cell monolayers. Apart from identifying the long-elusive stalk-inducing morphogen, our work also identifies a role for c-di-GMP in eukaryotes.
C1 [Chen, Zhi-hui; Schaap, Pauline] Univ Dundee, Coll Life Sci, Dundee DD1 5EH, Scotland.
C3 University of Dundee
RP Schaap, P (corresponding author), Univ Dundee, Coll Life Sci, Dundee DD1 5EH, Scotland.
EM p.schaap@dundee.ac.uk
FU Wellcome Trust [090276]; BBSRC [BB/G020426]; BBSRC [BB/E016308/1, BB/G020426/1] Funding Source: UKRI; Biotechnology and Biological Sciences Research Council [BB/G020426/1, BB/E016308/1] Funding Source: researchfish
NR 27
TC 90
Z9 118
U1 3
U2 46
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 30
PY 2012
VL 488
IS 7413
BP 680
EP 683
DI 10.1038/nature11313
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 996NC
UT WOS:000308095100061
PM 22864416
DA 2026-03-09
ER

PT J
AU Djebali, S
   Davis, CA
   Merkel, A
   Dobin, A
   Lassmann, T
   Mortazavi, A
   Tanzer, A
   Lagarde, J
   Lin, W
   Schlesinger, F
   Xue, CH
   Marinov, GK
   Khatun, J
   Williams, BA
   Zaleski, C
   Rozowsky, J
   Röder, M
   Kokocinski, F
   Abdelhamid, RF
   Alioto, T
   Antoshechkin, I
   Baer, MT
   Bar, NS
   Batut, P
   Bell, K
   Bell, I
   Chakrabortty, S
   Chen, X
   Chrast, J
   Curado, J
   Derrien, T
   Drenkow, J
   Dumais, E
   Dumais, J
   Duttagupta, R
   Falconnet, E
   Fastuca, M
   Fejes-Toth, K
   Ferreira, P
   Foissac, S
   Fullwood, MJ
   Gao, H
   Gonzalez, D
   Gordon, A
   Gunawardena, H
   Howald, C
   Jha, S
   Johnson, R
   Kapranov, P
   King, B
   Kingswood, C
   Luo, OJ
   Park, E
   Persaud, K
   Preall, JB
   Ribeca, P
   Risk, B
   Robyr, D
   Sammeth, M
   Schaffer, L
   See, LH
   Shahab, A
   Skancke, J
   Suzuki, AM
   Takahashi, H
   Tilgner, H
   Trout, D
   Walters, N
   Wang, H
   Wrobel, J
   Yu, YB
   Ruan, XA
   Hayashizaki, Y
   Harrow, J
   Gerstein, M
   Hubbard, T
   Reymond, A
   Antonarakis, SE
   Hannon, G
   Giddings, MC
   Ruan, YJ
   Wold, B
   Carninci, P
   Guigó, R
   Gingeras, TR
AF Djebali, Sarah
   Davis, Carrie A.
   Merkel, Angelika
   Dobin, Alex
   Lassmann, Timo
   Mortazavi, Ali
   Tanzer, Andrea
   Lagarde, Julien
   Lin, Wei
   Schlesinger, Felix
   Xue, Chenghai
   Marinov, Georgi K.
   Khatun, Jainab
   Williams, Brian A.
   Zaleski, Chris
   Rozowsky, Joel
   Roeder, Maik
   Kokocinski, Felix
   Abdelhamid, Rehab F.
   Alioto, Tyler
   Antoshechkin, Igor
   Baer, Michael T.
   Bar, Nadav S.
   Batut, Philippe
   Bell, Kimberly
   Bell, Ian
   Chakrabortty, Sudipto
   Chen, Xian
   Chrast, Jacqueline
   Curado, Joao
   Derrien, Thomas
   Drenkow, Jorg
   Dumais, Erica
   Dumais, Jacqueline
   Duttagupta, Radha
   Falconnet, Emilie
   Fastuca, Meagan
   Fejes-Toth, Kata
   Ferreira, Pedro
   Foissac, Sylvain
   Fullwood, Melissa J.
   Gao, Hui
   Gonzalez, David
   Gordon, Assaf
   Gunawardena, Harsha
   Howald, Cedric
   Jha, Sonali
   Johnson, Rory
   Kapranov, Philipp
   King, Brandon
   Kingswood, Colin
   Luo, Oscar J.
   Park, Eddie
   Persaud, Kimberly
   Preall, Jonathan B.
   Ribeca, Paolo
   Risk, Brian
   Robyr, Daniel
   Sammeth, Michael
   Schaffer, Lorian
   See, Lei-Hoon
   Shahab, Atif
   Skancke, Jorgen
   Suzuki, Ana Maria
   Takahashi, Hazuki
   Tilgner, Hagen
   Trout, Diane
   Walters, Nathalie
   Wang, Huaien
   Wrobel, John
   Yu, Yanbao
   Ruan, Xiaoan
   Hayashizaki, Yoshihide
   Harrow, Jennifer
   Gerstein, Mark
   Hubbard, Tim
   Reymond, Alexandre
   Antonarakis, Stylianos E.
   Hannon, Gregory
   Giddings, Morgan C.
   Ruan, Yijun
   Wold, Barbara
   Carninci, Piero
   Guigo, Roderic
   Gingeras, Thomas R.
TI Landscape of transcription in human cells
SO NATURE
LA English
DT Article
ID rna; genome; identification; enhancers; maps
AB Eukaryotic cells make many types of primary and processed RNAs that are found either in specific subcellular compartments or throughout the cells. A complete catalogue of these RNAs is not yet available and their characteristic subcellular localizations are also poorly understood. Because RNA represents the direct output of the genetic information encoded by genomes and a significant proportion of a cell's regulatory capabilities are focused on its synthesis, processing, transport, modification and translation, the generation of such a catalogue is crucial for understanding genome function. Here we report evidence that three-quarters of the human genome is capable of being transcribed, as well as observations about the range and levels of expression, localization, processing fates, regulatory regions and modifications of almost all currently annotated and thousands of previously unannotated RNAs. These observations, taken together, prompt a redefinition of the concept of a gene.
C1 [Djebali, Sarah; Merkel, Angelika; Tanzer, Andrea; Lagarde, Julien; Roeder, Maik; Alioto, Tyler; Curado, Joao; Derrien, Thomas; Ferreira, Pedro; Gonzalez, David; Johnson, Rory; King, Brandon; Kingswood, Colin; Ribeca, Paolo; Sammeth, Michael; Skancke, Jorgen; Tilgner, Hagen; Guigo, Roderic] Ctr Gen Regulat, Barcelona 08003, Catalonia, Spain.
   [Djebali, Sarah; Merkel, Angelika; Tanzer, Andrea; Lagarde, Julien; Roeder, Maik; Alioto, Tyler; Curado, Joao; Derrien, Thomas; Ferreira, Pedro; Gonzalez, David; Johnson, Rory; King, Brandon; Kingswood, Colin; Ribeca, Paolo; Sammeth, Michael; Skancke, Jorgen; Tilgner, Hagen; Guigo, Roderic] UPF, Barcelona 08003, Catalonia, Spain.
   [Davis, Carrie A.; Dobin, Alex; Lin, Wei; Schlesinger, Felix; Xue, Chenghai; Zaleski, Chris; Baer, Michael T.; Batut, Philippe; Bell, Kimberly; Chakrabortty, Sudipto; Drenkow, Jorg; Fastuca, Meagan; Fejes-Toth, Kata; Gordon, Assaf; Jha, Sonali; Persaud, Kimberly; Preall, Jonathan B.; See, Lei-Hoon; Wang, Huaien; Hannon, Gregory; Gingeras, Thomas R.] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11742 USA.
   [Lassmann, Timo; Abdelhamid, Rehab F.; Suzuki, Ana Maria; Takahashi, Hazuki; Hayashizaki, Yoshihide; Carninci, Piero] RIKEN Omics Sci Ctr, RIKEN Yokohama Inst, Tsurumi ku, Yokohama, Kanagawa 2300045, Japan.
   [Mortazavi, Ali; Marinov, Georgi K.; Williams, Brian A.; Antoshechkin, Igor; King, Brandon; Schaffer, Lorian; Trout, Diane; Wold, Barbara] CALTECH, Beckman Inst 2, Div Biol, Pasadena, CA 91125 USA.
   [Mortazavi, Ali; Park, Eddie] Univ Calif Irvine, Dept Dev & Cell Biol, Irvine, CA 92697 USA.
   [Khatun, Jainab; Risk, Brian; Wrobel, John] Boise State Univ, Coll Arts & Sci, Boise, ID 83725 USA.
   [Rozowsky, Joel; Gerstein, Mark] Yale Univ, Program Computat Biol & Bioinformat, New Haven, CT 06520 USA.
   [Rozowsky, Joel; Gerstein, Mark] Yale Univ, Dept Mol Biophys & Biochem, New Haven, CT 06520 USA.
   [Kokocinski, Felix; Harrow, Jennifer; Hubbard, Tim] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England.
   [Alioto, Tyler; Kingswood, Colin; Ribeca, Paolo; Sammeth, Michael] CNAG, Barcelona 08028, Catalonia, Spain.
   [Bar, Nadav S.; Skancke, Jorgen] Norwegian Univ Sci & Technol, Dept Chem Engn, NO-7491 Trondheim, Norway.
   [Bell, Ian; Dumais, Erica; Dumais, Jacqueline; Duttagupta, Radha; Foissac, Sylvain; Gao, Hui; Kapranov, Philipp; Gingeras, Thomas R.] Affymetrix Inc, Santa Clara, CA 95051 USA.
   [Chen, Xian; Gunawardena, Harsha; Yu, Yanbao; Giddings, Morgan C.] Univ N Carolina, Dept Biochem & Biophys, Chapel Hill, NC 27599 USA.
   [Chrast, Jacqueline; Howald, Cedric; Walters, Nathalie; Reymond, Alexandre] Univ Lausanne, Ctr Integrat Gen, CH-1015 Lausanne, Switzerland.
   [Falconnet, Emilie; Robyr, Daniel; Antonarakis, Stylianos E.] Univ Geneva, Sch Med, Dept Genet Med & Dev, CH-1211 Geneva, Switzerland.
   [Falconnet, Emilie; Robyr, Daniel; Antonarakis, Stylianos E.] IGE3 Inst Genet & Genom Geneva, CH-1211 Geneva, Switzerland.
   [Fullwood, Melissa J.; Luo, Oscar J.; Shahab, Atif; Ruan, Xiaoan; Ruan, Yijun] Genome Inst Singapore, Singapore 138672, Singapore.
   [Kapranov, Philipp] St Laurent Inst, Cambridge, MA 02141 USA.
   [Gerstein, Mark] Yale Univ, Dept Comp Sci, New Haven, CT 06520 USA.
   [Guigo, Roderic] Univ Pompeu Fabra, Dept Ciencies Expt & Salut, Barcelona, Catalonia, Spain.
C3 Barcelona Institute of Science & Technology; Pompeu Fabra University; Centre de Regulacio Genomica (CRG); Pompeu Fabra University; Cold Spring Harbor Laboratory; RIKEN; California Institute of Technology; University of California System; University of California Irvine; Boise State University; Yale University; Yale University; Wellcome Trust Sanger Institute; Norwegian University of Science & Technology (NTNU); Affymetrix; University of North Carolina; University of North Carolina Chapel Hill; University of Lausanne; University of Geneva; Agency for Science Technology & Research (A*STAR); A*STAR - Genome Institute of Singapore (GIS); Yale University; Pompeu Fabra University
RP Guigó, R (corresponding author), Ctr Gen Regulat, Doctor Aiguader 88, Barcelona 08003, Catalonia, Spain.
EM roderic.guigo@crg.eu; gingeras@cshl.edu
FU National Human Genome Research Institute (NHGRI) [U54HG004557, U54HG004555, U54HG004576, U54HG004558]; NHGRI pilot grant [R01HG003700]; NHGRI ARRA stimulus grant [1RC2HG005591]; National Science Foundation (SNF) [127375]; European Research Council (ERC) [249968]; Japanese Ministry of Education, Culture, Sports, Science and Technology; INB GNV-1 from the Spanish Ministry of Science;  [BIO2011-26205];  [CSD2007-00050]; National Cancer Institute [P30CA045508] Funding Source: NIH RePORTER; European Research Council (ERC) [249968] Funding Source: European Research Council (ERC)
NR 36
TC 4143
Z9 4799
U1 4
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 SEP 6
PY 2012
VL 489
IS 7414
BP 101
EP 108
DI 10.1038/nature11233
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 999WW
UT WOS:000308347000043
PM 22955620
DA 2026-03-09
ER

PT J
AU Clapier, CR
   Cairns, BR
AF Clapier, Cedric R.
   Cairns, Bradley R.
TI Regulation of ISWI involves inhibitory modules antagonized by nucleosomal epitopes
SO NATURE
LA English
DT Article
ID dna translocation; chromatin; mechanism; binding; rsc; identification; recognition; domain
AB Chromatin-remodelling complexes (CRCs) mobilize nucleosomes to mediate the access of DNA-binding factors to their sites in vivo. These CRCs contain a catalytic subunit that bears an ATPase/DNA-translocase domain and flanking regions that bind nucleosomal epitopes(1). A central question is whether and how these flanking regions regulate ATP hydrolysis or the coupling of hydrolysis to DNA translocation, to affect nucleosome-sliding efficiency. ISWI-family CRCs contain the protein ISWI2, which uses its ATPase/DNA-translocase domain to pump DNA around the histone octamer to enable sliding(3-7). ISWI is positively regulated by two 'activating' nucleosomal epitopes: the 'basic patch' on the histone H4 tail, and extranucleosomal (linker) DNA(8-13). Previous work defined the HAND-SANT-SLIDE (HSS) domain at the ISWI carboxy terminus that binds linker DNA, needed for ISWI activity(14,15). Here we define two new, conserved and separate regulatory regions on Drosophila ISWI, termed AutoN and NegC, which negatively regulate ATP hydrolysis (AutoN) or the coupling of ATP hydrolysis to productive DNA translocation (NegC). The two aforementioned nucleosomal epitopes promote remodelling indirectly by preventing the negative regulation of AutoN and NegC. Notably, mutation or removal of AutoN and NegC enables marked nucleosome sliding without the H4 basic patch or extranucleosomal DNA, or the HSS domain, conferring on ISWI the biochemical attributes normally associated with SWI/SNF-family ATPases. Thus, the ISWI ATPase catalytic core is an intrinsically active DNA translocase that conducts nucleosome sliding, onto which selective 'inhibition-of-inhibition' modules are placed, to help ensure that remodelling occurs only in the presence of proper nucleosomal epitopes. This supports a general concept for the specialization of chromatin-remodelling ATPases, in which specific regulatory modules adapt an ancient active DNA translocase to conduct particular tasks only on the appropriate chromatin landscape.
C1 [Clapier, Cedric R.; Cairns, Bradley R.] Univ Utah, Howard Hughes Med Inst, Sch Med, Salt Lake City, UT 84112 USA.
   [Clapier, Cedric R.; Cairns, Bradley R.] Univ Utah, Sch Med, Dept Oncol Sci, Huntsman Canc Inst, Salt Lake City, UT 84112 USA.
C3 Utah System of Higher Education; University of Utah; Howard Hughes Medical Institute; Utah System of Higher Education; University of Utah; Huntsman Cancer Institute
RP Cairns, BR (corresponding author), Univ Utah, Howard Hughes Med Inst, Sch Med, 2000 Circle Hope, Salt Lake City, UT 84112 USA.
EM cedric.clapier@hci.utah.edu; brad.cairns@hci.utah.edu
FU National Institutes of Health [GM60415, CA042014]; Howard Hughes Medical Institute; National Cancer Institute [P30CA042014] Funding Source: NIH RePORTER
NR 34
TC 129
Z9 162
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 DEC 13
PY 2012
VL 492
IS 7428
BP 280
EP +
DI 10.1038/nature11625
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 053GM
UT WOS:000312259300048
PM 23143334
DA 2026-03-09
ER

PT J
AU Ouyang, WM
   Liao, W
   Luo, CT
   Yin, N
   Huse, M
   Kim, MV
   Peng, M
   Chan, P
   Ma, Q
   Mo, YF
   Meijer, D
   Zhao, KJ
   Rudensky, AY
   Atwal, G
   Zhang, MQ
   Li, MO
AF Ouyang, Weiming
   Liao, Will
   Luo, Chong T.
   Yin, Na
   Huse, Morgan
   Kim, Myoungjoo V.
   Peng, Min
   Chan, Pamela
   Ma, Qian
   Mo, Yifan
   Meijer, Dies
   Zhao, Keji
   Rudensky, Alexander Y.
   Atwal, Gurinder
   Zhang, Michael Q.
   Li, Ming O.
TI Novel Foxo1-dependent transcriptional programs control Treg cell function
SO NATURE
LA English
DT Article
ID foxp3 expression; gene-expression; target genes; differentiation; foxo1; tool; akt; mechanisms; induction; profiles
AB Regulatory T (T-reg) cells, characterized by expression of the transcription factor forkhead box P3 (Foxp3), maintain immune homeostasis by suppressing self-destructive immune responses(1-4). Foxp3 operates as a late-acting differentiation factor controlling T-reg cell homeostasis and function(5), whereas the early T-reg-cell-lineage commitment is regulated by the Akt kinase and the forkhead box O (Foxo) family of transcription factors(6-10). However, whether Foxo proteins act beyond the T-reg-cell-commitment stage to control T-reg cell homeostasis and function remains largely unexplored. Here we show that Foxo1 is a pivotal regulator of T-reg cell function. T-reg cells express high amounts of Foxo1 and display reduced T-cell-receptor-induced Akt activation, Foxo1 phosphorylation and Foxo1 nuclear exclusion. Mice with T-reg-cell-specific deletion of Foxo1 develop a fatal inflammatory disorder similar in severity to that seen in Foxp3-deficient mice, but without the loss of T-reg cells. Genome-wide analysis of Foxo1 binding sites reveals similar to 300 Foxo1-bound target genes, including the pro-inflammatory cytokine Ifng, that do not seem to be directly regulated by Foxp3. These findings show that the evolutionarily ancient Akt-Foxo1 signalling module controls a novel genetic program indispensable for T-reg cell function.
C1 [Ouyang, Weiming; Luo, Chong T.; Yin, Na; Huse, Morgan; Kim, Myoungjoo V.; Peng, Min; Chan, Pamela; Ma, Qian; Rudensky, Alexander Y.; Li, Ming O.] Mem Sloan Kettering Canc Ctr, Program Immunol, New York, NY 10065 USA.
   [Liao, Will; Mo, Yifan; Atwal, Gurinder] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA.
   [Liao, Will; Mo, Yifan] SUNY Stony Brook, Dept Appl Math & Stat, Stony Brook, NY 11794 USA.
   [Luo, Chong T.] Mem Sloan Kettering Canc Ctr, Louis V Gerstner Jr Grad Sch Biomed Sci, New York, NY 10065 USA.
   [Meijer, Dies] Erasmus Univ, Med Ctr, Dept Cell Biol & Genet, NL-3000 DR Rotterdam, Netherlands.
   [Zhao, Keji] NHLBI, Syst Biol Ctr, NIH, Bethesda, MD 20892 USA.
   [Rudensky, Alexander Y.] Mem Sloan Kettering Canc Ctr, Howard Hughes Med Inst, New York, NY 10065 USA.
   [Zhang, Michael Q.] Univ Texas Dallas, Ctr Syst Biol, Dept Mol & Cell Biol, Richardson, TX 75080 USA.
   [Zhang, Michael Q.] Tsinghua Univ, TNLIST, Ctr Synthet & Syst Biol, Bioinformat Div, Beijing 100084, Peoples R China.
C3 Memorial Sloan Kettering Cancer Center; Cold Spring Harbor Laboratory; State University of New York (SUNY) System; Stony Brook University; Memorial Sloan Kettering Cancer Center; Erasmus University Rotterdam; Erasmus MC; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI); Howard Hughes Medical Institute; Memorial Sloan Kettering Cancer Center; University of Texas System; University of Texas Dallas; Tsinghua University
RP Li, MO (corresponding author), Mem Sloan Kettering Canc Ctr, Program Immunol, New York, NY 10065 USA.
EM mzhang@cshl.edu; lim@mskcc.org
FU Starr Cancer Consortium [13-A123]; Rita Allen Foundation; National Bio Resource Project (NBRPC) [2012CB316503]; National Institutes of Health [HG001696]; National Heart Lung and Blood Institute [ZIAHL006030, ZIAHL005801] Funding Source: NIH RePORTER
NR 44
TC 350
Z9 412
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 NOV 22
PY 2012
VL 491
IS 7425
BP 554
EP +
DI 10.1038/nature11581
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 040RE
UT WOS:000311339800043
PM 23135404
DA 2026-03-09
ER

PT J
AU Visbal, E
   Barkana, R
   Fialkov, A
   Tseliakhovich, D
   Hirata, CM
AF Visbal, Eli
   Barkana, Rennan
   Fialkov, Anastasia
   Tseliakhovich, Dmitriy
   Hirata, Christopher M.
TI The signature of the first stars in atomic hydrogen at redshift 20
SO NATURE
LA English
DT Article
ID cosmological reionization; power spectrum; early galaxy; dark-matter; universe; fluctuations; population; radiation; epoch
AB Dark and baryonic matter moved at different velocities in the early Universe, which strongly suppressed star formation in some regions(1). This was estimated(2) to imprint a large-scale fluctuation signal of about two millikelvin in the 21-centimetre spectral line of atomic hydrogen associated with stars at a redshift of 20, although this estimate ignored the critical contribution of gas heating due to X-rays(3,4) and major enhancements of the suppression. A large velocity difference reduces the abundance of haloes(1,5,6) and requires the first stars to form in haloes of about a million solar masses(7,8), substantially greater than previously expected(9,10). Here we report a simulation of the distribution of the first stars at redshift 20 (cosmic age of around 180 million years), incorporating all these ingredients within a 400-megaparsec box. We find that the 21-centimetre hydrogen signature of these stars is an enhanced (ten millikelvin) fluctuation signal on the hundred-megaparsec scale, characterized(2) by a flat power spectrum with prominent baryon acoustic oscillations. The required sensitivity to see this signal is achievable with an integration time of a thousand hours with an instrument like the Murchison Wide-field Array(11) or the Low Frequency Array(12) but designed to operate in the range of 50-100 megahertz.
C1 [Visbal, Eli] Harvard Univ, Jefferson Lab Phys, Cambridge, MA 02138 USA.
   [Visbal, Eli] Harvard Univ, Inst Theory & Computat, Cambridge, MA 02138 USA.
   [Barkana, Rennan; Fialkov, Anastasia] Tel Aviv Univ, Raymond & Beverly Sackler Sch Phys & Astron, IL-69978 Tel Aviv, Israel.
   [Tseliakhovich, Dmitriy; Hirata, Christopher M.] CALTECH, Pasadena, CA 91125 USA.
C3 Harvard University; Harvard University; Tel Aviv University; California Institute of Technology
RP Visbal, E (corresponding author), Harvard Univ, Jefferson Lab Phys, Cambridge, MA 02138 USA.
EM evisbal@fas.harvard.edu; barkana@wise.tau.ac.il
FU Israel Science Foundation; European Research Council; US Department of Energy; National Science Foundation; David & Lucile Packard Foundation
NR 32
TC 145
Z9 157
U1 0
U2 7
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUL 5
PY 2012
VL 487
IS 7405
BP 70
EP 73
DI 10.1038/nature11177
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 968LM
UT WOS:000305982900051
PM 22722853
DA 2026-03-09
ER

PT J
AU Korkhov, VM
   Mireku, SA
   Locher, KP
AF Korkhov, Vladimir M.
   Mireku, Samantha A.
   Locher, Kaspar P.
TI Structure of AMP-PNP-bound vitamin B12 transporter BtuCD-F
SO NATURE
LA English
DT Article
ID abc transporter; atp-binding; escherichia-coli; crystal-structure; protein complex; mechanism; domain; intermediate; suggest; system
AB The ATP-binding cassette (ABC) transporter BtuCD mediates the uptake of vitamin B-12 across the inner membrane of Escherichia coli. Previous structures have shown the conformations of apo states, but the transport mechanism has remained unclear. Here we report the 3.5 angstrom crystal structure of the transporter-binding protein complex BtuCD-BtuF (BtuCD-F) trapped in an beta-gamma-imidoadenosine 5'-phosphate (AMP-PNP)-bound intermediate state. Although the ABC domains (BtuD subunits) form the expected closed sandwich dimer, the membrane-spanning BtuC subunits adopt a new conformation, with the central translocation pathway sealed by a previously unrecognized cytoplasmic gate. A fully enclosed cavity is thus formed approximately halfway across the membrane. It is large enough to accommodate a vitamin B-12 molecule, and radioligand trapping showed that liposome-reconstituted BtuCD-F indeed contains bound B-12 in the presence of AMP-PNP. In combination with engineered disulphide crosslinking and functional assays, our data suggest an unexpected peristaltic transport mechanism that is distinct from those observed in other ABC transporters.
C1 [Korkhov, Vladimir M.; Mireku, Samantha A.; Locher, Kaspar P.] ETH, Inst Mol Biol & Biophys, CH-8093 Zurich, Switzerland.
C3 Swiss Federal Institutes of Technology Domain; ETH Zurich
RP Locher, KP (corresponding author), ETH, Inst Mol Biol & Biophys, CH-8093 Zurich, Switzerland.
EM locher@mol.biol.ethz.ch
FU NCCR Structural Biology Zurich; Swiss National Science Foundation [SNF 31003A-131075/1]
NR 44
TC 139
Z9 166
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 OCT 18
PY 2012
VL 490
IS 7420
BP 367
EP +
DI 10.1038/nature11442
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 021XI
UT WOS:000309918500038
PM 23000901
DA 2026-03-09
ER

PT J
AU Pollitz, FF
   Stein, RS
   Sevilgen, V
   Bürgmann, R
AF Pollitz, Fred F.
   Stein, Ross S.
   Sevilgen, Volkan
   Buergmann, Roland
TI The 11 April 2012 east Indian Ocean earthquake triggered large aftershocks worldwide
SO NATURE
LA English
DT Article
ID denali fault earthquake; seismicity; california; landers; slip
AB Large earthquakes trigger very small earthquakes globally during passage of the seismic waves and during the following several hours to days(1-10), but so far remote aftershocks of moment magnitude M >= 5.5 have not been identified(11), with the lone exception of an M = 6.9 quake remotely triggered by the surface waves from an M = 6.6 quake 4,800 kilometres away(12). The 2012 east Indian Ocean earthquake that had a moment magnitude of 8.6 is the largest strike-slip event ever recorded. Here we show that the rate of occurrence of remote M >= 5.5 earthquakes (>1,500 kilometres from the epicentre) increased nearly fivefold for six days after the 2012 event, and extended in magnitude to M <= 7. These global aftershocks were located along the four lobes of Love-wave radiation; all struck where the dynamic shear strain is calculated to exceed 10(-7) for at least 100 seconds during dynamic-wave passage. The other M >= 8.5 main-shocks during the past decade are thrusts; after these events, the global rate of occurrence of remote M >= 5.5 events increased by about one-third the rate following the 2012 shock and lasted for only two days, a weaker but possibly real increase. We suggest that the unprecedented delayed triggering power of the 2012 earthquake may have arisen because of its strike-slip source geometry or because the event struck at a time of an unusually low global earthquake rate, perhaps increasing the number of nucleation sites that were very close to failure.
C1 [Pollitz, Fred F.; Stein, Ross S.] US Geol Survey, Menlo Pk, CA 94025 USA.
   [Sevilgen, Volkan] Seism Net, San Carlos, CA 94070 USA.
   [Buergmann, Roland] Univ Calif Berkeley, Dept Earth & Planetary Sci, Berkeley, CA 94720 USA.
C3 United States Department of the Interior; United States Geological Survey; University of California System; University of California Berkeley
RP Pollitz, FF (corresponding author), US Geol Survey, 345 Middlefield Rd,MS 977, Menlo Pk, CA 94025 USA.
EM fpollitz@usgs.gov
NR 35
TC 155
Z9 175
U1 1
U2 53
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 11
PY 2012
VL 490
IS 7419
BP 250
EP +
DI 10.1038/nature11504
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 019IY
UT WOS:000309733300047
PM 23023131
DA 2026-03-09
ER

PT J
AU Cui, YJ
   Wang, W
   Dong, NZ
   Lou, JL
   Srinivasan, DK
   Cheng, WW
   Huang, XY
   Liu, M
   Fang, CD
   Peng, JH
   Chen, SH
   Wu, SN
   Liu, ZZ
   Dong, L
   Zhou, YQ
   Wu, QY
AF Cui, Yujie
   Wang, Wei
   Dong, Ningzheng
   Lou, Jinglei
   Srinivasan, Dinesh Kumar
   Cheng, Weiwei
   Huang, Xiaoyi
   Liu, Meng
   Fang, Chaodong
   Peng, Jianhao
   Chen, Shenghan
   Wu, Shannon
   Liu, Zhenzhen
   Dong, Liang
   Zhou, Yiqing
   Wu, Qingyu
TI Role of corin in trophoblast invasion and uterine spiral artery remodelling in pregnancy
SO NATURE
LA English
DT Article
ID proatrial natriuretic peptide; plasma soluble corin; serine-protease; pathogenesis; preeclampsia; implantation; hypertension
AB In pregnancy, trophoblast invasion and uterine spiral artery remodelling are important for lowering maternal vascular resistance and increasing uteroplacental blood flow. Impaired spiral artery remodelling has been implicated in pre-eclampsia, a major complication of pregnancy, for a long time but the underlying mechanisms remain unclear(1,2). Corin (also known as atrial natriuretic peptide-converting enzyme) is a cardiac protease that activates atrial natriuretic peptide (ANP), a cardiac hormone that is important in regulating blood pressure(3). Unexpectedly, corin expression was detected in the pregnant uterus(4). Here we identify a new function of corin and ANP in promoting trophoblast invasion and spiral artery remodelling. We show that pregnant corin-or ANP-deficient mice developed high blood pressure and proteinuria, characteristics of pre-eclampsia. In these mice, trophoblast invasion and uterine spiral artery remodelling were markedly impaired. Consistent with this, the ANP potently stimulated human trophoblasts in invading Matrigels. In patients with pre-eclampsia, uterine Corin messenger RNA and protein levels were significantly lower than that in normal pregnancies. Moreover, we have identified Corin gene mutations inpre-eclamptic patients, which decreased corin activity in processing pro-ANP. These results indicate that corin and ANP are essential for physiological changes at the maternal-fetal interface, suggesting that defects in corin and ANP function may contribute to pre-eclampsia.
C1 [Cui, Yujie; Wang, Wei; Lou, Jinglei; Srinivasan, Dinesh Kumar; Peng, Jianhao; Chen, Shenghan; Wu, Shannon; Wu, Qingyu] Cleveland Clin, Lerner Res Inst, Cleveland, OH 44195 USA.
   [Dong, Ningzheng; Liu, Meng; Fang, Chaodong; Liu, Zhenzhen; Dong, Liang; Zhou, Yiqing; Wu, Qingyu] Soochow Univ, Affiliated Hosp 1, Jiangsu Inst Hematol, Cyrus Tang Hematol Ctr, Suzhou 215123, Peoples R China.
   [Dong, Ningzheng] Soochow Univ, Affiliated Hosp 1, Jiangsu Inst Hematol, Key Lab Thrombosis & Hemostasis, Suzhou 215006, Peoples R China.
   [Cheng, Weiwei; Huang, Xiaoyi] Shanghai Jiao Tong Univ, Sch Med, Int Peace Matern & Child Hlth Hosp, Shanghai 200030, Peoples R China.
C3 Cleveland Clinic Foundation; Soochow University - China; Soochow University - China; Shanghai Jiao Tong University
RP Wu, QY (corresponding author), Cleveland Clin, Lerner Res Inst, 9500 Euclid Ave, Cleveland, OH 44195 USA.
EM wuq@ccf.org
FU Ralph Wilson Medical Foundation; Bakken Heart-Brain Institute; National Institutes of Health [HL089298, HD064634]; National Natural Science Foundation of China [31070716, 81170247, 31161130356]; Priority Academic Program Development of Jiangsu Higher Education Institutions
NR 33
TC 257
Z9 303
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 12
PY 2012
VL 484
IS 7393
BP 246
EP U134
DI 10.1038/nature10897
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 930OV
UT WOS:000303149900036
PM 22437503
DA 2026-03-09
ER

PT J
AU Olsen, SR
   Bortone, DS
   Adesnik, H
   Scanziani, M
AF Olsen, Shawn R.
   Bortone, Dante S.
   Adesnik, Hillel
   Scanziani, Massimo
TI Gain control by layer six in cortical circuits of vision
SO NATURE
LA English
DT Article
ID lateral geniculate-nucleus; primary visual-cortex; primary somatosensory cortex; response property; corticothalamic feedback; interlaminar connections; receptive-fields; end-inhibition; synaptic input; neurons
AB After entering the cerebral cortex, sensory information spreads through six different horizontal neuronal layers that are interconnected by vertical axonal projections. It is believed that through these projections layers can influence each other's response to sensory stimuli, but the specific role that each layer has in cortical processing is still poorly understood. Here we show that layer six in the primary visual cortex of the mouse has a crucial role in controlling the gain of visually evoked activity in neurons of the upper layers without changing their tuning to orientation. This gain modulation results from the coordinated action of layer six intracortical projections to superficial layers and deep projections to the thalamus, with a substantial role of the intracortical circuit. This study establishes layer six as a major mediator of cortical gain modulation and suggests that it could be a node through which convergent inputs from several brain areas can regulate the earliest steps of cortical visual processing.
C1 [Olsen, Shawn R.; Bortone, Dante S.; Adesnik, Hillel; Scanziani, Massimo] Univ Calif San Diego, Howard Hughes Med Inst, Ctr Neural Circuits & Behav, Neurobiol Sect, La Jolla, CA 92093 USA.
   [Olsen, Shawn R.; Bortone, Dante S.; Adesnik, Hillel; Scanziani, Massimo] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA.
C3 University of California System; University of California San Diego; Howard Hughes Medical Institute; University of California System; University of California San Diego
RP Scanziani, M (corresponding author), Univ Calif San Diego, Howard Hughes Med Inst, Ctr Neural Circuits & Behav, Neurobiol Sect, La Jolla, CA 92093 USA.
EM srolsen@ucsd.edu; massimo@biomail.ucsd.edu
FU Helen Hay Whitney Foundation; NINDS [5T32NS007220-28]; National Institutes of Health [RO1 NS069010]; Gatsby Charitable Foundation; National Institute of Neurological Disorders and Stroke [T32NS007220] Funding Source: NIH RePORTER
NR 50
TC 401
Z9 500
U1 0
U2 67
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD MAR 1
PY 2012
VL 483
IS 7387
BP 47
EP U83
DI 10.1038/nature10835
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 900HP
UT WOS:000300877900041
PM 22367547
DA 2026-03-09
ER

PT J
AU Shen, Y
   Yue, F
   McCleary, DF
   Ye, Z
   Edsall, L
   Kuan, S
   Wagner, U
   Dixon, J
   Lee, L
   Lobanenkov, VV
   Ren, B
AF Shen, Yin
   Yue, Feng
   McCleary, David F.
   Ye, Zhen
   Edsall, Lee
   Kuan, Samantha
   Wagner, Ulrich
   Dixon, Jesse
   Lee, Leonard
   Lobanenkov, Victor V.
   Ren, Bing
TI A map of the cis-regulatory sequences in the mouse genome
SO NATURE
LA English
DT Article
ID functional elements; enhancers; reveals; identification; vertebrate; promoters; dynamics; database; distinct
AB The laboratory mouse is the most widely used mammalian model organism in biomedical research. The 2.6 x 10(9) bases of the mouse genome possess a high degree of conservation with the human genome(1), so a thorough annotation of the mouse genome will be of significant value to understanding the function of the human genome. So far, most of the functional sequences in the mouse genome have yet to be found, and the cis-regulatory sequences in particular are still poorly annotated. Comparative genomics has been a powerful tool for the discovery of these sequences(2), but on its own it cannot resolve their temporal and spatial functions. Recently, ChIP-Seq has been developed to identify cis-regulatory elements in the genomes of several organisms including humans, Drosophila melanogaster and Caenorhabditis elegans(3-5). Here we apply the same experimental approach to a diverse set of 19 tissues and cell types in the mouse to produce a map of nearly 300,000 murine cis-regulatory sequences. The annotated sequences add up to 11% of the mouse [GRAPHICS] genome, and include more than 70% of conserved non-coding sequences. We define tissue-specific enhancers and identify potential transcription factors regulating gene expression in each tissue or cell type. Finally, we show that much of the mouse genome is organized into domains of coordinately regulated enhancers and promoters. Our results provide a resource for the annotation of functional elements in the mammalian genome and for the study of mechanisms regulating tissue-specific gene expression.
C1 [Shen, Yin; Yue, Feng; McCleary, David F.; Ye, Zhen; Edsall, Lee; Kuan, Samantha; Wagner, Ulrich; Dixon, Jesse; Lee, Leonard; Ren, Bing] Ludwig Inst Canc Res, La Jolla, CA 92093 USA.
   [Dixon, Jesse] Univ Calif San Diego, Sch Med, Med Scientist Training Program, La Jolla, CA 92093 USA.
   [Dixon, Jesse] Univ Calif San Diego, Sch Med, Biomed Sci Grad Program, La Jolla, CA 92093 USA.
   [Lobanenkov, Victor V.] NIAID, Immunogenet Lab, Twinbrook NIAID Facil 1, Rockville, MD 20852 USA.
   [Ren, Bing] Univ Calif San Diego, Sch Med, Moores Canc Ctr, Dept Cellular & Mol Med,Inst Genom Med, La Jolla, CA 92093 USA.
C3 Ludwig Institute for Cancer Research; University of California System; University of California San Diego; University of California System; University of California San Diego; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID); University of California System; University of California San Diego
RP Ren, B (corresponding author), Ludwig Inst Canc Res, 9500 Gilman Dr, La Jolla, CA 92093 USA.
EM biren@ucsd.edu
FU National Human Genome Research Institute [R01HG003991]; Ludwig Institute for Cancer Research; International Rett Syndrome Foundation; California Institute for Regenerative Medicine; National Institute of Allergy and Infectious Diseases [ZIAAI000860, ZIAAI001021] Funding Source: NIH RePORTER; National Institute of General Medical Sciences [T32GM007198] Funding Source: NIH RePORTER
NR 30
TC 1074
Z9 1342
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 AUG 2
PY 2012
VL 488
IS 7409
BP 116
EP 120
DI 10.1038/nature11243
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 981ZE
UT WOS:000307010700044
PM 22763441
DA 2026-03-09
ER

PT J
AU Dar, AC
   Das, TK
   Shokat, KM
   Cagan, RL
AF Dar, Arvin C.
   Das, Tirtha K.
   Shokat, Kevan M.
   Cagan, Ross L.
TI Chemical genetic discovery of targets and anti-targets for cancer polypharmacology
SO NATURE
LA English
DT Article
ID cell-proliferation; drosophila model; tyrosine kinase; inhibitor; pathways; carcinoma; ret; chromosome; pd-0325901; sorafenib
AB The complexity of cancer has led to recent interest in polypharmacological approaches for developing kinase-inhibitor drugs; however, optimal kinase-inhibition profiles remain difficult to predict. Using a Ret-kinase-driven Drosophila model of multiple endocrine neoplasia type 2 and kinome-wide drug profiling, here we identify that AD57 rescues oncogenic Ret-induced lethality, whereas related Ret inhibitors imparted reduced efficacy and enhanced toxicity. Drosophila genetics and compound profiling defined three pathways accounting for the mechanistic basis of efficacy and dose-limiting toxicity. Inhibition of Ret plus Raf, Src and S6K was required for optimal animal survival, whereas inhibition of the 'anti-target' Tor led to toxicity owing to release of negative feedback. Rational synthetic tailoring to eliminate Tor binding afforded AD80 and AD81, compounds featuring balanced pathway inhibition, improved efficacy and low toxicity in Drosophila and mammalian multiple endocrine neoplasia type 2 models. Combining kinase-focused chemistry, kinome-wide profiling and Drosophila genetics provides a powerful systems pharmacology approach towards developing compounds with a maximal therapeutic index.
C1 [Dar, Arvin C.; Shokat, Kevan M.] Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94158 USA.
   [Dar, Arvin C.; Shokat, Kevan M.] Univ Calif San Francisco, Dept Cellular & Mol Pharmacol, San Francisco, CA 94158 USA.
   [Das, Tirtha K.; Cagan, Ross L.] Mt Sinai Sch Med, Dept Dev & Regenerat Biol, New York, NY 10029 USA.
C3 Howard Hughes Medical Institute; University of California System; University of California San Francisco; University of California System; University of California San Francisco; Icahn School of Medicine at Mount Sinai
RP Shokat, KM (corresponding author), Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94158 USA.
EM shokat@cmp.ucsf.edu
FU National Institutes of Health [R01CA109730, R01CA084309, R01EB001987, P01 CA081403-11]; American Cancer Society [120616-RSGM-11-018-01-CDD, 120886-PFM-11-137-01-DDC]
NR 34
TC 282
Z9 313
U1 1
U2 98
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUN 7
PY 2012
VL 486
IS 7401
BP 80
EP U101
DI 10.1038/nature11127
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 953GD
UT WOS:000304854000030
PM 22678283
DA 2026-03-09
ER

PT J
AU Engel, P
   Goepfert, A
   Stanger, FV
   Harms, A
   Schmidt, A
   Schirmer, T
   Dehio, C
AF Engel, Philipp
   Goepfert, Arnaud
   Stanger, Frederic V.
   Harms, Alexander
   Schmidt, Alexander
   Schirmer, Tilman
   Dehio, Christoph
TI Adenylylation control by intra- or intermolecular active-site obstruction in Fic proteins
SO NATURE
LA English
DT Article
ID bartonella-henselae; ampylation; filamentation; binding; gtpases; doc; amp
AB Fic proteins that are defined by the ubiquitous FIC (filamentation induced by cyclic AMP) domain are known to catalyse adenylylation (also called AMPylation); that is, the transfer of AMP onto a target protein. In mammalian cells, adenylylation of small GTPases through Fic proteins injected by pathogenic bacteria can cause collapse of the actin cytoskeleton and cell death(1,2). It is unknown how this potentially deleterious adenylylation activity is regulated in the widespread Fic proteins that are found in all domains of life and that are thought to have critical roles in intrinsic signalling processes. Here we show that FIC-domain-mediated adenylylation is controlled by a conserved mechanism of ATP-binding-site obstruction that involves an inhibitory alpha-helix (alpha(inh)) with a conserved (S/T)XXXE(G/N) motif, and that in this mechanism the invariable glutamate competes with ATP gamma-phosphate binding. Consistent with this, FIC-domain-mediated growth arrest of bacteria by the VbhT toxin of Bartonella schoen-buchensis is intermolecularly repressed by the VbhA antitoxin through tight binding of its alpha(inh) to the FIC domain of VbhT, as shown by structure and function analysis. Furthermore, structural comparisons with other bacterial Fic proteins, such as Fic of Neisseria meningitidis and of Shewanella oneidensis, show that alpha(inh) frequently constitutes an amino-terminal or carboxy-terminal extension to the FIC domain, respectively, partially obstructing the ATP binding site in an intramolecular manner. After mutation of the inhibitory motif in various Fic proteins, including the human homologue FICD (also known as HYPE), adenylylation activity is considerably boosted, consistent with the anticipated relief of inhibition. Structural homology modelling of all annotated Fic proteins indicates that inhibition by alpha(inh) is universal and conserved through evolution, as the inhibitory motif is present in similar to 90% of all putatively adenylylation-active FIC domains, including examples from all domains of life and from viruses. Future studies should reveal how intrinsic or extrinsic factors modulate adenylylation activity by weakening the interaction of alpha(inh) with the FIC active site.
C1 [Goepfert, Arnaud; Stanger, Frederic V.; Schirmer, Tilman; Dehio, Christoph] Univ Basel, Biozentrum, Core Program Struct Biol & Biophys, CH-4056 Basel, Switzerland.
   [Schmidt, Alexander] Univ Basel, Biozentrum, Prote Core Facil, CH-4056 Basel, Switzerland.
C3 University of Basel; University of Basel
RP Dehio, C (corresponding author), Univ Basel, Biozentrum, Core Program Struct Biol & Biophys, CH-4056 Basel, Switzerland.
EM Tilman.Schirmer@unibas.ch; Christoph.Dehio@unibas.ch
FU Swiss National Science Foundation [3100-061777, 3100-138414]; SystemsX.ch Swiss Initiative for Systems Biology [51RT 0_126008 (InfectX)]
NR 32
TC 135
Z9 156
U1 1
U2 53
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 2
PY 2012
VL 482
IS 7383
BP 107
EP U138
DI 10.1038/nature10729
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 884RN
UT WOS:000299726000045
PM 22266942
DA 2026-03-09
ER

PT J
AU Molenaar, JJ
   Koster, J
   Zwijnenburg, DA
   van Sluis, P
   Valentijn, LJ
   van der Ploeg, I
   Hamdi, M
   van Nes, J
   Westerman, BA
   van Arkel, J
   Ebus, ME
   Haneveld, F
   Lakeman, A
   Schild, L
   Molenaar, P
   Stroeken, P
   van Noesel, MM
   Ora, I
   Santo, EE
   Caron, HN
   Westerhout, EM
   Versteeg, R
AF Molenaar, Jan J.
   Koster, Jan
   Zwijnenburg, Danny A.
   van Sluis, Peter
   Valentijn, Linda J.
   van der Ploeg, Ida
   Hamdi, Mohamed
   van Nes, Johan
   Westerman, Bart A.
   van Arkel, Jennemiek
   Ebus, Marli E.
   Haneveld, Franciska
   Lakeman, Arjan
   Schild, Linda
   Molenaar, Piet
   Stroeken, Peter
   van Noesel, Max M.
   Ora, Ingrid
   Santo, Evan E.
   Caron, Huib N.
   Westerhout, Ellen M.
   Versteeg, Rogier
TI Sequencing of neuroblastoma identifies chromothripsis and defects in neuritogenesis genes
SO NATURE
LA English
DT Article
ID activating mutations; tumor-suppressor; alk kinase; pathway; roles; expression; receptor; family; acid
AB Neuroblastomais a childhood tumour of the peripheral sympathetic nervous system. The pathogenesis has for a long time been quite enigmatic, as only very few gene defects were identified in this often lethal tumour(1). Frequently detected gene alterations are limited to MYCN amplification (20%) and ALK activations (7%)(2-5). Here we present a whole-genome sequence analysis of 87 neuroblastoma of all stages. Few recurrent amino-acid-changing mutations were found. In contrast, analysis of structural defects identified a local shredding of chromosomes, known as chromothripsis, in 18% of high-stage neuroblastoma(6). These tumours are associated with a poor outcome. Structural alterations recurrently affected ODZ3, PTPRD and CSMD1, which are involved in neuronal growth cone stabilization(7-9). In addition, ATRX, TIAM1 and a series of regulators of the Rac/Rho pathway were mutated, further implicating defects in neuritogenesis in neuroblastoma. Most tumours with defects in these genes were aggressive high-stage neuroblastomas, but did not carry MYCN amplifications. The genomic landscape of neuroblastoma therefore reveals two novel molecular defects, chromothripsis and neuritogenesis gene alterations, which frequently occur in high-risk tumours.
C1 [Molenaar, Jan J.; Koster, Jan; Zwijnenburg, Danny A.; van Sluis, Peter; Valentijn, Linda J.; van der Ploeg, Ida; Hamdi, Mohamed; van Nes, Johan; Westerman, Bart A.; van Arkel, Jennemiek; Ebus, Marli E.; Haneveld, Franciska; Lakeman, Arjan; Schild, Linda; Molenaar, Piet; Stroeken, Peter; Ora, Ingrid; Santo, Evan E.; Westerhout, Ellen M.; Versteeg, Rogier] Univ Amsterdam, Acad Med Ctr, Dept Oncogenom, NL-1105 AZ Amsterdam, Netherlands.
   [van Noesel, Max M.] Sophia Childrens Univ Hosp, Erasmus MC, Dept Pediat Oncol Hematol, NL-3015 GJ Rotterdam, Netherlands.
   [Ora, Ingrid] Lund Univ, Skane Univ Hosp, Dept Pediat Oncol & Hematol, S-22185 Lund, Sweden.
   [Caron, Huib N.] Univ Amsterdam, Acad Med Ctr, Emma Childrens Hosp, Dept Pediat Oncol, NL-1105 AZ Amsterdam, Netherlands.
C3 University of Amsterdam; Academic Medical Center Amsterdam; Erasmus University Rotterdam; Erasmus MC; Erasmus MC - Sophia Children's Hospital; Lund University; Skane University Hospital; Vrije Universiteit Amsterdam; Emma Children's Hospital; University of Amsterdam; Academic Medical Center Amsterdam
RP Versteeg, R (corresponding author), Univ Amsterdam, Acad Med Ctr, Dept Oncogenom, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands.
EM j.j.molenaar@amc.uva.nl; r.versteeg@amc.uva.nl
FU Villa Joep Foundation; KIKA; Tom Voute Fund; Netherlands Cancer Foundation
NR 36
TC 720
Z9 810
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 MAR 29
PY 2012
VL 483
IS 7391
BP 589
EP U107
DI 10.1038/nature10910
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 915EF
UT WOS:000302006100037
PM 22367537
DA 2026-03-09
ER

PT J
AU Wang, YF
   Wang, Y
   Breed, DR
   Manoharan, VN
   Feng, L
   Hollingsworth, AD
   Weck, M
   Pine, DJ
AF Wang, Yufeng
   Wang, Yu
   Breed, Dana R.
   Manoharan, Vinothan N.
   Feng, Lang
   Hollingsworth, Andrew D.
   Weck, Marcus
   Pine, David J.
TI Colloids with valence and specific directional bonding
SO NATURE
LA English
DT Article
ID asymmetric functionalization; clusters; nanoparticles; particles; anisotropy
AB The ability to design and assemble three-dimensional structures from colloidal particles is limited by the absence of specific directional bonds. As a result, complex or low-coordination structures, common in atomic and molecular systems, are rare in the colloidal domain. Here we demonstrate a general method for creating the colloidal analogues of atoms with valence: colloidal particles with chemically distinct surface patches that imitate hybridized atomic orbitals, including sp, sp(2), sp(3), sp(3)d, sp(3)d(2) and sp(3)d(3). Functionalized with DNA with single-stranded sticky ends, patches on different particles can form highly directional bonds through programmable, specific and reversible DNA hybridization. These features allow the particles to self-assemble into 'colloidal molecules' with triangular, tetrahedral and other bonding symmetries, and should also give access to a rich variety of new microstructured colloidal materials.
C1 [Feng, Lang; Hollingsworth, Andrew D.; Pine, David J.] NYU, Ctr Soft Matter Res, New York, NY 10003 USA.
   [Feng, Lang; Hollingsworth, Andrew D.; Pine, David J.] NYU, Dept Phys, New York, NY 10003 USA.
   [Wang, Yufeng; Wang, Yu; Weck, Marcus] NYU, Inst Mol Design, New York, NY 10003 USA.
   [Wang, Yufeng; Wang, Yu; Weck, Marcus] NYU, Dept Chem, New York, NY 10003 USA.
   [Breed, Dana R.] Dow Chem Co USA, Freeport, TX 77541 USA.
   [Manoharan, Vinothan N.] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA.
   [Manoharan, Vinothan N.] Harvard Univ, Dept Phys, Cambridge, MA 02138 USA.
C3 New York University; New York University; New York University; New York University; Dow Chemical Company; Harvard University; Harvard University
RP Pine, DJ (corresponding author), NYU, Ctr Soft Matter Res, New York, NY 10003 USA.
EM marcus.weck@nyu.edu; pine@nyu.edu
FU MRSEC Program of the National Science Foundation [DMR-0820341]; National Science Foundation [ChE-0911460]; MRI programme of the National Science Foundation [DMR-0923251]; Division Of Chemistry; Direct For Mathematical & Physical Scien [0911460] Funding Source: National Science Foundation; Division Of Materials Research; Direct For Mathematical & Physical Scien [0923251] Funding Source: National Science Foundation
NR 47
TC 931
Z9 1089
U1 9
U2 733
PU NATURE PUBLISHING 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 1
PY 2012
VL 491
IS 7422
BP 51
EP U61
DI 10.1038/nature11564
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 028PM
UT WOS:000310434500029
PM 23128225
DA 2026-03-09
ER

PT J
AU Stephens, PJ
   Tarpey, PS
   Davies, H
   Van Loo, P
   Greenman, C
   Wedge, DC
   Nik-Zainal, S
   Martin, S
   Varela, I
   Bignell, GR
   Yates, LR
   Papaemmanuil, E
   Beare, D
   Butler, A
   Cheverton, A
   Gamble, J
   Hinton, J
   Jia, MM
   Jayakumar, A
   Jones, D
   Latimer, C
   Lau, KW
   McLaren, S
   McBride, DJ
   Menzies, A
   Mudie, L
   Raine, K
   Rad, R
   Chapman, MS
   Teague, J
   Easton, D
   Langerod, A
   Lee, MTM
   Shen, CY
   Tee, BTK
   Huimin, BW
   Broeks, A
   Vargas, AC
   Turashvili, G
   Martens, J
   Fatima, A
   Miron, P
   Chin, SF
   Thomas, G
   Boyault, S
   Mariani, O
   Lakhani, SR
   van de Vijver, M
   Van 'Tveer, L
   Foekens, J
   Desmedt, C
   Sotiriou, C
   Tutt, A
   Caldas, C
   Reis, JS
   Aparicio, SAJR
   Salomon, AV
   Borresen-Dale, AL
   Richardson, AL
   Campbell, PJ
   Futreal, PA
   Stratton, MR
AF Stephens, Philip J.
   Tarpey, Patrick S.
   Davies, Helen
   Van Loo, Peter
   Greenman, Chris
   Wedge, David C.
   Nik-Zainal, Serena
   Martin, Sancha
   Varela, Ignacio
   Bignell, Graham R.
   Yates, Lucy R.
   Papaemmanuil, Elli
   Beare, David
   Butler, Adam
   Cheverton, Angela
   Gamble, John
   Hinton, Jonathan
   Jia, Mingming
   Jayakumar, Alagu
   Jones, David
   Latimer, Calli
   Lau, King Wai
   McLaren, Stuart
   McBride, David J.
   Menzies, Andrew
   Mudie, Laura
   Raine, Keiran
   Rad, Roland
   Chapman, Michael Spencer
   Teague, Jon
   Easton, Douglas
   Langerod, Anita
   Lee, Ming Ta Michael
   Shen, Chen-Yang
   Tee, Benita Tan Kiat
   Huimin, Bernice Wong
   Broeks, Annegien
   Vargas, Ana Cristina
   Turashvili, Gulisa
   Martens, John
   Fatima, Aquila
   Miron, Penelope
   Chin, Suet-Feung
   Thomas, Gilles
   Boyault, Sandrine
   Mariani, Odette
   Lakhani, Sunil R.
   van de Vijver, Marc
   Van 'tVeer, Laura
   Foekens, John
   Desmedt, Christine
   Sotiriou, Christos
   Tutt, Andrew
   Caldas, Carlos
   Reis-Filho, Jorge S.
   Aparicio, Samuel A. J. R.
   Salomon, Anne Vincent
   Borresen-Dale, Anne-Lise
   Richardson, Andrea L.
   Campbell, Peter J.
   Futreal, P. Andrew
   Stratton, Michael R.
TI The landscape of cancer genes and mutational processes in breast cancer
SO NATURE
LA English
DT Article
ID nucleotide excision-repair; genome-wide association; swi/snf complex; susceptibility; mechanisms; arid1a; cells
AB All cancers carry somatic mutations in their genomes. A subset, known as driver mutations, confer clonal selective advantage on cancer cells and are causally implicated in oncogenesis(1), and the remainder are passenger mutations. The driver mutations and mutational processes operative in breast cancer have not yet been comprehensively explored. Here we examine the genomes of 100 tumours for somatic copy number changes and mutations in the coding exons of protein-coding genes. The number of somatic mutations varied markedly between individual tumours. We found strong correlations between mutation number, age at which cancer was diagnosed and cancer histological grade, and observed multiple mutational signatures, including one present in about ten per cent of tumours characterized by numerous mutations of cytosine at TpC dinucleotides. Driver mutations were identified in several new cancer genes including AKT2, ARID1B, CASP8, CDKN1B, MAP3K1, MAP3K13, NCOR1, SMARCD1 and TBX3. Among the 100 tumours, we found driver mutations in at least 40 cancer genes and 73 different combinations of mutated cancer genes. The results highlight the substantial genetic diversity underlying this common disease.
C1 [Stephens, Philip J.; Tarpey, Patrick S.; Davies, Helen; Van Loo, Peter; Greenman, Chris; Wedge, David C.; Nik-Zainal, Serena; Martin, Sancha; Varela, Ignacio; Bignell, Graham R.; Yates, Lucy R.; Papaemmanuil, Elli; Beare, David; Butler, Adam; Cheverton, Angela; Gamble, John; Hinton, Jonathan; Jia, Mingming; Jayakumar, Alagu; Jones, David; Latimer, Calli; Lau, King Wai; McLaren, Stuart; McBride, David J.; Menzies, Andrew; Mudie, Laura; Raine, Keiran; Rad, Roland; Chapman, Michael Spencer; Teague, Jon; Campbell, Peter J.; Futreal, P. Andrew; Stratton, Michael R.] Wellcome Trust Sanger Inst, Canc Genome Project, Hinxton CB10 1SA, England.
   [Van Loo, Peter] VIB, Human Genome Lab, Dept Human Genet, B-3000 Louvain, Belgium.
   [Van Loo, Peter] Katholieke Univ Leuven, B-3000 Louvain, Belgium.
   [Greenman, Chris] Univ E Anglia, Sch Comp Sci, Norwich NR4 7TJ, Norfolk, England.
   [Greenman, Chris] Genome Anal Ctr, Norwich NR4 7TJ, Norfolk, England.
   [Yates, Lucy R.; Tutt, Andrew] Kings Coll London, Breakthrough Breast Canc Res Unit, Sch Med, London SE1 9RT, England.
   [Yates, Lucy R.] Guys & St Thomas NHS Trust, Dept Clin Oncol, London SE1 7EH, England.
   [Easton, Douglas] Ctr Canc Genet Epidemiol, Dept Oncol, Strangeways Res Lab, Cambridge CB1 8RN, England.
   [Easton, Douglas] Ctr Canc Genet Epidemiol, Dept Publ Hlth & Primary Care, Strangeways Res Lab, Cambridge CB1 8RN, England.
   [Langerod, Anita; Borresen-Dale, Anne-Lise] Oslo Univ Hosp, Dept Genet, Inst Canc Res, Norwegian Radium Hosp, N-0310 Oslo, Norway.
   [Lee, Ming Ta Michael; Shen, Chen-Yang] Acad Sinica, Natl Genotyping Ctr, Inst Biomed Sci, Taipei 115, Taiwan.
   [Tee, Benita Tan Kiat] Singapore Gen Hosp, Dept Gen Surg, Singapore 169608, Singapore.
   [Huimin, Bernice Wong] Natl Canc Ctr Singapore, NCCS VARI Translat Res Lab, Singapore 169610, Singapore.
   [Broeks, Annegien; Van 'tVeer, Laura] Netherlands Canc Inst, Dept Expt Therapy, NL-1066 CX Amsterdam, Netherlands.
   [Vargas, Ana Cristina; Lakhani, Sunil R.] Univ Queensland, Clin Res Ctr, Royal Brisbane & Womens Hosp, Brisbane, Qld 4029, Australia.
   [Turashvili, Gulisa; Aparicio, Samuel A. J. R.] Univ British Columbia, Dept Pathol & Lab Med, Vancouver, BC V6T 2B5, Canada.
   [Turashvili, Gulisa; Aparicio, Samuel A. J. R.] British Columbia Canc Res Ctr, Vancouver, BC V5Z 1L3, Canada.
   [Martens, John; Foekens, John] Erasmus Univ, Dept Med Oncol, Med Ctr, Daniel den Hoed Canc Ctr, NL-3000 CA Rotterdam, Netherlands.
   [Martens, John; Foekens, John] Canc Genom Ctr, NL-3000 CA Rotterdam, Netherlands.
   [Fatima, Aquila; Miron, Penelope; Richardson, Andrea L.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA.
   [Chin, Suet-Feung; Caldas, Carlos] Univ Cambridge, Dept Oncol, Cambridge CB2 0RE, England.
   [Chin, Suet-Feung; Caldas, Carlos] Canc Res UK, Cambridge Res Inst, Li Ka Shin Ctr, Cambridge CB2 0RE, England.
   [Thomas, Gilles; Boyault, Sandrine] Univ Lyon 1, INCa Synergie, Ctr Leon Berard, F-69365 Lyon 08, France.
   [Mariani, Odette; Salomon, Anne Vincent] Inst Curie, Dept Tumor Biol, F-75248 Paris 05, France.
   [Lakhani, Sunil R.] Univ Queensland, Sch Med, Brisbane, Qld 4006, Australia.
   [Lakhani, Sunil R.] Royal Brisbane & Womens Hosp, Brisbane, Qld 4029, Australia.
   [van de Vijver, Marc] Univ Amsterdam, Acad Med Ctr, Dept Pathol, NL-1105 AZ Amsterdam, Netherlands.
   [Desmedt, Christine; Sotiriou, Christos] Univ Libre Bruxelles, Breast Canc Translat Lab, Inst Jules Bordet, B-1000 Brussels, Belgium.
   [Caldas, Carlos] Cambridge Univ Hosp NHS Fdn Trust, NIHR Cambridge Biomed Res Ctr, Cambridge CB2 2QQ, England.
   [Caldas, Carlos] Cambridge Univ Hosp NHS Fdn Trust, Cambridge Expt Canc Med Ctr, Cambridge CB2 2QQ, England.
   [Reis-Filho, Jorge S.] Inst Canc Res, Breakthrough Breast Canc Res Ctr, London SW3 6JB, England.
   [Salomon, Anne Vincent] INSERM, U830, Inst Curie, F-75248 Paris 05, France.
   [Borresen-Dale, Anne-Lise] Univ Oslo, KG Jebsen Ctr Breast Canc Res, Inst Clin Med, Fac Med, N-0318 Oslo, Norway.
   [Richardson, Andrea L.] Harvard Univ, Dept Pathol, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA.
   [Campbell, Peter J.] Addenbrookes Hosp, Dept Haematol, Cambridge CB2 0QQ, England.
   [Campbell, Peter J.] Univ Cambridge, Dept Haematol, Cambridge CB2 2XY, England.
C3 Wellcome Trust Sanger Institute; Flanders Institute for Biotechnology (VIB); KU Leuven; University of East Anglia; UK Research & Innovation (UKRI); Biotechnology and Biological Sciences Research Council (BBSRC); Earlham Institute; University of London; King's College London; Guy's & St Thomas' NHS Foundation Trust; University of Oslo; Academia Sinica - Taiwan; Singapore General Hospital; National Cancer Centre Singapore (NCCS); Netherlands Cancer Institute; Royal Brisbane & Women's Hospital; University of Queensland; University of British Columbia; British Columbia Cancer Agency; Erasmus University Rotterdam; Erasmus MC; Erasmus MC Cancer Institute; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; University of Cambridge; CRUK Cambridge Institute; Cancer Research UK; University of Cambridge; Institut National du Cancer (INCA) France; Universite Lyon 1; UNICANCER; Centre Leon Berard; UNICANCER; Universite PSL; Institut Curie; University of Queensland; Royal Brisbane & Women's Hospital; University of Amsterdam; Academic Medical Center Amsterdam; Vrije Universiteit Amsterdam; Institut Jules Bordet; Universite Libre de Bruxelles; University of Cambridge; University of Cambridge; Royal Marsden NHS Foundation Trust; University of London; Institute of Cancer Research - UK; Universite PSL; UNICANCER; Institut Curie; Institut National de la Sante et de la Recherche Medicale (Inserm); University of Oslo; Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Brigham & Women's Hospital; Cambridge University Hospitals NHS Foundation Trust; Addenbrooke's Hospital; University of Cambridge; University of Cambridge
RP Stratton, MR (corresponding author), Wellcome Trust Sanger Inst, Canc Genome Project, Wellcome Trust Genome Campus, Hinxton CB10 1SA, England.
EM mrs@sanger.ac.uk
FU Wellcome Trust [077012/Z/05/Z]; Breakthrough Breast Cancer; Wellcome Trust Senior Clinical Research Fellowship [WT088340MA]; Research Foundation - Flanders (FWO); travel grant from the FWO; International Human Frontier Science Program Organization; Norwegian Research Council; Norwegian Cancer Society; Radium Hospital Foundation; Health Region SO; 'Interface INSERM' grant; Department of Health via the National Institute for Health Research comprehensive Biomedical Research Centre award; St Thomas' NHS Foundation Trust; King's College London; King's College Hospital NHS Foundation Trust; Cancer Research UK; National Institute for Health Research; Welsh Assembly Government; HSC R&D Office for Northern Ireland and the Chief Scientist Office, Scotland; MEDIC foundation; Fonds National de Recherche Scientifique; Netherlands Genomics Initiative/Netherlands Organization for Scientific Research; Institut National du Cancer; Fondation Synergie-Lyon-Cancer; Canceropole Lyon Auverge Rhone Alpes; Centre Leon Berard; Ludwig Institute for Cancer Research; Dutch Genomics Initiative-Cancer Genomics Center; Biotechnology and Biological Sciences Research Council [BBS/E/T/000PR6193] Funding Source: researchfish; Cancer Research UK [11022, 10118] Funding Source: researchfish; National Institute for Health Research [NF-SI-0611-10154] Funding Source: researchfish; National Cancer Institute [P30CA016672] Funding Source: NIH RePORTER; BBSRC [BBS/E/T/000PR6193] Funding Source: UKRI
NR 34
TC 1367
Z9 1583
U1 0
U2 233
PU NATURE PUBLISHING 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 21
PY 2012
VL 486
IS 7403
BP 400
EP +
DI 10.1038/nature11017
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 961LV
UT WOS:000305466800043
PM 22722201
DA 2026-03-09
ER

PT J
AU McCabe, MT
   Ott, HM
   Ganji, G
   Korenchuk, S
   Thompson, C
   Van Aller, GS
   Liu, Y
   Graves, AP
   Della Pietra, A
   Diaz, E
   LaFrance, LV
   Mellinger, M
   Duquenne, C
   Tian, XR
   Kruger, RG
   McHugh, CF
   Brandt, M
   Miller, WH
   Dhanak, D
   Verma, SK
   Tummino, PJ
   Creasy, CL
AF McCabe, Michael T.
   Ott, Heidi M.
   Ganji, Gopinath
   Korenchuk, Susan
   Thompson, Christine
   Van Aller, Glenn S.
   Liu, Yan
   Graves, Alan P.
   Della Pietra, Anthony, III
   Diaz, Elsie
   LaFrance, Louis V.
   Mellinger, Mark
   Duquenne, Celine
   Tian, Xinrong
   Kruger, Ryan G.
   McHugh, Charles F.
   Brandt, Martin
   Miller, William H.
   Dhanak, Dashyant
   Verma, Sharad K.
   Tummino, Peter J.
   Creasy, Caretha L.
TI EZH2 inhibition as a therapeutic strategy for lymphoma with EZH2-activating mutations
SO NATURE
LA English
DT Article
ID histone methyltransferase ezh2; lysine 27; somatic mutations; genes; h3; hypertrimethylation; methylation; substrate; cancer; h3k27
AB In eukaryotes, post-translational modification of histones is critical for regulation of chromatin structure and gene expression. EZH2 is the catalytic subunit of the polycomb repressive complex 2 (PRC2) and is involved in repressing gene expression through methylation of histone H3 on lysine 27 (H3K27). EZH2 overexpression is implicated in tumorigenesis and correlates with poor prognosis in several tumour types(1-5). Additionally, somatic heterozygous mutations of Y641 and A677 residues within the catalytic SET domain of EZH2 occur in diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma(6-10). The Y641 residue is the most frequently mutated residue, with up to 22% of germinal centre B-cell DLBCL and follicular lymphoma harbouring mutations at this site. These lymphomas have increased H3K27 tri-methylation (H3K27me3) owing to altered substrate preferences of the mutant enzymes(9,11-13). However, it is unknown whether specific, direct inhibition of EZH2 methyltransferase activity will be effective in treating EZH2 mutant lymphomas. Here we demonstrate that GSK126, a potent, highly selective, S-adenosyl-methionine-competitive, small-molecule inhibitor of EZH2 methyltransferase activity, decreases global H3K27me3 levels and reactivates silenced PRC2 target genes. GSK126 effectively inhibits the proliferation of EZH2 mutant DLBCL cell lines and markedly inhibits the growth of EZH2 mutant DLBCL xenografts in mice. Together, these data demonstrate that pharmacological inhibition of EZH2 activity may provide a promising treatment for EZH2 mutant lymphoma.
C1 [McCabe, Michael T.; Ott, Heidi M.; Ganji, Gopinath; Korenchuk, Susan; Thompson, Christine; Van Aller, Glenn S.; Liu, Yan; Della Pietra, Anthony, III; LaFrance, Louis V.; Mellinger, Mark; Duquenne, Celine; Tian, Xinrong; Kruger, Ryan G.; McHugh, Charles F.; Miller, William H.; Dhanak, Dashyant; Verma, Sharad K.; Tummino, Peter J.; Creasy, Caretha L.] GlaxoSmithKline, Canc Epigenet Discovery Performance Unit, Canc Res, Oncol R&D, Collegeville, PA 19426 USA.
   [Graves, Alan P.; Diaz, Elsie; Brandt, Martin] GlaxoSmithKline, Platform Technol & Sci, Collegeville, PA 19426 USA.
C3 GlaxoSmithKline; Glaxosmithkline USA; GlaxoSmithKline; Glaxosmithkline USA
RP Creasy, CL (corresponding author), GlaxoSmithKline, Canc Epigenet Discovery Performance Unit, Canc Res, Oncol R&D, 1250 S Collegeville Rd, Collegeville, PA 19426 USA.
EM caretha.l.creasy@gsk.com
NR 30
TC 1498
Z9 1774
U1 1
U2 242
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 6
PY 2012
VL 492
IS 7427
BP 108
EP +
DI 10.1038/nature11606
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 048EQ
UT WOS:000311893400055
PM 23051747
DA 2026-03-09
ER

PT J
AU Kuo, AJ
   Song, JK
   Cheung, P
   Ishibe-Murakami, S
   Yamazoe, S
   Chen, JK
   Patel, DJ
   Gozani, O
AF Kuo, Alex J.
   Song, Jikui
   Cheung, Peggie
   Ishibe-Murakami, Satoko
   Yamazoe, Sayumi
   Chen, James K.
   Patel, Dinshaw J.
   Gozani, Or
TI The BAH domain of ORC1 links H4K20me2 to DNA replication licensing and Meier-Gorlin syndrome
SO NATURE
LA English
DT Article
ID origin recognition complex; 20 methyltransferase pr-set7; hbo1 histone acetylase; structural basis; chromatin modifications; primordial dwarfism; phd finger; methylation; mutations; h3
AB The recognition of distinctly modified histones by specialized 'effector' proteins constitutes a key mechanism for transducing molecular events at chromatin to biological outcomes(1). Effector proteins influence DNA-templated processes, including transcription, DNA recombination and DNA repair; however, no effector functions have yet been identified within the mammalian machinery that regulate DNA replication. Here we show that ORC1-a component of ORC (origin of replication complex), which mediates pre-DNA replication licensing(2)-contains a bromo adjacent homology (BAH) domain that specifically recognizes histone H4 dimethylated at lysine 20 (H4K20me2). Recognition of H4K20me2 is a property common to BAH domains present within diverse metazoan ORC1 proteins. Structural studies reveal that the specificity of the BAH domain for H4K20me2 is mediated by a dynamic aromatic dimethyl-lysine-binding cage and multiple intermolecular contacts involving the bound peptide. H4K20me2 is enriched at replication origins, and abrogating ORC1 recognition of H4K20me2 in cells impairs ORC1 occupancy at replication origins, ORC chromatin loading and cell-cycle progression. Mutation of the ORC1 BAH domain has been implicated in the aetiology of Meier-Gorlin syndrome (MGS)(3,4), a form of primordial dwarfism(5), and ORC1 depletion in zebrafish results in an MGS-like phenotype(4). We find that wild-type human ORC1, but not ORC1-H4K20me2-binding mutants, rescues the growth retardation of orc1 morphants. Moreover, zebrafish depleted of H4K20me2 have diminished body size, mirroring the phenotype of orc1 morphants. Together, our results identify the BAH domain as a novel methyl-lysine-binding module, thereby establishing the first direct link between histone methylation and the metazoan DNA replication machinery, and defining a pivotal aetiological role for the canonical H4K20me2 mark, via ORC1, in primordial dwarfism.
C1 [Song, Jikui; Ishibe-Murakami, Satoko; Patel, Dinshaw J.] Mem Sloan Kettering Canc Ctr, Struct Biol Program, New York, NY 10065 USA.
   [Kuo, Alex J.; Cheung, Peggie; Gozani, Or] Stanford Univ, Dept Biol, Stanford, CA 94305 USA.
   [Yamazoe, Sayumi; Chen, James K.] Stanford Univ, Sch Med, Dept Chem & Syst Biol, Stanford, CA 94305 USA.
C3 Memorial Sloan Kettering Cancer Center; Stanford University; Stanford University
RP Patel, DJ (corresponding author), Mem Sloan Kettering Canc Ctr, Struct Biol Program, New York, NY 10065 USA.
EM pateld@mskcc.org; ogozani@stanford.edu
FU Abby Rockefeller Mauze Foundation; STARR Foundation; Maloris Foundation; Genentech Foundation; Ellison Senior Scholar in Aging Award;  [R01 GM079641];  [DP1 OD003792]; National Cancer Institute [P30CA008748] Funding Source: NIH RePORTER
NR 37
TC 287
Z9 357
U1 1
U2 45
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 5
PY 2012
VL 484
IS 7392
BP 115
EP +
DI 10.1038/nature10956
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 919QN
UT WOS:000302343400045
PM 22398447
DA 2026-03-09
ER

PT J
AU Næraa, T
   Scherstén, A
   Rosing, MT
   Kemp, AIS
   Hoffmann, JE
   Kokfelt, TF
   Whitehouse, MJ
AF Naeraa, T.
   Schersten, A.
   Rosing, M. T.
   Kemp, A. I. S.
   Hoffmann, J. E.
   Kokfelt, T. F.
   Whitehouse, M. J.
TI Hafnium isotope evidence for a transition in the dynamics of continental growth 3.2Gyr ago
SO NATURE
LA English
DT Article
ID southern west greenland; plasma-mass spectrometry; itsaq gneiss complex; jack hills zircons; situ u-pb; lu-hf; crustal evolution; plate-tectonics; greenstone-belt; constraints
AB Earth's lithosphere probably experienced an evolution towards the modern plate tectonic regime, owing to secular changes in mantle temperature(1,2). Radiogenic isotope variations are interpreted as evidence for the declining rates of continental crustal growth over time(3-5), with some estimates suggesting that over 70% of the present continental crustal reservoir was extracted by the end of the Archaean eon(3,5). Patterns of crustal growth and reworking in rocks younger than three billion years (Gyr) are thought to reflect the assembly and break-up of supercontinents by Wilson cycle processes and mark an important change in lithosphere dynamics(6). In southern West Greenland numerous studies have, however, argued for subduction settings and crust growth by arc accretion back to 3.8 Gyr ago(7-9), suggesting that modern-day tectonic regimes operated during the formation of the earliest crustal rock record. Here we report in situ uranium-lead, hafnium and oxygen isotope data from zircons of basement rocks in southern West Greenland across the critical time period during which modern-like tectonic regimes could have initiated. Our data show pronounced differences in the hafnium isotope-time patterns across this interval, requiring changes in the characteristics of the magmatic protolith. The observations suggest that 3.9-3.5-Gyr-old rocks differentiated from a >3.9-Gyr-old source reservoir with a chondritic to slightly depleted hafnium isotope composition. In contrast, rocks formed after 3.2 Gyr ago register the first additions of juvenile depleted material (that is, new mantle-derived crust) since 3.9 Gyr ago, and are characterized by striking shifts in hafnium isotope ratios similar to those shown by Phanerozoic subduction-related orogens(10-12). These data suggest a transitional period 3.5-3.2 Gyr ago from an ancient (3.9-3.5 Gyr old) crustal evolutionary regime unlike that of modern plate tectonics to a geodynamic setting after 3.2 Gyr ago that involved juvenile crust generation by plate tectonic processes.
C1 [Naeraa, T.; Kokfelt, T. F.] Geol Survey Denmark & Greenland GEUS, DK-1350 Copenhagen K, Denmark.
   [Naeraa, T.; Rosing, M. T.] Univ Copenhagen, Nat Hist Museum Denmark, Nord Ctr Earth Evolut NordCEE, DK-1350 Copenhagen K, Denmark.
   [Schersten, A.] Lund Univ, Dept Geol, S-22362 Lund, Sweden.
   [Kemp, A. I. S.] Univ Western Australia, Sch Earth & Environm, Ctr Explorat Targeting, Crawley, WA 6009, Australia.
   [Kemp, A. I. S.] James Cook Univ, Sch Earth & Environm Sci, Townsville, Qld 4811, Australia.
   [Hoffmann, J. E.] Univ Cologne, Inst Geol & Mineral, D-50674 Cologne, Germany.
   [Hoffmann, J. E.] Univ Bonn, Steinmann Inst Geol Mineral & Palaontol, D-53115 Bonn, Germany.
   [Whitehouse, M. J.] Swedish Museum Nat Hist, SE-10405 Stockholm, Sweden.
C3 Geological Survey Of Denmark & Greenland; University of Copenhagen; Lund University; University of Western Australia; James Cook University; University of Cologne; University of Bonn; Swedish Museum of Natural History
RP Næraa, T (corresponding author), Geol Survey Denmark & Greenland GEUS, Oster Voldgade 10, DK-1350 Copenhagen K, Denmark.
EM tomn@geus.dk
FU Geocenter Denmark [7-2006]; Swedish research council [2008-3447]; Danish National Research Foundation; Deutsche Forschungsgemeinschaft (DFG) [Mu 1406/8, HO 4794/1-1]; Australian Research Council [DP0773029, FT100100059]; Geological Survey of Finland; Swedish Museum of Natural History; Geological Survey of Denmark; Geological Survey of Greenland; Australian Research Council [FT100100059, DP0773029] Funding Source: Australian Research Council
NR 43
TC 265
Z9 289
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 MAY 31
PY 2012
VL 485
IS 7400
BP 627
EP +
DI 10.1038/nature11140
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 949WP
UT WOS:000304608000045
PM 22660324
DA 2026-03-09
ER

PT J
AU Herink, G
   Solli, DR
   Gulde, M
   Ropers, C
AF Herink, G.
   Solli, D. R.
   Gulde, M.
   Ropers, C.
TI Field-driven photoemission from nanostructures quenches the quiver motion
SO NATURE
LA English
DT Article
ID ionization; acceleration; limit
AB Strong-field physics, an extreme limit of light-matter interaction(1-3), is expanding into the realm of surfaces(4,5) and nanostructures(6-11) from its origin in atomic and molecular science(12-15). The attraction of nanostructures lies in two intimately connected features: local intensity enhancement and sub-wavelength confinement of optical fields. Local intensity enhancement facilitates access to the strong-field regime and has already sparked various applications, whereas spatial localization has the potential to generate strong-field dynamics exclusive to nanostructures. However, the observation of features unattainable in gaseous media is challenged by many-body effects and material damage, which arise under intense illumination of dense systems(16-19). Here, we non-destructively access this regime in the solid state by employing single plasmonic nanotips and few-cycle mid-infrared pulses, making use of the wavelength-dependence of the interaction, that is, the ponderomotive energy. We investigate strong-field photoelectron emission and acceleration from single nanostructures over a broad spectral range, and find kinetic energies of hundreds of electronvolts. We observe the transition to a new regime in strong-field dynamics, in which the electrons escape the nanolocalized field within a fraction of an optical half-cycle. The transition into this regime, characterized by a spatial adiabaticity parameter, would require relativistic electrons in the absence of nanostructures. These results establish new degrees of freedom for the manipulation and control of electron dynamics on femtosecond and attosecond timescales, combining optical near-fields and nanoscopic sources.
C1 [Herink, G.; Solli, D. R.; Gulde, M.; Ropers, C.] Univ Gottingen, Courant Res Ctr Nanospect & Xray Imaging, D-37077 Gottingen, Germany.
C3 University of Gottingen
RP Ropers, C (corresponding author), Univ Gottingen, Courant Res Ctr Nanospect & Xray Imaging, D-37077 Gottingen, Germany.
EM cropers@gwdg.de
FU Deutsche Forschungsgemeinschaft [DFG-ZUK 45/1, SPP 1391]
NR 30
TC 412
Z9 454
U1 1
U2 194
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD MAR 8
PY 2012
VL 483
IS 7388
BP 190
EP 193
DI 10.1038/nature10878
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 904DT
UT WOS:000301174900033
PM 22398557
DA 2026-03-09
ER

PT J
AU Scott, MC
   Chen, CC
   Mecklenburg, M
   Zhu, C
   Xu, R
   Ercius, P
   Dahmen, U
   Regan, BC
   Miao, JW
AF Scott, M. C.
   Chen, Chien-Chun
   Mecklenburg, Matthew
   Zhu, Chun
   Xu, Rui
   Ercius, Peter
   Dahmen, Ulrich
   Regan, B. C.
   Miao, Jianwei
TI Electron tomography at 2.4-angstrom resolution
SO NATURE
LA English
DT Article
ID atomic-scale; microscopy; contrast; cells
AB Transmission electron microscopy is a powerful imaging tool that has found broad application in materials science, nanoscience and biology(1-3). With the introduction of aberration-corrected electron lenses, both the spatial resolution and the image quality in transmission electron microscopy have been significantly improved(4,5) and resolution below 0.5 angstroms has been demonstrated(6). To reveal the three-dimensional (3D) structure of thin samples, electron tomography is the method of choice(7-11), with cubic-nanometre resolution currently achievable(10,11). Discrete tomography has recently been used to generate a 3D atomic reconstruction of a silver nanoparticle two to three nanometres in diameter(12), but this statistical method assumes prior knowledge of the particle's lattice structure and requires that the atoms fit rigidly on that lattice. Here we report the experimental demonstration of a general electron tomography method that achieves atomic-scale resolution without initial assumptions about the sample structure. By combining a novel projection alignment and tomographic reconstruction method with scanning transmission electron microscopy, we have determined the 3D structure of an approximately ten-nanometre gold nanoparticle at 2.4-angstrom resolution. Although we cannot definitively locate all of the atoms inside the nanoparticle, individual atoms are observed in some regions of the particle and several grains are identified in three dimensions. The 3D surface morphology and internal lattice structure revealed are consistent with a distorted icosahedral multiply twinned particle. We anticipate that this general method can be applied not only to determine the 3D structure of nanomaterials at atomic-scale resolution(13-15), but also to improve the spatial resolution and image quality in other tomography fields(7,9,16-20).
C1 [Scott, M. C.; Chen, Chien-Chun; Mecklenburg, Matthew; Zhu, Chun; Xu, Rui; Regan, B. C.; Miao, Jianwei] Univ Calif Los Angeles, Dept Phys & Astron, Los Angeles, CA 90095 USA.
   [Scott, M. C.; Chen, Chien-Chun; Mecklenburg, Matthew; Zhu, Chun; Xu, Rui; Regan, B. C.; Miao, Jianwei] Univ Calif Los Angeles, Calif NanoSyst Inst, Los Angeles, CA 90095 USA.
   [Ercius, Peter; Dahmen, Ulrich] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Natl Ctr Electron Microscopy, Berkeley, CA 94720 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 Berkeley; United States Department of Energy (DOE); Lawrence Berkeley National Laboratory
RP Miao, JW (corresponding author), Univ Calif Los Angeles, Dept Phys & Astron, Los Angeles, CA 90095 USA.
EM miao@physics.ucla.edu
FU UC Discovery/TomoSoft Technologies [IT107-10166]
NR 37
TC 362
Z9 439
U1 3
U2 299
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 22
PY 2012
VL 483
IS 7390
BP 444
EP U91
DI 10.1038/nature10934
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 912CC
UT WOS:000301771200038
PM 22437612
DA 2026-03-09
ER

PT J
AU Reich, D
   Patterson, N
   Campbell, D
   Tandon, A
   Mazieres, S
   Ray, N
   Parra, MV
   Rojas, W
   Duque, C
   Mesa, N
   García, LF
   Triana, O
   Blair, S
   Maestre, A
   Dib, JC
   Bravi, CM
   Bailliet, G
   Corach, D
   Hünemeier, T
   Bortolini, MC
   Salzano, FM
   Petzl-Erler, ML
   Acuña-Alonzo, V
   Aguilar-Salinas, C
   Canizales-Quinteros, S
   Tusié-Luna, T
   Riba, L
   Rodríguez-Cruz, M
   Lopez-Alarcón, M
   Coral-Vazquez, R
   Canto-Cetina, T
   Silva-Zolezzi, I
   Fernandez-Lopez, JC
   Contreras, AV
   Jimenez-Sanchez, G
   Gómez-Vázquez, MJ
   Molina, J
   Carracedo, A
   Salas, A
   Gallo, C
   Poletti, G
   Witonsky, DB
   Alkorta-Aranburu, G
   Sukernik, RI
   Osipova, L
   Fedorova, SA
   Vasquez, R
   Villena, M
   Moreau, C
   Barrantes, R
   Pauls, D
   Excoffier, L
   Bedoya, G
   Rothhammer, F
   Dugoujon, JM
   Larrouy, G
   Klitz, W
   Labuda, D
   Kidd, J
   Kidd, K
   Di Rienzo, A
   Freimer, NB
   Price, AL
   Ruiz-Linares, A
AF Reich, David
   Patterson, Nick
   Campbell, Desmond
   Tandon, Arti
   Mazieres, Stephane
   Ray, Nicolas
   Parra, Maria V.
   Rojas, Winston
   Duque, Constanza
   Mesa, Natalia
   Garcia, Luis F.
   Triana, Omar
   Blair, Silvia
   Maestre, Amanda
   Dib, Juan C.
   Bravi, Claudio M.
   Bailliet, Graciela
   Corach, Daniel
   Huenemeier, Tabita
   Bortolini, Maria Catira
   Salzano, Francisco M.
   Petzl-Erler, Maria Luiza
   Acuna-Alonzo, Victor
   Aguilar-Salinas, Carlos
   Canizales-Quinteros, Samuel
   Tusie-Luna, Teresa
   Riba, Laura
   Rodriguez-Cruz, Maricela
   Lopez-Alarcon, Mardia
   Coral-Vazquez, Ramon
   Canto-Cetina, Thelma
   Silva-Zolezzi, Irma
   Fernandez-Lopez, Juan Carlos
   Contreras, Alejandra V.
   Jimenez-Sanchez, Gerardo
   Gomez-Vazquez, Maria Jose
   Molina, Julio
   Carracedo, Angel
   Salas, Antonio
   Gallo, Carla
   Poletti, Giovanni
   Witonsky, David B.
   Alkorta-Aranburu, Gorka
   Sukernik, Rem I.
   Osipova, Ludmila
   Fedorova, Sardana A.
   Vasquez, Rene
   Villena, Mercedes
   Moreau, Claudia
   Barrantes, Ramiro
   Pauls, David
   Excoffier, Laurent
   Bedoya, Gabriel
   Rothhammer, Francisco
   Dugoujon, Jean-Michel
   Larrouy, Georges
   Klitz, William
   Labuda, Damian
   Kidd, Judith
   Kidd, Kenneth
   Di Rienzo, Anna
   Freimer, Nelson B.
   Price, Alkes L.
   Ruiz-Linares, Andres
TI Reconstructing Native American population history
SO NATURE
LA English
DT Article
ID colonization; settlement; dispersal; diversity; patterns; origin; model; asia
AB The peopling of the Americas has been the subject of extensive genetic, archaeological and linguistic research; however, central questions remain unresolved(1-5). One contentious issue is whether the settlement occurred by means of a single(6-8) migration or multiple streams of migration from Siberia(9-15). The pattern of dispersals within the Americas is also poorly understood. To address these questions at a higher resolution than was previously possible, we assembled data from 52 Native American and 17 Siberian groups genotyped at 364,470 single nucleotide polymorphisms. Here we show that Native Americans descend from at least three streams of Asian gene flow. Most descend entirely from a single ancestral population that we call `First American'. However, speakers of Eskimo-Aleut languages from the Arctic inherit almost half their ancestry from a second stream of Asian gene flow, and the Na-Dene-speaking Chipewyan from Canada inherit roughly one-tenth of their ancestry from a third stream. We show that the initial peopling followed a southward expansion facilitated by the coast, with sequential population splits and little gene flow after divergence, especially in South America. A major exception is in Chibchan speakers on both sides of the Panama isthmus, who have ancestry from both North and South America.
C1 [Reich, David; Tandon, Arti] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
   [Reich, David; Patterson, Nick; Tandon, Arti; Price, Alkes L.] Broad Inst Harvard, Cambridge, MA 02142 USA.
   [Reich, David; Patterson, Nick; Tandon, Arti] MIT, Cambridge, MA 02142 USA.
   [Campbell, Desmond; Mazieres, Stephane; Parra, Maria V.; Rojas, Winston; Duque, Constanza; Mesa, Natalia; Bravi, Claudio M.; Huenemeier, Tabita; Ruiz-Linares, Andres] UCL, Dept Genet Evolut & Environm, London WC1E 6BT, England.
   Univ Hong Kong, Dept Psychiat, Pokfulam, Hong Kong, Peoples R China.
   [Campbell, Desmond] Univ Hong Kong, Ctr Genom Sci, Pokfulam, Hong Kong, Peoples R China.
   [Mazieres, Stephane] Aix Marseille Univ, CNRS, EFS, ADES,UMR7268, F-13344 Marseille, France.
   [Ray, Nicolas] Univ Geneva, Inst Environm Sci, CH-1227 Geneva, Switzerland.
   [Ray, Nicolas] Univ Geneva, Forel Inst, CH-1227 Geneva, Switzerland.
   [Parra, Maria V.; Rojas, Winston; Duque, Constanza; Mesa, Natalia; Garcia, Luis F.; Triana, Omar; Blair, Silvia; Maestre, Amanda; Bedoya, Gabriel] Univ Antioquia, Medellin, Colombia.
   [Dib, Juan C.] Fdn Salud Trop, Santa Marta, Colombia.
   [Bravi, Claudio M.; Bailliet, Graciela] Consejo Nacl Invest Cient & Tecn, CICPCA, CCT La Plata, Inst Multidisciplinario Biol Celular, RA-1900 La Plata, Argentina.
   [Corach, Daniel] Univ Buenos Aires, Serv Huellas Digitales Genet, RA-1053 Buenos Aires, DF, Argentina.
   [Corach, Daniel] Univ Buenos Aires, CONICET, RA-1053 Buenos Aires, DF, Argentina.
   [Huenemeier, Tabita; Bortolini, Maria Catira; Salzano, Francisco M.] Univ Fed Rio Grande do Sul, Inst Biociencias, Dept Genet, BR-91501970 Porto Alegre, RS, Brazil.
   [Petzl-Erler, Maria Luiza] Univ Fed Parana, Dept Genet, BR-81531980 Curitiba, Parana, Brazil.
   [Acuna-Alonzo, Victor] Natl Inst Anthropol & Hist, Mexico City 06100, DF, Mexico.
   [Aguilar-Salinas, Carlos] Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Endocrinol & Metab, Mexico City 14100, DF, Mexico.
   [Canizales-Quinteros, Samuel; Tusie-Luna, Teresa; Riba, Laura] Univ Nacl Autonoma Mexico, Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Unidad Biol Mol & Med Genom, Mexico City 14100, DF, Mexico.
   [Canizales-Quinteros, Samuel] Univ Nacl Autonoma Mexico, Fac Quim, Dept Biol, Mexico City 04510, DF, Mexico.
   [Rodriguez-Cruz, Maricela; Lopez-Alarcon, Mardia] Hosp Pediat Mexico City, Inst Mexicano Seguro Social, CMNSXXI, Unidad Invest Med Nutr, Mexico City 06720, DF, Mexico.
   [Coral-Vazquez, Ramon] Inst Politecn Nacl, Escuela Super Med, Secc Posgrado, Mexico City 11340, DF, Mexico.
   [Canto-Cetina, Thelma] Ctr Invest Reg, Dept Salud Reprod & Genet, Lab Biol Reproducc, Merida 97000, Mexico.
   [Silva-Zolezzi, Irma; Fernandez-Lopez, Juan Carlos; Contreras, Alejandra V.; Jimenez-Sanchez, Gerardo] Inst Nacl Med Genom, Mexico City 14610, DF, Mexico.
   [Gomez-Vazquez, Maria Jose] Univ Autonoma Nuevo Leon, San Nicolas De Los Garza 66451, Nuevo Leon, Mexico.
   [Molina, Julio] Ctr Invest Biomed Guatemala, Guatemala City, Guatemala.
   [Carracedo, Angel; Salas, Antonio] Univ Santiago de Compostela, Fdn Med Xenom SERGAS, Inst Ciencias Forenses, Santiago De Compostela, Spain.
   [Gallo, Carla; Poletti, Giovanni] Univ Peruana Cayetano Heredia, Fac Ciencias & Filosofia, Labs Invest & Desarrollo, Lima 15102, Peru.
   [Witonsky, David B.; Alkorta-Aranburu, Gorka; Di Rienzo, Anna] Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA.
   [Sukernik, Rem I.] Russian Acad Sci, Siberian Branch, Inst Mol & Cellular Biol, Lab Human Mol Genet, Novosibirsk 630090, Russia.
   [Osipova, Ludmila] Russian Acad Sci, Siberian Branch, Inst Cytol & Genet, Novosibirsk 630090, Russia.
   [Fedorova, Sardana A.] Yakut Res Ctr Complex Med Problems, Dept Mol Genet, Sakha 677010, Yakutia, Russia.
   [Fedorova, Sardana A.] NE Fed Univ, Sakha 677010, Yakutia, Russia.
   [Vasquez, Rene; Villena, Mercedes] Univ Autonoma Tomas Frias, Inst Boliviano Biol Altura, Potosi, Bolivia.
   [Moreau, Claudia; Labuda, Damian] Univ Montreal, Dept Pediat, Ctr Rech, CHU St Justine, Montreal, PQ H3T 1C5, Canada.
   [Barrantes, Ramiro] Univ Costa Rica, Escuela Biol, San Jose, Costa Rica.
   [Pauls, David] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
   [Excoffier, Laurent] Univ Bern, Inst Ecol & Evolut, Computat & Mol Populat Genet Lab, CH-3012 Bern, Switzerland.
   [Excoffier, Laurent] Swiss Inst Bioinformat, CH-1015 Lausanne, Switzerland.
   [Rothhammer, Francisco] Univ Chile, Fac Med, Programa Genet Humana ICBM, Inst Alta Invest ,Univ Tarapaca, Arica 1001236, Chile.
   [Rothhammer, Francisco] Ctr Invest Hombre El Desierto, Arica 1001236, Chile.
   [Dugoujon, Jean-Michel; Larrouy, Georges] Univ Toulouse 3, CNRS, UMR 5288, F-31000 Toulouse, France.
   [Klitz, William] Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA.
   [Kidd, Judith; Kidd, Kenneth] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06520 USA.
   [Freimer, Nelson B.] Univ Calif Los Angeles, Ctr Neurobehav Genet, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90095 USA.
   [Price, Alkes L.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
   [Price, Alkes L.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
C3 Harvard University; Harvard Medical School; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Massachusetts Institute of Technology (MIT); University of London; University College London; University of Hong Kong; University of Hong Kong; Centre National de la Recherche Scientifique (CNRS); Universite Bordeaux-Montaigne; CNRS - Institute of Ecology & Environment (INEE); Aix-Marseille Universite; University of Geneva; University of Geneva; Universidad de Antioquia; National University of La Plata; Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET); University of Buenos Aires; Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET); University of Buenos Aires; Universidade Federal do Rio Grande do Sul; Universidade Federal do Parana; Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran - Mexico; Universidad Nacional Autonoma de Mexico; Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran - Mexico; Universidad Nacional Autonoma de Mexico; Instituto Mexicano del Seguro Social; Instituto Politecnico Nacional - Mexico; Instituto Nacional de Medicina Genomica; Universidad Autonoma de Nuevo Leon; Universidade de Santiago de Compostela; Universidad Peruana Cayetano Heredia; University of Chicago; Russian Academy of Sciences; Siberian Branch of the Russian Academy of Sciences; Russian Academy of Sciences; Siberian Branch of the Russian Academy of Sciences; Institute of Cytology & Genetics ICG SB RAS; North-Eastern Federal University in Yakutsk; Universidad Mayor de San Andres; Instituto Boliviano de Biologica de Altura; Universite de Montreal; Centre Hospitalier Universitaire Sainte-Justine; Universidad Costa Rica; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard Medical School; University of Bern; Swiss Institute of Bioinformatics; Universidad de Chile; Universidad de Tarapaca; Universite de Toulouse; Universite Toulouse III - Paul Sabatier; Universites de Strasbourg Etablissements Associes; Universite de Strasbourg; Centre National de la Recherche Scientifique (CNRS); CNRS - Institute of Ecology & Environment (INEE); University of California System; University of California Berkeley; Yale University; University of California System; University of California Los Angeles; Harvard University; Harvard T.H. Chan School of Public Health; Harvard University; Harvard T.H. Chan School of Public Health
RP Reich, D (corresponding author), Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
EM reich@genetics.med.harvard.edu; a.ruizlin@ucl.ac.uk
FU National Institutes of Health [NS043538, NS037484, MH075007, GM079558, GM079558-S1, GM057672, HG006399]; Biotechnology and Biological Sciences Research Council [BB/1021213/1]; National Science Foundation HOMINID [BCS-1032255]; Canadian Institutes of Health Research grant; Universidad de Antioquia CODI grant; Fondo de Investigacion Sanitaria grant [PS 09/2368]; Ministerio de Ciencia e Innovacion [SAF2011-26983]; Wenner-Gren Foundation [ICRG-65]; Russian Foundation for Basic Research [06-04-048182, 02-06-80524a]; Siberian Branch Russian Academy of Sciences field grant; Centre National de la Recherche Scientifique Programme Interdisciplinaire de Recherche Amazonie grant; Harvard Medical School; Harvard School of Public Health; BBSRC [BB/I021213/1] Funding Source: UKRI; National Human Genome Research Institute [R01HG006399] Funding Source: NIH RePORTER; Biotechnology and Biological Sciences Research Council [BB/I021213/1] Funding Source: researchfish
NR 37
TC 568
Z9 662
U1 2
U2 257
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 16
PY 2012
VL 488
IS 7411
BP 370
EP +
DI 10.1038/nature11258
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 988OS
UT WOS:000307501000040
PM 22801491
DA 2026-03-09
ER

PT J
AU Johnson, BC
   Melosh, HJ
AF Johnson, B. C.
   Melosh, H. J.
TI Impact spherules as a record of an ancient heavy bombardment of Earth
SO NATURE
LA English
DT Article
ID major asteroid impact; western-australia; hamersley basin; iridium anomaly; south-africa; ejecta; layer; boundary; crustal; origin
AB Impact craters are the most obvious indication of asteroid impacts, but craters on Earth are quickly obscured or destroyed by surface weathering and tectonic processes(1). Earth's impact history is inferred therefore either from estimates of the present-day impactor flux as determined by observations of near-Earth asteroids, or from the Moon's incomplete impact chronology(2-4). Asteroids hitting Earth typically vaporize a mass of target rock comparable to the projectile's mass. As this vapour expands in a large plume or fireball, it cools and condenses into molten droplets called spherules(5). For asteroids larger than about ten kilometres in diameter, these spherules are deposited in a global layer. Spherule layers preserved in the geologic record accordingly provide information about an impact even when the source crater cannot be found(1). Here we report estimates of the sizes and impact velocities of the asteroids that created global spherule layers. The impact chronology from these spherule layers reveals that the impactor flux was significantly higher 3.5 billion years ago than it is now. This conclusion is consistent with a gradual decline of the impactor flux after the Late Heavy Bombardment.
C1 [Johnson, B. C.; Melosh, H. J.] Purdue Univ, Dept Phys, W Lafayette, IN 47907 USA.
   [Melosh, H. J.] Purdue Univ, Dept Earth & Atmospher Sci, W Lafayette, IN 47907 USA.
C3 Purdue University System; Purdue University; Purdue University System; Purdue University
RP Johnson, BC (corresponding author), Purdue Univ, Dept Phys, 525 Northwestern Ave, W Lafayette, IN 47907 USA.
EM johns477@purdue.edu
FU NASA
NR 29
TC 99
Z9 112
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 MAY 3
PY 2012
VL 485
IS 7396
BP 75
EP 77
DI 10.1038/nature10982
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 934NV
UT WOS:000303451900036
PM 22535246
DA 2026-03-09
ER

PT J
AU Yuan, JH
   Branch, RW
   Hosu, BG
   Berg, HC
AF Yuan, Junhua
   Branch, Richard W.
   Hosu, Basarab G.
   Berg, Howard C.
TI Adaptation at the output of the chemotaxis signalling pathway
SO NATURE
LA English
DT Article
ID escherichia-coli chemotaxis; bacterial flagellar motor; resonance energy-transfer; rotary motor; zero load; in-vivo; sensitivity; protein; expression; receptors
AB In the bacterial chemotaxis network, receptor clusters process input(1-3), and flagellar motors generate output(4). Receptor and motor complexes are coupled by the diffusible protein CheY-P. Receptor output (the steady-state concentration of CheY-P) varies from cell to cell(5). However, the motor is ultrasensitive, with a narrow operating range of CheY-P concentrations(6). How the match between receptor output and motor input might be optimized is unclear. Here we show that the motor can shift its operating range by changing its composition. The number of FliM subunits in the C-ring increases in response to a decrement in the concentration of CheY-P, increasing motor sensitivity. This shift in sensitivity explains the slow partial adaptation observed in mutants that lack the receptor methyltransferase and methylesterase(7,8) and why motors show signal-dependent FliM turnover(9). Adaptive remodelling is likely to be a common feature in the operation of many molecular machines.
C1 [Yuan, Junhua; Branch, Richard W.; Hosu, Basarab G.; Berg, Howard C.] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA.
C3 Harvard University
RP Berg, HC (corresponding author), Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA.
EM hberg@mcb.harvard.edu
FU National Institutes of Health [AI016478]; EMBO
NR 36
TC 121
Z9 135
U1 0
U2 82
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 12
PY 2012
VL 484
IS 7393
BP 233
EP U115
DI 10.1038/nature10964
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 930OV
UT WOS:000303149900033
PM 22498629
DA 2026-03-09
ER

PT J
AU Abbasi, R
   Abdou, Y
   Abu-Zayyad, T
   Ackermann, M
   Adams, J
   Aguilar, JA
   Ahlers, M
   Altmann, D
   Andeen, K
   Auffenberg, J
   Bai, X
   Baker, M
   Barwick, SW
   Bay, R
   Alba, JLB
   Beattie, K
   Beatty, JJ
   Bechet, S
   Becker, JK
   Becker, KH
   Bell, M
   Benabderrahmane, ML
   BenZvi, S
   Berdermann, J
   Berghaus, P
   Berley, D
   Bernardini, E
   Bertrand, D
   Besson, DZ
   Bindig, D
   Bissok, M
   Blaufuss, E
   Blumenthal, J
   Boersma, DJ
   Bohm, C
   Bose, D
   Böser, S
   Botner, O
   Brayeur, L
   Brown, AM
   Buitink, S
   Caballero-Mora, KS
   Carson, M
   Casier, M
   Chirkin, D
   Christy, B
   Clevermann, F
   Cohen, S
   Colnard, C
   Cowen, DF
   Silva, AHC
   D'Agostino, MV
   Danninger, M
   Daughhetee, J
   Davis, JC
   DeClercq, C
   Degner, T
   Descamps, F
   Desiati, P
   de Vries-Uiterweerd, G
   DeYoung, T
   Díaz-Vélez, JC
   Dierckxsens, M
   Dreyer, J
   Dumm, JP
   Dunkman, M
   Eisch, J
   Ellsworth, RW
   Engdegård, O
   Euler, S
   Evenson, PA
   Fadiran, O
   Fazely, AR
   Fedynitch, A
   Feintzeig, J
   Feusels, T
   Filimonov, K
   Finley, C
   Fischer-Wasels, T
   Flis, S
   Franckowiak, A
   Franke, R
   Gaisser, TK
   Gallagher, J
   Gerhardt, L
   Gladstone, L
   Glüsenkamp, T
   Goldschmidt, A
   Goodman, JA
   Góra, D
   Grant, D
   Griesel, T
   Gross, A
   Grullon, S
   Gurtner, M
   Ha, C
   Ismail, AH
   Hallgren, A
   Halzen, F
   Han, K
   Hanson, K
   Heereman, D
   Heinen, D
   Helbing, K
   Hellauer, R
   Hickford, S
   Hill, GC
   Hoffman, KD
   Hoffmann, B
   Homeier, A
   Hoshina, K
   Huelsnitz, W
   Hülss, JP
   Hulth, PO
   Hultqvist, K
   Hussain, S
   Ishihara, A
   Jacobi, E
   Jacobsen, J
   Japaridze, S
   Johansson, H
   Kappes, A
   Karg, T
   Karle, A
   Kiryluk, J
   Kislat, F
   Klein, SR
   Köhne, JH
   Kohnen, G
   Kolanoski, H
   Köpke, L
   Kopper, S
   Koskinen, DJ
   Kowalski, M
   Kowarik, T
   Krasberg, M
   Kroll, G
   Kunnen, J
   Kurahashi, N
   Kuwabara, T
   Labare, M
   Laihem, K
   Landsman, H
   Larson, MJ
   Lauer, R
   Lünemann, J
   Madsen, J
   Marotta, A
   Maruyama, R
   Mase, K
   Matis, HS
   Meagher, K
   Merck, M
   Mészáros, P
   Meures, T
   Miarecki, S
   Middell, E
   Milke, N
   Miller, J
   Montaruli, T
   Morse, R
   Movit, SM
   Nahnhauer, R
   Nam, JW
   Naumann, U
   Nowicki, SC
   Nygren, DR
   Odrowski, S
   Olivas, A
   Olivo, M
   O'Murchadha, A
   Panknin, S
   Paul, L
   de los Heros, CP
   Piegsa, A
   Pieloth, D
   Posselt, J
   Price, PB
   Przybylski, GT
   Rawlins, K
   Redl, P
   Resconi, E
   Rhode, W
   Ribordy, M
   Richman, M
   Riedel, B
   Rizzo, A
   Rodrigues, JP
   Rothmaier, F
   Rott, C
   Ruhe, T
   Rutledge, D
   Ruzybayev, B
   Ryckbosch, D
   Sander, HG
   Santander, M
   Sarkar, S
   Schatto, K
   Schmidt, T
   Schöneberg, S
   Schönwald, A
   Schukraft, A
   Schulte, L
   Schultes, A
   Schulz, O
   Schunck, M
   Seckel, D
   Semburg, B
   Seo, SH
   Sestayo, Y
   Seunarine, S
   Silvestri, A
   Smith, MWE
   Spiczak, GM
   Spiering, C
   Stamatikos, M
   Stanev, T
   Stezelberger, T
   Stokstad, RG
   Stössl, A
   Strahler, EA
   Ström, R
   Stüer, M
   Sullivan, GW
   Taavola, H
   Taboada, I
   Tamburro, A
   Ter-Antonyan, S
   Tilav, S
   Toale, PA
   Toscano, S
   Tosi, D
   van Eijndhoven, N
   Van Overloop, A
   van Santen, J
   Vehring, M
   Voge, M
   Walck, C
   Waldenmaier, T
   Wallraff, M
   Walter, M
   Wasserman, R
   Weaver, C
   Wendt, C
   Westerhoff, S
   Whitehorn, N
   Wiebe, K
   Wiebusch, CH
   Williams, DR
   Wischnewski, R
   Wissing, H
   Wolf, M
   Wood, TR
   Woschnagg, K
   Xu, C
   Xu, DL
   Xu, XW
   Yanez, JP
   Yodh, G
   Yoshida, S
   Zarzhitsky, P
   Zoll, M
AF Abbasi, R.
   Abdou, Y.
   Abu-Zayyad, T.
   Ackermann, M.
   Adams, J.
   Aguilar, J. A.
   Ahlers, M.
   Altmann, D.
   Andeen, K.
   Auffenberg, J.
   Bai, X.
   Baker, M.
   Barwick, S. W.
   Bay, R.
   Alba, J. L. Bazo
   Beattie, K.
   Beatty, J. J.
   Bechet, S.
   Becker, J. K.
   Becker, K. -H.
   Bell, M.
   Benabderrahmane, M. L.
   BenZvi, S.
   Berdermann, J.
   Berghaus, P.
   Berley, D.
   Bernardini, E.
   Bertrand, D.
   Besson, D. Z.
   Bindig, D.
   Bissok, M.
   Blaufuss, E.
   Blumenthal, J.
   Boersma, D. J.
   Bohm, C.
   Bose, D.
   Boeser, S.
   Botner, O.
   Brayeur, L.
   Brown, A. M.
   Buitink, S.
   Caballero-Mora, K. S.
   Carson, M.
   Casier, M.
   Chirkin, D.
   Christy, B.
   Clevermann, F.
   Cohen, S.
   Colnard, C.
   Cowen, D. F.
   Silva, A. H. Cruz
   D'Agostino, M. V.
   Danninger, M.
   Daughhetee, J.
   Davis, J. C.
   DeClercq, C.
   Degner, T.
   Descamps, F.
   Desiati, P.
   de Vries-Uiterweerd, G.
   DeYoung, T.
   Diaz-Velez, J. C.
   Dierckxsens, M.
   Dreyer, J.
   Dumm, J. P.
   Dunkman, M.
   Eisch, J.
   Ellsworth, R. W.
   Engdegard, O.
   Euler, S.
   Evenson, P. A.
   Fadiran, O.
   Fazely, A. R.
   Fedynitch, A.
   Feintzeig, J.
   Feusels, T.
   Filimonov, K.
   Finley, C.
   Fischer-Wasels, T.
   Flis, S.
   Franckowiak, A.
   Franke, R.
   Gaisser, T. K.
   Gallagher, J.
   Gerhardt, L.
   Gladstone, L.
   Gluesenkamp, T.
   Goldschmidt, A.
   Goodman, J. A.
   Gora, D.
   Grant, D.
   Griesel, T.
   Gross, A.
   Grullon, S.
   Gurtner, M.
   Ha, C.
   Ismail, A. Haj
   Hallgren, A.
   Halzen, F.
   Han, K.
   Hanson, K.
   Heereman, D.
   Heinen, D.
   Helbing, K.
   Hellauer, R.
   Hickford, S.
   Hill, G. C.
   Hoffman, K. D.
   Hoffmann, B.
   Homeier, A.
   Hoshina, K.
   Huelsnitz, W.
   Huelss, J. -P.
   Hulth, P. O.
   Hultqvist, K.
   Hussain, S.
   Ishihara, A.
   Jacobi, E.
   Jacobsen, J.
   Japaridze, S.
   Johansson, H.
   Kappes, A.
   Karg, T.
   Karle, A.
   Kiryluk, J.
   Kislat, F.
   Klein, S. R.
   Koehne, J. -H.
   Kohnen, G.
   Kolanoski, H.
   Koepke, L.
   Kopper, S.
   Koskinen, D. J.
   Kowalski, M.
   Kowarik, T.
   Krasberg, M.
   Kroll, G.
   Kunnen, J.
   Kurahashi, N.
   Kuwabara, T.
   Labare, M.
   Laihem, K.
   Landsman, H.
   Larson, M. J.
   Lauer, R.
   Luenemann, J.
   Madsen, J.
   Marotta, A.
   Maruyama, R.
   Mase, K.
   Matis, H. S.
   Meagher, K.
   Merck, M.
   Meszaros, P.
   Meures, T.
   Miarecki, S.
   Middell, E.
   Milke, N.
   Miller, J.
   Montaruli, T.
   Morse, R.
   Movit, S. M.
   Nahnhauer, R.
   Nam, J. W.
   Naumann, U.
   Nowicki, S. C.
   Nygren, D. R.
   Odrowski, S.
   Olivas, A.
   Olivo, M.
   O'Murchadha, A.
   Panknin, S.
   Paul, L.
   Perez de los Heros, C.
   Piegsa, A.
   Pieloth, D.
   Posselt, J.
   Price, P. B.
   Przybylski, G. T.
   Rawlins, K.
   Redl, P.
   Resconi, E.
   Rhode, W.
   Ribordy, M.
   Richman, M.
   Riedel, B.
   Rizzo, A.
   Rodrigues, J. P.
   Rothmaier, F.
   Rott, C.
   Ruhe, T.
   Rutledge, D.
   Ruzybayev, B.
   Ryckbosch, D.
   Sander, H. -G.
   Santander, M.
   Sarkar, S.
   Schatto, K.
   Schmidt, T.
   Schoeneberg, S.
   Schoenwald, A.
   Schukraft, A.
   Schulte, L.
   Schultes, A.
   Schulz, O.
   Schunck, M.
   Seckel, D.
   Semburg, B.
   Seo, S. H.
   Sestayo, Y.
   Seunarine, S.
   Silvestri, A.
   Smith, M. W. E.
   Spiczak, G. M.
   Spiering, C.
   Stamatikos, M.
   Stanev, T.
   Stezelberger, T.
   Stokstad, R. G.
   Stoessl, A.
   Strahler, E. A.
   Stroem, R.
   Stueer, M.
   Sullivan, G. W.
   Taavola, H.
   Taboada, I.
   Tamburro, A.
   Ter-Antonyan, S.
   Tilav, S.
   Toale, P. A.
   Toscano, S.
   Tosi, D.
   van Eijndhoven, N.
   Van Overloop, A.
   van Santen, J.
   Vehring, M.
   Voge, M.
   Walck, C.
   Waldenmaier, T.
   Wallraff, M.
   Walter, M.
   Wasserman, R.
   Weaver, Ch.
   Wendt, C.
   Westerhoff, S.
   Whitehorn, N.
   Wiebe, K.
   Wiebusch, C. H.
   Williams, D. R.
   Wischnewski, R.
   Wissing, H.
   Wolf, M.
   Wood, T. R.
   Woschnagg, K.
   Xu, C.
   Xu, D. L.
   Xu, X. W.
   Yanez, J. P.
   Yodh, G.
   Yoshida, S.
   Zarzhitsky, P.
   Zoll, M.
TI An absence of neutrinos associated with cosmic-ray acceleration in γ-ray bursts
SO NATURE
LA English
DT Article
ID high-energy neutrinos; icecube; flux; telescope; search
AB Very energetic astrophysical events are required to accelerate cosmic rays to above 10(18) electronvolts. GRBs (c-ray bursts) have been proposed as possible candidate sources(1-3). In the GRB 'fireball' model, cosmic-ray acceleration should be accompanied by neutrinos produced in the decay of charged pions created in interactions between the high-energy cosmic-ray protons and gamma-rays(4). Previous searches for such neutrinos found none, but the constraints were weak because the sensitivity was at best approximately equal to the predicted flux(5-7). Here we report an upper limit on the flux of energetic neutrinos associated with GRBs that is at least a factor of 3.7 below the predictions(4,8-10). This implies either that GRBs are not the only sources of cosmic rays with energies exceeding 10(18) electronvolts or that the efficiency of neutrino production is much lower than has been predicted.
C1 [Abbasi, R.; Ahlers, M.; Andeen, K.; Auffenberg, J.; Baker, M.; BenZvi, S.; Brown, A. M.; Chirkin, D.; Desiati, P.; Diaz-Velez, J. C.; Dumm, J. P.; Eisch, J.; Fadiran, O.; Feintzeig, J.; Gladstone, L.; Grullon, S.; Halzen, F.; Hoshina, K.; Jacobsen, J.; Karle, A.; Krasberg, M.; Kurahashi, N.; Landsman, H.; Maruyama, R.; Merck, M.; Morse, R.; O'Murchadha, A.; Riedel, B.; Rodrigues, J. P.; Santander, M.; Toscano, S.; van Santen, J.; Weaver, Ch.; Wendt, C.; Westerhoff, S.; Whitehorn, N.] Univ Wisconsin, Dept Phys, 1150 Univ Ave, Madison, WI 53706 USA.
   [Abdou, Y.; Carson, M.; Descamps, F.; de Vries-Uiterweerd, G.; Feusels, T.; Ismail, A. Haj; Ryckbosch, D.; Van Overloop, A.] Univ Ghent, Dept Phys & Astron, B-9000 Ghent, Belgium.
   [Abu-Zayyad, T.; Madsen, J.; Spiczak, G. M.] Univ Wisconsin, Dept Phys, River Falls, WI 54022 USA.
   [Ackermann, M.; Alba, J. L. Bazo; Benabderrahmane, M. L.; Berdermann, J.; Bernardini, E.; Silva, A. H. Cruz; Franke, R.; Gluesenkamp, T.; Gora, D.; Han, K.; Jacobi, E.; Kislat, F.; Lauer, R.; Middell, E.; Nahnhauer, R.; Schoenwald, A.; Spiering, C.; Stoessl, A.; Tosi, D.; Walter, M.; Wischnewski, R.; Yanez, J. P.] DESY, D-15735 Zeuthen, Germany.
   [Adams, J.; Hickford, S.] Univ Canterbury, Dept Phys & Astron, Christchurch 1, New Zealand.
   [Aguilar, J. A.; Montaruli, T.] Univ Geneva, Dept Phys Nucl & Corpusculaire, CH-1211 Geneva, Switzerland.
   [Altmann, D.; Bissok, M.; Blumenthal, J.; Boersma, D. J.; Euler, S.; Heinen, D.; Hoffmann, B.; Huelss, J. -P.; Laihem, K.; Paul, L.; Schukraft, A.; Schunck, M.; Vehring, M.; Wallraff, M.; Wiebusch, C. H.] Rhein Westfal TH Aachen, Phys Inst 3, D-52056 Aachen, Germany.
   [Bai, X.; Berghaus, P.; Evenson, P. A.; Gaisser, T. K.; Hussain, S.; Kuwabara, T.; Ruzybayev, B.; Seckel, D.; Stanev, T.; Tamburro, A.; Tilav, S.; Xu, C.] Univ Delaware, Bartol Res Inst, Newark, DE 19716 USA.
   [Bai, X.; Berghaus, P.; Evenson, P. A.; Gaisser, T. K.; Hussain, S.; Kuwabara, T.; Ruzybayev, B.; Seckel, D.; Stanev, T.; Tamburro, A.; Tilav, S.; Xu, C.] Univ Delaware, Dept Phys & Astron, Newark, DE 19716 USA.
   [Bai, X.] S Dakota Sch Mines & Technol, Dept Phys, Rapid City, SD 57701 USA.
   [Barwick, S. W.; Nam, J. W.; Silvestri, A.; Yodh, G.] Univ Calif Irvine, Dept Phys & Astron, Irvine, CA 92697 USA.
   [Bay, R.; D'Agostino, M. V.; Filimonov, K.; Gerhardt, L.; Ha, C.; Klein, S. R.; Miarecki, S.; Price, P. B.; Woschnagg, K.] Univ Calif Berkeley, Dept Phys, Berkeley, CA 94720 USA.
   [Beattie, K.; Gerhardt, L.; Goldschmidt, A.; Matis, H. S.; Nygren, D. R.; Przybylski, G. T.; Stezelberger, T.; Stokstad, R. G.] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Berkeley, CA 94720 USA.
   [Beatty, J. J.; Davis, J. C.; Rott, C.; Stamatikos, M.] Ohio State Univ, Dept Phys, Columbus, OH 43210 USA.
   [Beatty, J. J.; Davis, J. C.; Rott, C.; Stamatikos, M.] Ohio State Univ, Ctr Cosmol & Astroparticle Phys, Columbus, OH 43210 USA.
   [Beatty, J. J.] Ohio State Univ, Dept Astron, Columbus, OH 43210 USA.
   [Bechet, S.; Bertrand, D.; Dierckxsens, M.; Hanson, K.; Heereman, D.; Marotta, A.; Meures, T.] Univ Libre Bruxelles, B-1050 Brussels, Belgium.
   [Becker, J. K.; DeYoung, T.; Dreyer, J.; Fedynitch, A.; Olivo, M.; Schoeneberg, S.] Ruhr Univ Bochum, Fak Phys & Astron, D-44780 Bochum, Germany.
   [Becker, K. -H.; Bindig, D.; Fischer-Wasels, T.; Gurtner, M.; Helbing, K.; Karg, T.; Kopper, S.; Naumann, U.; Posselt, J.; Schultes, A.; Semburg, B.] Univ Wuppertal, Dept Phys, D-42119 Wuppertal, Germany.
   [Bell, M.; Caballero-Mora, K. S.; Cowen, D. F.; Dunkman, M.; Koskinen, D. J.; Larson, M. J.; Meszaros, P.; Rutledge, D.; Smith, M. W. E.; Wasserman, R.] Penn State Univ, Dept Phys, University Pk, PA 16802 USA.
   [Berley, D.; Blaufuss, E.; Buitink, S.; Christy, B.; Ellsworth, R. W.; Goodman, J. A.; Hellauer, R.; Hoffman, K. D.; Huelsnitz, W.; Meagher, K.; Olivas, A.; Redl, P.; Richman, M.; Schmidt, T.; Sullivan, G. W.; Wissing, H.] Univ Maryland, Dept Phys, College Pk, MD 20742 USA.
   [Besson, D. Z.] Univ Kansas, Dept Phys & Astron, Lawrence, KS 66045 USA.
   [Bohm, C.; Danninger, M.; Finley, C.; Flis, S.; Hulth, P. O.; Hultqvist, K.; Johansson, H.; Seo, S. H.; Walck, C.; Wolf, M.; Zoll, M.] Stockholm Univ, Oskar Klein Ctr, SE-10691 Stockholm, Sweden.
   [Bohm, C.; Danninger, M.; Finley, C.; Flis, S.; Hulth, P. O.; Hultqvist, K.; Johansson, H.; Walck, C.; Wolf, M.; Zoll, M.] Stockholm Univ, Dept Phys, SE-10691 Stockholm, Sweden.
   [Bose, D.; Brayeur, L.; Casier, M.; DeClercq, C.; Kunnen, J.; Labare, M.; Rizzo, A.; Strahler, E. A.; van Eijndhoven, N.] Vrije Univ Brussel, Dienst ELEM, B-1050 Brussels, Belgium.
   [Boeser, S.; Degner, T.; Franckowiak, A.; Homeier, A.; Kowalski, M.; Panknin, S.; Schulte, L.; Stueer, M.; Voge, M.] Univ Bonn, Inst Phys, D-53115 Bonn, Germany.
   [Botner, O.; Engdegard, O.; Hallgren, A.; Miller, J.; Perez de los Heros, C.; Stroem, R.; Taavola, H.] Uppsala Univ, Dept Phys & Astron, S-75120 Uppsala, Sweden.
   [Clevermann, F.; Koehne, J. -H.; Milke, N.; Pieloth, D.; Rhode, W.; Ruhe, T.] TU Dortmund Univ, Dept Phys, D-44221 Dortmund, Germany.
   [Cohen, S.; Ribordy, M.] Ecole Polytech Fed Lausanne, Lab High Energy Phys, CH-1015 Lausanne, Switzerland.
   [Colnard, C.; Gross, A.; Odrowski, S.; Resconi, E.; Schulz, O.; Sestayo, Y.] Max Planck Inst Kernphys, D-69177 Heidelberg, Germany.
   [Meszaros, P.; Movit, S. M.] Penn State Univ, Dept Astron & Astrophys, University Pk, PA 16802 USA.
   [Daughhetee, J.; Taboada, I.] Georgia Inst Technol, Sch Phys, Atlanta, GA 30332 USA.
   [Daughhetee, J.; Taboada, I.] Georgia Inst Technol, Ctr Relativist Astrophys, Atlanta, GA 30332 USA.
   [Fazely, A. R.; Ter-Antonyan, S.; Xu, X. W.] So Univ, Dept Phys, Baton Rouge, LA 70813 USA.
   [Gallagher, J.] Univ Wisconsin, Dept Astron, Madison, WI 53706 USA.
   [Grant, D.; Nowicki, S. C.; Wood, T. R.] Univ Alberta, Dept Phys, Edmonton, AB T6G 2G7, Canada.
   [Griesel, T.; Koepke, L.; Kowarik, T.; Kroll, G.; Luenemann, J.; Piegsa, A.; Rothmaier, F.; Sander, H. -G.; Schatto, K.; Wiebe, K.] Johannes Gutenberg Univ Mainz, Inst Phys, D-55099 Mainz, Germany.
   [Hill, G. C.] Univ Adelaide, Sch Chem & Phys, Adelaide, SA 5005, Australia.
   [Hill, G. C.] Los Alamos Natl Lab, Los Alamos, NM 87545 USA.
   [Ishihara, A.; Kolanoski, H.; Mase, K.; Yoshida, S.] Chiba Univ, Dept Phys, Chiba 2638522, Japan.
   [Japaridze, S.] Clark Atlanta Univ, CTSPS, Atlanta, GA 30314 USA.
   [Kappes, A.; Waldenmaier, T.] Humboldt Univ, Inst Phys, D-12489 Berlin, Germany.
   [Kiryluk, J.] SUNY Stony Brook, Dept Phys & Astron, Stony Brook, NY 11794 USA.
   [Montaruli, T.] Sezione Ist Nazl Fis Nucl, Dipartimento Fis, I-70126 Bari, Italy.
   [Kohnen, G.] Univ Mons, B-7000 Mons, Belgium.
   [Rawlins, K.] Univ Alaska Anchorage, Dept Phys & Astron, Anchorage, AK 99508 USA.
   [Resconi, E.; Schulz, O.] Tech Univ Munich, D-85748 Garching, Germany.
   [Sarkar, S.] Univ Oxford, Dept Phys, Oxford OX1 3NP, England.
   [Seunarine, S.] Univ W Indies, Dept Phys, BB-11000 Bridgetown, Barbados.
   [Stamatikos, M.] NASA, Goddard Space Flight Ctr, Greenbelt, MD 20771 USA.
   [Toale, P. A.; Williams, D. R.; Xu, D. L.; Zarzhitsky, P.] Univ Alabama, Dept Phys & Astron, Tuscaloosa, AL 35487 USA.
C3 University of Wisconsin System; University of Wisconsin Madison; Ghent University; University of Wisconsin System; Helmholtz Association; Deutsches Elektronen-Synchrotron (DESY); University of Canterbury; University of Geneva; RWTH Aachen University; University of Delaware; University of Delaware; South Dakota School Mines & Technology; University of California System; University of California Irvine; 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 System of Ohio; Ohio State University; University System of Ohio; Ohio State University; University System of Ohio; Ohio State University; Universite Libre de Bruxelles; Ruhr University Bochum; University of Wurzburg; University of Wuppertal; Pennsylvania Commonwealth System of Higher Education (PCSHE); Pennsylvania State University; Pennsylvania State University - University Park; University System of Maryland; University of Maryland College Park; University of Kansas; Stockholm University; Oskar Klein Centre; Stockholm University; Vrije Universiteit Brussel; University of Bonn; Uppsala University; Dortmund University of Technology; Swiss Federal Institutes of Technology Domain; Ecole Polytechnique Federale de Lausanne; Max Planck Society; Pennsylvania Commonwealth System of Higher Education (PCSHE); Pennsylvania State University; Pennsylvania State University - University Park; University System of Georgia; Georgia Institute of Technology; University System of Georgia; Georgia Institute of Technology; Southern University System; Southern University & A&M College; University of Wisconsin System; University of Wisconsin Madison; University of Alberta; Johannes Gutenberg University of Mainz; Adelaide University; University of Adelaide; United States Department of Energy (DOE); Los Alamos National Laboratory; Chiba University; Clark Atlanta University; Humboldt University of Berlin; State University of New York (SUNY) System; Stony Brook University; Istituto Nazionale di Fisica Nucleare (INFN); University of Mons; University of Alaska System; University of Alaska Anchorage; Technical University of Munich; University of Oxford; University West Indies Mona Jamaica; University of the West Indies Open Campus; National Aeronautics & Space Administration (NASA); NASA Goddard Space Flight Center; University of Alabama System; University of Alabama Tuscaloosa
RP Whitehorn, N (corresponding author), Univ Wisconsin, Dept Phys, 1150 Univ Ave, Madison, WI 53706 USA.
EM nwhitehorn@icecube.wisc.edu
FU US NSF; Office of Polar Programs; US NSF, Physics Division; University of Wisconsin Alumni Research Foundation; GLOW; OSG grids; US DOE, NERSCC; LONI grid; NSERC, Canada; Swedish Research Council; Swedish Polar Research Secretariat; SNIC; K. and A. Wallenberg Foundation, Sweden; German Ministry for Education and Research, Deutsche Forschungsgemeinschaft; Research Department of Plasmas; Complex Interactions (Bochum), Germany; FSR; FWO Odysseus; IWT; BELSPO, Belgium; University of Oxford, UK; Marsden Fund, New Zealand; Australian Research Council; JSPS, Japan; SNSF, Switzerland; Capes Foundation, Brazil; NSF GRFP; STFC [ST/J000507/1] Funding Source: UKRI; Direct For Mathematical & Physical Scien [0855241] Funding Source: National Science Foundation; Direct For Mathematical & Physical Scien; Division Of Physics [1205403, 0855486] Funding Source: National Science Foundation; Direct For Mathematical & Physical Scien; Division Of Physics [0969661, 0856253] Funding Source: National Science Foundation; Division Of Physics [0855241] Funding Source: National Science Foundation; Science and Technology Facilities Council [ST/J000507/1] Funding Source: researchfish; Grants-in-Aid for Scientific Research [22340048, 10J40081] Funding Source: KAKEN
NR 20
TC 259
Z9 294
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 APR 19
PY 2012
VL 484
IS 7394
BP 351
EP 354
DI 10.1038/nature11068
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 927YM
UT WOS:000302946500027
PM 22517161
DA 2026-03-09
ER

PT J
AU Kasahara, S
   Shi, HJ
   Hashimoto, K
   Tonegawa, S
   Mizukami, Y
   Shibauchi, T
   Sugimoto, K
   Fukuda, T
   Terashima, T
   Nevidomskyy, AH
   Matsuda, Y
AF Kasahara, S.
   Shi, H. J.
   Hashimoto, K.
   Tonegawa, S.
   Mizukami, Y.
   Shibauchi, T.
   Sugimoto, K.
   Fukuda, T.
   Terashima, T.
   Nevidomskyy, Andriy H.
   Matsuda, Y.
TI Electronic nematicity above the structural and superconducting transition in BaFe2(As1-xPx)2</sub >
SO NATURE
LA English
DT Article
ID rotational symmetry; anisotropy; breaking; state; phase
AB Electronic nematicity, a unidirectional self-organized state that breaks the rotational symmetry of the underlying lattice(1,2), has been observed in the iron pnictide(3-7) and copper oxide(8-11) high-temperature superconductors. Whether nematicity plays an equally important role in these two systems is highly controversial. In iron pnictides, the nematicity has usually been associated with the tetragonal-to-orthorhombic structural transition at temperature T-s. Although recent experiments(3-7) have provided hints of nematicity, they were performed either in the low-temperature orthorhombic phase(3,5) or in the tetragonal phase under uniaxial strain(4,6,7), both of which break the 90 degrees rotational C-4 symmetry. Therefore, the question remains open whether the nematicity can exist above T-s without an external driving force. Here we report magnetic torque measurements of the isovalent-doping system BaFe2(As1-xPx)(2), showing that the nematicity develops well above T-s and, moreover, persists to the non-magnetic superconducting regime, resulting in a phase diagram similar to the pseudogap phase diagram of the copper oxides(8,12). By combining these results with synchrotron X-ray measurements, we identify two distinct temperatures-one at T*, signifying a true nematic transition, and the other at T-s (<T*), which we show not to be a true phase transition, but rather what we refer to as a 'meta-nematic transition', in analogy to the well-known meta-magnetic transition in the theory of magnetism.
C1 [Kasahara, S.; Shi, H. J.; Hashimoto, K.; Tonegawa, S.; Mizukami, Y.; Shibauchi, T.; Matsuda, Y.] Kyoto Univ, Dept Phys, Kyoto 6068502, Japan.
   [Kasahara, S.; Terashima, T.] Kyoto Univ, Res Ctr Low Temp & Mat Sci, Kyoto 6068501, Japan.
   [Sugimoto, K.] JASRI SPring 8, Res & Utilizat Div, Sayo, Hyogo 6795198, Japan.
   [Sugimoto, K.] RIKEN SPring 8, Struct Mat Sci Lab, Sayo, Hyogo 6795148, Japan.
   [Fukuda, T.] JAEA SPring 8, Quantum Beam Sci Directorate, Sayo, Hyogo 6795148, Japan.
   [Fukuda, T.] RIKEN SPring 8, Mat Dynam Lab, Sayo, Hyogo 6795148, Japan.
   [Fukuda, T.] Transformat Res Project Iron Pnictides TRIP, JST, Chiyoda Ku, Tokyo 1020075, Japan.
   [Nevidomskyy, Andriy H.] Rice Univ, Dept Phys & Astron, Houston, TX 77005 USA.
C3 Kyoto University; Kyoto University; Japan Synchrotron Radiation Research Institute; RIKEN; Japan Atomic Energy Agency; RIKEN; Japan Science & Technology Agency (JST); Rice University
RP Matsuda, Y (corresponding author), Kyoto Univ, Dept Phys, Kyoto 6068502, Japan.
EM shibauchi@scphys.kyoto-u.ac.jp; matsuda@scphys.kyoto-u.ac.jp
FU Global COE programme 'The Next Generation of Physics, Spun from Universality and Emergence' from MEXT of Japan; KAKENHI programme from JSPS; Grants-in-Aid for Scientific Research [23102713, 23654119, 24684026, 20102006, 23654118, 20224008, 24790061] Funding Source: KAKEN
NR 30
TC 413
Z9 458
U1 1
U2 239
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUN 21
PY 2012
VL 486
IS 7403
BP 382
EP 385
DI 10.1038/nature11178
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 961LV
UT WOS:000305466800039
PM 22722198
DA 2026-03-09
ER

PT J
AU Grant, J
   Mahadevaiah, SK
   Khil, P
   Sangrithi, MN
   Royo, H
   Duckworth, J
   McCarrey, JR
   VandeBerg, JL
   Renfree, MB
   Taylor, W
   Elgar, G
   Camerini-Otero, RD
   Gilchrist, MJ
   Turner, JMA
AF Grant, Jennifer
   Mahadevaiah, Shantha K.
   Khil, Pavel
   Sangrithi, Mahesh N.
   Royo, Helene
   Duckworth, Janine
   McCarrey, John R.
   VandeBerg, John L.
   Renfree, Marilyn B.
   Taylor, Willie
   Elgar, Greg
   Camerini-Otero, R. Daniel
   Gilchrist, Mike J.
   Turner, James M. A.
TI Rsx is a metatherian RNA with Xist-like properties in X-chromosome inactivation
SO NATURE
LA English
DT Article
ID primordial germ-cells; dosage compensation; mouse; gene; methylation; expression; mammals
AB In female (XX) mammals, one of the two X chromosomes is inactivated to ensure an equal dose of X-linked genes with males (XY)(1). X-chromosome inactivation in eutherian mammals is mediated by the non-coding RNA Xist(2). Xist is not found in metatherians(3) (marsupials), and how X-chromosome inactivation is initiated in these mammals has been the subject of speculation for decades(4). Using the marsupial Monodelphis domestica, here we identify Rsx (RNA-on-the-silent X), an RNA that has properties consistent with a role in X-chromosome inactivation. Rsx is a large, repeat-rich RNA that is expressed only in females and is transcribed from, and coats, the inactive X chromosome. In female germ cells, in which both X chromosomes are active, Rsx is silenced, linking Rsx expression to X-chromosome inactivation and reactivation. Integration of an Rsx transgene on an autosome in mouse embryonic stem cells leads to gene silencing in cis. Our findings permit comparative studies of X-chromosome inactivation in mammals and pose questions about the mechanisms by which X-chromosome inactivation is achieved in eutherians.
C1 [Grant, Jennifer; Mahadevaiah, Shantha K.; Sangrithi, Mahesh N.; Royo, Helene; Taylor, Willie; Elgar, Greg; Gilchrist, Mike J.; Turner, James M. A.] Natl Inst Med Res, MRC, London NW7 1AA, England.
   [Khil, Pavel; Camerini-Otero, R. Daniel] NIDDKD, NIH, Bethesda, MD 20892 USA.
   [Duckworth, Janine] Landcare Res Manaaki Whenua, Pest Control Technol Grp, Lincoln 7640, New Zealand.
   [McCarrey, John R.] Univ Texas San Antonio, San Antonio, TX 78249 USA.
   [VandeBerg, John L.] Texas Biomed Res Inst, San Antonio, TX 78227 USA.
   [Renfree, Marilyn B.] Univ Melbourne, Dept Zool, Victoria 3010, Australia.
C3 MRC National Institute for Medical Research; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK); Landcare Research - New Zealand; University of Texas System; University of Texas at San Antonio; Texas Biomedical Research Institute; University of Melbourne
RP Turner, JMA (corresponding author), Natl Inst Med Res, MRC, Mill Hill, London NW7 1AA, England.
EM jturner@nimr.mrc.ac.uk
FU Medical Research Council (MRC) [U117588498, U117597141, U117581331, U117597137]; NIH [HD60858]; Robert J. Kleberg Jr and Helen C. Kleberg Foundation; New Zealand Foundation for Research, Science and Technology, Possum Biocontrol [C10X0501]; Australian National Health and Medical Research Council [1010453]; NIDDK (NIH); Medical Research Council [MC_U117597141, MC_U117597137] Funding Source: researchfish; MRC [MC_U117597141, MC_U117597137] Funding Source: UKRI; National Health and Medical Research Council (NHMRC) [1010453] Funding Source: National Health and Medical Research Council (NHMRC)
NR 38
TC 128
Z9 152
U1 1
U2 60
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUL 12
PY 2012
VL 487
IS 7406
BP 254
EP U1511
DI 10.1038/nature11171
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 972LP
UT WOS:000306278900044
PM 22722828
DA 2026-03-09
ER

PT J
AU Mulvaney, R
   Abram, NJ
   Hindmarsh, RCA
   Arrowsmith, C
   Fleet, L
   Triest, J
   Sime, LC
   Alemany, O
   Foord, S
AF Mulvaney, Robert
   Abram, Nerilie J.
   Hindmarsh, Richard C. A.
   Arrowsmith, Carol
   Fleet, Louise
   Triest, Jack
   Sime, Louise C.
   Alemany, Olivier
   Foord, Susan
TI Recent Antarctic Peninsula warming relative to Holocene climate and ice-shelf history
SO NATURE
LA English
DT Article
ID sea-ice; surface; cores
AB Rapid warming over the past 50 years on the Antarctic Peninsula is associated with the collapse of a number of ice shelves and accelerating glacier mass loss(1-7). In contrast, warming has been comparatively modest over West Antarctica and significant changes have not been observed over most of East Antarctica(8,9), suggesting that the ice-core palaeoclimate records available from these areas may not be representative of the climate history of the Antarctic Peninsula. Here we show that the Antarctic Peninsula experienced an early-Holocene warm period followed by stable temperatures, from about 9,200 to 2,500 years ago, that were similar to modern-day levels. Our temperature estimates are based on an ice-core record of deuterium variations from James Ross Island, off the northeastern tip of the Antarctic Peninsula. We find that the late-Holocene development of ice shelves near James Ross Island was coincident with pronounced cooling from 2,500 to 600 years ago. This cooling was part of a millennial-scale climate excursion with opposing anomalies on the eastern and western sides of the Antarctic Peninsula. Although warming of the northeastern Antarctic Peninsula began around 600 years ago, the high rate of warming over the past century is unusual (but not unprecedented) in the context of natural climate variability over the past two millennia. The connection shown here between past temperature and ice-shelf stability suggests that warming for several centuries rendered ice shelves on the northeastern Antarctic Peninsula vulnerable to collapse. Continued warming to temperatures that now exceed the stable conditions of most of the Holocene epoch is likely to cause ice-shelf instability to encroach farther southward along the Antarctic Peninsula.
C1 [Mulvaney, Robert; Abram, Nerilie J.; Hindmarsh, Richard C. A.; Fleet, Louise; Triest, Jack; Sime, Louise C.; Foord, Susan] British Antarctic Survey, NERC, Cambridge CB3 0ET, England.
   [Abram, Nerilie J.] Australian Natl Univ, Res Sch Earth Sci, Canberra, ACT 0200, Australia.
   [Arrowsmith, Carol] NERC, Isotope Geosci Lab, Keyworth NG12 5GG, Notts, England.
   [Alemany, Olivier] UJF Grenoble 1, CNRS, LGGE, UMR 5183, F-38041 Grenoble, France.
C3 UK Research & Innovation (UKRI); Natural Environment Research Council (NERC); NERC British Antarctic Survey; Australian National University; UK Research & Innovation (UKRI); Natural Environment Research Council (NERC); NERC British Geological Survey; Communaute Universite Grenoble Alpes; Universite Grenoble Alpes (UGA); Centre National de la Recherche Scientifique (CNRS)
RP Mulvaney, R (corresponding author), British Antarctic Survey, NERC, Cambridge CB3 0ET, England.
EM rmu@bas.ac.uk
FU Natural Environment Research Council; Institut Polaire Francais - Paul Emile Victor (IPEV); Institut National des Sciences de l'Univers in France (INSU/PNEDC "AMANCAY" project); Natural Environment Research Council [bas0100024, NE/F015526/1] Funding Source: researchfish; NERC [NE/F015526/1, bas0100024] Funding Source: UKRI
NR 30
TC 266
Z9 308
U1 0
U2 174
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 6
PY 2012
VL 489
IS 7414
BP 141
EP U204
DI 10.1038/nature11391
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 999WW
UT WOS:000308347000051
PM 22914090
DA 2026-03-09
ER

PT J
AU Milucka, J
   Ferdelman, TG
   Polerecky, L
   Franzke, D
   Wegener, G
   Schmid, M
   Lieberwirth, I
   Wagner, M
   Widdel, F
   Kuypers, MMM
AF Milucka, Jana
   Ferdelman, Timothy G.
   Polerecky, Lubos
   Franzke, Daniela
   Wegener, Gunter
   Schmid, Markus
   Lieberwirth, Ingo
   Wagner, Michael
   Widdel, Friedrich
   Kuypers, Marcel M. M.
TI Zero-valent sulphur is a key intermediate in marine methane oxidation
SO NATURE
LA English
DT Article
ID mediating anaerobic oxidation; in-situ hybridization; mosby mud volcano; sulfate reduction; elemental sulfur; equilibrium distribution; oligonucleotide probes; microbial community; aqueous-solutions; polysulfide ions
AB Emissions of methane, a potent greenhouse gas, from marine sediments are controlled by anaerobic oxidation of methane coupled primarily to sulphate reduction (AOM). Sulphate-coupled AOM is believed to be mediated by a consortium of methanotrophic archaea (ANME) and sulphate-reducing Deltaproteobacteria but the underlying mechanism has not yet been resolved. Here we show that zero-valent sulphur compounds (S-0) are formed during AOM through a new pathway for dissimilatory sulphate reduction performed by the methanotrophic archaea. Hence, AOM might not be an obligate syntrophic process but may be carried out by the ANME alone. Furthermore, we show that the produced S-0-in the form of disulphide-is disproportionated by the Deltaproteobacteria associated with the ANME. Our observations expand the diversity of known microbially mediated sulphur transformations and have significant implications for our understanding of the biogeochemical carbon and sulphur cycles.
C1 [Milucka, Jana; Ferdelman, Timothy G.; Polerecky, Lubos; Franzke, Daniela; Wegener, Gunter; Widdel, Friedrich; Kuypers, Marcel M. M.] Max Planck Inst Marine Microbiol, D-28359 Bremen, Germany.
   [Wegener, Gunter] Alfred Wegener Inst Polar & Marine Res, D-27570 Bremerhaven, Germany.
   [Schmid, Markus; Wagner, Michael] Univ Vienna, A-1090 Vienna, Austria.
   [Lieberwirth, Ingo] Max Planck Inst Polymer Res, D-55128 Mainz, Germany.
C3 Max Planck Society; Helmholtz Association; Alfred Wegener Institute, Helmholtz Centre for Polar & Marine Research; University of Vienna; Max Planck Society
RP Milucka, J (corresponding author), Max Planck Inst Marine Microbiol, Celsiusstr 1, D-28359 Bremen, Germany.
EM jmilucka@mpi-bremen.de
FU Max Planck Society; ERC [294343]; European Research Council (ERC) [294343] Funding Source: European Research Council (ERC)
NR 73
TC 443
Z9 521
U1 3
U2 531
PU NATURE PUBLISHING 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 22
PY 2012
VL 491
IS 7425
BP 541
EP +
DI 10.1038/nature11656
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 040RE
UT WOS:000311339800041
PM 23135396
DA 2026-03-09
ER

PT J
AU Zeigerer, A
   Gilleron, J
   Bogorad, RL
   Marsico, G
   Nonaka, H
   Seifert, S
   Epstein-Barash, H
   Kuchimanchi, S
   Peng, CG
   Ruda, VM
   Del Conte-Zerial, P
   Hengstler, JG
   Kalaidzidis, Y
   Koteliansky, V
   Zerial, M
AF Zeigerer, Anja
   Gilleron, Jerome
   Bogorad, Roman L.
   Marsico, Giovanni
   Nonaka, Hidenori
   Seifert, Sarah
   Epstein-Barash, Hila
   Kuchimanchi, Satya
   Peng, Chang Geng
   Ruda, Vera M.
   Del Conte-Zerial, Perla
   Hengstler, Jan G.
   Kalaidzidis, Yannis
   Koteliansky, Victor
   Zerial, Marino
TI Rab5 is necessary for the biogenesis of the endolysosomal system in vivo
SO NATURE
LA English
DT Article
ID polarized epithelial-cells; lipid-like materials; recycling endosm; membrane-fusion; plasma-membrane; rnai therapeutics; endocytic pathway; trafficking; proteins; transport
AB An outstanding question is how cells control the number and size of membrane organelles. The small GTPase Rab5 has been proposed to be a master regulator of endosome biogenesis. Here, to test this hypothesis, we developed a mathematical model of endosome dependency on Rab5 and validated it by titrating down all three Rab5 isoforms in adult mouse liver using state-of-the-art RNA interference technology. Unexpectedly, the endocytic system was resilient to depletion of Rab5 and collapsed only when Rab5 decreased to a critical level. Loss of Rab5 below this threshold caused a marked reduction in the number of early endosomes, late endosomes and lysosomes, associated with a block of low-density lipoprotein endocytosis. Loss of endosomes caused failure to deliver apical proteins to the bile canaliculi, suggesting a requirement for polarized cargo sorting. Our results demonstrate for the first time, to our knowledge, the role of Rab5 as an endosome organizer in vivo and reveal the resilience mechanisms of the endocytic system.
C1 [Zeigerer, Anja; Gilleron, Jerome; Marsico, Giovanni; Nonaka, Hidenori; Seifert, Sarah; Del Conte-Zerial, Perla; Kalaidzidis, Yannis; Zerial, Marino] Max Planck Inst Mol Cell Biol & Genet, D-01307 Dresden, Germany.
   [Bogorad, Roman L.; Koteliansky, Victor] MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA.
   [Epstein-Barash, Hila; Kuchimanchi, Satya; Peng, Chang Geng; Koteliansky, Victor] Alnylam Pharmaceut Inc, Cambridge, MA 02142 USA.
   [Ruda, Vera M.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.
   [Ruda, Vera M.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
   [Ruda, Vera M.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
   [Hengstler, Jan G.] Leibniz Res Ctr Working Environm & Human Factors, D-44139 Dortmund, Germany.
   [Kalaidzidis, Yannis] Moscow MV Lomonosov State Univ, Belozersky Inst Physicochem Biol, Moscow 119899, Russia.
C3 Max Planck Society; Massachusetts Institute of Technology (MIT); Alnylam Pharmaceuticals; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard Medical School; Dortmund University of Technology; Leibniz Association; Leibniz Institut for Arbeitsforschung an der TU Dortmund (IFADO); Lomonosov Moscow State University
RP Zerial, M (corresponding author), Max Planck Inst Mol Cell Biol & Genet, D-01307 Dresden, Germany.
EM zerial@mpi-cbg.de
FU Virtual Liver initiative; German Federal Ministry of Research and Education (BMBF); Max Planck Society (MPG); DFG; Marie Curie Action, Intra-European Fellowship [fp7-people-ief-2008]; EMBO
NR 49
TC 293
Z9 343
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 MAY 24
PY 2012
VL 485
IS 7399
BP 465
EP 470
DI 10.1038/nature11133
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 946IH
UT WOS:000304344500035
PM 22622570
DA 2026-03-09
ER

PT J
AU Liu, X
   Ramirez, S
   Pang, PT
   Puryear, CB
   Govindarajan, A
   Deisseroth, K
   Tonegawa, S
AF Liu, Xu
   Ramirez, Steve
   Pang, Petti T.
   Puryear, Corey B.
   Govindarajan, Arvind
   Deisseroth, Karl
   Tonegawa, Susumu
TI Optogenetic stimulation of a hippocampal engram activates fear memory recall
SO NATURE
LA English
DT Article
ID dentate gyrus; pattern separation; amygdala; expression; retrieval; plasticity; strategy; allocation; ca3
AB A specific memory is thought to be encoded by a sparse population of neurons(1,2). These neurons can be tagged during learning for subsequent identification(3) and manipulation(4-6). Moreover, their ablation or inactivation results in reduced memory expression, suggesting their necessity in mnemonic processes. However, the question of sufficiency remains: it is unclear whether it is possible to elicit the behavioural output of a specific memory by directly activating a population of neurons that was active during learning. Here we show in mice that optogenetic reactivation of hippocampal neurons activated during fear conditioning is sufficient to induce freezing behaviour. We labelled a population of hippocampal dentate gyrus neurons activated during fear learning with channelrhodopsin-2 (ChR2)(7,8) and later optically reactivated these neurons in a different context. The mice showed increased freezing only upon light stimulation, indicating light-induced fear memory recall. This freezing was not detected in non-fear-conditioned mice expressing ChR2 in a similar proportion of cells, nor in fear-conditioned mice with cells labelled by enhanced yellow fluorescent protein instead of ChR2. Finally, activation of cells labelled in a context not associated with fear did not evoke freezing in mice that were previously fear-conditioned in a different context, suggesting that light-induced fear memory recall is context-specific. Together, our findings indicate that activating a sparse but specific ensemble of hippocampal neurons that contribute to a memory engram is sufficient for the recall of that memory. Moreover, our experimental approach offers a general method of mapping cellular populations bearing memory engrams.
C1 [Liu, Xu; Ramirez, Steve; Pang, Petti T.; Puryear, Corey B.; Govindarajan, Arvind; Tonegawa, Susumu] MIT, RIKEN MIT Ctr Neural Circuit Genet, Picower Inst Learning & Memory, Dept Biol, Cambridge, MA 02139 USA.
   [Liu, Xu; Ramirez, Steve; Pang, Petti T.; Puryear, Corey B.; Govindarajan, Arvind; Tonegawa, Susumu] MIT, RIKEN MIT Ctr Neural Circuit Genet, Picower Inst Learning & Memory, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA.
   [Deisseroth, Karl] Stanford Univ, Dept Bioengn, Stanford, CA 94305 USA.
   [Deisseroth, Karl] Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA.
C3 RIKEN; Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); RIKEN; Stanford University; Stanford University
RP Tonegawa, S (corresponding author), MIT, RIKEN MIT Ctr Neural Circuit Genet, Picower Inst Learning & Memory, Dept Biol, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
EM tonegawa@mit.edu
FU Tonegawa laboratory; National Institutes of Health [R01-MH078821, P50-MH58880]; RIKEN Brain Science Institute
NR 30
TC 1184
Z9 1481
U1 3
U2 480
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD APR 19
PY 2012
VL 484
IS 7394
BP 381
EP U415
DI 10.1038/nature11028
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 927YM
UT WOS:000302946500034
PM 22441246
DA 2026-03-09
ER

PT J
AU Bhullar, BAS
   Marugán-Lobón, J
   Racimo, F
   Bever, GS
   Rowe, TB
   Norell, MA
   Abzhanov, A
AF Bhullar, Bhart-Anjan S.
   Marugan-Lobon, Jesus
   Racimo, Fernando
   Bever, Gabe S.
   Rowe, Timothy B.
   Norell, Mark A.
   Abzhanov, Arhat
TI Birds have paedomorphic dinosaur skulls
SO NATURE
LA English
DT Article
ID evolution; size; ontogeny; growth; brain; ear
AB The interplay of evolution and development has been at the heart of evolutionary theory for more than a century(1). Heterochrony-change in the timing or rate of developmental events-has been implicated in the evolution of major vertebrate lineages such as mammals(2), including humans(1). Birds are the most speciose land vertebrates, with more than 10,000 living species(3) representing a bewildering array of ecologies. Their anatomy is radically different from that of other vertebrates. The unique bird skull houses two highly specialized systems: the sophisticated visual and neuromuscular coordination system(4,5) allows flight coordination and exploitation of diverse visual landscapes, and the astonishing variations of the beak enable a wide range of avian lifestyles. Here we use a geometric morphometric approach integrating developmental, neontological and palaeontological data to show that the heterochronic process of paedomorphosis, by which descendants resemble the juveniles of their ancestors, is responsible for several major evolutionary transitions in the origin of birds. We analysed the variability of a series of landmarks on all known theropod dinosaur skull ontogenies as well as outgroups and birds. The first dimension of variability captured ontogeny, indicating a conserved ontogenetic trajectory. The second dimension accounted for phylogenetic change towards more bird-like dinosaurs. Basally branching eumaniraptorans and avialans clustered with embryos of other archosaurs, indicating paedomorphosis. Our results reveal at least four paedomorphic episodes in the history of birds combined with localized peramorphosis (development beyond the adult state of ancestors) in the beak. Paedomorphic enlargement of the eyes and associated brain regions parallels the enlargement of the nasal cavity and olfactory brain in mammals(6). This study can be a model for investigations of heterochrony in evolutionary transitions, illuminating the origin of adaptive features and inspiring studies of developmental mechanisms.
C1 [Bhullar, Bhart-Anjan S.; Racimo, Fernando; Abzhanov, Arhat] Harvard Univ, Dept Organism & Evolutionary Biol, Cambridge, MA 02138 USA.
   [Marugan-Lobon, Jesus] Univ Autonoma Madrid, Dept Biol, Unidad Paleontol, E-28049 Madrid, Spain.
   [Bever, Gabe S.] New York Inst Technol, New York Coll Osteopath Med, Dept Anat, Old Westbury, NY 11568 USA.
   [Rowe, Timothy B.] Univ Texas Austin, Jackson Sch Geosci, Dept Geol Sci, Austin, TX 78712 USA.
   [Norell, Mark A.] Amer Museum Nat Hist, Div Paleontol, New York, NY 10024 USA.
C3 Harvard University; Autonomous University of Madrid; New York Institute Technology; University of Texas System; University of Texas Austin; American Museum of Natural History (AMNH)
RP Bhullar, BAS (corresponding author), Harvard Univ, Dept Organism & Evolutionary Biol, 16 Divin Ave, Cambridge, MA 02138 USA.
EM bhartanjan.bhullar@gmail.com; abzhanov@fas.harvard.edu
FU National Science Foundation [1110564];  [BFU2008-00642]; Division Of Earth Sciences; Directorate For Geosciences [0948842] Funding Source: National Science Foundation; Division Of Environmental Biology; Direct For Biological Sciences [1110564] Funding Source: National Science Foundation
NR 29
TC 188
Z9 219
U1 2
U2 267
PU NATURE PUBLISHING 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 12
PY 2012
VL 487
IS 7406
BP 223
EP 226
DI 10.1038/nature11146
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 972LP
UT WOS:000306278900037
PM 22722850
DA 2026-03-09
ER

PT J
AU Tobin, JJ
   Hartmann, L
   Chiang, HF
   Wilner, DJ
   Looney, LW
   Loinard, L
   Calvet, N
   D'Alessio, P
AF Tobin, John J.
   Hartmann, Lee
   Chiang, Hsin-Fang
   Wilner, David J.
   Looney, Leslie W.
   Loinard, Laurent
   Calvet, Nuria
   D'Alessio, Paola
TI A ∼0.2-solar-mass protostar with a Keplerian disk in the very young L1527 IRS system
SO NATURE
LA English
DT Article
ID complex structure; envelope; ii.; accretion; evolution; outflows; core
AB In their earliest stages, protostars accrete mass from their surrounding envelopes through circumstellar disks. Until now, the smallest observed protostar-to-envelope mass ratio was about 2.1 (ref. 1). The protostar L1527 IRS is thought to be in the earliest stages of star formation(2). Its envelope contains about one solar mass of material within a radius of about 0.05 parsecs (refs 3, 4), and earlier observations suggested the presence of an edge-on disk(5). Here we report observations of dust continuum emission and (CO)-C-13 (rotational quantum number J = 2 -> 1) line emission from the disk around L1527 IRS, from which we determine a protostellar mass of 0.19 +/- 0.04 solar masses and a protostar-to-envelope mass ratio of about 0.2. We conclude that most of the luminosity is generated through the accretion process, with an accretion rate of about 6.6 x 10(-7) solar masses per year. If it has been accreting at that rate through much of its life, its age is approximately 300,000 years, although theory suggests larger accretion rates earlier(6), so it may be younger. The presence of a rotationally supported disk is confirmed, and significantly more mass may be added to its planet-forming region as well as to the protostar itself in the future.
C1 [Tobin, John J.] Natl Radio Astron Observ, Charlottesville, VA 22903 USA.
   [Hartmann, Lee; Calvet, Nuria] Univ Michigan, Dept Astron, Ann Arbor, MI 48109 USA.
   [Chiang, Hsin-Fang; Looney, Leslie W.] Univ Illinois, Dept Astron, Urbana, IL 61801 USA.
   [Chiang, Hsin-Fang] Univ Hawaii Manoa, Inst Astron, Hilo, HI 96720 USA.
   [Chiang, Hsin-Fang] Univ Hawaii Manoa, NASA Astrobiol Inst, Hilo, HI 96720 USA.
   [Wilner, David J.] Harvard Smithsonian Ctr Astrophys, Cambridge, MA 02138 USA.
   [Loinard, Laurent; D'Alessio, Paola] UNAM, Ctr Radioastron & Astrofis, Morelia 58089, Michoacan, Mexico.
   [Loinard, Laurent] Max Planck Inst Radioastron, D-53121 Bonn, Germany.
C3 National Radio Astronomy Observatory (NRAO); University of Michigan System; University of Michigan; University of Illinois System; University of Illinois Urbana-Champaign; University of Hawaii System; University of Hawaii Manoa; University of Hawaii System; University of Hawaii Manoa; National Aeronautics & Space Administration (NASA); Harvard University; Smithsonian Institution; Smithsonian Astrophysical Observatory; Universidad Nacional Autonoma de Mexico; Max Planck Society
RP Tobin, JJ (corresponding author), Natl Radio Astron Observ, Edgemont Rd, Charlottesville, VA 22903 USA.
EM jtobin@nrao.edu
FU NASA [HSTHF-51300.01-A, NAS 5-26555]; Space Telescope Science Institute; University of Michigan; NASA through the NASA Astrobiology Institute through the Office of Space Science [NNA09DA77A]; Laboratory for Astronomical Imaging at the University of Illinois; NSF [AST-07-09206]; PAPIIT-UNAM; DGAPA; UNAM; CONACyT (Mexico); Alexander von Humboldt Stiftung; Smithsonian Institution; Academia Sinica; Division Of Astronomical Sciences; Direct For Mathematical & Physical Scien [1139950] Funding Source: National Science Foundation
NR 27
TC 226
Z9 245
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 DEC 6
PY 2012
VL 492
IS 7427
BP 83
EP 85
DI 10.1038/nature11610
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 048EQ
UT WOS:000311893400049
PM 23222612
DA 2026-03-09
ER

PT J
AU Walter, F
   Decarli, R
   Carilli, C
   Bertoldi, F
   Cox, P
   Da Cunha, E
   Daddi, E
   Dickinson, M
   Downes, D
   Elbaz, D
   Ellis, R
   Hodge, J
   Neri, R
   Riechers, DA
   Weiss, A
   Bell, E
   Dannerbauer, H
   Krips, M
   Krumholz, M
   Lentati, L
   Maiolino, R
   Menten, K
   Rix, HW
   Robertson, B
   Spinrad, H
   Stark, DP
   Stern, D
AF Walter, Fabian
   Decarli, Roberto
   Carilli, Chris
   Bertoldi, Frank
   Cox, Pierre
   Da Cunha, Elisabete
   Daddi, Emanuele
   Dickinson, Mark
   Downes, Dennis
   Elbaz, David
   Ellis, Richard
   Hodge, Jacqueline
   Neri, Roberto
   Riechers, Dominik A.
   Weiss, Axel
   Bell, Eric
   Dannerbauer, Helmut
   Krips, Melanie
   Krumholz, Mark
   Lentati, Lindley
   Maiolino, Roberto
   Menten, Karl
   Rix, Hans-Walter
   Robertson, Brant
   Spinrad, Hyron
   Stark, Dan P.
   Stern, Daniel
TI The intense starburst HDF 850.1 in a galaxy overdensity at z ≈ 5.2 in the Hubble Deep Field
SO NATURE
LA English
DT Article
ID brightest submillimeter source; molecular gas; high-redshift; star-formation; big-bang; north; identification; constraints; indicator; object
AB The Hubble Deep Field provides one of the deepest multiwave-length views of the distant Universe and has led to the detection of thousands of galaxies seen throughout cosmic time(1). An early map of the Hubble Deep Field at a wavelength of 850 micrometres, which is sensitive to dust emission powered by star formation, revealed the brightest source in the field, dubbed HDF 850.1 (ref. 2). For more than a decade, and despite significant efforts, no counterpart was found at shorter wavelengths, and it was not possible to determine its redshift, size or mass(3-7). Here we report a redshift of z = 5.183 for HDF 850.1, from a millimetre-wave molecular line scan. This places HDF 850.1 in a galaxy overdensity at z approximate to 5.2, corresponding to a cosmic age of only 1.1 billion years after the Big Bang. This redshift is significantly higher than earlier estimates(3,4,6,8) and higher than those of most of the hundreds of submillimetre-bright galaxies identified so far. The source has a star-formation rate of 850 solar masses per year and is spatially resolved on scales of 5 kiloparsecs, with an implied dynamical mass of about 1.3 x 10(11) solar masses, a significant fraction of which is present in the form of molecular gas. Despite our accurate determination of redshift and position, a counterpart emitting starlight remains elusive.
C1 [Walter, Fabian; Decarli, Roberto; Da Cunha, Elisabete; Hodge, Jacqueline; Rix, Hans-Walter] Max Planck Inst Astron, D-69117 Heidelberg, Germany.
   [Walter, Fabian; Carilli, Chris] Natl Radio Astron Observ, Pete V Domenici Array Sci Ctr, Socorro, NM 87801 USA.
   [Carilli, Chris; Lentati, Lindley; Maiolino, Roberto] Univ Cambridge, Cavendish Lab, Cambridge CB3 0HE, England.
   [Bertoldi, Frank] Univ Bonn, Argelander Inst Astron, D-53121 Bonn, Germany.
   [Cox, Pierre; Downes, Dennis; Neri, Roberto; Krips, Melanie] IRAM, F-38406 St Martin Dheres, France.
   [Da Cunha, Elisabete; Elbaz, David] Univ Paris Diderot, Lab AIM, CEA, DSM,CNRS,Irfu Serv Astrophys,CEA Saclay, F-91191 Gif Sur Yvette, France.
   [Dickinson, Mark] Natl Opt Astron Observ, Tucson, AZ 85719 USA.
   [Ellis, Richard; Riechers, Dominik A.] CALTECH, Dept Astron, Pasadena, CA 91125 USA.
   [Weiss, Axel; Menten, Karl] Max Planck Inst Radioastron, D-53121 Bonn, Germany.
   [Bell, Eric] Univ Michigan, Dept Astron, Ann Arbor, MI 48109 USA.
   [Dannerbauer, Helmut] Univ Vienna, Inst Astron, A-1080 Vienna, Austria.
   [Krumholz, Mark] Univ Calif Santa Cruz, Dept Astron & Astrophys, Santa Cruz, CA 95064 USA.
   [Maiolino, Roberto] INAF Osservatorio Astron Roma, I-00040 Monte Porzio Catone, Italy.
   [Robertson, Brant; Stark, Dan P.] Univ Arizona, Dept Astron, Tucson, AZ 85721 USA.
   [Spinrad, Hyron] Univ Calif Berkeley, Dept Astron, Berkeley, CA 94720 USA.
   [Stern, Daniel] CALTECH, Jet Prop Lab, Pasadena, CA 91109 USA.
C3 Max Planck Society; National Radio Astronomy Observatory (NRAO); University of Cambridge; University of Bonn; Universite Paris Saclay; CEA; Centre National de la Recherche Scientifique (CNRS); Universite Paris Cite; National Optical Astronomy Observatory; California Institute of Technology; Max Planck Society; University of Michigan System; University of Michigan; University of Vienna; University of California System; University of California Santa Cruz; Istituto Nazionale Astrofisica (INAF); University of Arizona; University of California System; University of California Berkeley; National Aeronautics & Space Administration (NASA); NASA Jet Propulsion Laboratory (JPL); California Institute of Technology
RP Walter, F (corresponding author), Max Planck Inst Astron, Konigstuhl 17, D-69117 Heidelberg, Germany.
EM walter@mpia.de
FU MPG (Germany); INSU/CNRS (France); IGN (Spain); NASA; DLR [FKZ 50OR1004]; Division Of Astronomical Sciences; Direct For Mathematical & Physical Scien [0955300] Funding Source: National Science Foundation
NR 30
TC 262
Z9 284
U1 0
U2 4
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 14
PY 2012
VL 486
IS 7402
BP 233
EP 236
DI 10.1038/nature11073
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 957UH
UT WOS:000305189000029
PM 22699613
DA 2026-03-09
ER

PT J
AU Stuhl, BK
   Hummon, MT
   Yeo, M
   Quéméner, G
   Bohn, JL
   Ye, J
AF Stuhl, Benjamin K.
   Hummon, Matthew T.
   Yeo, Mark
   Quemener, Goulven
   Bohn, John L.
   Ye, Jun
TI Evaporative cooling of the dipolar hydroxyl radical
SO NATURE
LA English
DT Article
ID bose-einstein condensation; polar-molecules; atoms; gas
AB Atomic physics was revolutionized by the development of forced evaporative cooling, which led directly to the observation of Bose-Einstein condensation(1,2), quantum-degenerate Fermi gases(3) and ultracold optical lattice simulations of condensed-matter phenomena(4). More recently, substantial progress has been made in the production of cold molecular gases(5). Their permanent electric dipole moment is expected to generate systems with varied and controllable phases(6-8), dynamics(9-11) and chemistry(12-14). However, although advances have been made(15) in both direct cooling and cold-association techniques, evaporative cooling has not been achieved so far. This is due to unfavourable ratios of elastic to inelastic scattering(13) and impractically slow thermalization rates in the available trapped species. Here we report the observation of microwave-forced evaporative cooling of neutral hydroxyl (OH center dot) molecules loaded from a Stark-decelerated beam into an extremely high-gradient magnetic quadrupole trap. We demonstrate cooling by at least one order of magnitude in temperature, and a corresponding increase in phase-space density by three orders of magnitude, limited only by the low-temperature sensitivity of our spectroscopic thermometry technique. With evaporative cooling and a sufficiently large initial population, much colder temperatures are possible; even a quantum-degenerate gas of this dipolar radical (or anything else it can sympathetically cool) may be within reach.
C1 [Stuhl, Benjamin K.; Hummon, Matthew T.; Yeo, Mark; Quemener, Goulven; Bohn, John L.; Ye, Jun] Univ Colorado, NIST, Joint Inst Lab Astrophys, Boulder, CO 80309 USA.
   [Stuhl, Benjamin K.; Hummon, Matthew T.; Yeo, Mark; Quemener, Goulven; Bohn, John L.; Ye, Jun] 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), Univ Colorado, NIST, Joint Inst Lab Astrophys, Boulder, CO 80309 USA.
EM ye@jila.colorado.edu
FU NSF Physics Frontier Center; DOE; AFOSR (MURI); DARPA; NIST
NR 33
TC 156
Z9 189
U1 0
U2 113
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD DEC 20
PY 2012
VL 492
IS 7429
BP 396
EP +
DI 10.1038/nature11718
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 056KQ
UT WOS:000312488200049
PM 23257881
DA 2026-03-09
ER

PT J
AU Gamuyao, R
   Chin, JH
   Pariasca-Tanaka, J
   Pesaresi, P
   Catausan, S
   Dalid, C
   Slamet-Loedin, I
   Tecson-Mendoza, EM
   Wissuwa, M
   Heuer, S
AF Gamuyao, Rico
   Chin, Joong Hyoun
   Pariasca-Tanaka, Juan
   Pesaresi, Paolo
   Catausan, Sheryl
   Dalid, Cheryl
   Slamet-Loedin, Inez
   Tecson-Mendoza, Evelyn Mae
   Wissuwa, Matthias
   Heuer, Sigrid
TI The protein kinase Pstol1 from traditional rice confers tolerance of phosphorus deficiency
SO NATURE
LA English
DT Article
ID reproductive-stage; response-factor; drought stress; gene; pup1; expression; inference; sequence; family; yield
AB As an essential macroelement for all living cells, phosphorus is indispensable in agricultural production systems. Natural phosphorus reserves are limited(1), and it is therefore important to develop phosphorus-efficient crops. A major quantitative trait locus for phosphorus-deficiency tolerance, Pup1, was identified in the traditional aus-type rice variety Kasalath about a decade ago(2,3). However, its functional mechanism remained elusive(4,5) until the locus was sequenced, showing the presence of a Pup1-specific protein kinase gene(6), which we have named phosphorus-starvation tolerance 1 (PSTOL1). This gene is absent from the rice reference genome and other phosphorus-starvation-intolerant modern varieties(7,8). Here we show that overexpression of PSTOL1 in such varieties significantly enhances grain yield in phosphorus-deficient soil. Further analyses show that PSTOL1 acts as an enhancer of early root growth, thereby enabling plants to acquire more phosphorus and other nutrients. The absence of PSTOL1 and other genes-for example, the submergence-tolerance gene SUB1A-from modern rice varieties underlines the importance of conserving and exploring traditional germplasm. Introgression of this quantitative trait locus into locally adapted rice varieties in Asia and Africa is expected to considerably enhance productivity under low phosphorus conditions.
C1 [Gamuyao, Rico; Chin, Joong Hyoun; Catausan, Sheryl; Dalid, Cheryl; Slamet-Loedin, Inez; Heuer, Sigrid] Int Rice Res Inst, Manila 1301, Philippines.
   [Pariasca-Tanaka, Juan; Wissuwa, Matthias] JIRCAS, Tsukuba, Ibaraki 3058686, Japan.
   [Pesaresi, Paolo] Univ Milan, Dipartimento Biosci, I-20133 Milan, Italy.
   [Tecson-Mendoza, Evelyn Mae] Univ Philippines, Los Banos 4031, Laguna, Philippines.
C3 CGIAR; International Rice Research Institute (IRRI); Japan International Research Center for Agricultural Sciences; University of Milan; University of the Philippines System; University of the Philippines Open University; University of the Philippines Los Banos
RP Heuer, S (corresponding author), Int Rice Res Inst, DAPO Box 7777, Manila 1301, Philippines.
EM s.heuer@cgiar.org
FU Generation Challenge Program (GCP)
NR 47
TC 609
Z9 692
U1 9
U2 430
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 23
PY 2012
VL 488
IS 7412
BP 535
EP +
DI 10.1038/nature11346
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 992FS
UT WOS:000307761600042
PM 22914168
DA 2026-03-09
ER

PT J
AU Altshuler, DM
   Durbin, RM
   Abecasis, GR
   Bentley, DR
   Chakravarti, A
   Clark, AG
   Donnelly, P
   Eichler, EE
   Flicek, P
   Gabriel, SB
   Gibbs, RA
   Green, ED
   Hurles, ME
   Knoppers, BM
   Korbel, JO
   Lander, ES
   Lee, C
   Lehrach, H
   Mardis, ER
   Marth, GT
   McVean, GA
   Nickerson, DA
   Schmidt, JP
   Sherry, ST
   Wang, J
   Wilson, RK
   Gibbs, RA
   Dinh, H
   Kovar, C
   Lee, S
   Lewis, L
   Muzny, D
   Reid, J
   Wang, M
   Wang, J
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   Smith, Richard E.
   Zheng-Bradley, Xiangqun
   Bentley, David R.
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   Lienhard, Matthias
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   McVean, Gil A.
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   Fulton, Lucinda
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   Balasubramaniam, Senduran
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   Danecek, Petr
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   Kolb-Kokocinski, Anja
   McCarthy, Shane
   Stalker, James
   Quail, Michael
   Schmidt, Jeanette P.
   Davies, Christopher J.
   Gollub, Jeremy
   Webster, Teresa
   Wong, Brant
   Zhan, Yiping
   Auton, Adam
   Gibbs, Richard A.
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   Lu, James
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   Zhang, Chengsheng
   Daly, Mark J.
   DePristo, Mark A.
   Altshuler, David M.
   Banks, Eric
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   Carneiro, Mauricio O.
   del Angel, Guillermo
   Gabriel, Stacey B.
   Genovese, Giulio
   Gupta, Namrata
   Handsaker, Robert E.
   Hartl, Chris
   Lander, Eric S.
   McCarroll, Steven A.
   Nemesh, James C.
   Poplin, Ryan E.
   Schaffner, Stephen F.
   Shakir, Khalid
   Yoon, Seungtai C.
   Lihm, Jayon
   Makarov, Vladimir
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   Kim, Ki Cheol
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   Rausch, Tobias
   Flicek, Paul
   Beal, Kathryn
   Clarke, Laura
   Cunningham, Fiona
   Herrero, Javier
   McLaren, William M.
   Ritchie, Graham R. S.
   Smith, Richard E.
   Zheng-Bradley, Xiangqun
   Clark, Andrew G.
   Gottipati, Srikanth
   Keinan, Alon
   Rodriguez-Flores, Juan L.
   Sabeti, Pardis C.
   Grossman, Sharon R.
   Tabrizi, Shervin
   Tariyal, Ridhi
   Cooper, David N.
   Ball, Edward V.
   Stenson, Peter D.
   Bentley, David R.
   Barnes, Bret
   Bauer, Markus
   Cheetham, R. Keira
   Cox, Tony
   Eberle, Michael
   Humphray, Sean
   Kahn, Scott
   Murray, Lisa
   Peden, John
   Shaw, Richard
   Ye, Kai
   Batzer, Mark A.
   Konkel, Miriam K.
   Walker, Jerilyn A.
   MacArthur, Daniel G.
   Lek, Monkol
   Sudbrak, Ralf
   Amstislavskiy, Vyacheslav S.
   Herwig, Ralf
   Shriver, Mark D.
   Bustamante, Carlos D.
   Byrnes, Jake K.
   De la Vega, Francisco M.
   Gravel, Simon
   Kenny, Eimear E.
   Kidd, Jeffrey M.
   Lacroute, Phil
   Maples, Brian K.
   Moreno-Estrada, Andres
   Zakharia, Fouad
   Halperin, Eran
   Baran, Yael
   Craig, David W.
   Christoforides, Alexis
   Homer, Nils
   Izatt, Tyler
   Kurdoglu, Ahmet A.
   Sinari, Shripad A.
   Squire, Kevin
   Sherry, Stephen T.
   Xiao, Chunlin
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   Gignoux, Christopher R.
   Haussler, David
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   Kent, W. James
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   Liu, Xinyue
   Maroo, Ankit
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   Michelson, Leslie P.
   Abecasis, Goncalo R.
   Kang, Hyun Min
   Anderson, Paul
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   Blackwell, Tom
   Busonero, Fabio
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   Fuchsberger, Christian
   Jones, Chris
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   Li, Yun
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   Reinier, Fred
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   Tan, Adrian
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   Lunter, Gerton
   McVean, Gil A.
   Marchini, Jonathan L.
   Myers, Simon
   Churchhouse, Claire
   Delaneau, Olivier
   Gupta-Hinch, Anjali
   Iqbal, Zamin
   Mathieson, Iain
   Rimmer, Andy
   Xifara, Dionysia K.
   Oleksyk, Taras K.
   Fu, Yunxin
   Liu, Xiaoming
   Xiong, Momiao
   Jorde, Lynn
   Witherspoon, David
   Xing, Jinchuan
   Eichler, Evan E.
   Browning, Brian L.
   Alkan, Can
   Hajirasouliha, Iman
   Hormozdiari, Fereydoun
   Ko, Arthur
   Sudmant, Peter H.
   Mardis, Elaine R.
   Chen, Ken
   Chinwalla, Asif
   Ding, Li
   Dooling, David
   Koboldt, Daniel C.
   McLellan, Michael D.
   Wallis, John W.
   Wendl, Michael C.
   Zhang, Qunyuan
   Durbin, Richard M.
   Hurles, Matthew E.
   Tyler-Smith, Chris
   Albers, Cornelis A.
   Ayub, Qasim
   Balasubramaniam, Senduran
   Chen, Yuan
   Coffey, Alison J.
   Colonna, Vincenza
   Danecek, Petr
   Huang, Ni
   Jostins, Luke
   Keane, Thomas M.
   Li, Heng
   McCarthy, Shane
   Scally, Aylwyn
   Stalker, James
   Walter, Klaudia
   Xue, Yali
   Zhang, Yujun
   Gerstein, Mark B.
   Abyzov, Alexej
   Balasubramanian, Suganthi
   Chen, Jieming
   Clarke, Declan
   Fu, Yao
   Habegger, Lukas
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TI An integrated map of genetic variation from 1,092 human genomes
SO NATURE
LA English
DT Article
ID copy number variation; wide association; population-structure; rare; variants; loci; mutation; risk
AB By characterizing the geographic and functional spectrum of human genetic variation, the 1000 Genomes Project aims to build a resource to help to understand the genetic contribution to disease. Here we describe the genomes of 1,092 individuals from 14 populations, constructed using a combination of low-coverage whole-genome and exome sequencing. By developing methods to integrate information across several algorithms and diverse data sources, we provide a validated haplotype map of 38 million single nucleotide polymorphisms, 1.4 million short insertions and deletions, and more than 14,000 larger deletions. We show that individuals from different populations carry different profiles of rare and common variants, and that low-frequency variants show substantial geographic differentiation, which is further increased by the action of purifying selection. We show that evolutionary conservation and coding consequence are key determinants of the strength of purifying selection, that rare-variant load varies substantially across biological pathways, and that each individual contains hundreds of rare non-coding variants at conserved sites, such as motif-disrupting changes in transcription-factor-binding sites. This resource, which captures up to 98% of accessible single nucleotide polymorphisms at a frequency of 1% in related populations, enables analysis of common and low-frequency variants in individuals from diverse, including admixed, populations.
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   [Kaye, Jane S.] Univ Oxford, Ctr Hlth Law & Emerging Technol, Oxford OX3 7LF, England.
   [Kent, Alastair] Genet Alliance, London N1 3QP, England.
   [Mathias, Rasika] Johns Hopkins Univ, Sch Med, Baltimore, MD 21205 USA.
   [Ossorio, Pilar N.] Univ Wisconsin Madison, Morgridge Inst Res, Dept Med Hist & Bioeth, Madison, WI 53706 USA.
   [Ossorio, Pilar N.] Univ Wisconsin, Sch Law, Madison, WI 53706 USA.
   [Parker, Michael] Univ Oxford, Dept Publ Hlth, Ethox Ctr, Oxford OX3 7LF, England.
   [Royal, Charmaine D.] Duke Univ, Inst Genome Sci & Policy, Durham, NC 27708 USA.
   [Tishkoff, Sarah] Univ Penn, Sch Med, Dept Genet, Philadelphia, PA 19104 USA.
   [Via, Marc] Univ Barcelona, Dept Anim Biol, Unit Anthropol, E-08028 Barcelona, Spain.
   [Bodmer, Walter] Univ Oxford, John Radcliffe Hosp, Canc & Immunogenet Lab, Oxford OX3 9DS, England.
   [Bedoya, Gabriel] Univ Antioquia, Inst Biol, Mol Genet Lab, Medellin, Colombia.
   [Yang, Gao] Peking Univ, Shenzhen Hosp, Shenzhen 518036, Peoples R China.
   [You, Chu Jia] Chinese Acad Med Sci, Inst Med Biol, Kunming 650118, Peoples R China.
   [You, Chu Jia] Peking Union Med Coll, Kunming 650118, Peoples R China.
   [Garcia-Montero, Andres; Orfao, Alberto] Univ Salamanca, Inst Biomed Res Salamanca IBSAL, Ctr Invest Canc IBMCC CSIC USAL, Inst Biol Mol & Celular Canc, Salamanca 37007, Spain.
   [Garcia-Montero, Andres] Univ Salamanca, Banco Nacl ADN Carlos 3, Salamanca 37007, Spain.
   [Orfao, Alberto] Univ Salamanca, Cytometry Serv, Salamanca 37007, Spain.
   [Orfao, Alberto] Univ Salamanca, Dept Med, Salamanca 37007, Spain.
   [Dutil, Julie] Ponce Sch Med & Hlth Sci, Ponce, PR 00716 USA.
   [Duncanson, Audrey; Dunn, Michael] Wellcome Trust Res Labs, London NW1 2BE, England.
C3 University of Oxford; Wellcome Centre for Human Genetics; University of Oxford; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Wellcome Trust Sanger Institute; University of Michigan System; University of Michigan; Illumina; Johns Hopkins University; Cornell University; University of Washington; University of Washington Seattle; Howard Hughes Medical Institute; European Molecular Biology Laboratory (EMBL); European Bioinformatics Institute; Baylor College of Medicine; McGill University; European Molecular Biology Laboratory (EMBL); Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard University; Harvard Medical School; Max Planck Society; Washington University (WUSTL); Boston College; University of Washington; University of Washington Seattle; Affymetrix; National Institutes of Health (NIH) - USA; Beijing Genomics Institute (BGI); Novo Nordisk Foundation; University of Copenhagen; University of Copenhagen; Montefiore Medical Center; Albert Einstein College of Medicine; Yeshiva University; University of Michigan System; University of Michigan; Cold Spring Harbor Laboratory; Icahn School of Medicine at Mount Sinai; Icahn School of Medicine at Mount Sinai; Dankook University; Dankook University; Cornell University; Harvard University; Harvard University; Cardiff University; Illumina; Leiden University; Leiden University Medical Center (LUMC); Leiden University - Excl LUMC; Louisiana State University System; Louisiana State University; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Pennsylvania Commonwealth System of Higher Education (PCSHE); Pennsylvania State University; Pennsylvania State University - University Park; Stanford University; Tel Aviv University; Tel Aviv University; Translational Genomics Research Institute; Thermo Fisher Scientific; 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 San Diego; University of California System; University of California San Diego; University of California System; University of California San Diego; Yeshiva University; Montefiore Medical Center; Albert Einstein College of Medicine; University of California System; University of California San Francisco; University of California System; University of California Santa Cruz; Howard Hughes Medical Institute; University of Chicago; University of London; University College London; University of Geneva; University of Geneva; Swiss Institute of Bioinformatics; University System of Maryland; University of Maryland Baltimore; Rutgers University System; Rutgers University New Brunswick; Rutgers University Biomedical & Health Sciences; American Museum of Natural History (AMNH); Consiglio Nazionale delle Ricerche (CNR); Istituto di Ricerca Genetica e Biomedica (IRGB-CNR); University of Michigan System; University of Michigan; University of Sassari; University of North Carolina; University of North Carolina Chapel Hill; University of Michigan System; University of Michigan; National Institutes of Health (NIH) - USA; NIH National Institute on Aging (NIA); Universite de Montreal; University of Puerto Rico; University of Puerto Rico Mayaguez; University of Texas System; University of Texas Health Science Center Houston; Utah System of Higher Education; University of Utah; Rutgers University System; Rutgers University New Brunswick; University of Washington; University of Washington Seattle; Ihsan Dogramaci Bilkent University; Simon Fraser University; University of Texas System; UTMD Anderson Cancer Center; University of Cambridge; NHS Blood & Transplant (NHSBT); Consiglio Nazionale delle Ricerche (CNR); Istituto di Genetica e Biofisica Adriano Buzzati-Traverso (IGB-CNR); Yale University; Yale University; Yale University; Yale University; University of California System; University of California San Diego; National Institutes of Health (NIH) - USA; NIH National Human Genome Research Institute (NHGRI); Johns Hopkins University; Coriell Institute for Medical Research; University of Oxford; Johns Hopkins University; University of Wisconsin System; University of Wisconsin Madison; The Morgridge Institute for Research, Inc.; University of Wisconsin System; University of Wisconsin Madison; University of Oxford; Duke University; University of Pennsylvania; University of Barcelona; University of Oxford; Universidad de Antioquia; Peking University; Chinese Academy of Medical Sciences - Peking Union Medical College; Institute of Medical Biology - CAMS; Chinese Academy of Medical Sciences - Peking Union Medical College; Peking Union Medical College; Consejo Superior de Investigaciones Cientificas (CSIC); CSIC-USAL - Instituto de Biologia Molecular y Celular del Cancer de Salamanca (IBMCC); University of Salamanca; University of Salamanca; University of Salamanca; University of Salamanca
RP McVean, GA (corresponding author), Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.
EM mcvean@well.ox.ac.uk
FU Wellcome Trust [WT098051, WT090532/Z/09/Z, WT085475/Z/08/Z, WT095552/Z/11/Z, WT086084/Z/08/Z, WT089250/Z/09/Z, WT085532AIA]; Medical Research Council [G0900747(91070)]; British Heart Foundation [RG/09/12/28096]; National Basic Research Program of China (973 program) [2011CB809201, 2011CB809202, 2011CB809203]; Chinese 863 program [2012AA02A201]; National Natural Science Foundation of China [30890032, 31161130357]; Shenzhen Key Laboratory of Transomics Biotechnologies [CXB201108250096A]; Shenzhen Municipal Government of China [ZYC200903240080A, ZYC201105170397A]; Guangdong Innovative Research Team Program [2009010016]; BMBF [01GS08201, 0315428A]; Max Planck Society; Swiss National Science Foundation [31003A_130342]; Swiss National Science Foundation NCCR 'Frontiers in Genetics' grant; Louis Jeantet Foundation; Biotechnology and Biological Sciences Research Council (BBSRC) [BB/I021213/1]; German Research Foundation [KO 4037/1-1]; Netherlands Organization for Scientific Research VENI [639.021.125]; Beatriu de Pinos Program [2006BP-A 10144, 2009BP-B 00274]; Israeli Science Foundation [04514831]; Genome Quebec and the Ministry of Economic Development, Innovation and Trade [PSR-SIIRI-195]; National Institutes of Health (NIH) [UO1HG5214, RC2HG5581, RO1MH84698, R01HG4719, R01HG3698, RC2HG5552, UO1HG6513, R01HG4960, R01HG5701, U01HG5715, T32GM8283, U01HG5208, U01HG6569, R01HG2898, R01CA166661, UO1HG5209, UO1HG5725, P41HG4221, P01HG4120, U01HG5728]; BAA-NIAID-DAIT-NIHAI [2009061, T32GM7748, U54HG3079, UL1RR024131, HHSN268201100040C]; BBSRC [BB/I021213/1, BB/I02593X/1] Funding Source: UKRI; MRC [G0801823, G0900747, G0701805] Funding Source: UKRI; Swiss National Science Foundation (SNF) [31003A_130342] Funding Source: Swiss National Science Foundation (SNF); National Cancer Institute [P30CA016672] Funding Source: NIH RePORTER; National Human Genome Research Institute [R01HG005701] Funding Source: NIH RePORTER; National Institute of Allergy and Infectious Diseases [U19AI077439] Funding Source: NIH RePORTER; National Institute of Allergy and Infectious Diseases; National Library of Medicine [T15LM007033] Funding Source: NIH RePORTER; National Institute of General Medical Sciences [T32GM007748, T32GM008283] Funding Source: NIH RePORTER; National Library of Medicine [T15LM007056] Funding Source: NIH RePORTER; Biotechnology and Biological Sciences Research Council [BB/I02593X/1, BB/I021213/1] Funding Source: researchfish; British Heart Foundation [RG/09/012/28096] Funding Source: researchfish; Medical Research Council [G0801823, G0701805, G0900747] Funding Source: researchfish
NR 47
TC 4121
Z9 4552
U1 6
U2 107
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 1
PY 2012
VL 491
IS 7422
BP 56
EP 65
DI 10.1038/nature11632
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 028PM
UT WOS:000310434500030
DA 2026-03-09
ER

PT J
AU Boyden, LM
   Choi, M
   Choate, KA
   Nelson-Williams, CJ
   Farhi, A
   Toka, HR
   Tikhonova, IR
   Bjornson, R
   Mane, SM
   Colussi, G
   Lebel, M
   Gordon, RD
   Semmekrot, BA
   Poujol, A
   Välimäki, MJ
   De Ferrari, ME
   Sanjad, SA
   Gutkin, M
   Karet, FE
   Tucci, JR
   Stockigt, JR
   Keppler-Noreuil, KM
   Porter, CC
   Anand, SK
   Whiteford, ML
   Davis, ID
   Dewar, SB
   Bettinelli, A
   Fadrowski, JJ
   Belsha, CW
   Hunley, TE
   Nelson, RD
   Trachtman, H
   Cole, TRP
   Pinsk, M
   Bockenhauer, D
   Shenoy, M
   Vaidyanathan, P
   Foreman, JW
   Rasoulpour, M
   Thameem, F
   Al-Shahrouri, HZ
   Radhakrishnan, J
   Gharavi, AG
   Goilav, B
   Lifton, RP
AF Boyden, Lynn M.
   Choi, Murim
   Choate, Keith A.
   Nelson-Williams, Carol J.
   Farhi, Anita
   Toka, Hakan R.
   Tikhonova, Irina R.
   Bjornson, Robert
   Mane, Shrikant M.
   Colussi, Giacomo
   Lebel, Marcel
   Gordon, Richard D.
   Semmekrot, Ben A.
   Poujol, Alain
   Valimaki, Matti J.
   De Ferrari, Maria E.
   Sanjad, Sami A.
   Gutkin, Michael
   Karet, Fiona E.
   Tucci, Joseph R.
   Stockigt, Jim R.
   Keppler-Noreuil, Kim M.
   Porter, Craig C.
   Anand, Sudhir K.
   Whiteford, Margo L.
   Davis, Ira D.
   Dewar, Stephanie B.
   Bettinelli, Alberto
   Fadrowski, Jeffrey J.
   Belsha, Craig W.
   Hunley, Tracy E.
   Nelson, Raoul D.
   Trachtman, Howard
   Cole, Trevor R. P.
   Pinsk, Maury
   Bockenhauer, Detlef
   Shenoy, Mohan
   Vaidyanathan, Priya
   Foreman, John W.
   Rasoulpour, Majid
   Thameem, Farook
   Al-Shahrouri, Hania Z.
   Radhakrishnan, Jai
   Gharavi, Ali G.
   Goilav, Beatrice
   Lifton, Richard P.
TI Mutations in kelch-like 3 and cullin 3 cause hypertension and electrolyte abnormalities
SO NATURE
LA English
DT Article
ID wnk kinases; k+ channel; proteins; sequence; gene; ubiquitination; cotransporter; tubule; romk
AB Hypertension affects one billion people and is a principal reversible risk factor for cardiovascular disease. Pseudohypoaldosteronism type II (PHAII), a rare Mendelian syndrome featuring hypertension, hyperkalaemia and metabolic acidosis, has revealed previously unrecognized physiology orchestrating the balance between renal salt reabsorption and K(+) and H(+) excretion(1). Here we used exome sequencing to identify mutations in kelch-like 3 (KLHL3) or cullin 3 (CUL3) in PHAII patients from 41 unrelated families. KLHL3 mutations are either recessive or dominant, whereas CUL3 mutations are dominant and predominantly de novo. CUL3 and BTB-domain-containing kelch proteins such as KLHL3 are components of cullin-RING E3 ligase complexes that ubiquitinate substrates bound to kelch propeller domains(2-8). Dominant KLHL3 mutations are clustered in short segments within the kelch propeller and BTB domains implicated in substrate(9) and cullin(5) binding, respectively. Diverse CUL3 mutations all result in skipping of exon 9, producing an in-frame deletion. Because dominant KLHL3 and CUL3 mutations both phenocopy recessive loss-of-function KLHL3 mutations, they may abrogate ubiquitination of KLHL3 substrates. Disease features are reversed by thiazide diuretics, which inhibit the Na-Cl cotransporter in the distal nephron of the kidney; KLHL3 and CUL3 are expressed in this location, suggesting a mechanistic link between KLHL3 and CUL3 mutations, increased Na-Cl reabsorption, and disease pathogenesis. These findings demonstrate the utility of exome sequencing in disease gene identification despite the combined complexities of locus heterogeneity, mixed models of transmission and frequent de novo mutation, and establish a fundamental role for KLHL3 and CUL3 in blood pressure, K(+) and pH homeostasis.
C1 [Boyden, Lynn M.; Choi, Murim; Nelson-Williams, Carol J.; Farhi, Anita] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06510 USA.
   [Boyden, Lynn M.; Choi, Murim; Nelson-Williams, Carol J.; Farhi, Anita] Yale Univ, Sch Med, Howard Hughes Med Inst, New Haven, CT 06510 USA.
   [Choate, Keith A.] Yale Univ, Sch Med, Dept Dermatol, New Haven, CT 06510 USA.
   [Toka, Hakan R.] Brigham & Womens Hosp, Div Renal, Boston, MA 02115 USA.
   [Tikhonova, Irina R.; Bjornson, Robert; Mane, Shrikant M.] Yale Univ, Yale Ctr Genome Anal, New Haven, CT 06510 USA.
   [Colussi, Giacomo; De Ferrari, Maria E.] Osped Niguarda Ca Granda, Nephrol Unit, I-20162 Milan, Italy.
   [Lebel, Marcel] Univ Laval, Dept Med, Ste Foy, PQ G1K 7P4, Canada.
   [Gordon, Richard D.] Univ Queensland, Sch Med, Endocrine Hypertens Res Ctr, Brisbane, Qld 4006, Australia.
   [Semmekrot, Ben A.] Canisius Wilhelmina Hosp, Dept Pediat, NL-6500 GS Nijmegen, Netherlands.
   [Poujol, Alain] Pays Aix Hosp, Dept Pediat, F-13616 Aix En Provence, France.
   [Valimaki, Matti J.] Univ Helsinki, Cent Hosp, Dept Med, Div Endocrinol, FIN-00290 Helsinki, Finland.
   [Sanjad, Sami A.] American Univ, Med Ctr, Dept Pediat & Adolescent Med, Beirut 11072020, Lebanon.
   [Gutkin, Michael] Univ Med & Dent New Jersey, Hypertens Res Ctr, Newark, NJ 07103 USA.
   [Karet, Fiona E.] Univ Cambridge, Dept Med Genet, Cambridge CB2 1TN, England.
   [Tucci, Joseph R.] Roger Williams Med Ctr, Div Endocrinol, Providence, RI 02908 USA.
   [Stockigt, Jim R.] Alfred Hosp, Dept Endocrinol & Diabet, Ewen Downie Metab Unit, Melbourne, Vic 3004, Australia.
   [Keppler-Noreuil, Kim M.] Univ Iowa, Childrens Hosp, Dept Pediat, Div Med Genet, Iowa City, IA 52242 USA.
   [Porter, Craig C.] Med Coll Wisconsin, Dept Pediat, Div Nephrol, Milwaukee, WI 53226 USA.
   [Anand, Sudhir K.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pediat, Los Angeles, CA USA.
   [Whiteford, Margo L.] Royal Hosp Sick Children, Duncan Guthrie Inst Med Genet, Glasgow G3 8SJ, Lanark, Scotland.
   [Davis, Ira D.] Baxter Healthcare Corp, McGaw Pk, IL 60085 USA.
   [Dewar, Stephanie B.] Univ Pittsburgh, Sch Med, Dept Pediat, Pittsburgh, PA 15261 USA.
   [Bettinelli, Alberto] Mandic Hosp, Div Pediat, I-23807 Merate, Italy.
   [Fadrowski, Jeffrey J.] Johns Hopkins Sch Med, Dept Pediat, Baltimore, MD 21287 USA.
   [Belsha, Craig W.] St Louis Univ, Hlth Sci Ctr, Dept Pediat, Div Nephrol, St Louis, MO 63110 USA.
   [Hunley, Tracy E.] Vanderbilt Univ, Dept Pediat, Med Ctr, Div Nephrol, Nashville, TN 37232 USA.
   [Nelson, Raoul D.] Univ Utah, Dept Pediat, Div Nephrol, Salt Lake City, UT 84132 USA.
   [Trachtman, Howard] Cohen Childrens Med Ctr New York, Div Nephrol, New Hyde Pk, NY 11040 USA.
   [Cole, Trevor R. P.] Birmingham Womens Hosp, W Midlands Reg Genet Serv, Birmingham B15 2TG, W Midlands, England.
   [Pinsk, Maury] Univ Alberta, Dept Pediat, Div Nephrol, Edmonton, AB T6G 2M7, Canada.
   [Bockenhauer, Detlef] UCL, Inst Child Hlth, Renal Unit, London WC1N 1EH, England.
   [Shenoy, Mohan] Royal Manchester Childrens Hosp, Dept Nephrol, Manchester M27 4HA, Lancs, England.
   [Vaidyanathan, Priya] Childrens Natl Med Ctr, Dept Endocrinol, Washington, DC 20010 USA.
   [Foreman, John W.] Duke Univ, Med Ctr, Dept Pediat, Durham, NC 27710 USA.
   [Rasoulpour, Majid] Connecticut Childrens Med Ctr, Div Nephrol, Hartford, CT 06106 USA.
   [Thameem, Farook; Al-Shahrouri, Hania Z.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Nephrol, San Antonio, TX 78229 USA.
   [Radhakrishnan, Jai; Gharavi, Ali G.] Columbia Univ Coll Phys & Surg, Dept Med, New York, NY 10032 USA.
   [Goilav, Beatrice] Childrens Hosp Montefiore, Div Nephrol, Bronx, NY 10467 USA.
C3 Yale University; Howard Hughes Medical Institute; Yale University; Yale University; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Yale University; Ospedale Niguarda Ca' Granda; IRCCS Ca Granda Ospedale Maggiore Policlinico; Laval University; University of Queensland; Canisius-Wilhelmina Hospital; University of Helsinki; Helsinki University Central Hospital; American University of Beirut; Rutgers University System; Rutgers University New Brunswick; Rutgers University Biomedical & Health Sciences; University of Cambridge; Roger Williams Medical Center; Florey Institute of Neuroscience & Mental Health; Howard Florey Institute Affiliates; University of Iowa; Medical College of Wisconsin; 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 Glasgow; Baxter International Inc; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh; Johns Hopkins University; Johns Hopkins Medicine; Saint Louis University; Vanderbilt University; Utah System of Higher Education; University of Utah; Northwell Health; North Shore University Hospital; Steven & Alexandra Cohen Children's Medical Center of New York; Birmingham Women's Hospital; University of Alberta; University of London; University College London; Manchester University NHS Foundation Trust; Royal Manchester Children's Hospital; Children's National Health System; Duke University; Connecticut Children's Medical Center; University of Texas System; University of Texas at San Antonio; Columbia University; Montefiore Medical Center; Albert Einstein College of Medicine; Childrens Hospital at Montefiore
RP Lifton, RP (corresponding author), Yale Univ, Sch Med, Dept Genet, New Haven, CT 06510 USA.
EM richard.lifton@yale.edu
FU Leducq Transatlantic Network on Hypertension; National Institutes of Health [P30-DK079310, UL1-RR024139]; National Institute of Diabetes and Digestive and Kidney Diseases [P30DK079310] Funding Source: NIH RePORTER; Great Ormond Street Hospital Childrens Charity [V0901] Funding Source: researchfish
NR 39
TC 499
Z9 554
U1 0
U2 47
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD FEB 2
PY 2012
VL 482
IS 7383
BP 98
EP U126
DI 10.1038/nature10814
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 884RN
UT WOS:000299726000043
PM 22266938
DA 2026-03-09
ER

PT J
AU Kim, TW
   Michniewicz, M
   Bergmann, DC
   Wang, ZY
AF Kim, Tae-Wuk
   Michniewicz, Marta
   Bergmann, Dominique C.
   Wang, Zhi-Yong
TI Brassinosteroid regulates stomatal development by GSK3-mediated inhibition of a MAPK pathway
SO NATURE
LA English
DT Article
ID receptor kinase bri1; signal-transduction; transcription factors; gsk3-like kinases; plant-growth; arabidopsis; bzr1; differentiation; integration; perception
AB Plants must coordinate the regulation of biochemistry and anatomy to optimize photosynthesis and water-use efficiency. The formation of stomata, epidermal pores that facilitate gas exchange, is highly coordinated with other aspects of photosynthetic development. The signalling pathways controlling stomata development are not fully understood(1,2), although mitogen-activated protein kinase (MAPK) signalling is known to have key roles. Here we demonstrate in Arabidopsis that brassinosteroid regulates stomatal development by activating the MAPK kinase kinase (MAPKKK) YDA (also known as YODA). Genetic analyses indicate that receptor kinase-mediated brassinosteroid signalling inhibits stomatal development through the glycogen synthase kinase 3 (GSK3)-like kinase BIN2, and BIN2 acts upstream of YDA but downstream of the ERECTA family of receptor kinases. Complementary in vitro and in vivo assays show that BIN2 phosphorylates YDA to inhibit YDA phosphorylation of its substrate MKK4, and that activities of downstream MAPKs are reduced in brassinosteroid-deficient mutants but increased by treatment with either brassinosteroid or GSK3-kinase inhibitor. Our results indicate that brassinosteroid inhibits stomatal development by alleviating GSK3-mediated inhibition of this MAPK module, providing two key links; that of a plant MAPKKK to its upstream regulators and of brassinosteroid to a specific developmental output.
C1 [Kim, Tae-Wuk; Wang, Zhi-Yong] Carnegie Inst Sci, Dept Plant Biol, Stanford, CA 94305 USA.
   [Kim, Tae-Wuk] Hanyang Univ, Dept Life Sci, Seoul 133791, South Korea.
   [Michniewicz, Marta; Bergmann, Dominique C.] Stanford Univ, Dept Biol, Stanford, CA 94305 USA.
C3 Carnegie Institution for Science; Hanyang University; Stanford University
RP Wang, ZY (corresponding author), Carnegie Inst Sci, Dept Plant Biol, Stanford, CA 94305 USA.
EM zywang24@stanford.edu
FU National Institutes of Health [R01GM066258]; US Department of Energy [DE-FG02-08ER15973]; Herman Frasch Foundation; National Institute of General Medical Sciences [R01GM066258] Funding Source: NIH RePORTER; U.S. Department of Energy (DOE) [DE-FG02-08ER15973] Funding Source: U.S. Department of Energy (DOE)
NR 33
TC 429
Z9 502
U1 5
U2 219
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD FEB 16
PY 2012
VL 482
IS 7385
BP 419
EP U1526
DI 10.1038/nature10794
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 892LG
UT WOS:000300287100050
PM 22307275
DA 2026-03-09
ER

PT J
AU Keller, CB
   Schoene, B
AF Keller, C. Brenhin
   Schoene, Blair
TI Statistical geochemistry reveals disruption in secular lithospheric evolution about 2.5 Gyr ago
SO NATURE
LA English
DT Article
ID atmospheric oxygen; oxidation-state; oceanic basalts; redox state; mantle; model; minerals; genesis; melts; rise
AB The Earth has cooled over the past 4.5 billion years (Gyr) as a result of surface heat loss and declining radiogenic heat production. Igneous geochemistry has been used to understand how changing heat flux influenced Archaean geodynamics(1,2), but records of systematic geochemical evolution are complicated by heterogeneity of the rock record and uncertainties regarding selection and preservation bias(3-5). Here we apply statistical sampling techniques to a geochemical database of about 70,000 samples from the continental igneous rock record to produce a comprehensive record of secular geochemical evolution throughout Earth history. Consistent with secular mantle cooling, compatible and incompatible elements in basalts record gradually decreasing mantle melt fraction through time. Superimposed on this gradual evolution is a pervasive geochemical discontinuity occurring about 2.5 Gyr ago, involving substantial decreases in mantle melt fraction in basalts, and in indicators of deep crustal melting and fractionation, such as Na/K, Eu/Eu* (europium anomaly(4)) and La/Yb ratios in felsic rocks. Along with an increase in preserved crustal thickness across the Archaean/Proterozoic boundary(6,7), these data are consistent with a model in which high-degree Archaean mantle melting produced a thick, mafic lower crust and consequent deep crustal delamination and melting-leading to abundant tonalite-trondhjemite-granodiorite magmatism and a thin preserved Archaean crust. The coincidence of the observed changes in geochemistry and crustal thickness with stepwise atmospheric oxidation(8) at the end of the Archaean eon provides a significant temporal link between deep Earth geochemical processes and the rise of atmospheric oxygen on the Earth.
C1 [Keller, C. Brenhin; Schoene, Blair] Princeton Univ, Dept Geosci, Princeton, NJ 08544 USA.
C3 Princeton University
RP Keller, CB (corresponding author), Princeton Univ, Dept Geosci, Guyot Hall,Washington Rd, Princeton, NJ 08544 USA.
EM cbkeller@princeton.edu
FU Princeton University
NR 47
TC 324
Z9 352
U1 3
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 MAY 24
PY 2012
VL 485
IS 7399
BP 490
EP U100
DI 10.1038/nature11024
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 946IH
UT WOS:000304344500040
PM 22622575
DA 2026-03-09
ER

PT J
AU Jonker, JW
   Suh, JM
   Atkins, AR
   Ahmadian, M
   Li, PP
   Whyte, J
   He, MX
   Juguilon, H
   Yin, YQ
   Phillips, CT
   Yu, RT
   Olefsky, JM
   Henry, RR
   Downes, M
   Evans, RM
AF Jonker, Johan W.
   Suh, Jae Myoung
   Atkins, Annette R.
   Ahmadian, Maryam
   Li, Pingping
   Whyte, Jamie
   He, Mingxiao
   Juguilon, Henry
   Yin, Yun-Qiang
   Phillips, Colin T.
   Yu, Ruth T.
   Olefsky, Jerrold M.
   Henry, Robert R.
   Downes, Michael
   Evans, Ronald M.
TI A PPARγ-FGF1 axis is required for adaptive adipose remodelling and metabolic homeostasis
SO NATURE
LA English
DT Article
ID causes insulin-resistance; ppar-gamma; fat necrosis; obesity; tissue; fibroblast-growth-factor-1; adipocytes; biology; family; muscle
AB Although feast and famine cycles illustrate that remodelling of adipose tissue in response to fluctuations in nutrient availability is essential for maintaining metabolic homeostasis, the underlying mechanisms remain poorly understood(1,2). Here we identify fibroblast growth factor 1 (FGF1) as a critical transducer in this process in mice, and link its regulation to the nuclear receptor PPAR gamma (peroxisome proliferator activated receptor gamma), which is the adipocyte master regulator and the target of the thiazolidinedione class of insulin sensitizing drugs(3-5). FGF1 is the prototype of the 22-member FGF family of proteins and has been implicated in a range of physiological processes, including development, wound healing and cardiovascular changes(6). Surprisingly, FGF1 knockout mice display no significant phenotype under standard laboratory conditions(7-9). We show that FGF1 is highly induced in adipose tissue in response to a high-fat diet and that mice lacking FGF1 develop an aggressive diabetic phenotype coupled to aberrant adipose expansion when challenged with a high-fat diet. Further analysis of adipose depots in FGF1-deficient mice revealed multiple histopathologies in the vasculature network, an accentuated inflammatory response, aberrant adipocyte size distribution and ectopic expression of pancreatic lipases. On withdrawal of the high-fat diet, this inflamed adipose tissue fails to properly resolve, resulting in extensive fat necrosis. In terms of mechanisms, we show that adipose induction of FGF1 in the fed state is regulated by PPAR gamma acting through an evolutionarily conserved promoter proximal PPAR response element within the FGF1 gene. The discovery of a phenotype for the FGF1 knockout mouse establishes the PPAR gamma-FGF1 axis as critical for maintaining metabolic homeostasis and insulin sensitization.
C1 [Jonker, Johan W.; Suh, Jae Myoung; Atkins, Annette R.; Ahmadian, Maryam; Whyte, Jamie; He, Mingxiao; Juguilon, Henry; Yin, Yun-Qiang; Phillips, Colin T.; Yu, Ruth T.; Downes, Michael; Evans, Ronald M.] Salk Inst Biol Studies, Gene Express Lab, La Jolla, CA 92037 USA.
   [Li, Pingping; Olefsky, Jerrold M.; Henry, Robert R.] Univ Calif San Diego, Div Endocrinol & Metab, Dept Med, La Jolla, CA 92093 USA.
   [Henry, Robert R.] Vet Affairs San Diego Healthcare Syst, Sect Diabetes Metab, San Diego, CA 92161 USA.
   [Evans, Ronald M.] Salk Inst Biol Studies, Howard Hughes Med Inst, La Jolla, CA 92037 USA.
C3 Salk Institute; University of California System; University of California San Diego; US Department of Veterans Affairs; Veterans Health Administration (VHA); VA San Diego Healthcare System; Salk Institute; Howard Hughes Medical Institute
RP Evans, RM (corresponding author), Salk Inst Biol Studies, Gene Express Lab, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA.
EM downes@salk.edu; evans@salk.edu
FU National Institutes of Health [DK062434, DK057978, DK090962, DK063491, HL105278]; Helmsley Charitable Trust; Howard Hughes Medical Institute; Human Frontier Science Program (HFSP); Netherlands Organization for Scientific Research (NWO); EU [IRG-277169]; NIDDK; National Cancer Institute [P30CA014195] Funding Source: NIH RePORTER; National Institute of Diabetes and Digestive and Kidney Diseases [R01DK057978, P30DK063491] Funding Source: NIH RePORTER
NR 31
TC 246
Z9 305
U1 0
U2 62
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 17
PY 2012
VL 485
IS 7398
BP 391
EP U143
DI 10.1038/nature10998
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 943CW
UT WOS:000304099100047
PM 22522926
DA 2026-03-09
ER

PT J
AU Korevaar, PA
   George, SJ
   Markvoort, AJ
   Smulders, MMJ
   Hilbers, PAJ
   Schenning, APHJ
   De Greef, TFA
   Meijer, EW
AF Korevaar, Peter A.
   George, Subi J.
   Markvoort, Albert J.
   Smulders, Maarten M. J.
   Hilbers, Peter A. J.
   Schenning, Albert P. H. J.
   De Greef, Tom F. A.
   Meijer, E. W.
TI Pathway complexity in supramolecular polymerization
SO NATURE
LA English
DT Article
ID self-organization; fibril formation; kinetics; nucleation; assembly; amplification; aggregation; evolution
AB Self-assembly provides an attractive route to functional organic materials, with properties and hence performance depending sensitively on the organization of the molecular building blocks(1-5). Molecular organization is a direct consequence of the pathways involved in the supramolecular assembly process, which is more amenable to detailed study when using one-dimensional systems. In the case of protein fibrils, formation and growth have been attributed to complex aggregation pathways(6-8) that go beyond traditional concepts of homogeneous(9-11) and secondary (12-14) nucleation events. The self-assembly of synthetic supramolecular polymers has also been studied and even modulated(15-18), but our quantitative understanding of the processes involved remains limited. Here we report time-resolved observations of the formation of supramolecular polymers from pi-conjugated oligomers. Our kinetic experiments show the presence of a kinetically favoured metastable assembly that forms quickly but then transforms into the thermodynamically favoured form. Quantitative insight into the kinetic experiments was obtained from kinetic model calculations, which revealed two parallel and competing pathways leading to assemblies with opposite helicity. These insights prompt us to use a chiral tartaric acid as an auxiliary to change the thermodynamic preference of the assembly process(19). We find that we can force aggregation completely down the kinetically favoured pathway so that, on removal of the auxiliary, we obtain only metastable assemblies.
C1 [Korevaar, Peter A.; Markvoort, Albert J.; Smulders, Maarten M. J.; Hilbers, Peter A. J.; De Greef, Tom F. A.; Meijer, E. W.] Eindhoven Univ Technol, Inst Complex Mol Syst, NL-5600 MB Eindhoven, Netherlands.
   [Korevaar, Peter A.; George, Subi J.; Smulders, Maarten M. J.; Schenning, Albert P. H. J.; De Greef, Tom F. A.; Meijer, E. W.] Eindhoven Univ Technol, Lab Macromol & Organ Chem, NL-5600 MB Eindhoven, Netherlands.
   [Markvoort, Albert J.; Hilbers, Peter A. J.; De Greef, Tom F. A.] Eindhoven Univ Technol, Biomodeling & Bioinformat Grp, NL-5600 MB Eindhoven, Netherlands.
C3 Eindhoven University of Technology; Eindhoven University of Technology; Eindhoven University of Technology
RP De Greef, TFA (corresponding author), Eindhoven Univ Technol, Inst Complex Mol Syst, POB 513, NL-5600 MB Eindhoven, Netherlands.
EM t.f.a.d.greef@tue.nl; e.w.meijer@tue.nl
FU European Research Council under the European Union [246829]; Netherlands Organization for Scientific Research
NR 27
TC 861
Z9 942
U1 7
U2 683
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JAN 26
PY 2012
VL 481
IS 7382
BP 492
EP U103
DI 10.1038/nature10720
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 881GY
UT WOS:000299471800037
PM 22258506
DA 2026-03-09
ER

PT J
AU Lim, BK
   Huang, KW
   Grueter, BA
   Rothwell, PE
   Malenka, RC
AF Lim, Byung Kook
   Huang, Kee Wui
   Grueter, Brad A.
   Rothwell, Patrick E.
   Malenka, Robert C.
TI Anhedonia requires MC4R-mediated synaptic adaptations in nucleus accumbens
SO NATURE
LA English
DT Article
ID long-term depression; conditioned place preference; distinct roles; receptor; expression; neurons; plasticity; pathways; circuit; reward
AB Chronic stress is a strong diathesis for depression in humans and is used to generate animal models of depression. It commonly leads to several major symptoms of depression, including dysregulated feeding behaviour, anhedonia and behavioural despair. Although hypotheses defining the neural pathophysiology of depression have been proposed, the critical synaptic adaptations in key brain circuits that mediate stress-induced depressive symptoms remain poorly understood. Here we show that chronic stress in mice decreases the strength of excitatory synapses on D1 dopamine receptor-expressing nucleus accumbens medium spiny neurons owing to activation of the melanocortin 4 receptor. Stress-elicited increases in behavioural measurements of anhedonia, but not increases in measurements of behavioural despair, are prevented by blocking these melanocortin 4 receptor-mediated synaptic changes in vivo. These results establish that stress-elicited anhedonia requires a neuropeptide-triggered, cell-type-specific synaptic adaptation in the nucleus accumbens and that distinct circuit adaptations mediate other major symptoms of stress-elicited depression.
C1 [Lim, Byung Kook; Huang, Kee Wui; Grueter, Brad A.; Rothwell, Patrick E.; Malenka, Robert C.] Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Nancy Pritzker Lab, Stanford, CA 94305 USA.
C3 Stanford University
RP Malenka, RC (corresponding author), Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Nancy Pritzker Lab, 265 Campus Dr, Stanford, CA 94305 USA.
EM malenka@stanford.edu
FU Davis Foundation Postdoctoral Fellowship in Eating Disorders Research; National Institutes of Health
NR 46
TC 300
Z9 372
U1 1
U2 63
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 12
PY 2012
VL 487
IS 7406
BP 183
EP U64
DI 10.1038/nature11160
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 972LP
UT WOS:000306278900029
PM 22785313
DA 2026-03-09
ER

PT J
AU Brown, KM
   Fialko, Y
AF Brown, Kevin M.
   Fialko, Yuri
TI 'Melt welt' mechanism of extreme weakening of gabbro at seismic slip rates
SO NATURE
LA English
DT Article
ID friction; fault; instability
AB Laboratory studies of frictional properties of rocks at slip velocities approaching the seismic range (similar to 0.1-1 m s(-1)), and at moderate normal stresses (1-10 MPa), have revealed a complex evolution of the dynamic shear strength, with at least two phases of weakening separated by strengthening at the onset of wholesale melting(1-4). The second post-melting weakening phase is governed by viscous properties of the melt layer and is reasonably well understood(5,6). The initial phase of extreme weakening, however, remains a subject of much debate. Here we show that the initial weakening of gabbro is associated with the formation of hotspots and macroscopic streaks of melt ('melt welts'), which partially unload the rest of the slip interface. Melt welts begin to form when the average rate of frictional heating exceeds 0.1-0.4 MW m(-2), while the average temperature of the shear zone is well below the solidus (250-450 degrees C). Similar heterogeneities in stress and temperature are likely to occur on natural fault surfaces during rapid slip, and to be important for earthquake rupture dynamics.
C1 [Brown, Kevin M.; Fialko, Yuri] Univ Calif San Diego, Scripps Inst Oceanog, Inst Geophys & Planetary Phys, La Jolla, CA 92093 USA.
C3 University of California System; University of California San Diego; Scripps Institution of Oceanography
RP Brown, KM (corresponding author), Univ Calif San Diego, Scripps Inst Oceanog, Inst Geophys & Planetary Phys, La Jolla, CA 92093 USA.
EM kmbrown@ucsd.edu; yfialko@ucsd.edu
FU NSF [EAR-0838255]; Directorate For Geosciences; Division Of Earth Sciences [0838255] Funding Source: National Science Foundation
NR 24
TC 58
Z9 72
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 AUG 30
PY 2012
VL 488
IS 7413
BP 638
EP +
DI 10.1038/nature11370
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 996NC
UT WOS:000308095100052
PM 22932388
DA 2026-03-09
ER

PT J
AU Dixon, JR
   Selvaraj, S
   Yue, F
   Kim, A
   Li, Y
   Shen, Y
   Hu, M
   Liu, JS
   Ren, B
AF Dixon, Jesse R.
   Selvaraj, Siddarth
   Yue, Feng
   Kim, Audrey
   Li, Yan
   Shen, Yin
   Hu, Ming
   Liu, Jun S.
   Ren, Bing
TI Topological domains in mammalian genomes identified by analysis of chromatin interactions
SO NATURE
LA English
DT Article
ID embryonic stem-cells; nuclear lamina interactions; gene-expression; organization; architecture; drosophila; pluripotent; principles; boundary; locus
AB The spatial organization of the genome is intimately linked to its biological function, yet our understanding of higher order genomic structure is coarse, fragmented and incomplete. In the nucleus of eukaryotic cells, interphase chromosomes occupy distinct chromosome territories, and numerous models have been proposed for how chromosomes fold within chromosome territories(1). These models, however, provide only few mechanistic details about the relationship between higher order chromatin structure and genome function. Recent advances in genomic technologies have led to rapid advances in the study of three-dimensional genome organization. In particular, Hi-C has been introduced as a method for identifying higher order chromatin interactions genome wide(2). Here we investigate the three-dimensional organization of the human and mouse genomes in embryonic stem cells and terminally differentiated cell types at unprecedented resolution. We identify large, megabase-sized local chromatin interaction domains, which we term 'topological domains', as a pervasive structural feature of the genome organization. These domains correlate with regions of the genome that constrain the spread of heterochromatin. The domains are stable across different cell types and highly conserved across species, indicating that topological domains are an inherent property of mammalian genomes. Finally, we find that the boundaries of topological domains are enriched for the insulator binding protein CTCF, housekeeping genes, transfer RNAs and short interspersed element (SINE) retrotransposons, indicating that these factors may have a role in establishing the topological domain structure of the genome.
C1 [Dixon, Jesse R.; Selvaraj, Siddarth; Yue, Feng; Kim, Audrey; Li, Yan; Shen, Yin; Ren, Bing] Ludwig Inst Canc Res, La Jolla, CA 92093 USA.
   [Dixon, Jesse R.] Univ Calif San Diego, Med Scientist Training Program, La Jolla, CA 92093 USA.
   [Dixon, Jesse R.] Univ Calif San Diego, Biomed Sci Grad Program, La Jolla, CA 92093 USA.
   [Selvaraj, Siddarth] Univ Calif San Diego, Bioinformat & Syst Biol Grad Program, La Jolla, CA 92093 USA.
   [Hu, Ming; Liu, Jun S.] Harvard Univ, Dept Stat, Cambridge, MA 02138 USA.
   [Ren, Bing] Univ Calif San Diego, Sch Med, UCSD Moores Canc Ctr, Inst Genom Med,Dept Cellular & Mol Med, La Jolla, CA 92093 USA.
C3 Ludwig Institute for Cancer Research; 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; Harvard University; University of California System; University of California San Diego
RP Ren, B (corresponding author), Ludwig Inst Canc Res, 9500 Gilman Dr, La Jolla, CA 92093 USA.
EM biren@ucsd.edu
FU Ludwig Institute for Cancer Research; California Institute for Regenerative Medicine (CIRM) [RN2-00905-1]; NIH [B.R. R01GH003991]; Rett Syndrome Research Foundation
NR 29
TC 4970
Z9 6066
U1 5
U2 604
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD MAY 17
PY 2012
VL 485
IS 7398
BP 376
EP 380
DI 10.1038/nature11082
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 943CW
UT WOS:000304099100044
PM 22495300
DA 2026-03-09
ER

PT J
AU Davis, JG
   Gierszal, KP
   Wang, P
   Ben-Amotz, D
AF Davis, Joel G.
   Gierszal, Kamil P.
   Wang, Ping
   Ben-Amotz, Dor
TI Water structural transformation at molecular hydrophobic interfaces
SO NATURE
LA English
DT Article
ID hydration; methane
AB Hydrophobic hydration is considered to have a key role in biological processes ranging from membrane formation to protein folding and ligand binding(1). Historically, hydrophobic hydration shells were thought to resemble solid clathrate hydrates(2-4), with solutes surrounded by polyhedral cages composed of tetrahedrally hydrogen-bonded water molecules. But more recent experimental(5-8) and theoretical(9-16) studies have challenged this view and emphasized the importance of the length scales involved. Here we report combined polarized, isotopic and temperature-dependent Raman scattering measurements with multivariate curve resolution (Raman-MCR)(17-19) that explore hydrophobic hydration by mapping the vibrational spectroscopic features arising from the hydrophobic hydration shells of linear alcohols ranging from methanol to heptanol. Our data, covering the entire 0-100 degrees C temperature range, show clear evidence that at low temperatures the hydration shells have a hydrophobically enhanced water structure with greater tetrahedral order and fewer weak hydrogen bonds than the surrounding bulk water. This structure disappears with increasing temperature and is then, for hydrophobic chains longer than similar to 1 nm, replaced by a more disordered structure with weaker hydrogen bonds than bulk water. These observations support our current understanding of hydrophobic hydration, including the thermally induced water structural transformation that is suggestive of the hydrophobic crossover predicted to occur at lengths of similar to 1 nm (refs 5, 9, 10, 14).
C1 [Davis, Joel G.; Gierszal, Kamil P.; Wang, Ping; Ben-Amotz, Dor] Purdue Univ, Dept Chem, W Lafayette, IN 47907 USA.
C3 Purdue University System; Purdue University
RP Ben-Amotz, D (corresponding author), Purdue Univ, Dept Chem, W Lafayette, IN 47907 USA.
EM bendor@purdue.edu
FU National Science Foundation [CHE-0847928]; Division Of Chemistry; Direct For Mathematical & Physical Scien [0847928] Funding Source: National Science Foundation
NR 30
TC 504
Z9 576
U1 9
U2 729
PU NATURE PUBLISHING 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 22
PY 2012
VL 491
IS 7425
BP 582
EP 585
DI 10.1038/nature11570
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 040RE
UT WOS:000311339800049
PM 23172216
DA 2026-03-09
ER

PT J
AU Hughes, JF
   Skaletsky, H
   Brown, LG
   Pyntikova, T
   Graves, T
   Fulton, RS
   Dugan, S
   Ding, Y
   Buhay, CJ
   Kremitzki, C
   Wang, QY
   Shen, H
   Holder, M
   Villasana, D
   Nazareth, LV
   Cree, A
   Courtney, L
   Veizer, J
   Kotkiewicz, H
   Cho, TJ
   Koutseva, N
   Rozen, S
   Muzny, DM
   Warren, WC
   Gibbs, RA
   Wilson, RK
   Page, DC
AF Hughes, Jennifer F.
   Skaletsky, Helen
   Brown, Laura G.
   Pyntikova, Tatyana
   Graves, Tina
   Fulton, Robert S.
   Dugan, Shannon
   Ding, Yan
   Buhay, Christian J.
   Kremitzki, Colin
   Wang, Qiaoyan
   Shen, Hua
   Holder, Michael
   Villasana, Donna
   Nazareth, Lynne V.
   Cree, Andrew
   Courtney, Laura
   Veizer, Joelle
   Kotkiewicz, Holland
   Cho, Ting-Jan
   Koutseva, Natalia
   Rozen, Steve
   Muzny, Donna M.
   Warren, Wesley C.
   Gibbs, Richard A.
   Wilson, Richard K.
   Page, David C.
TI Strict evolutionary conservation followed rapid gene loss on human and rhesus Y chromosomes
SO NATURE
LA English
DT Article
ID human x-chromosome; sex-chromosm; degeneration; sequence; genome; proteins; primates; weight
AB The human X and Y chromosomes evolved from an ordinary pair of autosomes during the past 200-300 million years(1-3). The human MSY (male-specific region of Y chromosome) retains only three percent of the ancestral autosomes' genes owing to genetic decay(4,5). This evolutionary decay was driven by a series of five 'stratification' events. Each event suppressed X-Y crossing over within a chromosome segment or 'stratum', incorporated that segment into the MSY and subjected its genes to the erosive forces that attend the absence of crossing over(2,6). The last of these events occurred 30 million years ago, 5 million years before the human and Old World monkey lineages diverged. Although speculation abounds regarding ongoing decay and looming extinction of the human Y chromosome(7-10), remarkably little is known about how many MSY genes were lost in the human lineage in the 25 million years that have followed its separation from the Old World monkey lineage. To investigate this question, we sequenced the MSY of the rhesus macaque, an Old World monkey, and compared it to the human MSY. We discovered that during the last 25 million years MSY gene loss in the human lineage was limited to the youngest stratum (stratum 5), which comprises three percent of the human MSY. In the older strata, which collectively comprise the bulk of the human MSY, gene loss evidently ceased more than 25 million years ago. Likewise, the rhesus MSY has not lost any older genes (from strata 1-4) during the past 25 million years, despite its major structural differences to the human MSY. The rhesus MSY is simpler, with few amplified gene families or palindromes that might enable intrachromosomal recombination and repair. We present an empirical reconstruction of human MSY evolution in which each stratum transitioned from rapid, exponential loss of ancestral genes to strict conservation through purifying selection.
C1 [Hughes, Jennifer F.; Skaletsky, Helen; Brown, Laura G.; Pyntikova, Tatyana; Cho, Ting-Jan; Koutseva, Natalia; Rozen, Steve; Page, David C.] MIT, Howard Hughes Med Inst, Whitehead Inst, Cambridge, MA 02142 USA.
   [Hughes, Jennifer F.; Skaletsky, Helen; Brown, Laura G.; Pyntikova, Tatyana; Cho, Ting-Jan; Koutseva, Natalia; Rozen, Steve; Page, David C.] MIT, Dept Biol, Cambridge, MA 02142 USA.
   [Graves, Tina; Fulton, Robert S.; Kremitzki, Colin; Courtney, Laura; Veizer, Joelle; Kotkiewicz, Holland; Warren, Wesley C.; Wilson, Richard K.] Washington Univ, Sch Med, Genome Inst, St Louis, MO 63108 USA.
   [Dugan, Shannon; Ding, Yan; Buhay, Christian J.; Wang, Qiaoyan; Shen, Hua; Holder, Michael; Villasana, Donna; Nazareth, Lynne V.; Cree, Andrew; Muzny, Donna M.; Gibbs, Richard A.] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA.
C3 Howard Hughes Medical Institute; Massachusetts Institute of Technology (MIT); Whitehead Institute; Massachusetts Institute of Technology (MIT); Washington University (WUSTL); Baylor College of Medicine
RP Hughes, JF (corresponding author), MIT, Howard Hughes Med Inst, Whitehead Inst, 9 Cambridge Ctr, Cambridge, MA 02142 USA.
EM jhughes@wi.mit.edu
FU National Institutes of Health; Howard Hughes Medical Institute; Charles A. King Trust
CR Aitken RJ, 2002, NATURE, V415, P963, DOI 10.1038/415963a
   Bachtrog D, 2008, GENETICS, V179, P1513, DOI 10.1534/genetics.107.084012
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   Karere GM, 2008, GENOMICS, V92, P210, DOI 10.1016/j.ygeno.2008.05.013
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NR 30
TC 206
Z9 241
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 MAR 1
PY 2012
VL 483
IS 7387
BP 82
EP U124
DI 10.1038/nature10843
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 900HP
UT WOS:000300877900049
PM 22367542
DA 2026-03-09
ER

PT J
AU Penney, HD
   Hassall, C
   Skevington, JH
   Abbott, KR
   Sherratt, TN
AF Penney, Heather D.
   Hassall, Christopher
   Skevington, Jeffrey H.
   Abbott, Kevin R.
   Sherratt, Thomas N.
TI A comparative analysis of the evolution of imperfect mimicry
SO NATURE
LA English
DT Article
ID syrphidae diptera; phylogeny; size; hoverfly; pigeons; mtdna
AB Although exceptional examples of adaptation are frequently celebrated, some outcomes of natural selection seem far from perfect. For example, many hoverflies (Diptera: Syrphidae) are harmless (Batesian(1)) mimics of stinging Hymenoptera(2). However, although some hoverfly species are considered excellent mimics, other species bear only a superficial resemblance to their models(3) and it is unclear why this is so. To evaluate hypotheses that have been put forward to explain interspecific variation in the mimetic fidelity of Palearctic Syrphidae we use a comparative approach. We show that the most plausible explanation is that predators impose less selection for mimetic fidelity on smaller hoverfly species because they are less profitable prey items. In particular, our findings, in combination with previous results, allow us to reject several key hypotheses for imperfect mimicry: first, human ratings of mimetic fidelity are positively correlated with both morphometric measures and avian rankings, indicating that variation in mimetic fidelity is not simply an illusion based on human perception(4); second, no species of syrphid maps out in multidimensional space as being intermediate in appearance between several different hymenopteran model species, as the multimodel hypothesis(5) requires; and third, we find no evidence for a negative relationship between mimetic fidelity and abundance, which calls into question the kin-selection(6) hypothesis. By contrast, a strong positive relationship between mimetic fidelity and body size supports the relaxed-selection hypothesis(7,8), suggesting that reduced predation pressure on less profitable prey species limits the selection for mimetic perfection.
C1 [Penney, Heather D.; Hassall, Christopher; Skevington, Jeffrey H.; Abbott, Kevin R.; Sherratt, Thomas N.] Carleton Univ, Dept Biol, Ottawa, ON K1S 5B6, Canada.
   [Skevington, Jeffrey H.] Agr & Agri Food Canada, Canadian Natl Collect Insects Arachnids & Nematod, Ottawa, ON K1A 0C6, Canada.
C3 Carleton University; Agriculture & Agri Food Canada
RP Sherratt, TN (corresponding author), Carleton Univ, Dept Biol, 1125 Colonel Dr, Ottawa, ON K1S 5B6, Canada.
EM sherratt@connect.carleton.ca
FU Natural Sciences and Engineering Research Council of Canada (NSERC); Canada Foundation for Innovation; Ontario Innovation Trust; Agriculture and Agri-Food Canada; Canadian Centre for DNA Barcoding; NSERC Canpolin; Ontario MRI
NR 37
TC 167
Z9 182
U1 2
U2 250
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 22
PY 2012
VL 483
IS 7390
BP 461
EP U110
DI 10.1038/nature10961
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 912CC
UT WOS:000301771200042
PM 22437614
DA 2026-03-09
ER

PT J
AU Perron, JT
   Richardson, PW
   Ferrier, KL
   Lapôtre, M
AF Perron, J. Taylor
   Richardson, Paul W.
   Ferrier, Ken L.
   Lapotre, Mathieu
TI The root of branching river networks
SO NATURE
LA English
DT Article
ID triple junction region; erosion rates; model; landscape; be-10; evolution; hillslope; bedrock; creep; al-26
AB Branching river networks are one of the most widespread and recognizable features of Earth's landscapes and have also been discovered elsewhere in the Solar System(1,2). But the mechanisms that create these patterns and control their spatial scales are poorly understood. Theories based on probability(3-5) or optimality(3,6-8) have proven useful(9), but do not explain how river networks develop over time through erosion and sediment transport. Here we show that branching at the uppermost reaches of river networks is rooted in two coupled instabilities: first, valleys widen at the expense of their smaller neighbours, and second, side slopes of the widening valleys become susceptible to channel incision. Each instability occurs at a critical ratio of the characteristic timescales for soil transport and channel incision. Measurements from two field sites demonstrate that our theory correctly predicts the size of the smallest valleys with tributaries. We also show that the dominant control on the scale of landscape dissection in these sites is the strength of channel incision, which correlates with aridity and rock weakness, rather than the strength of soil transport. These results imply that the fine-scale structure of branching river networks is an organized signature of erosional mechanics, not a consequence of random topology.
C1 [Perron, J. Taylor; Richardson, Paul W.; Ferrier, Ken L.] MIT, Dept Earth Atmospher & Planetary Sci, Cambridge, MA 02139 USA.
   [Lapotre, Mathieu] Univ Strasbourg, Ecole & Observ Sci Terre, F-67084 Strasbourg, France.
C3 Massachusetts Institute of Technology (MIT); Universites de Strasbourg Etablissements Associes; Universite de Strasbourg
RP Perron, JT (corresponding author), MIT, Dept Earth Atmospher & Planetary Sci, Cambridge, MA 02139 USA.
EM perron@mit.edu
FU US National Science Foundation Geomorphology and Land Use Dynamics programme [EAR-0951672]; US Department of Defense through a National Defense Science and Engineering Graduate Fellowship; Directorate For Geosciences; Division Of Earth Sciences [0951672] Funding Source: National Science Foundation
NR 57
TC 121
Z9 142
U1 5
U2 180
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 6
PY 2012
VL 492
IS 7427
BP 100
EP +
DI 10.1038/nature11672
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 048EQ
UT WOS:000311893400053
PM 23222614
DA 2026-03-09
ER

PT J
AU Miyake, F
   Nagaya, K
   Masuda, K
   Nakamura, T
AF Miyake, Fusa
   Nagaya, Kentaro
   Masuda, Kimiaki
   Nakamura, Toshio
TI A signature of cosmic-ray increase in AD 774-775 from tree rings in Japan
SO NATURE
LA English
DT Article
ID radiocarbon age calibration; solar; events; ice
AB Increases in C-14 concentrations in tree rings could be attributed to cosmic-ray events(1-7), as have increases in Be-10 and nitrate in ice cores(8,9). The record of the past 3,000 years in the IntCal09 data set(10), which is a time series at 5-year intervals describing the C-14 content of trees over a period of approximately 10,000 years, shows three periods during which C-14 increased at a rate greater than 3 parts per thousand over 10 years. Two of these periods have been measured at high time resolution, but neither showed increases on a timescale of about 1 year (refs 11 and 12). Here we report C-14 measurements in annual rings of Japanese cedar trees from AD 750 to AD 820 (the remaining period), with 1- and 2-year resolution. We find a rapid increase of about 12 parts per thousand in the C-14 content from AD 774 to 775, which is about 20 times larger than the change attributed to ordinary solar modulation. When averaged over 10 years, the data are consistent with the decadal IntCal C-14 data from North American and European trees(13). We argue that neither a solar flare nor a local supernova is likely to have been responsible.
C1 [Miyake, Fusa; Nagaya, Kentaro; Masuda, Kimiaki] Nagoya Univ, Solar Terr Environm Lab, Chikusa Ku, Nagoya, Aichi 4648601, Japan.
   [Nakamura, Toshio] Nagoya Univ, Ctr Chronol Res, Chikusa Ku, Nagoya, Aichi 4648601, Japan.
C3 Nagoya University; Nagoya University
RP Miyake, F (corresponding author), Nagoya Univ, Solar Terr Environm Lab, Chikusa Ku, Nagoya, Aichi 4648601, Japan.
EM fmiyake@stelab.nagoya-u.ac.jp
FU Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan [B: 22340144]; Grants-in-Aid for Scientific Research [22340144] Funding Source: KAKEN
NR 29
TC 377
Z9 401
U1 2
U2 90
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 14
PY 2012
VL 486
IS 7402
BP 240
EP 242
DI 10.1038/nature11123
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 957UH
UT WOS:000305189000031
PM 22699615
DA 2026-03-09
ER

PT J
AU Scimia, MC
   Hurtado, C
   Ray, S
   Metzler, S
   Wei, K
   Wang, JM
   Woods, CE
   Purcell, NH
   Catalucci, D
   Akasaka, T
   Bueno, OF
   Vlasuk, GP
   Kaliman, P
   Bodmer, R
   Smith, LH
   Ashley, E
   Mercola, M
   Brown, JH
   Ruiz-Lozano, P
AF Scimia, Maria Cecilia
   Hurtado, Cecilia
   Ray, Saugata
   Metzler, Scott
   Wei, Ke
   Wang, Jianming
   Woods, Chris E.
   Purcell, Nicole H.
   Catalucci, Daniele
   Akasaka, Takeshi
   Bueno, Orlando F.
   Vlasuk, George P.
   Kaliman, Perla
   Bodmer, Rolf
   Smith, Layton H.
   Ashley, Euan
   Mercola, Mark
   Brown, Joan Heller
   Ruiz-Lozano, Pilar
TI APJ acts as a dual receptor in cardiac hypertrophy
SO NATURE
LA English
DT Article
ID in-vivo; gene-expression; angiotensin-ii; apelin; stretch; protein; contractility; myocytes; cardiomyocytes; involvement
AB Cardiac hypertrophy is initiated as an adaptive response to sustained overload but progresses pathologically as heart failure ensues(1). Here we report that genetic loss of APJ, a G-protein-coupled receptor, confers resistance to chronic pressure overload by markedly reducing myocardial hypertrophy and heart failure. In contrast, mice lacking apelin (the endogenous APJ ligand) remain sensitive, suggesting an apelin-independent function of APJ. Freshly isolated APJ-null cardiomyocytes exhibit an attenuated response to stretch, indicating that APJ is a mechanosensor. Activation of APJ by stretch increases cardiomyocyte cell size and induces molecular markers of hypertrophy. Whereas apelin stimulates APJ to activate G alpha(i) and elicits a protective response, stretch signals in an APJ-dependent, G-protein-independent fashion to induce hypertrophy. Stretch-mediated hypertrophy is prevented by knockdown of beta-arrestins or by pharmacological doses of apelin acting through G alpha(i). Taken together, our data indicate that APJ is a bifunctional receptor for both mechanical stretch and the endogenous peptide apelin. By sensing the balance between these stimuli, APJ occupies a pivotal point linking sustained overload to cardiomyocyte hypertrophy.
C1 [Scimia, Maria Cecilia; Hurtado, Cecilia; Ray, Saugata; Wei, Ke; Wang, Jianming; Akasaka, Takeshi; Bodmer, Rolf; Smith, Layton H.; Mercola, Mark; Ruiz-Lozano, Pilar] Sanford Burnham Med Res Inst, La Jolla, CA 92037 USA.
   [Metzler, Scott; Ruiz-Lozano, Pilar] Stanford Univ, Sch Med, Dept Pediat, Stanford, CA 94305 USA.
   [Woods, Chris E.; Ashley, Euan] Stanford Univ, Sch Med, Dept Med, Stanford, CA 94305 USA.
   [Purcell, Nicole H.; Brown, Joan Heller] Univ Calif San Diego, Dept Pharmacol, San Diego, CA 92103 USA.
   [Catalucci, Daniele] CNR, Biomed & Genet Res Inst, I-20138 Milan, Italy.
   [Catalucci, Daniele] Humanitas Clin & Res Ctr, I-20089 Milan, Italy.
   [Bueno, Orlando F.; Vlasuk, George P.] Wyeth Pharmaceut, Madison, NJ USA.
   [Kaliman, Perla] Inst Biomed Res August Pi & Sunyer IDIBAPS, E-08036 Barcelona, Spain.
C3 Sanford Burnham Prebys Medical Discovery Institute; Stanford University; Stanford University; University of California System; University of California San Diego; Consiglio Nazionale delle Ricerche (CNR); Pfizer; Pfizer USA; Wyeth; University of Barcelona; Hospital Clinic de Barcelona; IDIBAPS
RP Ruiz-Lozano, P (corresponding author), Sanford Burnham Med Res Inst, La Jolla, CA 92037 USA.
EM prlozano@stanford.edu
FU Wyeth Sponsored Research Agreement; National Institutes of Health (NIH) [R01HL086879, R37HL059502, R01HL083463, R01HL054732, NS05422, RO1HL28143, P01 HL085577]; Sanford Children's Center; Ellison Medical Foundation; Muscular Dystrophy association; Florida Department of Health [06-NIR-09]; California Institute for Regenerative Medicine; Italian Ministry of Research and Education; Italian Society of Cardiology (SIC and Sanofi-Aventis Foundation); American Heart Association Postdoctoral Award; Ministerio de Ciencia e Innovacion (MICINN) Spain [SAF2010-15050]; National Heart Lung and Blood Institute [R01HL054732] Funding Source: NIH RePORTER
NR 27
TC 212
Z9 240
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 16
PY 2012
VL 488
IS 7411
BP 394
EP 398
DI 10.1038/nature11263
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 988OS
UT WOS:000307501000045
PM 22810587
DA 2026-03-09
ER

PT J
AU Dasmahapatra, KK
   Walters, JR
   Briscoe, AD
   Davey, JW
   Whibley, A
   Nadeau, NJ
   Zimin, AV
   Hughes, DST
   Ferguson, LC
   Martin, SH
   Salazar, C
   Lewis, JJ
   Adler, S
   Ahn, SJ
   Baker, DA
   Baxter, SW
   Chamberlain, NL
   Chauhan, R
   Counterman, BA
   Dalmay, T
   Gilbert, LE
   Gordon, K
   Heckel, DG
   Hines, HM
   Hoff, KJ
   Holland, PWH
   Jacquin-Joly, E
   Jiggins, FM
   Jones, RT
   Kapan, DD
   Kersey, P
   Lamas, G
   Lawson, D
   Mapleson, D
   Maroja, LS
   Martin, A
   Moxon, S
   Palmer, WJ
   Papa, R
   Papanicolaou, A
   Pauchet, Y
   Ray, DA
   Rosser, N
   Salzberg, SL
   Supple, MA
   Surridge, A
   Tenger-Trolander, A
   Vogel, H
   Wilkinson, PA
   Wilson, D
   Yorke, JA
   Yuan, FR
   Balmuth, AL
   Eland, C
   Gharbi, K
   Thomson, M
   Gibbs, RA
   Han, Y
   Jayaseelan, JC
   Kovar, C
   Mathew, T
   Muzny, DM
   Ongeri, F
   Pu, LL
   Qu, JX
   Thornton, RL
   Worley, KC
   Wu, YQ
   Linares, M
   Blaxter, ML
   Ffrench-Constant, RH
   Joron, M
   Kronforst, MR
   Mullen, SP
   Reed, RD
   Scherer, SE
   Richards, S
   Mallet, J
   McMillan, WO
   Jiggins, CD
AF Dasmahapatra, Kanchon K.
   Walters, James R.
   Briscoe, Adriana D.
   Davey, John W.
   Whibley, Annabel
   Nadeau, Nicola J.
   Zimin, Aleksey V.
   Hughes, Daniel S. T.
   Ferguson, Laura C.
   Martin, Simon H.
   Salazar, Camilo
   Lewis, James J.
   Adler, Sebastian
   Ahn, Seung-Joon
   Baker, Dean A.
   Baxter, Simon W.
   Chamberlain, Nicola L.
   Chauhan, Ritika
   Counterman, Brian A.
   Dalmay, Tamas
   Gilbert, Lawrence E.
   Gordon, Karl
   Heckel, David G.
   Hines, Heather M.
   Hoff, Katharina J.
   Holland, Peter W. H.
   Jacquin-Joly, Emmanuelle
   Jiggins, Francis M.
   Jones, Robert T.
   Kapan, Durrell D.
   Kersey, Paul
   Lamas, Gerardo
   Lawson, Daniel
   Mapleson, Daniel
   Maroja, Luana S.
   Martin, Arnaud
   Moxon, Simon
   Palmer, William J.
   Papa, Riccardo
   Papanicolaou, Alexie
   Pauchet, Yannick
   Ray, David A.
   Rosser, Neil
   Salzberg, Steven L.
   Supple, Megan A.
   Surridge, Alison
   Tenger-Trolander, Ayse
   Vogel, Heiko
   Wilkinson, Paul A.
   Wilson, Derek
   Yorke, James A.
   Yuan, Furong
   Balmuth, Alexi L.
   Eland, Cathlene
   Gharbi, Karim
   Thomson, Marian
   Gibbs, Richard A.
   Han, Yi
   Jayaseelan, Joy C.
   Kovar, Christie
   Mathew, Tittu
   Muzny, Donna M.
   Ongeri, Fiona
   Pu, Ling-Ling
   Qu, Jiaxin
   Thornton, Rebecca L.
   Worley, Kim C.
   Wu, Yuan-Qing
   Linares, Mauricio
   Blaxter, Mark L.
   Ffrench-Constant, Richard H.
   Joron, Mathieu
   Kronforst, Marcus R.
   Mullen, Sean P.
   Reed, Robert D.
   Scherer, Steven E.
   Richards, Stephen
   Mallet, James
   McMillan, W. Owen
   Jiggins, Chris D.
TI Butterfly genome reveals promiscuous exchange of mimicry adaptations among species
SO NATURE
LA English
DT Article
ID gene flow; heliconius; evolution; hybridization; synteny; lepidoptera; speciation; karyotype; insights
AB The evolutionary importance of hybridization and introgression has long been debated(1). Hybrids are usually rare and unfit, but even infrequent hybridization can aid adaptation by transferring beneficial traits between species. Here we use genomic tools to investigate introgression in Heliconius, a rapidly radiating genus of neotropical butterflies widely used in studies of ecology, behaviour, mimicry and speciation(2-5). We sequenced the genome of Heliconius melpomene and compared it with other taxa to investigate chromosomal evolution in Lepidoptera and gene flow among multiple Heliconius species and races. Among 12,669 predicted genes, biologically important expansions of families of chemosensory and Hox genes are particularly noteworthy. Chromosomal organization has remained broadly conserved since the Cretaceous period, when butterflies split from the Bombyx (silkmoth) lineage. Using genomic resequencing, we show hybrid exchange of genes between three co-mimics, Heliconius melpomene, Heliconius timareta and Heliconius elevatus, especially at two genomic regions that control mimicry pattern. We infer that closely related Heliconius species exchange protective colour-pattern genes promiscuously, implying that hybridization has an important role in adaptive radiation.
C1 [Dasmahapatra, Kanchon K.; Rosser, Neil; Mallet, James] UCL, Dept Genet Evolut & Environm, London WC1E 6BT, England.
   [Walters, James R.; Nadeau, Nicola J.; Martin, Simon H.; Salazar, Camilo; Baxter, Simon W.; Surridge, Alison; Jiggins, Chris D.] Univ Cambridge, Dept Zool, Cambridge CB2 3EJ, England.
   [Briscoe, Adriana D.; Lewis, James J.; Martin, Arnaud; Yuan, Furong; Reed, Robert D.] Univ Calif Irvine, Dept Ecol & Evolutionary Biol, Irvine, CA 92697 USA.
   [Davey, John W.; Blaxter, Mark L.] Univ Edinburgh, Inst Evolutionary Biol, Ashworth Labs, Edinburgh EH9 3JT, Midlothian, Scotland.
   [Whibley, Annabel; Jones, Robert T.; Joron, Mathieu] Museum Natl Hist Nat, CNRS UMR 7205, F-75005 Paris, France.
   [Zimin, Aleksey V.; Yorke, James A.] Univ Maryland, Inst Phys Sci & Technol, College Pk, MD 20742 USA.
   [Hughes, Daniel S. T.; Kersey, Paul; Lawson, Daniel; Wilson, Derek] European Bioinformat Inst, Hinxton CB10 1SD, England.
   [Ferguson, Laura C.; Holland, Peter W. H.] Univ Oxford, Dept Zool, Oxford OX1 3PS, England.
   [Salazar, Camilo; McMillan, W. Owen; Jiggins, Chris D.] Smithsonian Trop Res Inst, Panama City, Panama.
   [Adler, Sebastian; Hoff, Katharina J.] Univ Greifswald, Inst Math & Informat, D-17487 Greifswald, Germany.
   [Ahn, Seung-Joon; Heckel, David G.; Pauchet, Yannick; Vogel, Heiko] Max Planck Inst Chem Biol, D-07745 Jena, Germany.
   [Baker, Dean A.] Univ London Imperial Coll Sci Technol & Med, London SW7 2AZ, England.
   [Chamberlain, Nicola L.; Tenger-Trolander, Ayse; Kronforst, Marcus R.] Harvard Univ, FAS Ctr Syst Biol, Cambridge, MA 02138 USA.
   [Chauhan, Ritika; Ffrench-Constant, Richard H.] Univ Exeter, Sch Biosci, Ctr Ecol & Conservat, Penryn TR10 9EZ, England.
   [Counterman, Brian A.] Mississippi State Univ, Dept Biol, Mississippi State, MS 39762 USA.
   [Dalmay, Tamas] Univ E Anglia, Sch Biol Sci, Norwich NR4 7TJ, Norfolk, England.
   [Gilbert, Lawrence E.] Univ Texas Austin, Sect Integrat Biol, Austin, TX 78712 USA.
   [Gilbert, Lawrence E.] Univ Texas Austin, Brackenridge Field Lab, Austin, TX 78712 USA.
   [Gordon, Karl; Papanicolaou, Alexie] CSIRO Ecosyst Sci, Black Mt Labs, Canberra, ACT 2601, Australia.
   [Hines, Heather M.] N Carolina State Univ, Dept Genet, Raleigh, NC 27695 USA.
   [Jacquin-Joly, Emmanuelle] Univ Paris 06, INRA, UMR A 1272, F-78026 Versailles, France.
   [Jiggins, Francis M.; Palmer, William J.] Univ Cambridge, Dept Genet, Cambridge CB2 3EH, England.
   [Kapan, Durrell D.] Calif Acad Sci, Dept Entomol, Ctr Comparat Genom, San Francisco, CA 94118 USA.
   [Kapan, Durrell D.] Univ Hawaii Manoa, Pacific Biosci Res Ctr, Ctr Conservat & Res Training, Honolulu, HI 96822 USA.
   [Lamas, Gerardo] Univ Nacl Mayor San Marcos, Museo Hist Nat, Lima 14, Peru.
   [Mapleson, Daniel; Maroja, Luana S.] Univ E Anglia, Sch Comp Sci, Norwich NR4 7TJ, Norfolk, England.
   [Maroja, Luana S.] Williams Coll, Dept Biol, Williamstown, MA 01267 USA.
   [Moxon, Simon] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06520 USA.
   [Papa, Riccardo] Univ Puerto Rico, Dept Biol, Rio Piedras, PR 00931 USA.
   [Ray, David A.] Mississippi State Univ, Dept Biochem Mol Biol Entomol & Plant Pathol, Mississippi State, MS 39762 USA.
   [Ray, David A.] Mississippi State Univ, Inst Genom Biocomp & Biotechnol, Mississippi State, MS 39759 USA.
   [Salzberg, Steven L.] Johns Hopkins Univ, McKusick Nathans Inst Genet Med, Baltimore, MD 21205 USA.
   [Supple, Megan A.] N Carolina State Univ, Biomath Program, Raleigh, NC 27695 USA.
   [Wilkinson, Paul A.] Univ Bristol, Sch Biol Sci, Bristol BS8 1UG, Avon, England.
   [Balmuth, Alexi L.; Eland, Cathlene; Gharbi, Karim; Thomson, Marian; Blaxter, Mark L.] Univ Edinburgh, Ashworth Labs, Edinburgh EH9 3JT, Midlothian, Scotland.
   [Gibbs, Richard A.; Han, Yi; Jayaseelan, Joy C.; Kovar, Christie; Mathew, Tittu; Muzny, Donna M.; Ongeri, Fiona; Pu, Ling-Ling; Qu, Jiaxin; Thornton, Rebecca L.; Worley, Kim C.; Wu, Yuan-Qing; Scherer, Steven E.; Richards, Stephen] Baylor Coll Med, Human GenomeSequencing Ctr, Houston, TX 77030 USA.
   [Linares, Mauricio] Univ Nacl Rosario, Fac Ciencias Nat & Matemat, Bogota, Colombia.
   [Linares, Mauricio] Univ Los Andes, Inst Genet, Bogota, Colombia.
   [Mullen, Sean P.] Boston Univ, Dept Biol, Boston, MA 02215 USA.
   [Mallet, James] Harvard Univ, Dept Organism & Evolutionary Biol, Cambridge, MA 02138 USA.
C3 University of London; University College London; University of Cambridge; University of California System; University of California Irvine; University of Edinburgh; Centre National de la Recherche Scientifique (CNRS); CNRS - Institute of Ecology & Environment (INEE); Museum National d'Histoire Naturelle (MNHN); University System of Maryland; University of Maryland College Park; European Molecular Biology Laboratory (EMBL); European Bioinformatics Institute; University of Oxford; Smithsonian Institution; Smithsonian Tropical Research Institute; Universitat Greifswald; Max Planck Society; Imperial College London; Harvard University; University of Exeter; Mississippi State University; University of East Anglia; University of Texas System; University of Texas Austin; University of Texas System; University of Texas Austin; Commonwealth Scientific & Industrial Research Organisation (CSIRO); Ecosystem Sciences; North Carolina State University; Universite Paris Saclay; Sorbonne Universite; INRAE; University of Cambridge; California Academy of Sciences; University of Hawaii System; University of Hawaii Manoa; Universidad Nacional Mayor de San Marcos; University of East Anglia; Williams College; Yale University; University of Puerto Rico; University of Puerto Rico Rio Piedras; University of Puerto Rico Medical Sciences Campus; Mississippi State University; Mississippi State University; Johns Hopkins University; North Carolina State University; University of Bristol; University of Edinburgh; Baylor College of Medicine; Universidad de los Andes (Colombia); Boston University; Harvard University
RP Mallet, J (corresponding author), UCL, Dept Genet Evolut & Environm, Gower St, London WC1E 6BT, England.
EM jmallet@oeb.harvard.edu
FU Leverhulme Trust; John Fell Fund; Christ Church College, Oxford; Royal Society; NSF; NIH; CNRS; ERC; Banco de la Republica; COLCIENCAS; BBSRC; National Human Genome Research Institute [R01HG006677] Funding Source: NIH RePORTER; Biotechnology and Biological Sciences Research Council [BB/E006191/1, BB/G006903/1, BB/H01439X/1, BB/G530425/1, BB/G00661X/1, BB/H014357/1, BB/H014268/1] Funding Source: researchfish; Medical Research Council [G0900740] Funding Source: researchfish; Division Of Environmental Biology; Direct For Biological Sciences [1020355, 1020136, 0844244, 1316037] Funding Source: National Science Foundation; Division Of Integrative Organismal Systems; Direct For Biological Sciences [1305686] Funding Source: National Science Foundation; Div Of Biological Infrastructure; Direct For Biological Sciences [0959864, 0905698] Funding Source: National Science Foundation; BBSRC [BB/H014357/1, BB/G00661X/1, BB/G530425/1, BB/H014268/1, BB/H01439X/1, BB/G006903/1, BB/E006191/1] Funding Source: UKRI; MRC [G0900740] Funding Source: UKRI
NR 27
TC 910
Z9 1135
U1 8
U2 639
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 5
PY 2012
VL 487
IS 7405
BP 94
EP 98
DI 10.1038/nature11041
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 968LM
UT WOS:000305982900057
PM 22722851
DA 2026-03-09
ER

PT J
AU Malanchi, I
   Santamaria-Martínez, A
   Susanto, E
   Peng, H
   Lehr, HA
   Delaloye, JF
   Huelsken, J
AF Malanchi, Ilaria
   Santamaria-Martinez, Albert
   Susanto, Evelyn
   Peng, Hong
   Lehr, Hans-Anton
   Delaloye, Jean-Francois
   Huelsken, Joerg
TI Interactions between cancer stem cells and their niche govern metastatic colonization
SO NATURE
LA English
DT Article
ID tumor-initiating cells; periostin-null mice; breast-cancer; mammary-tumors; beta-catenin; mouse model; long-term; expression; identification; dissemination
AB Metastatic growth in distant organs is the major cause of cancer mortality. The development of metastasis is a multistage process with several rate-limiting steps(1). Although dissemination of tumour cells seems to be an early and frequent event(2), the successful initiation of metastatic growth, a process termed 'metastatic colonization', is inefficient for many cancer types and is accomplished only by a minority of cancer cells that reach distant sites(3,4). Prevalent target sites are characteristic of many tumour entities(5), suggesting that inadequate support by distant tissues contributes to the inefficiency of the metastatic process. Here we show that a small population of cancer stem cells is critical for metastatic colonization, that is, the initial expansion of cancer cells at the secondary site, and that stromal niche signals are crucial to this expansion process. We find that periostin (POSTN), a component of the extracellular matrix, is expressed by fibroblasts in the normal tissue and in the stroma of the primary tumour. Infiltrating tumour cells need to induce stromal POSTN expression in the secondary target organ (in this case lung) to initiate colonization. POSTN is required to allow cancer stem cell maintenance, and blocking its function prevents metastasis. POSTN recruits Wnt ligands and thereby increases Wnt signalling in cancer stem cells. We suggest that the education of stromal cells by infiltrating tumour cells is an important step in metastatic colonization and that preventing de novo niche formation may be a novel strategy for the treatment of metastatic disease.
C1 [Malanchi, Ilaria; Santamaria-Martinez, Albert; Susanto, Evelyn; Peng, Hong; Huelsken, Joerg] Swiss Inst Expt Canc Res, Ecole Polytech Fed Lausanne, CH-1015 Lausanne, Switzerland.
   [Malanchi, Ilaria; Santamaria-Martinez, Albert; Susanto, Evelyn; Peng, Hong; Huelsken, Joerg] Natl Ctr Competence Res Mol Oncol, CH-1015 Lausanne, Switzerland.
   [Peng, Hong] So Med Univ, Nanfang Hosp, Dept Otorhinolaryngol Head & Neck Surg, Guangzhou 510515, Guangdong, Peoples R China.
   [Lehr, Hans-Anton] Univ Lausanne, CHUV, Univ Inst Pathol, CH-1011 Lausanne, Switzerland.
   [Delaloye, Jean-Francois] CHU Vaudois, Dept Obstet & Gynecol, CH-1011 Lausanne, Switzerland.
C3 Swiss Institute Experimental Cancer Research; Swiss Federal Institutes of Technology Domain; Ecole Polytechnique Federale de Lausanne; Southern Medical University - China; University of Lausanne; Centre Hospitalier Universitaire Vaudois (CHUV); University of Lausanne; Centre Hospitalier Universitaire Vaudois (CHUV)
RP Huelsken, J (corresponding author), Swiss Inst Expt Canc Res, Ecole Polytech Fed Lausanne, CH-1015 Lausanne, Switzerland.
EM joerg.huelsken@epfl.ch
FU Swiss League against Cancer; SNF; NCCR in Molecular Oncology; Anna Fuller Fund; Debiopharm
NR 34
TC 1089
Z9 1250
U1 1
U2 343
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JAN 5
PY 2012
VL 481
IS 7379
BP 85
EP U95
DI 10.1038/nature10694
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 872VD
UT WOS:000298836900034
PM 22158103
DA 2026-03-09
ER

PT J
AU Besnard, J
   Ruda, GF
   Setola, V
   Abecassis, K
   Rodriguiz, RM
   Huang, XP
   Norval, S
   Sassano, MF
   Shin, AI
   Webster, LA
   Simeons, FRC
   Stojanovski, L
   Prat, A
   Seidah, NG
   Constam, DB
   Bickerton, GR
   Read, KD
   Wetsel, WC
   Gilbert, IH
   Roth, BL
   Hopkins, AL
AF Besnard, Jeremy
   Ruda, Gian Filippo
   Setola, Vincent
   Abecassis, Keren
   Rodriguiz, Ramona M.
   Huang, Xi-Ping
   Norval, Suzanne
   Sassano, Maria F.
   Shin, Antony I.
   Webster, Lauren A.
   Simeons, Frederick R. C.
   Stojanovski, Laste
   Prat, Annik
   Seidah, Nabil G.
   Constam, Daniel B.
   Bickerton, G. Richard
   Read, Kevin D.
   Wetsel, William C.
   Gilbert, Ian H.
   Roth, Bryan L.
   Hopkins, Andrew L.
TI Automated design of ligands to polypharmacological profiles
SO NATURE
LA English
DT Article
ID de-novo design; drug-discovery; small-molecule; identification; optimization; pharmacology; antagonists; inhibitors; prediction; program
AB The clinical efficacy and safety of a drug is determined by its activity profile across many proteins in the proteome. However, designing drugs with a specific multi-target profile is both complex and difficult. Therefore methods to design drugs rationally a priori against profiles of several proteins would have immense value in drug discovery. Here we describe a new approach for the automated design of ligands against profiles of multiple drug targets. The method is demonstrated by the evolution of an approved acetylcholinesterase inhibitor drug into brain-penetrable ligands with either specific polypharmacology or exquisite selectivity profiles for G-protein-coupled receptors. Overall, 800 ligand-target predictions of prospectively designed ligands were tested experimentally, of which 75% were confirmed to be correct. We also demonstrate target engagement in vivo. The approach can be a useful source of drug leads when multi-target profiles are required to achieve either selectivity over other drug targets or a desired polypharmacology.
C1 [Besnard, Jeremy; Ruda, Gian Filippo; Abecassis, Keren; Norval, Suzanne; Webster, Lauren A.; Simeons, Frederick R. C.; Stojanovski, Laste; Bickerton, G. Richard; Read, Kevin D.; Gilbert, Ian H.; Hopkins, Andrew L.] Univ Dundee, Coll Life Sci, Div Biol Chem & Drug Discovery, Dundee DD1 5EH, Scotland.
   [Setola, Vincent; Huang, Xi-Ping; Roth, Bryan L.] Univ N Carolina Chapel Hill, Sch Med, Dept Pharmacol, NIMH Psychoact Drug Screening Program, Chapel Hill, NC 27759 USA.
   [Rodriguiz, Ramona M.; Shin, Antony I.; Wetsel, William C.] Duke Univ, Sch Med, Mouse Behav & Neuroendocrine Anal Core Facil, Durham, NC 27710 USA.
   [Sassano, Maria F.; Roth, Bryan L.] Univ N Carolina Chapel Hill, Sch Med, Div Chem Biol & Med Chem, Chapel Hill, NC 27759 USA.
   [Prat, Annik; Seidah, Nabil G.] Univ Montreal, Clin Res Inst Montreal IRCM, Lab Biochem Neuroendocrinol, Montreal, PQ H2W 1R7, Canada.
   [Constam, Daniel B.] Ecole Polytech Fed Lausanne EPFL SV ISREC, CH-1015 Lausanne, Switzerland.
   [Wetsel, William C.] Duke Univ, Sch Med, Dept Psychiat & Behav Sci, Durham, NC 27710 USA.
   [Wetsel, William C.] Duke Univ, Sch Med, Dept Cell Biol, Durham, NC 27710 USA.
   [Wetsel, William C.] Duke Univ, Sch Med, Dept Neurobiol, Durham, NC 27710 USA.
C3 University of Dundee; University of North Carolina; University of North Carolina Chapel Hill; National Institutes of Health (NIH) - USA; NIH National Institute of Mental Health (NIMH); Duke University; University of North Carolina; University of North Carolina Chapel Hill; Universite de Montreal; Institut de Recherche Clinique de Montreal (IRCM); Swiss Institute Experimental Cancer Research; Swiss Federal Institutes of Technology Domain; Ecole Polytechnique Federale de Lausanne; Duke University; Duke University; Duke University
RP Hopkins, AL (corresponding author), Univ Dundee, Coll Life Sci, Div Biol Chem & Drug Discovery, Dundee DD1 5EH, Scotland.
EM bryan_roth@med.unc.edu; a.hopkins@dundee.ac.uk
FU SULSA [HR07019]; BBSRC Doctoral Training Programme; BBSRC Pathfinder [BB/FOF/PF/15/09]; BBSRC [BB/J010510/1]; University of Dundee's Pump Priming Fund for Translational Medical Research; National Institutes of Health (NIH) [MH082441]; Wellcome Trust [WT 083481]; North Carolina Biotechnology Center; Michael Hooker Chair of Pharmacology; BBSRC [BB/J010510/1] Funding Source: UKRI; Biotechnology and Biological Sciences Research Council [BB/J010510/1] Funding Source: researchfish
NR 58
TC 670
Z9 769
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 DEC 13
PY 2012
VL 492
IS 7428
BP 215
EP +
DI 10.1038/nature11691
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 053GM
UT WOS:000312259300034
PM 23235874
DA 2026-03-09
ER

PT J
AU Huber, D
   Gutnisky, DA
   Peron, S
   O'Connor, DH
   Wiegert, JS
   Tian, L
   Oertner, TG
   Looger, LL
   Svoboda, K
AF Huber, D.
   Gutnisky, D. A.
   Peron, S.
   O'Connor, D. H.
   Wiegert, J. S.
   Tian, L.
   Oertner, T. G.
   Looger, L. L.
   Svoboda, K.
TI Multiple dynamic representations in the motor cortex during sensorimotor learning
SO NATURE
LA English
DT Article
ID cellular resolution; object localization; neural activity; barrel cortex; neurons; organization; mouse; microstimulation; connections; plasticity
AB The mechanisms linking sensation and action during learning are poorly understood. Layer 2/3 neurons in the motor cortex might participate in sensorimotor integration and learning; they receive input from sensory cortex and excite deep layer neurons, which control movement. Here we imaged activity in the same set of layer 2/3 neurons in the motor cortex over weeks, while mice learned to detect objects with their whiskers and report detection with licking. Spatially intermingled neurons represented sensory (touch) and motor behaviours (whisker movements and licking). With learning, the population-level representation of task-related licking strengthened. In trained mice, population-level representations were redundant and stable, despite dynamism of single-neuron representations. The activity of a subpopulation of neurons was consistent with touch driving licking behaviour. Our results suggest that ensembles of motor cortex neurons couple sensory input to multiple, related motor programs during learning.
C1 [Huber, D.; Gutnisky, D. A.; Peron, S.; O'Connor, D. H.; Tian, L.; Looger, L. L.; Svoboda, K.] Howard Hughes Med Inst, Ashburn, VA 20147 USA.
   [Wiegert, J. S.; Oertner, T. G.] Ctr Mol Neurobiol Hamburg, D-20251 Hamburg, Germany.
C3 Howard Hughes Medical Institute
RP Svoboda, K (corresponding author), Howard Hughes Med Inst, Janelia Farm Res Campus,19700 Helix Dr, Ashburn, VA 20147 USA.
EM svobodak@janelia.hhmi.org
FU Howard Hughes Medical Institute Funding Source: Medline
NR 59
TC 383
Z9 472
U1 1
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 26
PY 2012
VL 484
IS 7395
BP 473
EP U95
DI 10.1038/nature11039
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 931FF
UT WOS:000303200400042
PM 22538608
DA 2026-03-09
ER

PT J
AU Mauldin, RL
   Berndt, T
   Sipilä, M
   Paasonen, P
   Petäjä, T
   Kim, S
   Kurtén, T
   Stratmann, F
   Kerminen, VM
   Kulmala, M
AF Mauldin, R. L., III
   Berndt, T.
   Sipilae, M.
   Paasonen, P.
   Petaja, T.
   Kim, S.
   Kurten, T.
   Stratmann, F.
   Kerminen, V-M
   Kulmala, M.
TI A new atmospherically relevant oxidant of sulphur dioxide
SO NATURE
LA English
DT Article
ID oh measurements; forest; oxidation; ozone; acid; so2; mechanism; system; ch2oo; air
AB Atmospheric oxidation is a key phenomenon that connects atmospheric chemistry with globally challenging environmental issues, such as climate change(1), stratospheric ozone loss(2), acidification of soils and water(3), and health effects of air quality(4). Ozone, the hydroxyl radical and the nitrate radical are generally considered to be the dominant oxidants that initiate the removal of trace gases, including pollutants, from the atmosphere. Here we present atmospheric observations from a boreal forest region in Finland, supported by laboratory experiments and theoretical considerations, that allow us to identify another compound, probably a stabilized Criegee intermediate (a carbonyl oxide with two free-radical sites) or its derivative, which has a significant capacity to oxidize sulphur dioxide and potentially other trace gases. This compound probably enhances the reactivity of the atmosphere, particularly with regard to the production of sulphuric acid, and consequently atmospheric aerosol formation. Our findings suggest that this new atmospherically relevant oxidation route is important relative to oxidation by the hydroxyl radical, at least at moderate concentrations of that radical. We also find that the oxidation chemistry of this compound seems to be tightly linked to the presence of alkenes of biogenic origin.
C1 [Mauldin, R. L., III; Sipilae, M.; Paasonen, P.; Petaja, T.; Kurten, T.; Kerminen, V-M; Kulmala, M.] Univ Helsinki, Dept Phys, FI-00014 Helsinki, Finland.
   [Mauldin, R. L., III; Kim, S.] Natl Ctr Atmospher Res, Boulder, CO 80307 USA.
   [Mauldin, R. L., III] Univ Colorado Boulder, Dept Atmospher & Ocean Sci, Boulder, CO 80309 USA.
   [Berndt, T.; Sipilae, M.; Stratmann, F.] Leibniz Inst Tropospher Res, D-04318 Leipzig, Germany.
   [Sipilae, M.] Helsinki Inst Phys, FI-00014 Helsinki, Finland.
   [Kurten, T.] Univ Helsinki, Dept Chem, FI-00014 Helsinki, Finland.
C3 University of Helsinki; National Center Atmospheric Research (NCAR) - USA; University of Colorado System; University of Colorado Boulder; Leibniz Association; Leibniz Institut fur Tropospharenforschung (TROPOS); Helsinki Institute of Physics; University of Helsinki
RP Mauldin, RL (corresponding author), Univ Helsinki, Dept Phys, FI-00014 Helsinki, Finland.
EM roy.mauldin@helsinki.fi
FU European Commission Sixth Framework programme project EUCAARI [036833-2]; Academy of Finland [251427, 139656, 141135]; European Research Council (ATMNUCLE); Kone Foundation; Vaisala Foundation; Maj and Tor Nessling Foundation [2010212]; Otto Malm Foundation; US National Science Foundation; Academy of Finland (AKA) [141135, 251427] Funding Source: Academy of Finland (AKA)
NR 34
TC 428
Z9 480
U1 10
U2 699
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 9
PY 2012
VL 488
IS 7410
BP 193
EP 196
DI 10.1038/nature11278
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 985LE
UT WOS:000307267000029
PM 22874964
DA 2026-03-09
ER

PT J
AU Koschorreck, M
   Pertot, D
   Vogt, E
   Fröhlich, B
   Feld, M
   Köhl, M
AF Koschorreck, Marco
   Pertot, Daniel
   Vogt, Enrico
   Froehlich, Bernd
   Feld, Michael
   Koehl, Michael
TI Attractive and repulsive Fermi polarons in two dimensions
SO NATURE
LA English
DT Article
ID spectroscopy
AB The dynamics of a single impurity in an environment is a fundamental problem in many-body physics. In the solid state, a well known case is an impurity coupled to a bosonic bath (such as lattice vibrations); the impurity and its accompanying lattice distortion form a new entity, a polaron. This quasiparticle plays an important role in the spectral function of high-transition-temperature superconductors, as well as in colossal magnetoresistance in manganites(1). For impurities in a fermionic bath, studies have considered heavy or immobile impurities which exhibit Anderson's orthogonality catastrophe(2) and the Kondo effect(3). More recently, mobile impurities have moved into the focus of research, and they have been found to form new quasiparticles known as Fermi polarons(4-7). The Fermi polaron problem constitutes the extreme, but conceptually simple, limit of two important quantum many-body problems: the crossover between a molecular Bose-Einstein condensate and a superfluid with BCS (Bardeen-Cooper-Schrieffer) pairing with spin-imbalance(8) for attractive interactions, and Stoner's itinerant ferromagnetism(9) for repulsive interactions. It has been proposed that such quantum phases (and other elusive exotic states) might become realizable in Fermi gases confined to two dimensions(10,11). Their stability and observability are intimately related to the theoretically debated(12-16) properties of the Fermi polaron in a two-dimensional Fermi gas. Here we create and investigate Fermi polarons in a two-dimensional, spin-imbalanced Fermi gas, measuring their spectral function using momentum-resolved photoemission spectroscopy(17-19). For attractive interactions, we find evidence for a disputed pairing transition between polarons and tightly bound dimers, which provides insight into the elementary pairing mechanism of imbalanced, strongly coupled two-dimensional Fermi gases. Additionally, for repulsive interactions, we study novel quasiparticles-repulsive polarons-the lifetime of which determines the possibility of stabilizing repulsively interacting Fermi systems.
C1 [Koschorreck, Marco; Pertot, Daniel; Vogt, Enrico; Froehlich, Bernd; Feld, Michael; Koehl, Michael] Univ Cambridge, Cavendish Lab, Cambridge CB3 0HE, England.
C3 University of Cambridge
RP Köhl, M (corresponding author), Univ Cambridge, Cavendish Lab, JJ Thomson Ave, Cambridge CB3 0HE, England.
EM mk540@cam.ac.uk
FU EPSRC [EP/G029547/1]; Daimler-Benz Foundation; Studienstiftung; DAAD; EPSRC [EP/G029547/1] Funding Source: UKRI; Engineering and Physical Sciences Research Council [EP/G029547/1] Funding Source: researchfish
NR 32
TC 397
Z9 427
U1 0
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 MAY 31
PY 2012
VL 485
IS 7400
BP 619
EP +
DI 10.1038/nature11151
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 949WP
UT WOS:000304608000043
PM 22660322
DA 2026-03-09
ER

PT J
AU Loh, ND
   Hampton, CY
   Martin, AV
   Starodub, D
   Sierra, RG
   Barty, A
   Aquila, A
   Schulz, J
   Lomb, L
   Steinbrener, J
   Shoeman, RL
   Kassemeyer, S
   Bostedt, C
   Bozek, J
   Epp, SW
   Erk, B
   Hartmann, R
   Rolles, D
   Rudenko, A
   Rudek, B
   Foucar, L
   Kimmel, N
   Weidenspointner, G
   Hauser, G
   Holl, P
   Pedersoli, E
   Liang, M
   Hunter, MM
   Gumprecht, L
   Coppola, N
   Wunderer, C
   Graafsma, H
   Maia, FRNC
   Ekeberg, T
   Hantke, M
   Fleckenstein, H
   Hirsemann, H
   Nass, K
   White, TA
   Tobias, HJ
   Farquar, GR
   Benner, WH
   Hau-Riege, SP
   Reich, C
   Hartmann, A
   Soltau, H
   Marchesini, S
   Bajt, S
   Barthelmess, M
   Bucksbaum, P
   Hodgson, KO
   Strüder, L
   Ullrich, J
   Frank, M
   Schlichting, I
   Chapman, HN
   Bogan, MJ
AF Loh, N. D.
   Hampton, C. Y.
   Martin, A. V.
   Starodub, D.
   Sierra, R. G.
   Barty, A.
   Aquila, A.
   Schulz, J.
   Lomb, L.
   Steinbrener, J.
   Shoeman, R. L.
   Kassemeyer, S.
   Bostedt, C.
   Bozek, J.
   Epp, S. W.
   Erk, B.
   Hartmann, R.
   Rolles, D.
   Rudenko, A.
   Rudek, B.
   Foucar, L.
   Kimmel, N.
   Weidenspointner, G.
   Hauser, G.
   Holl, P.
   Pedersoli, E.
   Liang, M.
   Hunter, M. M.
   Gumprecht, L.
   Coppola, N.
   Wunderer, C.
   Graafsma, H.
   Maia, F. R. N. C.
   Ekeberg, T.
   Hantke, M.
   Fleckenstein, H.
   Hirsemann, H.
   Nass, K.
   White, T. A.
   Tobias, H. J.
   Farquar, G. R.
   Benner, W. H.
   Hau-Riege, S. P.
   Reich, C.
   Hartmann, A.
   Soltau, H.
   Marchesini, S.
   Bajt, S.
   Barthelmess, M.
   Bucksbaum, P.
   Hodgson, K. O.
   Strueder, L.
   Ullrich, J.
   Frank, M.
   Schlichting, I.
   Chapman, H. N.
   Bogan, M. J.
TI Fractal morphology, imaging and mass spectrometry of single aerosol particles in flight
SO NATURE
LA English
DT Article
ID free-electron laser; optical-property; soot aerosols; black carbon; mixing state; scattering; climate; flame
AB The morphology of micrometre-size particulate matter is of critical importance in fields ranging from toxicology(1) to climate science(2), yet these properties are surprisingly difficult to measure in the particles' native environment. Electron microscopy requires collection of particles on a substrate(3); visible light scattering provides insufficient resolution(4); and X-ray synchrotron studies have been limited to ensembles of particles(5). Here we demonstrate an in situ method for imaging individual sub-micrometre particles to nanometre resolution in their native environment, using intense, coherent X-ray pulses from the Linac Coherent Light Source(6) free-electron laser. We introduced individual aerosol particles into the pulsed X-ray beam, which is sufficiently intense that diffraction from individual particles can be measured for morphological analysis. At the same time, ion fragments ejected from the beam were analysed using mass spectrometry, to determine the composition of single aerosol particles. Our results show the extent of internal dilation symmetry of individual soot particles subject to non-equilibrium aggregation, and the surprisingly large variability in their fractal dimensions. More broadly, our methods can be extended to resolve both static and dynamic morphology of general ensembles of disordered particles. Such general morphology has implications in topics such as solvent accessibilities in proteins(7), vibrational energy transfer by the hydrodynamic interaction of amino acids(8), and large-scale production of nanoscale structures by flame synthesis(9).
C1 [Loh, N. D.; Hampton, C. Y.; Starodub, D.; Sierra, R. G.; Bucksbaum, P.; Hodgson, K. O.; Bogan, M. J.] PULSE Inst, SLAC Natl Accelerator Lab, Menlo Pk, CA 94025 USA.
   [Martin, A. V.; Barty, A.; Aquila, A.; Schulz, J.; Liang, M.; Gumprecht, L.; Fleckenstein, H.; Nass, K.; White, T. A.; Chapman, H. N.] DESY, Ctr Free Electron Laser Sci, D-22607 Hamburg, Germany.
   [Aquila, A.; Schulz, J.; Coppola, N.] European XFEL GmbH, D-22761 Hamburg, Germany.
   [Lomb, L.; Steinbrener, J.; Shoeman, R. L.; Kassemeyer, S.; Rolles, D.; Foucar, L.; Schlichting, I.] Max Planck Inst Med Res, D-69120 Heidelberg, Germany.
   [Bostedt, C.; Bozek, J.] SLAC Natl Accelerator Lab, LCLS, Menlo Pk, CA 94025 USA.
   [Epp, S. W.; Erk, B.; Rolles, D.; Rudenko, A.; Rudek, B.; Foucar, L.; Schlichting, I.] Ctr Free Electron Laser Sci CFEL, Max Planck Adv Study Grp, D-22607 Hamburg, Germany.
   [Epp, S. W.; Erk, B.; Rudenko, A.; Rudek, B.; Ullrich, J.] Max Planck Inst Kernphys, D-69117 Heidelberg, Germany.
   [Hartmann, R.; Holl, P.; Reich, C.; Hartmann, A.; Soltau, H.] PNSensor GmbH, D-81739 Munich, Germany.
   [Kimmel, N.; Weidenspointner, G.; Hauser, G.; Strueder, L.] Max Planck Inst Halbleiterlab, D-81739 Munich, Germany.
   [Kimmel, N.; Weidenspointner, G.; Hauser, G.; Strueder, L.] Max Planck Inst Extraterr Phys, D-85741 Garching, Germany.
   [Pedersoli, E.] Sincrotrone Trieste, Microscopy Sect, I-34149 Trieste, Italy.
   [Hunter, M. M.; Farquar, G. R.; Benner, W. H.; Hau-Riege, S. P.; Frank, M.] Lawrence Livermore Natl Lab, Livermore, CA 94551 USA.
   [Wunderer, C.; Graafsma, H.; Hirsemann, H.; Bajt, S.; Barthelmess, M.] DESY, Photon Sci, D-22607 Hamburg, Germany.
   [Maia, F. R. N. C.] Natl Energy Res Sci Comp Ctr NERSC, Berkeley, CA 94720 USA.
   [Ekeberg, T.; Hantke, M.] Uppsala Univ, Dept Cell & Mol Biol, Lab Mol Biophys, SE-75124 Uppsala, Sweden.
   [Nass, K.; Chapman, H. N.] Univ Hamburg, D-22761 Hamburg, Germany.
   [Tobias, H. J.] Cornell Univ, Div Nutr Sci, Ithaca, NY 14853 USA.
   [Marchesini, S.] Lawrence Berkeley Natl Lab, Berkeley, CA 94720 USA.
C3 Stanford University; United States Department of Energy (DOE); SLAC National Accelerator Laboratory; Helmholtz Association; Deutsches Elektronen-Synchrotron (DESY); European XFEL; Max Planck Society; Stanford University; United States Department of Energy (DOE); SLAC National Accelerator Laboratory; Max Planck Society; Max Planck Society; PNSensor GmbH; Max Planck Society; Max Planck Society; Elettra Sincrotrone Trieste; United States Department of Energy (DOE); Lawrence Livermore National Laboratory; Helmholtz Association; Deutsches Elektronen-Synchrotron (DESY); Uppsala University; University of Hamburg; Cornell University; United States Department of Energy (DOE); Lawrence Berkeley National Laboratory
RP Loh, ND (corresponding author), PULSE Inst, SLAC Natl Accelerator Lab, 2575 Sand Hill Rd, Menlo Pk, CA 94025 USA.
EM duaneloh@slac.stanford.edu; mbogan@slac.stanford.edu
FU AMOS program within the Chemical Sciences, Geosciences, and Biosciences Division of the Office of Basic Energy Sciences, Office of Science, US Department of Energy; SLAC Laboratory Directed Research and Development Program; Max Planck Society; Hamburg Ministry of Science and Research; Joachim Herz Stiftung as part of the Hamburg Initiative for Excellence in Research (LEXI); Hamburg School for Structure and Dynamics in Infection, CBST at UC [PHY 0120999]; US Department of Energy, National Nuclear Security Administration [DE-AC52-07NA27344]; University of California [09-LR-05-118036-BARA]; Swedish Research Council; European Research Council; Knut och Alice Wallenbergs Stiftelse; DFG Cluster of Excellence at the Munich Centre for Advanced Photonics
NR 31
TC 165
Z9 174
U1 1
U2 284
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUN 28
PY 2012
VL 486
IS 7404
BP 513
EP 517
DI 10.1038/nature11222
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 965IJ
UT WOS:000305760600039
PM 22739316
DA 2026-03-09
ER

PT J
AU Batygin, K
AF Batygin, Konstantin
TI A primordial origin for misalignments between stellar spin axes and planetary orbits
SO NATURE
LA English
DT Article
ID multiple-star-formation; hot jupiters; dynamics; binary; environment; scattering; migration; evolution; rotation; systems
AB The existence of gaseous giant planets whose orbits lie close to their host stars ('hot Jupiters') can largely be accounted for by planetary migration associated with viscous evolution of proto-planetary nebulae(1). Recently, observations of the Rossiter-McLaughlin effect(2) during planetary transits have revealed that a considerable fraction of hot Jupiters are on orbits that are misaligned with respect to the spin axes of their host stars(3). This observation has cast doubt on the importance of disk-driven migration as a mechanism for producing hot Jupiters. Here I show that misaligned orbits can be a natural consequence of disk migration in binary systems whose orbital plane is uncorrelated with the spin axes of the individual stars(4-6). The gravitational torques arising from the dynamical evolution of idealized proto-planetary disks under perturbations from massive distant bodies act to misalign the orbital planes of the disks relative to the spin poles of their host stars. As a result, I suggest that in the absence of strong coupling between the angular momentum of the disk and that of the host star, or of sufficient dissipation that acts to realign the stellar spin axis and the planetary orbits, the fraction of planetary systems (including systems of 'hot Neptunes' and 'super-Earths') whose angular momentum vectors are misaligned with respect to their host stars will be commensurate with the rate of primordial stellar multiplicity.
C1 [Batygin, Konstantin] CALTECH, Div Geol & Planetary Sci, Pasadena, CA 91125 USA.
   [Batygin, Konstantin] Harvard Smithsonian Ctr Astrophys, Inst Theory & Computat, Cambridge, MA 02138 USA.
C3 California Institute of Technology; Smithsonian Astrophysical Observatory; Harvard University; Smithsonian Institution
RP Batygin, K (corresponding author), CALTECH, Div Geol & Planetary Sci, Pasadena, CA 91125 USA.
EM kbatygin@gps.caltech.edu
NR 29
TC 254
Z9 278
U1 0
U2 10
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 15
PY 2012
VL 491
IS 7424
BP 418
EP 420
DI 10.1038/nature11560
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 036MY
UT WOS:000311031600040
PM 23151584
DA 2026-03-09
ER

PT J
AU Nakanishi, K
   Weinberg, DE
   Bartel, DP
   Patel, DJ
AF Nakanishi, Kotaro
   Weinberg, David E.
   Bartel, David P.
   Patel, Dinshaw J.
TI Structure of yeast Argonaute with guide RNA
SO NATURE
LA English
DT Article
ID crystal-structure; recognition; sirna; drosophila; risc; dna; mechanisms; micrornas; cleavage; system
AB The RNA-induced silencing complex, comprising Argonaute and guide RNA, mediates RNA interference. Here we report the 3.2 angstrom crystal structure of Kluyveromyces polysporus Argonaute (KpAGO) fortuitously complexed with guide RNA originating from small-RNA duplexes autonomously loaded and processed by recombinant KpAGO. Despite their diverse sequences, guide-RNA nucleotides 1-8 are positioned similarly, with sequence-independent contacts to bases, phosphates and 2'-hydroxyl groups pre-organizing the backbone of nucleotides 2-8 in a near-A-form conformation. Compared with prokaryotic Argonautes, KpAGO has numerous surface-exposed insertion segments, with a cluster of conserved insertions repositioning the N domain to enable full propagation of guide-target pairing. Compared with Argonautes in inactive conformations, KpAGO has a hydrogen-bond network that stabilizes an expanded and repositioned loop, which inserts an invariant glutamate into the catalytic pocket. Mutation analyses and analogies to ribonuclease H indicate that insertion of this glutamate finger completes a universally conserved catalytic tetrad, thereby activating Argonaute for RNA cleavage.
C1 [Nakanishi, Kotaro; Patel, Dinshaw J.] Mem Sloan Kettering Canc Ctr, Struct Biol Program, New York, NY 10065 USA.
   [Weinberg, David E.; Bartel, David P.] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA.
   [Weinberg, David E.; Bartel, David P.] MIT, Howard Hughes Med Inst, Cambridge, MA 02139 USA.
   [Weinberg, David E.; Bartel, David P.] MIT, Dept Biol, Cambridge, MA 02139 USA.
C3 Memorial Sloan Kettering Cancer Center; Massachusetts Institute of Technology (MIT); Whitehead Institute; Howard Hughes Medical Institute; Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT)
RP Patel, DJ (corresponding author), Mem Sloan Kettering Canc Ctr, Struct Biol Program, New York, NY 10065 USA.
EM dbartel@wi.mit.edu; pateld@mskcc.org
FU National Institutes of Health [AI068776, GM61835]; Human Frontier Science Program Long-term Fellowship; Japan Society for the Promotion of Science; National Science Foundation graduate research fellowship; National Cancer Institute [P30CA008748] Funding Source: NIH RePORTER
NR 64
TC 287
Z9 340
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 JUN 21
PY 2012
VL 486
IS 7403
BP 368
EP +
DI 10.1038/nature11211
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 961LV
UT WOS:000305466800036
PM 22722195
DA 2026-03-09
ER

PT J
AU Bernitt, S
   Brown, GV
   Rudolph, JK
   Steinbrügge, R
   Graf, A
   Leutenegger, M
   Epp, SW
   Eberle, S
   Kubicek, K
   Mäckel, V
   Simon, MC
   Träbert, E
   Magee, EW
   Beilmann, C
   Hell, N
   Schippers, S
   Müller, A
   Kahn, SM
   Surzhykov, A
   Harman, Z
   Keitel, CH
   Clementson, J
   Porter, FS
   Schlotter, W
   Turner, JJ
   Ullrich, J
   Beiersdorfer, P
   López-Urrutia, JRC
AF Bernitt, S.
   Brown, G. V.
   Rudolph, J. K.
   Steinbruegge, R.
   Graf, A.
   Leutenegger, M.
   Epp, S. W.
   Eberle, S.
   Kubicek, K.
   Maeckel, V.
   Simon, M. C.
   Traebert, E.
   Magee, E. W.
   Beilmann, C.
   Hell, N.
   Schippers, S.
   Mueller, A.
   Kahn, S. M.
   Surzhykov, A.
   Harman, Z.
   Keitel, C. H.
   Clementson, J.
   Porter, F. S.
   Schlotter, W.
   Turner, J. J.
   Ullrich, J.
   Beiersdorfer, P.
   Lopez-Urrutia, J. R. Crespo
TI An unexpectedly low oscillator strength as the origin of the Fe XVII emission problem
SO NATURE
LA English
DT Article
ID spectral-line intensity; atomic data; laboratory measurements; chandra; solar; density
AB Highly charged iron (Fe16+, here referred to as Fe XVII) produces some of the brightest X-ray emission lines from hot astrophysical objects(1), including galaxy clusters and stellar coronae, and it dominates the emission of the Sun at wavelengths near 15 angstroms. The Fe XVII spectrum is, however, poorly fitted by even the best astrophysical models. A particular problem has been that the intensity of the strongest Fe XVII line is generally weaker than predicted(2,3). This has affected the interpretation of observations by the Chandra and XMM-Newton orbiting X-ray missions(1), fuelling a continuing controversy over whether this discrepancy is caused by incomplete modelling of the plasma environment in these objects or by shortcomings in the treatment of the underlying atomic physics. Here we report the results of an experiment in which a target of iron ions was induced to fluoresce by subjecting it to femtosecond X-ray pulses from a free-electron laser(4); our aim was to isolate a key aspect of the quantum mechanical description of the line emission. Surprisingly, we find a relative oscillator strength that is unexpectedly low, differing by 3.6 sigma from the best quantum mechanical calculations. Our measurements suggest that the poor agreement is rooted in the quality of the underlying atomic wavefunctions rather than in insufficient modelling of collisional processes.
C1 [Bernitt, S.; Rudolph, J. K.; Steinbruegge, R.; Epp, S. W.; Eberle, S.; Kubicek, K.; Maeckel, V.; Beilmann, C.; Harman, Z.; Keitel, C. H.; Ullrich, J.; Lopez-Urrutia, J. R. Crespo] Max Planck Inst Kernphys, D-69117 Heidelberg, Germany.
   [Brown, G. V.; Graf, A.; Traebert, E.; Magee, E. W.; Hell, N.; Clementson, J.; Beiersdorfer, P.] Lawrence Livermore Natl Lab, Livermore, CA 94550 USA.
   [Rudolph, J. K.; Schippers, S.; Mueller, A.] Univ Giessen, Inst Atom & Mol Phys, D-35392 Giessen, Germany.
   [Leutenegger, M.; Porter, F. S.] NASA, Goddard Space Flight Ctr, Greenbelt, MD 20771 USA.
   [Leutenegger, M.] Univ Maryland, Dept Phys, Baltimore, MD 21250 USA.
   [Epp, S. W.] Ctr Free Electron Laser Sci, Max Planck Adv Study Grp, D-22607 Hamburg, Germany.
   [Simon, M. C.] TRIUMF, Vancouver, BC V6T 2A3, Canada.
   [Hell, N.] Univ Erlangen Nurnberg, Dr Karl Remeis Sternwarte Bamberg, D-96049 Bamberg, Germany.
   [Hell, N.] Univ Erlangen Nurnberg, Erlangen Ctr Astroparticle Phys, D-96049 Bamberg, Germany.
   [Kahn, S. M.] SLAC Natl Accelerator Lab, Kavli Inst Particle Astrophys & Cosmol, Menlo Pk, CA 94025 USA.
   [Surzhykov, A.] Heidelberg Univ, Inst Phys, D-69120 Heidelberg, Germany.
   [Surzhykov, A.] GSI Helmholtzzentrum Schwerionenforsch GmbH, D-64291 Darmstadt, Germany.
   [Harman, Z.] ExtreMe Matter Inst EMMI, D-64291 Darmstadt, Germany.
   [Schlotter, W.; Turner, J. J.] SLAC Natl Accelerator Lab, Linac Coherent Light Source, Menlo Pk, CA 94025 USA.
C3 Max Planck Society; United States Department of Energy (DOE); Lawrence Livermore National Laboratory; Justus Liebig University Giessen; National Aeronautics & Space Administration (NASA); NASA Goddard Space Flight Center; University System of Maryland; University of Maryland Baltimore; Max Planck Society; University of British Columbia; University of Erlangen Nuremberg; University of Erlangen Nuremberg; Stanford University; United States Department of Energy (DOE); SLAC National Accelerator Laboratory; Ruprecht Karls University Heidelberg; Helmholtz Association; GSI Helmholtz-Center for Heavy Ion Research; Stanford University; United States Department of Energy (DOE); SLAC National Accelerator Laboratory
RP Bernitt, S (corresponding author), Max Planck Inst Kernphys, D-69117 Heidelberg, Germany.
EM sven.bernitt@mpi-hd.mpg.de
FU LCLS; Stanford University through the Stanford Institute for Materials Energy Sciences; Stanford University through Lawrence Berkeley National Laboratory; University of Hamburg through the BMBF; Center for Free Electron Laser Science; US Department of Energy; Helmholtz Alliance.; Helmholtz association; EMMI; BMBF; Deutsche Forschungsgemeinschaft
NR 30
TC 148
Z9 158
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 DEC 13
PY 2012
VL 492
IS 7428
BP 225
EP 228
DI 10.1038/nature11627
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 053GM
UT WOS:000312259300036
PM 23235875
DA 2026-03-09
ER

PT J
AU Feng, Y
   Li, WF
   Li, J
   Wang, JW
   Ge, JP
   Xu, D
   Liu, YJ
   Wu, KQ
   Zeng, QY
   Wu, JW
   Tian, CL
   Zhou, B
   Yang, MJ
AF Feng, Yue
   Li, Wenfei
   Li, Jian
   Wang, Jiawei
   Ge, Jingpeng
   Xu, Duo
   Liu, Yanjing
   Wu, Kaiqi
   Zeng, Qingyin
   Wu, Jia-Wei
   Tian, Changlin
   Zhou, Bing
   Yang, Maojun
TI Structural insight into the type-II mitochondrial NADH dehydrogenases
SO NATURE
LA English
DT Article
ID quinone oxidoreductase; complex-i; saccharomyces-cerevisiae; respiratory-chain; electron-transfer; proton; ndi1; identification; software; oxidase
AB The single-component type-II NADH dehydrogenases (NDH-2s) serve as alternatives to the multisubunit respiratory complex I (type-I NADH dehydrogenase (NDH-1), also called NADH: ubiquinone oxidoreductase; EC 1.6.5.3) in catalysing electron transfer from NADH to ubiquinone in the mitochondrial respiratory chain(1). The yeast NDH-2 (Ndi1) oxidizes NADH on the matrix side and reduces ubiquinone to maintain mitochondrial NADH/NAD(+) homeostasis. Ndi1 is a potential therapeutic agent for human diseases caused by complex I defects(2-9), particularly Parkinson's disease, because its expression restores the mitochondrial activity in animals with complex I deficiency. NDH-2s in pathogenic microorganisms are viable targets for new antibiotics(10,11). Here we solve the crystal structures of Ndi1 in its substrate-free, NADH-, ubiquinone-and NADH-ubiquinone-bound states, to help understand the catalytic mechanism of NDH-2s. We find that Ndi1 homodimerization through its carboxy-terminal domain is critical for its catalytic activity and membrane targeting. The structures reveal two ubiquinone-binding sites (UQ(I) and UQ(II)) in Ndi1. NADH and UQ(I) can bind to Ndi1 simultaneously to form a substrate-protein complex. We propose that UQ(I) interacts with FAD to act as an intermediate for electron transfer, and that NADH transfers electrons through this FAD-UQ(I) complex to UQ(II). Together our data reveal the regulatory and catalytic mechanisms of Ndi1 and may facilitate the development or targeting of NDH-2s for potential therapeutic applications.
C1 [Feng, Yue; Li, Wenfei; Li, Jian; Wang, Jiawei; Ge, Jingpeng; Xu, Duo; Wu, Jia-Wei; Zhou, Bing; Yang, Maojun] Tsinghua Univ, State Key Lab Biomembrane & Membrane Biotechnol, Tsinghua Peking Ctr Life Sci, Sch Life Sci, Beijing 100084, Peoples R China.
   [Liu, Yanjing; Zeng, Qingyin] Chinese Acad Sci, Inst Bot, State Key Lab Systemat & Evolutionary Bot, Beijing 100093, Peoples R China.
   [Wu, Kaiqi; Tian, Changlin] Univ Sci & Technol China, Sch Life Sci, Hefei Natl Lab Phys Sci Microscale, Hefei 230026, Anhui, Peoples R China.
   [Tian, Changlin] Chinese Acad Sci, High Magnet Field Lab, Hefei 230031, Anhui, Peoples R China.
C3 Tsinghua University; Chinese Academy of Sciences; Institute of Botany, CAS; Chinese Academy of Sciences; University of Science & Technology of China, CAS; Chinese Academy of Sciences; Hefei Institutes of Physical Science, CAS
RP Yang, MJ (corresponding author), Tsinghua Univ, State Key Lab Biomembrane & Membrane Biotechnol, Tsinghua Peking Ctr Life Sci, Sch Life Sci, Beijing 100084, Peoples R China.
EM maojunyang@tsinghua.edu.cn
FU Ministry of Science and Technology of China [2011CB910502, 2011CB910900, 2012CB911101]; National Natural Science Foundation of China [31030020, 31170679]; Chinese Key Research Plan-Protein Sciences [2011CB911104]
NR 42
TC 113
Z9 126
U1 6
U2 199
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 15
PY 2012
VL 491
IS 7424
BP 478
EP +
DI 10.1038/nature11541
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 036MY
UT WOS:000311031600053
PM 23086143
DA 2026-03-09
ER

PT J
AU Lounkine, E
   Keiser, MJ
   Whitebread, S
   Mikhailov, D
   Hamon, J
   Jenkins, JL
   Lavan, P
   Weber, E
   Doak, AK
   Côté, S
   Shoichet, BK
   Urban, L
AF Lounkine, Eugen
   Keiser, Michael J.
   Whitebread, Steven
   Mikhailov, Dmitri
   Hamon, Jacques
   Jenkins, Jeremy L.
   Lavan, Paul
   Weber, Eckhard
   Doak, Allison K.
   Cote, Serge
   Shoichet, Brian K.
   Urban, Laszlo
TI Large-scale prediction and testing of drug activity on side-effect targets
SO NATURE
LA English
DT Article
ID pharmacology; network; database; identification; inhibition; generation; toxicity; herg
AB Discovering the unintended 'off-targets' that predict adverse drug reactions is daunting by empirical methods alone. Drugs can act on several protein targets, some of which can be unrelated by conventional molecular metrics, and hundreds of proteins have been implicated in side effects. Here we use a computational strategy to predict the activity of 656 marketed drugs on 73 unintended 'side-effect' targets. Approximately half of the predictions were confirmed, either from proprietary databases unknown to the method or by new experimental assays. Affinities for these new off-targets ranged from 1nM to 30 mu M. To explore relevance, we developed an association metric to prioritize those new off-targets that explained side effects better than any known target of a given drug, creating a drug-target-adverse drug reaction network. Among these new associations was the prediction that the abdominal pain side effect of the synthetic oestrogen chlorotrianisene was mediated through its newly discovered inhibition of the enzyme cyclooxygenase-1. The clinical relevance of this inhibition was borne out in whole human blood platelet aggregation assays. This approach may have wide application to de-risking toxicological liabilities in drug discovery.
C1 [Lounkine, Eugen; Whitebread, Steven; Mikhailov, Dmitri; Jenkins, Jeremy L.; Urban, Laszlo] Novartis Inst Biomed Res, Cambridge, MA 02139 USA.
   [Keiser, Michael J.] SeaChange Pharmaceut Inc, San Francisco, CA 94158 USA.
   [Keiser, Michael J.; Doak, Allison K.; Shoichet, Brian K.] Univ Calif San Francisco, Dept Pharmaceut Chem, San Francisco, CA 94158 USA.
   [Hamon, Jacques; Lavan, Paul; Weber, Eckhard; Cote, Serge] Novartis Inst Biomed Res, CH-4056 Basel, Switzerland.
C3 Novartis; Novartis USA; University of California System; University of California San Francisco; Novartis
RP Jenkins, JL (corresponding author), Novartis Inst Biomed Res, Cambridge, MA 02139 USA.
EM jeremy.jenkins@novartis.com; shoichet@cgl.ucsf.edu; laszlo.urban@novartis.com
FU US National Institutes of Health [GM71896, AG002132, GM93456]; QB3 Rogers Family Foundation 'Bridging-the-Gap' Award; National Institute of General Medical Sciences [R01GM071896] Funding Source: NIH RePORTER; National Institute on Aging [P01AG002132] Funding Source: NIH RePORTER
NR 53
TC 694
Z9 784
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 JUN 21
PY 2012
VL 486
IS 7403
BP 361
EP +
DI 10.1038/nature11159
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 961LV
UT WOS:000305466800035
PM 22722194
DA 2026-03-09
ER

PT J
AU Lane, JE
   Kruuk, LEB
   Charmantier, A
   Murie, JO
   Dobson, FS
AF Lane, Jeffrey E.
   Kruuk, Loeske E. B.
   Charmantier, Anne
   Murie, Jan O.
   Dobson, F. Stephen
TI Delayed phenology and reduced fitness associated with climate change in a wild hibernator
SO NATURE
LA English
DT Article
ID columbian ground-squirrels; spermophilus-columbianus; phenotypic plasticity; spring emergence; migratory bird; body-mass; population; patterns
AB The most commonly reported ecological effects of climate change are shifts in phenologies, in particular of warmer spring temperatures leading to earlier timing of key events(1,2). Among animals, however, these reports have been heavily biased towards avian phenologies, whereas we still know comparatively little about other seasonal adaptations, such as mammalian hibernation. Here we show a significant delay (0.47 days per year, over a 20-year period) in the hibernation emergence date of adult females in a wild population of Columbian ground squirrels in Alberta, Canada. This finding was related to the climatic conditions at our study location: owing to within-individual phenotypic plasticity, females emerged later during years of lower spring temperature and delayed snowmelt. Although there has not been a significant annual trend in spring temperature, the date of snowmelt has become progressively later owing to an increasing prevalence of late-season snowstorms. Importantly, years of later emergence were also associated with decreased individual fitness. There has consequently been a decline in mean fitness (that is, population growth rate) across the past two decades. Our results show that plastic responses to climate change may be driven by climatic trends other than increasing temperature, and may be associated with declines in individual fitness and, hence, population viability.
C1 [Lane, Jeffrey E.; Kruuk, Loeske E. B.] Univ Edinburgh, Sch Biol Sci, Inst Evolutionary Biol, Edinburgh EH9 3JT, Midlothian, Scotland.
   [Lane, Jeffrey E.; Charmantier, Anne; Dobson, F. Stephen] CNRS, Ctr Ecol Fonct & Evolut, Unite Mixte Rech 5175, F-34293 Montpellier 5, France.
   [Lane, Jeffrey E.; Murie, Jan O.] Univ Alberta, Dept Biol Sci, Edmonton, AB T6G 2E9, Canada.
   [Dobson, F. Stephen] Auburn Univ, Dept Biol Sci, Auburn, AL 36849 USA.
C3 University of Edinburgh; 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 Alberta; Auburn University System; Auburn University
RP Lane, JE (corresponding author), Univ Edinburgh, Sch Biol Sci, Inst Evolutionary Biol, Edinburgh EH9 3JT, Midlothian, Scotland.
EM u.columbianus@hotmail.com
FU Natural Sciences and Engineering Research Council of Canada (NSERC); National Science Foundation [DEB-0089473]; Royal Society of London; Agence Nationale de la Recherche of France [ANR-08-JCJC-0041-01]; Alberta Conservation Association
NR 31
TC 223
Z9 258
U1 2
U2 288
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD SEP 27
PY 2012
VL 489
IS 7417
BP 554
EP +
DI 10.1038/nature11335
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 046RG
UT WOS:000311781500001
PM 22878721
DA 2026-03-09
ER

PT J
AU Tussiwand, R
   Lee, WL
   Murphy, TL
   Mashayekhi, M
   Wumesh, KC
   Albring, JC
   Satpathy, AT
   Rotondo, JA
   Edelson, BT
   Kretzer, NM
   Wu, XD
   Weiss, LA
   Glasmacher, E
   Li, P
   Liao, W
   Behnke, M
   Lam, SSK
   Aurthur, CT
   Leonard, WJ
   Singh, H
   Stallings, CL
   Sibley, LD
   Schreiber, RD
   Murphy, KM
AF Tussiwand, Roxane
   Lee, Wan-Ling
   Murphy, Theresa L.
   Mashayekhi, Mona
   Wumesh, K. C.
   Albring, Joern C.
   Satpathy, Ansuman T.
   Rotondo, Jeffrey A.
   Edelson, Brian T.
   Kretzer, Nicole M.
   Wu, Xiaodi
   Weiss, Leslie A.
   Glasmacher, Elke
   Li, Peng
   Liao, Wei
   Behnke, Michael
   Lam, Samuel S. K.
   Aurthur, Cora T.
   Leonard, Warren J.
   Singh, Harinder
   Stallings, Christina L.
   Sibley, L. David
   Schreiber, Robert D.
   Murphy, Kenneth M.
TI Compensatory dendritic cell development mediated by BATF-IRF interactions
SO NATURE
LA English
DT Article
ID negative regulator; b-atf; cd8-alpha(+); transcription; expression; infection; ap-1; reveals; mice; activation
AB The AP1 transcription factor Batf3 is required for homeostatic development of CD8 alpha(+) classical dendritic cells that prime CD8 T-cell responses against intracellular pathogens. Here we identify an alternative, Batf3-independent pathway in mice for CD8 alpha(+) dendritic cell development operating during infection with intracellular pathogens and mediated by the cytokines interleukin (IL)-12 and interferon-gamma. This alternative pathway results from molecular compensation for Batf3 provided by the related AP1 factors Batf, which also functions in T and B cells, and Batf2 induced by cytokines in response to infection. Reciprocally, physiological compensation between Batf and Batf3 also occurs in T cells for expression of IL-10 and CTLA4. Compensation among BATF factors is based on the shared capacity of their leucine zipper domains to interact with non-AP1 factors such as IRF4 and IRF8 to mediate cooperative gene activation. Conceivably, manipulating this alternative pathway of dendritic cell development could be of value in augmenting immune responses to vaccines.
C1 [Tussiwand, Roxane; Lee, Wan-Ling; Murphy, Theresa L.; Mashayekhi, Mona; Wumesh, K. C.; Albring, Joern C.; Satpathy, Ansuman T.; Rotondo, Jeffrey A.; Edelson, Brian T.; Kretzer, Nicole M.; Wu, Xiaodi; Lam, Samuel S. K.; Aurthur, Cora T.; Schreiber, Robert D.; Murphy, Kenneth M.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA.
   [Weiss, Leslie A.; Behnke, Michael; Stallings, Christina L.; Sibley, L. David] Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO 63110 USA.
   [Glasmacher, Elke; Singh, Harinder] Genentech Inc, Dept Discovery Immunol, San Francisco, CA 94080 USA.
   [Li, Peng; Liao, Wei; Leonard, Warren J.] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA.
   [Li, Peng; Liao, Wei; Leonard, Warren J.] NHLBI, Ctr Immunol, NIH, Bethesda, MD 20892 USA.
   [Murphy, Kenneth M.] Washington Univ, Sch Med, Howard Hughes Med Inst, St Louis, MO 63110 USA.
C3 Washington University (WUSTL); Washington University (WUSTL); Roche Holding; Genentech; Roche Holding USA; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI); National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI); Howard Hughes Medical Institute; Washington University (WUSTL)
RP Murphy, KM (corresponding author), Washington Univ, Sch Med, Dept Pathol & Immunol, 660 S Euclid Ave, St Louis, MO 63110 USA.
EM kmurphy@wustl.edu
FU Howard Hughes Medical Institute; National Institutes of Health [AI076427-02]; Department of Defense [W81XWH-09-1-0185]; American Heart Association [12PRE8610005]; German Research Foundation [AL 1038/1-1]; American Society of Hematology; Cancer Research Institute; NCI Cancer Center [P30 CA91842]; National Cancer Institute [P30CA091842] Funding Source: NIH RePORTER; National Heart Lung and Blood Institute [ZIAHL005408, ZIAHL005402] Funding Source: NIH RePORTER; National Institute of Allergy and Infectious Diseases [T32AI007163] Funding Source: NIH RePORTER; National Institute of Diabetes and Digestive and Kidney Diseases [P30DK020579] Funding Source: NIH RePORTER; American Heart Association (AHA) [12PRE8610005] Funding Source: American Heart Association (AHA)
NR 46
TC 331
Z9 387
U1 0
U2 34
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 25
PY 2012
VL 490
IS 7421
BP 502
EP +
DI 10.1038/nature11531
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 025NK
UT WOS:000310196200034
PM 22992524
DA 2026-03-09
ER

PT J
AU Cai, WJ
   Lengaigne, M
   Borlace, S
   Collins, M
   Cowan, T
   McPhaden, MJ
   Timmermann, A
   Power, S
   Brown, J
   Menkes, C
   Ngari, A
   Vincent, EM
   Widlansky, MJ
AF Cai, Wenju
   Lengaigne, Matthieu
   Borlace, Simon
   Collins, Matthew
   Cowan, Tim
   McPhaden, Michael J.
   Timmermann, Axel
   Power, Scott
   Brown, Josephine
   Menkes, Christophe
   Ngari, Arona
   Vincent, Emmanuel M.
   Widlansky, Matthew J.
TI More extreme swings of the South Pacific convergence zone due to greenhouse warming
SO NATURE
LA English
DT Article
ID el-nino; climate-change; oscillation; ocean; atmosphere; mortality; future; spcz
AB The South Pacific convergence zone (SPCZ) is the Southern Hemisphere's most expansive and persistent rain band, extending from the equatorial western Pacific Ocean southeastward towards French Polynesia(1,2). Owing to its strong rainfall gradient, a small displacement in the position of the SPCZ causes drastic changes to hydroclimatic conditions and the frequency of extreme weather events-such as droughts, floods and tropical cyclones-experienced by vulnerable island countries in the region(1-7). The SPCZ position varies from its climatological mean location with the El Nino/Southern Oscillation (ENSO), moving a few degrees northward during moderate El Nino events and southward during La Nina events(2,5,6). During strong El Nino events, however, the SPCZ undergoes an extreme swing-by up to ten degrees of latitude toward the Equator-and collapses to a more zonally oriented structure(5) with commensurately severe weather impacts(5,8-11). Understanding changes in the characteristics of the SPCZ in a changing climate is therefore of broad scientific and socioeconomic interest. Here we present climate modelling evidence for a near doubling in the occurrences of zonal SPCZ events between the periods 1891-1990 and 1991-2090 in response to greenhouse warming, even in the absence of a consensus on how ENSO will change(12-14). We estimate the increase in zonal SPCZ events from an aggregation of the climate models in the Coupled Model Intercomparison Project phases 3 and 5 (CMIP3(15) and CMIP5) multi-model database that are able to simulate such events. The change is caused by a projected enhanced equatorial warming in the Pacific(16) and may lead to more frequent occurrences of extreme events across the Pacific island nations most affected by zonal SPCZ events.
C1 [Cai, Wenju; Lengaigne, Matthieu; Cowan, Tim] CSIRO Marine & Atmospher Res, Aspendale, Vic 3195, Australia.
   [Lengaigne, Matthieu; Vincent, Emmanuel M.] UPMC, LOCEAN, F-75252 Paris 05, France.
   [Collins, Matthew] Univ Exeter, Coll Engn Math & Phys Sci, Exeter EX4 4QF, Devon, England.
   [Collins, Matthew] Met Off Hadley Ctr, Exeter EX1 3PB, Devon, England.
   [McPhaden, Michael J.] NOAA, Pacific Marine Environm Lab, Seattle, WA 98115 USA.
   [Timmermann, Axel] Univ Hawaii, SOEST, Dept Oceanog, IPRC, Honolulu, HI 96822 USA.
   [Power, Scott; Brown, Josephine] Bur Meteorol, Ctr Australian Weather & Climate Res, Melbourne, Vic 3001, Australia.
   [Menkes, Christophe] Inst Rech Dev, Noumea 98848, New Caledonia.
   [Ngari, Arona] Meteorol Serv, Avarua, Rarotonga, Cook Islands.
   [Widlansky, Matthew J.] Univ Hawaii Manoa, Int Pacific Res Ctr, Honolulu, HI 96822 USA.
C3 Commonwealth Scientific & Industrial Research Organisation (CSIRO); Sorbonne Universite; Museum National d'Histoire Naturelle (MNHN); University of Exeter; Met Office - UK; Hadley Centre; National Oceanic Atmospheric Admin (NOAA) - USA; University of Hawaii System; Commonwealth Scientific & Industrial Research Organisation (CSIRO); Bureau of Meteorology - Australia; Institut de Recherche pour le Developpement (IRD); University of Hawaii System; University of Hawaii Manoa
RP Cai, WJ (corresponding author), CSIRO Marine & Atmospher Res, Aspendale, Vic 3195, Australia.
EM wenju.cai@csiro.au
FU Australian Climate Change Science Program; CSIRO Office of Chief Executive Science Leader programme; Pacific-Australia Climate Change Science and Adaptation Planning Program; Office of Science (BER) US Department of Energy [DE-FG02-07ER64469]; US National Science Foundation [1049219]; Japan Agency for Marine-Earth Science and Technology (JAMSTEC); NOAA; CSIRO; Institut de Recherche pour le Developpement (IRD);  [3830]; Directorate For Geosciences [1049219] Funding Source: National Science Foundation; Div Atmospheric & Geospace Sciences [1049219] Funding Source: National Science Foundation
NR 31
TC 181
Z9 202
U1 2
U2 134
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 16
PY 2012
VL 488
IS 7411
BP 365
EP +
DI 10.1038/nature11358
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 988OS
UT WOS:000307501000039
PM 22895343
DA 2026-03-09
ER

PT J
AU Shim, SB
   Kwan, KY
   Li, MF
   Lefebvre, V
   Sestan, N
AF Shim, Sungbo
   Kwan, Kenneth Y.
   Li, Mingfeng
   Lefebvre, Veronique
   Sestan, Nenad
TI Cis-regulatory control of corticospinal system development and evolution
SO NATURE
LA English
DT Article
ID developing cerebral-cortex; subcortical projection neurons; reelin signaling pathway; zinc-finger gene; expression patterns; mammalian neocortex; descending pathways; laminar identity; pyramidal tract; axon guidance
AB The co-emergence of a six-layered cerebral neocortex and its corticospinal output system is one of the evolutionary hallmarks of mammals. However, the genetic programs that underlie their development and evolution remain poorly understood. Hereweidentify a conserved non-exonic element (E4) that acts as a cortex-specific enhancer for the nearby gene Fezf2 (also known as Fezl and Zfp312), which is required for the specification of corticospinal neuron identity and connectivity. We find that SOX4 and SOX11 functionally compete with the repressor SOX5 in the transactivation of E4. Cortex-specific double deletion of Sox4 and Sox11 leads to the loss of Fezf2 expression, failed specification of corticospinal neurons and, independent of Fezf2, a reeler-like inversion of layers. We show evidence supporting the emergence of functional SOX-binding sites in E4 during tetrapod evolution, and their subsequent stabilization in mammals and possibly amniotes. These findings reveal that SOX transcription factors converge onto a cis-acting element of Fezf2 and form critical components of a regulatory network controlling the identity and connectivity of corticospinal neurons.
C1 [Shim, Sungbo; Kwan, Kenneth Y.; Li, Mingfeng; Sestan, Nenad] Yale Univ, Sch Med, Dept Neurobiol, New Haven, CT 06510 USA.
   [Shim, Sungbo; Kwan, Kenneth Y.; Li, Mingfeng; Sestan, Nenad] Yale Univ, Sch Med, Kavli Inst Neurosci, New Haven, CT 06510 USA.
   [Lefebvre, Veronique] Cleveland Clin, Lerner Res Inst, Dept Cell Biol, Cleveland, OH 44195 USA.
   [Lefebvre, Veronique] Cleveland Clin, Lerner Res Inst, Orthopaed & Rheumatol Res Ctr, Cleveland, OH 44195 USA.
C3 Yale University; Yale University; Cleveland Clinic Foundation; Cleveland Clinic Foundation
RP Sestan, N (corresponding author), Yale Univ, Sch Med, Dept Neurobiol, New Haven, CT 06510 USA.
EM nenad.sestan@yale.edu
FU National Institutes of Health [NS054273, MH081896, AR54153]; March of Dimes Foundation; McDonnell Scholar Award
NR 55
TC 142
Z9 182
U1 0
U2 35
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUN 7
PY 2012
VL 486
IS 7401
BP 74
EP U177
DI 10.1038/nature11094
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 953GD
UT WOS:000304854000029
PM 22678282
DA 2026-03-09
ER

PT J
AU Choat, B
   Jansen, S
   Brodribb, TJ
   Cochard, H
   Delzon, S
   Bhaskar, R
   Bucci, SJ
   Feild, TS
   Gleason, SM
   Hacke, UG
   Jacobsen, AL
   Lens, F
   Maherali, H
   Martinez-Vilalta, J
   Mayr, S
   Mencuccini, M
   Mitchell, PJ
   Nardini, A
   Pittermann, J
   Pratt, RB
   Sperry, JS
   Westoby, M
   Wright, IJ
   Zanne, AE
AF Choat, Brendan
   Jansen, Steven
   Brodribb, Tim J.
   Cochard, Herve
   Delzon, Sylvain
   Bhaskar, Radika
   Bucci, Sandra J.
   Feild, Taylor S.
   Gleason, Sean M.
   Hacke, Uwe G.
   Jacobsen, Anna L.
   Lens, Frederic
   Maherali, Hafiz
   Martinez-Vilalta, Jordi
   Mayr, Stefan
   Mencuccini, Maurizio
   Mitchell, Patrick J.
   Nardini, Andrea
   Pittermann, Jarmila
   Pratt, R. Brandon
   Sperry, John S.
   Westoby, Mark
   Wright, Ian J.
   Zanne, Amy E.
TI Global convergence in the vulnerability of forests to drought
SO NATURE
LA English
DT Article
ID hydraulic architecture; tropical forests; xylem cavitation; woody-plants; rain-forest; die-off; water; vegetation; mortality; embolism
AB Shifts in rainfall patterns and increasing temperatures associated with climate change are likely to cause widespread forest decline in regions where droughts are predicted to increase in duration and severity(1). One primary cause of productivity loss and plant mortality during drought is hydraulic failure(2-4). Drought stress creates trapped gas emboli in the water transport system, which reduces the ability of plants to supply water to leaves for photosynthetic gas exchange and can ultimately result in desiccation and mortality. At present we lack a clear picture of how thresholds to hydraulic failure vary across a broad range of species and environments, despite many individual experiments. Here we draw together published and unpublished data on the vulnerability of the transport system to drought-induced embolism for a large number of woody species, with a view to examining the likely consequences of climate change for forest biomes. We show that 70% of 226 forest species from 81 sites worldwide operate with narrow (<1 megapascal) hydraulic safety margins against injurious levels of drought stress and therefore potentially face long-term reductions in productivity and survival if temperature and aridity increase as predicted for many regions across the globe(5,6). Safety margins are largely independent of mean annual precipitation, showing that there is global convergence in the vulnerability of forests to drought, with all forest biomes equally vulnerable to hydraulic failure regardless of their current rainfall environment. These findings provide insight into why drought-induced forest decline is occurring not only in arid regions but also in wet forests not normally considered at drought risk(7,8).
C1 [Jansen, Steven] Ulm Univ, Inst Systemat Bot & Ecol, D-89081 Ulm, Germany.
   [Choat, Brendan] Univ Western Sydney, Hawkesbury Inst Environm, Richmond, NSW 2753, Australia.
   [Brodribb, Tim J.] Univ Tasmania, Sch Plant Sci, Hobart, Tas 7001, Australia.
   [Cochard, Herve] INRA, PIAF UMR547, F-63100 Clermont Ferrand, France.
   [Delzon, Sylvain] Univ Bordeaux, INRA, UMR BIOGECO, F-33450 Talence, France.
   [Bhaskar, Radika] Brown Univ, Environm Change Initiat, Providence, RI 02912 USA.
   [Bucci, Sandra J.] Univ Nacl Patagonia San Juan Bosco, Dept Biol, Fac Ciencias Nat, RA-9000 Comodoro Rivadavia, Argentina.
   [Feild, Taylor S.] James Cook Univ, Sch Marine & Trop Biol, Townsville, Qld 4811, Australia.
   [Gleason, Sean M.; Westoby, Mark; Wright, Ian J.] Macquarie Univ, Dept Biol Sci, N Ryde, NSW 2109, Australia.
   [Hacke, Uwe G.] Univ Alberta, Dept Renewable Resources, Edmonton, AB T6G 2E3, Canada.
   [Jacobsen, Anna L.; Pratt, R. Brandon] Calif State Univ, Dept Biol, Bakersfield, CA 93311 USA.
   [Lens, Frederic] Leiden Univ, Nat Biodivers Ctr, NL-2300 RA Leiden, Netherlands.
   [Maherali, Hafiz] Univ Guelph, Dept Integrat Biol, Guelph, ON N1G 2W1, Canada.
   [Martinez-Vilalta, Jordi] CREAF, Cerdanyola Del Valles 08193, Spain.
   [Mencuccini, Maurizio] Univ Autonoma Barcelona, ICREA, CREAF, Cerdanyola Del Valles 08193, Spain.
   [Mayr, Stefan] Univ Innsbruck, Inst Bot, A-6020 Innsbruck, Austria.
   [Mencuccini, Maurizio] Univ Edinburgh, Sch GeoSci, Edinburgh EH9 3JN, Midlothian, Scotland.
   [Mitchell, Patrick J.] CSIRO, Sandy Bay, Tas 7005, Australia.
   [Nardini, Andrea] Univ Trieste, Dipartimento Sci Vita, I-34127 Trieste, Italy.
   [Pittermann, Jarmila] Univ Calif Santa Cruz, Dept Ecol & Evolutionary Biol, Santa Cruz, CA 95064 USA.
   [Sperry, John S.] Univ Utah, Dept Biol, Salt Lake City, UT 84112 USA.
   [Zanne, Amy E.] Ctr Conservat & Sustainable Dev, Missouri Bot Garden, St Louis, MO 63166 USA.
   [Zanne, Amy E.] George Washington Univ, Dept Biol Sci, Washington, DC 20052 USA.
C3 Ulm University; Western Sydney University; University of Tasmania; INRAE; INRAE; Universite de Bordeaux; Brown University; Universidad Nacional de la Patagonia San Juan Bosco; James Cook University; Macquarie University; University of Alberta; California State University System; California State University Bakersfield; Leiden University; Naturalis Biodiversity Center; Leiden University - Excl LUMC; University of Guelph; Centro de Investigacion Ecologica y Aplicaciones Forestales (CREAF-CERCA); Autonomous University of Barcelona; ICREA; Centro de Investigacion Ecologica y Aplicaciones Forestales (CREAF-CERCA); University of Innsbruck; University of Edinburgh; Commonwealth Scientific & Industrial Research Organisation (CSIRO); University of Trieste; University of California System; University of California Santa Cruz; Utah System of Higher Education; University of Utah; Missouri Botanical Gardens; George Washington University
RP Jansen, S (corresponding author), Ulm Univ, Inst Systemat Bot & Ecol, Albert Einstein Allee 11, D-89081 Ulm, Germany.
EM steven.jansen@uni-ulm.de
FU Alexander von Humboldt Foundation; NERC [NE/I011749/1] Funding Source: UKRI; Austrian Science Fund (FWF) [P 20852] Funding Source: researchfish; Natural Environment Research Council [NE/I011749/1] Funding Source: researchfish; Division Of Integrative Organismal Systems; Direct For Biological Sciences [0845125, 0743148] Funding Source: National Science Foundation; ICREA Funding Source: Custom
NR 30
TC 2150
Z9 2479
U1 69
U2 2124
PU NATURE PUBLISHING 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 29
PY 2012
VL 491
IS 7426
BP 752
EP +
DI 10.1038/nature11688
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 044FY
UT WOS:000311606000044
PM 23172141
DA 2026-03-09
ER

PT J
AU Feng, F
   Yang, F
   Rong, W
   Wu, XG
   Zhang, J
   Chen, S
   He, CZ
   Zhou, JM
AF Feng, Feng
   Yang, Fan
   Rong, Wei
   Wu, Xiaogang
   Zhang, Jie
   Chen, She
   He, Chaozu
   Zhou, Jian-Min
TI A Xanthomonas uridine 5′-monophosphate transferase inhibits plant immune kinases
SO NATURE
LA English
DT Article
ID pseudomonas-syringae effector; innate immunity; fic domain; cytoplasmic kinase; iii effectors; host target; receptor; arabidopsis; campestris; ampylation
AB Plant innate immunity is activated on the detection of pathogen-associated molecular patterns (PAMPs) at the cell surface, or of pathogen effector proteins inside the plant cell(1-4). Together, PAMP-triggered immunity and effector-triggered immunity constitute powerful defences against various phytopathogens. Pathogenic bacteria inject a variety of effector proteins into the host cell to assist infection or propagation. A number of effector proteins have been shown to inhibit plant immunity(5), but the biochemical basis remains unknown for the vast majority of these effectors. Here we show that the Xanthomonas campestris pathovar campestris type III effector AvrAC enhances virulence and inhibits plant immunity by specifically targeting Arabidopsis BIK1 and RIPK, two receptor-like cytoplasmic kinases known to mediate immune signalling(6-8). AvrAC is a uridylyl transferase that adds uridine 5'-monophosphate to and conceals conserved phosphorylation sites in the activation loop of BIK1 and RIPK, reducing their kinase activity and consequently inhibiting downstream signalling.
C1 [Feng, Feng; Yang, Fan; Wu, Xiaogang; Zhang, Jie; Chen, She; Zhou, Jian-Min] Natl Inst Biol Sci, Beijing 102206, Peoples R China.
   [Feng, Feng] Tsinghua Univ, Sch Life Sci, Beijing 100084, Peoples R China.
   [Feng, Feng; He, Chaozu] Tsinghua Univ, Grad Sch Shenzhen, Shenzhen 518055, Peoples R China.
   [Rong, Wei; He, Chaozu] Hainan Univ, Hainan Key Lab Sustainable Utilizat Trop Bioresou, Haikou 570228, Hainan, Peoples R China.
   [Zhou, Jian-Min] Chinese Acad Sci, Inst Genet & Dev Biol, State Key Lab Plant Genom, Beijing 100101, Peoples R China.
   [Zhou, Jian-Min] Chinese Acad Sci, Inst Genet & Dev Biol, Natl Ctr Plant Gene Res, Beijing 100101, Peoples R China.
C3 National Institute of Biological Sciences, Beijing; Tsinghua University; Tsinghua Shenzhen International Graduate School; Tsinghua University; Hainan University; Chinese Academy of Sciences; Institute of Genetics & Developmental Biology, CAS; Chinese Academy of Sciences; Institute of Genetics & Developmental Biology, CAS
RP Zhou, JM (corresponding author), Natl Inst Biol Sci, Beijing 102206, Peoples R China.
EM czhe@hainu.edu.cn; zhoujianmin@nibs.ac.cn
FU Chinese Ministry of Science and Technology [2011CB100700, 2010CB835301, 2010CB835204]; Hainan University
NR 39
TC 273
Z9 336
U1 2
U2 212
PU NATURE PUBLISHING 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 3
PY 2012
VL 485
IS 7396
BP 114
EP U149
DI 10.1038/nature10962
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 934NV
UT WOS:000303451900045
PM 22504181
DA 2026-03-09
ER

PT J
AU Winkelmann, R
   Levermann, A
   Martin, MA
   Frieler, K
AF Winkelmann, R.
   Levermann, A.
   Martin, M. A.
   Frieler, K.
TI Increased future ice discharge from Antarctica owing to higher snowfall
SO NATURE
LA English
DT Article
ID model pism-pik; climate-change; sheet; beneath; shelf
AB Anthropogenic climate change is likely to cause continuing global sea level rise(1), but some processes within the Earth system may mitigate the magnitude of the projected effect. Regional and global climate models simulate enhanced snowfall over Antarctica, which would provide a direct offset of the future contribution to global sea level rise from cryospheric mass loss(2,3) and ocean expansion(4). Uncertainties exist in modelled snowfall(5), but even larger uncertainties exist in the potential changes of dynamic ice discharge from Antarctica(1,6) and thus in the ultimate fate of the precipitation-deposited ice mass. Here we show that snowfall and discharge are not independent, but that future ice discharge will increase by up to three times as a result of additional snowfall under global warming. Our results, based on an ice-sheet model(7) forced by climate simulations through to the end of 2500 (ref. 8), show that the enhanced discharge effect exceeds the effect of surface warming as well as that of basal ice-shelf melting, and is due to the difference in surface elevation change caused by snowfall on grounded versus floating ice. Although different underlying forcings drive ice loss from basal melting versus increased snowfall, similar ice dynamical processes are nonetheless at work in both; therefore results are relatively independent of the specific representation of the transition zone. In an ensemble of simulations designed to capture ice-physics uncertainty, the additional dynamic ice loss along the coastline compensates between 30 and 65 per cent of the ice gain due to enhanced snowfall over the entire continent. This results in a dynamic ice loss of up to 1.25 metres in the year 2500 for the strongest warming scenario. The reported effect thus strongly counters a potential negative contribution to global sea level by the Antarctic Ice Sheet.
C1 [Winkelmann, R.; Levermann, A.; Martin, M. A.; Frieler, K.] Potsdam Inst Climate Impact Res PIK, D-14473 Potsdam, Germany.
   [Winkelmann, R.; Levermann, A.; Martin, M. A.] Univ Potsdam, Inst Phys, D-14476 Potsdam, Germany.
C3 Potsdam Institut fur Klimafolgenforschung; University of Potsdam
RP Winkelmann, R (corresponding author), Potsdam Inst Climate Impact Res PIK, D-14473 Potsdam, Germany.
EM ricarda.winkelmann@pik-potsdam.de
FU German Federal Ministry of Education and Research (BMBF) [01LP1171A]; German Federal Ministry for the Environment, Nature Conservation and Nuclear Safety (BMU) [11_II_093_Global_A_SIDS, 11_II_093_Global_A_LDCs]
NR 31
TC 76
Z9 84
U1 1
U2 141
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 13
PY 2012
VL 492
IS 7428
BP 239
EP +
DI 10.1038/nature11616
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 053GM
UT WOS:000312259300039
PM 23235878
DA 2026-03-09
ER

PT J
AU White, JF
   Noinaj, N
   Shibata, Y
   Love, J
   Kloss, B
   Xu, F
   Gvozdenovic-Jeremic, J
   Shah, P
   Shiloach, J
   Tate, CG
   Grisshammer, R
AF White, Jim F.
   Noinaj, Nicholas
   Shibata, Yoko
   Love, James
   Kloss, Brian
   Xu, Feng
   Gvozdenovic-Jeremic, Jelena
   Shah, Priyanka
   Shiloach, Joseph
   Tate, Christopher G.
   Grisshammer, Reinhard
TI Structure of the agonist-bound neurotensin receptor
SO NATURE
LA English
DT Article
ID protein-coupled receptor; crystal-structure; membrane-proteins; opioid receptor; binding-site; active state; peptide; gpcr; activation; insights
AB Neurotensin (NTS) is a 13-amino-acid peptide that functions as both a neurotransmitter and a hormone through the activation of the neurotensin receptor NTSR1, a G-protein-coupled receptor (GPCR). In the brain, NTS modulates the activity of dopaminergic systems, opioid-independent analgesia, and the inhibition of food intake; in the gut, NTS regulates a range of digestive processes. Here we present the structure at 2.8 angstrom resolution of Rattus norvegicus NTSR1 in an active-like state, bound to NTS8-13, the carboxy-terminal portion of NTS responsible for agonist-induced activation of the receptor. The peptide agonist binds to NTSR1 in an extended conformation nearly perpendicular to the membrane plane, with the C terminus oriented towards the receptor core. Our findings provide, to our knowledge, the first insight into the binding mode of a peptide agonist to a GPCR and may support the development of non-peptide ligands that could be useful in the treatment of neurological disorders, cancer and obesity.
C1 [White, Jim F.; Xu, Feng; Gvozdenovic-Jeremic, Jelena; Shah, Priyanka; Grisshammer, Reinhard] Natl Inst Neurol Disorders & Stroke, Membrane Prot Struct Funct Unit, NIH, US Dept HHS, Rockville, MD 20852 USA.
   [Noinaj, Nicholas] NIDDKD, Mol Biol Lab, NIH, US Dept HHS, Bethesda, MD 20892 USA.
   [Shibata, Yoko; Tate, Christopher G.] MRC, Mol Biol Lab, Cambridge CB2 0QH, England.
   [Love, James; Kloss, Brian] New York Struct Biol Ctr, New York Consortium Membrane Prot Struct, Prot Prod Facil, New York, NY 10027 USA.
   [Shiloach, Joseph] NIDDKD, Biotechnol Core Lab, NIH, US Dept HHS, Bethesda, MD 20892 USA.
C3 National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS); National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK); MRC Laboratory Molecular Biology; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK)
RP Grisshammer, R (corresponding author), Natl Inst Neurol Disorders & Stroke, Membrane Prot Struct Funct Unit, NIH, US Dept HHS, Rockville, MD 20852 USA.
EM rkgriss@helix.nih.gov
FU National Institutes of Health (National Institute of Neurological Disorders and Stroke); National Institutes of Health (National Institute of Diabetes and Digestive and Kidney Diseases); Pfizer Global Research and Development; MRCT Development Gap Fund; UK Medical Research Council [MRC U105197215]; National Institutes of Health [U54GM075026]; NIH Roadmap grant [P50 GM073197]; US Department of Energy, Basic Energy Sciences, Office of Science [DE-AC02-06CH11357]; MRC [MC_U105197215] Funding Source: UKRI; Medical Research Council [MC_U105197215] Funding Source: researchfish
NR 59
TC 416
Z9 471
U1 3
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 OCT 25
PY 2012
VL 490
IS 7421
BP 508
EP +
DI 10.1038/nature11558
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 025NK
UT WOS:000310196200035
PM 23051748
DA 2026-03-09
ER

PT J
AU Lee, GS
   Subramanian, N
   Kim, AI
   Aksentijevich, I
   Goldbach-Mansky, R
   Sacks, DB
   Germain, RN
   Kastner, DL
   Chae, JJ
AF Lee, Geun-Shik
   Subramanian, Naeha
   Kim, Andrew I.
   Aksentijevich, Ivona
   Goldbach-Mansky, Raphaela
   Sacks, David B.
   Germain, Ronald N.
   Kastner, Daniel L.
   Chae, Jae Jin
TI The calcium-sensing receptor regulates the NLRP3 inflammasome through Ca2+ and cAMP
SO NATURE
LA English
DT Article
ID nalp3 inflammasome; activation; atp; lipopolysaccharide; secretion; crystals
AB Mutations in the gene encoding NLRP3 cause a spectrum of auto-inflammatory diseases known as cryopyrin-associated periodic syndromes (CAPS)(1). NLRP3 is a key component of one of several distinct cytoplasmic multiprotein complexes (inflammasomes) that mediate the maturation of the proinflammatory cytokine interleukin-1 beta (IL-1 beta) by activating caspase-1. Although several models for inflammasome activation, such as K+ efflux(2), generation of reactive oxygen species(3) and lysosomal destabilization(4), have been proposed, the precise molecular mechanism of NLRP3 inflammasome activation, as well as the mechanism by which CAPS-associated mutations activate NLRP3, remain to be elucidated. Here we show that the murine calcium-sensing receptor (CASR) activates the NLRP3 inflammasome, mediated by increased intracellular Ca2+ and decreased cellular cyclic AMP(cAMP). Ca2+ or other CASR agonists activate the NLRP3 inflammasome in the absence of exogenous ATP, whereas knockdown of CASR reduces inflammasome activation in response to known NLRP3 activators. CASR activates the NLRP3 inflammasome through phospholipase C, which catalyses inositol-1,4,5-trisphosphate production and thereby induces release of Ca2+ from endoplasmic reticulum stores. The increased cytoplasmic Ca2+ promotes the assembly of inflammasome components, and intracellular Ca2+ is required for spontaneous inflammasome activity in cells from patients with CAPS. CASR stimulation also results in reduced intracellular cAMP, which independently activates the NLRP3 inflammasome. cAMP binds to NLRP3 directly to inhibit inflammasome assembly, and downregulation of cAMP relieves this inhibition. The binding affinity of cAMP for CAPS-associated mutant NLRP3 is substantially lower than for wild-type NLRP3, and the uncontrolled mature IL-1 beta production from CAPS patients' peripheral blood mononuclear cells is attenuated by increasing cAMP. Taken together, these findings indicate that Ca2+ and cAMP are two key molecular regulators of the NLRP3 inflammasome that have critical roles in the molecular pathogenesis of CAPS.
C1 [Lee, Geun-Shik; Kim, Andrew I.; Aksentijevich, Ivona; Kastner, Daniel L.; Chae, Jae Jin] NHGRI, Inflammatory Dis Sect, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
   [Lee, Geun-Shik] Kangwon Natl Univ, Coll Vet Med, Chunchon 200701, Gangwon, South Korea.
   [Subramanian, Naeha; Germain, Ronald N.] NIAID, Lab Syst Biol, NIH, Bethesda, MD 20892 USA.
   [Goldbach-Mansky, Raphaela] NIAMSD, Translat Autoinflammatory Dis Sect, NIH, Bethesda, MD 20892 USA.
   [Sacks, David B.] NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA.
C3 National Institutes of Health (NIH) - USA; NIH National Human Genome Research Institute (NHGRI); Kangwon National University; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID); National Institutes of Health (NIH) - USA; NIH National Institute of Arthritis & Musculoskeletal & Skin Diseases (NIAMS); National Institutes of Health (NIH) - USA; NIH Clinical Center (CC)
RP Kastner, DL (corresponding author), NHGRI, Inflammatory Dis Sect, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
EM kastnerd@mail.nih.gov; chaej@mail.nih.gov
FU NIAMS; NHGRI; NIAID, NIH; National Human Genome Research Institute [ZIAHG200373, ZIAHG200372] Funding Source: NIH RePORTER; National Institute of Allergy and Infectious Diseases [ZIAAI000545] Funding Source: NIH RePORTER; National Institute of Arthritis and Musculoskeletal and Skin Diseases [ZIEAR041176] Funding Source: NIH RePORTER
CR Bos JL, 2003, NAT REV MOL CELL BIO, V4, P733, DOI 10.1038/nrm1197
   Brough D, 2003, J IMMUNOL, V170, P3029, DOI 10.4049/jimmunol.170.6.3029
   Chae JJ, 2011, IMMUNITY, V34, P755, DOI 10.1016/j.immuni.2011.02.020
   COCKCROFT S, 1979, J PHYSIOL-LONDON, V296, P229, DOI 10.1113/jphysiol.1979.sp013002
   Duewell P, 2010, NATURE, V464, P1357, DOI 10.1038/nature08938
   Duncan JA, 2007, P NATL ACAD SCI USA, V104, P8041, DOI 10.1073/pnas.0611496104
   Gattorno M, 2007, ARTHRITIS RHEUM, V56, P3138, DOI 10.1002/art.22842
   Halle A, 2008, NAT IMMUNOL, V9, P857, DOI 10.1038/ni.1636
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   Kim C, 2007, CELL, V130, P1032, DOI 10.1016/j.cell.2007.07.018
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   Masters SL, 2009, ANNU REV IMMUNOL, V27, P621, DOI 10.1146/annurev.immunol.25.022106.141627
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   Peters-Golden M, 2009, SCI SIGNAL, V2, P0, DOI 10.1126/scisignal.275pe37
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   Vandanmagsar B, 2011, NAT MED, V17, P179, DOI 10.1038/nm.2279
   Xi YH, 2010, MOL CELL BIOCHEM, V342, P233, DOI 10.1007/s11010-010-0489-3
   Zhou RB, 2010, NAT IMMUNOL, V11, P136, DOI 10.1038/ni.1831
NR 24
TC 881
Z9 1017
U1 1
U2 183
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 6
PY 2012
VL 492
IS 7427
BP 123
EP +
DI 10.1038/nature11588
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 048EQ
UT WOS:000311893400058
PM 23143333
DA 2026-03-09
ER

PT J
AU Wilson, GP
   Evans, AR
   Corfe, IJ
   Smits, PD
   Fortelius, M
   Jernvall, J
AF Wilson, Gregory P.
   Evans, Alistair R.
   Corfe, Ian J.
   Smits, Peter D.
   Fortelius, Mikael
   Jernvall, Jukka
TI Adaptive radiation of multituberculate mammals before the extinction of dinosaurs
SO NATURE
LA English
DT Article
ID diversity; evolution
AB The Cretaceous-Paleogene mass extinction approximately 66 million years ago is conventionally thought to have been a turning point in mammalian evolution(1,2). Prior to that event and for the first two-thirds of their evolutionary history, mammals were mostly confined to roles as generalized, small-bodied, nocturnal insectivores(3), presumably under selection pressures from dinosaurs(4). Release from these pressures, by extinction of non-avian dinosaurs at the Cretaceous-Paleogene boundary, triggered ecological diversification of mammals(1,2). Although recent individual fossil discoveries have shown that some mammalian lineages diversified ecologically during the Mesozoic era(5), comprehensive ecological analyses of mammalian groups crossing the Cretaceous-Paleogene boundary are lacking. Such analyses are needed because diversification analyses of living taxa(6,7) allow only indirect inferences of past ecosystems. Here we show that in arguably the most evolutionarily successful clade of Mesozoic mammals, the Multituberculata, an adaptive radiation began at least 20 million years before the extinction of non-avian dinosaurs and continued across the Cretaceous-Paleogene boundary. Disparity in dental complexity, which relates to the range of diets, rose sharply in step with generic richness and disparity in body size. Moreover, maximum dental complexity and body size demonstrate an adaptive shift towards increased herbivory. This dietary expansion tracked the ecological rise of angiosperms(8) and suggests that the resources that were available to multituberculates were relatively unaffected by the Cretaceous-Paleogene mass extinction. Taken together, our results indicate that mammals were able to take advantage of new ecological opportunities in the Mesozoic and that at least some of these opportunities persisted through the Cretaceous-Paleogene mass extinction. Similar broad-scale ecomorphological inventories of other radiations may help to constrain the possible causes of mass extinctions(9,10).
C1 [Wilson, Gregory P.; Smits, Peter D.] Univ Washington, Dept Biol, Seattle, WA 98195 USA.
   [Evans, Alistair R.; Smits, Peter D.] Monash Univ, Sch Biol Sci, Clayton, Vic 3800, Australia.
   [Corfe, Ian J.; Fortelius, Mikael; Jernvall, Jukka] Univ Helsinki, Inst Biotechnol, Dev Biol Program, FIN-00014 Helsinki, Finland.
   [Fortelius, Mikael] Univ Helsinki, Dept Geosci & Geog, FIN-00014 Helsinki, Finland.
C3 University of Washington; University of Washington Seattle; Monash University; University of Helsinki; University of Helsinki
RP Wilson, GP (corresponding author), Univ Washington, Dept Biol, Seattle, WA 98195 USA.
EM gpwilson@u.washington.edu
FU National Science Foundation; Denver Museum; University of Washington; Australian Research Council; Monash University; Academy of Finland; EU SYNTHESYS [GB-TAF-4779]
NR 29
TC 223
Z9 265
U1 2
U2 178
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 22
PY 2012
VL 483
IS 7390
BP 457
EP 460
DI 10.1038/nature10880
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 912CC
UT WOS:000301771200041
PM 22419156
DA 2026-03-09
ER

PT J
AU Ng, SW
   Bakowski, D
   Nelson, C
   Mehta, R
   Almeyda, R
   Bates, G
   Parekh, AB
AF Ng, Siaw-Wei
   Bakowski, Daniel
   Nelson, Charmaine
   Mehta, Ravi
   Almeyda, Robert
   Bates, Grant
   Parekh, Anant B.
TI Cysteinyl leukotriene type I receptor desensitization sustains Ca2+-dependent gene expression
SO NATURE
LA English
DT Article
ID activated calcium current; basophilic leukemia-cells; tyrosine kinase syk; dependent inactivation; feedback inhibition; ca2+ channels; rbl-2h3 cells; c-fos; crac; exocytosis
AB Receptor desensitization is a universal mechanism to turn off a biological response; in this process, the ability of a physiological trigger to activate a cell is lost despite the continued presence of the stimulus. Receptor desensitization of G-protein-coupled receptors involves uncoupling of the receptor from its G-protein or second-messenger pathway followed by receptor internalization(1). G-protein-coupled cysteinyl leukotriene type I (CysLT1) receptors regulate immune-cell function and CysLT1 receptors are an established therapeutic target for allergies, including asthma(2). Desensitization of CysLT1 receptors arises predominantly from protein-kinase-C-dependent phosphorylation of three serine residues in the receptor carboxy terminus(3). Physiological concentrations of the receptor agonist leukotriene C-4 (LTC4) evoke repetitive cytoplasmic Ca2+ oscillations, reflecting regenerative Ca2+ release from stores, which is sustained by Ca2+ entry through store-operated calcium-release-activated calcium (CRAC) channels(4). CRAC channels are tightly linked to expression of the transcription factor c-fos(5), a regulator of numerous genes important to cell growth and development(6). Here we show that abolishing leukotriene receptor desensitization suppresses agonist-driven gene expression in a rat cell line. Mechanistically, stimulation of non-desensitizing receptors evoked prolonged inositol-trisphosphate-mediated Ca2+ release, which led to accelerated Ca2+-dependent slow inactivation of CRAC channels and a subsequent loss of excitation-transcription coupling. Hence, rather than serving to turn off a biological response, reversible desensitization of a Ca2+ mobilizing receptor acts as an 'on' switch, sustaining long-term signalling in the immune system.
C1 [Ng, Siaw-Wei; Bakowski, Daniel; Nelson, Charmaine; Mehta, Ravi; Parekh, Anant B.] Univ Oxford, Dept Physiol Anat & Genet, Oxford OX1 3PT, England.
   [Almeyda, Robert; Bates, Grant] John Radcliffe Hosp, Dept Ear Nose Throat Surg, Oxford OX3 9DH, England.
C3 University of Oxford; University of Oxford
RP Parekh, AB (corresponding author), Univ Oxford, Dept Physiol Anat & Genet, Parks Rd, Oxford OX1 3PT, England.
EM anant.parekh@dpag.ox.ac.uk
FU Medical Research Council; BBSRC-Glaxo-Smith-Kline; MRC [G1000813] Funding Source: UKRI; Medical Research Council [G1000813] Funding Source: researchfish
NR 25
TC 33
Z9 34
U1 0
U2 11
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD FEB 2
PY 2012
VL 482
IS 7383
BP 111
EP U144
DI 10.1038/nature10731
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 884RN
UT WOS:000299726000046
PM 22230957
DA 2026-03-09
ER

PT J
AU Miyanari, Y
   Torres-Padilla, ME
AF Miyanari, Yusuke
   Torres-Padilla, Maria-Elena
TI Control of ground-state pluripotency by allelic regulation of Nanog
SO NATURE
LA English
DT Article
ID embryonic stem-cells; transcription factor; replication; maintenance; expression
AB Pluripotency is established through genome-wide reprogramming during mammalian pre-implantation development, resulting in the formation of the naive epiblast. Reprogramming involves both the resetting of epigenetic marks and the activation of pluripotent-cell-specific genes such as Nanog and Oct4 (also known as Pou5f1)(1-4). The tight regulation of these genes is crucial for reprogramming, but the mechanisms that regulate their expression in vivo have not been uncovered. Here we show that Nanog-but not Oct4-is monoallelically expressed in early pre-implantation embryos. Nanog then undergoes a progressive switch to biallelic expression during the transition towards ground-state pluripotency in the naive epiblast of the late blastocyst. Embryonic stem (ES) cells grown in leukaemia inhibitory factor (LIF) and serum express Nanog mainly monoallelically and show asynchronous replication of the Nanog locus, a feature of monoallelically expressed genes(5), but ES cells activate both alleles when cultured under 2i conditions, which mimic the pluripotent ground state in vitro. Live-cell imaging with reporter ES cells confirmed the allelic expression of Nanog and revealed allelic switching. The allelic expression of Nanog is regulated through the fibroblast growth factor-extracellular signal-regulated kinase signalling pathway, and it is accompanied by chromatin changes at the proximal promoter but occurs independently of DNA methylation. Nanog-heterozygous blastocysts have fewer inner-cell-mass derivatives and delayed primitive endoderm formation, indicating a role for the biallelic expression of Nanog in the timely maturation of the inner cell mass into a fully reprogrammed pluripotent epiblast. We suggest that the tight regulation of Nanog dose at the chromosome level is necessary for the acquisition of ground-state pluripotency during development. Our data highlight an unexpected role for allelic expression in controlling the dose of pluripotency factors in vivo, adding an extra level to the regulation of reprogramming.
C1 [Miyanari, Yusuke; Torres-Padilla, Maria-Elena] Univ Strasbourg, Cite Univ Strasbourg, CNRS, Inst Genet & Biol Mol & Cellulaire,INSERM,U964, F-67404 Illkirch Graffenstaden, France.
C3 Centre National de la Recherche Scientifique (CNRS); Institut National de la Sante et de la Recherche Medicale (Inserm); Universites de Strasbourg Etablissements Associes; Universite de Strasbourg
RP Torres-Padilla, ME (corresponding author), Univ Strasbourg, Cite Univ Strasbourg, CNRS, Inst Genet & Biol Mol & Cellulaire,INSERM,U964, F-67404 Illkirch Graffenstaden, France.
EM metp@igbmc.fr
FU AVENIR/INSERM; Epigenesys NoE; FRM Alsace; EMBO [ALTF864-2008]; JSPS;  [ANR-09-Blanc-0114]
NR 27
TC 191
Z9 226
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 MAR 22
PY 2012
VL 483
IS 7390
BP 470
EP U123
DI 10.1038/nature10807
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 912CC
UT WOS:000301771200044
PM 22327294
DA 2026-03-09
ER

PT J
AU Metallo, CM
   Gameiro, PA
   Bell, EL
   Mattaini, KR
   Yang, JJ
   Hiller, K
   Jewell, CM
   Johnson, ZR
   Irvine, DJ
   Guarente, L
   Kelleher, JK
   Vander Heiden, MG
   Iliopoulos, O
   Stephanopoulos, G
AF Metallo, Christian M.
   Gameiro, Paulo A.
   Bell, Eric L.
   Mattaini, Katherine R.
   Yang, Juanjuan
   Hiller, Karsten
   Jewell, Christopher M.
   Johnson, Zachary R.
   Irvine, Darrell J.
   Guarente, Leonard
   Kelleher, Joanne K.
   Vander Heiden, Matthew G.
   Iliopoulos, Othon
   Stephanopoulos, Gregory
TI Reductive glutamine metabolism by IDH1 mediates lipogenesis under hypoxia
SO NATURE
LA English
DT Article
ID fatty-acid synthesis; cell-proliferation; flux analysis; hif-alpha; growth; cancer; dehydrogenase; suppression; distributions; hydroxylation
AB Acetyl coenzyme A (AcCoA) is the central biosynthetic precursor for fatty-acid synthesis and protein acetylation. In the conventional view of mammalian cell metabolism, AcCoA is primarily generated from glucose-derived pyruvate through the citrate shuttle and ATP citrate lyase in the cytosol(1-3). However, proliferating cells that exhibit aerobic glycolysis and those exposed to hypoxia convert glucose to lactate at near-stoichiometric levels, directing glucose carbon away from the tricarboxylic acid cycle and fatty-acid synthesis(4). Although glutamine is consumed at levels exceeding that required for nitrogen biosynthesis(5), the regulation and use of glutamine metabolism in hypoxic cells is not well understood. Here we show that human cells use reductive metabolism of alpha-ketoglutarate to synthesize AcCoA for lipid synthesis. This isocitrate dehydrogenase-1 (IDH1)-dependent pathway is active in most cell lines under normal culture conditions, but cells grown under hypoxia rely almost exclusively on the reductive carboxylation of glutamine-derived alpha-ketoglutarate for de novo lipogenesis. Furthermore, renal cell lines deficient in the von Hippel-Lindau tumour suppressor protein preferentially use reductive glutamine metabolism for lipid biosynthesis even at normal oxygen levels. These results identify a critical role for oxygen in regulating carbon use to produce AcCoA and support lipid synthesis in mammalian cells.
C1 [Metallo, Christian M.; Gameiro, Paulo A.; Hiller, Karsten; Kelleher, Joanne K.; Stephanopoulos, Gregory] MIT, Dept Chem Engn, Cambridge, MA 02139 USA.
   [Gameiro, Paulo A.] Univ Coimbra, Dept Life Sci, P-3004517 Coimbra, Portugal.
   [Gameiro, Paulo A.; Yang, Juanjuan; Iliopoulos, Othon] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
   [Gameiro, Paulo A.; Yang, Juanjuan; Iliopoulos, Othon] Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA 02129 USA.
   [Bell, Eric L.; Mattaini, Katherine R.; Guarente, Leonard; Vander Heiden, Matthew G.] MIT, Dept Biol, Cambridge, MA 02139 USA.
   [Mattaini, Katherine R.; Jewell, Christopher M.; Johnson, Zachary R.; Irvine, Darrell J.; Vander Heiden, Matthew G.] MIT, Koch Inst Canc Res, Cambridge, MA 02139 USA.
   [Irvine, Darrell J.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA.
   [Vander Heiden, Matthew G.] Dana Farber Canc Inst, Boston, MA 02115 USA.
C3 Massachusetts Institute of Technology (MIT); Universidade de Coimbra; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); Howard Hughes Medical Institute; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute
RP Stephanopoulos, G (corresponding author), MIT, Dept Chem Engn, Cambridge, MA 02139 USA.
EM iliopoul@helix.mgh.harvard.edu; gregstep@mit.edu
FU National Institutes of Health [R01 DK075850-01]; American Cancer Society; German Research Foundation (DFG) [HI1400]; Glenn Foundation for Medical Research; Burrough's Wellcome Fund; Smith Family; Damon Runyon Cancer Research Foundation; National Cancer Institute; Dana Farber/Harvard Cancer Center;  [R01 CA122591]; National Cancer Institute [P30CA014051] Funding Source: NIH RePORTER
NR 40
TC 1491
Z9 1773
U1 3
U2 336
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 19
PY 2012
VL 481
IS 7381
BP 380
EP U166
DI 10.1038/nature10602
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 877VK
UT WOS:000299210600046
PM 22101433
DA 2026-03-09
ER

PT J
AU Reed, MD
   DiCarlo, L
   Nigg, SE
   Sun, L
   Frunzio, L
   Girvin, SM
   Schoelkopf, RJ
AF Reed, M. D.
   DiCarlo, L.
   Nigg, S. E.
   Sun, L.
   Frunzio, L.
   Girvin, S. M.
   Schoelkopf, R. J.
TI Realization of three-qubit quantum error correction with superconducting circuits
SO NATURE
LA English
DT Article
ID algorithms; computer; qubits
AB Quantum computers could be used to solve certain problems exponentially faster than classical computers, but are challenging to build because of their increased susceptibility to errors. However, it is possible to detect and correct errors without destroying coherence, by using quantum error correcting codes(1). The simplest of these are three-quantum-bit (three-qubit) codes, which map a one-qubit state to an entangled three-qubit state; they can correct any single phase-flip or bit-flip error on one of the three qubits, depending on the code used(2). Here we demonstrate such phase-and bit-flip error correcting codes in a superconducting circuit. We encode a quantum state(3,4), induce errors on the qubits and decode the error syndrome-a quantum state indicating which error has occurred-by reversing the encoding process. This syndrome is then used as the input to a three-qubit gate that corrects the primary qubit if it was flipped. As the code can recover from a single error on any qubit, the fidelity of this process should decrease only quadratically with error probability. We implement the correcting three-qubit gate (known as a conditional-conditional NOT, or Toffoli, gate) in 63 nanoseconds, using an interaction with the third excited state of a single qubit. We find 85 +/- 1 per cent fidelity to the expected classical action of this gate, and 78 +/- 1 per cent fidelity to the ideal quantum process matrix. Using this gate, we perform a single pass of both quantum bit- and phase-flip error correction and demonstrate the predicted first-order insensitivity to errors. Concatenation of these two codes in a nine-qubit device would correct arbitrary single-qubit errors. In combination with recent advances in superconducting qubit coherence times(5,6), this could lead to scalable quantum technology.
C1 [Reed, M. D.; Nigg, S. E.; Sun, L.; Frunzio, L.; Girvin, S. M.; Schoelkopf, R. J.] Yale Univ, Dept Phys & Appl Phys, New Haven, CT 06520 USA.
   [DiCarlo, L.] Delft Univ Technol, Kavli Inst Nanosci, NL-2628 CJ Delft, Netherlands.
C3 Yale University; Delft University of Technology
RP Reed, MD (corresponding author), Yale Univ, Dept Phys & Appl Phys, New Haven, CT 06520 USA.
EM matthew.reed@yale.edu; robert.schoelkopf@yale.edu
FU LPS/NSA under ARO [W911NF-09-1-0514]; NSF [DMR-0653377, DMR-1004406]; CNR-Istituto di Cibernetica, Pozzuoli, Italy; Swiss NSF; Dutch NWO; Division Of Materials Research; Direct For Mathematical & Physical Scien [1004406] Funding Source: National Science Foundation; National Health and Medical Research Council (NHMRC) [1004406] Funding Source: National Health and Medical Research Council (NHMRC)
NR 27
TC 499
Z9 592
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 FEB 16
PY 2012
VL 482
IS 7385
BP 382
EP 385
DI 10.1038/nature10786
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 892LG
UT WOS:000300287100042
PM 22297844
DA 2026-03-09
ER

PT J
AU Simcoe, RA
   Sullivan, PW
   Cooksey, KL
   Kao, MM
   Matejek, MS
   Burgasser, AJ
AF Simcoe, Robert A.
   Sullivan, Peter W.
   Cooksey, Kathy L.
   Kao, Melodie M.
   Matejek, Michael S.
   Burgasser, Adam J.
TI Extremely metal-poor gas at a redshift of 7
SO NATURE
LA English
DT Article
ID intergalactic medium; quasar; abundances; evolution
AB In typical astrophysical environments, the abundance of heavy elements ranges from 0.001 to 2 times the solar value. Lower abundances have been seen in selected stars in the Milky Way's halo(1-3) and in two quasar absorption systems at redshift z = 3 (ref. 4). These are widely interpreted as relics from the early Universe, when all gas possessed a primordial chemistry. Before now there have been no direct abundance measurements from the first billion years after the Big Bang, when the earliest stars began synthesizing elements. Here we report observations of hydrogen and heavy-element absorption in a spectrum of a quasar at z = 7.04, when the Universe was just 772 million years old (5.6 per cent of its present age). We detect a large column of neutral hydrogen but no corresponding metals (defined as elements heavier than helium), limiting the chemical abundance to less than 1/10,000 times the solar level if the gas is in a gravitationally bound proto-galaxy, or to less than 1/1,000 times the solar value if it is diffuse and unbound. If the absorption is truly intergalactic(5,6), it would imply that the Universe was neither ionized by starlight nor chemically enriched in this neighbourhood at z approximate to 7. If it is gravitationally bound, the inferred abundance is too low to promote efficient cooling(7,8), and the system would be a viable site to form the predicted but as yet unobserved massive population III stars.
C1 [Simcoe, Robert A.; Sullivan, Peter W.; Cooksey, Kathy L.; Kao, Melodie M.; Matejek, Michael S.] MIT Kavli Inst Astrophys & Space Res, Cambridge, MA 02139 USA.
   [Kao, Melodie M.] CALTECH, Dept Astron, Pasadena, CA 91125 USA.
   [Burgasser, Adam J.] Univ Calif San Diego, Ctr Astrophys & Space Sci, La Jolla, CA 92093 USA.
C3 Massachusetts Institute of Technology (MIT); California Institute of Technology; University of California System; University of California San Diego
RP Simcoe, RA (corresponding author), MIT Kavli Inst Astrophys & Space Res, 77 Massachusetts Ave,Bldg 37,Room 664L, Cambridge, MA 02139 USA.
EM simcoe@space.mit.edu
FU NSF [AST-0908920, AST-1109115]; Division Of Astronomical Sciences; Direct For Mathematical & Physical Scien [1109115, 1003139] Funding Source: National Science Foundation
NR 25
TC 86
Z9 92
U1 0
U2 10
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 6
PY 2012
VL 492
IS 7427
BP 79
EP 82
DI 10.1038/nature11612
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 048EQ
UT WOS:000311893400048
PM 23222611
DA 2026-03-09
ER

PT J
AU Mosca, TJ
   Hong, WZ
   Dani, VS
   Favaloro, V
   Luo, LQ
AF Mosca, Timothy J.
   Hong, Weizhe
   Dani, Vardhan S.
   Favaloro, Vincenzo
   Luo, Liqun
TI Trans-synaptic Teneurin signalling in neuromuscular synapse organization and target choice
SO NATURE
LA English
DT Article
ID mosaic analysis; beta-spectrin; pair-rule; in-vivo; drosophila; gene; junction; growth; localization; specificity
AB Synapse assembly requires trans-synaptic signals between the pre- and postsynapse(1), but our understanding of the essential organizational molecules involved in this process remains incomplete(2). Teneurin proteins are conserved, epidermal growth factor (EGF)-repeat-containing transmembrane proteins with large extracellular domains(3). Here we show that two Drosophila Teneurins, Ten-m and Ten-a, are required for neuromuscular synapse organization and target selection. Ten-a is presynaptic whereas Ten-m is mostly postsynaptic; neuronal Ten-a and muscle Ten-m form a complex in vivo. Pre- or postsynaptic Teneurin perturbations cause severe synapse loss and impair many facets of organization trans-synaptically and cell autonomously. These include defects in active zone apposition, release sites, membrane and vesicle organization, and synaptic transmission. Moreover, the presynaptic microtubule and postsynaptic spectrin cytoskeletons are severely disrupted, suggesting a mechanism whereby Teneurins organize the cytoskeleton, which in turn affects other aspects of synapse development. Supporting this, Ten-m physically interacts with a-Spectrin. Genetic analyses of teneurin and neuroligin reveal that they have differential roles that synergize to promote synapse assembly. Finally, at elevated endogenous levels, Ten-m regulates target selection between specific motor neurons and muscles. Our study identifies the Teneurins as a key bi-directional trans-synaptic signal involved in general synapse organization, and demonstrates that proteins such as these can also regulate target selection.
C1 [Mosca, Timothy J.; Hong, Weizhe; Dani, Vardhan S.; Favaloro, Vincenzo; Luo, Liqun] Stanford Univ, Howard Hughes Med Inst, Dept Biol, Stanford, CA 94305 USA.
C3 Howard Hughes Medical Institute; Stanford University
RP Mosca, TJ (corresponding author), Stanford Univ, Howard Hughes Med Inst, Dept Biol, Stanford, CA 94305 USA.
EM tmosca@stanford.edu
FU National Institutes of Health (NIH) [R01 DC-005982, 5T32 NS007280, HD007249]; National Institute on Deafness and Other Communication Disorders [R01DC005982] Funding Source: NIH RePORTER
NR 57
TC 164
Z9 210
U1 0
U2 32
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 12
PY 2012
VL 484
IS 7393
BP 237
EP U122
DI 10.1038/nature10923
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 930OV
UT WOS:000303149900034
PM 22426000
DA 2026-03-09
ER

PT J
AU Leung, CT
   Brugge, JS
AF Leung, Cheuk T.
   Brugge, Joan S.
TI Outgrowth of single oncogene-expressing cells from suppressive epithelial environments
SO NATURE
LA English
DT Article
ID in-vivo; breast-cancer; extrusion; morphogenesis; apoptosis; migration; acini
AB Tumorigenesis is a clonal evolution process that is initiated from single cells within otherwise histologically normal tissue(1). It is unclear how single, sporadic mutant cells that have sustained oncogenic alterations evolve within a tightly regulated tissue environment. Here we investigated the effects of inducing oncogene expression in single cells in organotypic mammary acini as a model to elucidate the processes by which oncogenic alterations initiate clonal progression from organized epithelial environments. Sporadic cells induced to overexpress oncogenes that specifically perturb cell-cycle checkpoints (for example, E7 from human papilloma virus 16, and cyclin D1), deregulate Myc transcription or activate AKT signalling remained quiescent within growth-arrested acini. By contrast, single cells that overexpress ERBB2 initiated a cellular cascade involving cell translocation from the epithelial layer, as well as luminal outgrowth that is characteristic of neoplastic progression in early-stage epithelial tumours. In addition, ERBB2-mediated cell translocation to the lumen was found to depend on extracellular-regulated kinase and matrix metalloproteinase activities, and genetic alterations that perturb local cell-matrix adhesion drove cell translocation. We also provide evidence that luminal cell translocation may drive clonal selection by promoting either the death or the expansion of quiescent oncogene-expressing cells, depending on whether the pre-existing alterations allow anchorage-independent survival and growth. Our data show that the initial outgrowth of single oncogene-expressing cells from organized epithelial structures is a highly regulated process, and we propose that a cell translocation mechanism allows sporadic mutant cells to evade suppressive micro-environments and elicits clonal selection for survival and proliferative expansion outside the native niches of these cells.
C1 [Leung, Cheuk T.; Brugge, Joan S.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA.
C3 Harvard University; Harvard Medical School
RP Brugge, JS (corresponding author), Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA.
EM Joan_Brugge@hms.harvard.edu
FU National Cancer Institute [CA080111]; American Cancer Society
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NR 26
TC 187
Z9 224
U1 0
U2 41
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD FEB 16
PY 2012
VL 482
IS 7385
BP 410
EP U160
DI 10.1038/nature10826
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 892LG
UT WOS:000300287100048
PM 22318515
DA 2026-03-09
ER

PT J
AU Wu, Q
   Clark, MS
   Palmiter, RD
AF Wu, Qi
   Clark, Michael S.
   Palmiter, Richard D.
TI Deciphering a neuronal circuit that mediates appetite
SO NATURE
LA English
DT Article
ID food-intake; parabrachial nucleus; energy homeostasis; serotonin; brain; rat; anorexia; taste; fos; starvation
AB Hypothalamic neurons that co-express agouti-related protein (AgRP), neuropeptide Y and gamma-aminobutyric acid (GABA) are known to promote feeding and weight gain by integration of various nutritional, hormonal, and neuronal signals(1,2). Ablation of these neurons in mice leads to cessation of feeding that is accompanied by activation of Fos in most regions where they project(3-6). Previous experiments have indicated that the ensuing starvation is due to aberrant activation of the parabrachial nucleus (PBN) and it could be prevented by facilitating GABA(A) receptor signalling in the PBN within a critical adaptation period(5). We speculated that loss of GABA signalling from AgRP-expressing neurons (AgRP neurons) within the PBN results in unopposed excitation of the PBN, which in turn inhibits feeding. However, the source of the excitatory inputs to the PBN was unknown. Here we show that glutamatergic neurons in the nucleus tractus solitarius (NTS) and caudal serotonergic neurons control the excitability of PBN neurons and inhibit feeding. Blockade of serotonin (5-HT3) receptor signalling in the NTS by either the chronic administration of ondansetron or the genetic inactivation of Tph2 in caudal serotonergic neurons that project to the NTS protects against starvation when AgRP neurons are ablated. Likewise, genetic inactivation of glutamatergic signalling by the NTS onto N-methyl D-aspartate-type glutamate receptors in the PBN prevents starvation. We also show that suppressing glutamatergic output of the PBN reinstates normal appetite after AgRP neuron ablation, whereas it promotes weight gain without AgRP neuron ablation. Thus we identify the PBN as a hub that integrates signals from several brain regions to bidirectionally modulate feeding and body weight.
C1 [Wu, Qi; Palmiter, Richard D.] Univ Washington, Sch Med, Howard Hughes Med Inst, Seattle, WA 98195 USA.
   [Wu, Qi; Palmiter, Richard D.] Univ Washington, Sch Med, Dept Biochem, Seattle, WA 98195 USA.
   [Clark, Michael S.] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA.
C3 University of Washington; University of Washington Seattle; Howard Hughes Medical Institute; University of Washington; University of Washington Seattle; University of Washington; University of Washington Seattle
RP Palmiter, RD (corresponding author), Univ Washington, Sch Med, Howard Hughes Med Inst, Seattle, WA 98195 USA.
EM palmiter@uw.edu
FU National Institutes of Health [DA024908]; National Institute on Drug Abuse [R01DA024908] Funding Source: NIH RePORTER
NR 30
TC 280
Z9 329
U1 0
U2 55
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD MAR 29
PY 2012
VL 483
IS 7391
BP 594
EP U112
DI 10.1038/nature10899
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 915EF
UT WOS:000302006100038
PM 22419158
DA 2026-03-09
ER

PT J
AU Methé, BA
   Nelson, KE
   Pop, M
   Creasy, HH
   Giglio, MG
   Huttenhower, C
   Gevers, D
   Petrosino, JF
   Abubucker, S
   Badger, JH
   Chinwalla, AT
   Earl, AM
   FitzGerald, MG
   Fulton, RS
   Hallsworth-Pepin, K
   Lobos, EA
   Madupu, R
   Magrini, V
   Martin, JC
   Mitreva, M
   Muzny, DM
   Sodergren, EJ
   Versalovic, J
   Wollam, AM
   Worley, KC
   Wortman, JR
   Young, SK
   Zeng, Q
   Aagaard, KM
   Abolude, OO
   Allen-Vercoe, E
   Alm, EJ
   Alvarado, L
   Andersen, GL
   Anderson, S
   Appelbaum, E
   Arachchi, HM
   Armitage, G
   Arze, CA
   Ayvaz, T
   Baker, CC
   Begg, L
   Belachew, T
   Bhonagiri, V
   Bihan, M
   Blaser, MJ
   Bloom, T
   Bonazzi, VR
   Brooks, P
   Buck, G
   Buhay, CJ
   Busam, DA
   Campbell, JL
   Canon, SR
   Cantarel, BL
   Chain, PS
   Chen, IMA
   Chen, L
   Chhibba, S
   Chu, K
   Ciulla, DM
   Clemente, JC
   Clifton, SW
   Conlan, S
   Crabtree, J
   Cutting, MA
   Davidovics, NJ
   Davis, CC
   DeSantis, TZ
   Deal, C
   Delehaunty, KD
   Dewhisrst, FE
   Deych, E
   Ding, Y
   Dooling, DJ
   Dugan, SP
   Dunne, WM
   Durkin, AS
   Edgar, RC
   Erlich, RL
   Farmer, CN
   Farrell, RM
   Faust, K
   Feldgarden, M
   Felix, VM
   Fisher, S
   Fodor, AA
   Forney, L
   Foster, L
   Di Francesco, V
   Friedman, J
   Friedrich, DC
   Fronick, CC
   Fulton, LL
   Gao, H
   Garcia, N
   Giannoukos, G
   Giblin, C
   Giovanni, MY
   Goldberg, JM
   Goll, J
   Gonzalez, A
   Griggs, A
   Gujja, S
   Haas, BJ
   Hamilton, HA
   Harris, EL
   Hepburn, TA
   Herter, B
   Hoffmann, DE
   Holder, ME
   Howarth, C
   Huang, KH
   Huse, SM
   Izard, J
   Jansson, JK
   Jiang, HY
   Jordan, C
   Joshi, V
   Katancik, J
   Keitel, W
   Kelley, ST
   Kells, C
   Kinder-Haake, S
   King, NB
   Knight, R
   Knights, D
   Kong, HH
   Koren, O
   Koren, S
   Kota, KC
   Kovar, CL
   Kyrpides, NC
   La Rosa, PS
   Lee, SL
   Lemon, KP
   Lennon, N
   Lewis, CM
   Lewis, L
   Ley, RE
   Li, K
   Liolios, K
   Liu, B
   Liu, Y
   Lo, CC
   Lozupone, CA
   Lunsford, RD
   Madden, T
   Mahurkar, AA
   Mannon, PJ
   Mardis, ER
   Markowitz, VM
   Mavrommatis, K
   McCorrison, JM
   McDonald, D
   McEwen, J
   McGuire, AL
   McInnes, P
   Mehta, T
   Mihindukulasuriya, KA
   Miller, JR
   Minx, PJ
   Newsham, I
   Nusbaum, C
   O'Laughlin, M
   Orvis, J
   Pagani, I
   Palaniappan, K
   Patel, SM
   Pearson, M
   Peterson, J
   Podar, M
   Pohl, C
   Pollard, KS
   Priest, ME
   Proctor, LM
   Qin, X
   Raes, J
   Ravel, J
   Reid, JG
   Rho, M
   Rhodes, R
   Riehle, KP
   Rivera, MC
   Rodriguez-Mueller, B
   Rogers, YH
   Ross, MC
   Russ, C
   Sanka, RK
   Sankar, P
   Sathirapongsasuti, JF
   Schloss, JA
   Schloss, PD
   Schmidt, TM
   Scholz, M
   Schriml, L
   Schubert, AM
   Segata, N
   Segre, JA
   Shannon, WD
   Sharp, RR
   Sharpton, TJ
   Shenoy, N
   Sheth, NU
   Simone, GA
   Singh, I
   Smillie, CS
   Sobel, JD
   Sommer, DD
   Spicer, P
   Sutton, GG
   Sykes, SM
   Tabbaa, DG
   Thiagarajan, M
   Tomlinson, CM
   Torralba, M
   Treangen, TJ
   Truty, RM
   Vishnivetskaya, TA
   Walker, J
   Wang, L
   Wang, Z
   Ward, DV
   Warren, W
   Watson, MA
   Wellington, C
   Wetterstrand, KA
   White, JR
   Wilczek-Boney, K
   Wu, YQ
   Wylie, KM
   Wylie, T
   Yandava, C
   Ye, L
   Ye, Y
   Yooseph, S
   Youmans, BP
   Zhang, L
   Zhou, YJ
   Zhu, YM
   Zoloth, L
   Zucker, JD
   Birren, BW
   Gibbs, RA
   Highlander, SK
   Weinstock, GM
   Wilson, RK
   White, O
AF Methe, Barbara A.
   Nelson, Karen E.
   Pop, Mihai
   Creasy, Heather H.
   Giglio, Michelle G.
   Huttenhower, Curtis
   Gevers, Dirk
   Petrosino, Joseph F.
   Abubucker, Sahar
   Badger, Jonathan H.
   Chinwalla, Asif T.
   Earl, Ashlee M.
   FitzGerald, Michael G.
   Fulton, Robert S.
   Hallsworth-Pepin, Kymberlie
   Lobos, Elizabeth A.
   Madupu, Ramana
   Magrini, Vincent
   Martin, John C.
   Mitreva, Makedonka
   Muzny, Donna M.
   Sodergren, Erica J.
   Versalovic, James
   Wollam, Aye M.
   Worley, Kim C.
   Wortman, Jennifer R.
   Young, Sarah K.
   Zeng, Qiandong
   Aagaard, Kjersti M.
   Abolude, Olukemi O.
   Allen-Vercoe, Emma
   Alm, Eric J.
   Alvarado, Lucia
   Andersen, Gary L.
   Anderson, Scott
   Appelbaum, Elizabeth
   Arachchi, Harindra M.
   Armitage, Gary
   Arze, Cesar A.
   Ayvaz, Tulin
   Baker, Carl C.
   Begg, Lisa
   Belachew, Tsegahiwot
   Bhonagiri, Veena
   Bihan, Monika
   Blaser, Martin J.
   Bloom, Toby
   Bonazzi, Vivien R.
   Brooks, Paul
   Buck, GregoryA.
   Buhay, Christian J.
   Busam, Dana A.
   Campbell, Joseph L.
   Canon, Shane R.
   Cantarel, Brandi L.
   Chain, Patrick S.
   Chen, I-Min A.
   Chen, Lei
   Chhibba, Shaila
   Chu, Ken
   Ciulla, Dawn M.
   Clemente, Jose C.
   Clifton, Sandra W.
   Conlan, Sean
   Crabtree, Jonathan
   Cutting, Mary A.
   Davidovics, Noam J.
   Davis, Catherine C.
   DeSantis, Todd Z.
   Deal, Carolyn
   Delehaunty, Kimberley D.
   Dewhisrst, Floyd E.
   Deych, Elena
   Ding, Yan
   Dooling, David J.
   Dugan, Shannon P.
   Dunne, W. Michael, Jr.
   Durkin, A. Scott
   Edgar, Robert C.
   Erlich, Rachel L.
   Farmer, Candace N.
   Farrell, Ruth M.
   Faust, Karoline
   Feldgarden, Michael
   Felix, Victor M.
   Fisher, Sheila
   Fodor, Anthony A.
   Forney, Larry
   Foster, Leslie
   Di Francesco, Valentina
   Friedman, Jonathan
   Friedrich, Dennis C.
   Fronick, Catrina C.
   Fulton, Lucinda L.
   Gao, Hongyu
   Garcia, Nathalia
   Giannoukos, Georgia
   Giblin, Christina
   Giovanni, Maria Y.
   Goldberg, Jonathan M.
   Goll, Johannes
   Gonzalez, Antonio
   Griggs, Allison
   Gujja, Sharvari
   Haas, Brian J.
   Hamilton, Holli A.
   Harris, Emily L.
   Hepburn, Theresa A.
   Herter, Brandi
   Hoffmann, Diane E.
   Holder, Michael E.
   Howarth, Clinton
   Huang, Katherine H.
   Huse, Susan M.
   Izard, Jacques
   Jansson, Janet K.
   Jiang, Huaiyang
   Jordan, Catherine
   Joshi, Vandita
   Katancik, JamesA.
   Keitel, WendyA.
   Kelley, Scott T.
   Kells, Cristyn
   Kinder-Haake, Susan
   King, Nicholas B.
   Knight, Rob
   Knights, Dan
   Kong, Heidi H.
   Koren, Omry
   Koren, Sergey
   Kota, Karthik C.
   Kovar, Christie L.
   Kyrpides, Nikos C.
   La Rosa, Patricio S.
   Lee, Sandra L.
   Lemon, Katherine P.
   Lennon, Niall
   Lewis, Cecil M.
   Lewis, Lora
   Ley, Ruth E.
   Li, Kelvin
   Liolios, Konstantinos
   Liu, Bo
   Liu, Yue
   Lo, Chien-Chi
   Lozupone, Catherine A.
   Lunsford, R. Dwayne
   Madden, Tessa
   Mahurkar, Anup A.
   Mannon, Peter J.
   Mardis, Elaine R.
   Markowitz, Victor M.
   Mavrommatis, Konstantinos
   McCorrison, Jamison M.
   McDonald, Daniel
   McEwen, Jean
   McGuire, Amy L.
   McInnes, Pamela
   Mehta, Teena
   Mihindukulasuriya, Kathie A.
   Miller, Jason R.
   Minx, Patrick J.
   Newsham, Irene
   Nusbaum, Chad
   O'Laughlin, Michelle
   Orvis, Joshua
   Pagani, Ioanna
   Palaniappan, Krishna
   Patel, Shital M.
   Pearson, Matthew
   Peterson, Jane
   Podar, Mircea
   Pohl, Craig
   Pollard, Katherine S.
   Priest, Margaret E.
   Proctor, Lita M.
   Qin, Xiang
   Raes, Jeroen
   Ravel, Jacques
   Reid, Jeffrey G.
   Rho, Mina
   Rhodes, Rosamond
   Riehle, Kevin P.
   Rivera, Maria C.
   Rodriguez-Mueller, Beltran
   Rogers, Yu-Hui
   Ross, Matthew C.
   Russ, Carsten
   Sanka, Ravi K.
   Sankar, Pamela
   Sathirapongsasuti, J. Fah
   Schloss, Jeffery A.
   Schloss, Patrick D.
   Schmidt, Thomas M.
   Scholz, Matthew
   Schriml, Lynn
   Schubert, Alyxandria M.
   Segata, Nicola
   Segre, Julia A.
   Shannon, William D.
   Sharp, Richard R.
   Sharpton, Thomas J.
   Shenoy, Narmada
   Sheth, Nihar U.
   Simone, Gina A.
   Singh, Indresh
   Smillie, Chris S.
   Sobel, Jack D.
   Sommer, Daniel D.
   Spicer, Paul
   Sutton, Granger G.
   Sykes, Sean M.
   Tabbaa, Diana G.
   Thiagarajan, Mathangi
   Tomlinson, Chad M.
   Torralba, Manolito
   Treangen, Todd J.
   Truty, Rebecca M.
   Vishnivetskaya, Tatiana A.
   Walker, Jason
   Wang, Lu
   Wang, Zhengyuan
   Ward, Doyle V.
   Warren, Wesley
   Watson, Mark A.
   Wellington, Christopher
   Wetterstrand, Kris A.
   White, James R.
   Wilczek-Boney, Katarzyna
   Wu, Yuan Qing
   Wylie, Kristine M.
   Wylie, Todd
   Yandava, Chandri
   Ye, Liang
   Ye, Yuzhen
   Yooseph, Shibu
   Youmans, Bonnie P.
   Zhang, Lan
   Zhou, Yanjiao
   Zhu, Yiming
   Zoloth, Laurie
   Zucker, Jeremy D.
   Birren, Bruce W.
   Gibbs, Richard A.
   Highlander, Sarah K.
   Weinstock, George M.
   Wilson, Richard K.
   White, Owen
TI A framework for human microbiome research
SO NATURE
LA English
DT Article
ID catalog
AB A variety of microbial communities and their genes (the microbiome) exist throughout the human body, with fundamental roles in human health and disease. The National Institutes of Health (NIH)-funded Human Microbiome Project Consortium has established a population-scale framework to develop metagenomic protocols, resulting in a broad range of quality-controlled resources and data including standardized methods for creating, processing and interpreting distinct types of high-throughput metagenomic data available to the scientific community. Here we present resources from a population of 242 healthy adults sampled at 15 or 18 body sites up to three times, which have generated 5,177 microbial taxonomic profiles from 16S ribosomal RNA genes and over 3.5 terabases of metagenomic sequence so far. In parallel, approximately 800 reference strains isolated from the human body have been sequenced. Collectively, these data represent the largest resource describing the abundance and variety of the human microbiome, while providing a framework for current and future studies.
C1 [Methe, Barbara A.; Nelson, Karen E.; Madupu, Ramana; Bihan, Monika; Busam, Dana A.; Durkin, A. Scott; Foster, Leslie; Goll, Johannes; Li, Kelvin; McCorrison, Jamison M.; Miller, Jason R.; Orvis, Joshua; Rogers, Yu-Hui; Sanka, Ravi K.; Singh, Indresh; Sutton, Granger G.; Thiagarajan, Mathangi; Torralba, Manolito] J Craig Venter Inst, Rockville, MD 20850 USA.
   [Pop, Mihai; Koren, Sergey; Liu, Bo; Sommer, Daniel D.] Univ Maryland, Ctr Bioinformat & Computat Biol, College Pk, MD 20742 USA.
   [Pop, Mihai; Koren, Sergey; Liu, Bo; Sommer, Daniel D.] Univ Maryland, Dept Comp Sci, College Pk, MD 20742 USA.
   [Creasy, Heather H.; Giglio, Michelle G.; Abolude, Olukemi O.; Arze, Cesar A.; Cantarel, Brandi L.; Crabtree, Jonathan; Davidovics, Noam J.; Felix, Victor M.; Jordan, Catherine; Mahurkar, Anup A.; Ravel, Jacques; Schriml, Lynn; White, James R.; White, Owen] Univ Maryland, Sch Med, Inst Genome Sci, Baltimore, MD 21201 USA.
   [Huttenhower, Curtis; Sathirapongsasuti, J. Fah; Segata, Nicola] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
   [Huttenhower, Curtis; Gevers, Dirk; Earl, Ashlee M.; FitzGerald, Michael G.; Wortman, Jennifer R.; Young, Sarah K.; Zeng, Qiandong; Alm, Eric J.; Alvarado, Lucia; Anderson, Scott; Arachchi, Harindra M.; Bloom, Toby; Ciulla, Dawn M.; Erlich, Rachel L.; Feldgarden, Michael; Fisher, Sheila; Friedrich, Dennis C.; Giannoukos, Georgia; Goldberg, Jonathan M.; Griggs, Allison; Gujja, Sharvari; Haas, Brian J.; Hepburn, Theresa A.; Howarth, Clinton; Huang, Katherine H.; Jiang, Huaiyang; Kells, Cristyn; McDonald, Daniel; Mehta, Teena; Nusbaum, Chad; Pearson, Matthew; Priest, Margaret E.; Russ, Carsten; Shenoy, Narmada; Sykes, Sean M.; Tabbaa, Diana G.; Wang, Zhengyuan; Ward, Doyle V.; Wilczek-Boney, Katarzyna; Yandava, Chandri; Zucker, Jeremy D.; Birren, Bruce W.] Broad Inst & Harvard, Cambridge, MA 02142 USA.
   [Petrosino, Joseph F.; Muzny, Donna M.; Worley, Kim C.; Buhay, Christian J.; Ding, Yan; Dugan, Shannon P.; Holder, Michael E.; Joshi, Vandita; Kovar, Christie L.; Lee, Sandra L.; Lennon, Niall; Lewis, Lora; Liu, Yue; Newsham, Irene; Qin, Xiang; Reid, Jeffrey G.; Wu, Yuan Qing; Zhang, Lan; Zhu, Yiming; Gibbs, Richard A.; Highlander, Sarah K.] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA.
   [Abubucker, Sahar; Chinwalla, Asif T.; Fulton, Robert S.; Hallsworth-Pepin, Kymberlie; Lobos, Elizabeth A.; Magrini, Vincent; Martin, John C.; Mitreva, Makedonka; Sodergren, Erica J.; Wollam, Aye M.; Appelbaum, Elizabeth; Bhonagiri, Veena; Chen, Lei; Clifton, Sandra W.; Delehaunty, Kimberley D.; Deych, Elena; Dooling, David J.; Farmer, Candace N.; Fronick, Catrina C.; Fulton, Lucinda L.; Herter, Brandi; Kota, Karthik C.; Mardis, Elaine R.; Mihindukulasuriya, Kathie A.; Minx, Patrick J.; O'Laughlin, Michelle; Pagani, Ioanna; Pohl, Craig; Tomlinson, Chad M.; Walker, Jason; Warren, Wesley; Wylie, Kristine M.; Wylie, Todd; Ye, Liang; Zhou, Yanjiao; Weinstock, George M.; Wilson, Richard K.] Washington Univ, Sch Med, Genome Inst, St Louis, MO 63108 USA.
   [Versalovic, James; Gao, Hongyu] Baylor Coll Med, Dept Pathol & Immunol, Houston, TX 77030 USA.
   [Versalovic, James] Texas Childrens Hosp, Dept Pathol, Houston, TX 77030 USA.
   [Aagaard, Kjersti M.] Baylor Coll Med, Dept Obstet & Gynecol, Div Maternal Fetal Med, Houston, TX 77030 USA.
   [Allen-Vercoe, Emma] Univ Guelph, Dept Mol & Cellular Biol, Guelph, ON N1G 2W1, Canada.
   [Alm, Eric J.] MIT, Dept Civil & Environm Engn, Parsons Lab, Cambridge, MA 02139 USA.
   [Andersen, Gary L.] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Ctr Environm Biotechnol, Berkeley, CA 94720 USA.
   [Armitage, Gary] Univ Calif San Francisco, Sch Dent, San Francisco, CA 94143 USA.
   [Baker, Carl C.; Deal, Carolyn] Natl Inst Arthrit & Musculoskeletal & Skin Dis NI, NIH, Bethesda, MD 20892 USA.
   [Begg, Lisa] NIH, Off Res Womens Hlth, Bethesda, MD 20892 USA.
   [Belachew, Tsegahiwot; Campbell, Joseph L.; Di Francesco, Valentina; Giblin, Christina; Giovanni, Maria Y.] NIAID, NIH, Bethesda, MD 20892 USA.
   [Blaser, Martin J.] NYU, Langone Med Ctr, Dept Med, New York, NY 10016 USA.
   [Bonazzi, Vivien R.; Campbell, Joseph L.; Chhibba, Shaila; McEwen, Jean; Peterson, Jane; Proctor, Lita M.; Schloss, Jeffery A.; Wang, Lu; Wellington, Christopher; Wetterstrand, Kris A.] NHGRI, NIH, Bethesda, MD 20892 USA.
   [Brooks, Paul] Virginia Commonwealth Univ, Dept Stat Sci & Operat Res, Richmond, VA 23284 USA.
   [Brooks, Paul; Buck, GregoryA.; Rivera, Maria C.; Sheth, Nihar U.] Virginia Commonwealth Univ, Ctr Study Biol Complex, Richmond, VA 23284 USA.
   [Buck, GregoryA.; Rivera, Maria C.] Virginia Commonwealth Univ, Dept Biol, Richmond, VA 23284 USA.
   [Canon, Shane R.] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Technol Integrat Grp, Natl Energy Res Sci Comp, Berkeley, CA 94720 USA.
   [Chain, Patrick S.; Lo, Chien-Chi; Scholz, Matthew] Los Alamos Natl Lab, Genome Sci Grp, Biosci Div, HRL, Los Alamos, NM 87545 USA.
   [Chain, Patrick S.; Kyrpides, Nikos C.; Liolios, Konstantinos; Markowitz, Victor M.; Mavrommatis, Konstantinos] Joint Genome Inst, Walnut Creek, CA 94598 USA.
   [Chen, I-Min A.; Chu, Ken; Markowitz, Victor M.; Palaniappan, Krishna] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Biol Data Management & Technol Ctr, Computat Res Div, Berkeley, CA 94720 USA.
   [Clemente, Jose C.; Knight, Rob; Lozupone, Catherine A.; McDonald, Daniel] Univ Colorado, Dept Chem & Biochem, Boulder, CO 80309 USA.
   [Cutting, Mary A.; Hamilton, Holli A.; Harris, Emily L.; Lunsford, R. Dwayne; McInnes, Pamela] NIDCR, NIH, Bethesda, MD 20892 USA.
   [Davis, Catherine C.] Procter & Gamble Co, FemCare Prod Safety & Regulatory Affairs, Cincinnati, OH 45224 USA.
   [DeSantis, Todd Z.] Second Genome Inc, San Bruno, CA 94066 USA.
   [Dewhisrst, Floyd E.; Izard, Jacques; Lemon, Katherine P.] Forsyth Inst, Dept Mol Genet, Cambridge, MA 02142 USA.
   [Dewhisrst, Floyd E.] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA.
   [Dunne, W. Michael, Jr.; Watson, Mark A.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA.
   [Dunne, W. Michael, Jr.] bioMerieux Inc, Durham, NC 27712 USA.
   [Edgar, Robert C.] Drive5 Com, Tiburon, CA 94920 USA.
   [Farrell, Ruth M.; Sharp, Richard R.] Cleveland Clin, Ctr Bioeth Human & Spiritual Care, Cleveland, OH 44195 USA.
   [Faust, Karoline; Raes, Jeroen] VIB, Dept Biol Struct, B-1050 Brussels, Belgium.
   [Faust, Karoline; Raes, Jeroen] Vrije Univ Brussel, Dept Appl Biol Sci DBIT, B-1050 Brussels, Belgium.
   [Fodor, Anthony A.] Univ N Carolina, Dept Bioinformat & Genom, Charlotte, NC 28223 USA.
   [Forney, Larry] Univ Idaho, Dept Biol Sci, Moscow, ID 83844 USA.
   [Friedman, Jonathan; Smillie, Chris S.] MIT, Parsons Lab, Cambridge, MA 02139 USA.
   [Garcia, Nathalia] St Louis Univ, Ctr Adv Dent Educ, St Louis, MO 63104 USA.
   [Gonzalez, Antonio; Knights, Dan] Univ Colorado, Dept Comp Sci, Boulder, CO 80309 USA.
   [Hoffmann, Diane E.] Univ Maryland, Francis King Carey Sch Law, Baltimore, MD 21201 USA.
   [Huse, Susan M.] Josephine Bay Paul Ctr, Marine Biol Lab, Woods Hole, MA 02543 USA.
   [Jansson, Janet K.] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Dept Ecol, Div Earth Sci, Berkeley, CA 94720 USA.
   [Katancik, JamesA.] Univ Texas Hlth Sci Ctr Houston, Sch Dent, Dept Periodont, Houston, TX 77030 USA.
   [Kelley, Scott T.; Rodriguez-Mueller, Beltran] San Diego State Univ, Dept Biol, San Diego, CA 92182 USA.
   [Kinder-Haake, Susan] Univ Calif Los Angeles, Sch Dent, Div Associated Clin Specialties, Los Angeles, CA 90095 USA.
   [Kinder-Haake, Susan] Univ Calif Los Angeles, Dent Res Inst, Los Angeles, CA 90095 USA.
   [King, Nicholas B.] McGill Univ, Fac Med, Montreal, PQ H3A 1X1, Canada.
   [Knight, Rob] Howard Hughes Med Inst, Boulder, CO 80309 USA.
   [Kong, Heidi H.] NCI, NIH, Bethesda, MD 20892 USA.
   [Koren, Omry; Ley, Ruth E.] Cornell Univ, Dept Microbiol, Ithaca, NY USA.
   [La Rosa, Patricio S.; Shannon, William D.] Washington Univ, Sch Med, Dept Med, Div Gen Med Sci, St Louis, MO 63110 USA.
   [Lemon, Katherine P.; Ravel, Jacques] Harvard Univ, Sch Med, Childrens Hosp Boston, Div Infect Dis, Boston, MA 02115 USA.
   [Lewis, Cecil M.; Rho, Mina; Spicer, Paul] Univ Oklahoma, Dept Anthropol, Norman, OK 73019 USA.
   [Madden, Tessa] Washington Univ, Sch Med, Dept Obstet & Gynecol, St Louis, MO 63110 USA.
   [Mannon, Peter J.] Univ Alabama Birmingham, Div Gastroenterol & Hepatol, Birmingham, AL 35294 USA.
   [Podar, Mircea; Vishnivetskaya, Tatiana A.] Oak Ridge Natl Lab, Biosci Div, Oak Ridge, TN 37831 USA.
   [Pollard, Katherine S.; Sharpton, Thomas J.; Truty, Rebecca M.] Univ Calif San Francisco, Gladstone Inst, San Francisco, CA 94158 USA.
   [Pollard, Katherine S.] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94158 USA.
   [Pollard, Katherine S.] Univ Calif San Francisco, Div Biostat, San Francisco, CA 94158 USA.
   [Pollard, Katherine S.] Univ Maryland, Sch Med, Dept Microbiol & Immunol, Baltimore, MD 21201 USA.
   [Ye, Yuzhen] Indiana Univ, Sch Informat & Comp, Bloomington, IN 47405 USA.
   [Rhodes, Rosamond] Mt Sinai Sch Med, New York, NY 10029 USA.
   [Riehle, Kevin P.] Baylor Coll Med Mol & Human Genet, Houston, TX 77030 USA.
   [Sankar, Pamela] Univ Penn, Ctr Bioeth, Philadelphia, PA 19104 USA.
   [Sankar, Pamela] Univ Penn, Dept Med Eth, Philadelphia, PA 19104 USA.
   [Schloss, Patrick D.; Schubert, Alyxandria M.] Univ Michigan, Dept Microbiol & Immunol, Ann Arbor, MI 48109 USA.
   [Schmidt, Thomas M.] Michigan State Univ, Dept Microbiol, E Lansing, MI 48824 USA.
   [Simone, Gina A.] EMMES Corp, Rockville, MD 20850 USA.
   [Sobel, Jack D.] Wayne State Univ, Sch Med, Harper Univ Hosp, Detroit, MI 48201 USA.
   [Treangen, Todd J.] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA.
   [Badger, Jonathan H.; Yooseph, Shibu] J Craig Venter Inst, San Diego, CA 92121 USA.
   [Zoloth, Laurie] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA.
   [Petrosino, Joseph F.] Baylor Coll Med, Alkek Ctr Metagen & Microbiome Res, Houston, TX 77030 USA.
   [Conlan, Sean; Segre, Julia A.] NHGRI, NIH, Genet & Mol Biol Branch, Bethesda, MD 20892 USA.
C3 J. Craig Venter Institute; University System of Maryland; University of Maryland College Park; University System of Maryland; University of Maryland College Park; University System of Maryland; University of Maryland Baltimore; Harvard University; Harvard T.H. Chan School of Public Health; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Baylor College of Medicine; Washington University (WUSTL); Baylor College of Medicine; Baylor College of Medicine; Baylor College Medical Hospital; Baylor College of Medicine; University of Guelph; Massachusetts Institute of Technology (MIT); 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 San Francisco; National Institutes of Health (NIH) - USA; NIH National Institute of Arthritis & Musculoskeletal & Skin Diseases (NIAMS); National Institutes of Health (NIH) - USA; NIH Office of Research on Women's Health (ORWH); National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID); New York University; NYU Langone Medical Center; National Institutes of Health (NIH) - USA; NIH National Human Genome Research Institute (NHGRI); Virginia Commonwealth University; Virginia Commonwealth University; Virginia Commonwealth University; United States Department of Energy (DOE); Lawrence Berkeley National Laboratory; University of California System; University of California Berkeley; United States Department of Energy (DOE); Los Alamos National Laboratory; HRL Laboratories; United States Department of Energy (DOE); Joint Genome Institute - JGI; Joint BioEnergy Institute - JBEI; United States Department of Energy (DOE); Lawrence Berkeley National Laboratory; University of California System; University of California Berkeley; University of Colorado System; University of Colorado Boulder; National Institutes of Health (NIH) - USA; NIH National Institute of Dental & Craniofacial Research (NIDCR); Procter & Gamble; Harvard University; Harvard University Medical Affiliates; Forsyth Institute; Harvard University; Washington University (WUSTL); bioMerieux; Cleveland Clinic Foundation; Flanders Institute for Biotechnology (VIB); Vrije Universiteit Brussel; University of North Carolina; University of North Carolina Charlotte; University of Idaho; Massachusetts Institute of Technology (MIT); Saint Louis University; University of Colorado System; University of Colorado Boulder; University System of Maryland; University of Maryland Baltimore; Marine Biological Laboratory - Woods Hole; University of California System; University of California Berkeley; United States Department of Energy (DOE); Lawrence Berkeley National Laboratory; University of Texas System; University of Texas Health Science Center Houston; California State University System; San Diego State University; University of California System; University of California Los Angeles; University of California System; University of California Los Angeles; McGill University; Howard Hughes Medical Institute; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); Cornell University; Washington University (WUSTL); Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Boston Children's Hospital; University of Oklahoma System; University of Oklahoma - Norman; Washington University (WUSTL); University of Alabama System; University of Alabama Birmingham; United States Department of Energy (DOE); Oak Ridge National Laboratory; 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 System of Maryland; University of Maryland Baltimore; Indiana University System; Indiana University Bloomington; Icahn School of Medicine at Mount Sinai; Baylor College of Medicine; University of Pennsylvania; University of Pennsylvania; University of Michigan System; University of Michigan; Michigan State University; Emmes Corporation; Wayne State University; Johns Hopkins University; Johns Hopkins Bloomberg School of Public Health; J. Craig Venter Institute; Northwestern University; Feinberg School of Medicine; Baylor College of Medicine; National Institutes of Health (NIH) - USA; NIH National Human Genome Research Institute (NHGRI)
RP Methé, BA (corresponding author), J Craig Venter Inst, 9704 Med Ctr Dr, Rockville, MD 20850 USA.
FU NIH [U54HG004969, U54HG003273, U54HG004973, U54HG003067, U54AI084844, N01AI30071, U54HG004968, U01HG004866, U54HG003079, R01HG005969, R01HG004872, R01HG004885, R01HG005975, R01HG004908, R01HG004900, R01HG005171, R01HG004853, R01HG004856, R01HG004877, R01HG005172, R01HG004857, R01HG004906, R21HG005811, UH2AI083263, UH3AI083263, UH2AR057506, UH3DK083993, UH2DK083990, UH2AR057504, UH3AR057504, DP2OD001500, N01HG62088, U01DE016937, RC1DE020298, R01DE021574, R21CA139193, P30DE020751, T32AI007528]; Army Research Office [W911NF-11-1-0473]; National Science Foundation [NSF DBI-1053486, NSF IIS-0812111]; Office of Science of the US Department of Energy [DE-AC02-05CH11231]; LANL Laboratory [20100034DR]; US Defense Threat Reduction Agency [B104153I, B084531I]; Research Foundation - Flanders (FWO); Gordon & Betty Moore Foundation from the J. David Gladstone Institutes; Rackham Graduate School; Crohn's and Colitis Foundation of Canada; IBM; Direct For Biological Sciences; Div Of Biological Infrastructure [1053486] Funding Source: National Science Foundation; National Cancer Institute [ZIABC010938] Funding Source: NIH RePORTER; National Institute of Allergy and Infectious Diseases [T32AI007528] Funding Source: NIH RePORTER
NR 16
TC 1858
Z9 2216
U1 7
U2 467
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 14
PY 2012
VL 486
IS 7402
BP 215
EP 221
DI 10.1038/nature11209
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 957UH
UT WOS:000305189000026
PM 22699610
DA 2026-03-09
ER

PT J
AU Wedemeyer-Böhm, S
   Scullion, E
   Steiner, O
   van der Voort, LR
   Rodriguez, JD
   Fedun, V
   Erdélyi, R
AF Wedemeyer-Bohm, Sven
   Scullion, Eamon
   Steiner, Oskar
   van der Voort, Luc Rouppe
   Rodriguez, Jaime de la Cruz
   Fedun, Viktor
   Erdelyi, Robert
TI Magnetic tornadoes as energy channels into the solar corona
SO NATURE
LA English
DT Article
ID driven vortex flows; alfvenic waves; quiet sun; wind; simulations; granulation; photosphere; convection; turbulence; power
AB Heating the outer layers of the magnetically quiet solar atmosphere to more than one million kelvin and accelerating the solar wind requires an energy flux of approximately 100 to 300 watts per square metre(1-6), but how this energy is transferred and dissipated there is a puzzle and several alternative solutions have been proposed. Braiding and twisting of magnetic field structures, which is caused by the convective flows at the solar surface, was suggested as an efficient mechanism for atmospheric heating(7). Convectively driven vortex flows that harbour magnetic fields are observed(8-10) to be abundant in the photosphere (the visible surface of the Sun). Recently, corresponding swirling motions have been discovered(11) in the chromosphere, the atmospheric layer sandwiched between the photosphere and the corona. Here we report the imprints of these chromospheric swirls in the transition region and low corona, and identify them as observational signatures of rapidly rotating magnetic structures. These ubiquitous structures, which resemble super-tornadoes under solar conditions, reach from the convection zone into the upper solar atmosphere and provide an alternative mechanism for channelling energy from the lower into the upper solar atmosphere.
C1 [Wedemeyer-Bohm, Sven; Scullion, Eamon; van der Voort, Luc Rouppe] Univ Oslo, Inst Theoret Astrophys, N-0315 Oslo, Norway.
   [Wedemeyer-Bohm, Sven] Univ Oslo, Ctr Math Applicat, N-0316 Oslo, Norway.
   [Steiner, Oskar] Kiepenheuer Inst Solar Phys, D-79104 Freiburg, Germany.
   [Rodriguez, Jaime de la Cruz] Uppsala Univ, Dept Phys & Astron, SE-75120 Uppsala, Sweden.
   [Fedun, Viktor; Erdelyi, Robert] Univ Sheffield, Sch Math & Stat, Solar Phys & Space Plasma Res Ctr, Sheffield S3 7RH, S Yorkshire, England.
C3 University of Oslo; University of Oslo; Kiepenheuer Institut fur Sonnenphysik; Uppsala University; University of Sheffield
RP Wedemeyer-Böhm, S (corresponding author), Univ Oslo, Inst Theoret Astrophys, POB 1029 Blindern, N-0315 Oslo, Norway.
EM svenwe@astro.uio.no
FU Research Council of Norway; Science and Technology Facilities, UK; STFC [ST/J001430/1] Funding Source: UKRI; Science and Technology Facilities Council [ST/J001430/1] Funding Source: researchfish
NR 30
TC 294
Z9 302
U1 0
U2 30
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 28
PY 2012
VL 486
IS 7404
BP 505
EP 508
DI 10.1038/nature11202
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 965IJ
UT WOS:000305760600037
PM 22739314
DA 2026-03-09
ER

PT J
AU Gleeson, T
   Wada, Y
   Bierkens, MFP
   van Beek, LPH
AF Gleeson, Tom
   Wada, Yoshihide
   Bierkens, Marc F. P.
   van Beek, Ludovicus P. H.
TI Water balance of global aquifers revealed by groundwater footprint
SO NATURE
LA English
DT Article
ID human appropriation; resources
AB Groundwater is a life-sustaining resource that supplies water to billions of people, plays a central part in irrigated agriculture and influences the health of many ecosystems(1,2). Most assessments of global water resources have focused on surface water(3-6), but unsustainable depletion of groundwater has recently been documented on both regional(7,8) and global scales(9-11). It remains unclear how the rate of global groundwater depletion compares to the rate of natural renewal and the supply needed to support ecosystems. Here we define the groundwater footprint (the area required to sustain groundwater use and groundwater-dependent ecosystem services) and show that humans are overexploiting groundwater in many large aquifers that are critical to agriculture, especially in Asia and North America. We estimate that the size of the global groundwater footprint is currently about 3.5 times the actual area of aquifers and that about 1.7 billion people live in areas where groundwater resources and/or groundwater-dependent ecosystems are under threat. That said, 80 per cent of aquifers have a groundwater footprint that is less than their area, meaning that the net global value is driven by a few heavily overexploited aquifers. The groundwater footprint is the first tool suitable for consistently evaluating the use, renewal and ecosystem requirements of groundwater at an aquifer scale. It can be combined with the water footprint and virtual water calculations(12-14), and be used to assess the potential for increasing agricultural yields with renewable groundwaterref(15). The method could be modified to evaluate other resources with renewal rates that are slow and spatially heterogeneous, such as fisheries, forestry or soil.
C1 [Gleeson, Tom] McGill Univ, Dept Civil Engn, Montreal, PQ H3A 0C3, Canada.
   [Wada, Yoshihide; Bierkens, Marc F. P.; van Beek, Ludovicus P. H.] Univ Utrecht, Fac Geosci, Dept Phys Geog, NL-3508 TC Utrecht, Netherlands.
   [Bierkens, Marc F. P.] Deltares, NL-3508 AL Utrecht, Netherlands.
C3 McGill University; Utrecht University; Deltares
RP Gleeson, T (corresponding author), McGill Univ, Dept Civil Engn, Montreal, PQ H3A 0C3, Canada.
EM tom.gleeson@mcgill.ca
FU Natural Sciences and Engineering Research Council of Canada; Canadian Institute for Advanced Research junior fellowship; Utrecht University Focus Areas Theme 'Earth and sustainability'
NR 29
TC 1116
Z9 1335
U1 18
U2 858
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD AUG 9
PY 2012
VL 488
IS 7410
BP 197
EP 200
DI 10.1038/nature11295
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 985LE
UT WOS:000307267000030
PM 22874965
DA 2026-03-09
ER

PT J
AU Chiang, N
   Fredman, G
   Bäckhed, F
   Oh, SF
   Vickery, T
   Schmidt, BA
   Serhan, CN
AF Chiang, Nan
   Fredman, Gabrielle
   Backhed, Fredrik
   Oh, Sungwhan F.
   Vickery, Thad
   Schmidt, Birgitta A.
   Serhan, Charles N.
TI Infection regulates pro-resolving mediators that lower antibiotic requirements
SO NATURE
LA English
DT Article
ID acute lung injury; inflammation; resolution; aspirin; innate; mice; phagocytosis; macrophages; inhibition; responses
AB Underlying mechanisms for how bacterial infections contribute to active resolution of acute inflammation are unknown(1-4). Here, we performed exudate leukocyte trafficking and mediator-metabololipidomics of murine peritoneal Escherichia coli infections with temporal identification of pro-inflammatory (prostaglandins and leukotrienes) and specialized pro-resolving mediators (SPMs). In self-resolving E. coli exudates (10(5) colony forming units, c.f.u.), the dominant SPMs identified were resolvin (Rv) D5 and protectin D1 (PD1), which at 12 h were at significantly greater levels than in exudates from higher titre E. coli (10(7) c.f.u.)-challenged mice. Germfree mice had endogenous RvD1 and PD1 levels higher than in conventional mice. RvD1 and RvD5 (nanograms per mouse) each reduced bacterial titres in blood and exudates, E. coli-induced hypothermia and increased survival, demonstrating the first actions of RvD5. With human polymorphonuclear neutrophils and macrophages, RvD1, RvD5 and PD1 each directly enhanced phagocytosis of E. coli, and RvD5 counter-regulated a panel of pro-inflammatory genes, including NF-kappa B and TNF-alpha. RvD5 activated the RvD1 receptor, GPR32, to enhance phagocytosis. With self-limited E. coli infections, RvD1 and the antibiotic ciprofloxacin accelerated resolution, each shortening resolution intervals (R-i). Host-directed RvD1 actions enhanced ciprofloxacin's therapeutic actions. In 10(7) c.f.u. E. coli infections, SPMs (RvD1, RvD5, PD1) together with ciprofloxacin also heightened host antimicrobial responses. In skin infections, SPMs enhanced vancomycin clearance of Staphylococcus aureus. These results demonstrate that specific SPMs are temporally and differentially regulated during infections and that they are anti-phlogistic, enhance containment and lower antibiotic requirements for bacterial clearance.
C1 [Chiang, Nan; Fredman, Gabrielle; Oh, Sungwhan F.; Vickery, Thad; Schmidt, Birgitta A.; Serhan, Charles N.] Brigham & Womens Hosp, Ctr Expt Therapeut & Reperfus Injury, Dept Anesthesiol Perioperat & Pain Med, Harvard Inst Med, Boston, MA 02115 USA.
   [Backhed, Fredrik] Univ Gothenburg, Sahlgrenska Ctr Cardiovasc & Metab Res, Wallenberg Lab, SE-41345 Gothenburg, Sweden.
C3 Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Brigham & Women's Hospital; University of Gothenburg
RP Serhan, CN (corresponding author), Brigham & Womens Hosp, Ctr Expt Therapeut & Reperfus Injury, Dept Anesthesiol Perioperat & Pain Med, Harvard Inst Med, 75 Francis St, Boston, MA 02115 USA.
EM cnserhan@zeus.bwh.harvard.edu
FU NIH [P01GM095467, R01GM38765]
NR 30
TC 574
Z9 621
U1 1
U2 102
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD APR 26
PY 2012
VL 484
IS 7395
BP 524
EP U152
DI 10.1038/nature11042
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 931FF
UT WOS:000303200400053
PM 22538616
DA 2026-03-09
ER

PT J
AU Duong, DL
   Han, GH
   Lee, SM
   Gunes, F
   Kim, ES
   Kim, ST
   Kim, H
   Ta, QH
   So, KP
   Yoon, SJ
   Chae, SJ
   Jo, YW
   Park, MH
   Chae, SH
   Lim, SC
   Choi, JY
   Lee, YH
AF Dinh Loc Duong
   Han, Gang Hee
   Lee, Seung Mi
   Gunes, Fethullah
   Kim, Eun Sung
   Kim, Sung Tae
   Kim, Heetae
   Quang Huy Ta
   So, Kang Pyo
   Yoon, Seok Jun
   Chae, Seung Jin
   Jo, Young Woo
   Park, Min Ho
   Chae, Sang Hoon
   Lim, Seong Chu
   Choi, Jae Young
   Lee, Young Hee
TI Probing graphene grain boundaries with optical microscopy
SO NATURE
LA English
DT Article
ID chemical-vapor-deposition; polycrystalline graphene; ozone; films
AB Grain boundaries in graphene are formed by the joining of islands during the initial growth stage, and these boundaries govern transport properties and related device performance(1,2). Although information on the atomic rearrangement at graphene grain boundaries can be obtained using transmission electron microscopy(3,4) and scanning tunnelling microscopy(2,5-8), large-scale information regarding the distribution of graphene grain boundaries is not easily accessible. Here we use optical microscopy to observe the grain boundaries of large-area graphene (grown on copper foil) directly, without transfer of the graphene. This imaging technique was realized by selectively oxidizing the underlying copper foil through graphene grain boundaries functionalized with O and OH radicals generated by ultraviolet irradiation under moisture-rich ambient conditions: selective diffusion of oxygen radicals through OH-functionalized defect sites was demonstrated by density functional calculations. The sheet resistance of large-area graphene decreased as the graphene grain sizes increased, but no strong correlation with the grain size of the copper was revealed, in contrast to a previous report(9). Furthermore, the influence of graphene grain boundaries on crack propagation (initialized by bending) and termination was clearly visualized using our technique. Our approach can be used as a simple protocol for evaluating the grain boundaries of other two-dimensional layered structures, such as boron nitride and exfoliated clays.
C1 [Dinh Loc Duong; Chae, Seung Jin; Lee, Young Hee] Sungkyunkwan Univ, Sungkyunkwan Adv Inst Nanotechnol, Suwon 440746, South Korea.
   [Dinh Loc Duong; Han, Gang Hee; Gunes, Fethullah; Kim, Eun Sung; Kim, Sung Tae; Kim, Heetae; Quang Huy Ta; So, Kang Pyo; Yoon, Seok Jun; Chae, Seung Jin; Jo, Young Woo; Chae, Sang Hoon; Lim, Seong Chu; Choi, Jae Young; Lee, Young Hee] Sungkyunkwan Univ, Graphene Ctr, Dept Energy Sci, Phys Div BK21, Suwon 440746, South Korea.
   [Lee, Seung Mi] Korea Res Inst Stand & Sci, Ctr Nanocharacterizat, Taejon 305340, South Korea.
   [Park, Min Ho] Sungkyunkwan Univ, Sch Adv Mat Sci & Engn, Suwon 440746, South Korea.
   [Choi, Jae Young] Samsung Adv Inst Technol SAIT, Graphene Ctr, Suwon 440600, South Korea.
C3 Sungkyunkwan University (SKKU); Sungkyunkwan University (SKKU); Korea Research Institute of Standards & Science (KRISS); Sungkyunkwan University (SKKU); Samsung
RP Lee, YH (corresponding author), Sungkyunkwan Univ, Sungkyunkwan Adv Inst Nanotechnol, Suwon 440746, South Korea.
EM leeyoung@skku.edu
FU Star Faculty programme of the NRF of Korea [2010-0029653]; International Research and Development programme of the NRF of Korea [2011-00242]; WCU programme of the NRF of Korea [R31-2008-10029]; MEST; Formas [2011-00242] Funding Source: Formas
NR 30
TC 354
Z9 392
U1 5
U2 641
PU NATURE PUBLISHING 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 11
PY 2012
VL 490
IS 7419
BP 235
EP +
DI 10.1038/nature11562
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 019IY
UT WOS:000309733300044
PM 23034653
DA 2026-03-09
ER

PT J
AU Alsford, S
   Eckert, S
   Baker, N
   Glover, L
   Sanchez-Flores, A
   Leung, KF
   Turner, DJ
   Field, MC
   Berriman, M
   Horn, D
AF Alsford, Sam
   Eckert, Sabine
   Baker, Nicola
   Glover, Lucy
   Sanchez-Flores, Alejandro
   Leung, Ka Fai
   Turner, Daniel J.
   Field, Mark C.
   Berriman, Matthew
   Horn, David
TI High-throughput decoding of antitrypanosomal drug efficacy and resistance
SO NATURE
LA English
DT Article
ID blood-stream forms; trypanosoma-brucei; expression; glycoprotein; rnai; diamidine; lysosome; protease; suramin; genome
AB The concept of disease-specific chemotherapy was developed a century ago. Dyes and arsenical compounds that displayed selectivity against trypanosomes were central to this work(1,2), and the drugs that emerged remain in use for treating human African trypanosomiasis (HAT)(3). The importance of understanding the mechanisms underlying selective drug action and resistance for the development of improved HAT therapies has been recognized, but these mechanisms have remained largely unknown. Here we use all five current HAT drugs for genome-scale RNA interference target sequencing (RIT-seq) screens in Trypanosoma brucei, revealing the transporters, organelles, enzymes and metabolic pathways that function to facilitate antitrypanosomal drug action. RIT-seq profiling identifies both known drug importers(4,5) and the only known prodrug activator(6), and links more than fifty additional genes to drug action. A bloodstream stage-specific invariant surface glycoprotein (ISG75) family mediates suramin uptake, and the AP1 adaptin complex, lysosomal proteases and major lysosomal transmembrane protein, as well as spermidine and N-acetylglucosamine biosynthesis, all contribute to suramin action. Further screens link ubiquinone availability to nitro-drug action, plasma membrane P-type H+-ATPases to pentamidine action, and trypanothione and several putative kinases to melarsoprol action. We also demonstrate a major role for aquaglyceroporins in pentamidine and melarsoprol cross-resistance. These advances in our understanding of mechanisms of antitrypanosomal drug efficacy and resistance will aid the rational design of new therapies and help to combat drug resistance, and provide unprecedented molecular insight into the mode of action of antitrypanosomal drugs.
C1 [Alsford, Sam; Baker, Nicola; Glover, Lucy; Horn, David] London Sch Hyg & Trop Med, London WC1E 7HT, England.
   [Eckert, Sabine; Sanchez-Flores, Alejandro; Turner, Daniel J.; Berriman, Matthew] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England.
   [Leung, Ka Fai; Field, Mark C.] Univ Cambridge, Dept Pathol, Cambridge CB2 1QP, England.
C3 University of London; London School of Hygiene & Tropical Medicine; Wellcome Trust Sanger Institute; University of Cambridge
RP Horn, D (corresponding author), London Sch Hyg & Trop Med, Keppel St, London WC1E 7HT, England.
EM david.horn@lshtm.ac.uk
FU Wellcome Trust [093010/Z/10/Z, 085775/Z/08/Z, 090007/Z/09/Z]; Bloomsbury colleges PhD studentship; Wellcome Trust [090007/Z/09/Z, 093010/Z/10/Z] Funding Source: Wellcome Trust
NR 45
TC 254
Z9 274
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 FEB 9
PY 2012
VL 482
IS 7384
BP 232
EP U125
DI 10.1038/nature10771
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 888HI
UT WOS:000299994100041
PM 22278056
DA 2026-03-09
ER

PT J
AU Straub, AC
   Lohman, AW
   Billaud, M
   Johnstone, SR
   Dwyer, ST
   Lee, MY
   Bortz, PS
   Best, AK
   Columbus, L
   Gaston, B
   Isakson, BE
AF Straub, Adam C.
   Lohman, Alexander W.
   Billaud, Marie
   Johnstone, Scott R.
   Dwyer, Scott T.
   Lee, Monica Y.
   Bortz, Pamela Schoppee
   Best, Angela K.
   Columbus, Linda
   Gaston, Benjamin
   Isakson, Brant E.
TI Endothelial cell expression of haemoglobin α regulates nitric oxide signalling
SO NATURE
LA English
DT Article
ID relaxing factor; smooth-muscle; no; propylthiouracil; nitrosylation; hemoproteins; myoglobin; oxidation; reductase; proteins
AB Models of unregulated nitric oxide (NO) diffusion do not consistently account for the biochemistry of NO synthase (NOS)-dependent signalling in many cell systems(1-3). For example, endothelial NOS controls blood pressure, blood flow and oxygen delivery through its effect on vascular smooth muscle tone(4), but the regulation of these processes is not adequately explained by simple NO diffusion from endothelium to smooth muscle(3,5). Here we report a new model for the regulation of NO signalling by demonstrating that haemoglobin (Hb) alpha (encoded by the HBA1 and HBA2 genes in humans) is expressed in human and mouse arterial endothelial cells and enriched at the myoendothelial junction, where it regulates the effects of NO on vascular reactivity. Notably, this function is unique to Hb alpha and is abrogated by its genetic depletion. Mechanistically, endothelial Hb alpha haem iron in the Fe3+ state permits NO signalling, and this signalling is shut off when Hb alpha is reduced to the Fe2+ state by endothelial cytochrome b5 reductase 3 (CYB5R3, also known as diaphorase 1)(6). Genetic and pharmacological inhibition of CYB5R3 increases NO bioactivity in small arteries. These data reveal a new mechanism by which the regulation of the intracellular Hb alpha oxidation state controls NOS signalling in non-erythroid cells. This model may be relevant to haem-containing globins in a broad range of NOS-containing somatic cells(7-13).
C1 [Straub, Adam C.; Lohman, Alexander W.; Billaud, Marie; Johnstone, Scott R.; Lee, Monica Y.; Bortz, Pamela Schoppee; Best, Angela K.; Isakson, Brant E.] Univ Virginia, Robert M Berne Cardiovasc Res Ctr, Charlottesville, VA 22908 USA.
   [Lohman, Alexander W.; Billaud, Marie; Isakson, Brant E.] Univ Virginia, Dept Mol Physiol & Biol Phys, Charlottesville, VA 22908 USA.
   [Dwyer, Scott T.; Gaston, Benjamin] Univ Virginia, Dept Pediat, Charlottesville, VA 22908 USA.
   [Columbus, Linda] Univ Virginia, Dept Chem, Charlottesville, VA 22908 USA.
C3 University of Virginia; University of Virginia; University of Virginia; University of Virginia
RP Isakson, BE (corresponding author), Univ Virginia, Robert M Berne Cardiovasc Res Ctr, Charlottesville, VA 22908 USA.
EM brant@virginia.edu
FU American Heart Association; National Institutes of Health [HL088554, HL107963, HL059337, HL101871, HL112904, HL007284]; National Heart Lung and Blood Institute [T32HL007284] Funding Source: NIH RePORTER
NR 30
TC 273
Z9 311
U1 1
U2 81
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD NOV 15
PY 2012
VL 491
IS 7424
BP 473
EP 477
DI 10.1038/nature11626
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 036MY
UT WOS:000311031600052
PM 23123858
DA 2026-03-09
ER

PT J
AU Koboldt, DC
   Fulton, RS
   McLellan, MD
   Schmidt, H
   Kalicki-Veizer, J
   McMichael, JF
   Fulton, LL
   Dooling, DJ
   Ding, L
   Mardis, ER
   Wilson, RK
   Ally, A
   Balasundaram, M
   Butterfield, YSN
   Carlsen, R
   Carter, C
   Chu, A
   Chuah, E
   Chun, HJE
   Coope, RJN
   Dhalla, N
   Guin, R
   Hirst, C
   Hirst, M
   Holt, RA
   Lee, D
   Li, HYI
   Mayo, M
   Moore, RA
   Mungall, AJ
   Pleasance, E
   Robertson, AG
   Schein, JE
   Shafiei, A
   Sipahimalani, P
   Slobodan, JR
   Stoll, D
   Tam, A
   Thiessen, N
   Varhol, RJ
   Wye, N
   Zeng, T
   Zhao, YJ
   Birol, I
   Jones, SJM
   Marra, MA
   Cherniack, AD
   Saksena, G
   Onofrio, RC
   Pho, NH
   Carter, SL
   Schumacher, SE
   Tabak, B
   Hernandez, B
   Gentry, J
   Nguyen, H
   Crenshaw, A
   Ardlie, K
   Beroukhim, R
   Winckler, W
   Getz, G
   Gabriel, SB
   Meyerson, M
   Chin, L
   Park, PJ
   Kucherlapati, R
   Hoadley, KA
   Auman, JT
   Fan, C
   Turman, YJ
   Shi, Y
   Li, L
   Topal, MD
   He, XP
   Chao, HH
   Prat, A
   Silva, GO
   Iglesia, MD
   Zhao, W
   Usary, J
   Berg, JS
   Adams, M
   Booker, J
   Wu, JY
   Gulabani, A
   Bodenheimer, T
   Hoyle, AP
   Simons, JV
   Soloway, MG
   Mose, LE
   Jefferys, SR
   Balu, S
   Parker, JS
   Hayes, DN
   Perou, CM
   Malik, S
   Mahurkar, S
   Shen, H
   Weisenberger, DJ
   Triche, T
   Lai, PH
   Bootwalla, MS
   Maglinte, DT
   Berman, BP
   Van den Berg, DJ
   Baylin, SB
   Laird, PW
   Creighton, CJ
   Donehower, LA
   Getz, G
   Noble, M
   Voet, D
   Saksena, G
   Gehlenborg, N
   DiCara, D
   Zhang, JH
   Zhang, HL
   Wu, CJ
   Liu, SY
   Lawrence, MS
   Zou, LH
   Sivachenko, A
   Lin, P
   Stojanov, P
   Jing, R
   Cho, J
   Sinha, R
   Park, RW
   Nazaire, MD
   Robinson, J
   Thorvaldsdottir, H
   Mesirov, J
   Park, PJ
   Chin, L
   Reynolds, S
   Kreisberg, RB
   Bernard, B
   Bressler, R
   Erkkila, T
   Lin, J
   Thorsson, V
   Zhang, W
   Shmulevich, I
   Ciriello, G
   Weinhold, N
   Schultz, N
   Gao, JJ
   Cerami, E
   Gross, B
   Jacobsen, A
   Sinha, R
   Aksoy, BA
   Antipin, Y
   Reva, B
   Shen, RL
   Taylor, BS
   Ladanyi, M
   Sander, C
   Anur, P
   Spellman, PT
   Lu, YL
   Liu, WB
   Verhaak, RRG
   Mills, GB
   Akbani, R
   Zhang, NX
   Broom, BM
   Casasent, TD
   Wakefield, C
   Unruh, AK
   Baggerly, K
   Coombes, K
   Weinstein, JN
   Haussler, D
   Benz, CC
   Stuart, JM
   Benz, SC
   Zhu, JC
   Szeto, CC
   Scott, GK
   Yau, C
   Paul, EO
   Carlin, D
   Wong, C
   Sokolov, A
   Thusberg, J
   Mooney, S
   Ng, S
   Goldstein, TC
   Ellrott, K
   Grifford, M
   Wilks, C
   Ma, S
   Craft, B
   Yan, CH
   Hu, Y
   Meerzaman, D
   Gastier-Foster, JM
   Bowen, J
   Ramirez, NC
   Black, AD
   Pyatt, RE
   White, P
   Zmuda, EJ
   Frick, J
   Lichtenberg, T
   Brookens, R
   George, MM
   Gerken, MA
   Harper, HA
   Leraas, KM
   Wise, LJ
   Tabler, TR
   McAllister, C
   Barr, T
   Hart-Kothari, M
   Tarvin, K
   Saller, C
   Sandusky, G
   Mitchell, C
   Iacocca, MV
   Brown, J
   Rabeno, B
   Czerwinski, C
   Petrelli, N
   Dolzhansky, O
   Abramov, M
   Voronina, O
   Potapova, O
   Marks, JR
   Suchorska, WM
   Murawa, D
   Kycler, W
   Ibbs, M
   Korski, K
   Spychala, A
   Murawa, P
   Brzezinski, JJ
   Perz, H
   Lazniak, R
   Teresiak, M
   Tatka, H
   Leporowska, E
   Bogusz-Czerniewicz, M
   Malicki, J
   Mackiewicz, A
   Wiznerowicz, M
   Le, XV
   Kohl, B
   Tien, NV
   Thorp, R
   Bang, NV
   Sussman, H
   Phu, BD
   Hajek, R
   Hung, NP
   Tran, VTP
   Thang, HQ
   Khan, KZ
   Penny, R
   Mallery, D
   Curley, E
   Shelton, C
   Yena, P
   Ingle, JN
   Couch, FJ
   Lingle, WL
   King, TA
   Gonzalez-Angulo, AM
   Mills, GB
   Dyer, MD
   Liu, SY
   Meng, XL
   Patangan, M
   Waldman, F
   Stöppler, H
   Rathmell, WK
   Thorne, L
   Huang, M
   Boice, L
   Hill, A
   Morrison, C
   Gaudioso, C
   Bshara, W
   Daily, K
   Egea, SC
   Pegram, MD
   Gomez-Fernandez, C
   Dhir, R
   Bhargava, R
   Brufsky, A
   Shriver, CD
   Hooke, JA
   Campbell, JL
   Mural, RJ
   Hu, H
   Somiari, S
   Larson, C
   Deyarmin, B
   Kvecher, L
   Kovatich, AJ
   Ellis, MJ
   King, TA
   Hu, H
   Couch, FJ
   Mural, RJ
   Stricker, T
   White, K
   Olopade, O
   Ingle, JN
   Luo, CQ
   Chen, YQ
   Marks, JR
   Waldman, F
   Wiznerowicz, M
   Bose, R
   Chang, LW
   Beck, AH
   Gonzalez-Angulo, AM
   Pihl, T
   Jensen, M
   Sfeir, R
   Kahn, A
   Chu, A
   Kothiyal, P
   Wang, ZN
   Snyder, E
   Pontius, J
   Ayala, B
   Backus, M
   Walton, J
   Baboud, J
   Berton, D
   Nicholls, M
   Srinivasan, D
   Raman, R
   Girshik, S
   Kigonya, P
   Alonso, S
   Sanbhadti, R
   Barletta, S
   Pot, D
   Sheth, M
   Demchok, JA
   Shaw, KRM
   Yang, LM
   Eley, G
   Ferguson, ML
   Tarnuzzer, RW
   Zhang, JS
   Dillon, LAL
   Buetow, K
   Fielding, P
   Ozenberger, BA
   Guyer, MS
   Sofia, HJ
   Palchik, JD
AF Koboldt, Daniel C.
   Fulton, Robert S.
   McLellan, Michael D.
   Schmidt, Heather
   Kalicki-Veizer, Joelle
   McMichael, Joshua F.
   Fulton, Lucinda L.
   Dooling, David J.
   Ding, Li
   Mardis, Elaine R.
   Wilson, Richard K.
   Ally, Adrian
   Balasundaram, Miruna
   Butterfield, Yaron S. N.
   Carlsen, Rebecca
   Carter, Candace
   Chu, Andy
   Chuah, Eric
   Chun, Hye-Jung E.
   Coope, Robin J. N.
   Dhalla, Noreen
   Guin, Ranabir
   Hirst, Carrie
   Hirst, Martin
   Holt, Robert A.
   Lee, Darlene
   Li, Haiyan I.
   Mayo, Michael
   Moore, Richard A.
   Mungall, Andrew J.
   Pleasance, Erin
   Robertson, A. Gordon
   Schein, Jacqueline E.
   Shafiei, Arash
   Sipahimalani, Payal
   Slobodan, Jared R.
   Stoll, Dominik
   Tam, Angela
   Thiessen, Nina
   Varhol, Richard J.
   Wye, Natasja
   Zeng, Thomas
   Zhao, Yongjun
   Birol, Inanc
   Jones, Steven J. M.
   Marra, Marco A.
   Cherniack, Andrew D.
   Saksena, Gordon
   Onofrio, Robert C.
   Pho, Nam H.
   Carter, Scott L.
   Schumacher, Steven E.
   Tabak, Barbara
   Hernandez, Bryan
   Gentry, Jeff
   Huy Nguyen
   Crenshaw, Andrew
   Ardlie, Kristin
   Beroukhim, Rameen
   Winckler, Wendy
   Getz, Gad
   Gabriel, Stacey B.
   Meyerson, Matthew
   Chin, Lynda
   Park, Peter J.
   Kucherlapati, Raju
   Hoadley, Katherine A.
   Auman, J. Todd
   Fan, Cheng
   Turman, Yidi J.
   Shi, Yan
   Li, Ling
   Topal, Michael D.
   He, Xiaping
   Chao, Hann-Hsiang
   Prat, Aleix
   Silva, Grace O.
   Iglesia, Michael D.
   Zhao, Wei
   Usary, Jerry
   Berg, Jonathan S.
   Adams, Michael
   Booker, Jessica
   Wu, Junyuan
   Gulabani, Anisha
   Bodenheimer, Tom
   Hoyle, Alan P.
   Simons, Janae V.
   Soloway, Matthew G.
   Mose, Lisle E.
   Jefferys, Stuart R.
   Balu, Saianand
   Parker, Joel S.
   Hayes, D. Neil
   Perou, Charles M.
   Malik, Simeen
   Mahurkar, Swapna
   Shen, Hui
   Weisenberger, Daniel J.
   Triche, Timothy, Jr.
   Lai, Phillip H.
   Bootwalla, Moiz S.
   Maglinte, Dennis T.
   Berman, Benjamin P.
   Van den Berg, David J.
   Baylin, Stephen B.
   Laird, Peter W.
   Creighton, Chad J.
   Donehower, Lawrence A.
   Getz, Gad
   Noble, Michael
   Voet, Doug
   Saksena, Gordon
   Gehlenborg, Nils
   DiCara, Daniel
   Zhang, Juinhua
   Zhang, Hailei
   Wu, Chang-Jiun
   Liu, Spring Yingchun
   Lawrence, Michael S.
   Zou, Lihua
   Sivachenko, Andrey
   Lin, Pei
   Stojanov, Petar
   Jing, Rui
   Cho, Juok
   Sinha, Raktim
   Park, Richard W.
   Nazaire, Marc-Danie
   Robinson, Jim
   Thorvaldsdottir, Helga
   Mesirov, Jill
   Park, Peter J.
   Chin, Lynda
   Reynolds, Sheila
   Kreisberg, Richard B.
   Bernard, Brady
   Bressler, Ryan
   Erkkila, Timo
   Lin, Jake
   Thorsson, Vesteinn
   Zhang, Wei
   Shmulevich, Ilya
   Ciriello, Giovanni
   Weinhold, Nils
   Schultz, Nikolaus
   Gao, Jianjiong
   Cerami, Ethan
   Gross, Benjamin
   Jacobsen, Anders
   Sinha, Rileen
   Aksoy, B. Arman
   Antipin, Yevgeniy
   Reva, Boris
   Shen, Ronglai
   Taylor, Barry S.
   Ladanyi, Marc
   Sander, Chris
   Anur, Pavana
   Spellman, Paul T.
   Lu, Yiling
   Liu, Wenbin
   Verhaak, Roel R. G.
   Mills, Gordon B.
   Akbani, Rehan
   Zhang, Nianxiang
   Broom, Bradley M.
   Casasent, Tod D.
   Wakefield, Chris
   Unruh, Anna K.
   Baggerly, Keith
   Coombes, Kevin
   Weinstein, John N.
   Haussler, David
   Benz, Christopher C.
   Stuart, Joshua M.
   Benz, Stephen C.
   Zhu, Jingchun
   Szeto, Christopher C.
   Scott, Gary K.
   Yau, Christina
   Paul, Evan O.
   Carlin, Daniel
   Wong, Christopher
   Sokolov, Artem
   Thusberg, Janita
   Mooney, Sean
   Sam Ng
   Goldstein, Theodore C.
   Ellrott, Kyle
   Grifford, Mia
   Wilks, Christopher
   Ma, Singer
   Craft, Brian
   Yan, Chunhua
   Hu, Ying
   Meerzaman, Daoud
   Gastier-Foster, Julie M.
   Bowen, Jay
   Ramirez, Nilsa C.
   Black, Aaron D.
   Pyatt, Robert E.
   White, Peter
   Zmuda, Erik J.
   Frick, Jessica
   Lichtenberg, Taram.
   Brookens, Robin
   George, Myra M.
   Gerken, Mark A.
   Harper, Hollie A.
   Leraas, Kristen M.
   Wise, Lisa J.
   Tabler, Teresa R.
   McAllister, Cynthia
   Barr, Thomas
   Hart-Kothari, Melissa
   Tarvin, Katie
   Saller, Charles
   Sandusky, George
   Mitchell, Colleen
   Iacocca, Mary V.
   Brown, Jennifer
   Rabeno, Brenda
   Czerwinski, Christine
   Petrelli, Nicholas
   Dolzhansky, Oleg
   Abramov, Mikhail
   Voronina, Olga
   Potapova, Olga
   Marks, Jeffrey R.
   Suchorska, Wiktoria M.
   Murawa, Dawid
   Kycler, Witold
   Ibbs, Matthew
   Korski, Konstanty
   Spychala, Arkadiusz
   Murawa, Pawel
   Brzezinski, Jacek J.
   Perz, Hanna
   Lazniak, Radoslaw
   Teresiak, Marek
   Tatka, Honorata
   Leporowska, Ewa
   Bogusz-Czerniewicz, Marta
   Malicki, Julian
   Mackiewicz, Andrzej
   Wiznerowicz, Maciej
   Xuan Van Le
   Kohl, Bernard
   Nguyen Viet Tien
   Thorp, Richard
   Nguyen Van Bang
   Sussman, Howard
   Bui Duc Phu
   Hajek, Richard
   Nguyen Phi Hung
   Tran Viet The Phuong
   Huynh Quyet Thang
   Khan, Khurram Zaki
   Penny, Robert
   Mallery, David
   Curley, Erin
   Shelton, Candace
   Yena, Peggy
   Ingle, James N.
   Couch, Fergus J.
   Lingle, Wilma L.
   King, Tari A.
   Gonzalez-Angulo, Ana Maria
   Mills, Gordon B.
   Dyer, Mary D.
   Liu, Shuying
   Meng, Xiaolong
   Patangan, Modesto
   Waldman, Frederic
   Stoeppler, Hubert
   Rathmell, W. Kimryn
   Thorne, Leigh
   Huang, Mei
   Boice, Lori
   Hill, Ashley
   Morrison, Carl
   Gaudioso, Carmelo
   Bshara, Wiam
   Daily, Kelly
   Egea, Sophie C.
   Pegram, Mark D.
   Gomez-Fernandez, Carmen
   Dhir, Rajiv
   Bhargava, Rohit
   Brufsky, Adam
   Shriver, Craig D.
   Hooke, Jeffrey A.
   Campbell, Jamie Leigh
   Mural, Richard J.
   Hu, Hai
   Somiari, Stella
   Larson, Caroline
   Deyarmin, Brenda
   Kvecher, Leonid
   Kovatich, Albert J.
   Ellis, Matthew J.
   King, Tari A.
   Hu, Hai
   Couch, Fergus J.
   Mural, Richard J.
   Stricker, Thomas
   White, Kevin
   Olopade, Olufunmilayo
   Ingle, James N.
   Luo, Chunqing
   Chen, Yaqin
   Marks, Jeffrey R.
   Waldman, Frederic
   Wiznerowicz, Maciej
   Bose, Ron
   Chang, Li-Wei
   Beck, Andrew H.
   Gonzalez-Angulo, Ana Maria
   Pihl, Todd
   Jensen, Mark
   Sfeir, Robert
   Kahn, Ari
   Chu, Anna
   Kothiyal, Prachi
   Wang, Zhining
   Snyder, Eric
   Pontius, Joan
   Ayala, Brenda
   Backus, Mark
   Walton, Jessica
   Baboud, Julien
   Berton, Dominique
   Nicholls, Matthew
   Srinivasan, Deepak
   Raman, Rohini
   Girshik, Stanley
   Kigonya, Peter
   Alonso, Shelley
   Sanbhadti, Rashmi
   Barletta, Sean
   Pot, David
   Sheth, Margi
   Demchok, John A.
   Shaw, Kenna R. Mills
   Yang, Liming
   Eley, Greg
   Ferguson, Martin L.
   Tarnuzzer, Roy W.
   Zhang, Jiashan
   Dillon, Laura A. L.
   Buetow, Kenneth
   Fielding, Peter
   Ozenberger, Bradley A.
   Guyer, Mark S.
   Sofia, Heidi J.
   Palchik, Jacqueline D.
TI Comprehensive molecular portraits of human breast tumours
SO NATURE
LA English
DT Article
ID basal-like; mutational evolution; high-frequency; pik3ca gene; luminal-b; cancer; suppressor; subtypes; pathways; target
AB We analysed primary breast cancers by genomic DNA copy number arrays, DNA methylation, exome sequencing, messenger RNA arrays, microRNA sequencing and reverse-phase protein arrays. Our ability to integrate information across platforms provided key insights into previously defined gene expression subtypes and demonstrated the existence of four main breast cancer classes when combining data from five platforms, each of which shows significant molecular heterogeneity. Somatic mutations in only three genes (TP53, PIK3CA and GATA3) occurred at >10% incidence across all breast cancers; however, there were numerous subtype-associated and novel gene mutations including the enrichment of specific mutations in GATA3, PIK3CA and MAP3K1 with the luminal A subtype. We identified two novel protein-expression-defined subgroups, possibly produced by stromal/microenvironmental elements, and integrated analyses identified specific signalling pathways dominant in each molecular subtype including a HER2/phosphorylated HER2/EGFR/phosphorylated EGFR signature within the HER2-enriched expression subtype. Comparison of basal-like breast tumours with high-grade serous ovarian tumours showed many molecular commonalities, indicating a related aetiology and similar therapeutic opportunities. The biological finding of the four main breast cancer subtypes caused by different subsets of genetic and epigenetic abnormalities raises the hypothesis that much of the clinically observable plasticity and heterogeneity occurs within, and not across, these major biological subtypes of breast cancer.
C1 [Hoadley, Katherine A.; He, Xiaping; Chao, Hann-Hsiang; Prat, Aleix; Silva, Grace O.; Iglesia, Michael D.; Zhao, Wei; Berg, Jonathan S.; Adams, Michael; Weisenberger, Daniel J.] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA.
   [Koboldt, Daniel C.; Fulton, Robert S.; McLellan, Michael D.; Schmidt, Heather; Kalicki-Veizer, Joelle; McMichael, Joshua F.; Fulton, Lucinda L.; Dooling, David J.; Ding, Li; Mardis, Elaine R.; Wilson, Richard K.] Washington Univ, Genome Inst, St Louis, MO 63108 USA.
   [Ding, Li; Mardis, Elaine R.; Wilson, Richard K.] Washington Univ, Dept Genet, St Louis, MO 63110 USA.
   [Mardis, Elaine R.; Wilson, Richard K.; Ellis, Matthew J.; Bose, Ron] Washington Univ, Siteman Canc Ctr, St Louis, MO 63110 USA.
   [Ally, Adrian; Balasundaram, Miruna; Butterfield, Yaron S. N.; Carlsen, Rebecca; Carter, Candace; Chu, Andy; Chuah, Eric; Chun, Hye-Jung E.; Coope, Robin J. N.; Dhalla, Noreen; Guin, Ranabir; Hirst, Carrie; Hirst, Martin; Holt, Robert A.; Lee, Darlene; Li, Haiyan I.; Mayo, Michael; Moore, Richard A.; Mungall, Andrew J.; Pleasance, Erin; Robertson, A. Gordon; Schein, Jacqueline E.; Shafiei, Arash; Sipahimalani, Payal; Slobodan, Jared R.; Stoll, Dominik; Tam, Angela; Thiessen, Nina; Varhol, Richard J.; Wye, Natasja; Zeng, Thomas; Zhao, Yongjun; Birol, Inanc; Jones, Steven J. M.; Marra, Marco A.] BC Canc Agcy, Canadas Michael Smith Genome Sci Ctr, Vancouver, BC V5Z, Canada.
   [Cherniack, Andrew D.; Saksena, Gordon; Onofrio, Robert C.; Pho, Nam H.; Carter, Scott L.; Schumacher, Steven E.; Tabak, Barbara; Hernandez, Bryan; Gentry, Jeff; Huy Nguyen; Crenshaw, Andrew; Ardlie, Kristin; Beroukhim, Rameen; Winckler, Wendy; Getz, Gad; Gabriel, Stacey B.; Meyerson, Matthew] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.
   [Schumacher, Steven E.; Tabak, Barbara; Beroukhim, Rameen; Nguyen Phi Hung] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
   [Beroukhim, Rameen] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.
   [Beroukhim, Rameen; Meyerson, Matthew; Chin, Lynda] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
   [Beroukhim, Rameen; Meyerson, Matthew; Chin, Lynda] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA.
   [Meyerson, Matthew; Beck, Andrew H.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
   [Chin, Lynda] Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, Boston, MA 02115 USA.
   [Park, Peter J.; Gehlenborg, Nils; Park, Peter J.] Harvard Univ, Sch Med, Ctr Biomed Informat, Boston, MA 02115 USA.
   [Kucherlapati, Raju] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
   [Kucherlapati, Raju] Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA.
   [Hoadley, Katherine A.; Fan, Cheng; Turman, Yidi J.; Shi, Yan; Li, Ling; Topal, Michael D.; He, Xiaping; Chao, Hann-Hsiang; Prat, Aleix; Silva, Grace O.; Iglesia, Michael D.; Zhao, Wei; Usary, Jerry; Berg, Jonathan S.; Wu, Junyuan; Gulabani, Anisha; Bodenheimer, Tom; Hoyle, Alan P.; Simons, Janae V.; Soloway, Matthew G.; Mose, Lisle E.; Jefferys, Stuart R.; Balu, Saianand; Parker, Joel S.; Hayes, D. Neil; Perou, Charles M.; Malik, Simeen; Mahurkar, Swapna; Shen, Hui; Weisenberger, Daniel J.; Rathmell, W. Kimryn; Thorne, Leigh; Huang, Mei; Boice, Lori; Hill, Ashley] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA.
   [Auman, J. Todd] Univ N Carolina, Eshelman Sch Pharm, Chapel Hill, NC 27599 USA.
   [Auman, J. Todd] Univ N Carolina, Inst Pharmacogenet & Individualized Therapy, Chapel Hill, NC 27599 USA.
   [Topal, Michael D.; Booker, Jessica; Weisenberger, Daniel J.] Univ N Carolina, Dept Pathol & Lab Med, Chapel Hill, NC 27599 USA.
   [Shen, Hui] Univ N Carolina, Div Med Oncol, Dept Internal Med, Chapel Hill, NC 27599 USA.
   [Triche, Timothy, Jr.; Lai, Phillip H.; Bootwalla, Moiz S.; Maglinte, Dennis T.; Berman, Benjamin P.; Van den Berg, David J.; Laird, Peter W.] Univ So Calif, USC Epigenome Ctr, Los Angeles, CA 90033 USA.
   [Baylin, Stephen B.] Johns Hopkins Univ, Div Canc Biol, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21231 USA.
   [Creighton, Chad J.; Donehower, Lawrence A.] Baylor Coll Med, Dan L Duncan Canc Ctr, Houston, TX 77030 USA.
   [Creighton, Chad J.; Donehower, Lawrence A.] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA.
   [Donehower, Lawrence A.] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA.
   [Donehower, Lawrence A.] Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA.
   [Getz, Gad; Noble, Michael; Voet, Doug; Saksena, Gordon; Gehlenborg, Nils; DiCara, Daniel; Zhang, Hailei; Liu, Spring Yingchun; Lawrence, Michael S.; Zou, Lihua; Sivachenko, Andrey; Lin, Pei; Stojanov, Petar; Jing, Rui; Cho, Juok; Sinha, Raktim; Park, Richard W.; Nazaire, Marc-Danie; Robinson, Jim; Thorvaldsdottir, Helga; Mesirov, Jill; Chin, Lynda] Eli & Edythe L Broad Inst Massachusetts Inst Tech, Cambridge, MA 02142 USA.
   [Zhang, Juinhua; Chin, Lynda] Univ Texas MD Anderson Canc Ctr, Dept Genom Med, Inst Appl Canc Sci, Houston, TX 77054 USA.
   [Wu, Chang-Jiun] Univ Texas MD Anderson Canc Ctr, Dept Genom Med, Houston, TX 77054 USA.
   [Park, Peter J.] Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA.
   [Park, Peter J.] Childrens Hosp, Informat Program, Boston, MA 02115 USA.
   [Reynolds, Sheila; Kreisberg, Richard B.; Bernard, Brady; Bressler, Ryan; Lin, Jake; Thorsson, Vesteinn; Shmulevich, Ilya] Inst Syst Biol, Seattle, WA 98109 USA.
   [Erkkila, Timo] Tampere Univ Technol, FIN-33101 Tampere, Finland.
   [Zhang, Wei] Univ Texas MD Anderson Canc Ctr, Canc Genom Core Lab, Houston, TX 77030 USA.
   [Ciriello, Giovanni; Weinhold, Nils; Schultz, Nikolaus; Gao, Jianjiong; Cerami, Ethan; Gross, Benjamin; Jacobsen, Anders; Sinha, Rileen; Aksoy, B. Arman; Antipin, Yevgeniy; Reva, Boris; Taylor, Barry S.; Sander, Chris] 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.
   [Ladanyi, Marc] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10065 USA.
   [Anur, Pavana; Spellman, Paul T.] Oregon Hlth & Sci Univ, Portland, OR 97239 USA.
   [Lu, Yiling; Mills, Gordon B.; Gonzalez-Angulo, Ana Maria] Univ Texas MD Anderson Canc Ctr, Dept Syst Biol, Houston, TX 77030 USA.
   [Lu, Yiling; Mills, Gordon B.] Univ Texas MD Anderson Canc Ctr, Kleberg Ctr Mol Markers, Houston, TX 77030 USA.
   [Liu, Wenbin; Verhaak, Roel R. G.; Akbani, Rehan; Zhang, Nianxiang; Broom, Bradley M.; Casasent, Tod D.; Wakefield, Chris; Unruh, Anna K.; Baggerly, Keith; Coombes, Kevin; Weinstein, John N.] Univ Texas MD Anderson Canc Ctr, Dept Bioinformat & Computat Biol, Houston, TX 77030 USA.
   [Haussler, David; Stuart, Joshua M.; Benz, Stephen C.; Zhu, Jingchun; Szeto, Christopher C.; Paul, Evan O.; Carlin, Daniel; Wong, Christopher; Sokolov, Artem; Sam Ng; Goldstein, Theodore C.; Ellrott, Kyle; Grifford, Mia; Wilks, Christopher; Ma, Singer; Craft, Brian] Univ Calif Santa Cruz, Dept Biomol Engn, Santa Cruz, CA 95064 USA.
   [Haussler, David; Stuart, Joshua M.; Benz, Stephen C.; Zhu, Jingchun; Szeto, Christopher C.; Paul, Evan O.; Carlin, Daniel; Wong, Christopher; Sokolov, Artem; Sam Ng; Goldstein, Theodore C.; Ellrott, Kyle; Grifford, Mia; Wilks, Christopher; Ma, Singer; Craft, Brian] Univ Calif Santa Cruz, Ctr Biomol Sci & Engn, Santa Cruz, CA 95064 USA.
   [Haussler, David] Univ Calif Santa Cruz, Howard Hughes Med Inst, Santa Cruz, CA 95064 USA.
   [Benz, Christopher C.; Scott, Gary K.; Yau, Christina; Thusberg, Janita; Mooney, Sean] Buck Inst Res Aging, Novato, CA 94945 USA.
   [Yan, Chunhua; Hu, Ying; Meerzaman, Daoud; Buetow, Kenneth] NCI, Ctr Bioinformat & Informat Technol, Rockville, MD 20852 USA.
   [Gastier-Foster, Julie M.; Ramirez, Nilsa C.; Pyatt, Robert E.; White, Peter] Ohio State Univ, Coll Med, Dept Pathol, Columbus, OH 43205 USA.
   [Gastier-Foster, Julie M.] Ohio State Univ, Coll Med, Dept Pediat, Columbus, OH 43205 USA.
   [Gastier-Foster, Julie M.; Bowen, Jay; Ramirez, Nilsa C.; Black, Aaron D.; Pyatt, Robert E.; White, Peter; Zmuda, Erik J.; Frick, Jessica; Lichtenberg, Taram.; Brookens, Robin; George, Myra M.; Gerken, Mark A.; Harper, Hollie A.; Leraas, Kristen M.; Wise, Lisa J.; Tabler, Teresa R.; McAllister, Cynthia; Barr, Thomas; Hart-Kothari, Melissa] Nationwide Childrens Hosp, Res Inst, Columbus, OH 43205 USA.
   [Tarvin, Katie] ABS Inc, Indianapolis, IN 46204 USA.
   [Saller, Charles] ABS Inc, Wilmington, DE 19801 USA.
   [Sandusky, George; Mitchell, Colleen] Indiana Univ Sch Med, Indianapolis, IN 46202 USA.
   [Iacocca, Mary V.; Brown, Jennifer; Rabeno, Brenda; Czerwinski, Christine; Petrelli, Nicholas] Christiana Care, Helen F Graham Canc Ctr, Newark, DE 19713 USA.
   [Dolzhansky, Oleg] Moscow Hlth Dept, Moscow City Clin Oncol Dispensary 1, Moscow 105005, Russia.
   [Dolzhansky, Oleg] Moscow Hlth Dept, Cent IHC Lab, Moscow 105005, Russia.
   [Abramov, Mikhail] Russian Canc Res Ctr, Moscow 115478, Russia.
   [Voronina, Olga; Potapova, Olga] Cureline Inc, San Francisco, CA 94080 USA.
   [Marks, Jeffrey R.] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA.
   [Suchorska, Wiktoria M.; Murawa, Dawid; Kycler, Witold; Ibbs, Matthew; Korski, Konstanty; Spychala, Arkadiusz; Murawa, Pawel; Brzezinski, Jacek J.; Perz, Hanna; Lazniak, Radoslaw; Teresiak, Marek; Tatka, Honorata; Leporowska, Ewa; Bogusz-Czerniewicz, Marta; Malicki, Julian; Mackiewicz, Andrzej; Wiznerowicz, Maciej] Greater Poland Canc Ctr, PL-61866 Poznan, Poland.
   [Bogusz-Czerniewicz, Marta; Malicki, Julian; Mackiewicz, Andrzej] Poznan Univ Med Sci, PL-61701 Poznan, Poland.
   [Xuan Van Le; Kohl, Bernard] ILSBio LLC, Chestertown, MD 21620 USA.
   [Nguyen Viet Tien] Minist Hlth, Hanoi, Vietnam.
   [Thorp, Richard; Khan, Khurram Zaki] ILSBio LLC, Karachi, Pakistan.
   [Nguyen Van Bang; Bui Duc Phu] Hue Cent Hosp, Hue City, Vietnam.
   [Sussman, Howard] Stanford Univ, Med Ctr, Stanford, CA 94305 USA.
   [Hajek, Richard] Univ Texas MD Anderson Canc Ctr, Ctr Minor Hlth Res, Houston, TX 77030 USA.
   [Nguyen Phi Hung] Natl Canc Inst, Hanoi, Vietnam.
   [Tran Viet The Phuong] Ho Chi Minh City Canc Ctr, Ho Chi Minh City, Vietnam.
   [Huynh Quyet Thang] Can Tho Canc Ctr, Can Tho, Vietnam.
   [Penny, Robert; Mallery, David; Curley, Erin; Shelton, Candace; Yena, Peggy] Int Genom Consortium, Phoenix, AZ 85004 USA.
   [Ingle, James N.; Couch, Fergus J.; Lingle, Wilma L.] Mayo Clin, Rochester, MN 55905 USA.
   [King, Tari A.] Mem Sloan Kettering Canc Ctr, Dept Surg, Breast Serv, New York, NY 10065 USA.
   [Mills, Gordon B.; Dyer, Mary D.; Liu, Shuying; Meng, Xiaolong; Patangan, Modesto] Univ Texas MD Anderson Canc Ctr, Dept Breast Med Oncol, Houston, TX 77030 USA.
   [Waldman, Frederic] Univ Calif San Francisco, San Francisco, CA 94143 USA.
   Canc Diagnost, San Juan Capistrano, CA 92675 USA.
   Quest Diagnost, Nichols Inst, San Juan Capistrano, CA 92675 USA.
   [Stoeppler, Hubert] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94115 USA.
   [Thorne, Leigh; Huang, Mei; Boice, Lori] UNC Lineberger Canc Ctr, Dept Pathol, UNC Tissue Procurement Facil, Chapel Hill, NC 27599 USA.
   [Morrison, Carl; Gaudioso, Carmelo; Bshara, Wiam] Roswell Pk Canc Inst, Dept Pathol, Buffalo, NY 14263 USA.
   [Daily, Kelly; Egea, Sophie C.; Pegram, Mark D.; Gomez-Fernandez, Carmen] Univ Miami, Miller Sch Med, Sylvester Comprehens Canc Ctr, Dept Pathol, Miami, FL 33136 USA.
   [Dhir, Rajiv] Univ Pittsburgh, Pittsburgh, PA 15213 USA.
   [Bhargava, Rohit; Brufsky, Adam] Univ Pittsburgh Med Ctr, Magee Womens Hosp, Pittsburgh, PA 15213 USA.
   [Shriver, Craig D.; Hooke, Jeffrey A.; Campbell, Jamie Leigh] Walter Reed Natl Mil Med Ctr, Bethesda, MD 20899 USA.
   [Mural, Richard J.; Hu, Hai; Somiari, Stella; Larson, Caroline; Deyarmin, Brenda; Kvecher, Leonid; Luo, Chunqing; Chen, Yaqin] Windber Res Inst, Windber, PA 15963 USA.
   [Kovatich, Albert J.] MDR Global LLC, Windber, PA 15963 USA.
   [Ellis, Matthew J.; Bose, Ron] Washington Univ, Breast Canc Program, St Louis, MO 63110 USA.
   [Ellis, Matthew J.; Bose, Ron] Washington Univ, Dept Internal Med, Div Oncol, St Louis, MO 63110 USA.
   [Stricker, Thomas; White, Kevin] Univ Chicago, Inst Genom & Syst Biol, Chicago, IL 60637 USA.
   [Olopade, Olufunmilayo] Univ Chicago, Ctr Clin Canc Genet, Chicago, IL 60637 USA.
   [Chang, Li-Wei] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA.
   [Pihl, Todd; Jensen, Mark; Sfeir, Robert; Kahn, Ari; Chu, Anna; Kothiyal, Prachi; Wang, Zhining; Snyder, Eric; Pontius, Joan; Ayala, Brenda; Backus, Mark; Walton, Jessica; Baboud, Julien; Berton, Dominique; Nicholls, Matthew; Srinivasan, Deepak; Raman, Rohini; Girshik, Stanley; Kigonya, Peter; Alonso, Shelley; Sanbhadti, Rashmi; Barletta, Sean; Pot, David] SRA Int, Fairfax, VA 22033 USA.
   [Sheth, Margi; Demchok, John A.; Shaw, Kenna R. Mills; Yang, Liming; Tarnuzzer, Roy W.; Zhang, Jiashan; Dillon, Laura A. L.; Fielding, Peter] NCI, Canc Genome Atlas Program Off, Ctr Canc Genom, Bethesda, MD 20892 USA.
   [Eley, Greg] Scimentis LLC, TCGA, Statham, GA 30666 USA.
   [Ferguson, Martin L.] MLF Consulting, Arlington, MA 02474 USA.
   [Ozenberger, Bradley A.; Guyer, Mark S.; Sofia, Heidi J.; Palchik, Jacqueline D.] NHGRI, NIH, Bethesda, MD 20892 USA.
C3 University of North Carolina; University of North Carolina Chapel Hill; Washington University (WUSTL); Washington University (WUSTL); Siteman Cancer Center; Washington University (WUSTL); British Columbia Cancer Agency; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard Medical School; Harvard University; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; 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; University of Southern California; Johns Hopkins University; Johns Hopkins 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; University of Texas System; UTMD Anderson Cancer Center; University of Texas System; UTMD Anderson Cancer Center; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Institute for Systems Biology (ISB); Tampere University; University of Texas System; UTMD Anderson Cancer Center; Memorial Sloan Kettering Cancer Center; Memorial Sloan Kettering Cancer Center; Memorial Sloan Kettering Cancer Center; Oregon Health & Science University; 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 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; Buck Institute for Research on Aging; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); University System of Ohio; Ohio State University; University System of Ohio; Ohio State University; University System of Ohio; Ohio State University; Nationwide Childrens Hospital; Research Institute at Nationwide Children's Hospital; Indiana University System; Indiana University Bloomington; Helen F. Graham Cancer Center & Research Institute; Christiana Care Health System; Duke University; Wielkopolskie Centrum Onkologii; Poznan University of Medical Sciences; Stanford University; University of Texas System; UTMD Anderson Cancer Center; International Genomics Consortium; Mayo Clinic; Memorial Sloan Kettering Cancer Center; University of Texas System; UTMD Anderson Cancer Center; University of California System; University of California San Francisco; Quest Diagnostics Inc; Nichols Institute; University of California System; University of California San Francisco; UCSF Medical Center; UCSF Helen Diller Family Comprehensive Cancer Center; Roswell Park Comprehensive Cancer Center; University of Miami; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh; University of Pittsburgh Medical Center; Walter Reed National Military Medical Center; Windber Research Institute; Washington University (WUSTL); Washington University (WUSTL); University of Chicago; University of Chicago; Washington University (WUSTL); SRA International; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); Center for Cancer Genomics (CCG); International Genomics Consortium; International Genomics Consortium; National Institutes of Health (NIH) - USA; NIH National Human Genome Research Institute (NHGRI)
RP Perou, CM (corresponding author), Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA.
EM cperou@med.unc.edu
FU USA National Institutes of Health [U24CA143883, U24CA143858, U24CA143840, U24CA143799, U24CA143835, U24CA143845, U24CA143882, U24CA143867, U24CA143866, U24CA143848, U24CA144025, U54HG003079, P50CA116201, P50CA58223]; Susan G. Komen for the Cure; US Department of Defense through the Henry M. Jackson Foundation for the Advancement of Military Medicine; Breast Cancer Research Foundation; National Cancer Institute [P30CA016086, P30CA016672, P30CA016058, P50CA058223, P50CA116201] Funding Source: NIH RePORTER
NR 56
TC 10225
Z9 11720
U1 42
U2 1770
PU NATURE PUBLISHING 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 4
PY 2012
VL 490
IS 7418
BP 61
EP 70
DI 10.1038/nature11412
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 015LG
UT WOS:000309446800032
PM 23000897
DA 2026-03-09
ER

PT J
AU Hugall, AF
   Stuart-Fox, D
AF Hugall, Andrew F.
   Stuart-Fox, Devi
TI Accelerated speciation in colour-polymorphic birds
SO NATURE
LA English
DT Article
ID frequency-dependent selection; sympatric speciation; extinction rates; sexual selection; evolution; consequences; maintenance; mechanisms; fish
AB Colour polymorphism exemplifies extreme morphological diversity within populations(1,2). It is taxonomically widespread but generally rare. Theory suggests that where colour polymorphism does occur, processes generating and maintaining it can promote speciation but the generality of this claim is unclear(1). Here we confirm, using species-level molecular phylogenies for five families of non-passerine birds, that colour polymorphism is associated with accelerated speciation rates in the three groups in which polymorphism is most prevalent. In all five groups, colour polymorphism is lost at a significantly greater rate than it is gained. Thus, the general rarity and phylogenetic dispersion of colour polymorphism is accounted for by a combination of higher speciation rate and higher transition rate from polymorphism to monomorphism, consistent with theoretical models where speciation is driven by fixation of one or more morphs(3). This is corroborated by evidence from a species-level molecular phylogeny of passerines, incorporating 4,128 (66.5%) extant species, that polymorphic species tend to be younger than monomorphic species. Our results provide empirical support for the general proposition, dating from classical evolutionary theory(2,4-6), that colour polymorphism can increase speciation rates.
C1 [Hugall, Andrew F.; Stuart-Fox, Devi] Univ Melbourne, Dept Zool, Melbourne, Vic 3010, Australia.
C3 University of Melbourne
RP Stuart-Fox, D (corresponding author), Univ Melbourne, Dept Zool, Melbourne, Vic 3010, Australia.
EM ahugall@museum.vic.gov.au; devis@unimelb.edu.au
FU Australian Research Council [DP1092908]; Australian Research Council [DP1092908] Funding Source: Australian Research Council
NR 35
TC 177
Z9 206
U1 2
U2 179
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 31
PY 2012
VL 485
IS 7400
BP 631
EP +
DI 10.1038/nature11050
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 949WP
UT WOS:000304608000046
PM 22660325
DA 2026-03-09
ER

PT J
AU Lee, SH
   Kwan, AC
   Zhang, SY
   Phoumthipphavong, V
   Flannery, JG
   Masmanidis, SC
   Taniguchi, H
   Huang, ZJ
   Zhang, F
   Boyden, ES
   Deisseroth, K
   Dan, Y
AF Lee, Seung-Hee
   Kwan, Alex C.
   Zhang, Siyu
   Phoumthipphavong, Victoria
   Flannery, John G.
   Masmanidis, Sotiris C.
   Taniguchi, Hiroki
   Huang, Z. Josh
   Zhang, Feng
   Boyden, Edward S.
   Deisseroth, Karl
   Dan, Yang
TI Activation of specific interneurons improves V1 feature selectivity and visual perception
SO NATURE
LA English
DT Article
ID orientation selectivity; cortical-neurons; electrode arrays; cortex; inhibition; responses; innervation; populations; performance; modulation
AB Inhibitory interneurons are essential components of the neural circuits underlying various brain functions. In the neocortex, a large diversity of GABA (gamma-aminobutyric acid) interneurons has been identified on the basis of their morphology, molecular markers, biophysical properties and innervation pattern(1-3). However, how the activity of each subtype of interneurons contributes to sensory processing remains unclear. Here we show that optogenetic activation of parvalbumin-positive (PV+) interneurons in the mouse primary visual cortex (V1) sharpens neuronal feature selectivity and improves perceptual discrimination. Using multichannel recording with silicon probes(4,5) and channelrhodopsin-2 (ChR2)-mediated optical activation(6), we found that increased spiking of PV+ interneurons markedly sharpened orientation tuning and enhanced direction selectivity of nearby neurons. These effects were caused by the activation of inhibitory neurons rather than a decreased spiking of excitatory neurons, as archaerhodopsin-3 (Arch)-mediated optical silencing(7) of calcium/calmodulindependent protein kinase II alpha (CAMKII alpha)-positive excitatory neurons caused no significant change in V1 stimulus selectivity. Moreover, the improved selectivity specifically required PV+ neuron activation, as activating somatostatin or vasointestinal peptide interneurons had no significant effect. Notably, PV+ neuron activation in awake mice caused a significant improvement in their orientation discrimination, mirroring the sharpened V1 orientation tuning. Together, these results provide the first demonstration that visual coding and perception can be improved by increased spiking of a specific subtype of cortical inhibitory interneurons.
C1 [Lee, Seung-Hee; Kwan, Alex C.; Zhang, Siyu; Phoumthipphavong, Victoria; Flannery, John G.; Dan, Yang] Univ Calif Berkeley, Dept Mol & Cell Biol, Div Neurobiol, Helen Wills Neurosci Inst, Berkeley, CA 94720 USA.
   [Lee, Seung-Hee; Dan, Yang] Univ Calif Berkeley, Howard Hughes Med Inst, Berkeley, CA 94720 USA.
   [Masmanidis, Sotiris C.] CALTECH, Kavli Nanosci Inst, Broad Fellows Program Brain Circuitry, Pasadena, CA 91125 USA.
   [Taniguchi, Hiroki; Huang, Z. Josh] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA.
   [Zhang, Feng; Deisseroth, Karl] Stanford Univ, Howard Hughes Med Inst, Dept Bioengn, Stanford, CA 94305 USA.
   [Boyden, Edward S.] MIT, Media Lab, Cambridge, MA 02139 USA.
   [Boyden, Edward S.] MIT, McGovern Inst, Cambridge, MA 02139 USA.
C3 University of California System; University of California Berkeley; Howard Hughes Medical Institute; University of California System; University of California Berkeley; California Institute of Technology; Cold Spring Harbor Laboratory; Stanford University; Howard Hughes Medical Institute; Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT)
RP Dan, Y (corresponding author), Univ Calif Berkeley, Dept Mol & Cell Biol, Div Neurobiol, Helen Wills Neurosci Inst, Berkeley, CA 94720 USA.
EM ydan@berkeley.edu
FU National Institutes of Health [R01 EY018861, PN2 EY018241]; National Science Foundation [22250400-42533]; Emerging Frontiers & Multidisciplinary Activities; Directorate For Engineering [0835878] Funding Source: National Science Foundation
NR 36
TC 464
Z9 579
U1 3
U2 143
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 16
PY 2012
VL 488
IS 7411
BP 379
EP +
DI 10.1038/nature11312
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 988OS
UT WOS:000307501000042
PM 22878719
DA 2026-03-09
ER

PT J
AU Raymo, ME
   Mitrovica, JX
AF Raymo, Maureen E.
   Mitrovica, Jerry X.
TI Collapse of polar ice sheets during the stage 11 interglacial
SO NATURE
LA English
DT Article
ID marine isotope stage-11; sea-level highstand; mantle viscosity; mass-loss; pleistocene; holocene; bermuda; analog; rise
AB Contentious observations of Pleistocene shoreline features on the tectonically stable islands of Bermuda and the Bahamas have suggested that sea level about 400,000 years ago was more than 20 metres higher than it is today(1-4). Geochronologic and geomorphic evidence indicates that these features formed during interglacial marine isotope stage (MIS) 11, an unusually long interval of warmth during the ice age(1-4). Previous work has advanced two divergent hypotheses for these shoreline features: first, significant melting of the East Antarctic Ice Sheet, in addition to the collapse of the West Antarctic Ice Sheet and the Greenland Ice Sheet(1-3); or second, emplacement by a mega-tsunami during MIS 11 (ref. 4, 5). Here we show that the elevations of these features are corrected downwards by similar to 10 metres when we account for post-glacial crustal subsidence of these sites over the course of the anomalously long interglacial. On the basis of this correction, we estimate that eustatic sea level rose to similar to 6-13 m above the present-day value in the second half of MIS 11. This suggests that both the Greenland Ice Sheet and the West Antarctic Ice Sheet collapsed during the protracted warm period while changes in the volume of the East Antarctic Ice Sheet were relatively minor, thereby resolving the long-standing controversy over the stability of the East Antarctic Ice Sheet during MIS 11.
C1 [Raymo, Maureen E.] Columbia Univ, Lamont Doherty Earth Observ, Palisades, NY 10964 USA.
   [Mitrovica, Jerry X.] Harvard Univ, Dept Earth & Planetary Sci, Cambridge, MA 02138 USA.
C3 Columbia University; Harvard University
RP Raymo, ME (corresponding author), Columbia Univ, Lamont Doherty Earth Observ, POB 1000,61 Route 9W, Palisades, NY 10964 USA.
EM raymo@ldeo.columbia.edu
FU Harvard University; Canadian Institute for Advanced Research;  [NSF-OCE-0825293];  [OCE-1202632]; Directorate For Geosciences; Division Of Ocean Sciences [1202632] Funding Source: National Science Foundation; Division Of Ocean Sciences; Directorate For Geosciences [1238405] Funding Source: National Science Foundation
NR 28
TC 194
Z9 220
U1 3
U2 105
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 22
PY 2012
VL 483
IS 7390
BP 453
EP 456
DI 10.1038/nature10891
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 912CC
UT WOS:000301771200040
PM 22419155
DA 2026-03-09
ER

PT J
AU Gilman, RT
   Nuismer, SL
   Jhwueng, DC
AF Gilman, R. Tucker
   Nuismer, Scott L.
   Jhwueng, Dwueng-Chwuan
TI Coevolution in multidimensional trait space favours escape from parasites and pathogens
SO NATURE
LA English
DT Article
ID g-matrix; evolution; diversity; stability; selection; constraints; parsnip; hosts
AB Almost all species are subject to continuous attack by parasites and pathogens. Because parasites and pathogens tend to have shorter generation times(1,2) and often experience stronger selection due to interaction than their victims do(3,4), it is frequently argued that they should evolve more rapidly and thus maintain an advantage in the evolutionary race between defence and counter-defence(1,5). This prediction generates an apparent paradox: how do victim species survive and even thrive in the face of a continuous onslaught of more rapidly evolving enemies(5)? One potential explanation is that defence is physiologically, mechanically or behaviourally easier than attack, so that evolution is less constrained for victims than for parasites or pathogens(6). Another possible explanation is that parasites and pathogens have enemies themselves and that victim species persist because parasites and pathogens are regulated from the top down and thus generally have only modest demographic impacts on victimpopulations(7,8). Here we explore a third possibility: that victim species are not as evolutionarily impotent as conventional wisdom holds, but instead have unique evolutionary advantages that help to level the playing field. We use quantitative genetic analysis and individual-based simulations to show that victims can achieve such an advantage when coevolution involves multiple traits in both the host and the parasite.
C1 [Gilman, R. Tucker; Jhwueng, Dwueng-Chwuan] Natl Inst Math & Biol Synth, Knoxville, TN 37916 USA.
   [Nuismer, Scott L.] Univ Idaho, Dept Biol Sci, Moscow, ID 83844 USA.
   [Nuismer, Scott L.] Univ Idaho, Inst Bioinformat & Evolutionary Studies, Moscow, ID 83844 USA.
C3 University of Tennessee System; University of Tennessee Knoxville; University of Idaho; University of Idaho
RP Gilman, RT (corresponding author), Natl Inst Math & Biol Synth, Knoxville, TN 37916 USA.
EM rtgilman@nimbios.org
FU National Science Foundation (NSF) [DMS 0540392, DEB 1118947]; US Department of Homeland Security; US Department of Agriculture through NSF [EF-0832858]; The University of Tennessee, Knoxville; Division Of Environmental Biology; Direct For Biological Sciences [1118947] Funding Source: National Science Foundation
CR Abrams PA, 2000, ANNU REV ECOL SYST, V31, P79, DOI 10.1146/annurev.ecolsys.31.1.79
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   Arnold SJ, 2008, EVOLUTION, V62, P2451, DOI 10.1111/j.1558-5646.2008.00472.x
   BERENBAUM MR, 1986, EVOLUTION, V40, P1215, DOI 10.1111/j.1558-5646.1986.tb05746.x
   Costamagna AC, 2006, ECOL APPL, V16, P1619, DOI 10.1890/1051-0761(2006)016[1619:PETCOS]2.0.CO;2
   Doebeli M, 2010, SCIENCE, V328, P494, DOI 10.1126/science.1187468
   Dowton M, 1995, J MOL EVOL, V41, P958, DOI 10.1007/BF00173176
   FRANK SA, 1993, EVOLUTION, V47, P1721, DOI 10.2307/2410216
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   Hochberg ME, 1997, OIKOS, V80, P342
   Jones AG, 2004, EVOLUTION, V58, P1639
   Jones AG, 2003, EVOLUTION, V57, P1747
   Jones SRM, 2001, DEV COMP IMMUNOL, V25, P841, DOI 10.1016/S0145-305X(01)00039-8
   King KC, 2011, BIOL LETTERS, V7, P265, DOI 10.1098/rsbl.2010.0857
   Kirkpatrick M, 2009, GENETICA, V136, P271, DOI 10.1007/s10709-008-9302-6
   LANDE R, 1979, EVOLUTION, V33, P402, DOI 10.1111/j.1558-5646.1979.tb04694.x
   LANDE R, 1983, EVOLUTION, V37, P1210, DOI 10.1111/j.1558-5646.1983.tb00236.x
   Nuismer SL, 2008, J EVOLUTION BIOL, V21, P958, DOI 10.1111/j.1420-9101.2008.01551.x
   Nuismer SL, 2005, EVOLUTION, V59, P2073
   Page RDM, 1998, MOL PHYLOGENET EVOL, V9, P276, DOI 10.1006/mpev.1997.0458
   Rasmann S, 2011, J ECOL, V99, P16, DOI 10.1111/j.1365-2745.2010.01713.x
   THOMPSON JN, 1986, TRENDS ECOL EVOL, V1, P105, DOI 10.1016/0169-5347(86)90036-4
   Toju H, 2011, AM NAT, V177, P562, DOI 10.1086/659624
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   Zalucki MP, 2001, ECOL ENTOMOL, V26, P212, DOI 10.1046/j.1365-2311.2001.00313.x
   Zangerl AR, 2003, EVOLUTION, V57, P806, DOI 10.1111/j.0014-3820.2003.tb00292.x
NR 29
TC 63
Z9 70
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 MAR 15
PY 2012
VL 483
IS 7389
BP 328
EP 330
DI 10.1038/nature10853
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 908HP
UT WOS:000301481800048
PM 22388815
DA 2026-03-09
ER

PT J
AU Killian, NJ
   Jutras, MJ
   Buffalo, EA
AF Killian, Nathaniel J.
   Jutras, Michael J.
   Buffalo, Elizabeth A.
TI A map of visual space in the primate entorhinal cortex
SO NATURE
LA English
DT Article
ID spatial representation system; monkey hippocampal-neurons; grid cells; theta oscillations; macaque hippocampus; memory; place; organization; periodicity; navigation
AB Place-modulated activity among neurons in the hippocampal formation presents a means to organize contextual information in the service of memory formation and recall(1,2). One particular spatial representation, that of grid cells, has been observed in the entorhinal cortex (EC) of rats and bats(3-5), but has yet to be described in single units in primates. Here we examined spatial representations in the EC of head-fixed monkeys performing a free-viewing visual memory task(6,7). Individual neurons were identified in the primate EC that emitted action potentials when the monkey fixated multiple discrete locations in the visual field in each of many sequentially presented complex images. These firing fields possessed spatial periodicity similar to a triangular tiling with a corresponding well-defined hexagonal structure in the spatial auto-correlation. Further, these neurons showed theta-band oscillatory activity and changing spatial scale as a function of distance from the rhinal sulcus, which is consistent with previous findings in rodents(4,8-10). These spatial representations may provide a framework to anchor the encoding of stimulus content in a complex visual scene. Together, our results provide a direct demonstration of grid cells in the primate and suggest that EC neurons encode space during visual exploration, even without locomotion.
C1 [Killian, Nathaniel J.; Jutras, Michael J.; Buffalo, Elizabeth A.] Yerkes Natl Primate Res Ctr, Atlanta, GA 30329 USA.
   [Killian, Nathaniel J.] Georgia Inst Technol, Wallace H Coulter Dept Biomed Engn, Atlanta, GA 30332 USA.
   [Buffalo, Elizabeth A.] Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30332 USA.
C3 University System of Georgia; Georgia Institute of Technology; Emory University
RP Buffalo, EA (corresponding author), Yerkes Natl Primate Res Ctr, 954 Gatewood Rd, Atlanta, GA 30329 USA.
EM elizabeth.buffalo@emory.edu
FU National Institute of Mental Health [R01MH093807, R01MH080007, MH082559]; National Center for Research Resources [P51RR165]; Office of Research Infrastructure Programs/OD [P51OD11132]; NSF IGERT program [DGE-0333411]
NR 30
TC 326
Z9 411
U1 0
U2 74
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 29
PY 2012
VL 491
IS 7426
BP 761
EP 764
DI 10.1038/nature11587
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 044FY
UT WOS:000311606000046
PM 23103863
DA 2026-03-09
ER

PT J
AU Fedorov, A
   Steffen, L
   Baur, M
   da Silva, MP
   Wallraff, A
AF Fedorov, A.
   Steffen, L.
   Baur, M.
   da Silva, M. P.
   Wallraff, A.
TI Implementation of a Toffoli gate with superconducting circuits
SO NATURE
LA English
DT Article
ID quantum error-correction; qubits
AB The Toffoli gate is a three-quantum-bit (three-qubit) operation that inverts the state of a target qubit conditioned on the state of two control qubits. It makes universal reversible classical computation(1) possible and, together with a Hadamard gate(2), forms a universal set of gates in quantum computation. It is also a key element in quantum error correction schemes(3-7). The Toffoli gate has been implemented in nuclear magnetic resonance(3), linear optics(8) and ion trap systems(9). Experiments with superconducting qubits have also shown significant progress recently: two-qubit algorithms(10) and two-qubit process tomography have been implemented(11), three-qubit entangled states have been prepared(12,13), first steps towards quantum teleportation have been taken(14) and work on quantum computing architectures has been done(15). Implementation of the Toffoli gate with only single-and two-qubit gates requires six controlled-NOT gates and ten single-qubit operations(16), and has not been realized in any system owing to current limits on coherence. Here we implement a Toffoli gate with three superconducting transmon qubits coupled to a microwave resonator. By exploiting the third energy level of the transmon qubits, we have significantly reduced the number of elementary gates needed for the implementation of the Toffoli gate, relative to that required in theoretical proposals using only two-level systems. Using full process tomography and Monte Carlo process certification, we completely characterize the Toffoli gate acting on three independent qubits, measuring a fidelity of 68.5 +/- 0.5 per cent. A similar approach(15) to realizing characteristic features of a Toffoli-class gate has been demonstrated with two qubits and a resonator and achieved a limited characterization considering only the phase fidelity. Our results reinforce the potential of macroscopic superconducting qubits for the implementation of complex quantum operations with the possibility of quantum error correction(17).
C1 [Fedorov, A.; Steffen, L.; Baur, M.; Wallraff, A.] ETH, Dept Phys, CH-8093 Zurich, Switzerland.
   [da Silva, M. P.] Raytheon BBN Technol, Disrupt Informat Proc Technol Grp, Cambridge, MA 02138 USA.
   [da Silva, M. P.] Univ Sherbrooke, Dept Phys, Sherbrooke, PQ J1K 2R1, Canada.
C3 Swiss Federal Institutes of Technology Domain; ETH Zurich; RTX Corporation; Raytheon BBN Technologies; University of Sherbrooke
RP Fedorov, A (corresponding author), ETH, Dept Phys, CH-8093 Zurich, Switzerland.
EM fedoroar@phys.ethz.ch; andreas.wallraff@phys.ethz.ch
FU Swiss National Science Foundation; EU IP SOLID; ETH Zurich
NR 33
TC 333
Z9 368
U1 3
U2 101
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JAN 12
PY 2012
VL 481
IS 7380
BP 170
EP 172
DI 10.1038/nature10713
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 874TO
UT WOS:000298981200032
PM 22170609
DA 2026-03-09
ER

PT J
AU Montagner, M
   Enzo, E
   Forcato, M
   Zanconato, F
   Parenti, A
   Rampazzo, E
   Basso, G
   Leo, G
   Rosato, A
   Bicciato, S
   Cordenonsi, M
   Piccolo, S
AF Montagner, Marco
   Enzo, Elena
   Forcato, Mattia
   Zanconato, Francesca
   Parenti, Anna
   Rampazzo, Elena
   Basso, Giuseppe
   Leo, Genesio
   Rosato, Antonio
   Bicciato, Silvio
   Cordenonsi, Michelangelo
   Piccolo, Stefano
TI SHARP1 suppresses breast cancer metastasis by promoting degradation of hypoxia-inducible factors
SO NATURE
LA English
DT Article
ID p53; proteasome; expression; hif-1-alpha; complex; growth; p63
AB The molecular determinants of malignant cell behaviours in breast cancer remain only partially understood(1). Here we show that SHARP1 (also known as BHLHE41 or DEC2) is a crucial regulator of the invasive and metastatic phenotype in triple-negative breast cancer (TNBC), one of the most aggressive types of breast cancer. SHARP1 is regulated by the p63 metastasis suppressor and inhibits TNBC aggressiveness through inhibition of hypoxia-inducible factor 1 alpha (HIF-1 alpha) and HIF-2 alpha (HIFs). SHARP1 opposes HIF-dependent TNBC cell migration in vitro, and invasive or metastatic behaviours in vivo. SHARP1 is required, and sufficient, to limit expression of HIF-target genes. In primary TNBC, endogenous SHARP1 levels are inversely correlated with those of HIF targets. Mechanistically, SHARP1 binds to HIFs and promotes HIF proteasomal degradation by serving as the HIF-presenting factor to the proteasome. This process is independent of pVHL (von Hippel-Lindau tumour suppressor), hypoxia and the ubiquitination machinery. SHARP1 therefore determines the intrinsic instability of HIF proteins to act in parallel to, and cooperate with, oxygen levels. This work sheds light on the mechanisms and pathways by which TNBC acquires invasiveness and metastatic propensity.
C1 [Montagner, Marco; Enzo, Elena; Zanconato, Francesca; Cordenonsi, Michelangelo; Piccolo, Stefano] Univ Padua, Sch Med, Dept Med Biotechnol, I-35131 Padua, Italy.
   [Forcato, Mattia; Bicciato, Silvio] Univ Modena & Reggio Emilia, Dept Biomed Sci, Ctr Genome Res, I-41100 Modena, Italy.
   [Parenti, Anna] Univ Padua, Sect Pathol, Dept Med Diagnost Sci & Special Therapies, I-35126 Padua, Italy.
   [Rampazzo, Elena; Basso, Giuseppe] Univ Padua, Dept Pediat, I-35128 Padua, Italy.
   [Leo, Genesio] Hosp San Bassiano, Div Anat Pathol, I-36061 Bassano Del Grappa, Italy.
   [Rosato, Antonio] Dept Surg Oncol & Gastroenterol, I-35126 Padua, Italy.
   [Rosato, Antonio] Ist Oncol Veneto IRCCS, I-35126 Padua, Italy.
C3 University of Padua; Universita di Modena e Reggio Emilia; University of Padua; University of Padua; ULSS 7 Pedemontana; Ospedale San Bassiano; IRCCS Istituto Oncologico Veneto (IOV)
RP Piccolo, S (corresponding author), Univ Padua, Sch Med, Dept Med Biotechnol, Viale Colombo 3, I-35131 Padua, Italy.
EM piccolo@bio.unipd.it
FU FIRC (Federazione Italiana Ricerca Cancro); Cariparo PhD fellowship; AIRC (Italian Association for Cancer Research); Italian Welfare Ministry; AIRC (Associazione Italiana per la Ricerca sul Cancro); Fondazione Citta della Speranza; MIUR (Ministero dell'Istruzione dell'Universita e della Ricerca Italia); PRIN grants; AIRC; HSFP; University of Padua; IIT Excellence grant; CNR-Miur Epigenetics Flagship project; Comitato Promotore Telethon
NR 24
TC 213
Z9 241
U1 3
U2 87
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 19
PY 2012
VL 487
IS 7407
BP 380
EP 384
DI 10.1038/nature11207
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 975JB
UT WOS:000306506500046
PM 22801492
DA 2026-03-09
ER

PT J
AU Kalirai, JS
AF Kalirai, Jason S.
TI The age of the Milky Way inner halo
SO NATURE
LA English
DT Article
ID digital sky survey; da white-dwarfs; globular-clusters; spectroscopic analysis; stellar evolution; galactic halo; acs survey; branch; masses; stars
AB The Milky Way galaxy has several components, such as the bulge, disk and halo. Unravelling the assembly history of these stellar populations is often restricted because of difficulties in measuring accurate ages for low-mass, hydrogen-burning stars(1,2). Unlike these progenitors, white dwarf stars(3), the 'cinders' of stellar evolution, are remarkably simple objects and their fundamental properties can be measured with little ambiguity(4,5). Here I report observations of newly formed white dwarf stars in the halo of the Milky Way, and a separate analysis of archival data in the well studied 12.5-billion-year-old globular cluster Messier 4. I measure the mass distribution of the remnant stars and invert the stellar evolution process to develop a mathematical relation that links this final stellar mass to the mass of their immediate progenitors, and therefore to the age of the parent population. By applying this technique to a small sample of four nearby and kinematically confirmed halo white dwarf stars, I calculate the age of local field halo stars to be 11.4 +/- 0.7 billion years. The oldest globular clusters formed 13.5 billion years ago. Future observations of newly formed white dwarf stars in the halo could be used to reduce the uncertainty, and to probe relative differences between the formation times of the youngest globular clusters and the inner halo.
C1 [Kalirai, Jason S.] Space Telescope Sci Inst, Baltimore, MD 21218 USA.
   [Kalirai, Jason S.] Johns Hopkins Univ, Ctr Astrophys Sci, Baltimore, MD 21218 USA.
C3 Space Telescope Science Institute; Johns Hopkins University
RP Kalirai, JS (corresponding author), Space Telescope Sci Inst, 3700 San Martin Dr, Baltimore, MD 21218 USA.
EM jkalirai@stsci.edu
FU W. M. Keck Foundation
NR 28
TC 82
Z9 91
U1 0
U2 3
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUN 7
PY 2012
VL 486
IS 7401
BP 90
EP 92
DI 10.1038/nature11062
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 953GD
UT WOS:000304854000032
PM 22678285
DA 2026-03-09
ER

PT J
AU Gonzalez-Perez, V
   Zeng, XH
   Henzler-Wildman, K
   Lingle, CJ
AF Gonzalez-Perez, Vivian
   Zeng, Xu-Hui
   Henzler-Wildman, Katie
   Lingle, Christopher J.
TI Stereospecific binding of a disordered peptide segment mediates BK channel inactivation
SO NATURE
LA English
DT Article
ID activated potassium channels; beta-subunit; k+ channel; quaternary ammonium; rapid inactivation; molecular-basis; nmr structure; voltage; mechanism; block
AB A number of functionally important actions of proteins are mediated by short, intrinsically disordered peptide segments(1), but the molecular interactions that allow disordered domains to mediate their effects remain a topic of active investigation(2-5). Many K+ channel proteins, after initial channel opening, show a time-dependent reduction in current flux, termed 'inactivation', which involves movement of mobile cytosolic peptide segments (approximately 20-30 residues) into a position that physically occludes ion permeation(6-8). Peptide segments that produce inactivation show little amino-acid identity(6,9-13) and tolerate appreciable mutational substitutions(13) without disrupting the inactivation process. Solution nuclear magnetic resonance of several isolated inactivation domains reveals substantial conformational heterogeneity with only minimal tendency to ordered structures(14-17). Channel inactivation mechanisms may therefore help us to decipher how intrinsically disordered regions mediate functional effects. Whereas many aspects of inactivation of voltage-dependent K+ channels (Kv) can be described by a simple one-step occlusion mechanism(6,7,18,19), inactivation of the voltage-dependent large-conductance Ca2+-gated K+ (BK) channel mediated by peptide segments of auxiliary beta-subunits involves two distinguishable kinetic steps(20,21). Here we show that two-step inactivation mediated by an intrinsically disordered BK beta-subunit peptide involves a stereospecific binding interaction that precedes blockade. In contrast, blocking mediated by a Shaker Kv inactivation peptide is consistent with direct, simple occlusion by a hydrophobic segment without substantial steric requirement. The results indicate that two distinct types of molecular interaction between disordered peptide segments and their binding sites produce qualitatively similar functions.
C1 [Gonzalez-Perez, Vivian; Zeng, Xu-Hui; Lingle, Christopher J.] Washington Univ, Sch Med, Dept Anesthesiol, St Louis, MO 63110 USA.
   [Henzler-Wildman, Katie] Washington Univ, Sch Med, Dept Biochem, St Louis, MO 63110 USA.
C3 Washington University (WUSTL); Washington University (WUSTL)
RP Lingle, CJ (corresponding author), Washington Univ, Sch Med, Dept Anesthesiol, St Louis, MO 63110 USA.
EM clingle@morpheus.wustl.edu
FU Searle Scholars Program;  [GM-081748]
NR 35
TC 23
Z9 24
U1 0
U2 30
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 3
PY 2012
VL 485
IS 7396
BP 133
EP U171
DI 10.1038/nature10994
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 934NV
UT WOS:000303451900049
PM 22522931
DA 2026-03-09
ER

PT J
AU Lee, YJ
   Morrison, BM
   Li, Y
   Lengacher, S
   Farah, MH
   Hoffman, PN
   Liu, YT
   Tsingalia, A
   Jin, L
   Zhang, PW
   Pellerin, L
   Magistretti, PJ
   Rothstein, JD
AF Lee, Youngjin
   Morrison, Brett M.
   Li, Yun
   Lengacher, Sylvain
   Farah, Mohamed H.
   Hoffman, Paul N.
   Liu, Yiting
   Tsingalia, Akivaga
   Jin, Lin
   Zhang, Ping-Wu
   Pellerin, Luc
   Magistretti, Pierre J.
   Rothstein, Jeffrey D.
TI Oligodendroglia metabolically support axons and contribute to neurodegeneration
SO NATURE
LA English
DT Article
ID monocarboxylate transporter mct1; amyotrophic-lateral-sclerosis; central-nervous-system; mouse-brain; in-vivo; neuronal-activity; glutamate uptake; transgenic mice; adult brain; spinal-cord
AB Oligodendroglia support axon survival and function through mechanisms independent of myelination, and their dysfunction leads to axon degeneration in several diseases. The cause of this degeneration has not been determined, but lack of energy metabolites such as glucose or lactate has been proposed. Lactate is transported exclusively by monocarboxylate transporters, and changes to these transporters alter lactate production and use. Here we show that the most abundant lactate transporter in the central nervous system, monocarboxylate transporter 1 (MCT1, also known as SLC16A1), is highly enriched within oligodendroglia and that disruption of this transporter produces axon damage and neuron loss in animal and cell culture models. In addition, this same transporter is reduced in patients with, and in mouse models of, amyotrophic lateral sclerosis, suggesting a role for oligodendroglial MCT1 in pathogenesis. The role of oligodendroglia in axon function and neuron survival has been elusive; this study defines a new fundamental mechanism by which oligodendroglia support neurons and axons.
C1 [Lee, Youngjin; Morrison, Brett M.; Li, Yun; Farah, Mohamed H.; Hoffman, Paul N.; Liu, Yiting; Tsingalia, Akivaga; Jin, Lin; Zhang, Ping-Wu; Rothstein, Jeffrey D.] Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21205 USA.
   [Lengacher, Sylvain; Magistretti, Pierre J.] Ecole Polytech Fed Lausanne, Brain Mind Inst, Sch Life Sci, Stn 19, CH-1015 Lausanne, Switzerland.
   [Pellerin, Luc] Univ Lausanne, Dept Physiol, CH-1005 Lausanne, Switzerland.
   [Rothstein, Jeffrey D.] Johns Hopkins Univ, Dept Neurosci, Baltimore, MD 21205 USA.
   [Rothstein, Jeffrey D.] Johns Hopkins Univ, Brain Sci Inst, Baltimore, MD 21205 USA.
C3 Johns Hopkins University; Swiss Federal Institutes of Technology Domain; Ecole Polytechnique Federale de Lausanne; Swiss School of Public Health (SSPH+); University of Lausanne; Johns Hopkins University; Johns Hopkins University
RP Rothstein, JD (corresponding author), Johns Hopkins Univ, Dept Neurol, 855 N Wolfe St,Rangos 248, Baltimore, MD 21205 USA.
EM jrothstein@jhmi.edu
FU National Institutes of Health [P50AG05146, PO1NS16375]; Muscular Dystrophy Association; Packard Center for ALS; Human Frontier Science Program [RG118/1998-B]; Swiss Fonds National de Recherche Scientifique [31003A-125063]; Swiss National Science Foundation (FNRS) [3100AO-108336/1]; Biaggi Foundation; Puccini Foundation;  [NIH-NS33958];  [P2ALS]; Swiss National Science Foundation (SNF) [31003A_125063] Funding Source: Swiss National Science Foundation (SNF)
NR 48
TC 1303
Z9 1555
U1 3
U2 146
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUL 26
PY 2012
VL 487
IS 7408
BP 443
EP U1502
DI 10.1038/nature11314
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 979KD
UT WOS:000306815300030
PM 22801498
DA 2026-03-09
ER

PT J
AU de Vanssay, A
   Bougé, AL
   Boivin, A
   Hermant, C
   Teysset, L
   Delmarre, V
   Antoniewski, C
   Ronsseray, S
AF de Vanssay, Augustin
   Bouge, Anne-Laure
   Boivin, Antoine
   Hermant, Catherine
   Teysset, Laure
   Delmarre, Valerie
   Antoniewski, Christophe
   Ronsseray, Stephane
TI Paramutation in Drosophila linked to emergence of a piRNA-producing locus
SO NATURE
LA English
DT Article
ID p-element repression; heterochromatin formation; b1 locus; maize; melanogaster; trans; gene; establishment; sequences; cytotype
AB A paramutation is an epigenetic interaction between two alleles of a locus, through which one allele induces a heritable modification in the other allele without modifying the DNA sequence(1,2). The paramutated allele itself becomes paramutagenic, that is, capable of epigenetically converting a new paramutable allele. Here we describe a case of paramutation in animals showing long-term transmission over generations. We previously characterized a homology-dependent silencing mechanism referred to as the trans-silencing effect (TSE), involved in P-transposable-element repression in the germ line(3-5). We now show that clusters of P-element-derived transgenes that induce strong TSE6,7 can convert other homologous transgene clusters incapable of TSE into strong silencers, which transmit the acquired silencing capacity through 50 generations. The paramutation occurs without any need for chromosome pairing between the paramutagenic and the paramutated loci, and is mediated by maternal inheritance of cytoplasm carrying Piwi-interacting RNAs (piRNAs) homologous to the transgenes. The repression capacity of the paramutated locus is abolished by a loss-of-function mutation of the aubergine gene involved in piRNA biogenesis, but not by a loss-of-function mutation of the Dicer-2 gene involved in siRNA production. The paramutated cluster, previously producing barely detectable levels of piRNAs, is converted into a stable, strong piRNA-producing locus by the paramutation and becomes fully paramutagenic itself. Our work provides a genetic model for the emergence of piRNA loci, as well as for RNA-mediated trans-generational repression of transposable elements.
C1 [de Vanssay, Augustin; Boivin, Antoine; Hermant, Catherine; Teysset, Laure; Delmarre, Valerie; Ronsseray, Stephane] Univ Paris 06, CNRS, UMR7622, Dev Biol Lab, F-75005 Paris, France.
   [Bouge, Anne-Laure; Antoniewski, Christophe] Inst Pasteur, CNRS, URA2578, F-75015 Paris, France.
C3 Sorbonne Universite; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB); Pasteur Network; Universite Paris Cite; Institut Pasteur Paris; Centre National de la Recherche Scientifique (CNRS)
RP Ronsseray, S (corresponding author), Univ Paris 06, CNRS, UMR7622, Dev Biol Lab, 9 Quai St Bernard, F-75005 Paris, France.
EM christophe.antoniewski@upmc.fr; stephane.ronsseray@upmc.fr
FU Ministere de l'Enseignement Superieur et de la Recherche; Fondation pour la Recherche Medicale; Association Nationale de la Recherche (ANR); Association pour la Recherche contre le Cancer; ANR (project "Nuclear endosiRNAs")
CR Alleman M, 2006, NATURE, V442, P295, DOI 10.1038/nature04884
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   HOLLICK JB, 1995, GENETICS, V141, P709
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   Stam M, 2009, MOL PLANT, V2, P578, DOI 10.1093/mp/ssp020
   Stuart JR, 2002, GENETICS, V162, P1641
   Todeschini AL, 2010, PLOS ONE, V5, P0, DOI 10.1371/journal.pone.0011032
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NR 37
TC 178
Z9 207
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 4
PY 2012
VL 490
IS 7418
BP 112
EP U132
DI 10.1038/nature11416
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 015LG
UT WOS:000309446800043
PM 22922650
DA 2026-03-09
ER

PT J
AU Gao, WB
   Fallahi, P
   Togan, E
   Miguel-Sanchez, J
   Imamoglu, A
AF Gao, W. B.
   Fallahi, P.
   Togan, E.
   Miguel-Sanchez, J.
   Imamoglu, A.
TI Observation of entanglement between a quantum dot spin and a single photon
SO NATURE
LA English
DT Article
ID computation; atom
AB Entanglement has a central role in fundamental tests of quantum mechanics(1) as well as in the burgeoning field of quantum information processing. Particularly in the context of quantum networks and communication, a main challenge is the efficient generation of entanglement between stationary (spin) and propagating (photon) quantum bits(2). Here we report the observation of quantum entanglement between a semiconductor quantum dot spin and the colour of a propagating optical photon. The demonstration of entanglement relies on the use of fast, single-photon detection, which allows us to project the photon into a superposition of red and blue frequency components. Our results extend the previous demonstrations of single-spin/single-photon entanglement in trapped ions(3), neutral atoms(4,5) and nitrogen-vacancy centres(6) to the domain of artificial atoms in semiconductor nanostructures that allow for on-chip integration of electronic and photonic elements(7,8). As a result of its fast optical transitions and favourable selection rules, the scheme we implement could in principle generate nearly deterministic entangled spin-photon pairs at a rate determined ultimately by the high spontaneous emission rate. Our observation constitutes a first step towards implementation of a quantum network with nodes(9) consisting of semiconductor spin quantum bits(10-12).
C1 [Gao, W. B.; Fallahi, P.; Togan, E.; Miguel-Sanchez, J.; Imamoglu, A.] Swiss Fed Inst Technol, Inst Quantum Elect, CH-8093 Zurich, Switzerland.
C3 Swiss Federal Institutes of Technology Domain; ETH Zurich
RP Gao, WB (corresponding author), Swiss Fed Inst Technol, Inst Quantum Elect, CH-8093 Zurich, Switzerland.
EM weibo@phys.ethz.ch; imamoglu@phys.ethz.ch
FU NCCR Quantum Science and Technology; Swiss National Science Foundation; Swiss NSF [200021-140818]; ERC; Marie Curie International Incoming Fellowship within FP7; Swiss National Science Foundation (SNF) [200021_140818] Funding Source: Swiss National Science Foundation (SNF)
NR 30
TC 402
Z9 453
U1 0
U2 201
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD NOV 15
PY 2012
VL 491
IS 7424
BP 426
EP 430
DI 10.1038/nature11573
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 036MY
UT WOS:000311031600042
PM 23151586
DA 2026-03-09
ER

PT J
AU Van Dyck, D
   Jinschek, JR
   Chen, FR
AF Van Dyck, Dirk
   Jinschek, Joerg R.
   Chen, Fu-Rong
TI 'Big Bang' tomography as a new route to atomic-resolution electron tomography
SO NATURE
LA English
DT Article
ID reconstruction
AB Until now it has not been possible to image at atomic resolution using classical electron tomographic methods(1), except when the target is a perfectly crystalline nano-object imaged along a few zone axes(2). The main reasons are that mechanical tilting in an electron microscope with sub-angstrom precision over a very large angular range is difficult, that many real-life objects such as dielectric layers in microelectronic devices impose geometrical constraints and that many radiation-sensitive objects such as proteins limit the total electron dose. Hence, there is a need for a new tomographic scheme that is able to deduce three-dimensional information from only one or a few projections. Here we present an electron tomographic method that can be used to determine, from only one viewing direction and with sub-angstrom precision, both the position of individual atoms in the plane of observation and their vertical position. The concept is based on the fact that an experimentally reconstructed exit wave(3,4) consists of the superposition of the spherical waves that have been scattered by the individual atoms of the object. Furthermore, the phase of a Fourier component of a spherical wave increases with the distance of propagation at a known 'phase speed'. If we assume that an atom is a point-like object, the relationship between the phase and the phase speed of each Fourier component is linear, and the distance between the atom and the plane of observation can therefore be determined by linear fitting. This picture has similarities with Big Bang cosmology, in which the Universe expands from a point-like origin such that the distance of any galaxy from the origin is linearly proportional to the speed at which it moves away from the origin (Hubble expansion). The proof of concept of the method has been demonstrated experimentally for graphene with a two-layer structure and it will work optimally for similar layered materials, such as boron nitride and molybdenum disulphide.
C1 [Van Dyck, Dirk] Univ Antwerp, Groenenborgerlaan 171, B-2020 Antwerp, Belgium.
   [Jinschek, Joerg R.] FEI Europe, Europe NanoPort, NL-5651 CG Eindhoven, Netherlands.
   [Chen, Fu-Rong] Natl Tsing Hua Univ, Hsinchu 300, Taiwan.
C3 University of Antwerp; National Tsing Hua University
RP Van Dyck, D (corresponding author), Univ Antwerp, Groenenborgerlaan 171, B-2020 Antwerp, Belgium.
EM dirk.vandyck@ua.ac.be; frchen@ess.nthu.edu.tw
FU Research foundation - Flanders (FWO) [G.0220.05, G.0188.08];  [NSC-100-2120-M-007-005];  [NSC-99-2120-M-007-008]
NR 12
TC 100
Z9 113
U1 1
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 JUN 14
PY 2012
VL 486
IS 7402
BP 243
EP 246
DI 10.1038/nature11074
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 957UH
UT WOS:000305189000032
PM 22699616
DA 2026-03-09
ER

PT J
AU Bertolotti, J
   van Putten, EG
   Blum, C
   Lagendijk, A
   Vos, WL
   Mosk, AP
AF Bertolotti, Jacopo
   van Putten, Elbert G.
   Blum, Christian
   Lagendijk, Ad
   Vos, Willem L.
   Mosk, Allard P.
TI Non-invasive imaging through opaque scattering layers
SO NATURE
LA English
DT Article
ID phase retrieval; tomography; microscopy; waves; time
AB Non-invasive optical imaging techniques, such as optical coherence tomography(1-3), are essential diagnostic tools in many disciplines, from the life sciences to nanotechnology. However, present methods are not able to image through opaque layers that scatter all the incident light(4,5). Even a very thin layer of a scattering material can appear opaque and hide any objects behind it(6). Although great progress has been made recently with methods such as ghost imaging(7,8) and wavefront shaping(9-11), present procedures are still invasive because they require either a detector(12) or a nonlinear material(13) to be placed behind the scattering layer. Here we report an optical method that allows non-invasive imaging of a fluorescent object that is completely hidden behind an opaque scattering layer. We illuminate the object with laser light that has passed through the scattering layer. We scan the angle of incidence of the laser beam and detect the total fluorescence of the object from the front. From the detected signal, we obtain the image of the hidden object using an iterative algorithm(14,15). As a proof of concept, we retrieve a detailed image of a fluorescent object, comparable in size (50 micrometres) to a typical human cell, hidden 6 millimetres behind an opaque optical diffuser, and an image of a complex biological sample enclosed between two opaque screens. This approach to non-invasive imaging through strongly scattering media can be generalized to other contrast mechanisms and geometries.
C1 [Bertolotti, Jacopo; van Putten, Elbert G.; Lagendijk, Ad; Vos, Willem L.; Mosk, Allard P.] Univ Twente, MESA Inst Nanotechnol, Complex Photon Syst COPS, NL-7500 AE Enschede, Netherlands.
   [Bertolotti, Jacopo] Univ Florence, Dipartimento Fis, I-50019 Sesto Fiorentino, Italy.
   [Blum, Christian] Univ Twente, MESA Inst Nanotechnol, Nanobiophys NBP, NL-7500 AE Enschede, Netherlands.
   [Lagendijk, Ad] FOM Inst Atom & Mol Phys, NL-1098 XG Amsterdam, Netherlands.
C3 University of Twente; University of Florence; University of Twente; AMOLF
RP Bertolotti, J (corresponding author), Univ Twente, MESA Inst Nanotechnol, Complex Photon Syst COPS, POB 217, NL-7500 AE Enschede, Netherlands.
EM j.bertolotti@utwente.nl
FU Stichting Technische Wetenschappen; Stichting voor Fundamenteel Onderzoek der Materie; Nederlandse Organisatie voor Wetenschappelijk Onderzoek (NWO); FIRB-MIUR 'Futuro in Ricerca' [RBFR08UH60]; NWO; European Research Council [279248]
NR 30
TC 1010
Z9 1152
U1 9
U2 582
PU NATURE PUBLISHING 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 8
PY 2012
VL 491
IS 7423
BP 232
EP 234
DI 10.1038/nature11578
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 033DP
UT WOS:000310774300039
PM 23135468
DA 2026-03-09
ER

PT J
AU Mullen, AR
   Wheaton, WW
   Jin, ES
   Chen, PH
   Sullivan, LB
   Cheng, T
   Yang, YF
   Linehan, WM
   Chandel, NS
   DeBerardinis, RJ
AF Mullen, Andrew R.
   Wheaton, William W.
   Jin, Eunsook S.
   Chen, Pei-Hsuan
   Sullivan, Lucas B.
   Cheng, Tzuling
   Yang, Youfeng
   Linehan, W. Marston
   Chandel, Navdeep S.
   DeBerardinis, Ralph J.
TI Reductive carboxylation supports growth in tumour cells with defective mitochondria
SO NATURE
LA English
DT Article
ID glutamine-metabolism; cancer; dehydrogenase; gene; paraganglioma; mutations; liver; line; flux; ros
AB Mitochondrial metabolism provides precursors to build macromolecules in growing cancer cells(1,2). In normally functioning tumour cell mitochondria, oxidative metabolism of glucose- and glutamine-derived carbon produces citrate and acetyl-coenzyme A for lipid synthesis, which is required for tumorigenesis(3). Yet some tumours harbour mutations in the citric acid cycle (CAC) or electron transport chain (ETC) that disable normal oxidative mitochondrial function(4-7), and it is unknown how cells from such tumours generate precursors for macromolecular synthesis. Here we show that tumour cells with defective mitochondria use glutamine-dependent reductive carboxylation rather than oxidative metabolism as the major pathway of citrate formation. This pathway uses mitochondrial and cytosolic isoforms of NADP(+)/NADPH-dependent isocitrate dehydrogenase, and subsequent metabolism of glutamine-derived citrate provides both the acetylcoenzyme A for lipid synthesis and the four-carbon intermediates needed to produce the remaining CAC metabolites and related macromolecular precursors. This reductive, glutamine-dependent pathway is the dominant mode of metabolism in rapidly growing malignant cells containing mutations in complex I or complex III of the ETC, in patient-derived renal carcinoma cells with mutations in fumarate hydratase, and in cells with normal mitochondria subjected to acute pharmacological ETC inhibition. Our findings reveal the novel induction of a versatile glutamine-dependent pathway that reverses many of the reactions of the canonical CAC, supports tumour cell growth, and explains how cells generate pools of CAC intermediates in the face of impaired mitochondrial metabolism.
C1 [Mullen, Andrew R.; Chen, Pei-Hsuan; Cheng, Tzuling; DeBerardinis, Ralph J.] Univ Texas SW Med Ctr Dallas, Dept Pediat, Dallas, TX 75390 USA.
   [Wheaton, William W.; Sullivan, Lucas B.; Chandel, Navdeep S.] Northwestern Univ, Dept Med, Chicago, IL 60611 USA.
   [Wheaton, William W.; Sullivan, Lucas B.; Chandel, Navdeep S.] Northwestern Univ, Dept Cell & Mol Biol, Chicago, IL 60611 USA.
   [Jin, Eunsook S.] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Dallas, TX 75390 USA.
   [Jin, Eunsook S.] Univ Texas SW Med Ctr Dallas, Adv Imaging Res Ctr, Dallas, TX 75390 USA.
   [Yang, Youfeng; Linehan, W. Marston] NCI, Urol Oncol Branch, Bethesda, MD 20892 USA.
   [DeBerardinis, Ralph J.] Univ Texas SW Med Ctr Dallas, McDermott Ctr Human Growth & Dev, Dallas, TX 75390 USA.
   [DeBerardinis, Ralph J.] Univ Texas SW Med Ctr Dallas, Harold C Simmons Comprehens Canc Ctr, Dallas, TX 75235 USA.
C3 University of Texas System; University of Texas Southwestern Medical Center; Northwestern University; Northwestern University; University of Texas System; University of Texas Southwestern Medical Center; University of Texas System; University of Texas Southwestern Medical Center; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); University of Texas System; University of Texas Southwestern Medical Center; University of Texas System; University of Texas Southwestern Medical Center
RP DeBerardinis, RJ (corresponding author), Univ Texas SW Med Ctr Dallas, Dept Pediat, Dallas, TX 75390 USA.
EM nav@northwestern.edu; ralph.deberardinis@utsouthwestern.edu
FU NIH [K08DK072565, R01CA157996, R01CA123067, DK078933, RR02584, 5T32GM083831, T32CA009560, T32GM008061]; Cancer Prevention and Research Institute of Texas (CPRIT) [HIRP100437]; Robert A. Welch Foundation [I1733]; LUNGevity Foundation; Consortium of Independent Lung Health Organizations; NIH, National Cancer Institute Center for Cancer Research; National Cancer Institute [ZIDBC011089, ZIABC011028, T32CA009560, ZIABC011038, ZIABC011043] Funding Source: NIH RePORTER; National Institute of General Medical Sciences [T32GM008061] Funding Source: NIH RePORTER
NR 26
TC 1071
Z9 1251
U1 4
U2 201
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 19
PY 2012
VL 481
IS 7381
BP 385
EP U171
DI 10.1038/nature10642
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 877VK
UT WOS:000299210600047
PM 22101431
DA 2026-03-09
ER

PT J
AU Brunoud, G
   Wells, DM
   Oliva, M
   Larrieu, A
   Mirabet, V
   Burrow, AH
   Beeckman, T
   Kepinski, S
   Traas, J
   Bennett, MJ
   Vernoux, T
AF Brunoud, Geraldine
   Wells, Darren M.
   Oliva, Marina
   Larrieu, Antoine
   Mirabet, Vincent
   Burrow, Amy H.
   Beeckman, Tom
   Kepinski, Stefan
   Traas, Jan
   Bennett, Malcolm J.
   Vernoux, Teva
TI A novel sensor to map auxin response and distribution at high spatio-temporal resolution
SO NATURE
LA English
DT Article
ID box protein tir1; arabidopsis root; aux/iaa proteins; plant development; gene-expression; transport; growth; degradation; meristem; receptor
AB Auxin is a key plant morphogenetic signal(1) but tools to analyse dynamically its distribution and signalling during development are still limited. Auxin perception directly triggers the degradation of Aux/IAA repressor proteins(2-6). Here we describe a novel Aux/IAA-based auxin signalling sensor termed DII-VENUS that was engineered in the model plant Arabidopsis thaliana. The VENUS fast maturing form of yellow fluorescent protein(7) was fused in-frame to the Aux/IAA auxin-interaction domain (termed domain II; DII)(5) and expressed under a constitutive promoter. We initially show that DII-VENUS abundance is dependent on auxin, its TIR1/AFBs co-receptors(4-6,8) and proteasome activities. Next, we demonstrate that DII-VENUS provides a map of relative auxin distribution at cellular resolution in different tissues. DII-VENUS is also rapidly degraded in response to auxin and we used it to visualize dynamic changes in cellular auxin distribution successfully during two developmental responses, the root gravitropic response and lateral organ production at the shoot apex. Our results illustrate the value of developing response input sensors such as DII-VENUS to provide high-resolution spatio-temporal information about hormone distribution and response during plant growth and development.
C1 [Brunoud, Geraldine; Oliva, Marina; Mirabet, Vincent; Traas, Jan; Vernoux, Teva] Univ Lyon, Lab Reprod & Dev Plantes, UCBL, ENS Lyon,INRA,CNRS, F-69364 Lyon, France.
   [Wells, Darren M.; Larrieu, Antoine; Bennett, Malcolm J.] Univ Nottingham, Ctr Plant Integrat Biol, Loughborough LE12 5RD, England.
   [Larrieu, Antoine; Beeckman, Tom] Univ Ghent VIB, Dept Plant Syst Biol, B-9052 Ghent, Belgium.
   [Burrow, Amy H.; Kepinski, Stefan] Univ Leeds, Fac Biol Sci, Ctr Plant Sci, Leeds LS2 9JT, W Yorkshire, England.
C3 Universite Lyon 1; Ecole Normale Superieure de Lyon (ENS de LYON); INRAE; Centre National de la Recherche Scientifique (CNRS); University of Nottingham; Flanders Institute for Biotechnology (VIB); Ghent University; University of Leeds
RP Vernoux, T (corresponding author), Univ Lyon, Lab Reprod & Dev Plantes, UCBL, ENS Lyon,INRA,CNRS, F-69364 Lyon, France.
EM teva.vernoux@ens-lyon.fr
FU Human Frontier Science Program Organization [CDA 0047/2007 HFSPO]; Agence National de la Recherche [ANR-07-JCJC-0115, EraSysBio+ iSAM]; Biotechnology and Biological Sciences Research Council (BBSRC) [BB/F013981/1, BB/F007418/1]; Engineering and Physical Sciences Research Council (EPSRC); Agence Nationale de la Recherche (ANR) [ANR-07-JCJC-0115] Funding Source: Agence Nationale de la Recherche (ANR); Biotechnology and Biological Sciences Research Council [BB/D019613/1, REI20541, BB/F013981/1, BB/J009717/1, BB/F007418/1] Funding Source: researchfish; BBSRC [BB/D019613/1, BB/F013981/1, BB/J009717/1, BB/F007418/1] Funding Source: UKRI
NR 42
TC 597
Z9 659
U1 3
U2 351
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD FEB 2
PY 2012
VL 482
IS 7383
BP 103
EP U132
DI 10.1038/nature10791
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 884RN
UT WOS:000299726000044
PM 22246322
DA 2026-03-09
ER

PT J
AU Chakkalakal, JV
   Jones, KM
   Basson, MA
   Brack, AS
AF Chakkalakal, Joe V.
   Jones, Kieran M.
   Basson, M. Albert
   Brack, Andrew S.
TI The aged niche disrupts muscle stem cell quiescence
SO NATURE
LA English
DT Article
ID fibroblast-growth-factor; satellite cells; self-renewal; progenitor cells; progression; myogenesis; sprouty; differentiation; heterogeneity; contributes
AB The niche is a conserved regulator of stem cell quiescence and function. During ageing, stem cell function declines. To what extent and by what means age-related changes within the niche contribute to this phenomenon are unknown. Here we demonstrate that the aged muscle stem cell niche, the muscle fibre, expresses Fgf2 under homeostatic conditions, driving a subset of satellite cells to break quiescence and lose their self-renewing capacity. We show in mice that relatively dormant aged satellite cells robustly express sprouty 1 (Spry1), an inhibitor of fibroblast growth factor (FGF) signalling. Increasing FGF signalling in aged satellite cells under homeostatic conditions by removing Spry1 results in the loss of quiescence, satellite cell depletion and diminished regenerative capacity. Conversely, reducing niche-derived FGF activity through inhibition of Fgfr1 signalling or overexpression of Spry1 in satellite cells prevents their depletion. These experiments identify an age-dependent change in the stem cell niche that directly influences stem cell quiescence and function.
C1 [Chakkalakal, Joe V.; Brack, Andrew S.] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA.
   [Jones, Kieran M.; Basson, M. Albert] Kings Coll London, Dept Craniofacial Dev & Stem Cell Biol, London SE1 9RT, England.
   [Brack, Andrew S.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA.
   [Brack, Andrew S.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
C3 Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; University of London; King's College London; Harvard University; Harvard University; Harvard Medical School
RP Brack, AS (corresponding author), Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA.
EM Brack.Andrew@mgh.harvard.edu
FU MGH; Harvard Stem Cell Institute; NIH [R01 AR060868, R01 AR061002]; Wellcome Trust [WT091475]; MGH ECOR Postdoctoral Fellow Award; BBSRC Doctoral Training Award [BB/F017626/1]; BBSRC [BB/F017626/1] Funding Source: UKRI
NR 55
TC 634
Z9 781
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 OCT 18
PY 2012
VL 490
IS 7420
BP 355
EP +
DI 10.1038/nature11438
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 021XI
UT WOS:000309918500036
PM 23023126
DA 2026-03-09
ER

PT J
AU Ausländer, S
   Ausländer, D
   Müller, M
   Wieland, M
   Fussenegger, M
AF Auslaender, Simon
   Auslaender, David
   Mueller, Marius
   Wieland, Markus
   Fussenegger, Martin
TI Programmable single-cell mammalian biocomputers
SO NATURE
LA English
DT Article
ID cancer-cells; mice; networks; circuit; communication; homeostasis; switches
AB Synthetic biology has advanced the design of standardized control devices that program cellular functions and metabolic activities in living organisms(1). Rational interconnection of these synthetic switches resulted in increasingly complex designer networks that execute input-triggered genetic instructions with precision, robustness and computational logic reminiscent of electronic circuits(2,3). Using trigger-controlled transcription factors, which independently control gene expression(4,5), and RNA-binding proteins that inhibit the translation of transcripts harbouring specific RNA target motifs(6,7), we have designed a set of synthetic transcription-translation control devices that could be rewired in a plug-and-play manner. Here we show that these combinatorial circuits integrated a two-molecule input and performed digital computations with NOT, AND, NAND and N-IMPLY expression logic in single mammalian cells. Functional interconnection of two N-IMPLY variants resulted in bitwise intracellular XOR operations, and a combinatorial arrangement of three logic gates enabled independent cells to perform programmable half-subtractor and half-adder calculations. Individual mammalian cells capable of executing basic molecular arithmetic functions isolated or coordinated to metabolic activities in a predictable, precise and robust manner may provide new treatment strategies and bio-electronic interfaces in future gene-based and cell-based therapies.
C1 [Auslaender, Simon; Auslaender, David; Mueller, Marius; Wieland, Markus; Fussenegger, Martin] ETH, Dept Biosyst Sci & Engn, CH-4058 Basel, Switzerland.
   [Fussenegger, Martin] Univ Basel, Fac Sci, CH-4058 Basel, Switzerland.
C3 Swiss Federal Institutes of Technology Domain; ETH Zurich; University of Basel
RP Fussenegger, M (corresponding author), ETH, Dept Biosyst Sci & Engn, Mattenstr 26, CH-4058 Basel, Switzerland.
EM fussenegger@bsse.ethz.ch
FU Swiss National Science Foundation [31003A-126022]; EC Framework 7 (Persist)
NR 30
TC 293
Z9 352
U1 3
U2 225
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUL 5
PY 2012
VL 487
IS 7405
BP 123
EP +
DI 10.1038/nature11149
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 968LM
UT WOS:000305982900063
PM 22722847
DA 2026-03-09
ER

PT J
AU Xu, NL
   Harnett, MT
   Williams, SR
   Huber, D
   O'Connor, DH
   Svoboda, K
   Magee, JC
AF Xu, Ning-long
   Harnett, Mark T.
   Williams, Stephen R.
   Huber, Daniel
   O'Connor, Daniel H.
   Svoboda, Karel
   Magee, Jeffrey C.
TI Nonlinear dendritic integration of sensory and motor input during an active sensing task
SO NATURE
LA English
DT Article
ID primary somatosensory cortex; cortical-neurons; object localization; pyramidal neurons; neural activity; circuits; organization; dynamics; whisking; motion
AB Active dendrites provide neurons with powerful processing capabilities. However, little is known about the role of neuronal dendrites in behaviourally related circuit computations. Here we report that a novel global dendritic nonlinearity is involved in the integration of sensory and motor information within layer 5 pyramidal neurons during an active sensing behaviour. Layer 5 pyramidal neurons possess elaborate dendritic arborizations that receive functionally distinct inputs, each targeted to spatially separate regions(1,2). At the cellular level, coincident input from these segregated pathways initiates regenerative dendritic electrical events that produce bursts of action potential output(3,4) and circuits featuring this powerful dendritic nonlinearity can implement computations based on input correlation(5). To examine this in vivo we recorded dendritic activity in layer 5 pyramidal neurons in the barrel cortex using two-photon calcium imagingin mice performing an object-localization task. Large-amplitude, global calcium signals were observed throughout the apical tuft dendrites when active touch occurred at particular object locations or whisker angles. Such global calcium signals are produced by dendritic plateau potentials that require both vibrissal sensory input and primary motor cortex activity. These data provide direct evidence of nonlinear dendritic processing of correlated sensory and motor information in the mammalian neocortex during active sensation.
C1 [Xu, Ning-long; Harnett, Mark T.; Huber, Daniel; O'Connor, Daniel H.; Svoboda, Karel; Magee, Jeffrey C.] Howard Hughes Med Inst, Ashburn, VA 20147 USA.
   [Williams, Stephen R.] Univ Queensland, Queensland Brain Inst, St Lucia, Qld 4072, Australia.
C3 Howard Hughes Medical Institute; University of Queensland
RP Magee, JC (corresponding author), Howard Hughes Med Inst, Janelia Farm Res Campus, Ashburn, VA 20147 USA.
EM mageej@janelia.hhmi.org
FU Australian research council [FT100100502]; Australian National Health and Medical Research Council [APP1004575]; Australian Research Council [FT100100502] Funding Source: Australian Research Council
NR 38
TC 384
Z9 466
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 DEC 13
PY 2012
VL 492
IS 7428
BP 247
EP +
DI 10.1038/nature11601
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 053GM
UT WOS:000312259300041
PM 23143335
DA 2026-03-09
ER

PT J
AU Simini, F
   González, MC
   Maritan, A
   Barabási, AL
AF Simini, Filippo
   Gonzalez, Marta C.
   Maritan, Amos
   Barabasi, Albert-Laszlo
TI A universal model for mobility and migration patterns
SO NATURE
LA English
DT Article
ID intervening opportunity; network; growth; trade
AB Introduced in its contemporary form in 1946 (ref. 1), but with roots that go back to the eighteenth century(2), the gravity law(1,3,4) is the prevailing framework with which to predict population movement(3,5,6), cargo shipping volume(7) and inter-city phone calls(8,9), as well as bilateral trade flows between nations(10). Despite its widespread use, it relies on adjustable parameters that vary from region to region and suffers from known analytic inconsistencies. Here we introduce a stochastic process capturing local mobility decisions that helps us analytically derive commuting and mobility fluxes that require as input only information on the population distribution. The resulting radiation model predicts mobility patterns in good agreement with mobility and transport patterns observed in a wide range of phenomena, from long-term migration patterns to communication volume between different regions. Given its parameter-free nature, the model can be applied in areas where we lack previous mobility measurements, significantly improving the predictive accuracy of most of the phenomena affected by mobility and transport processes(11-23).
C1 [Simini, Filippo; Barabasi, Albert-Laszlo] Northeastern Univ, Ctr Complex Network Res, Boston, MA 02115 USA.
   [Simini, Filippo; Barabasi, Albert-Laszlo] Northeastern Univ, Dept Phys Biol & Comp Sci, Boston, MA 02115 USA.
   [Simini, Filippo; Maritan, Amos] Univ Padua, Dipartimento Fis G Galilei, CNISM, I-35131 Padua, Italy.
   [Simini, Filippo; Maritan, Amos] Ist Nazl Fis Nucl, I-35131 Padua, Italy.
   [Simini, Filippo] Budapest Univ Technol & Econ, Inst Phys, H-1111 Budapest, Hungary.
   [Gonzalez, Marta C.] MIT, Dept Civil & Environm Engn, Cambridge, MA 02139 USA.
   [Barabasi, Albert-Laszlo] Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA.
   [Barabasi, Albert-Laszlo] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
C3 Northeastern University; Northeastern University; University of Padua; Istituto Nazionale di Fisica Nucleare (INFN); Budapest University of Technology & Economics; Massachusetts Institute of Technology (MIT); Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Brigham & Women's Hospital
RP Barabási, AL (corresponding author), Northeastern Univ, Ctr Complex Network Res, Boston, MA 02115 USA.
EM amos.maritan@pd.infn.it; alb@neu.edu
FU Cariparo foundation; Network Science Collaborative Technology Alliance; US Army Research Laboratory [W911NF-09-2-0053]; Office of Naval Research [N000141010968]; Defense Threat Reduction Agency [WMD BRBAA07-J-2-0035, BRBAA08-Per4-C-2-0033]; James S. McDonnell Foundation 21st Century Initiative in Studying Complex Systems
NR 30
TC 1086
Z9 1276
U1 14
U2 650
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 5
PY 2012
VL 484
IS 7392
BP 96
EP 100
DI 10.1038/nature10856
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 919QN
UT WOS:000302343400041
PM 22367540
DA 2026-03-09
ER

PT J
AU McLaskey, GC
   Thomas, AM
   Glaser, SD
   Nadeau, RM
AF McLaskey, Gregory C.
   Thomas, Amanda M.
   Glaser, Steven D.
   Nadeau, Robert M.
TI Fault healing promotes high-frequency earthquakes in laboratory experiments and on natural faults
SO NATURE
LA English
DT Article
ID recurrence interval; dependent friction; stick-slip; state; asperity; velocity; moment; rocks; creep; model
AB Faults strengthen or heal with time in stationary contact(1,2), and this healing may be an essential ingredient for the generation of earthquakes(1-3). In the laboratory, healing is thought to be the result of thermally activated mechanisms that weld together micrometre-sized asperity contacts on the fault surface, but the relationship between laboratory measures of fault healing and the seismically observable properties of earthquakes is at present not well defined. Here we report on laboratory experiments and seismological observations that show how the spectral properties of earthquakes vary as a function of fault healing time. In the laboratory, we find that increased healing causes a disproportionately large amount of high-frequency seismic radiation to be produced during fault rupture. We observe a similar connection between earthquake spectra and recurrence time for repeating earthquake sequences on natural faults. Healing rates depend on pressure, temperature(4) and mineralogy(1), so the connection between seismicity and healing may help to explain recent observations of large megathrust earthquakes which indicate that energetic, high-frequency seismic radiation originates from locations that are distinct from the geodetically inferred locations of large-amplitude fault slip(5-7).
C1 [McLaskey, Gregory C.; Glaser, Steven D.] Univ Calif Berkeley, Dept Civil & Environm Engn, Berkeley, CA 94720 USA.
   [Thomas, Amanda M.; Nadeau, Robert M.] Univ Calif Berkeley, Berkeley Seismol Lab, Dept Earth & Planetary Sci, Berkeley, CA 94720 USA.
C3 University of California System; University of California Berkeley; University of California System; University of California Berkeley
RP McLaskey, GC (corresponding author), US Geol Survey, 345 Middlefield Rd,MS 977, Menlo Pk, CA 94025 USA.
EM gmclaskey@usgs.gov
FU US NSF GRF; NSF [CMMI-1131582, EAR-0738342, EAR-0910322]; Directorate For Engineering [1131582] Funding Source: National Science Foundation; Div Of Civil, Mechanical, & Manufact Inn [1131582] Funding Source: National Science Foundation
NR 29
TC 91
Z9 107
U1 10
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 NOV 1
PY 2012
VL 491
IS 7422
BP 101
EP U114
DI 10.1038/nature11512
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 028PM
UT WOS:000310434500038
PM 23128232
DA 2026-03-09
ER

PT J
AU Landsberg, J
   Kohlmeyer, J
   Renn, M
   Bald, T
   Rogava, M
   Cron, M
   Fatho, M
   Lennerz, V
   Wölfel, T
   Hölzel, M
   Tüting, T
AF Landsberg, Jennifer
   Kohlmeyer, Judith
   Renn, Marcel
   Bald, Tobias
   Rogava, Meri
   Cron, Mira
   Fatho, Martina
   Lennerz, Volker
   Woelfel, Thomas
   Hoelzel, Michael
   Tueting, Thomas
TI Melanomas resist T-cell therapy through inflammation-induced reversible dedifferentiation
SO NATURE
LA English
DT Article
ID metastatic melanoma; cancer regression; in-vivo; immunotherapy; antigen; lymphocytes; mice; growth; autoimmunity; responses
AB Adoptive cell transfer therapies (ACTs) with cytotoxic T cells that target melanocytic antigens can achieve remissions in patients with metastatic melanomas, but tumours frequently relapse(1,2). Hypotheses explaining the acquired resistance to ACTs include the selection of antigen-deficient tumour cell variants(3-5) and the induction of T-cell tolerance(6). However, the lack of appropriate experimental melanoma models has so far impeded clear insights into the underlying mechanisms. Here we establish an effective ACT protocol in a genetically engineered mouse melanoma model that recapitulates tumour regression, remission and relapse as seen in patients. We report the unexpected observation that melanomas acquire ACT resistance through an inflammation-induced reversible loss of melanocytic antigens. In serial transplantation experiments, melanoma cells switch between a differentiated and a dedifferentiated phenotype in response to T-cell-driven inflammatory stimuli. We identified the proinflammatory cytokine tumour necrosis factor (TNF)-alpha as a crucial factor that directly caused reversible dedifferentiation of mouse and human melanoma cells. Tumour cells exposed to TNF-alpha were poorly recognized by T cells specific for melanocytic antigens, whereas recognition by T cells specific for non-melanocytic antigens was unaffected or even increased. Our results demonstrate that the phenotypic plasticity of melanoma cells in an inflammatory microenvironment contributes to tumour relapse after initially successful T-cell immunotherapy. On the basis of our work, we propose that future ACT protocols should simultaneously target melanocytic and non-melanocytic antigens to ensure broad recognition of both differentiated and dedifferentiated melanoma cells, and include strategies to sustain T-cell effector functions by blocking immune-inhibitory mechanisms in the tumour microenvironment.
C1 [Landsberg, Jennifer; Kohlmeyer, Judith; Renn, Marcel; Bald, Tobias; Rogava, Meri; Cron, Mira; Tueting, Thomas] Univ Bonn, Dept Dermatol & Allergy, Lab Expt Dermatol, D-53105 Bonn, Germany.
   [Fatho, Martina; Lennerz, Volker; Woelfel, Thomas] Johannes Gutenberg Univ Mainz, Univ Med Ctr, Dept Med 3, D-55101 Mainz, Germany.
   [Hoelzel, Michael] Univ Bonn, Unit RNA Biol, Dept Clin Chem & Clin Pharmacol, D-53105 Bonn, Germany.
C3 University of Bonn; Johannes Gutenberg University of Mainz; University of Bonn
RP Tüting, T (corresponding author), Univ Bonn, Dept Dermatol & Allergy, Lab Expt Dermatol, D-53105 Bonn, Germany.
EM thomas.tueting@ukb.uni-bonn.de
FU DFG [SFB832, SFB704, SFB 432]; Deutsche Krebshilfe (P9 in the Melanoma Research Network); BONFOR
NR 43
TC 494
Z9 556
U1 0
U2 77
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD OCT 18
PY 2012
VL 490
IS 7420
BP 412
EP +
DI 10.1038/nature11538
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 021XI
UT WOS:000309918500048
PM 23051752
DA 2026-03-09
ER

PT J
AU Cordier, P
   Amodeo, J
   Carrez, P
AF Cordier, Patrick
   Amodeo, Jonathan
   Carrez, Philippe
TI Modelling the rheology of MgO under Earth's mantle pressure, temperature and strain rates
SO NATURE
LA English
DT Article
ID initio molecular-dynamics; peierls-nabarro; shear-stress; dislocation; core; simulation; crystals; metals; energy; deformation
AB Plate tectonics, which shapes the surface of Earth, is the result of solid-state convection in Earth's mantle over billions of years. Simply driven by buoyancy forces, mantle convection is complicated by the nature of the convecting materials, which are not fluids but polycrystalline rocks. Crystalline materials can flow as the result of the motion of defects-point defects, dislocations, grain boundaries and so on. Reproducing in the laboratory the extreme deformation conditions of the mantle is extremely challenging. In particular, experimental strain rates are at least six orders of magnitude larger than in nature(1). Here we show that the rheology of MgO at the pressure, temperature and strain rates of the mantle is accessible by multiscale numerical modelling starting from first principles and with no adjustable parameters. Our results demonstrate that extremely low strain rates counteract the influence of pressure. In the mantle, MgO deforms in the athermal regime and this leads to a very weak phase. It is only in the lowermost lower mantle that the pressure effect could dominate and that, under the influence of lattice friction, a viscosity of the order of 10(21)-10(22) pascal seconds can be defined for MgO.
C1 [Cordier, Patrick; Amodeo, Jonathan; Carrez, Philippe] Univ Lille 1, Unite Mat & Transformat, CNRS, UMR 8207, F-59650 Villeneuve Dascq, France.
C3 Centre National de la Recherche Scientifique (CNRS); CNRS - Institute of Chemistry (INC); Universite de Lille
RP Cordier, P (corresponding author), Univ Lille 1, Unite Mat & Transformat, CNRS, UMR 8207, F-59650 Villeneuve Dascq, France.
EM Patrick.Cordier@univ-lille1.fr
FU ANR
NR 44
TC 102
Z9 107
U1 1
U2 110
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JAN 12
PY 2012
VL 481
IS 7380
BP 177
EP +
DI 10.1038/nature10687
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 874TO
UT WOS:000298981200034
PM 22237109
DA 2026-03-09
ER

PT J
AU Sato, S
   Tabata, S
   Hirakawa, H
   Asamizu, E
   Shirasawa, K
   Isobe, S
   Kaneko, T
   Nakamura, Y
   Shibata, D
   Aoki, K
   Egholm, M
   Knight, J
   Bogden, R
   Li, CB
   Shuang, Y
   Xu, X
   Pan, SK
   Cheng, SF
   Liu, X
   Ren, YY
   Wang, J
   Albiero, A
   Dal Pero, F
   Todesco, S
   Van Eck, J
   Buels, RM
   Bombarely, A
   Gosselin, JR
   Huang, MY
   Leto, JA
   Menda, N
   Strickler, S
   Mao, LY
   Gao, S
   Tecle, IY
   York, T
   Zheng, Y
   Vrebalov, JT
   Lee, J
   Zhong, SL
   Mueller, LA
   Stiekema, WJ
   Ribeca, P
   Alioto, T
   Yang, WC
   Huang, SW
   Du, YC
   Zhang, ZH
   Gao, JC
   Guo, YM
   Wang, XX
   Li, Y
   He, J
   Li, CY
   Cheng, ZK
   Zuo, JR
   Ren, JF
   Zhao, JH
   Yan, LH
   Jiang, HL
   Wang, B
   Li, HS
   Li, ZJ
   Fu, FY
   Chen, BT
   Han, B
   Feng, Q
   Fan, DL
   Wang, Y
   Ling, HQ
   Xue, YBA
   Ware, D
   McCombie, WR
   Lippman, ZB
   Chia, JM
   Jiang, K
   Pasternak, S
   Gelley, L
   Kramer, M
   Anderson, LK
   Chang, SB
   Royer, SM
   Shearer, LA
   Stack, SM
   Rose, JKC
   Xu, YM
   Eannetta, N
   Matas, AJ
   McQuinn, R
   Tanksley, SD
   Camara, F
   Guigó, R
   Rombauts, S
   Fawcett, J
   Van de Peer, Y
   Zamir, D
   Liang, CB
   Spannagl, M
   Gundlach, H
   Bruggmann, R
   Mayer, K
   Jia, ZQ
   Zhang, JH
   Ye, ZBA
   Bishop, GJ
   Butcher, S
   Lopez-Cobollo, R
   Buchan, D
   Filippis, I
   Abbott, J
   Dixit, R
   Singh, M
   Singh, A
   Pal, JK
   Pandit, A
   Singh, PK
   Mahato, AK
   Dogra, V
   Gaikwad, K
   Sharma, TR
   Mohapatra, T
   Singh, NK
   Causse, M
   Rothan, C
   Schiex, T
   Noirot, C
   Bellec, A
   Klopp, C
   Delalande, C
   Berges, H
   Mariette, J
   Frasse, P
   Vautrin, S
   Zouine, M
   Latché, A
   Rousseau, C
   Regad, F
   Pech, JC
   Philippot, M
   Bouzayen, M
   Pericard, P
   Osorio, S
   del Carmen, AF
   Monforte, A
   Granell, A
   Fernandez-Muñoz, R
   Conte, M
   Lichtenstein, G
   Carrari, F
   De Bellis, G
   Fuligni, F
   Peano, C
   Grandillo, S
   Termolino, P
   Pietrella, M
   Fantini, E
   Falcone, G
   Fiore, A
   Giuliano, G
   Lopez, L
   Facella, P
   Perrotta, G
   Daddiego, L
   Bryan, G
   Orozco, M
   Pastor, X
   Torrents, D
   van Schriek, KNVMGM
   Feron, RMC
   van Oeveren, J
   de Heer, P
   daPonte, L
   Jacobs-Oomen, S
   Cariaso, M
   Prins, M
   van Eijk, MJT
   Janssen, A
   van Haaren, MJJ
   Jo, SH
   Kim, J
   Kwon, SY
   Kim, S
   Koo, DH
   Lee, S
   Hur, CG
   Clouser, C
   Rico, A
   Hallab, A
   Gebhardt, C
   Klee, K
   Jöcker, A
   Warfsmann, J
   Göbel, U
   Kawamura, S
   Yano, K
   Sherman, JD
   Fukuoka, H
   Negoro, S
   Bhutty, S
   Chowdhury, P
   Chattopadhyay, D
   Datema, E
   Smit, S
   Schijlen, EWM
   van de Belt, J
   van Haarst, JC
   Peters, SA
   van Staveren, MJ
   Henkens, MHC
   Mooyman, PJW
   Hesselink, T
   van Ham, RCHJ
   Jiang, GY
   Droege, M
   Choi, D
   Kang, BC
   Kim, BD
   Park, M
   Kim, S
   Yeom, SI
   Lee, YH
   Choi, YD
   Li, GC
   Gao, JW
   Liu, YS
   Huang, SX
   Fernandez-Pedrosa, V
   Collado, C
   Zuñiga, S
   Wang, GP
   Cade, R
   Dietrich, RA
   Rogers, J
   Knapp, S
   Fei, ZJ
   White, RA
   Thannhauser, TW
   Giovannoni, JJ
   Botella, MA
   Gilbert, L
   Gonzalez, R
   Goicoechea, JL
   Yu, Y
   Kudrna, D
   Collura, K
   Wissotski, M
   Wing, R
   Schoof, H
   Meyers, BC
   Gurazada, AB
   Green, PJ
   Mathur, S
   Vyas, S
   Solanke, AU
   Kumar, R
   Gupta, V
   Sharma, AK
   Khurana, P
   Khurana, JP
   Tyagi, AK
   Dalmay, T
   Mohorianu, I
   Walts, B
   Chamala, S
   Barbazuk, WB
   Li, JP
   Guo, H
   Lee, TH
   Wang, YP
   Zhang, D
   Paterson, AH
   Wang, XY
   Tang, HB
   Barone, A
   Chiusano, ML
   Ercolano, MR
   D'Agostino, N
   Di Filippo, M
   Traini, A
   Sanseverino, W
   Frusciante, L
   Seymour, GB
   Elharam, M
   Fu, Y
   Hua, A
   Kenton, S
   Lewis, J
   Lin, SP
   Najar, F
   Lai, HS
   Qin, BF
   Qu, CM
   Shi, RH
   White, D
   White, J
   Xing, YB
   Yang, KQ
   Yi, J
   Yao, ZY
   Zhou, LP
   Roe, BA
   Vezzi, A
   D'Angelo, M
   Zimbello, R
   Schiavon, R
   Caniato, E
   Rigobello, C
   Campagna, D
   Vitulo, N
   Valle, G
   Nelson, DR
   De Paoli, E
   Szinay, D
   de Jong, HH
   Bai, YL
   Visser, RGF
   Lankhorst, RMK
   Beasley, H
   McLaren, K
   Nicholson, C
   Riddle, C
   Gianese, G
AF Sato, Shusei
   Tabata, Satoshi
   Hirakawa, Hideki
   Asamizu, Erika
   Shirasawa, Kenta
   Isobe, Sachiko
   Kaneko, Takakazu
   Nakamura, Yasukazu
   Shibata, Daisuke
   Aoki, Koh
   Egholm, Michael
   Knight, James
   Bogden, Robert
   Li, Changbao
   Shuang, Yang
   Xu, Xun
   Pan, Shengkai
   Cheng, Shifeng
   Liu, Xin
   Ren, Yuanyuan
   Wang, Jun
   Albiero, Alessandro
   Dal Pero, Francesca
   Todesco, Sara
   Van Eck, Joyce
   Buels, Robert M.
   Bombarely, Aureliano
   Gosselin, Joseph R.
   Huang, Minyun
   Leto, Jonathan A.
   Menda, Naama
   Strickler, Susan
   Mao, Linyong
   Gao, Shan
   Tecle, Isaak Y.
   York, Thomas
   Zheng, Yi
   Vrebalov, Julia T.
   Lee, JeMin
   Zhong, Silin
   Mueller, Lukas A.
   Stiekema, Willem J.
   Ribeca, Paolo
   Alioto, Tyler
   Yang, Wencai
   Huang, Sanwen
   Du, Yongchen
   Zhang, Zhonghua
   Gao, Jianchang
   Guo, Yanmei
   Wang, Xiaoxuan
   Li, Ying
   He, Jun
   Li, Chuanyou
   Cheng, Zhukuan
   Zuo, Jianru
   Ren, Jianfeng
   Zhao, Jiuhai
   Yan, Liuhua
   Jiang, Hongling
   Wang, Bao
   Li, Hongshuang
   Li, Zhenjun
   Fu, Fuyou
   Chen, Bingtang
   Han, Bin
   Feng, Qi
   Fan, Danlin
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   Monforte, Antonio
   Granell, Antonio
   Fernandez-Munoz, Rafael
   Conte, Mariana
   Lichtenstein, Gabriel
   Carrari, Fernando
   De Bellis, Gianluca
   Fuligni, Fabio
   Peano, Clelia
   Grandillo, Silvana
   Termolino, Pasquale
   Pietrella, Marco
   Fantini, Elio
   Falcone, Giulia
   Fiore, Alessia
   Giuliano, Giovanni
   Lopez, Loredana
   Facella, Paolo
   Perrotta, Gaetano
   Daddiego, Loretta
   Bryan, Glenn
   Orozco, Modesto
   Pastor, Xavier
   Torrents, David
   van Schriek, Keygene N. V. Marco G. M.
   Feron, Richard M. C.
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   de Heer, Peter
   daPonte, Lorena
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   Cariaso, Mike
   Prins, Marcel
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   Barbazuk, W. Brad
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   Guo, Hui
   Lee, Tae-Ho
   Wang, Yupeng
   Zhang, Dong
   Paterson, Andrew H.
   Wang, Xiyin
   Tang, Haibao
   Barone, Amalia
   Chiusano, Maria Luisa
   Ercolano, Maria Raffaella
   D'Agostino, Nunzio
   Di Filippo, Miriam
   Traini, Alessandra
   Sanseverino, Walter
   Frusciante, Luigi
   Seymour, Graham B.
   Elharam, Mounir
   Fu, Ying
   Hua, Axin
   Kenton, Steven
   Lewis, Jennifer
   Lin, Shaoping
   Najar, Fares
   Lai, Hongshing
   Qin, Baifang
   Qu, Chunmei
   Shi, Ruihua
   White, Douglas
   White, James
   Xing, Yanbo
   Yang, Keqin
   Yi, Jing
   Yao, Ziyun
   Zhou, Liping
   Roe, Bruce A.
   Vezzi, Alessandro
   D'Angelo, Michela
   Zimbello, Rosanna
   Schiavon, Riccardo
   Caniato, Elisa
   Rigobello, Chiara
   Campagna, Davide
   Vitulo, Nicola
   Valle, Giorgio
   Nelson, David R.
   De Paoli, Emanuele
   Szinay, Dora
   de Jong, Hans H.
   Bai, Yuling
   Visser, Richard G. F.
   Lankhorst, Rene M. Klein
   Beasley, Helen
   McLaren, Karen
   Nicholson, Christine
   Riddle, Claire
   Gianese, Giulio
TI The tomato genome sequence provides insights into fleshy fruit evolution
SO NATURE
LA English
DT Article
ID lycopersicon-esculentum; gene; diversification; arabidopsis; patterns; ortholog; history; sorghum; potato
AB Tomato (Solanum lycopersicum) is a major crop plant and a model system for fruit development. Solanum is one of the largest angiosperm genera(1) and includes annual and perennial plants from diverse habitats. Here we present a high-quality genome sequence of domesticated tomato, a draft sequence of its closest wild relative, Solanum pimpinellifolium(2), and compare them to each other and to the potato genome (Solanum tuberosum). The two tomato genomes show only 0.6% nucleotide divergence and signs of recent admixture, but show more than 8% divergence from potato, with nine large and several smaller inversions. In contrast to Arabidopsis, but similar to soybean, tomato and potato small RNAs map predominantly to gene-rich chromosomal regions, including gene promoters. The Solanum lineage has experienced two consecutive genome triplications: one that is ancient and shared with rosids, and a more recent one. These triplications set the stage for the neofunctionalization of genes controlling fruit characteristics, such as colour and fleshiness.
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   [Beasley, Helen; McLaren, Karen; Nicholson, Christine; Riddle, Claire] Wellcome Trust Sanger Inst Hinxton, Cambridge CB10 1SA, England.
   [Gianese, Giulio] Ylichron SrL, Casaccia Res Ctr, I-00123 Rome, Italy.
C3 Kazusa DNA Research Institute; Beijing Academy of Agriculture & Forestry Sciences (BAAFS); Beijing Genomics Institute (BGI); Chinese Academy of Sciences; Cornell University; Boyce Thompson Institute for Plant Research; Centre for BioSystems Genomics; China Agricultural University; Chinese Academy of Agricultural Sciences; Institute of Vegetables & Flowers, CAAS; Chinese Academy of Sciences; Institute of Genetics & Developmental Biology, CAS; Chinese Academy of Sciences; Institute of Genetics & Developmental Biology, CAS; Chinese Academy of Sciences; Wuhan Botanical Garden, CAS; Chinese Academy of Sciences; Institute of Genetics & Developmental Biology, CAS; Chinese Academy of Sciences; Institute of Genetics & Developmental Biology, CAS; Cold Spring Harbor Laboratory; Colorado State University System; Colorado State University Fort Collins; National Taiwan University; Cornell University; Barcelona Institute of Science & Technology; Pompeu Fabra University; Centre de Regulacio Genomica (CRG); Ghent University; Flanders Institute for Biotechnology (VIB); Hebrew University of Jerusalem; Heilongjiang Academy of Agricultural Sciences; Henan Agricultural University; Huazhong Agricultural University; Imperial College London; Indian Council of Agricultural Research (ICAR); ICAR - National Institute For Plant Biotechnology (NIPB); ICAR - Indian Agricultural Research Institute; INRAE; Universite de Bordeaux; INRAE; INRAE; INRAE; INRAE; Universite de Toulouse; Consejo Superior de Investigaciones Cientificas (CSIC); Universitat Politecnica de Valencia; CSIC-UPV - Instituto de Biologia Molecular y Celular de Plantas (IBMCP); Consejo Superior de Investigaciones Cientificas (CSIC); Universidad de Malaga; CSIC-UMA - Instituto de Hortofruticultura Subtropical y Mediterranea La Mayora (IHSM); Consiglio Nazionale delle Ricerche (CNR); Istituto di Tecnologie Biomediche (ITB-CNR); Consiglio Nazionale delle Ricerche (CNR); Italian National Agency New Technical Energy & Sustainable Economics Development; Italian National Agency New Technical Energy & Sustainable Economics Development; Scuola Superiore Sant'Anna; Italian National Agency New Technical Energy & Sustainable Economics Development; Italian National Agency New Technical Energy & Sustainable Economics Development; James Hutton Institute; Universitat Politecnica de Catalunya; Barcelona Supercomputer Center (BSC-CNS); Barcelona Institute of Science & Technology; Institute for Research in Biomedicine - IRB Barcelona; ICREA; Keygene N.V.; Korea Research Institute of Bioscience & Biotechnology (KRIBB); Thermo Fisher Scientific; Thermo Fisher Scientific; Max Planck Society; Meiji University; Montana State University System; Montana State University Bozeman; Department of Biotechnology (DBT) India; National Institute of Plant Genome Research (NIPGR); Qingdao Agricultural University; Roche Holding; Roche Holding Germany; Seoul National University (SNU); Seoul National University (SNU); Seoul National University (SNU); Seoul National University (SNU); Shandong Academy of Agricultural Sciences; Shandong Academy of Agricultural Sciences; Sichuan University; South China Agricultural University; Syngenta; UK Research & Innovation (UKRI); Biotechnology and Biological Sciences Research Council (BBSRC); Earlham Institute; Natural History Museum London; United States Department of Agriculture (USDA); Consejo Superior de Investigaciones Cientificas (CSIC); Universidad de Malaga; CSIC-UMA - Instituto de Hortofruticultura Subtropical y Mediterranea La Mayora (IHSM); Barcelona Institute of Science & Technology; Pompeu Fabra University; Centre de Regulacio Genomica (CRG); University of Arizona; University of Bonn; University of Delaware; University of Delaware; University of Delhi; University of Delhi; University of East Anglia; University of East Anglia; University System of Georgia; University of Georgia; North China University of Science & Technology; North China University of Science & Technology; J. Craig Venter Institute; University of Naples Federico II; University of Nottingham; University of Oklahoma System; University of Oklahoma - Norman; University of Padua; University of Tennessee System; University of Tennessee Health Science Center; University of Udine; Wageningen University & Research; Wageningen University & Research; Wellcome Trust Sanger Institute; Italian National Agency New Technical Energy & Sustainable Economics Development; Italian National Agency New Technical Energy & Sustainable Economics Development
RP Sato, S (corresponding author), Kazusa DNA Res Inst, 2-6-7 Kazusa Kamatari, Kisarazu, Chiba 2920818, Japan.
FU Argentina: INTA; Argentina: CONICET; Belgium: Flemish Institute for Biotechnology; Belgium: Ghent University; China: The State Key Laboratory of Plant Genomics, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences; Ministry of Science and Technology [2006AA10A116, 2004CB720405, 2006CB101907, 2007DFB30080]; Ministry of Agriculture [2007-Z5]; National Natural Science Foundation [36171319]; Postdoctoral Science Foundation [20070420446]; European Union [EU-SOL PL 016214]; France: Institute National de la Recherche Agronomique; France: Agence Nationale de la Recherche; Germany: the Max Planck Society; India: Department of Biotechnology, Government of India; Indian Council of Agricultural Research; Italy: Ministry of Research; Ministry of Agriculture; FILAS foundation; ENEA; CNR-ENEA [L. 191/2009]; Japan: Kazusa DNA Research Institute Foundation; Japan: National Institute of Vegetable and Tea Science; Korea: KRIBB; Korea: Crop Functional Genomics Research Center (CFGC), MEST; Netherlands: Centre for BioSystemsGenomics, Netherlands Organization for Scientific Research; Spain: Fundacion Genoma Espana; Cajamar; FEPEX; Fundacion Seneca; ICIA; IFAPA; Fundacion Manrique de Lara; Instituto Nacional de Bioinformatica; UK: BBSRC [BB/C509731/1]; DEFRA; SEERAD; USA: NSF [DBI-0116076, DBI-0421634, DBI-0606595, IOS-0923312, DBI-0820612, DBI-0605659, DEB-0316614, DBI 0849896, MCB 1021718]; USDA [2007-02773, 2007-35300-19739]; USDA-ARS; NSF; Biotechnology and Biological Sciences Research Council [BB/C509731/1, BB/G02491X/1, BB/G006199/1, BBS/E/T/000PR6193] Funding Source: researchfish; Direct For Biological Sciences; Division Of Integrative Organismal Systems [0820612] Funding Source: National Science Foundation; Grants-in-Aid for Scientific Research [24113518] Funding Source: KAKEN; ICREA Funding Source: Custom; BBSRC [BB/G02491X/1, BBS/E/T/000PR6193, BB/G006199/1] Funding Source: UKRI
NR 28
TC 2485
Z9 2945
U1 43
U2 1450
PU NATURE PUBLISHING 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 31
PY 2012
VL 485
IS 7400
BP 635
EP 641
DI 10.1038/nature11119
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 949WP
UT WOS:000304608000047
PM 22660326
DA 2026-03-09
ER

PT J
AU Lomstein, BA
   Langerhuus, AT
   D'Hondt, S
   Jorgensen, BB
   Spivack, AJ
AF Lomstein, Bente Aa
   Langerhuus, Alice T.
   D'Hondt, Steven
   Jorgensen, Bo B.
   Spivack, Arthur J.
TI Endospore abundance, microbial growth and necromass turnover in deep sub-seafloor sediment
SO NATURE
LA English
DT Article
ID amino-acids; peru margin; subseafloor; bacteria; majority; biomass
AB Two decades of scientific ocean drilling have demonstrated widespread microbial life in deep sub-seafloor sediment, and surprisingly high microbial-cell numbers. Despite the ubiquity of life in the deep biosphere, the large community sizes and the low energy fluxes in this vast buried ecosystemare not yet understood(1,2). It is not known whether organisms of the deep biosphere are specifically adapted to extremely low energy fluxes or whether most of the observed cells are in a dormant, spore-like state(3). Here we apply a new approach-the D:L-amino-acid model-to quantify the distributions and turnover times of living microbial biomass, endospores and microbial necromass, as well as to determine their role in the sub-seafloor carbon budget. The approach combines sensitive analyses of unique bacterial markers (muramic acid and D-amino acids) and the bacterial endospore marker, dipicolinic acid, with racemization dynamics of stereo-isomeric amino acids. Endospores are as abundant as vegetative cells and microbial activity is extremely low, leading to microbial biomass turnover times of hundreds to thousands of years. We infer from model calculations that biomass production is sustained by organic carbon deposited from the surface photosynthetic world millions of years ago and that microbial necromass is recycled over timescales of hundreds of thousands of years.
C1 [Lomstein, Bente Aa; Langerhuus, Alice T.] Aarhus Univ, Microbiol Sect, Dept Biosci, DK-8000 Aarhus C, Denmark.
   [D'Hondt, Steven; Spivack, Arthur J.] Univ Rhode Isl, Grad Sch Oceanog, Narragansett, RI 02882 USA.
   [Jorgensen, Bo B.] Aarhus Univ, Dept Biosci, Ctr Geomicrobiol, DK-8000 Aarhus C, Denmark.
C3 Aarhus University; University of Rhode Island; Aarhus University
RP Lomstein, BA (corresponding author), Aarhus Univ, Microbiol Sect, Dept Biosci, Bldg 1540,Ny Munkegade 114, DK-8000 Aarhus C, Denmark.
EM bente.lomstein@biology.au.dk
FU US National Science Foundation; Max Planck Society; Danish National Research Foundation; Danish National Science Research Council; Danish Agency for Science, Technology and Innovation; Faculty of Science and Technology at the University of Aarhus
NR 24
TC 259
Z9 288
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 APR 5
PY 2012
VL 484
IS 7392
BP 101
EP 104
DI 10.1038/nature10905
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 919QN
UT WOS:000302343400042
PM 22425999
DA 2026-03-09
ER

PT J
AU Sumino, Y
   Nagai, KH
   Shitaka, Y
   Tanaka, D
   Yoshikawa, K
   Chaté, H
   Oiwa, K
AF Sumino, Yutaka
   Nagai, Ken H.
   Shitaka, Yuji
   Tanaka, Dan
   Yoshikawa, Kenichi
   Chate, Hugues
   Oiwa, Kazuhiro
TI Large-scale vortex lattice emerging from collectively moving microtubules
SO NATURE
LA English
DT Article
ID cortical microtubules; self-organization; translocation; motors; array
AB Spontaneous collective motion, as in some flocks of bird and schools of fish, is an example of an emergent phenomenon. Such phenomena are at present of great interest(1-5) and physicists have put forward a number of theoretical results that so far lack experimental verification(6-8). In animal behaviour studies, large-scale data collection is now technologically possible, but data are still scarce and arise from observations rather than controlled experiments. Multicellular biological systems, such as bacterial colonies or tissues(9,10), allow more control, but may have many hidden variables and interactions, hindering proper tests of theoretical ideas. However, in systems on the subcellular scale such tests may be possible, particularly in in vitro experiments with only few purified components(11-13). Motility assays, in which protein filaments are driven by molecular motors grafted to a substrate in the presence of ATP, can show collective motion for high densities of motors and attached filaments. This was demonstrated recently for the actomyosin system(14,15), but a complete understanding of the mechanisms at work is still lacking. Here we report experiments in which microtubules are propelled by surface-bound dyneins. In this system it is possible to study the local interaction: we find that colliding microtubules align with each other with high probability. At high densities, this alignment results in self-organization of the microtubules, which are on average 15 mu m long, into vortices with diameters of around 400 mu m. Inside the vortices, the microtubules circulate both clockwise and anticlockwise. On longer timescales, the vortices form a lattice structure. The emergence of these structures, as verified by a mathematical model, is the result of the smooth, reptation-like motion of single microtubules in combination with local interactions (the nematic alignment due to collisions)-there is no need for long-range interactions. Apart from its potential relevance to cortical arrays in plant cells(16,17) and other biological situations, our study provides evidence for the existence of previously unsuspected universality classes of collective motion phenomena.
C1 [Shitaka, Yuji; Oiwa, Kazuhiro] Natl Inst Informat & Commun Technol, Adv ICT Res Inst, Kobe, Hyogo 6512492, Japan.
   [Nagai, Ken H.] Univ Tokyo, Grad Sch Sci, Dept Phys, Tokyo 1130033, Japan.
   [Tanaka, Dan] Nagoya Univ, Grad Sch Informat Sci, Dept Complex Syst Sci, Nagoya, Aichi 4648601, Japan.
   [Yoshikawa, Kenichi] Kyoto Univ, Grad Sch Sci, Dept Phys, Kyoto 6068502, Japan.
   [Yoshikawa, Kenichi] JST, ICORP, Kyoto 6068502, Japan.
   [Chate, Hugues] CEA Saclay, Serv Phys Etat Condense, F-91191 Gif Sur Yvette, France.
   [Oiwa, Kazuhiro] Univ Hyogo, Grad Sch Life Sci, Harima, Hyogo 6781297, Japan.
C3 National Institute of Information & Communications Technology (NICT) - Japan; University of Tokyo; Nagoya University; Kyoto University; Japan Science & Technology Agency (JST); Universite Paris Saclay; CEA; Centre National de la Recherche Scientifique (CNRS); University of Hyogo
RP Oiwa, K (corresponding author), Natl Inst Informat & Commun Technol, Adv ICT Res Inst, Kobe, Hyogo 6512492, Japan.
EM oiwa@nict.go.jp
FU JSPS [23-1819];  [23840019];  [21340023];  [20244067]; Grants-in-Aid for Scientific Research [23840019, 21340023] Funding Source: KAKEN
CR Allard JF, 2010, BIOPHYS J, V99, P1082, DOI 10.1016/j.bpj.2010.05.037
   Ballerini M, 2008, P NATL ACAD SCI USA, V105, P1232, DOI 10.1073/pnas.0711437105
   Buhl J, 2006, SCIENCE, V312, P1402, DOI 10.1126/science.1125142
   Butt T, 2010, J BIOL CHEM, V285, P4964, DOI 10.1074/jbc.M109.044792
   Dixit R, 2004, PLANT CELL, V16, P3274, DOI 10.1105/tpc.104.026930
   Ginelli F, 2010, PHYS REV LETT, V104, P0, DOI 10.1103/PhysRevLett.104.184502
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   Kikushima K, 2008, BIOPHYS J, V94, P4014, DOI 10.1529/biophysj.107.123083
   Kudrolli A, 2008, PHYS REV LETT, V100, P0, DOI 10.1103/PhysRevLett.100.058001
   Loose M, 2008, SCIENCE, V320, P789, DOI 10.1126/science.1154413
   Lukeman R, 2010, P NATL ACAD SCI USA, V107, P12576, DOI 10.1073/pnas.1001763107
   Nedelec FJ, 1997, NATURE, V389, P305, DOI 10.1038/38532
   Peruani F, 2006, PHYS REV E, V74, P0, DOI 10.1103/PhysRevE.74.030904
   Poujade M, 2007, P NATL ACAD SCI USA, V104, P15988, DOI 10.1073/pnas.0705062104
   Ramaswamy S, 2010, ANNU REV CONDEN MA P, V1, P323, DOI 10.1146/annurev-conmatphys-070909-104101
   Riedel IH, 2005, SCIENCE, V309, P300, DOI 10.1126/science.1110329
   Sakakibara H, 1999, NATURE, V400, P586, DOI 10.1038/23066
   Schaller V, 2011, P NATL ACAD SCI USA, V108, P19183, DOI 10.1073/pnas.1107540108
   Schaller V, 2010, NATURE, V467, P73, DOI 10.1038/nature09312
   Sumpter D, 2010, COLLECTIVE ANIMAL BEHAVIOR, V0, P0, DOI DOI 10.1515/9781400837106
   Surrey T, 2001, SCIENCE, V292, P1167, DOI 10.1126/science.1059758
   Tindemans SH, 2010, PHYS REV LETT, V104, P0, DOI 10.1103/PhysRevLett.104.058103
   Toner J, 2005, ANN PHYS-NEW YORK, V318, P170, DOI 10.1016/j.aop.2005.04.011
   VICSEK T, 1995, PHYS REV LETT, V75, P1226, DOI 10.1103/PhysRevLett.75.1226
   Wasteneys GO, 2009, TRENDS CELL BIOL, V19, P62, DOI 10.1016/j.tcb.2008.11.004
   YUAN M, 1994, P NATL ACAD SCI USA, V91, P6050, DOI 10.1073/pnas.91.13.6050
   Zhang HP, 2010, P NATL ACAD SCI USA, V107, P13626, DOI 10.1073/pnas.1001651107
NR 29
TC 567
Z9 625
U1 3
U2 175
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 22
PY 2012
VL 483
IS 7390
BP 448
EP 452
DI 10.1038/nature10874
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 912CC
UT WOS:000301771200039
PM 22437613
DA 2026-03-09
ER

PT J
AU Fridley, JD
AF Fridley, Jason D.
TI Extended leaf phenology and the autumn niche in deciduous forest invasions
SO NATURE
LA English
DT Article
ID northern hardwood forest; eastern united-states; earthworm invasion; seasonal-variation; understory shrubs; nutrient dynamics; plant invasions; carbon-dioxide; woody-plants; temperate
AB The phenology of growth in temperate deciduous forests, including the timing of leaf emergence and senescence, has strong control over ecosystem properties such as productivity(1,2) and nutrient cycling(3,4), and has an important role in the carbon economy of understory plants(5-7). Extended leaf phenology, whereby understory species assimilate carbon in early spring before canopy closure or in late autumn after canopy fall, has been identified as a key feature of many forest species invasions(5,8-10), but it remains unclear whether there are systematic differences in the growth phenology of native and invasive forest species(11) or whether invaders are more responsive to warming trends that have lengthened the duration of spring or autumn growth(12). Here, in a 3-year monitoring study of 43 native and 30 non-native shrub and liana species common to deciduous forests in the eastern United States, I show that extended autumn leaf phenology is a common attribute of eastern US forest invasions, where non-native species are extending the autumn growing season by an average of 4 weeks compared with natives. In contrast, there was no consistent evidence that non-natives as a group show earlier spring growth phenology, and non-natives were not better able to track interannual variation in spring temperatures. Seasonal leaf production and photosynthetic data suggest that most non-native species capture a significant proportion of their annual carbon assimilate after canopy leaf fall, a behaviour that was virtually absent in natives and consistent across five phylogenetic groups. Pronounced differences in how native and non-native understory species use pre- and post-canopy environments suggest eastern US invaders are driving a seasonal redistribution of forest productivity that may rival climate change in its impact on forest processes.
C1 Syracuse Univ, Dept Biol, Syracuse, NY 13244 USA.
C3 Syracuse University
RP Fridley, JD (corresponding author), Syracuse Univ, Dept Biol, 107 Coll Pl, Syracuse, NY 13244 USA.
EM fridley@syr.edu
FU Syracuse University
NR 41
TC 307
Z9 387
U1 2
U2 379
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD MAY 17
PY 2012
VL 485
IS 7398
BP 359
EP U105
DI 10.1038/nature11056
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 943CW
UT WOS:000304099100040
PM 22535249
DA 2026-03-09
ER

PT J
AU Leakey, MG
   Spoor, F
   Dean, MC
   Feibel, CS
   Antón, SC
   Kiarie, C
   Leakey, LN
AF Leakey, Meave G.
   Spoor, Fred
   Dean, M. Christopher
   Feibel, Craig S.
   Anton, Susan C.
   Kiarie, Christopher
   Leakey, Louise N.
TI New fossils from Koobi Fora in northern Kenya confirm taxonomic diversity in early Homo
SO NATURE
LA English
DT Article
ID olduvai-gorge; turkana-basin; pliopleistocene hominid; east rudolf; habilis; ethiopia; evolution; tanzania; region; ma
AB Since its discovery in 1972 (ref. 1), the cranium KNM-ER 1470 has been at the centre of the debate over the number of species of early Homo present in the early Pleistocene epoch(2) of eastern Africa. KNM-ER 1470 stands out among other specimens attributed to early Homo because of its larger size, and its flat and subnasally orthognathic face with anteriorly placed maxillary zygomatic roots(3). This singular morphology and the incomplete preservation of the fossil have led to different views as to whether KNM-ER 1470 can be accommodated within a single species of early Homo that is highly variable because of sexual, geographical and temporal factors(4-9), or whether it provides evidence of species diversity marked by differences in cranial size and facial or masticatory adaptation(3,10-20). Here we report on three newly discovered fossils, aged between 1.78 and 1.95 million years (Myr) old, that clarify the anatomy and taxonomic status of KNM-ER 1470. KNM-ER 62000, a well-preserved face of a late juvenile hominin, closely resembles KNM-ER 1470 but is notably smaller. It preserves previously unknown morphology, including moderately sized, mesiodistally long postcanine teeth. The nearly complete mandible KNM-ER 60000 and mandibular fragment KNM-ER 62003 have a dental arcade that is short anteroposteriorly and flat across the front, with small incisors; these features are consistent with the arcade morphology of KNM-ER 1470 and KNM-ER 62000. The new fossils confirm the presence of two contemporary species of early Homo, in addition to Homo erectus, in the early Pleistocene of eastern Africa.
C1 [Leakey, Meave G.; Kiarie, Christopher; Leakey, Louise N.] Turkana Basin Inst, Nairobi 00502, Kenya.
   [Leakey, Meave G.; Leakey, Louise N.] SUNY Stony Brook, Dept Anthropol, Stony Brook, NY 11794 USA.
   [Spoor, Fred] Max Planck Inst Evolutionary Anthropol, Dept Human Evolut, D-04103 Leipzig, Germany.
   [Spoor, Fred; Dean, M. Christopher] UCL, Dept Cell & Dev Biol, London WC1E 6BT, England.
   [Feibel, Craig S.] Rutgers State Univ, Dept Earth & Planetary Sci, Piscataway, NJ 08854 USA.
   [Feibel, Craig S.] Rutgers State Univ, Dept Anthropol, Piscataway, NJ 08854 USA.
   [Anton, Susan C.] NYU, Dept Anthropol, New York, NY 10003 USA.
C3 State University of New York (SUNY) System; Stony Brook University; Max Planck Society; University of London; University College London; Rutgers University System; Rutgers University New Brunswick; Rutgers University System; Rutgers University New Brunswick; New York University
RP Leakey, MG (corresponding author), Turkana Basin Inst, POB 24926, Nairobi 00502, Kenya.
EM meaveleakey@gmail.com; f.spoor@eva.mpg.de
FU Turkana Basin Institute; National Geographic Society; Leakey Foundation; Max Planck Society
NR 30
TC 140
Z9 170
U1 1
U2 147
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD AUG 9
PY 2012
VL 488
IS 7410
BP 201
EP 204
DI 10.1038/nature11322
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 985LE
UT WOS:000307267000031
PM 22874966
DA 2026-03-09
ER

PT J
AU Grivennikov, SI
   Wang, KP
   Mucida, D
   Stewart, CA
   Schnabl, B
   Jauch, D
   Taniguchi, K
   Yu, GY
   Österreicher, CH
   Hung, KE
   Datz, C
   Feng, Y
   Fearon, ER
   Oukka, M
   Tessarollo, L
   Coppola, V
   Yarovinsky, F
   Cheroutre, H
   Eckmann, L
   Trinchieri, G
   Karin, M
AF Grivennikov, Sergei I.
   Wang, Kepeng
   Mucida, Daniel
   Stewart, C. Andrew
   Schnabl, Bernd
   Jauch, Dominik
   Taniguchi, Koji
   Yu, Guann-Yi
   Oesterreicher, Christoph H.
   Hung, Kenneth E.
   Datz, Christian
   Feng, Ying
   Fearon, Eric R.
   Oukka, Mohamed
   Tessarollo, Lino
   Coppola, Vincenzo
   Yarovinsky, Felix
   Cheroutre, Hilde
   Eckmann, Lars
   Trinchieri, Giorgio
   Karin, Michael
TI Adenoma-linked barrier defects and microbial products drive IL-23/IL-17-mediated tumour growth
SO NATURE
LA English
DT Article
ID promotes colon tumorigenesis; colorectal-cancer; helper-cells; cutting edge; mouse model; mice; inflammation; colitis; differentiation; carcinogenesis
AB Approximately 2% of colorectal cancer is linked to pre-existing inflammation known as colitis-associated cancer, but most develops in patients without underlying inflammatory bowel disease. Colorectal cancer often follows a genetic pathway whereby loss of the adenomatous polyposis coli (APC) tumour suppressor and activation of beta-catenin are followed by mutations in K-Ras, PIK3CA and TP53, as the tumour emerges and progresses(1,2). Curiously, however, 'inflammatory signature' genes characteristic of colitis-associated cancer are also upregulated in colorectal cancer(3,4). Further, like most solid tumours, colorectal cancer exhibits immune/inflammatory infiltrates(5), referred to as 'tumour-elicited inflammation'(6). Although infiltrating CD4(+) T(H)1 cells and CD8(+) cytotoxic T cells constitute a positive prognostic sign in colorectal cancer(7,8), myeloid cells and T-helper interleukin (IL)-17-producing (T(H)17) cells promote tumorigenesis(5,6), and a 'T(H)17 expression signature' in stage I/II colorectal cancer is associated with a drastic decrease in disease-free survival(9). Despite its pathogenic importance, the mechanisms responsible for the appearance of tumour-elicited inflammation are poorly understood. Many epithelial cancers develop proximally to microbial communities, which are physically separated from immune cells by an epithelial barrier(10). We investigated mechanisms responsible for tumour-elicited inflammation in a mouse model of colorectal tumorigenesis, which, like human colorectal cancer, exhibits upregulation of IL-23 and IL-17. Here we show that IL-23 signalling promotes tumour growth and progression, and development of a tumoural IL-17 response. IL-23 is mainly produced by tumour-associated myeloid cells that are likely to be activated by microbial products, which penetrate the tumours but not adjacent tissue. Both early and late colorectal neoplasms exhibit defective expression of several barrier proteins. We propose that barrier deterioration induced by colorectal-cancer-initiating genetic lesions results in adenoma invasion by microbial products that trigger tumour-elicited inflammation, which in turn drives tumour growth.
C1 [Grivennikov, Sergei I.; Wang, Kepeng; Jauch, Dominik; Taniguchi, Koji; Yu, Guann-Yi; Karin, Michael] Univ Calif San Diego, Lab Gene Regulat & Signal Transduct, Dept Pharmacol, La Jolla, CA 92093 USA.
   [Grivennikov, Sergei I.; Wang, Kepeng; Jauch, Dominik; Taniguchi, Koji; Yu, Guann-Yi; Karin, Michael] Univ Calif San Diego, Dept Pathol, Sch Med, La Jolla, CA 92093 USA.
   [Wang, Kepeng] Shenzhen PKU HKUST Med Ctr, Biomed Res Inst, Shenzhen, Guangdong, Peoples R China.
   [Mucida, Daniel; Cheroutre, Hilde] La Jolla Inst Allergy & Immunol, La Jolla, CA 92093 USA.
   [Mucida, Daniel] Rockefeller Univ, Lab Mucosal Immunol, New York, NY 10065 USA.
   [Stewart, C. Andrew; Trinchieri, Giorgio] NCI, Canc & Inflammat Program, Expt Immunol Lab, Ctr Canc Res,NIH, Frederick, MD 21702 USA.
   [Schnabl, Bernd; Oesterreicher, Christoph H.; Eckmann, Lars] Univ Calif San Diego, Sch Med, Dept Med, La Jolla, CA 92093 USA.
   [Taniguchi, Koji] Keio Univ, Sch Med, Dept Microbiol & Immunol, Tokyo 1608582, Japan.
   [Oesterreicher, Christoph H.] Med Univ Vienna, Ctr Physiol & Pharmacol, Inst Pharmacol, Vienna, Austria.
   [Hung, Kenneth E.] Tufts Med Ctr, Dept Med, Boston, MA 02111 USA.
   [Datz, Christian] Paracelsus Med Univ, Oberndorf Hosp, Dept Internal Med, Salzburg, Austria.
   [Feng, Ying; Fearon, Eric R.] Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI 48109 USA.
   [Feng, Ying; Fearon, Eric R.] Univ Michigan, Sch Med, Dept Human Genet, Ann Arbor, MI 48109 USA.
   [Feng, Ying; Fearon, Eric R.] Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI 48109 USA.
   [Oukka, Mohamed] Seattle Childrens Res Inst, Seattle, WA 98105 USA.
   [Tessarollo, Lino] NCI, Mouse Canc Genet Program, NIH, Frederick, MD 21702 USA.
   [Coppola, Vincenzo] Ohio State Univ, Ctr Comprehens Canc, Wexner Med Ctr, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43210 USA.
   [Yarovinsky, Felix] Univ Texas SW Med Ctr Dallas, Dept Immunol, Dallas, TX 75390 USA.
C3 University of California System; University of California San Diego; University of California System; University of California San Diego; Peking University; Hong Kong University of Science & Technology; Shenzhen PKU-HKUST Medical Center; La Jolla Institute for Immunology; Rockefeller University; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); University of California System; University of California San Diego; Keio University; Medical University of Vienna; Tufts Medical Center; Paracelsus Private Medical University; University of Michigan System; University of Michigan; University of Michigan System; University of Michigan; University of Michigan System; University of Michigan; Seattle Children's Hospital; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); University System of Ohio; Ohio State University; James Cancer Hospital & Solove Research Institute; University of Texas System; University of Texas Southwestern Medical Center
RP Karin, M (corresponding author), Univ Calif San Diego, Lab Gene Regulat & Signal Transduct, Dept Pharmacol, 9500 Gilman Dr, La Jolla, CA 92093 USA.
EM karinoffice@ucsd.edu
FU Crohn's and Colitis Foundation of America [2693]; NIH/National Institute of Diabetes and Digestive and Kidney Diseases [K99-DK088589]; University of California, San Diego, Digestive Disease Research Development Center Pilot Grant [DK080506]; Croucher Foundation; China Postdoctoral Science Foundation [20110490919]; Strategic Young Researcher Overseas Visits Program for Accelerating Brain Circulation; SPAR Austria; NIH [R01CA082223, AI043477, DK035108]; American Association for Cancer Research [07-60-21-KARI]; National Cancer Institute [ZICBC011265, ZIABC010793] Funding Source: NIH RePORTER
NR 44
TC 1061
Z9 1196
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 NOV 8
PY 2012
VL 491
IS 7423
BP 254
EP +
DI 10.1038/nature11465
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 033DP
UT WOS:000310774300044
PM 23034650
DA 2026-03-09
ER

PT J
AU Zénon, A
   Krauzlis, RJ
AF Zenon, Alexandre
   Krauzlis, Richard J.
TI Attention deficits without cortical neuronal deficits
SO NATURE
LA English
DT Article
ID areas mt; modulation; microstimulation; inactivation; selection; signals
AB The ability to process relevant stimuli selectively is a fundamental function of the primate visual system. The best-understood correlate of this function is the enhanced response of neurons in the visual cortex to attended stimuli(1,2). However, recent results show that the superior colliculus (SC), a midbrain structure, also has a crucial role in visual attention(3-5). It has been assumed that the SC acts through the same well-known mechanisms in the visual cortex(3,5). Here we tested this hypothesis by transiently inactivating the SC during a motion-change-detection task and measuring responses in two visual cortical areas. We found that despite large deficits in visual attention, the enhanced responses of neurons in the visual cortex to attended stimuli were unchanged. These results show that the SC contributes to visual attention through mechanisms that are independent of the classic effects in the visual cortex, demonstrating that other processes must have key roles in visual attention.
C1 [Zenon, Alexandre; Krauzlis, Richard J.] Salk Inst Biol Studies, Syst Neurobiol Lab, La Jolla, CA 92037 USA.
   [Zenon, Alexandre] Catholic Univ Louvain, Inst Neurosci, B-1200 Brussels, Belgium.
   [Krauzlis, Richard J.] NEI, Lab Sensorimotor Res, Bethesda, MD 20892 USA.
C3 Salk Institute; Universite Catholique Louvain; National Institutes of Health (NIH) - USA; NIH National Eye Institute (NEI)
RP Krauzlis, RJ (corresponding author), Salk Inst Biol Studies, Syst Neurobiol Lab, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA.
EM richard.krauzlis@nih.gov
FU F.M. Kirby Foundation; National Eye Institute Intramural Research Program at the National Institutes of Health; National Eye Institute [ZIAEY000511] Funding Source: NIH RePORTER
NR 37
TC 172
Z9 196
U1 0
U2 42
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 20
PY 2012
VL 489
IS 7416
BP 434
EP U124
DI 10.1038/nature11497
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 007AK
UT WOS:000308860900046
PM 22972195
DA 2026-03-09
ER

PT J
AU Chaneton, B
   Hillmann, P
   Zheng, L
   Martin, ACL
   Maddocks, ODK
   Chokkathukalam, A
   Coyle, JE
   Jankevics, A
   Holding, FP
   Vousden, KH
   Frezza, C
   O'Reilly, M
   Gottlieb, E
AF Chaneton, Barbara
   Hillmann, Petra
   Zheng, Liang
   Martin, Agnes C. L.
   Maddocks, Oliver D. K.
   Chokkathukalam, Achuthanunni
   Coyle, Joseph E.
   Jankevics, Andris
   Holding, Finn P.
   Vousden, Karen H.
   Frezza, Christian
   O'Reilly, Marc
   Gottlieb, Eyal
TI Serine is a natural ligand and allosteric activator of pyruvate kinase M2
SO NATURE
LA English
DT Article
ID mass-spectrometry data; x-ray data; tumor-growth; cancer; crystallography; contributes; glycolysis; metabolism; pathway; quality
AB Cancer cells exhibit several unique metabolic phenotypes that are critical for cell growth and proliferation(1). Specifically, they overexpress the M2 isoform of the tightly regulated enzyme pyruvate kinase (PKM2), which controls glycolytic flux, and are highly dependent on de novo biosynthesis of serine and glycine(2). Here we describe a new rheostat-like mechanistic relationship between PKM2 activity and serine biosynthesis. We show that serine can bind to and activate human PKM2, and that PKM2 activity in cells is reduced in response to serine deprivation. This reduction in PKM2 activity shifts cells to a fuel-efficient mode in which more pyruvate is diverted to the mitochondria and more glucose-derived carbon is channelled into serine biosynthesis to support cell proliferation.
C1 [Chaneton, Barbara; Zheng, Liang; Maddocks, Oliver D. K.; Vousden, Karen H.; Frezza, Christian; Gottlieb, Eyal] Canc Res UK, Beatson Inst Canc Res, Glasgow G61 1BD, Lanark, Scotland.
   [Hillmann, Petra; Martin, Agnes C. L.; Coyle, Joseph E.; Holding, Finn P.; O'Reilly, Marc] Astex Pharmaceut, Cambridge CB4 0QA, England.
   [Chokkathukalam, Achuthanunni; Jankevics, Andris] Univ Glasgow, Coll Med Vet & Life Sci, Inst Mol Cell & Syst Biol, Glasgow G12 8QQ, Lanark, Scotland.
   [Jankevics, Andris] Univ Groningen, Groningen Biomol Sci & Biotechnol Inst, Groningen Bioinformat Ctr, NL-9747 AG Groningen, Netherlands.
C3 Beatson Institute; Cancer Research UK; Astex Pharmaceuticals; University of Glasgow; University of Groningen
RP Gottlieb, E (corresponding author), Canc Res UK, Beatson Inst Canc Res, Switchback Rd, Glasgow G61 1BD, Lanark, Scotland.
EM marc.oreilly@astx.com; e.gottlieb@beatson.gla.ac.uk
FU Cancer Research UK; Medical Research Council [MC_UP_1101/3] Funding Source: researchfish
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   Altenberg B, 2004, GENOMICS, V84, P1014, DOI 10.1016/j.ygeno.2004.08.010
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NR 39
TC 526
Z9 618
U1 1
U2 169
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 15
PY 2012
VL 491
IS 7424
BP 458
EP +
DI 10.1038/nature11540
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 036MY
UT WOS:000311031600049
PM 23064226
DA 2026-03-09
ER

PT J
AU Moreau, A
   Ciraci, C
   Mock, JJ
   Hill, RT
   Wang, Q
   Wiley, BJ
   Chilkoti, A
   Smith, DR
AF Moreau, Antoine
   Ciraci, Cristian
   Mock, Jack J.
   Hill, Ryan T.
   Wang, Qiang
   Wiley, Benjamin J.
   Chilkoti, Ashutosh
   Smith, David R.
TI Controlled-reflectance surfaces with film-coupled colloidal nanoantennas
SO NATURE
LA English
DT Article
ID perfect absorber; negative-index; gold; silver
AB Efficient and tunable absorption is essential for a variety of applications, such as designing controlled-emissivity surfaces for thermophotovoltaic devices(1), tailoring an infrared spectrum for controlled thermal dissipation(2) and producing detector elements for imaging(3). Metamaterials based on metallic elements are particularly efficient as absorbing media, because both the electrical and the magnetic properties of a metamaterial can be tuned by structured design(4). So far, metamaterial absorbers in the infrared or visible range have been fabricated using lithographically patterned metallic structures(2,5-9), making them inherently difficult to produce over large areas and hence reducing their applicability. Here we demonstrate a simple method to create a metamaterial absorber by randomly adsorbing chemically synthesized silver nanocubes onto a nanoscale-thick polymer spacer layer on a gold film, making no effort to control the spatial arrangement of the cubes on the film. We show that the film-coupled nanocubes provide a reflectance spectrum that can be tailored by varying the geometry (the size of the cubes and/or the thickness of the spacer). Each nanocube is the optical analogue of a grounded patch antenna, with a nearly identical local field structure that is modified by the plasmonic response of the metal's dielectric function, and with an anomalously large absorption efficiency that can be partly attributed to an interferometric effect(10). The absorptivity of large surface areas can be controlled using this method, at scales out of reach of lithographic approaches (such as electron-beam lithography) that are otherwise required to manipulate matter on the nanoscale.
C1 [Moreau, Antoine; Ciraci, Cristian; Mock, Jack J.; Smith, David R.] Duke Univ, Ctr Metamat & Integrated Plasmon, Durham, NC 27708 USA.
   [Moreau, Antoine] Univ Blaise Pascal, Clermont Univ, F-63000 Clermont Ferrand, France.
   [Moreau, Antoine] CNRS, IP, UMR 6602, F-63171 Aubiere, France.
   [Hill, Ryan T.; Chilkoti, Ashutosh] Duke Univ, Ctr Biol Inspired Mat & Mat Syst, Durham, NC 27708 USA.
   [Wang, Qiang; Wiley, Benjamin J.] Duke Univ, Dept Chem, Durham, NC 27708 USA.
   [Wang, Qiang] Capital Normal Univ, Lab Microsized Funct Mat, Beijing 100048, Peoples R China.
   [Wang, Qiang] Capital Normal Univ, Coll Elementary Educ, Beijing 100048, Peoples R China.
   [Chilkoti, Ashutosh] Duke Univ, Dept Biomed Engn, Durham, NC 27708 USA.
C3 Duke University; Universite Clermont Auvergne (UCA); Centre National de la Recherche Scientifique (CNRS); Centre National de la Recherche Scientifique (CNRS); CNRS - Institute for Engineering & Systems Sciences (INSIS); Universite Clermont Auvergne (UCA); Duke University; Duke University; Capital Normal University; Capital Normal University; Duke University
RP Smith, DR (corresponding author), Duke Univ, Ctr Metamat & Integrated Plasmon, Durham, NC 27708 USA.
EM drsmith@ee.duke.edu
FU US Air Force Office of Scientific Research [FA9550-09-1-0562]; US Army Research Office through a Multidisciplinary University Research Initiative [W911NF-09-1-0539]; US NIH [R21EB009862, F32EB009299]
NR 30
TC 670
Z9 759
U1 3
U2 1143
PU NATURE PUBLISHING 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 6
PY 2012
VL 492
IS 7427
BP 86
EP +
DI 10.1038/nature11615
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 048EQ
UT WOS:000311893400050
PM 23222613
DA 2026-03-09
ER

PT J
AU Howk, JC
   Lehner, N
   Fields, BD
   Mathews, GJ
AF Howk, J. Christopher
   Lehner, Nicolas
   Fields, Brian D.
   Mathews, Grant J.
TI Observation of interstellar lithium in the low-metallicity Small Magellanic Cloud
SO NATURE
LA English
DT Article
ID high-resolution survey; spite plateau; diffuse bands; wmap data; galaxy; nucleosynthesis; absorption; abundances; parameters; evolution
AB The primordial abundances of light elements produced in the standard theory of Big Bang nucleosynthesis (BBN) depend only on the cosmic ratio of baryons to photons, a quantity inferred from observations of the microwave background(1). The predicted(2-4) primordial Li-7 abundance is four times that measured in the atmospheres of Galactic halo stars(5-7). This discrepancy could be caused by modification of surface lithium abundances during the stars' lifetimes(8) or by physics beyond the Standard Model that affects early nucleosynthesis(9,10). The lithium abundance of low-metallicity gas provides an alternative constraint on the primordial abundance and cosmic evolution of lithium(11) that is not susceptible to the in situ modifications that may affect stellar atmospheres. Here we report observations of interstellar Li-7 in the low-metallicity gas of the Small Magellanic Cloud, a nearby galaxy with a quarter the Sun's metallicity. The present-day Li-7 abundance of the Small Magellanic Cloud is nearly equal to the BBN predictions, severely constraining the amount of possible subsequent enrichment of the gas by stellar and cosmic-ray nucleosynthesis. Our measurements can be reconciled with standard BBN with an extremely fine-tuned depletion of stellar Li with metallicity. They are also consistent with non-standard BBN.
C1 [Howk, J. Christopher; Lehner, Nicolas; Mathews, Grant J.] Univ Notre Dame, Dept Phys, Ctr Astrophys, Notre Dame, IN 46556 USA.
   [Fields, Brian D.] Univ Illinois, Dept Astron, Urbana, IL 61801 USA.
   [Fields, Brian D.] Univ Illinois, Dept Phys, Urbana, IL 61801 USA.
C3 University of Notre Dame; University of Illinois System; University of Illinois Urbana-Champaign; University of Illinois System; University of Illinois Urbana-Champaign
RP Howk, JC (corresponding author), Univ Notre Dame, Dept Phys, Ctr Astrophys, Notre Dame, IN 46556 USA.
EM jhowk@nd.edu
FU European Southern Observatory [382.B-0556]
NR 27
TC 72
Z9 76
U1 0
U2 19
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD SEP 6
PY 2012
VL 489
IS 7414
BP 121
EP 123
DI 10.1038/nature11407
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 999WW
UT WOS:000308347000046
PM 22955622
DA 2026-03-09
ER

PT J
AU Zhang, DS
   Piazza, V
   Perrin, BJ
   Rzadzinska, AK
   Poczatek, JC
   Wang, M
   Prosser, HM
   Ervasti, JM
   Corey, DP
   Lechene, CP
AF Zhang, Duan-Sun
   Piazza, Valeria
   Perrin, Benjamin J.
   Rzadzinska, Agnieszka K.
   Poczatek, J. Collin
   Wang, Mei
   Prosser, Haydn M.
   Ervasti, James M.
   Corey, David P.
   Lechene, Claude P.
TI Multi-isotope imaging mass spectrometry reveals slow protein turnover in hair-cell stereocilia
SO NATURE
LA English
DT Article
ID molecular treadmill; bundles; renewal
AB Hair cells of the inner ear are not normally replaced during an animal's life, and must continually renew components of their various organelles(1). Among these are the stereocilia, each with a core of several hundred actin filaments that arise from their apical surfaces and that bear the mechanotransduction apparatus at their tips. Actin turnover in stereocilia has previously been studied(2) by transfecting neonatal rat hair cells in culture with a beta-actin-GFP fusion, and evidence was found that actin is replaced, from the top down, in 2-3 days. Overexpression of the actin-binding protein espin causes elongation of stereocilia within 12-24 hours, also suggesting rapid regulation of stereocilia lengths(3). Similarly, the mechanosensory 'tip links' are replaced in 5-10 hours after cleavage in chicken and mammalian hair cells(4,5). In contrast, turnover in chick stereocilia in vivo is much slower(6). It might be that only certain components of stereocilia turn over quickly, that rapid turnover occurs only in neonatal animals, only in culture, or only in response to a challenge like breakage or actin overexpression. Here we quantify protein turnover by feeding animals with a (15)N-labelled precursor amino acid and using multi-isotope imaging mass spectrometry to measure appearance of new protein. Surprisingly, in adult frogs and mice and in neonatal mice, in vivo and in vitro, the stereocilia were remarkably stable, incorporating newly synthesized protein at <10% per day. Only stereocilia tips had rapid turnover and no treadmilling was observed. Other methods confirmed this: in hair cells expressing beta-actin-GFP we bleached fiducial lines across hair bundles, but they did not move in 6 days. When we stopped expression of beta- or gamma-actin with tamoxifen-inducible recombination, neither actin isoform left the stereocilia, except at the tips. Thus, rapid turnover in stereocilia occurs only at the tips and not by a treadmilling process.
C1 [Poczatek, J. Collin; Wang, Mei; Lechene, Claude P.] Brigham & Womens Hosp, Div Genet, Cambridge, MA 02139 USA.
   [Zhang, Duan-Sun; Piazza, Valeria; Corey, David P.] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA.
   [Perrin, Benjamin J.; Ervasti, James M.] Univ Minnesota, Dept Biochem Mol Biol & Biophys, Minneapolis, MN 55455 USA.
   [Rzadzinska, Agnieszka K.; Prosser, Haydn M.] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England.
C3 Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard University; Harvard Medical School; University of Minnesota System; University of Minnesota Twin Cities; Wellcome Trust Sanger Institute
RP Lechene, CP (corresponding author), Brigham & Womens Hosp, Div Genet, Cambridge, MA 02139 USA.
EM dcorey@hms.harvard.edu; cpl@harvard.edu
FU National Institutes of Health/National Institute of Biomedical Imaging and Bioengineering (NIH/NIBIB) [P41RR14579, P41EB001974]; NIH [R01DC00033, R01DC03463, R01DC04179, R37DK39773, R01EY12963, R01GM47214, R01D K58762, R01DC02281, F32DC009539, R01AR049899]; National Science Foundation Division of Integrative Biology and Neuroscience (NSF/IBN) [IBN-998298]; Wellcome Trust [WT079643]; NIH National Center for Research Resources (NIH/NCRR) Center for Integrative Biomedical Computing [2P41 RR0112553-12]; Department of Energy SciDAC Visualization and Analytics Center for Enabling Technologies [DEFC0206ER25781]; National Eye Institute [R01EY012963] Funding Source: NIH RePORTER; National Institute of Arthritis and Musculoskeletal and Skin Diseases [R01AR049899, R01AR042423] Funding Source: NIH RePORTER; National Institute of Diabetes and Digestive and Kidney Diseases [R37DK039773] Funding Source: NIH RePORTER
NR 17
TC 171
Z9 201
U1 2
U2 97
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JAN 26
PY 2012
VL 481
IS 7382
BP 520
EP U137
DI 10.1038/nature10745
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 881GY
UT WOS:000299471800043
PM 22246323
DA 2026-03-09
ER

PT J
AU Yvon-Durocher, G
   Caffrey, JM
   Cescatti, A
   Dossena, M
   del Giorgio, P
   Gasol, JM
   Montoya, JM
   Pumpanen, J
   Staehr, PA
   Trimmer, M
   Woodward, G
   Allen, AP
AF Yvon-Durocher, Gabriel
   Caffrey, Jane M.
   Cescatti, Alessandro
   Dossena, Matteo
   del Giorgio, Paul
   Gasol, Josep M.
   Montoya, Jose M.
   Pumpanen, Jukka
   Staehr, Peter A.
   Trimmer, Mark
   Woodward, Guy
   Allen, Andrew P.
TI Reconciling the temperature dependence of respiration across timescales and ecosystem types
SO NATURE
LA English
DT Article
ID biomass distribution; metabolic balance; carbon exchange; patterns; emissions; linking; cycle
AB Ecosystem respiration is the biotic conversion of organic carbon to carbon dioxide by all of the organisms in an ecosystem, including both consumers and primary producers. Respiration exhibits an exponential temperature dependence at the subcellular and individual levels(1), but at the ecosystem level respiration can be modified by many variables(2-4) including community abundance and biomass(5), which vary substantially among ecosystems(6). Despite its importance for predicting the responses of the biosphere to climate change, it is as yet unknown whether the temperature dependence of ecosystem respiration varies systematically between aquatic and terrestrial environments. Here we use the largest database of respiratory measurements yet compiled to show that the sensitivity of ecosystem respiration to seasonal changes in temperature is remarkably similar for diverse environments encompassing lakes, rivers, estuaries, the open ocean and forested and non-forested terrestrial ecosystems, with an average activation energy similar to that of the respiratory complex(3) (approximately 0.65 electronvolts (eV)). By contrast, annual ecosystem respiration shows a substantially greater temperature dependence across aquatic (approximately 0.65 eV) versus terrestrial ecosystems (approximately 0.32 eV) that span broad geographic gradients in temperature. Using a model(5) derived from metabolic theory(7), these findings can be reconciled by similarities in the biochemical kinetics of metabolism at the subcellular level, and fundamental differences in the importance of other variables besides temperature-such as primary productivity and allochthonous carbon inputs-on the structure of aquatic and terrestrial biota at the community level.
C1 [Yvon-Durocher, Gabriel; Dossena, Matteo; Trimmer, Mark; Woodward, Guy] Queen Mary Univ London, Sch Biol & Chem Sci, London E1 4NS, England.
   [Yvon-Durocher, Gabriel] Univ Exeter, Environm & Sustainabil Inst, Penryn TR10 9EZ, Cornwall, England.
   [Caffrey, Jane M.] Univ W Florida, Ctr Environm Diagnost & Bioremediat, Pensacola, FL 32514 USA.
   [Cescatti, Alessandro] European Commiss, Joint Res Ctr, Inst Environm & Sustainabil, I-21027 Ispra, Italy.
   [del Giorgio, Paul] Univ Quebec Montreal, Dept Sci Biol, Montreal, PQ H2X 3X8, Canada.
   [Gasol, Josep M.; Montoya, Jose M.] Inst Marine Sci ICM CSIC, E-08003 Barcelona, Spain.
   [Pumpanen, Jukka] Univ Helsinki, Dept Forest Sci, FI-00014 Helsinki, Finland.
   [Staehr, Peter A.] Aarhus Univ, Inst Biosci, DK-4000 Roskilde, Denmark.
   [Allen, Andrew P.] Macquarie Univ, Dept Biol Sci, Sydney, NSW 2109, Australia.
C3 University of London; Queen Mary University London; University of Exeter; State University System of Florida; University of West Florida; European Commission Joint Research Centre; EC JRC ISPRA Site; University of Quebec; University of Quebec Montreal; Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Centro Mediterraneo de Investigaciones Marinas y Ambientales (CMIMA); CSIC - Instituto de Ciencias del Mar (ICM); University of Helsinki; Aarhus University; Macquarie University
RP Yvon-Durocher, G (corresponding author), Queen Mary Univ London, Sch Biol & Chem Sci, London E1 4NS, England.
EM g.yvon-durocher@exeter.ac.uk
FU Natural Environment Research Council, UK [NE/F004753/1]; Danish Council for Independent Research, Natural Sciences [10-085238]; Danish Centre for Lake Restoration(CLEAR); Academy of Finland Centre of Excellence program [218094]; Ramon y Cajal Fellowship [RYC-892 2008-03664]; Ministry of Economy [CGL2010-20091]; Generalitat de Catalunya [2009SGR142]; Natural Environment Research Council [NE/F004753/1, NE/H022511/1] Funding Source: researchfish; NERC [NE/F004753/1, NE/H022511/1] Funding Source: UKRI
NR 28
TC 405
Z9 457
U1 5
U2 537
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 26
PY 2012
VL 487
IS 7408
BP 472
EP 476
DI 10.1038/nature11205
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 979KD
UT WOS:000306815300036
PM 22722862
DA 2026-03-09
ER

PT J
AU Valet, JP
   Fournier, A
   Courtillot, V
   Herrero-Bervera, E
AF Valet, Jean-Pierre
   Fournier, Alexandre
   Courtillot, Vincent
   Herrero-Bervera, Emilio
TI Dynamical similarity of geomagnetic field reversals
SO NATURE
LA English
DT Article
ID earths magnetic-field; non-dipole field; lava flows; polarity transitions; secular variation; records; hawaii; paleointensity; excursions; directions
AB No consensus has been reached so far on the properties of the geomagnetic field during reversals or on the main features that might reveal its dynamics. A main characteristic of the reversing field is a large decrease in the axial dipole and the dominant role of non-dipole components(1-3). Other features strongly depend on whether they are derived from sedimentary or volcanic records. Only thermal remanent magnetization of lava flows can capture faithful records of a rapidly varying non-dipole field, but, because of episodic volcanic activity, sequences of overlying flows yield incomplete records. Here we show that the ten most detailed volcanic records of reversals can be matched in a very satisfactory way, under the assumption of a common duration, revealing common dynamical characteristics. We infer that the reversal process has remained unchanged, with the same time constants and durations, at least since 180 million years ago. We propose that the reversing field is characterized by three successive phases: a precursory event, a 1806 polarity switch and a rebound. The first and third phases reflect the emergence of the non-dipole field with large-amplitude secular variation. They are rarely both recorded at the same site owing to the rapidly changing field geometry and last for less than 2,500 years. The actual transit between the two polarities does not last longer than 1,000 years and might therefore result from mechanisms other than those governing normal secular variation. Such changes are too brief to be accurately recorded by most sediments.
C1 [Valet, Jean-Pierre; Fournier, Alexandre; Courtillot, Vincent] Univ Paris Diderot, CNRS, UMR 7154, Inst Phys Globe Paris, F-75238 Paris 05, France.
   [Herrero-Bervera, Emilio] Univ Hawaii Manoa, SOEST Hawaii Inst Geophys & Planetol, Honolulu, HI 96822 USA.
C3 Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Earth Sciences & Astronomy (INSU); Universite Paris Cite; University of Hawaii System; University of Hawaii Manoa
RP Valet, JP (corresponding author), Univ Paris Diderot, CNRS, UMR 7154, Inst Phys Globe Paris, 1 Rue Jussieu, F-75238 Paris 05, France.
EM valet@ipgp.fr
FU Directorate For Geosciences [1114065] Funding Source: National Science Foundation; Division Of Earth Sciences [1114065] Funding Source: National Science Foundation
NR 38
TC 95
Z9 100
U1 0
U2 65
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD OCT 4
PY 2012
VL 490
IS 7418
BP 89
EP +
DI 10.1038/nature11491
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 015LG
UT WOS:000309446800038
PM 23038471
DA 2026-03-09
ER

PT J
AU Kruidenier, L
   Chung, CW
   Cheng, ZJ
   Liddle, J
   Che, KH
   Joberty, G
   Bantscheff, M
   Bountra, C
   Bridges, A
   Diallo, H
   Eberhard, D
   Hutchinson, S
   Jones, E
   Katso, R
   Leveridge, M
   Mander, PK
   Mosley, J
   Ramirez-Molina, C
   Rowland, P
   Schofield, CJ
   Sheppard, RJ
   Smith, JE
   Swales, C
   Tanner, R
   Thomas, P
   Tumber, A
   Drewes, G
   Oppermann, U
   Patel, DJ
   Lee, K
   Wilson, DM
AF Kruidenier, Laurens
   Chung, Chun-wa
   Cheng, Zhongjun
   Liddle, John
   Che, KaHing
   Joberty, Gerard
   Bantscheff, Marcus
   Bountra, Chas
   Bridges, Angela
   Diallo, Hawa
   Eberhard, Dirk
   Hutchinson, Sue
   Jones, Emma
   Katso, Roy
   Leveridge, Melanie
   Mander, Palwinder K.
   Mosley, Julie
   Ramirez-Molina, Cesar
   Rowland, Paul
   Schofield, Christopher J.
   Sheppard, Robert J.
   Smith, Julia E.
   Swales, Catherine
   Tanner, Robert
   Thomas, Pamela
   Tumber, Anthony
   Drewes, Gerard
   Oppermann, Udo
   Patel, Dinshaw J.
   Lee, Kevin
   Wilson, David M.
TI A selective jumonji H3K27 demethylase inhibitor modulates the proinflammatory macrophage response
SO NATURE
LA English
DT Article
ID histone lysine demethylases; substrate-specificity; structural insights; gene-expression; jmjd3; methylation; disease; family; utx
AB The jumonji (JMJ) family of histone demethylases are Fe2+ - and a-ketoglutarate-dependent oxygenases that are essential components of regulatory transcriptional chromatin complexes(1-4). These enzymes demethylate lysine residues in histones in a methylation-state and sequence-specific context(5). Considerable effort has been devoted to gaining a mechanistic understanding of the roles of histone lysine demethylases in eukaryotic transcription, genome integrity and epigenetic inheritance(2,4,6), as well as in development, physiology and disease(3,7). However, because of the absence of any selective inhibitors, the relevance of the demethylase activity of JMJ enzymes in regulating cellular responses remains poorly understood. Here we present a structure-guided small-molecule and chemoproteomics approach to elucidating the functional role of the H3K27me3-specific demethylase subfamily (KDM6 subfamily members JMJD3 and UTX)(8). The liganded structures of human and mouse JMJD3 provide novel insight into the specificity determinants for cofactor, substrate and inhibitor recognition by the KDM6 subfamily of demethylases. We exploited these structural features to generate the first small-molecule catalytic site inhibitor that is selective for the H3K27me3-specific JMJ subfamily. We demonstrate that this inhibitor binds in a novel manner and reduces lipopolysaccharide-induced proinflammatory cytokine production by human primary macrophages, a process that depends on both JMJD3 and UTX. Our results resolve the ambiguity associated with the catalytic function of H3K27-specific JMJs in regulating disease-relevant inflammatory responses and provide encouragement for designing small-molecule inhibitors to allow selective pharmacological intervention across the JMJ family.
C1 [Kruidenier, Laurens; Liddle, John; Diallo, Hawa; Mander, Palwinder K.; Ramirez-Molina, Cesar; Sheppard, Robert J.; Smith, Julia E.; Lee, Kevin; Wilson, David M.] GlaxoSmithKline R&D, Med Res Ctr, Immunoinflammat Therapy Area, Epinova DPU, Stevenage SG1 2NY, Herts, England.
   [Chung, Chun-wa; Bridges, Angela; Hutchinson, Sue; Jones, Emma; Katso, Roy; Leveridge, Melanie; Mosley, Julie; Rowland, Paul; Tanner, Robert; Thomas, Pamela] GlaxoSmithKline R&D, Med Res Ctr, Platform Technol & Sci, Stevenage SG1 2NY, Herts, England.
   [Cheng, Zhongjun; Patel, Dinshaw J.] Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA.
   [Che, KaHing; Bountra, Chas; Schofield, Christopher J.; Tumber, Anthony; Oppermann, Udo] Univ Oxford, Struct Genom Consortium, Headington OX3 7DQ, England.
   [Che, KaHing; Swales, Catherine; Oppermann, Udo] Univ Oxford, NIHR Biomed Res Unit, Botnar Res Ctr, Oxford OX3 7LD, England.
   [Joberty, Gerard; Bantscheff, Marcus; Eberhard, Dirk; Drewes, Gerard] Cellzome AG, D-69117 Heidelberg, Germany.
C3 GlaxoSmithKline; Glaxosmithkline United Kingdom; GlaxoSmithKline; Glaxosmithkline United Kingdom; Memorial Sloan Kettering Cancer Center; University of Oxford; University of Oxford; GlaxoSmithKline; Cellzome GmbH
RP Wilson, DM (corresponding author), GlaxoSmithKline R&D, Med Res Ctr, Immunoinflammat Therapy Area, Epinova DPU, Gunnels Wood Rd, Stevenage SG1 2NY, Herts, England.
EM david.m.wilson@gsk.com
FU Starr Foundation; Abby Rockefeller Mauze Trust; Maloris Foundation; Canadian Institutes for Health Research; Canada Foundation for Innovation; Genome Canada; GlaxoSmithKline; Lilly Canada; Novartis Research Foundation; Pfizer; Takeda; Ontario Ministry of Economic Development and Innovation; Wellcome Trust; National Institute for Health and Research (NIHR) Biomedical Research Unit, Oxford; National Cancer Institute [P30CA008748] Funding Source: NIH RePORTER; Versus Arthritis [18358] Funding Source: researchfish
NR 25
TC 775
Z9 908
U1 2
U2 122
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 16
PY 2012
VL 488
IS 7411
BP 404
EP 408
DI 10.1038/nature11262
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 988OS
UT WOS:000307501000047
PM 22842901
DA 2026-03-09
ER

PT J
AU Giazotto, F
   Martínez-Pérez, MJ
AF Giazotto, Francesco
   Martinez-Perez, Maria Jose
TI The Josephson heat interferometer
SO NATURE
LA English
DT Article
ID junctions; transport; conductance; metals
AB The Josephson effect(1) is perhaps the prototypical manifestation of macroscopic phase coherence, and forms the basis of a widely used electronic interferometer-the superconducting quantum interference device(2) (SQUID). In 1965, Maki and Griffin predicted(3) that the thermal current through a temperature-biased Josephson tunnel junction coupling two superconductors should be a stationary periodic function of the quantum phase difference between the superconductors: a temperature-biased SQUID should therefore allow heat currents to interfere(4,5), resulting in a thermal version of the electric Josephson interferometer. This phase-dependent mechanism of thermal transport has been the subject of much discussion(4,6-8) but, surprisingly, has yet to be realized experimentally. Here we investigate heat exchange between two normal metal electrodes kept at different temperatures and tunnel-coupled to each other through a thermal 'modulator' (ref. 5) in the form of a direct-current SQUID. We find that heat transport in the system is phase dependent, in agreement with the original prediction. Our Josephson heat interferometer yields magnetic-flux-dependent temperature oscillations of up to 21 millikelvin in amplitude, and provides a flux-to-temperature transfer coefficient exceeding 60 millikelvin per flux quantum at 235 millikelvin. In addition to confirming the existence of a phase-dependent thermal current unique to Josephson junctions, our results point the way towards the phase-coherent manipulation of heat in solid-state nanocircuits.
C1 [Giazotto, Francesco; Martinez-Perez, Maria Jose] CNR, Ist Nanosci, NEST, I-56127 Pisa, Italy.
   [Giazotto, Francesco; Martinez-Perez, Maria Jose] Scuola Normale Super Pisa, I-56127 Pisa, Italy.
C3 Consiglio Nazionale delle Ricerche (CNR); Istituto Nanoscienze (NANO-CNR); Scuola Normale Superiore di Pisa
RP Giazotto, F (corresponding author), CNR, Ist Nanosci, NEST, Piazza San Silvestro 12, I-56127 Pisa, Italy.
EM giazotto@sns.it
FU EC FP7 programme [228464]
NR 25
TC 205
Z9 218
U1 1
U2 88
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD DEC 20
PY 2012
VL 492
IS 7429
BP 401
EP 405
DI 10.1038/nature11702
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 056KQ
UT WOS:000312488200050
PM 23257882
DA 2026-03-09
ER

PT J
AU Endres, M
   Fukuhara, T
   Pekker, D
   Cheneau, M
   Schauss, P
   Gross, C
   Demler, E
   Kuhr, S
   Bloch, I
AF Endres, Manuel
   Fukuhara, Takeshi
   Pekker, David
   Cheneau, Marc
   Schauss, Peter
   Gross, Christian
   Demler, Eugene
   Kuhr, Stefan
   Bloch, Immanuel
TI The 'Higgs' amplitude mode at the two-dimensional superfluid/Mott insulator transition
SO NATURE
LA English
DT Article
ID charge-density waves; optical lattices; mott insulator; gases
AB Spontaneous symmetry breaking plays a key role in our understanding of nature. In relativistic quantum field theory, a broken continuous symmetry leads to the emergence of two types of fundamental excitation: massless Nambu-Goldstone modes and a massive 'Higgs' amplitude mode. An excitation of Higgs type is of crucial importance in the standard model of elementary particle physics(1), and also appears as a fundamental collective mode in quantum many-body systems(2). Whether such a mode exists in low-dimensional systems as a resonance-like feature, or whether it becomes overdamped through coupling to Nambu-Goldstone modes, has been a subject of debate(2-9). Here we experimentally find and study a Higgs mode in a two-dimensional neutral superfluid close to a quantum phase transition to a Mott insulating phase. We unambiguously identify the mode by observing the expected reduction in frequency of the onset of spectral response when approaching the transition point. In this regime, our system is described by an effective relativistic field theory with a two-component quantum field(2,7), which constitutes a minimal model for spontaneous breaking of a continuous symmetry. Additionally, all microscopic parameters of our system are known from first principles and the resolution of our measurement allows us to detect excited states of the many-body system at the level of individual quasi-particles. This allows for an in-depth study of Higgs excitations that also addresses the consequences of the reduced dimensionality and confinement of the system. Our work constitutes a step towards exploring emergent relativistic models with ultracold atomic gases.
C1 [Endres, Manuel; Fukuhara, Takeshi; Cheneau, Marc; Schauss, Peter; Gross, Christian; Kuhr, Stefan; Bloch, Immanuel] Max Planck Inst Quantum Opt, D-85748 Garching, Germany.
   [Pekker, David] CALTECH, Dept Phys, Pasadena, CA 91125 USA.
   [Demler, Eugene] Harvard Univ, Dept Phys, Cambridge, MA 02138 USA.
   [Kuhr, Stefan] Univ Strathclyde, SUPA, Glasgow G4 0NG, Lanark, Scotland.
   [Bloch, Immanuel] Univ Munich, D-80799 Munich, Germany.
C3 Max Planck Society; California Institute of Technology; Harvard University; University of Strathclyde; University of Munich
RP Endres, M (corresponding author), Max Planck Inst Quantum Opt, D-85748 Garching, Germany.
EM manuel.endres@mpq.mpg.de
FU MPG; DFG; EU; JSPS; California Institute of Technology (IQIM
CR Altman E, 2002, PHYS REV LETT, V89, P0, DOI 10.1103/PhysRevLett.89.250404
   Bakr WS, 2010, SCIENCE, V329, P547, DOI 10.1126/science.1192368
   Bissbort U, 2011, PHYS REV LETT, V106, P0, DOI 10.1103/PhysRevLett.106.205303
   Bloch I, 2008, REV MOD PHYS, V80, P885, DOI 10.1103/RevModPhys.80.885
   Capogrosso-Sansone B, 2008, PHYS REV A, V77, P0, DOI 10.1103/PhysRevA.77.015602
   Cazalilla MA, 2006, NEW J PHYS, V8, P0, DOI 10.1088/1367-2630/8/8/158
   CHUBUKOV AV, 1994, PHYS REV B, V49, P11919, DOI 10.1103/PhysRevB.49.11919
   Endres M, 2011, SCIENCE, V334, P200, DOI 10.1126/science.1209284
   Gerbier F, 2007, PHYS REV LETT, V99, P0, DOI 10.1103/PhysRevLett.99.120405
   Grass TD, 2011, LASER PHYS, V21, P1459, DOI 10.1134/S1054660X11150096
   Huber SD, 2008, PHYS REV LETT, V100, P0, DOI 10.1103/PhysRevLett.100.050404
   Huber SD, 2007, PHYS REV B, V75, P0, DOI 10.1103/PhysRevB.75.085106
   LITTLEWOOD PB, 1981, PHYS REV LETT, V47, P811, DOI 10.1103/PhysRevLett.47.811
   Menotti C, 2008, PHYS REV B, V77, P0, DOI 10.1103/PhysRevB.77.235120
   Podolsky D, 2012, FEATURE REMOVAL ISOL, V0, P0
   Podolsky D, 2011, PHYS REV B, V84, P0, DOI 10.1103/PhysRevB.84.174522
   Pollet L, 2012, FEATURE REMOVAL ISOL, V0, P0
   Randall L, 1999, PHYS REV LETT, V83, P3370, DOI 10.1103/PhysRevLett.83.3370
   Rüegg C, 2008, PHYS REV LETT, V100, P0, DOI 10.1103/PhysRevLett.100.205701
   Sachdev S, 1999, PHYS REV B, V59, P14054, DOI 10.1103/PhysRevB.59.14054
   Schori C, 2004, PHYS REV LETT, V93, P0, DOI 10.1103/PhysRevLett.93.240402
   Sengupta K, 2005, PHYS REV A, V71, P0, DOI 10.1103/PhysRevA.71.033629
   Sherson JF, 2010, NATURE, V467, P68, DOI 10.1038/nature09378
   SOORYAKUMAR R, 1980, PHYS REV LETT, V45, P660, DOI 10.1103/PhysRevLett.45.660
   Spielman IB, 2007, PHYS REV LETT, V98, P0, DOI 10.1103/PhysRevLett.98.080404
   Stöferle T, 2004, PHYS REV LETT, V92, P0, DOI 10.1103/PhysRevLett.92.130403
   Varma CM, 2002, J LOW TEMP PHYS, V126, P901, DOI 10.1023/A:1013890507658
   Weinberg S, 2013, QUANTUM THEORY FIELD, V0, P0, DOI DOI 10.1017/CBO9781139644167
   Zwerger W, 2004, PHYS REV LETT, V92, P0, DOI 10.1103/PhysRevLett.92.027203
NR 30
TC 275
Z9 308
U1 0
U2 87
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUL 26
PY 2012
VL 487
IS 7408
BP 454
EP U64
DI 10.1038/nature11255
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 979KD
UT WOS:000306815300032
PM 22837000
DA 2026-03-09
ER

PT J
AU Koo, BK
   Spit, M
   Jordens, I
   Low, TY
   Stange, DE
   van de Wetering, M
   van Es, JH
   Mohammed, S
   Heck, AJR
   Maurice, MM
   Clevers, H
AF Koo, Bon-Kyoung
   Spit, Maureen
   Jordens, Ingrid
   Low, Teck Y.
   Stange, Daniel E.
   van de Wetering, Marc
   van Es, Johan H.
   Mohammed, Shabaz
   Heck, Albert J. R.
   Maurice, Madelon M.
   Clevers, Hans
TI Tumour suppressor RNF43 is a stem-cell E3 ligase that induces endocytosis of Wnt receptors
SO NATURE
LA English
DT Article
ID small-intestine; negative regulator; beta-catenin; in-vitro; lgr5; cancer; colon; ubiquitylation; transcription; inhibition
AB LGR5(+) stem cells reside at crypt bottoms, intermingled with Paneth cells that provide Wnt, Notch and epidermal growth factor signals(1). Here we find that the related RNF43 and ZNRF3 transmembrane E3 ubiquitin ligases are uniquely expressed in LGR5(+) stem cells. Simultaneous deletion of the two genes encoding these proteins in the intestinal epithelium of mice induces rapidly growing adenomas containing high numbers of Paneth and LGR5(+) stem cells. In vitro, growth of organoids derived from these adenomas is arrested when Wnt secretion is inhibited, indicating a dependence of the adenoma stem cells on Wnt produced by adenoma Paneth cells. In the HEK293T human cancer cell line, expression of RNF43 blocks Wnt responses and targets surface-expressed frizzled receptors to lysosomes. In the RNF43-mutant colorectal cancer cell line HCT116, reconstitution of RNF43 expression removes its response to exogenous Wnt. We conclude that RNF43 and ZNRF3 reduce Wnt signals by selectively ubiquitinating frizzled receptors, thereby targeting these Wnt receptors for degradation.
C1 [Spit, Maureen; Jordens, Ingrid; Maurice, Madelon M.] Univ Med Ctr Utrecht, Dept Cell Biol, NL-3584 CX Utrecht, Netherlands.
   [Koo, Bon-Kyoung; Stange, Daniel E.; van de Wetering, Marc; van Es, Johan H.; Clevers, Hans] KNAW, Hubrecht Inst, NL-3584 CT Utrecht, Netherlands.
   [Koo, Bon-Kyoung; Stange, Daniel E.; van de Wetering, Marc; van Es, Johan H.; Clevers, Hans] Univ Med Ctr Utrecht, NL-3584 CT Utrecht, Netherlands.
   [Low, Teck Y.; Mohammed, Shabaz; Heck, Albert J. R.] Univ Utrecht, Biomol Mass Spectrometry & Prote Grp, Bijvoet Ctr Biomol Res, NL-3584 CH Utrecht, Netherlands.
   [Low, Teck Y.; Mohammed, Shabaz; Heck, Albert J. R.] Univ Utrecht, Utrecht Inst Pharmaceut Sci, NL-3584 CH Utrecht, Netherlands.
   [Low, Teck Y.; Mohammed, Shabaz; Heck, Albert J. R.] Netherlands Prote Ctr, NL-3584 CH Utrecht, Netherlands.
C3 Utrecht University; Utrecht University Medical Center; Royal Netherlands Academy of Arts & Sciences; Hubrecht Institute (KNAW); Utrecht University; Utrecht University Medical Center; Utrecht University; Utrecht University
RP Maurice, MM (corresponding author), Univ Med Ctr Utrecht, Dept Cell Biol, NL-3584 CX Utrecht, Netherlands.
EM M.M.Maurice@umcutrecht.nl; h.clevers@hubrecht.eu
FU European Research Council [EU/232814-StemCeLLMark]; National Research Foundation of Korea [NRF-2011-357-C00093]; Centre van Biomedical Genetics; European Research Council, ERC-StG [242958]; KNAW/3V-fund;  [EU/Health-F4-2007-200720];  [Ti Pharma/T3-106]; European Research Council (ERC) [242958] Funding Source: European Research Council (ERC)
NR 31
TC 786
Z9 911
U1 1
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 AUG 30
PY 2012
VL 488
IS 7413
BP 665
EP +
DI 10.1038/nature11308
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 996NC
UT WOS:000308095100058
PM 22895187
DA 2026-03-09
ER

PT J
AU Zhu, WQ
   London, NR
   Gibson, CC
   Davis, CT
   Tong, ZZ
   Sorensen, LK
   Shi, DS
   Guo, JP
   Smith, MCP
   Grossmann, AH
   Thomas, KR
   Li, DY
AF Zhu, Weiquan
   London, Nyall R.
   Gibson, Christopher C.
   Davis, Chadwick T.
   Tong, Zongzhong
   Sorensen, Lise K.
   Shi, Dallas S.
   Guo, Jinping
   Smith, Matthew C. P.
   Grossmann, Allie H.
   Thomas, Kirk R.
   Li, Dean Y.
TI Interleukin receptor activates a MYD88-ARNO-ARF6 cascade to disrupt vascular stability
SO NATURE
LA English
DT Article
ID nf-kappa-b; collagen-induced arthritis; tumor-necrosis-factor; anti-tnf-alpha; endothelial permeability; inflammation; mechanisms; protein; gene; mice
AB The innate immune response is essential for combating infectious disease. Macrophages and other cells respond to infection by releasing cytokines, such as interleukin-1 beta (IL-1 beta), which in turn activate a well-described, myeloid-differentiation factor 88 (MYD88)-mediated, nuclear factor-kappa B (NF-kappa B)-dependent transcriptional pathway that results in inflammatory-cell activation and recruitment(1-4). Endothelial cells, which usually serve as a barrier to the movement of inflammatory cells out of the blood and into tissue, are also critical mediators of the inflammatory response(5,6). Paradoxically, the cytokines vital to a successful immune defence also have disruptive effects on endothelial cell-cell interactions and can trigger degradation of barrier function and dissociation of tissue architecture(7-9). The mechanism of this barrier dissolution and its relationship to the canonical NF-kappa B pathway remain poorly defined. Here we show that the direct, immediate and disruptive effects of IL-1 beta on endothelial stability in a human in vitro cell model are NF-kappa B independent and are instead the result of signalling through the small GTPase ADP-ribosylation factor 6 (ARF6) and its activator ARF nucleotide binding site opener (ARNO; also known as CYTH2). Moreover, we show that ARNO binds directly to the adaptor protein MYD88, and thus propose MYD88-ARNO-ARF6 as a proximal IL-1 beta signalling pathway distinct from that mediated by NF-kappa B. Finally, we show that SecinH3, an inhibitor of ARF guanine nucleotide-exchange factors such as ARNO, enhances vascular stability and significantly improves outcomes in animal models of inflammatory arthritis and acute inflammation.
C1 [Zhu, Weiquan; London, Nyall R.; Guo, Jinping; Smith, Matthew C. P.; Thomas, Kirk R.; Li, Dean Y.] Univ Utah, Dept Med, Salt Lake City, UT 84112 USA.
   [Zhu, Weiquan; London, Nyall R.; Gibson, Christopher C.; Davis, Chadwick T.; Sorensen, Lise K.; Shi, Dallas S.; Guo, Jinping; Smith, Matthew C. P.; Grossmann, Allie H.; Thomas, Kirk R.; Li, Dean Y.] Univ Utah, Program Mol Med, Salt Lake City, UT 84112 USA.
   [London, Nyall R.; Smith, Matthew C. P.; Li, Dean Y.] Univ Utah, Dept Oncol Sci, Salt Lake City, UT 84112 USA.
   [Gibson, Christopher C.] Univ Utah, Dept Bioengn, Salt Lake City, UT 84112 USA.
   [Davis, Chadwick T.; Shi, Dallas S.] Univ Utah, Dept Human Genet, Salt Lake City, UT 84112 USA.
   [Tong, Zongzhong] Navigen Inc, Salt Lake City, UT 84112 USA.
   [Guo, Jinping] Second Mil Med Univ, Dept Anat, Shanghai 200433, Peoples R China.
   [Grossmann, Allie H.] Univ Utah, Dept Pathol, Salt Lake City, UT 84112 USA.
   [Li, Dean Y.] VA Salt Lake City Hlth Care Syst, Cardiol Sect, Salt Lake City, UT 84112 USA.
   [Li, Dean Y.] Sichuan Acad Med Sci, Inst Lab Med, Key Lab Human Dis Gene Study Sichuan Prov, Chengdu 610072, Sichuan, Peoples R China.
   [Li, Dean Y.] Sichuan Prov Peoples Hosp, Chengdu 610072, Sichuan, Peoples R China.
C3 Utah System of Higher Education; University of Utah; Utah System of Higher Education; University of Utah; Utah System of Higher Education; University of Utah; Utah System of Higher Education; University of Utah; Utah System of Higher Education; University of Utah; Naval Medical University; Utah System of Higher Education; University of Utah; US Department of Veterans Affairs; Sichuan Provincial People's Hospital; Sichuan Provincial People's Hospital
RP Li, DY (corresponding author), Univ Utah, Dept Med, Salt Lake City, UT 84112 USA.
EM dean.li@u2m2.utah.edu
FU National Heart, Lung, and Blood Institute; Burroughs Wellcome Fund; Juvenile Diabetes Research Foundation; NIAID Rocky Mountain Regional Center of Excellence in Biodefense and Emerging Infectious Disease; American Asthma Foundation; Department of Defense
NR 30
TC 137
Z9 163
U1 0
U2 62
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 13
PY 2012
VL 492
IS 7428
BP 252
EP 255
DI 10.1038/nature11603
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 053GM
UT WOS:000312259300042
PM 23143332
DA 2026-03-09
ER

PT J
AU Delescluse, M
   Chamot-Rooke, N
   Cattin, R
   Fleitout, L
   Trubienko, O
   Vigny, C
AF Delescluse, Matthias
   Chamot-Rooke, Nicolas
   Cattin, Rodolphe
   Fleitout, Luce
   Trubienko, Olga
   Vigny, Christophe
TI April 2012 intra-oceanic seismicity off Sumatra boosted by the Banda-Aceh megathrust
SO NATURE
LA English
DT Article
ID central indian-ocean; andaman earthquake; fault reactivation; stress transfer; coseismic slip; deformation; plate; australia; inversion; zones
AB Large earthquakes nucleate at tectonic plate boundaries, and their occurrence within a plate's interior remains rare and poorly documented, especially offshore. The two large earthquakes that struck the northeastern Indian Ocean on 11 April 2012 are an exception: they are the largest strike-slip events reported in historical times(1,2) and triggered large aftershocks worldwide(3). Yet they occurred within an intra-oceanic setting along the fossil fabric of the extinct Wharton basin, rather than on a discrete plate boundary(4-8). Here we show that the 11 April 2012 twin earthquakes are part of a continuing boost of the intraplate deformation between India and Australia that followed the Aceh 2004 and Nias 2005 megathrust earthquakes, subsequent to a stress transfer process recognized at other subduction zones(9,10). Using Coulomb stress change calculations, we show that the coseismic slips of the Aceh and Nias earthquakes can promote oceanic left-lateral strike-slip earthquakes on preexisting meridian-aligned fault planes. We further show that persistent viscous relaxation in the asthenospheric mantle several years after the Aceh megathrust explains the time lag between the 2004 megathrust and the 2012 intraplate events. On a short timescale, the 2012 events provide new evidence for the interplay between megathrusts at the subduction interface and intraplate deformation offshore. On a longer geological timescale, the Australian plate, driven by slab-pull forces at the Sunda trench, is detaching from the Indian plate, which is subjected to resisting forces at the Himalayan front(6,8,11).
C1 [Delescluse, Matthias; Chamot-Rooke, Nicolas; Fleitout, Luce; Trubienko, Olga; Vigny, Christophe] Ecole Normale Super, Geol Lab, F-75005 Paris, France.
   [Delescluse, Matthias; Chamot-Rooke, Nicolas; Fleitout, Luce; Trubienko, Olga; Vigny, Christophe] CNRS, UMR8538, F-75005 Paris, France.
   [Cattin, Rodolphe] Univ Montpellier 2, F-34090 Montpellier, France.
   [Cattin, Rodolphe] CNRS, UMR5243, F-34090 Montpellier, France.
C3 Universite PSL; Ecole Normale Superieure (ENS); Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Earth Sciences & Astronomy (INSU); Universite de Montpellier; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Earth Sciences & Astronomy (INSU); Universite de Montpellier
RP Delescluse, M (corresponding author), Ecole Normale Super, Geol Lab, F-75005 Paris, France.
EM delescluse@geologie.ens.fr
NR 43
TC 88
Z9 97
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 11
PY 2012
VL 490
IS 7419
BP 240
EP +
DI 10.1038/nature11520
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 019IY
UT WOS:000309733300045
PM 23023134
DA 2026-03-09
ER

PT J
AU Harris, TH
   Banigan, EJ
   Christian, DA
   Konradt, C
   Wojno, EDT
   Norose, K
   Wilson, EH
   John, B
   Weninger, W
   Luster, AD
   Liu, AJ
   Hunter, CA
AF Harris, Tajie H.
   Banigan, Edward J.
   Christian, David A.
   Konradt, Christoph
   Wojno, Elia D. Tait
   Norose, Kazumi
   Wilson, Emma H.
   John, Beena
   Weninger, Wolfgang
   Luster, Andrew D.
   Liu, Andrea J.
   Hunter, Christopher A.
TI Generalized Levy walks and the role of chemokines in migration of effector CD8+ T cells
SO NATURE
LA English
DT Article
ID toxoplasma-gondii; resistance; movement; motility; success; laws
AB Chemokines have a central role in regulating processes essential to the immune function of T cells(1-3), such as their migration within lymphoid tissues and targeting of pathogens in sites of inflammation. Here we track T cells using multi-photon microscopy to demonstrate that the chemokine CXCL10 enhances the ability of CD8(+) T cells to control the pathogen Toxoplasma gondii in the brains of chronically infected mice. This chemokine boosts T-cell function in two different ways: it maintains the effector T-cell population in the brain and speeds up the average migration speed without changing the nature of the walk statistics. Notably, these statistics are not Brownian; rather, CD8(+) T-cell motility in the brain is well described by a generalized Levy walk. According to our model, this unexpected feature enables T cells to find rare targets with more than an order of magnitude more efficiency than Brownian random walkers. Thus, CD8(+) T-cell behaviour is similar to Levy strategies reported in organisms ranging from mussels to marine predators and monkeys(4-10), and CXCL10 aids T cells in shortening the average time taken to find rare targets.
C1 [Banigan, Edward J.; Liu, Andrea J.] Univ Penn, Sch Arts & Sci, Dept Phys & Astron, Philadelphia, PA 19104 USA.
   [Harris, Tajie H.; Christian, David A.; Konradt, Christoph; Wojno, Elia D. Tait; John, Beena; Hunter, Christopher A.] Univ Penn, Sch Vet Med, Dept Pathobiol, Philadelphia, PA 19104 USA.
   [Norose, Kazumi] Chiba Univ, Grad Sch Med, Dept Infect & Host Def, Chuo Ku, Chiba 2608670, Japan.
   [Wilson, Emma H.] Univ Calif Riverside, Div Biomed Sci, Riverside, CA 92521 USA.
   [Weninger, Wolfgang] Centenary Inst, Newtown, NSW 2042, Australia.
   [Weninger, Wolfgang] Sydney Med Sch, Discipline Dermatol, Sydney, NSW 2006, Australia.
   [Luster, Andrew D.] Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Ctr Immunol & Inflammatory Dis, Charlestown, MA 02129 USA.
C3 University of Pennsylvania; University of Pennsylvania; Chiba University; University of California System; University of California Riverside; University of Sydney; Centenary Institute; University of Sydney; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital
RP Liu, AJ (corresponding author), Univ Penn, Sch Arts & Sci, Dept Phys & Astron, 209 S 33rd St, Philadelphia, PA 19104 USA.
EM ajliu@physics.upenn.edu; chunter@vet.upenn.edu
FU National Institutes of Health [AI-41158, AI-42334, EY-021314, T32-AI-055400, AI-081478, CA-069212, RNS-072298, AI-090234]; National Science Foundation [DMR-0520020, DMR-1104637]; state of Pennsylvania; Japan Society for the Promotion of Science [20592071]; Ministry of Education, Culture, Sports, Science and Technology of Japan; Grants-in-Aid for Scientific Research [20592071] Funding Source: KAKEN; Direct For Mathematical & Physical Scien; Division Of Materials Research [1120901, 1104637] Funding Source: National Science Foundation; National Institute of Allergy and Infectious Diseases [T32AI007532, T32AI055400] Funding Source: NIH RePORTER
NR 33
TC 431
Z9 482
U1 0
U2 135
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 28
PY 2012
VL 486
IS 7404
BP 545
EP U145
DI 10.1038/nature11098
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 965IJ
UT WOS:000305760600046
PM 22722867
DA 2026-03-09
ER

PT J
AU Brown, MTC
   Tan, KR
   O'Connor, EC
   Nikonenko, I
   Muller, D
   Lüscher, C
AF Brown, Matthew T. C.
   Tan, Kelly R.
   O'Connor, Eoin C.
   Nikonenko, Irina
   Muller, Dominique
   Luescher, Christian
TI Ventral tegmental area GABA projections pause accumbal cholinergic interneurons to enhance associative learning
SO NATURE
LA English
DT Article
ID tonically active neurons; dopaminergic-neurons; nucleus-accumbens; reward; activation; striatum; release; cocaine
AB The ventral tegmental area (VTA) and nucleus accumbens (NAc) are essential for learning about environmental stimuli associated with motivationally relevant outcomes. The task of signalling such events, both rewarding and aversive, from the VTA to the NAc has largely been ascribed to dopamine neurons(1-3). The VTA also contains GABA (gamma-aminobutyric acid)-releasing neurons, which provide local inhibition(4,5) and also project to the NAc6,7. However, the cellular targets and functional importance of this long-range inhibitory projection have not been ascertained. Here we show that GABA-releasing neurons of the VTA that project to the NAc (VTA GABA projection neurons) inhibit accumbal cholinergic interneurons (CINs) to enhance stimulus-outcome learning. Combining optogenetics with structural imaging and electrophysiology, we found that VTA GABA projection neurons selectively target NAc CINs, forming multiple symmetrical synaptic contacts that generated inhibitory postsynaptic currents. This is remarkable considering that CINs represent a very small population of all accumbal neurons, and provide the primary source of cholinergic tone in the NAc. Brief activation of this projection was sufficient to halt the spontaneous activity of NAc CINs, resembling the pause recorded in animals learning stimulus-outcome associations(8-12). Indeed, we found that forcing CINs to pause in behaving mice enhanced discrimination of a motivationally important stimulus that had been associated with an aversive outcome. Our results demonstrate that VTA GABA projection neurons, through their selective targeting of accumbal CINs, provide a novel route through which the VTA communicates saliency to the NAc. VTA GABA projection neurons thus emerge as orchestrators of dopaminergic and cholinergic modulation in the NAc.
C1 [Brown, Matthew T. C.; Tan, Kelly R.; O'Connor, Eoin C.; Nikonenko, Irina; Muller, Dominique; Luescher, Christian] Univ Geneva, Fac Med, Dept Basic Neurosci, CH-1211 Geneva, Switzerland.
   [Luescher, Christian] Univ Hosp Geneva, Dept Clin Neurosci, Neurol Clin, CH-1211 Geneva, Switzerland.
C3 University of Geneva; 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
NR 30
TC 283
Z9 360
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 DEC 20
PY 2012
VL 492
IS 7429
BP 452
EP 456
DI 10.1038/nature11657
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 056KQ
UT WOS:000312488200061
PM 23178810
DA 2026-03-09
ER

PT J
AU Scholl, JA
   Koh, AL
   Dionne, JA
AF Scholl, Jonathan A.
   Koh, Ai Leen
   Dionne, Jennifer A.
TI Quantum plasmon resonances of individual metallic nanoparticles
SO NATURE
LA English
DT Article
ID dielectric functions; optical-absorption; gold; excitations; generation; resolution; spectra; cluster
AB The plasmon resonances of metallic nanoparticles have received considerable attention for their applications in nanophotonics, biology, sensing, spectroscopy and solar energy harvesting. Although thoroughly characterized for spheres larger than ten nanometres in diameter, the plasmonic properties of particles in the quantum size regime have been historically difficult to describe owing to weak optical scattering, metal-ligand interactions, and inhomogeneity in ensemble measurements. Such difficulties have precluded probing and controlling the plasmonic properties of quantum-sized particles in many natural and engineered processes, notably catalysis. Here we investigate the plasmon resonances of individual ligand-free silver nanoparticles using aberration-corrected transmission electron microscope (TEM) imaging and monochromated scanning TEM electron energy-loss spectroscopy (EELS). This technique allows direct correlation between a particle's geometry and its plasmon resonance. As the nanoparticle diameter decreases from 20 nanometres to less than two nanometres, the plasmon resonance shifts to higher energy by 0.5 electronvolts, a substantial deviation from classical predictions. We present an analytical quantum mechanical model that describes this shift due to a change in particle permittivity. Our results highlight the quantum plasmonic properties of small metallic nanospheres, with direct application to understanding and exploiting catalytically active and biologically relevant nanoparticles.
C1 [Scholl, Jonathan A.; Dionne, Jennifer A.] Stanford Univ, Dept Mat Sci & Engn, Stanford, CA 94305 USA.
   [Koh, Ai Leen] Stanford Univ, Stanford Nanocharacterizat Lab, Stanford, CA 94305 USA.
C3 Stanford University; Stanford University
RP Dionne, JA (corresponding author), Stanford Univ, Dept Mat Sci & Engn, Stanford, CA 94305 USA.
EM jscholl@stanford.edu; jdionne@stanford.edu
FU National Science Foundation; Stanford Terman Fellowship; Robert N. Noyce Family Faculty Fellowship
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NR 50
TC 1031
Z9 1193
U1 8
U2 1177
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 22
PY 2012
VL 483
IS 7390
BP 421
EP U68
DI 10.1038/nature10904
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 912CC
UT WOS:000301771200034
PM 22437611
DA 2026-03-09
ER

PT J
AU Chen, J
   Li, YJ
   Yu, TS
   McKay, RM
   Burns, DK
   Kernie, SG
   Parada, LF
AF Chen, Jian
   Li, Yanjiao
   Yu, Tzong-Shiue
   McKay, Renee M.
   Burns, Dennis K.
   Kernie, Steven G.
   Parada, Luis F.
TI A restricted cell population propagates glioblastoma growth after chemotherapy
SO NATURE
LA English
DT Article
ID expressing progenitors; initiating cells; mouse models; stem-cells; neurogenesis; glioma; astrocytomas; brain; rare
AB Glioblastoma multiforme is the most common primary malignant brain tumour, with a median survival of about one year(1). This poor prognosis is due to therapeutic resistance and tumour recurrence after surgical removal. Precisely how recurrence occurs is unknown. Using a genetically engineered mouse model of glioma, here we identify a subset of endogenous tumour cells that are the source of new tumour cells after the drug temozolomide (TMZ) is administered to transiently arrest tumour growth. A nestin-Delta TK-IRES-GFP (Nes-Delta TK-GFP) transgene that labels quiescent subventricular zone adult neural stem cells also labels a subset of endogenous glioma tumour cells. On arrest of tumour cell proliferation with TMZ, pulse-chase experiments demonstrate a tumour re-growth cell hierarchy originating with the Nes-Delta TK-GFP transgene subpopulation. Ablation of the GFP(+) cells with chronic ganciclovir administration significantly arrested tumour growth, and combined TMZ and ganciclovir treatment impeded tumour development. Thus, a relatively quiescent subset of endogenous glioma cells, with properties similar to those proposed for cancer stem cells, is responsible for sustaining long-term tumour growth through the production of transient populations of highly proliferative cells.
C1 [Chen, Jian; Li, Yanjiao; Yu, Tzong-Shiue; McKay, Renee M.; Kernie, Steven G.; Parada, Luis F.] Univ Texas SW Med Ctr Dallas, Dept Dev Biol, Dallas, TX 75390 USA.
   [Chen, Jian; Li, Yanjiao; Yu, Tzong-Shiue; McKay, Renee M.; Kernie, Steven G.; Parada, Luis F.] Univ Texas SW Med Ctr Dallas, Kent Waldrep Ctr Basic Res Nerve Growth & Regener, Dallas, TX 75390 USA.
   [Yu, Tzong-Shiue; Kernie, Steven G.] Univ Texas SW Med Ctr Dallas, Dept Pediat, Dallas, TX 75390 USA.
   [Burns, Dennis K.] Univ Texas SW Med Ctr Dallas, Dept Pathol, Dallas, TX 75390 USA.
C3 University of Texas System; University of Texas Southwestern Medical Center; University of Texas System; University of Texas Southwestern Medical Center; University of Texas System; University of Texas Southwestern Medical Center; University of Texas System; University of Texas Southwestern Medical Center
RP Parada, LF (corresponding author), Univ Texas SW Med Ctr Dallas, Dept Dev Biol, Dallas, TX 75390 USA.
EM luis.parada@utsouthwestern.edu
FU James S. McDonnell Foundation [JSMF-220020206]; Goldhirsh Foundation; Cancer Prevention Research Institute of Texas [RP 100782]; National Institutes of Health [R01 CA131313];  [RO1 NS048192-01]
NR 19
TC 1821
Z9 2130
U1 1
U2 382
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD AUG 23
PY 2012
VL 488
IS 7412
BP 522
EP +
DI 10.1038/nature11287
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 992FS
UT WOS:000307761600039
PM 22854781
DA 2026-03-09
ER

PT J
AU Huang, J
   Gurung, B
   Wan, BB
   Matkar, S
   Veniaminova, NA
   Wan, K
   Merchant, JL
   Hua, XX
   Lei, M
AF Huang, Jing
   Gurung, Buddha
   Wan, Bingbing
   Matkar, Smita
   Veniaminova, Natalia A.
   Wan, Ke
   Merchant, Juanita L.
   Hua, Xianxin
   Lei, Ming
TI The same pocket in menin binds both MLL and JUND but has opposite effects on transcription
SO NATURE
LA English
DT Article
ID histone methyltransferase complex; endocrine neoplasia type-1; protein; gene; interacts; family
AB Menin is a tumour suppressor protein whose loss or inactivation causes multiple endocrine neoplasia 1 (MEN1), a hereditary autosomal dominant tumour syndrome that is characterized by tumorigenesis in multiple endocrine organs(1). Menin interacts with many proteins and is involved in a variety of cellular processes(2-8). Menin binds the JUN family transcription factor JUND and inhibits its transcriptional activity(2,9). Several MEN1 missense mutations disrupt the menin-JUND interaction, suggesting a correlation between the tumour-suppressor function of menin and its suppression of JUND-activated transcription(2,10). Menin also interacts with mixed lineage leukaemia protein 1 (MLL1), a histone H3 lysine 4 methyltransferase, and functions as an oncogenic cofactor to upregulate gene transcription and promote MLL1-fusion-protein-induced leukaemogenesis(5,7,11,12). A recent report on the tethering of MLL1 to chromatin binding factor lens epithelium-derived growth factor (LEDGF) by menin indicates that menin is a molecular adaptor coordinating the functions of multiple proteins(13). Despite its importance, how menin interacts with many distinct partners and regulates their functions remains poorly understood. Here we present the crystal structures of human menin in its free form and in complexes with MLL1 or with JUND, or with an MLL1-LEDGF heterodimer. These structures show that menin contains a deep pocket that binds short peptides of MLL1 or JUND in the same manner, but that it can have opposite effects on transcription. The menin-JUND interaction blocks JUN N-terminal kinase (JNK)-mediated JUND phosphorylation and suppresses JUND-induced transcription. In contrast, menin promotes gene transcription by binding the transcription activator MLL1 through the peptide pocket while still interacting with the chromatin-anchoring protein LEDGF at a distinct surface formed by both menin and MLL1.
C1 [Huang, Jing; Wan, Bingbing; Wan, Ke; Lei, Ming] Univ Michigan, Sch Med, Howard Hughes Med Inst, Ann Arbor, MI 48109 USA.
   [Huang, Jing; Wan, Bingbing; Wan, Ke; Lei, Ming] Univ Michigan, Sch Med, Dept Biol Chem, Ann Arbor, MI 48109 USA.
   [Gurung, Buddha; Matkar, Smita; Hua, Xianxin] Univ Penn, Perelman Sch Med, Dept Canc Biol, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA.
   [Veniaminova, Natalia A.; Merchant, Juanita L.] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA.
   [Merchant, Juanita L.] Univ Michigan, Div Gastroenterol, Dept Mol & Integrat Physiol, Ann Arbor, MI 48109 USA.
C3 Howard Hughes Medical Institute; University of Michigan System; University of Michigan; University of Michigan System; University of Michigan; University of Pennsylvania; University of Michigan System; University of Michigan; University of Michigan System; University of Michigan
RP Lei, M (corresponding author), Univ Michigan, Sch Med, Howard Hughes Med Inst, 1150 W Med Ctr Dr, Ann Arbor, MI 48109 USA.
EM huax@mail.med.upenn.edu; leim@umich.edu
FU National Institutes of Health [GM 083015-01, R01-DK085121, R37-DK45729]; American Cancer Society; American Association for Cancer Research Caring for Carcinoid Foundation; National Cancer Institute [Y1-CO-1020]; National Institute of General Medical Science [Y1-GM-1104]; US Department of Energy, Office of Science, Office of Basic Energy Sciences [DE-AC02-06CH11357]
NR 27
TC 239
Z9 275
U1 0
U2 44
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 23
PY 2012
VL 482
IS 7386
BP 542
EP U141
DI 10.1038/nature10806
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 898VM
UT WOS:000300770500054
PM 22327296
DA 2026-03-09
ER

PT J
AU Abyzov, A
   Mariani, J
   Palejev, D
   Zhang, Y
   Haney, MS
   Tomasini, L
   Ferrandino, AF
   Belmaker, LAR
   Szekely, A
   Wilson, M
   Kocabas, A
   Calixto, NE
   Grigorenko, EL
   Huttner, A
   Chawarska, K
   Weissman, S
   Urban, AE
   Gerstein, M
   Vaccarino, FM
AF Abyzov, Alexej
   Mariani, Jessica
   Palejev, Dean
   Zhang, Ying
   Haney, Michael Seamus
   Tomasini, Livia
   Ferrandino, Anthony F.
   Belmaker, Lior A. Rosenberg
   Szekely, Anna
   Wilson, Michael
   Kocabas, Arif
   Calixto, Nathaniel E.
   Grigorenko, Elena L.
   Huttner, Anita
   Chawarska, Katarzyna
   Weissman, Sherman
   Urban, Alexander Eckehart
   Gerstein, Mark
   Vaccarino, Flora M.
TI Somatic copy number mosaicism in human skin revealed by induced pluripotent stem cells
SO NATURE
LA English
DT Article
ID genomic structural variants; nucleotide-resolution; retrotransposition; fibroblasts; framework; regions; brain; nanog
AB Reprogramming somatic cells into induced pluripotent stem cells (iPSCs) has been suspected of causing de novo copy number variation(1-4). To explore this issue, here we performa whole-genome and transcriptome analysis of 20 human iPSC lines derived from the primary skin fibroblasts of seven individuals using next-generation sequencing. We find that, on average, an iPSC line manifests two copy number variants (CNVs) not apparent in the fibroblasts from which the iPSC was derived. Using PCR and digital droplet PCR, we show that at least 50% of those CNVs are present as low-frequency somatic genomic variants in parental fibroblasts (that is, the fibroblasts from which each corresponding human iPSC line is derived), and are manifested in iPSC lines owing to their clonal origin. Hence, reprogramming does not necessarily lead to de novo CNVs in iPSCs, because most of the line-manifested CNVs reflect somatic mosaicism in the human skin. Moreover, our findings demonstrate that clonal expansion, and iPSC lines in particular, can be used as a discovery tool to reliably detect low-frequency CNVs in the tissue of origin. Overall, we estimate that approximately 30% of the fibroblast cells have somatic CNVs in their genomes, suggesting widespread somatic mosaicism in the human body. Our study paves the way to understanding the fundamental question of the extent to which cells of the human body normally acquire structural alterations in their DNA post-zygotically.
C1 [Abyzov, Alexej; Mariani, Jessica; Palejev, Dean; Zhang, Ying; Tomasini, Livia; Ferrandino, Anthony F.; Belmaker, Lior A. Rosenberg; Szekely, Anna; Wilson, Michael; Kocabas, Arif; Calixto, Nathaniel E.; Grigorenko, Elena L.; Huttner, Anita; Chawarska, Katarzyna; Weissman, Sherman; Urban, Alexander Eckehart; Gerstein, Mark; Vaccarino, Flora M.] Yale Univ, Program Neurodev & Regenerat, New Haven, CT 06520 USA.
   [Abyzov, Alexej; Wilson, Michael; Gerstein, Mark] Yale Univ, Program Computat Biol & Bioinformat, New Haven, CT 06520 USA.
   [Abyzov, Alexej; Gerstein, Mark] Yale Univ, Dept Mol Biophys & Biochem, New Haven, CT 06520 USA.
   [Mariani, Jessica; Palejev, Dean; Tomasini, Livia; Ferrandino, Anthony F.; Belmaker, Lior A. Rosenberg; Wilson, Michael; Kocabas, Arif; Calixto, Nathaniel E.; Grigorenko, Elena L.; Chawarska, Katarzyna; Vaccarino, Flora M.] Yale Univ, Ctr Child Study, New Haven, CT 06520 USA.
   [Zhang, Ying; Szekely, Anna; Weissman, Sherman] Yale Univ, Dept Genet, New Haven, CT 06520 USA.
   [Haney, Michael Seamus; Urban, Alexander Eckehart] Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA.
   [Haney, Michael Seamus; Urban, Alexander Eckehart] Stanford Univ, Sch Med, Dept Genet, Stanford, CA 94305 USA.
   [Szekely, Anna] Yale Univ, Dept Neurol, New Haven, CT 06520 USA.
   [Grigorenko, Elena L.] Yale Univ, Dept Psychol, New Haven, CT 06520 USA.
   [Grigorenko, Elena L.] Yale Univ, Dept Epidemiol & Publ Hlth, New Haven, CT 06520 USA.
   [Huttner, Anita] Yale Univ, Dept Pathol, New Haven, CT 06520 USA.
   [Gerstein, Mark] Yale Univ, Dept Comp Sci, New Haven, CT 06520 USA.
   [Vaccarino, Flora M.] Yale Univ, Dept Neurobiol, New Haven, CT 06520 USA.
C3 Yale University; Yale University; Yale University; Yale University; Yale University; Stanford University; Stanford University; Yale University; Yale University; Yale University; Yale University; Yale University; Yale University
RP Vaccarino, FM (corresponding author), Yale Univ, Program Neurodev & Regenerat, New Haven, CT 06520 USA.
EM aeurban@stanford.edu; mark.gerstein@yale.edu; flora.vaccarino@yale.edu
FU National Institutes of Health (NIH); AL Williams Professorship fund; Harris Professorship fund; NIMH [MH089176, MH087879]; Simons Foundation [SFARI 137055]; State of Connecticut; NIH [RR19895]
NR 48
TC 297
Z9 338
U1 0
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 DEC 20
PY 2012
VL 492
IS 7429
BP 438
EP +
DI 10.1038/nature11629
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 056KQ
UT WOS:000312488200058
PM 23160490
DA 2026-03-09
ER

PT J
AU Nandakumar, J
   Bell, CF
   Weidenfeld, I
   Zaug, AJ
   Leinwand, LA
   Cech, TR
AF Nandakumar, Jayakrishnan
   Bell, Caitlin F.
   Weidenfeld, Ina
   Zaug, Arthur J.
   Leinwand, Leslie A.
   Cech, Thomas R.
TI The TEL patch of telomere protein TPP1 mediates telomerase recruitment and processivity
SO NATURE
LA English
DT Article
ID single-stranded-dna; fission yeast; length regulator; pot1; protection; gene; localization; tel1(atm); interacts; requires
AB Human chromosome ends are capped by shelterin, a protein complex that protects the natural ends from being recognized as sites of DNA damage and also regulates the telomere-replicating enzyme, telomerase(1-3). Shelterin includes the heterodimeric POT1-TPP1 protein, which binds the telomeric single-stranded DNA tail(4-9). TPP1 has been implicated both in recruiting telomerase to telomeres and in stimulating telomerase processivity (the addition of multiple DNA repeats after a single primer-binding event)(9-14). Determining the mechanisms of these activities has been difficult, especially because genetic perturbations also tend to affect the essential chromosome end-protection function of TPP1 (refs 15-17). Here we identify separation-of-function mutants of human TPP1 that retain full telomere-capping function in vitro and in vivo, yet are defective in binding human telomerase. The seven separation-of-function mutations map to a patch of amino acids on the surface of TPP1, the TEL patch, that both recruits telomerase to telomeres and promotes high-processivity DNA synthesis, indicating that these two activities are manifestations of the same molecular interaction. Given that the interaction between telomerase and TPP1 is required for telomerase function in vivo, the TEL patch of TPP1 provides a new target for anticancer drug development.
C1 [Nandakumar, Jayakrishnan; Bell, Caitlin F.; Weidenfeld, Ina; Zaug, Arthur J.; Leinwand, Leslie A.; Cech, Thomas R.] Univ Colorado, BioFrontiers Inst, Boulder, CO 80309 USA.
   [Nandakumar, Jayakrishnan; Bell, Caitlin F.; Zaug, Arthur J.; Cech, Thomas R.] Univ Colorado, Dept Chem & Biochem, Boulder, CO 80309 USA.
   [Nandakumar, Jayakrishnan; Bell, Caitlin F.; Zaug, Arthur J.; Cech, Thomas R.] Univ Colorado, Howard Hughes Med Inst, Boulder, CO 80309 USA.
   [Weidenfeld, Ina; Leinwand, Leslie A.; Cech, Thomas R.] Univ Colorado, Dept Mol Cellular & Dev Biol, Boulder, CO 80309 USA.
C3 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
RP Cech, TR (corresponding author), Univ Colorado, BioFrontiers Inst, Boulder, CO 80309 USA.
EM thomas.cech@colorado.edu
FU National Cancer Institute of the National Institutes of Health [K99CA167644]; US National Institutes of Health [R01GM29090, R01GM099705]; National Institute of General Medical Sciences [R01GM029090] Funding Source: NIH RePORTER
NR 33
TC 284
Z9 359
U1 2
U2 44
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD DEC 13
PY 2012
VL 492
IS 7428
BP 285
EP +
DI 10.1038/nature11648
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 053GM
UT WOS:000312259300049
PM 23103865
DA 2026-03-09
ER

PT J
AU Deschamps, P
   Durand, N
   Bard, E
   Hamelin, B
   Camoin, G
   Thomas, AL
   Henderson, GM
   Okuno, J
   Yokoyama, Y
AF Deschamps, Pierre
   Durand, Nicolas
   Bard, Edouard
   Hamelin, Bruno
   Camoin, Gilbert
   Thomas, Alexander L.
   Henderson, Gideon M.
   Okuno, Jun'ichi
   Yokoyama, Yusuke
TI Ice-sheet collapse and sea-level rise at the Bolling warming 14,600 years ago
SO NATURE
LA English
DT Article
ID last glacial maximum; meltwater pulse 1a; younger dryas; southern-ocean; reef; deglaciation; constraints; circulation; resumption; trigger
AB Past sea-level records provide invaluable information about the response of ice sheets to climate forcing. Some such records suggest that the last deglaciation was punctuated by a dramatic period of sea-level rise, of about 20 metres, in less than 500 years. Controversy about the amplitude and timing of this meltwater pulse (MWP-1A) has, however, led to uncertainty about the source of the melt water and its temporal and causal relationships with the abrupt climate changes of the deglaciation. Here we show that MWP-1A started no earlier than 14,650 years ago and ended before 14,310 years ago, making it coeval with the Bolling warming. Our results, based on corals drilled offshore from Tahiti during Integrated Ocean Drilling Project Expedition 310, reveal that the increase in sea level at Tahiti was between 12 and 22 metres, with a most probable value between 14 and 18 metres, establishing a significant meltwater contribution from the Southern Hemisphere. This implies that the rate of eustatic sea-level rise exceeded 40 millimetres per year during MWP-1A.
C1 [Deschamps, Pierre; Durand, Nicolas; Bard, Edouard; Hamelin, Bruno; Camoin, Gilbert] UMR Aix Marseille Univ, CNRS, IRD, Coll France,CEREGE, F-13545 Aix En Provence 4, France.
   [Thomas, Alexander L.; Henderson, Gideon M.] Dept Earth Sci, Oxford OX1 3AN, England.
   [Okuno, Jun'ichi; Yokoyama, Yusuke] Univ Tokyo, Atmosphere & Ocean Res Inst, Kashiwa, Chiba 2778564, Japan.
   [Okuno, Jun'ichi; Yokoyama, Yusuke] Univ Tokyo, Dept Earth & Planetary Sci, Kashiwa, Chiba 2778564, Japan.
   [Okuno, Jun'ichi] Natl Inst Polar Res, Tachikawa, Tokyo 1908518, Japan.
   [Yokoyama, Yusuke] JAMSTEC, Inst Biogeosci, Yokosuka, Kanagawa 2370061, Japan.
C3 Universite PSL; College de France; Aix-Marseille Universite; Institut de Recherche pour le Developpement (IRD); Centre National de la Recherche Scientifique (CNRS); University of Tokyo; University of Tokyo; Research Organization of Information & Systems (ROIS); National Institute of Polar Research (NIPR) - Japan; Japan Agency for Marine-Earth Science & Technology (JAMSTEC)
RP Deschamps, P (corresponding author), UMR Aix Marseille Univ, CNRS, IRD, Coll France,CEREGE, Technopole Arbois,BP 80, F-13545 Aix En Provence 4, France.
EM deschamps@cerege.fr
FU Comer Science and Education Foundation; European Science Foundation (EuroMARC); European Community; College de France; IRD (Institut de Recherche pour le Developpement); UK Natural Environment Research Council [NE/D001250/1]; JSPS [GR031]; Natural Environment Research Council [NE/D001250/1] Funding Source: researchfish; NERC [NE/D001250/1] Funding Source: UKRI; Grants-in-Aid for Scientific Research [21253001, 23501255] Funding Source: KAKEN
NR 50
TC 452
Z9 514
U1 4
U2 210
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 29
PY 2012
VL 483
IS 7391
BP 559
EP 564
DI 10.1038/nature10902
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 915EF
UT WOS:000302006100031
PM 22460900
DA 2026-03-09
ER

PT J
AU Israel, MA
   Yuan, SH
   Bardy, C
   Reyna, SM
   Mu, YL
   Herrera, C
   Hefferan, MP
   Van Gorp, S
   Nazor, KL
   Boscolo, FS
   Carson, CT
   Laurent, LC
   Marsala, M
   Gage, FH
   Remes, AM
   Koo, EH
   Goldstein, LSB
AF Israel, Mason A.
   Yuan, Shauna H.
   Bardy, Cedric
   Reyna, Sol M.
   Mu, Yangling
   Herrera, Cheryl
   Hefferan, Michael P.
   Van Gorp, Sebastiaan
   Nazor, Kristopher L.
   Boscolo, Francesca S.
   Carson, Christian T.
   Laurent, Louise C.
   Marsala, Martin
   Gage, Fred H.
   Remes, Anne M.
   Koo, Edward H.
   Goldstein, Lawrence S. B.
TI Probing sporadic and familial Alzheimer's disease using induced pluripotent stem cells
SO NATURE
LA English
DT Article
ID amyloid beta-protein; microtubule-binding; senile plaques; down-syndrome; mouse model; tau; app; phosphorylation; fibroblasts; dysfunction
AB Our understanding of Alzheimer's disease pathogenesis is currently limited by difficulties in obtaining live neurons from patients and the inability to model the sporadic form of the disease. It may be possible to overcome these challenges by reprogramming primary cells from patients into induced pluripotent stem cells (iPSCs). Here we reprogrammed primary fibroblasts from two patients with familial Alzheimer's disease, both caused by a duplication of the amyloid-beta precursor protein gene(1) (APP; termed APP(Dp)), two with sporadic Alzheimer's disease (termed sAD1, sAD2) and two non-demented control individuals into iPSC lines. Neurons from differentiated cultures were purified with fluorescence-activated cell sorting and characterized. Purified cultures contained more than 90% neurons, clustered with fetal brain messenger RNA samples by microarray criteria, and could form functional synaptic contacts. Virtually all cells exhibited normal electrophysiological activity. Relative to controls, iPSC-derived, purified neurons from the two APP(Dp) patients and patient sAD2 exhibited significantly higher levels of the pathological markers amyloid-beta(1-40), phospho-tau(Thr 231) and active glycogen synthase kinase-3 beta (aGSK-3 beta). Neurons from APP(Dp) and sAD2 patients also accumulated large RAB5-positive early endosomes compared to controls. Treatment of purified neurons with beta-secretase inhibitors, but not gamma-secretase inhibitors, caused significant reductions in phospho-Tau(Thr 231) and aGSK-3 beta levels. These results suggest a direct relationship between APP proteolytic processing, but not amyloid-beta, in GSK-3 beta activation and tau phosphorylation in human neurons. Additionally, we observed that neurons with the genome of one sAD patient exhibited the phenotypes seen in familial Alzheimer's disease samples. More generally, we demonstrate that iPSC technology can be used to observe phenotypes relevant to Alzheimer's disease, even though it can take decades for overt disease to manifest in patients.
C1 [Israel, Mason A.; Yuan, Shauna H.; Reyna, Sol M.; Herrera, Cheryl; Goldstein, Lawrence S. B.] Univ Calif San Diego, Howard Hughes Med Inst, La Jolla, CA 92093 USA.
   [Israel, Mason A.; Yuan, Shauna H.; Reyna, Sol M.; Herrera, Cheryl; Goldstein, Lawrence S. B.] Univ Calif San Diego, Dept Cellular & Mol Med, La Jolla, CA 92093 USA.
   [Israel, Mason A.; Reyna, Sol M.] Univ Calif San Diego, Biomed Sci Grad Program, La Jolla, CA 92093 USA.
   [Yuan, Shauna H.; Koo, Edward H.; Goldstein, Lawrence S. B.] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA.
   [Bardy, Cedric; Mu, Yangling; Gage, Fred H.] Salk Inst Biol Studies, La Jolla, CA 92037 USA.
   [Hefferan, Michael P.; Marsala, Martin] Univ Calif San Diego, Dept Anesthesiol, La Jolla, CA 92093 USA.
   [Van Gorp, Sebastiaan] Maastricht Univ, Med Ctr, Dept Anesthesiol, NL-6202 AZ Maastricht, Netherlands.
   [Nazor, Kristopher L.] Scripps Res Inst, Dept Physiol Chem, La Jolla, CA 92037 USA.
   [Boscolo, Francesca S.; Laurent, Louise C.] Univ Calif San Diego, Dept Reprod Med, La Jolla, CA 92093 USA.
   [Carson, Christian T.] BD Biosci, La Jolla, CA 92037 USA.
   [Marsala, Martin] Slovak Acad Sci, Inst Neurobiol, SK-04001 Kosice, Slovakia.
   [Remes, Anne M.] Univ Oulu, Neurol & Clin Res Ctr, Dept Clin Med, FIN-90015 Oulu, Finland.
C3 University of California System; University of California San Diego; Howard Hughes Medical Institute; University of California System; University of California San Diego; University of California System; University of California San Diego; University of California System; University of California San Diego; Salk Institute; University of California System; University of California San Diego; Maastricht University; Scripps Research Institute; University of California System; University of California San Diego; Slovak Academy of Sciences; Institute of Neurobiology, SAS; University of Oulu
RP Goldstein, LSB (corresponding author), Univ Calif San Diego, Howard Hughes Med Inst, La Jolla, CA 92093 USA.
EM lgoldstein@ucsd.edu
FU University of California, San Diego (UCSD) Alzheimer's Disease Research Center [AGO 5131]; UCSD [P30 NS047101]; California Institute of Regenerative Medicine (CIRM) [TR1-01250, CL1-00502, RM1-01717]; FP7 Marie Curie IOF; Weatherstone Foundation; National Institutes of Health [K12 HD001259]; Hartwell Foundation; Lookout Fund; McDonnell Foundation; Eunice Kennedy Shriver National Institute of Child Health and Human Development [K12HD001259] Funding Source: NIH RePORTER; National Institute of General Medical Sciences [T32GM008666] Funding Source: NIH RePORTER; National Institute of Neurological Disorders and Stroke [P30NS047101] Funding Source: NIH RePORTER
NR 36
TC 954
Z9 1170
U1 2
U2 405
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 9
PY 2012
VL 482
IS 7384
BP 216
EP U107
DI 10.1038/nature10821
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 888HI
UT WOS:000299994100038
PM 22278060
DA 2026-03-09
ER

PT J
AU Durkin, K
   Coppieters, W
   Drögemüller, C
   Ahariz, N
   Cambisano, N
   Druet, T
   Fasquelle, C
   Haile, A
   Horin, P
   Huang, LS
   Kamatani, Y
   Karim, L
   Lathrop, M
   Moser, S
   Oldenbroek, K
   Rieder, S
   Sartelet, A
   Sölkner, J
   Stålhammar, H
   Zelenika, D
   Zhang, ZY
   Leeb, T
   Georges, M
   Charlier, C
AF Durkin, Keith
   Coppieters, Wouter
   Droegemueller, Cord
   Ahariz, Naima
   Cambisano, Nadine
   Druet, Tom
   Fasquelle, Corinne
   Haile, Aynalem
   Horin, Petr
   Huang, Lusheng
   Kamatani, Yohichiro
   Karim, Latifa
   Lathrop, Mark
   Moser, Simon
   Oldenbroek, Kor
   Rieder, Stefan
   Sartelet, Arnaud
   Soelkner, Johann
   Stalhammar, Hans
   Zelenika, Diana
   Zhang, Zhiyan
   Leeb, Tosso
   Georges, Michel
   Charlier, Carole
TI Serial translocation by means of circular intermediates underlies colour sidedness in cattle
SO NATURE
LA English
DT Article
ID gene; pattern
AB Colour sidedness is a dominantly inherited phenotype of cattle characterized by the polarization of pigmented sectors on the flanks, snout and ear tips(1). It is also referred to as 'lineback' or 'witrik' (which means white back), as colour-sided animals typically display a white band along their spine. Colour sidedness is documented at least since the Middle Ages and is presently segregating in several cattle breeds around the globe, including in Belgian blue and brown Swiss(1,2). Here we report that colour sidedness is determined by a first allele on chromosome 29 (Cs-29), which results from the translocation of a 492-kilobase chromosome 6 segment encompassing KIT to chromosome 29, and a second allele on chromosome 6 (Cs-6), derived from the first by repatriation of fused 575-kilobase chromosome 6 and 29 sequences to the KIT locus. We provide evidence that both translocation events involved circular intermediates. This is the first example, to our knowledge, of a phenotype determined by homologous yet non-syntenic alleles that result from a novel copy-number-variant-generating mechanism.
C1 [Durkin, Keith; Coppieters, Wouter; Ahariz, Naima; Cambisano, Nadine; Druet, Tom; Fasquelle, Corinne; Karim, Latifa; Sartelet, Arnaud; Zhang, Zhiyan; Georges, Michel; Charlier, Carole] Univ Liege B34, GIGA R, Unit Anim Genom, B-4000 Liege, Sart Tilman, Belgium.
   [Durkin, Keith; Coppieters, Wouter; Ahariz, Naima; Cambisano, Nadine; Druet, Tom; Fasquelle, Corinne; Karim, Latifa; Sartelet, Arnaud; Zhang, Zhiyan; Georges, Michel; Charlier, Carole] Univ Liege B34, Fac Vet Med, B-4000 Liege, Sart Tilman, Belgium.
   [Droegemueller, Cord; Leeb, Tosso] Univ Bern, Inst Genet, CH-3001 Bern, Switzerland.
   [Haile, Aynalem] ICARDA, Aleppo, Syria.
   [Horin, Petr] Univ Vet & Pharmaceut Sci Brno, Inst Genet, Brno 61242, Czech Republic.
   [Huang, Lusheng] Key Lab Anim Biotechnol Jiangxi Prov, Nanchang 330045, Jiangxi, Peoples R China.
   [Huang, Lusheng] Minist Agr China, Nanchang 330045, Jiangxi, Peoples R China.
   [Kamatani, Yohichiro; Lathrop, Mark; Zelenika, Diana] Ctr Etud Polymorphisme Humain, Fdn Jean Dausset, F-75012 Paris, France.
   [Kamatani, Yohichiro; Lathrop, Mark; Zelenika, Diana] CEA IC Ctr Natl Genotypage, F-91057 Evry, France.
   [Moser, Simon; Rieder, Stefan] Bern Univ Appl Sci, Swiss Coll Agr, CH-3052 Zollikofen, Switzerland.
   [Oldenbroek, Kor] Ctr Genet Resources Netherlands CGN, NL-6701 BH Wageningen, Netherlands.
   [Soelkner, Johann] Univ Nat Resources & Appl Life Sci, Div Livestock Sci, A-1180 Vienna, Austria.
   [Stalhammar, Hans] Viking Genet, S-53221 Ornsro, Skara, Sweden.
C3 University of Liege; University of Liege; University of Bern; CGIAR; International Center for Agricultural Research in the Dry Areas (ICARDA); University of Veterinary Sciences Brno; Foundation Jean Dausset-CEPH; CEA; Universite Paris Saclay; BOKU University
RP Georges, M (corresponding author), Univ Liege B34, GIGA R, Unit Anim Genom, 1 Ave Hop, B-4000 Liege, Sart Tilman, Belgium.
EM michel.georges@ulg.ac.be
FU Walloon Direction General Operationnelle Agriculture, Resources Naturelles et Environnement [D31-1206, D31-1214]; Swiss National Science Foundation [31003A_133034]; GIGA-R; Swiss National Science Foundation (SNF) [31003A_133034] Funding Source: Swiss National Science Foundation (SNF)
NR 22
TC 139
Z9 162
U1 1
U2 37
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 2
PY 2012
VL 482
IS 7383
BP 81
EP U103
DI 10.1038/nature10757
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 884RN
UT WOS:000299726000039
PM 22297974
DA 2026-03-09
ER

PT J
AU Hooper, DU
   Adair, EC
   Cardinale, BJ
   Byrnes, JEK
   Hungate, BA
   Matulich, KL
   Gonzalez, A
   Duffy, JE
   Gamfeldt, L
   O'Connor, MI
AF Hooper, David U.
   Adair, E. Carol
   Cardinale, Bradley J.
   Byrnes, Jarrett E. K.
   Hungate, Bruce A.
   Matulich, Kristin L.
   Gonzalez, Andrew
   Duffy, J. Emmett
   Gamfeldt, Lars
   O'Connor, Mary I.
TI A global synthesis reveals biodiversity loss as a major driver of ecosystem change
SO NATURE
LA English
DT Article
ID species-diversity; plant diversity; elevated co2; terrestrial ecosystems; productivity; community; nitrogen; consequences; grassland; responses
AB Evidence is mounting that extinctions are altering key processes important to the productivity and sustainability of Earth's ecosystems(1-4). Further species loss will accelerate change in ecosystem processes(5-8), but it is unclear how these effects compare to the direct effects of other forms of environmental change that are both driving diversity loss and altering ecosystem function. Here we use a suite of meta-analyses of published data to show that the effects of species loss on productivity and decomposition-two processes important in all ecosystems-are of comparable magnitude to the effects of many other global environmental changes. In experiments, intermediate levels of species loss (21-40%) reduced plant production by 5-10%, comparable to previously documented effects of ultraviolet radiation and climate warming. Higher levels of extinction (41-60%) had effects rivalling those of ozone, acidification, elevated CO2 and nutrient pollution. At intermediate levels, species loss generally had equal or greater effects on decomposition than did elevated CO2 and nitrogen addition. The identity of species lost also had a large effect on changes in productivity and decomposition, generating a wide range of plausible outcomes for extinction. Despite the need for more studies on interactive effects of diversity loss and environmental changes, our analyses clearly show that the ecosystem consequences of local species loss are as quantitatively significant as the direct effects of several global change stressors that have mobilized major international concern and remediation efforts(9).
C1 [Hooper, David U.] Western Washington Univ, Dept Biol, Bellingham, WA 98225 USA.
   [Adair, E. Carol; Byrnes, Jarrett E. K.; O'Connor, Mary I.] Natl Ctr Ecol Anal & Synth, Santa Barbara, CA 93101 USA.
   [Adair, E. Carol] Univ Vermont, Rubenstein Sch Environm & Nat Resources, Aiken Ctr, Burlington, VT 05405 USA.
   [Cardinale, Bradley J.] Univ Michigan, Sch Nat Resources & Environm, Ann Arbor, MI 48109 USA.
   [Hungate, Bruce A.] No Arizona Univ, Dept Biol Sci, Flagstaff, AZ 86011 USA.
   [Matulich, Kristin L.] Univ Calif Irvine, Dept Ecol & Evolutionary Biol, Irvine, CA 92697 USA.
   [Gonzalez, Andrew] McGill Univ, Dept Biol, Montreal, PQ H3A 1B1, Canada.
   [Duffy, J. Emmett] Coll William & Mary, Virginia Inst Marine Sci, Gloucester Point, VA 23062 USA.
   [Gamfeldt, Lars] Univ Gothenburg, Dept Biol & Environm Sci, SE-40530 Gothenburg, Sweden.
   [O'Connor, Mary I.] Univ British Columbia, Dept Zool, Vancouver, BC V6T 1Z4, Canada.
C3 Western Washington University; University of California System; University of California Santa Barbara; University of Vermont; University of Michigan System; University of Michigan; Northern Arizona University; University of California System; University of California Irvine; McGill University; William & Mary; Virginia Institute of Marine Science; University of Gothenburg; University of British Columbia
RP Hooper, DU (corresponding author), Western Washington Univ, Dept Biol, Bellingham, WA 98225 USA.
EM hooper@biol.wwu.edu
FU National Center for Ecological Analysis and Synthesis (NCEAS); University of California Santa Barbara; National Science Foundation [OCE-1031061, DEB-1046121]; Swedish Research Council VR [621-2009-5457]; Canada Research Chair Program; NSERC; Direct For Biological Sciences [1046121] Funding Source: National Science Foundation; Directorate For Geosciences; Division Of Ocean Sciences [1031061] Funding Source: National Science Foundation; Division Of Environmental Biology [1046121] Funding Source: National Science Foundation
NR 46
TC 1757
Z9 2142
U1 54
U2 2550
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUN 7
PY 2012
VL 486
IS 7401
BP 105
EP U129
DI 10.1038/nature11118
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 953GD
UT WOS:000304854000036
PM 22678289
DA 2026-03-09
ER

PT J
AU Smetacek, V
   Klaas, C
   Strass, VH
   Assmy, P
   Montresor, M
   Cisewski, B
   Savoye, N
   Webb, A
   d'Ovidio, F
   Arrieta, JM
   Bathmann, U
   Bellerby, R
   Berg, GM
   Croot, P
   Gonzalez, S
   Henjes, J
   Herndl, GJ
   Hoffmann, LJ
   Leach, H
   Losch, M
   Mills, MM
   Neill, C
   Peeken, I
   Röttgers, R
   Sachs, O
   Sauter, E
   Schmidt, MM
   Schwarz, J
   Terbrüggen, A
   Wolf-Gladrow, D
AF Smetacek, Victor
   Klaas, Christine
   Strass, Volker H.
   Assmy, Philipp
   Montresor, Marina
   Cisewski, Boris
   Savoye, Nicolas
   Webb, Adrian
   d'Ovidio, Francesco
   Arrieta, Jesus M.
   Bathmann, Ulrich
   Bellerby, Richard
   Berg, Gry Mine
   Croot, Peter
   Gonzalez, Santiago
   Henjes, Joachim
   Herndl, Gerhard J.
   Hoffmann, Linn J.
   Leach, Harry
   Losch, Martin
   Mills, Matthew M.
   Neill, Craig
   Peeken, Ilka
   Roettgers, Ruediger
   Sachs, Oliver
   Sauter, Eberhard
   Schmidt, Maike M.
   Schwarz, Jill
   Terbrueggen, Anja
   Wolf-Gladrow, Dieter
TI Deep carbon export from a Southern Ocean iron-fertilized diatom bloom
SO NATURE
LA English
DT Article
ID atmospheric co2; sea-floor; cycles; model
AB Fertilization of the ocean by adding iron compounds has induced diatom-dominated phytoplankton blooms accompanied by considerable carbon dioxide drawdown in the ocean surface layer. However, because the fate of bloom biomass could not be adequately resolved in these experiments, the timescales of carbon sequestration from the atmosphere are uncertain. Here we report the results of a five-week experiment carried out in the closed core of a vertically coherent, mesoscale eddy of the Antarctic Circumpolar Current, during which we tracked sinking particles from the surface to the deep-sea floor. A large diatom bloom peaked in the fourth week after fertilization. This was followed by mass mortality of several diatom species that formed rapidly sinking, mucilaginous aggregates of entangled cells and chains. Taken together, multiple lines of evidence-although each with important uncertainties-lead us to conclude that at least half the bloom biomass sank far below a depth of 1,000 metres and that a substantial portion is likely to have reached the sea floor. Thus, iron-fertilized diatom blooms may sequester carbon for timescales of centuries in ocean bottom water and for longer in the sediments.
C1 [Smetacek, Victor; Klaas, Christine; Strass, Volker H.; Assmy, Philipp; Cisewski, Boris; Bathmann, Ulrich; Henjes, Joachim; Losch, Martin; Peeken, Ilka; Sachs, Oliver; Sauter, Eberhard; Schwarz, Jill; Terbrueggen, Anja; Wolf-Gladrow, Dieter] Alfred Wegener Inst Polar & Marine Res, D-27570 Bremerhaven, Germany.
   [Smetacek, Victor] Natl Inst Oceanog, Panaji 403004, Goa, India.
   [Assmy, Philipp] Norwegian Polar Res Inst, Fram Ctr, N-9296 Tromso, Norway.
   [Montresor, Marina] Stn Zool Anton Dohrn, I-80121 Naples, Italy.
   [Cisewski, Boris] Johann Heinrich von Thunen Inst, Inst Sea Fisheries, D-22767 Hamburg, Germany.
   [Savoye, Nicolas] Vrije Univ Brussel, Dept Analyt & Environm Chem, B-1050 Brussels, Belgium.
   [Savoye, Nicolas] Univ Bordeaux, CNRS, EPOC, UMR 5805,Stn Marine Arcachon, F-33120 Arcachon, France.
   [Webb, Adrian] Univ Cape Town, Dept Oceanog, ZA-7701 Cape Town, South Africa.
   [d'Ovidio, Francesco] CNRS UPMC IRD MNHN, LOCEAN IPSL, F-75252 Paris, France.
   [Arrieta, Jesus M.; Gonzalez, Santiago; Herndl, Gerhard J.] Royal Netherlands Inst Sea Res, Dept Biol Oceanog, NL-1790 AB Den Burg, Netherlands.
   [Arrieta, Jesus M.] CSIC UIB, Inst Mediterraneo Estudios Avanzados, Dept Global Change Res, Esporles 07190, Mallorca, Spain.
   [Bathmann, Ulrich] Leibniz Inst Balt Sea Res Warnemunde, D-18119 Rostock, Germany.
   [Bellerby, Richard; Neill, Craig] Univ Bergen, Bjerknes Ctr Climate Res, N-5007 Bergen, Norway.
   [Bellerby, Richard] Norwegian Inst Water Res, N-5006 Bergen, Norway.
   [Berg, Gry Mine; Mills, Matthew M.] Stanford Univ, Dept Environm Earth Syst Sci, Stanford, CA 94305 USA.
   [Croot, Peter; Hoffmann, Linn J.] Helmholtz Ctr Ocean Res Kiel, D-24105 Kiel, Germany.
   [Croot, Peter] Natl Univ Ireland, Sch Nat Sci, Galway, Ireland.
   [Henjes, Joachim] Phytolut GmbH, D-28759 Bremen, Germany.
   [Herndl, Gerhard J.] Univ Vienna, Dept Marine Biol, A-1090 Vienna, Austria.
   [Leach, Harry] Univ Liverpool, Sch Environm Sci, Liverpool L69 3GP, Merseyside, England.
   [Neill, Craig] Commonwealth Sci & Ind Res Org, Wealth Oceans Flagship, Hobart, Tas 7000, Australia.
   [Peeken, Ilka] Univ Bremen, MARUM Ctr Marine Environm Sci, D-28359 Bremen, Germany.
   [Roettgers, Ruediger] Helmholtz Zentrum Geesthacht, Ctr Mat & Coastal Res, Inst Coastal Res, D-21502 Geesthacht, Germany.
   [Sachs, Oliver] Eberhard & Partner AG, CH-5000 Aarau, Switzerland.
   [Schmidt, Maike M.] Univ Bremen, Ctr Biomol Interact Bremen, FB 2, D-28359 Bremen, Germany.
   [Schwarz, Jill] Univ Plymouth, Sch Marine Sci & Engn, Plymouth PL4 8AA, Devon, England.
C3 Helmholtz Association; Alfred Wegener Institute, Helmholtz Centre for Polar & Marine Research; Council of Scientific & Industrial Research (CSIR) - India; CSIR - National Institute of Oceanography (NIO); Norwegian Polar Institute; Stazione Zoologica Anton Dohrn; Johann Heinrich von Thunen Institute; Vrije Universiteit Brussel; Universite de Bordeaux; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Earth Sciences & Astronomy (INSU); University of Cape Town; Sorbonne Universite; Museum National d'Histoire Naturelle (MNHN); Institut de Recherche pour le Developpement (IRD); Centre National de la Recherche Scientifique (CNRS); Utrecht University; Royal Netherlands Institute for Sea Research (NIOZ); Consejo Superior de Investigaciones Cientificas (CSIC); University of Barcelona; Universitat de les Illes Balears; Leibniz Institut fur Ostseeforschung Warnemunde; Bjerknes Centre for Climate Research; University of Bergen; Norwegian Institute for Water Research (NIVA); Stanford University; Helmholtz Association; GEOMAR Helmholtz Center for Ocean Research Kiel; Ollscoil na Gaillimhe-University of Galway; University of Vienna; University of Liverpool; Commonwealth Scientific & Industrial Research Organisation (CSIRO); University of Bremen; Helmholtz Association; Helmholtz-Zentrum Hereon; University of Bremen; University of Plymouth
RP Smetacek, V (corresponding author), Alfred Wegener Inst Polar & Marine Res, Handelshafen 12, D-27570 Bremerhaven, Germany.
EM victor.smetacek@awi.de; christine.klaas@awi.de
FU Cnes
NR 24
TC 329
Z9 383
U1 6
U2 500
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUL 19
PY 2012
VL 487
IS 7407
BP 313
EP 319
DI 10.1038/nature11229
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 975JB
UT WOS:000306506500032
PM 22810695
DA 2026-03-09
ER

PT J
AU Yu, M
   Ting, DT
   Stott, SL
   Wittner, BS
   Ozsolak, F
   Paul, S
   Ciciliano, JC
   Smas, ME
   Winokur, D
   Gilman, AJ
   Ulman, MJ
   Xega, K
   Contino, G
   Alagesan, B
   Brannigan, BW
   Milos, PM
   Ryan, DP
   Sequist, LV
   Bardeesy, N
   Ramaswamy, S
   Toner, M
   Maheswaran, S
   Haber, DA
AF Yu, Min
   Ting, David T.
   Stott, Shannon L.
   Wittner, Ben S.
   Ozsolak, Fatih
   Paul, Suchismita
   Ciciliano, Jordan C.
   Smas, Malgorzata E.
   Winokur, Daniel
   Gilman, Anna J.
   Ulman, Matthew J.
   Xega, Kristina
   Contino, Gianmarco
   Alagesan, Brinda
   Brannigan, Brian W.
   Milos, Patrice M.
   Ryan, David P.
   Sequist, Lecia V.
   Bardeesy, Nabeel
   Ramaswamy, Sridhar
   Toner, Mehmet
   Maheswaran, Shyamala
   Haber, Daniel A.
TI RNA sequencing of pancreatic circulating tumour cells implicates WNT signalling in metastasis
SO NATURE
LA English
DT Article
ID stem-cell; transcriptome; pathway
AB Circulating tumour cells (CTCs) shed into blood from primary cancers include putative precursors that initiate distal metastases(1). Although these cells are extraordinarily rare, they may identify cellular pathways contributing to the blood-borne dissemination of cancer. Here, we adapted a microfluidic device(2) for efficient capture of CTCs from an endogenous mouse pancreatic cancer model(3) and subjected CTCs to single-molecule RNA sequencing(4), identifying Wnt2 as a candidate gene enriched in CTCs. Expression of WNT2 in pancreatic cancer cells suppresses anoikis, enhances anchorage-independent sphere formation, and increases metastatic propensity in vivo. This effect is correlated with fibronectin upregulation and suppressed by inhibition of MAP3K7 (also known as TAK1) kinase. In humans, formation of non-adherent tumour spheres by pancreatic cancer cells is associated with upregulation of multiple WNT genes, and pancreatic CTCs revealed enrichment for WNT signalling in 5 out of 11 cases. Thus, molecular analysis of CTCs may identify candidate therapeutic targets to prevent the distal spread of cancer.
C1 [Yu, Min; Ting, David T.; Stott, Shannon L.; Wittner, Ben S.; Paul, Suchismita; Ciciliano, Jordan C.; Smas, Malgorzata E.; Winokur, Daniel; Gilman, Anna J.; Ulman, Matthew J.; Xega, Kristina; Contino, Gianmarco; Alagesan, Brinda; Brannigan, Brian W.; Ryan, David P.; Sequist, Lecia V.; Bardeesy, Nabeel; Ramaswamy, Sridhar; Toner, Mehmet; Maheswaran, Shyamala; Haber, Daniel A.] Massachusetts Gen Hosp, Ctr Canc, Ctr Engn Med, Boston, MA 02114 USA.
   [Yu, Min; Ting, David T.; Stott, Shannon L.; Wittner, Ben S.; Paul, Suchismita; Ciciliano, Jordan C.; Smas, Malgorzata E.; Winokur, Daniel; Gilman, Anna J.; Ulman, Matthew J.; Xega, Kristina; Contino, Gianmarco; Alagesan, Brinda; Brannigan, Brian W.; Ryan, David P.; Sequist, Lecia V.; Bardeesy, Nabeel; Ramaswamy, Sridhar; Toner, Mehmet; Maheswaran, Shyamala; Haber, Daniel A.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA.
   [Yu, Min; Ting, David T.; Stott, Shannon L.; Wittner, Ben S.; Paul, Suchismita; Ciciliano, Jordan C.; Smas, Malgorzata E.; Winokur, Daniel; Gilman, Anna J.; Ulman, Matthew J.; Xega, Kristina; Contino, Gianmarco; Alagesan, Brinda; Brannigan, Brian W.; Ryan, David P.; Sequist, Lecia V.; Bardeesy, Nabeel; Ramaswamy, Sridhar; Toner, Mehmet; Maheswaran, Shyamala; Haber, Daniel A.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02114 USA.
   [Yu, Min; Haber, Daniel A.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA.
   [Ozsolak, Fatih; Milos, Patrice M.] Helicos BioSci Corp, Cambridge, MA 02139 USA.
C3 Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard Medical School; Harvard University; Harvard Medical School; Howard Hughes Medical Institute
RP Maheswaran, S (corresponding author), Massachusetts Gen Hosp, Ctr Canc, Ctr Engn Med, Boston, MA 02114 USA.
EM maheswaran@helix.mgh.harvard.edu; haber@helix.mgh.harvard.edu
FU Stand Up To Cancer; Howard Hughes Medical Institute; NIBIB [5R01EB008047]; NIH [CA129933]; Pancreatic Cancer Action Network - AACR Fellowship; Warshaw Institute for Pancreatic Cancer Research; K12 Paul Calabresi Award for Clinical Oncology Clinical Research Career Development Program NIH [5K12CA87723-09]; National Cancer Institute [K12CA087723, R01CA129933, P01CA117969] Funding Source: NIH RePORTER
NR 14
TC 411
Z9 490
U1 1
U2 189
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUL 26
PY 2012
VL 487
IS 7408
BP 510
EP U130
DI 10.1038/nature11217
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 979KD
UT WOS:000306815300044
PM 22763454
DA 2026-03-09
ER

PT J
AU Lickwar, CR
   Mueller, F
   Hanlon, SE
   McNally, JG
   Lieb, JD
AF Lickwar, Colin R.
   Mueller, Florian
   Hanlon, Sean E.
   McNally, James G.
   Lieb, Jason D.
TI Genome-wide protein-DNA binding dynamics suggest a molecular clutch for transcription factor function
SO NATURE
LA English
DT Article
ID glucocorticoid-receptor; eukaryotic genome; budding yeast; living cells; chromatin; promoter; equilibrium; mechanism; exchange; sites
AB Dynamic access to genetic information is central to organismal development and environmental response. Consequently, genomic processes must be regulated by mechanisms that alter genome function relatively rapidly(1-4). Conventional chromatin immunoprecipitation (ChIP) experiments measure transcription factor occupancy(5), but give no indication of kinetics and are poor predictors of transcription factor function at a given locus. To measure transcription-factor-binding dynamics across the genome, we performed competition ChIP (refs 6, 7) with a sequence-specific Saccharomyces cerevisiae transcription factor, Rap1 (ref. 8). Rap1-binding dynamics and Rap1 occupancy were only weakly correlated (R-2 = 0.14), but binding dynamics were more strongly linked to function than occupancy. Long Rap1 residence was coupled to transcriptional activation, whereas fast binding turnover, which we refer to as 'treadmilling', was linked to low transcriptional output. Thus, DNA-binding events that seem identical by conventional ChIP may have different underlying modes of interaction that lead to opposing functional outcomes. We propose that transcription factor binding turnover is a major point of regulation in determining the functional consequences of transcription factor binding, and is mediated mainly by control of competition between transcription factors and nucleosomes. Our model predicts a clutch-like mechanism that rapidly engages a treadmilling transcription factor into a stable binding state, or vice versa, to modulate transcription factor function.
C1 [Lickwar, Colin R.; Hanlon, Sean E.; Lieb, Jason D.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Curriculum Genet & Mol Biol, Dept Biol,Carolina Ctr Genome Sci, Chapel Hill, NC 27599 USA.
   [Mueller, Florian; McNally, James G.] NCI, LRBGE, NIH, Bethesda, MD 20892 USA.
   [Mueller, Florian] Ctr Natl Rech Sci, Inst Pasteur, Grp Imagerie & Modelisat, Unite Rech Associee 2582, F-75015 Paris, France.
C3 University of North Carolina; University of North Carolina Chapel Hill; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); Pasteur Network; Universite Paris Cite; Institut Pasteur Paris; Centre National de la Recherche Scientifique (CNRS)
RP Lieb, JD (corresponding author), Univ N Carolina, Lineberger Comprehens Canc Ctr, Curriculum Genet & Mol Biol, Dept Biol,Carolina Ctr Genome Sci, CB 3280,408 Fordham Hall, Chapel Hill, NC 27599 USA.
EM jlieb@bio.unc.edu
FU US National Institutes of Health (NIH) [R01-GM072518]; NIH, National Cancer Institute, Center for Cancer Research; Region Ile-de-France in the framework of C'Nano IdF, the nanoscience competence center of Paris Region
NR 38
TC 196
Z9 253
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 APR 12
PY 2012
VL 484
IS 7393
BP 251
EP U141
DI 10.1038/nature10985
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 930OV
UT WOS:000303149900037
PM 22498630
DA 2026-03-09
ER

PT J
AU Jeon, SM
   Chandel, NS
   Hay, N
AF Jeon, Sang-Min
   Chandel, Navdeep S.
   Hay, Nissim
TI AMPK regulates NADPH homeostasis to promote tumour cell survival during energy stress
SO NATURE
LA English
DT Article
ID fatty-acid synthase; activated protein-kinase; reduced pyridine-nucleotides; cancer-cells; prostate-cancer; lung-cancer; apoptosis; metabolism; inhibition; growth
AB Overcoming metabolic stress is a critical step for solid tumour growth(1,2). However, the underlying mechanisms of cell death and survival under metabolic stress are not well understood. A key signalling pathway involved in metabolic adaptation is the liver kinase B1 (LKB1)-AMP-activated protein kinase (AMPK) pathway(2,3). Energy stress conditions that decrease intracellular ATP levels below a certain level promote AMPK activation by LKB1. Previous studies showed that LKB1-deficient or AMPK-deficient cells are resistant to oncogenic transformation and tumorigenesis(4-6), possibly because of the function of AMPK in metabolic adaptation. However, the mechanisms by which AMPK promotes metabolic adaptation in tumour cells are not fully understood. Here we show that AMPK activation, during energy stress, prolongs cell survival by redox regulation. Under these conditions, NADPH generation by the pentose phosphate pathway is impaired, but AMPK induces alternative routes to maintain NADPH and inhibit cell death. The inhibition of the acetyl-CoA carboxylases ACC1 and ACC2 by AMPK maintains NADPH levels by decreasing NADPH consumption in fatty-acid synthesis and increasing NADPH generation by means of fatty-acid oxidation. Knockdown of either ACC1 or ACC2 compensates for AMPK activation and facilitates anchorage-independent growth and solid tumour formation in vivo, whereas the activation of ACC1 or ACC2 attenuates these processes. Thus AMPK, in addition to its function in ATP homeostasis, has a key function in NADPH maintenance, which is critical for cancer cell survival under energy stress conditions, such as glucose limitations, anchorage-independent growth and solid tumour formation in vivo.
C1 [Jeon, Sang-Min; Hay, Nissim] Univ Illinois, Coll Med, Dept Biochem & Mol Genet, Chicago, IL 60607 USA.
   [Chandel, Navdeep S.] Northwestern Univ, Sch Med, Div Pulm & Crit Care Med, Dept Med, Chicago, IL 60611 USA.
C3 University of Illinois System; University of Illinois Chicago; University of Illinois Chicago Hospital; Northwestern University
RP Hay, N (corresponding author), Univ Illinois, Coll Med, Dept Biochem & Mol Genet, Chicago, IL 60607 USA.
EM nhay@uic.edu
FU National Institutes of Health [CA090764, AG016927, AG025953]; Chicago Biomedical Consortium; Chicago Community;  [P60DK20595]; National Cancer Institute [R01CA090764] Funding Source: NIH RePORTER; National Institute on Aging [R01AG016927] Funding Source: NIH RePORTER
NR 36
TC 982
Z9 1137
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 MAY 31
PY 2012
VL 485
IS 7400
BP 661
EP +
DI 10.1038/nature11066
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 949WP
UT WOS:000304608000052
PM 22660331
DA 2026-03-09
ER

PT J
AU Zhang, QC
   Petrey, D
   Deng, L
   Qiang, L
   Shi, Y
   Thu, CA
   Bisikirska, B
   Lefebvre, C
   Accili, D
   Hunter, T
   Maniatis, T
   Califano, A
   Honig, B
AF Zhang, Qiangfeng Cliff
   Petrey, Donald
   Deng, Lei
   Qiang, Li
   Shi, Yu
   Thu, Chan Aye
   Bisikirska, Brygida
   Lefebvre, Celine
   Accili, Domenico
   Hunter, Tony
   Maniatis, Tom
   Califano, Andrea
   Honig, Barry
TI Structure-based prediction of protein-protein interactions on a genome-wide scale
SO NATURE
LA English
DT Article
ID interaction networks; database; sequences; context
AB The genome-wide identification of pairs of interacting proteins is an important step in the elucidation of cell regulatory mechanisms(1,2). Much of our present knowledge derives from high-throughput techniques such as the yeast two-hybrid assay and affinity purification(3), as well as from manual curation of experiments on individual systems(4). A variety of computational approaches based, for example, on sequence homology, gene co-expression and phylogenetic profiles, have also been developed for the genome-wide inference of protein-protein interactions (PPIs)(5,6). Yet comparative studies suggest that the development of accurate and complete repertoires of PPIs is still in its early stages(7-9). Here we show that three-dimensional structural information can be used to predict PPIs with an accuracy and coverage that are superior to predictions based on non-structural evidence. Moreover, an algorithm, termed PrePPI, which combines structural information with other functional clues, is comparable in accuracy to high-throughput experiments, yielding over 30,000 high-confidence interactions for yeast and over 300,000 for human. Experimental tests of a number of predictions demonstrate the ability of the PrePPI algorithm to identify unexpected PPIs of considerable biological interest. The surprising effectiveness of three-dimensional structural information can be attributed to the use of homology models combined with the exploitation of both close and remote geometric relationships between proteins.
C1 [Zhang, Qiangfeng Cliff; Petrey, Donald; Deng, Lei; Thu, Chan Aye; Maniatis, Tom; Califano, Andrea; Honig, Barry] Columbia Univ, Dept Biochem & Mol Biophys, New York, NY 10032 USA.
   [Zhang, Qiangfeng Cliff; Petrey, Donald; Honig, Barry] Columbia Univ, Howard Hughes Med Inst, New York, NY 10032 USA.
   [Zhang, Qiangfeng Cliff; Petrey, Donald; Deng, Lei; Bisikirska, Brygida; Lefebvre, Celine; Califano, Andrea; Honig, Barry] Columbia Univ, Columbia Initiat Syst Biol, Ctr Computat Biol & Bioinformat, New York, NY 10032 USA.
   [Deng, Lei] Tongji Univ, Dept Comp Sci & Technol, Shanghai 201804, Peoples R China.
   [Qiang, Li; Accili, Domenico] Columbia Univ, Coll Phys & Surg, Dept Med, Naomi Berrie Diabet Ctr, New York, NY 10032 USA.
   [Shi, Yu; Hunter, Tony] Salk Inst Biol Studies, Mol & Cell Biol Lab, La Jolla, CA 92037 USA.
   [Lefebvre, Celine; Califano, Andrea] Columbia Univ, Inst Canc Genet, New York, NY 10032 USA.
   [Califano, Andrea] Columbia Univ, Dept Biomed Informat, New York, NY 10032 USA.
C3 Columbia University; Columbia University; Howard Hughes Medical Institute; Columbia University; Tongji University; Columbia University; Salk Institute; Columbia University; Columbia University
RP Califano, A (corresponding author), Columbia Univ, Dept Biochem & Mol Biophys, 630 W 168th St, New York, NY 10032 USA.
EM califano@c2b2.columbia.edu; bh6@columbia.edu
FU National Institutes of Health [GM030518, GM094597, CA121852, DK057539, CA082683, R01NS043915]; China Scholarship Council [2010626059]; National Institute of Diabetes and Digestive and Kidney Diseases [R01DK057539] Funding Source: NIH RePORTER
NR 44
TC 558
Z9 677
U1 0
U2 285
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 25
PY 2012
VL 490
IS 7421
BP 556
EP +
DI 10.1038/nature11503
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 025NK
UT WOS:000310196200046
PM 23023127
DA 2026-03-09
ER

PT J
AU LeGates, TA
   Altimus, CM
   Wang, H
   Lee, HK
   Yang, SG
   Zhao, HQ
   Kirkwood, A
   Weber, ET
   Hattar, S
AF LeGates, Tara A.
   Altimus, Cara M.
   Wang, Hui
   Lee, Hey-Kyoung
   Yang, Sunggu
   Zhao, Haiqing
   Kirkwood, Alfredo
   Weber, E. Todd
   Hattar, Samer
TI Aberrant light directly impairs mood and learning through melanopsin-expressing neurons
SO NATURE
LA English
DT Article
ID retinal ganglion-cells; long-term depression; morris water maze; behavioral despair; memory; clock; rats; projections; fluoxetine; anxiety
AB The daily solar cycle allows organisms to synchronize their circadian rhythms and sleep-wake cycles to the correct temporal niche(1). Changes in day-length, shift-work, and transmeridian travel lead to mood alterations and cognitive function deficits(2). Sleep deprivation and circadian disruption underlie mood and cognitive disorders associated with irregular light schedules(2). Whether irregular light schedules directly affect mood and cognitive functions in the context of normal sleep and circadian rhythms remains unclear. Here we show, using an aberrant light cycle that neither changes the amount and architecture of sleep nor causes changes in the circadian timing system, that light directly regulates mood-related behaviours and cognitive functions in mice. Animals exposed to the aberrant light cycle maintain daily corticosterone rhythms, but the overall levels of corticosterone are increased. Despite normal circadian and sleep structures, these animals show increased depression-like behaviours and impaired hippocampal long-term potentiation and learning. Administration of the antidepressant drugs fluoxetine or desipramine restores learning in mice exposed to the aberrant light cycle, suggesting that the mood deficit precedes the learning impairments. To determine the retinal circuits underlying this impairment of mood and learning, we examined the behavioural consequences of this light cycle in animals that lack intrinsically photosensitive retinal ganglion cells. In these animals, the aberrant light cycle does not impair mood and learning, despite the presence of the conventional retinal ganglion cells and the ability of these animals to detect light for image formation. These findings demonstrate the ability of light to influence cognitive and mood functions directly through intrinsically photosensitive retinal ganglion cells.
C1 [LeGates, Tara A.; Altimus, Cara M.; Zhao, Haiqing; Hattar, Samer] Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA.
   [Wang, Hui; Lee, Hey-Kyoung; Yang, Sunggu; Kirkwood, Alfredo; Hattar, Samer] Johns Hopkins Univ, Dept Neurosci, Baltimore, MD 21218 USA.
   [Weber, E. Todd] Rider Univ, Dept Biol, Lawrenceville, NJ 08648 USA.
C3 Johns Hopkins University; Johns Hopkins University; Rider University
RP Hattar, S (corresponding author), Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA.
EM shattar@jhu.edu
FU David and Lucile Packard Foundation
NR 27
TC 432
Z9 505
U1 5
U2 197
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD NOV 22
PY 2012
VL 491
IS 7425
BP 594
EP +
DI 10.1038/nature11673
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 040RE
UT WOS:000311339800052
PM 23151476
DA 2026-03-09
ER

PT J
AU Gillessen, S
   Genzel, R
   Fritz, TK
   Quataert, E
   Alig, C
   Burkert, A
   Cuadra, J
   Eisenhauer, F
   Pfuhl, O
   Dodds-Eden, K
   Gammie, CF
   Ott, T
AF Gillessen, S.
   Genzel, R.
   Fritz, T. K.
   Quataert, E.
   Alig, C.
   Burkert, A.
   Cuadra, J.
   Eisenhauer, F.
   Pfuhl, O.
   Dodds-Eden, K.
   Gammie, C. F.
   Ott, T.
TI A gas cloud on its way towards the supermassive black hole at the Galactic Centre
SO NATURE
LA English
DT Article
ID sagittarius-a-asterisk; stellar orbits; central parsec; eso vlt; accretion; galaxy; winds; resolution; emission; sinfoni
AB Measurements of stellar orbits(1-3) provide compelling evidence(4,5) that the compact radio source Sagittarius A* at the Galactic Centre is a black hole four million times the mass of the Sun. With the exception of modest X-ray and infrared flares(6,7), Sgr A* is surprisingly faint, suggesting that the accretion rate and radiation efficiency near the event horizon are currently very low(3,8). Here we report the presence of a dense gas cloud approximately three times the mass of Earth that is falling into the accretion zone of Sgr A*. Our observations tightly constrain the cloud's orbit to be highly eccentric, with an innermost radius of approach of only similar to 3,100 times the event horizon that will be reached in 2013. Over the past three years the cloud has begun to disrupt, probably mainly through tidal shearing arising from the black hole's gravitational force. The cloud's dynamic evolution and radiation in the next few years will probe the properties of the accretion flow and the feeding processes of the supermassive black hole. The kilo-electronvolt X-ray emission of Sgr A* may brighten significantly when the cloud reaches pericentre. There may also be a giant radiation flare several years from now if the cloud breaks up and its fragments feed gas into the central accretion zone.
C1 [Gillessen, S.; Genzel, R.; Fritz, T. K.; Burkert, A.; Eisenhauer, F.; Pfuhl, O.; Dodds-Eden, K.; Ott, T.] Max Planck Inst Extraterr Phys MPE, D-85748 Garching, Germany.
   [Genzel, R.] Univ Calif Berkeley, Dept Phys, Berkeley, CA 94720 USA.
   [Quataert, E.] Univ Calif Berkeley, Dept Astron, Berkeley, CA 94720 USA.
   [Alig, C.] Univ Munich, D-81679 Munich, Germany.
   [Cuadra, J.] Pontificia Univ Catolica Chile, Dept Astron & Astrofis, Santiago 7820436, Chile.
   [Gammie, C. F.] Univ Illinois, Ctr Theoret Astrophys, Dept Astron, Urbana, IL 61801 USA.
   [Gammie, C. F.] Univ Illinois, Ctr Theoret Astrophys, Dept Phys, Urbana, IL 61801 USA.
C3 Max Planck Society; University of California System; University of California Berkeley; University of California System; University of California Berkeley; University of Munich; Pontificia Universidad Catolica de Chile; University of Illinois System; University of Illinois Urbana-Champaign; University of Illinois System; University of Illinois Urbana-Champaign
RP Gillessen, S (corresponding author), Max Planck Inst Extraterr Phys MPE, Giessenbachstr 1, D-85748 Garching, Germany.
EM ste@mpe.mpg.de; genzel@mpe.mpg.de
FU FONDAP; FONDECYT; Basal; VRI-PUC; excellence cluster 'Origin and Structure of the Universe'
NR 28
TC 270
Z9 288
U1 0
U2 20
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JAN 5
PY 2012
VL 481
IS 7379
BP 51
EP 54
DI 10.1038/nature10652
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 872VD
UT WOS:000298836900026
PM 22170607
DA 2026-03-09
ER

PT J
AU Patten, IS
   Rana, S
   Shahul, S
   Rowe, GC
   Jang, C
   Liu, L
   Hacker, MR
   Rhee, JS
   Mitchell, J
   Mahmood, F
   Hess, P
   Farrell, C
   Koulisis, N
   Khankin, EV
   Burke, SD
   Tudorache, I
   Bauersachs, J
   del Monte, F
   Hilfiker-Kleiner, D
   Karumanchi, SA
   Arany, Z
AF Patten, Ian S.
   Rana, Sarosh
   Shahul, Sajid
   Rowe, Glenn C.
   Jang, Cholsoon
   Liu, Laura
   Hacker, Michele R.
   Rhee, Julie S.
   Mitchell, John
   Mahmood, Feroze
   Hess, Philip
   Farrell, Caitlin
   Koulisis, Nicole
   Khankin, Eliyahu V.
   Burke, Suzanne D.
   Tudorache, Igor
   Bauersachs, Johann
   del Monte, Federica
   Hilfiker-Kleiner, Denise
   Karumanchi, S. Ananth
   Arany, Zoltan
TI Cardiac angiogenic imbalance leads to peripartum cardiomyopathy
SO NATURE
LA English
DT Article
ID transcriptional coactivator pgc-1-alpha; tyrosine kinase 1; heart-failure; mitochondrial biogenesis; ejection fraction; skeletal-muscle; angiotensin-ii; united-states; mice lacking; preeclampsia
AB Peripartum cardiomyopathy (PPCM) is an often fatal disease that affects pregnant women who are near delivery, and it occurs more frequently in women with pre-eclampsia and/or multiple gestation. The aetiology of PPCM, and why it is associated with pre-eclampsia, remain unknown. Here we show that PPCM is associated with a systemic angiogenic imbalance, accentuated by pre-eclampsia. Mice that lack cardiac PGC-1 alpha, a powerful regulator of angiogenesis, develop profound PPCM. Importantly, the PPCM is entirely rescued by pro-angiogenic therapies. In humans, the placenta in late gestation secretes VEGF inhibitors like soluble FLT1 (sFLT1), and this is accentuated by multiple gestation and pre-eclampsia. This anti-angiogenic environment is accompanied by subclinical cardiac dysfunction, the extent of which correlates with circulating levels of sFLT1. Exogenous sFLT1 alone caused diastolic dysfunction in wild-type mice, and profound systolic dysfunction in mice lacking cardiac PGC-1a. Finally, plasma samples from women with PPCM contained abnormally high levels of sFLT1. These data indicate that PPCM is mainly a vascular disease, caused by excess anti-angiogenic signalling in the peripartum period. The data also explain how late pregnancy poses a threat to cardiac homeostasis, and why pre-eclampsia and multiple gestation are important risk factors for the development of PPCM.
C1 [Patten, Ian S.; Rowe, Glenn C.; Jang, Cholsoon; Liu, Laura; Farrell, Caitlin; Koulisis, Nicole; del Monte, Federica; Arany, Zoltan] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Cardiovasc Inst, Boston, MA 02115 USA.
   [Patten, Ian S.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Vasc Biol Res Ctr, Boston, MA 02115 USA.
   [Rana, Sarosh; Hacker, Michele R.; Rhee, Julie S.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Maternal Fetal Med,Dept Obstet & Gynecol, Boston, MA 02115 USA.
   [Shahul, Sajid; Mitchell, John; Mahmood, Feroze; Hess, Philip] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Anesthesia & Crit Care, Boston, MA 02115 USA.
   [Khankin, Eliyahu V.; Burke, Suzanne D.; Karumanchi, S. Ananth] Beth Israel Deaconess Med Ctr, Dept Med, Div Nephrol, Boston, MA 02115 USA.
   [Tudorache, Igor] Hannover Med Sch, Dept Cardiothorac Transplantat & Vasc Surg, D-30625 Hannover, Germany.
   [Bauersachs, Johann; Hilfiker-Kleiner, Denise] Hannover Med Sch, Dept Cardiol & Angiol, D-30625 Hannover, Germany.
   [Burke, Suzanne D.] Howard Hughes Med Inst, Boston, MA 02115 USA.
C3 Harvard University; Harvard University Medical Affiliates; Beth Israel Deaconess Medical Center; Harvard Medical School; 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 Medical School; 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; Hannover Medical School; Hannover Medical School; Howard Hughes Medical Institute
RP Arany, Z (corresponding author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Cardiovasc Inst, 330 Brookline Ave, Boston, MA 02115 USA.
EM hilfiker.denise@mh-hannover.de; zarany@bidmc.harvard.edu
FU Harvard Faculty; John Hedley White grant; Merck; Harvard Catalyst; Clinical and Translational Science Center; Harvard University; NHLBI; Smith Family Foundation; Ellison Medical Foundation; March of Dimes Foundation; Harvard Stem Cell Institute
NR 53
TC 419
Z9 477
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 MAY 17
PY 2012
VL 485
IS 7398
BP 333
EP U76
DI 10.1038/nature11040
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 943CW
UT WOS:000304099100034
PM 22596155
DA 2026-03-09
ER

PT J
AU Kääb, A
   Berthier, E
   Nuth, C
   Gardelle, J
   Arnaud, Y
AF Kaab, Andreas
   Berthier, Etienne
   Nuth, Christopher
   Gardelle, Julie
   Arnaud, Yves
TI Contrasting patterns of early twenty-first-century glacier mass change in the Himalayas
SO NATURE
LA English
DT Article
ID elevation changes; western himalaya; nepal himalaya; balance; precipitation; penetration; signals; snow
AB Glaciers are among the best indicators of terrestrial climate variability, contribute importantly to water resources in many mountainous regions(1,2) and are a major contributor to global sea level rise(3,4). In the Hindu Kush-Karakoram-Himalaya region (HKKH), a paucity of appropriate glacier data has prevented a comprehensive assessment of current regional mass balance(5). There is, however, indirect evidence of a complex pattern of glacial responses(5-8) in reaction to heterogeneous climate change signals(9). Here we use satellite laser altimetry and a global elevation model to show widespread glacier wastage in the eastern, central and southwestern parts of the HKKH during 2003-08. Maximal regional thinning rates were 0.66 +/- 0.09 metres per year in the Jammu-Kashmir region. Conversely, in the Karakoram, glaciers thinned only slightly by a few centimetres per year. Contrary to expectations, regionally averaged thinning rates under debris-mantled ice were similar to those of clean ice despite insulation by debris covers. The 2003-08 specific mass balance for our entire HKKH study region was -0.21 +/- 0.05 m yr(-1) water equivalent, significantly less negative than the estimated global average for glaciers and ice caps(4,10). This difference is mainly an effect of the balanced glacier mass budget in the Karakoram. The HKKH sea level contribution amounts to one per cent of the present-day sea level rise(11). Our 2003-08 mass budget of -12.8 +/- 3.5 gigatonnes (Gt) per year is more negative than recent satellite-gravimetry-based estimates of -5 +/- 3 Gt yr(-1) over 2003-10 (ref. 12). For the mountain catchments of the Indus and Ganges basins(13), the glacier imbalance contributed about 3.5% and about 2.0%, respectively, to the annual average river discharge(13), and up to 10% for the Upper Indus basin(14).
C1 [Kaab, Andreas; Nuth, Christopher] Univ Oslo, Dept Geosci, N-0316 Oslo, Norway.
   [Berthier, Etienne] Univ Toulouse, CNRS, LEGOS, F-31400 Toulouse, France.
   [Gardelle, Julie] Univ Grenoble 1, CNRS, LGGE, F-38402 St Martin Dheres, France.
   [Arnaud, Yves] Univ Grenoble 1, IRD, LTHE LGGE, F-38402 St Martin Dheres, France.
C3 University of Oslo; Universite de Toulouse; Universite Toulouse III - Paul Sabatier; Centre National d'Etudes Spatiales (CNES); Centre National de la Recherche Scientifique (CNRS); Institut de Recherche pour le Developpement (IRD); Laboratoire d'Etudes en Geophysique et oceanographie spatiales; Communaute Universite Grenoble Alpes; Universite Grenoble Alpes (UGA); Centre National de la Recherche Scientifique (CNRS); Communaute Universite Grenoble Alpes; Institut National Polytechnique de Grenoble; Universite Grenoble Alpes (UGA); Centre National de la Recherche Scientifique (CNRS); Institut de Recherche pour le Developpement (IRD)
RP Kääb, A (corresponding author), Univ Oslo, Dept Geosci, POB 1047, N-0316 Oslo, Norway.
EM kaeaeb@geo.uio.no
FU European Space Agency (ESA) [21088/07/I-EC, 4000101778/10/I-AM]; Centre National d'Etudes Spatiales (CNES) through the TOSCA programme; French National Research Agency [ANR-09-CEP-005-01/PAPRIKA]; PNTS; CNES/CNRS; Centre National d'Etudes Spatiales (CNES) through the ISIS programme
NR 30
TC 937
Z9 1029
U1 9
U2 401
PU NATURE PUBLISHING 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 23
PY 2012
VL 488
IS 7412
BP 495
EP 498
DI 10.1038/nature11324
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 992FS
UT WOS:000307761600033
PM 22914167
DA 2026-03-09
ER

PT J
AU Loquet, A
   Sgourakis, NG
   Gupta, R
   Giller, K
   Riedel, D
   Goosmann, C
   Griesinger, C
   Kolbe, M
   Baker, D
   Becker, S
   Lange, A
AF Loquet, Antoine
   Sgourakis, Nikolaos G.
   Gupta, Rashmi
   Giller, Karin
   Riedel, Dietmar
   Goosmann, Christian
   Griesinger, Christian
   Kolbe, Michael
   Baker, David
   Becker, Stefan
   Lange, Adam
TI Atomic model of the type III secretion system needle
SO NATURE
LA English
DT Article
ID solid-state nmr; supramolecular structure; electron cryomicroscopy; cross-polarization; microscopy; proteins; crystallography; resolution; machines; delivery
AB Pathogenic bacteria using a type III secretion system (T3SS)(1,2) to manipulate host cells cause many different infections including Shigella dysentery, typhoid fever, enterohaemorrhagic colitis and bubonic plague. An essential part of the T3SS is a hollow needle-like protein filament through which effector proteins are injected into eukaryotic host cells(3-6). Currently, the three-dimensional structure of the needle is unknown because it is not amenable to X-ray crystallography and solution NMR, as a result of its inherent non-crystallinity and insolubility. Cryo-electron microscopy combined with crystal or solution NMR subunit structures has recently provided a powerful hybrid approach for studying supramolecular assemblies(7-12), resulting in low-resolution and medium-resolution models(13-17). However, such approaches cannot deliver atomic details, especially of the crucial subunit-subunit interfaces, because of the limited cryo-electron microscopic resolution obtained in these studies. Here we report an alternative approach combining recombinant wild-type needle production, solid-state NMR, electron microscopy and Rosetta modelling to reveal the supramolecular interfaces and ultimately the complete atomic structure of the Salmonella typhimurium T3SS needle. We show that the 80-residue subunits form a right-handed helical assembly with roughly 11 subunits per two turns, similar to that of the flagellar filament of S. typhimurium. In contrast to established models of the needle in which the amino terminus of the protein subunit was assumed to be alpha-helical and positioned inside the needle, our model reveals an extended amino-terminal domain that is positioned on the surface of the needle, while the highly conserved carboxy terminus points towards the lumen.
C1 [Loquet, Antoine; Giller, Karin; Griesinger, Christian; Becker, Stefan; Lange, Adam] Max Planck Inst Biophys Chem, Dept NMR Based Struct Biol, D-37077 Gottingen, Germany.
   [Sgourakis, Nikolaos G.; Baker, David] Univ Washington, Dept Biochem, Seattle, WA 98195 USA.
   [Gupta, Rashmi; Kolbe, Michael] Max Planck Inst Infect Biol, Dept Cellular Microbiol, D-10117 Berlin, Germany.
   [Riedel, Dietmar] Max Planck Inst Biophys Chem, Lab Electron Microscopy, D-37077 Gottingen, Germany.
   [Griesinger, Christian] Max Planck Inst Infect Biol, D-10117 Berlin, Germany.
C3 Max Planck Society; University of Washington; University of Washington Seattle; Max Planck Society; Max Planck Society; Max Planck Society
RP Lange, A (corresponding author), Max Planck Inst Biophys Chem, Dept NMR Based Struct Biol, D-37077 Gottingen, Germany.
EM kolbe@mpiib-berlin.mpg.de; sabe@nmr.mpibpc.mpg.de; adla@nmr.mpibpc.mpg.de
FU Max Planck Society; Deutsche Forschungsgemeinschaft; Fondation Bettencourt Schueller; National Institutes of Health [1 R01 GM092802-01]; EMBO; European Union [261863]
NR 35
TC 298
Z9 341
U1 0
U2 168
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 14
PY 2012
VL 486
IS 7402
BP 276
EP +
DI 10.1038/nature11079
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 957UH
UT WOS:000305189000039
PM 22699623
DA 2026-03-09
ER

PT J
AU Wu, HX
   Wacker, D
   Mileni, M
   Katritch, V
   Han, GW
   Vardy, E
   Liu, W
   Thompson, AA
   Huang, XP
   Carroll, FI
   Mascarella, SW
   Westkaemper, RB
   Mosier, PD
   Roth, BL
   Cherezov, V
   Stevens, RC
AF Wu, Huixian
   Wacker, Daniel
   Mileni, Mauro
   Katritch, Vsevolod
   Han, Gye Won
   Vardy, Eyal
   Liu, Wei
   Thompson, Aaron A.
   Huang, Xi-Ping
   Carroll, F. Ivy
   Mascarella, S. Wayne
   Westkaemper, Richard B.
   Mosier, Philip D.
   Roth, Bryan L.
   Cherezov, Vadim
   Stevens, Raymond C.
TI Structure of the human κ-opioid receptor in complex with JDTic
SO NATURE
LA English
DT Article
ID protein-coupled receptors; crystal-structure; transmembrane domain; membrane-proteins; opiate receptor; salvinorin-a; in-vitro; docking; agonist; analogs
AB Opioid receptors mediate the actions of endogenous and exogenous opioids on many physiological processes, including the regulation of pain, respiratory drive, mood, and-in the case of kappa-opioid receptor (kappa-OR)-dysphoria and psychotomimesis. Here we report the crystal structure of the human kappa-OR in complex with the selective antagonist JDTic, arranged in parallel dimers, at 2.9 angstrom resolution. The structure reveals important features of the ligand-binding pocket that contribute to the high affinity and subtype selectivity of JDTic for the human kappa-OR. Modelling of other important kappa-OR-selective ligands, including the morphinan-derived antagonists norbinaltorphimine and 5'-guanidinonaltrindole, and the diterpene agonist salvinorin A analogue RB-64, reveals both common and distinct features for binding these diverse chemotypes. Analysis of site-directed mutagenesis and ligand structure-activity relationships confirms the interactions observed in the crystal structure, thereby providing a molecular explanation for kappa-OR subtype selectivity, and essential insights for the design of compounds with new pharmacological properties targeting the human kappa-OR.
C1 [Wu, Huixian; Wacker, Daniel; Mileni, Mauro; Katritch, Vsevolod; Han, Gye Won; Liu, Wei; Thompson, Aaron A.; Cherezov, Vadim; Stevens, Raymond C.] Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA.
   [Vardy, Eyal; Huang, Xi-Ping; Roth, Bryan L.] Univ N Carolina, Chapel Hill Med Sch, Natl Inst Mental Hlth Psychoact Drug Screening Pr, Dept Pharmacol, Chapel Hill, NC 27599 USA.
   [Vardy, Eyal; Huang, Xi-Ping; Roth, Bryan L.] Univ N Carolina, Chapel Hill Med Sch, Div Chem Biol & Med Chem, Chapel Hill, NC 27599 USA.
   [Carroll, F. Ivy; Mascarella, S. Wayne] Res Triangle Inst, Ctr Organ & Med Chem, Res Triangle Pk, NC 27709 USA.
   [Westkaemper, Richard B.; Mosier, Philip D.] Virginia Commonwealth Univ, Dept Med Chem, Richmond, VA 23298 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; University of North Carolina Chapel Hill; Research Triangle Institute; Virginia Commonwealth University
RP Stevens, RC (corresponding author), Scripps Res Inst, Dept Mol Biol, 10550 N Torrey Pines Rd, La Jolla, CA 92037 USA.
EM stevens@scripps.edu
FU PSI:Biology [U54 GM094618]; NIH [P50 GM073197, R01 DA017624, R01 DA027170, R01 DA009045]; NIMH; Michael Hooker Distinguished Chair of Pharmacology; Boehringer Ingelheim Fonds; National Cancer Institute [Y1-CO-1020]; National Institute of General Medical Sciences [Y1-GM-1104]
NR 50
TC 757
Z9 882
U1 3
U2 175
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 17
PY 2012
VL 485
IS 7398
BP 327
EP U69
DI 10.1038/nature10939
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 943CW
UT WOS:000304099100033
PM 22437504
DA 2026-03-09
ER

PT J
AU Schauss, P
   Cheneau, M
   Endres, M
   Fukuhara, T
   Hild, S
   Omran, A
   Pohl, T
   Gross, C
   Kuhr, S
   Bloch, I
AF Schauss, Peter
   Cheneau, Marc
   Endres, Manuel
   Fukuhara, Takeshi
   Hild, Sebastian
   Omran, Ahmed
   Pohl, Thomas
   Gross, Christian
   Kuhr, Stefan
   Bloch, Immanuel
TI Observation of spatially ordered structures in a two-dimensional Rydberg gas
SO NATURE
LA English
DT Article
ID neutral atoms; blockade
AB The ability to control and tune interactions in ultracold atomic gases has paved the way for the realization of new phases of matter. So far, experiments have achieved a high degree of control over short-range interactions, but the realization of long-range interactions has become a central focus of research because it would open up a new realm of many-body physics. Rydberg atoms are highly suited to this goal because the van der Waals forces between them are many orders of magnitude larger than those between ground-state atoms(1). Consequently, mere laser excitation of ultracold gases can cause strongly correlated many-body states to emerge directly when atoms are transferred to Rydberg states. A key example is a quantum crystal composed of coherent superpositions of different, spatially ordered configurations of collective excitations(2-5). Here we use high-resolution, in situ Rydberg atom imaging to measure directly strong correlations in a laser-excited, two-dimensional atomic Mott insulator(6). The observations reveal the emergence of spatially ordered excitation patterns with random orientation, but well-defined geometry, in the high-density components of the prepared many-body state. Together with a time-resolved analysis, this supports the description of the system in terms of a correlated quantum state of collective excitations delocalized throughout the gas. Our experiment demonstrates the potential of Rydberg gases to realize exotic phases of matter, thereby laying the basis for quantum simulations of quantum magnets with long-range interactions.
C1 [Schauss, Peter; Cheneau, Marc; Endres, Manuel; Fukuhara, Takeshi; Hild, Sebastian; Omran, Ahmed; Gross, Christian; Kuhr, Stefan; Bloch, Immanuel] Max Planck Inst Quantum Opt, D-85748 Garching, Germany.
   [Pohl, Thomas] Max Planck Inst Phys Komplexer Syst, D-01187 Dresden, Germany.
   [Kuhr, Stefan] Univ Strathclyde, Dept Phys, SUPA, Glasgow G4 0NG, Lanark, Scotland.
   [Bloch, Immanuel] Univ Munich, Fak Phys, D-80799 Munich, Germany.
C3 Max Planck Society; Max Planck Society; University of Strathclyde; University of Munich
RP Schauss, P (corresponding author), Max Planck Inst Quantum Opt, D-85748 Garching, Germany.
EM peter.schauss@mpq.mpg.de
FU MPG; DFG; EU; JSPS
NR 33
TC 464
Z9 506
U1 0
U2 133
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD NOV 1
PY 2012
VL 491
IS 7422
BP 87
EP 91
DI 10.1038/nature11596
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 028PM
UT WOS:000310434500035
PM 23128229
DA 2026-03-09
ER

PT J
AU Rhee, HS
   Pugh, BF
AF Rhee, Ho Sung
   Pugh, B. Franklin
TI Genome-wide structure and organization of eukaryotic pre-initiation complexes
SO NATURE
LA English
DT Article
ID rna-polymerase-ii; start site selection; photo-cross-linking; in-vivo; transcription initiation; saccharomyces-cerevisiae; pervasive transcription; bidirectional promoters; preinitiation complex; gene-regulation
AB Transcription and regulation of genes originate from transcription pre-initiation complexes (PICs). Their structural and positional organization across eukaryotic genomes is unknown. Here we applied lambda exonuclease to chromatin immunoprecipitates (termed ChIP-exo) to examine the precise location of 6,045 PICs in Saccharomyces. PICs, including RNA polymerase II and protein complexes TFIIA, TFIIB, TFIID (or TBP), TFIIE, TFIIF, TFIIH and TFIIK were positioned within promoters and excluded from coding regions. Exonuclease patterns were in agreement with crystallographic models of the PIC, and were sufficiently precise to identify TATA-like elements at so-called TATA-less promoters. These PICs and their transcription start sites were positionally constrained at TFIID-engaged downstream +1 nucleosomes. At TATA-box-containing promoters, which are depleted of TFIID, a 11 nucleosome was positioned to be in competition with the PIC, which may allow greater latitude in start-site selection. Our genomic localization of messenger RNA and non-coding RNA PICs reveals that two PICs, in inverted orientation, may occupy the flanking borders of nucleosome-free regions. Their unambiguous detection may help distinguish bona fide genes from transcriptional noise.
C1 [Rhee, Ho Sung; Pugh, B. Franklin] Penn State Univ, Dept Biochem & Mol Biol, Ctr Eukaryot Gene Regulat, University Pk, PA 16802 USA.
C3 Pennsylvania Commonwealth System of Higher Education (PCSHE); Pennsylvania State University; Pennsylvania State University - University Park
RP Pugh, BF (corresponding author), Penn State Univ, Dept Biochem & Mol Biol, Ctr Eukaryot Gene Regulat, University Pk, PA 16802 USA.
EM bfp2@psu.edu
FU National Institutes of Health [GM059055]
CR Ahn SH, 2009, EMBO J, V28, P205, DOI 10.1038/emboj.2008.280
   Albert I, 2008, BIOINFORMATICS, V24, P1305, DOI 10.1093/bioinformatics/btn119
   Ansari A, 2005, GENE DEV, V19, P2969, DOI 10.1101/gad.1362305
   Basehoar AD, 2004, CELL, V116, P699, DOI 10.1016/S0092-8674(04)00205-3
   Bhaumik SR, 2002, MOL CELL BIOL, V22, P7365, DOI 10.1128/MCB.22.21.7365-7371.2002
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NR 50
TC 395
Z9 527
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 MAR 15
PY 2012
VL 483
IS 7389
BP 295
EP 301
DI 10.1038/nature10799
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 908HP
UT WOS:000301481800041
PM 22258509
DA 2026-03-09
ER

PT J
AU Bharat, TAM
   Davey, NE
   Ulbrich, P
   Riches, JD
   de Marco, A
   Rumlova, M
   Sachse, C
   Ruml, T
   Briggs, JAG
AF Bharat, Tanmay A. M.
   Davey, Norman E.
   Ulbrich, Pavel
   Riches, James D.
   de Marco, Alex
   Rumlova, Michaela
   Sachse, Carsten
   Ruml, Tomas
   Briggs, John A. G.
TI Structure of the immature retroviral capsid at 8 Å resolution by cryo-electron microscopy
SO NATURE
LA English
DT Article
ID pfizer monkey virus; terminal domain; particle-production; assembly inhibitor; hiv-1 virions; nucleic-acid; protein; maturation; organization
AB The assembly of retroviruses such as HIV-1 is driven by oligomerization of their major structural protein, Gag. Gag is a multidomain polyprotein including three conserved folded domains: MA (matrix), CA (capsid) and NC (nucleocapsid)(1). Assembly of an infectious virion proceeds in two stages(2). In the first stage, Gag oligomerization into a hexameric protein lattice leads to the formation of an incomplete, roughly spherical protein shell that buds through the plasma membrane of the infected cell to release an enveloped immature virus particle. In the second stage, cleavage of Gag by the viral protease leads to rearrangement of the particle interior, converting the non-infectious immature virus particle into a mature infectious virion. The immature Gag shell acts as the pivotal intermediate in assembly and is a potential target for anti-retroviral drugs both in inhibiting virus assembly and in disrupting virus maturation(3). However, detailed structural information on the immature Gag shell has not previously been available. For this reason it is unclear what protein conformations and interfaces mediate the interactions between domains and therefore the assembly of retrovirus particles, and what structural transitions are associated with retrovirus maturation. Here we solve the structure of the immature retroviral Gag shell from Mason-Pfizer monkey virus by combining cryo-electron microscopy and tomography. The 8-angstrom resolution structure permits the derivation of a pseudo-atomic model of CA in the immature retrovirus, which defines the protein interfaces mediating retrovirus assembly. We show that transition of an immature retrovirus into its mature infectious form involves marked rotations and translations of CA domains, that the roles of the amino-terminal and carboxy-terminal domains of CA in assembling the immature and mature hexameric lattices are exchanged, and that the CA interactions that stabilize the immature and mature viruses are almost completely distinct.
C1 [Bharat, Tanmay A. M.; Davey, Norman E.; Riches, James D.; de Marco, Alex; Sachse, Carsten; Briggs, John A. G.] European Mol Biol Lab, Struct & Computat Biol Unit, D-69117 Heidelberg, Germany.
   [Ulbrich, Pavel; Ruml, Tomas] Inst Chem Technol, Dept Biochem & Microbiol, CR-16628 Prague, Czech Republic.
   [Rumlova, Michaela] Acad Sci Czech Republic, Inst Organ Chem & Biochem, Vvi, Prague 16610, Czech Republic.
C3 European Molecular Biology Laboratory (EMBL); University of Chemistry & Technology, Prague; Czech Academy of Sciences; Institute of Organic Chemistry & Biochemistry of the Czech Academy of Sciences
RP Briggs, JAG (corresponding author), European Mol Biol Lab, Struct & Computat Biol Unit, Meyerhofstr 1, D-69117 Heidelberg, Germany.
EM briggs@embl.de
FU Deutsche Forschungsgemeinschaft [SPP1175]; Czech Science foundation [P302/12/1895, 204/09/1388]
NR 30
TC 140
Z9 161
U1 0
U2 108
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUL 19
PY 2012
VL 487
IS 7407
BP 385
EP 389
DI 10.1038/nature11169
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 975JB
UT WOS:000306506500047
PM 22722831
DA 2026-03-09
ER

PT J
AU Stute, A
   Casabone, B
   Schindler, P
   Monz, T
   Schmidt, PO
   Brandstätter, B
   Northup, TE
   Blatt, R
AF Stute, A.
   Casabone, B.
   Schindler, P.
   Monz, T.
   Schmidt, P. O.
   Brandstaetter, B.
   Northup, T. E.
   Blatt, R.
TI Tunable ion-photon entanglement in an optical cavity
SO NATURE
LA English
DT Article
ID single-photon; deterministic generation; quantum teleportation; trapped ions; one-atom; state; qubits; matter
AB Proposed quantum networks require both a quantum interface between light and matter and the coherent control of quantum states(1,2). A quantum interface can be realized by entangling the state of a single photon with the state of an atomic or solid-state quantum memory, as demonstrated in recent experiments with trapped ions(3,4), neutral atoms(5,6), atomic ensembles(7,8) and nitrogen-vacancy spins(9). The entangling interaction couples an initial quantum memory state to two possible light-matter states, and the atomic level structure of the memory determines the available coupling paths. In previous work, the transition parameters of these paths determined the phase and amplitude of the final entangled state, unless the memory was initially prepared in a superposition state(4) (a step that requires coherent control). Here we report fully tunable entanglement between a single Ca-40(+) ion and the polarization state of a single photon within an optical resonator. Our method, based on a bichromatic, cavity-mediated Raman transition, allows us to select two coupling paths and adjust their relative phase and amplitude. The cavity setting enables intrinsically deterministic, high-fidelity generation of any two-qubit entangled state. This approach is applicable to a broad range of candidate systems and thus is a promising method for distributing information within quantum networks.
C1 [Stute, A.; Casabone, B.; Schindler, P.; Monz, T.; Brandstaetter, B.; Northup, T. E.; Blatt, R.] Univ Innsbruck, Inst Expt Phys, A-6020 Innsbruck, Austria.
   [Schmidt, P. O.] Phys Tech Bundesanstalt, QUEST Inst Expt Quantum Metrol, D-38116 Braunschweig, Germany.
   [Schmidt, P. O.] Leibniz Univ Hannover, Inst Quantenopt, D-30167 Hannover, Germany.
   [Blatt, R.] Austrian Acad Sci, Inst Quantenopt & Quanteninformat, A-6020 Innsbruck, Austria.
C3 University of Innsbruck; Physikalisch-Technische Bundesanstalt (PTB); Leibniz University Hannover; Austrian Academy of Sciences
RP Northup, TE (corresponding author), Univ Innsbruck, Inst Expt Phys, Technikerstr 25, A-6020 Innsbruck, Austria.
EM tracy.northup@uibk.ac.at
FU Austrian Science Fund (FWF); European Commission (AQUTE); Institut fur Quanteninformation GmbH; Marie Curie International Incoming Fellowship within the 7th European Framework Program
NR 30
TC 192
Z9 214
U1 1
U2 49
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD MAY 24
PY 2012
VL 485
IS 7399
BP 482
EP U89
DI 10.1038/nature11120
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 946IH
UT WOS:000304344500038
PM 22622573
DA 2026-03-09
ER

PT J
AU Zaks, B
   Liu, RB
   Sherwin, MS
AF Zaks, B.
   Liu, R. B.
   Sherwin, M. S.
TI Experimental observation of electron-hole recollisions
SO NATURE
LA English
DT Article
ID side-band generation; high-harmonic-generation; radiation; field
AB An intense laser field can remove an electron from an atom or molecule and pull the electron into a large-amplitude oscillation in which it repeatedly collides with the charged core it left behind(1-4). Such recollisions result in the emission of very energetic photons by means of high-order-harmonic generation, which has been observed in atomic and molecular gases(5-7) as well as in a bulk crystal(8). An exciton is an atom-like excitation of a solid in which an electron that is excited from the valence band is bound by the Coulomb interaction to the hole it left behind(9,10). It has been predicted that recollisions between electrons and holes in excitons will result in a new phenomenon: high-order-sideband generation(11,12). In this process, excitons are created by a weak near-infrared laser of frequency f(NIR). An intense laser field at a much lower frequency, f(THz), then removes the electron from the exciton and causes it to recollide with the resulting hole. New emission is predicted to occur as sidebands of frequency f(NIR) + 12nf(THz), wheren is an integer that can be much greater than one. Here we report the observation of high-order-sideband generation in semiconductor quantum wells. Sidebands are observed up to eighteenth order (+18f(THz), or n 59). The intensity of the high-order sidebands decays only weakly with increasing sideband order, confirming the non-perturbative nature of the effect. Sidebands are strongest for linearly polarized terahertz radiation and vanish when the terahertz radiation is circularly polarized. Beyond their fundamental scientific significance, our results suggest a new mechanism for the ultrafast modulation of light, which has potential applications in terabit-rate optical communications.
C1 [Zaks, B.; Sherwin, M. S.] Univ Calif Santa Barbara, Dept Phys, Santa Barbara, CA 93106 USA.
   [Zaks, B.; Sherwin, M. S.] Univ Calif Santa Barbara, Inst Terahertz Sci & Technol, Santa Barbara, CA 93106 USA.
   [Liu, R. B.] Chinese Univ Hong Kong, Dept Phys, Shatin, Hong Kong, Peoples R China.
   [Liu, R. B.] Chinese Univ Hong Kong, Ctr Opt Sci, Shatin, Hong Kong, Peoples R China.
C3 University of California System; University of California Santa Barbara; University of California System; University of California Santa Barbara; Chinese University of Hong Kong; Chinese University of Hong Kong
RP Sherwin, MS (corresponding author), Univ Calif Santa Barbara, Dept Phys, Santa Barbara, CA 93106 USA.
EM sherwin@physics.ucsb.edu
FU NSF [DMR-1006603]; Hong Kong RGC/GRF [401011]
NR 30
TC 266
Z9 285
U1 0
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 MAR 29
PY 2012
VL 483
IS 7391
BP 580
EP 583
DI 10.1038/nature10864
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 915EF
UT WOS:000302006100035
PM 22460904
DA 2026-03-09
ER

PT J
AU Kaufman, JJ
   Tao, GM
   Shabahang, S
   Banaei, EH
   Deng, DSS
   Liang, XD
   Johnson, SG
   Fink, Y
   Abouraddy, AF
AF Kaufman, Joshua J.
   Tao, Guangming
   Shabahang, Soroush
   Banaei, Esmaeil-Hooman
   Deng, Daosheng S.
   Liang, Xiangdong
   Johnson, Steven G.
   Fink, Yoel
   Abouraddy, Ayman F.
TI Structured spheres generated by an in-fibre fluid instability
SO NATURE
LA English
DT Article
ID monodisperse; particles; arrays; device
AB From drug delivery(1,2) to chemical and biological catalysis(3) and cosmetics(4), the need for efficient fabrication pathways for particles over a wide range of sizes, from a variety of materials, and in many different structures has been well established(5). Here we harness the inherent scalability of fibre production(6) and an in-fibre Plateau-Rayleigh capillary instability(7) for the fabrication of uniformly sized, structured spherical particles spanning an exceptionally wide range of sizes: from 2 mm down to 20 nm. Thermal processing of a multimaterial fibre(8) controllably induces the instability(9), resulting in a well-ordered, oriented emulsion(10) in three dimensions. The fibre core and cladding correspond to the dispersed and continuous phases, respectively, and are both frozen in situ on cooling, after which the particles are released when needed. By arranging a variety of structures and materials in a macroscopic scaled-up model of the fibre, we produce composite, structured, spherical particles, such as core-shell particles, two-compartment 'Janus' particles(11), and multi-sectioned 'beach ball' particles. Moreover, producing fibres with a high density of cores allows for an unprecedented level of parallelization. In principle, 10(8) 50-nm cores may be embedded in metres-long, 1-mm-diameter fibre, which can be induced to break up simultaneously throughout its length, into uniformly sized, structured spheres.
C1 [Kaufman, Joshua J.; Tao, Guangming; Shabahang, Soroush; Banaei, Esmaeil-Hooman; Abouraddy, Ayman F.] Univ Cent Florida, CREOL, Coll Opt & Photon, Orlando, FL 32816 USA.
   [Banaei, Esmaeil-Hooman] Univ Cent Florida, Dept Elect Engn & Comp Sci, Orlando, FL 32816 USA.
   [Deng, Daosheng S.] MIT, Dept Chem Engn, Cambridge, MA 02139 USA.
   [Liang, Xiangdong; Johnson, Steven G.] MIT, Dept Math, Cambridge, MA 02139 USA.
   [Fink, Yoel] MIT, Dept Mat Sci & Engn, Cambridge, MA 02139 USA.
C3 State University System of Florida; University of Central Florida; State University System of Florida; University of Central Florida; Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT)
RP Abouraddy, AF (corresponding author), Univ Cent Florida, CREOL, Coll Opt & Photon, Orlando, FL 32816 USA.
EM raddy@creol.ucf.edu
FU US National Science Foundation [ECCS-1002295]; Ralph E. Powe Junior Faculty Enhancement Award from the Oak Ridge Associated Universities (ORAU); US Air Force Office of Scientific Research (AFOSR) [FA-9550-12-1-0148]; CREOL; College of Optics Photonics; Materials Research Science and Engineering Program of the US NSF [DMR-0819762]; US Army Research Office through the Institute for Soldier Nanotechnologies [W911NF-07-D-0004]; Directorate For Engineering; Div Of Electrical, Commun & Cyber Sys [1002295] Funding Source: National Science Foundation
NR 32
TC 179
Z9 198
U1 5
U2 302
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUL 26
PY 2012
VL 487
IS 7408
BP 463
EP 467
DI 10.1038/nature11215
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 979KD
UT WOS:000306815300034
PM 22810590
DA 2026-03-09
ER

PT J
AU Seo, MD
   Velamakanni, S
   Ishiyama, N
   Stathopulos, PB
   Rossi, AM
   Khan, SA
   Dale, P
   Li, CM
   Ames, JB
   Ikura, M
   Taylor, CW
AF Seo, Min-Duk
   Velamakanni, Saroj
   Ishiyama, Noboru
   Stathopulos, Peter B.
   Rossi, Ana M.
   Khan, Samir A.
   Dale, Philippa
   Li, Congmin
   Ames, James B.
   Ikura, Mitsuhiko
   Taylor, Colin W.
TI Structural and functional conservation of key domains in InsP3 and ryanodine receptors
SO NATURE
LA English
DT Article
ID ligand-binding; crystal-structures; conformational-changes; transmembrane domains; molecular-cloning; inositol; forms; probe
AB Inositol-1,4,5-trisphosphate receptors (InsP(3)Rs) and ryanodine receptors (RyRs) are tetrameric intracellular Ca2+ channels(1). In each of these receptor families, the pore, which is formed by carboxy-terminal transmembrane domains, is regulated by signals that are detected by large cytosolic structures. InsP(3)R gating is initiated by InsP(3) binding to the InsP(3)-binding core (IBC, residues 224-604 of InsP(3)R1)(2) and it requires the suppressor domain (SD, residues 1-223 of InsP(3)R1)(2-8). Here we present structures of the amino-terminal region (NT, residues 1-604) of rat InsP(3)R1 with (3.6 angstrom) and without (3.0 angstrom) InsP(3) bound. The arrangement of the three NT domains, SD, IBC-beta and IBC-alpha, identifies two discrete interfaces (alpha and beta) between the IBC and SD. Similar interfaces occur between equivalent domains (A, B and C) in RyR1 (ref. 9). The orientations of the three domains when docked into a tetrameric structure of InsP(3)R(10) and of the ABC domains docked into RyR(9) are remarkably similar. The importance of the alpha-interface for activation of InsP(3)R and RyR is confirmed by mutagenesis and, for RyR, by disease-causing mutations(9,11,12). Binding of InsP(3) causes partial closure of the clam-like IBC, disrupting the beta-interface and pulling the SD towards the IBC. This reorients an exposedSDloop ('hotspot' (HS) loop) that is essential for InsP(3)R activation(7). The loop is conserved in RyR and includes mutations that are associated with malignant hyperthermia and central core disease(9,11,12). The HS loop interacts with an adjacent NT, suggesting that activation re-arranges inter-subunit interactions. The A domain of RyR functionally replaced the SD in full-length InsP(3)R, and an InsP(3)R in which its C-terminal transmembrane region was replaced by that from RyR1 was gated by InsP(3) and blocked by ryanodine. Activation mechanisms are conserved between InsP(3)R and RyR. Allosteric modulation of two similar domain interfaces within an N-terminal subunit reorients the first domain (SD or A domain), allowing it, through interactions of the second domain of an adjacent subunit (IBC-beta or B domain), to gate the pore.
C1 [Seo, Min-Duk; Ishiyama, Noboru; Stathopulos, Peter B.; Ikura, Mitsuhiko] Univ Toronto, Ontario Canc Inst, Toronto, ON M5G 1L7, Canada.
   [Seo, Min-Duk; Ishiyama, Noboru; Stathopulos, Peter B.; Ikura, Mitsuhiko] Univ Toronto, Dept Med Biophys, Toronto, ON M5G 1L7, Canada.
   [Velamakanni, Saroj; Rossi, Ana M.; Khan, Samir A.; Dale, Philippa; Taylor, Colin W.] Univ Cambridge, Dept Pharmacol, Cambridge CB2 1PD, England.
   [Li, Congmin; Ames, James B.] Univ Calif Davis, Dept Chem, Davis, CA 95616 USA.
C3 University of Toronto; University Health Network Toronto; University of Toronto; University of Cambridge; University of California System; University of California Davis
RP Ikura, M (corresponding author), Univ Toronto, Ontario Canc Inst, Toronto, ON M5G 1L7, Canada.
EM mikura@uhnres.utoronto.ca; cwt1000@cam.ac.uk
FU Heart and Stroke Foundation of Ontario [T-7181]; National Institutes of Health Research [EY012347, NS059969]; Wellcome Trust [085295]; Biotechnology and Biological Sciences Research Council [BB/H009736]; Medical Research Council [G0900049]; Canadian Institutes of Health Research; National Research Foundation of Korea [2009-352-E00006]; Biotechnology and Biological Sciences Research Council [BB/H009736/1] Funding Source: researchfish; Medical Research Council [G0900049] Funding Source: researchfish; National Eye Institute [R01EY012347] Funding Source: NIH RePORTER; BBSRC [BB/H009736/1] Funding Source: UKRI; MRC [G0900049] Funding Source: UKRI
NR 38
TC 148
Z9 160
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 MAR 1
PY 2012
VL 483
IS 7387
BP 108
EP U159
DI 10.1038/nature10751
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 900HP
UT WOS:000300877900055
PM 22286060
DA 2026-03-09
ER

PT J
AU Schwartzentruber, J
   Korshunov, A
   Liu, XY
   Jones, DTW
   Pfaff, E
   Jacob, K
   Sturm, D
   Fontebasso, AM
   Quang, DAK
   Tönjes, M
   Hovestadt, V
   Albrecht, S
   Kool, M
   Nantel, A
   Konermann, C
   Lindroth, A
   Jäger, N
   Rausch, T
   Ryzhova, M
   Korbel, JO
   Hielscher, T
   Hauser, P
   Garami, M
   Klekner, A
   Bognar, L
   Ebinger, M
   Schuhmann, MU
   Scheurlen, W
   Pekrun, A
   Frühwald, MC
   Roggendorf, W
   Kramm, C
   Dürken, M
   Atkinson, J
   Lepage, P
   Montpetit, A
   Zakrzewska, M
   Zakrzewski, K
   Liberski, PP
   Dong, ZF
   Siegel, P
   Kulozik, AE
   Zapatka, M
   Guha, A
   Malkin, D
   Felsberg, J
   Reifenberger, G
   von Deimling, A
   Ichimura, K
   Collins, VP
   Witt, H
   Milde, T
   Witt, O
   Zhang, CD
   Castelo-Branco, P
   Lichter, P
   Faury, D
   Tabori, U
   Plass, C
   Majewski, J
   Pfister, SM
   Jabado, N
AF Schwartzentruber, Jeremy
   Korshunov, Andrey
   Liu, Xiao-Yang
   Jones, David T. W.
   Pfaff, Elke
   Jacob, Karine
   Sturm, Dominik
   Fontebasso, Adam M.
   Quang, Dong-Anh Khuong
   Toenjes, Martje
   Hovestadt, Volker
   Albrecht, Steffen
   Kool, Marcel
   Nantel, Andre
   Konermann, Carolin
   Lindroth, Anders
   Jaeger, Natalie
   Rausch, Tobias
   Ryzhova, Marina
   Korbel, Jan O.
   Hielscher, Thomas
   Hauser, Peter
   Garami, Miklos
   Klekner, Almos
   Bognar, Laszlo
   Ebinger, Martin
   Schuhmann, Martin U.
   Scheurlen, Wolfram
   Pekrun, Arnulf
   Fruehwald, Michael C.
   Roggendorf, Wolfgang
   Kramm, Christoph
   Duerken, Matthias
   Atkinson, Jeffrey
   Lepage, Pierre
   Montpetit, Alexandre
   Zakrzewska, Magdalena
   Zakrzewski, Krzystof
   Liberski, Pawel P.
   Dong, Zhifeng
   Siegel, Peter
   Kulozik, Andreas E.
   Zapatka, Marc
   Guha, Abhijit
   Malkin, David
   Felsberg, Joerg
   Reifenberger, Guido
   von Deimling, Andreas
   Ichimura, Koichi
   Collins, V. Peter
   Witt, Hendrik
   Milde, Till
   Witt, Olaf
   Zhang, Cindy
   Castelo-Branco, Pedro
   Lichter, Peter
   Faury, Damien
   Tabori, Uri
   Plass, Christoph
   Majewski, Jacek
   Pfister, Stefan M.
   Jabado, Nada
TI Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma
SO NATURE
LA English
DT Article
ID integrated genomic analysis; embryonic stem-cells; high-grade gliomas; atrx; tumors; methylation; telomeres; aberrations; expression; multiforme
AB Glioblastoma multiforme (GBM) is a lethal brain tumour in adults and children. However, DNA copy number and gene expression signatures indicate differences between adult and paediatric cases(1-4). To explore the genetic events underlying this distinction, we sequenced the exomes of 48 paediatric GBM samples. Somatic mutations in the H3.3-ATRX-DAXX chromatin remodelling pathway were identified in 44% of tumours (21/48). Recurrent mutations in H3F3A, which encodes the replication-independent histone 3 variant H3.3, were observed in 31% of tumours, and led to amino acid substitutions at two critical positions within the histone tail (K27M, G34R/G34V) involved in key regulatory post-translational modifications. Mutations in ATRX (alpha-thalassaemia/mental retardation syndrome X-linked)(5) and DAXX (death-domain associated protein), encoding two subunits of a chromatin remodelling complex required for H3.3 incorporation at pericentric heterochromatin and telomeres(6,7), were identified in 31% of samples overall, and in 100% of tumours harbouring a G34R or G34V H3.3 mutation. Somatic TP53 mutations were identified in 54% of all cases, and in 86% of samples with H3F3A and/or ATRX mutations. Screening of a large cohort of gliomas of various grades and histologies (n = 784) showed H3F3A mutations to be specific to GBM and highly prevalent in children and young adults. Furthermore, the presence of H3F3A/ATRX-DAXX/TP53 mutations was strongly associated with alternative lengthening of telomeres and specific gene expression profiles. This is, to our knowledge, the first report to highlight recurrent mutations in a regulatory histone in humans, and our data suggest that defects of the chromatin architecture underlie paediatric and young adult GBM pathogenesis.
C1 [Liu, Xiao-Yang; Jacob, Karine; Fontebasso, Adam M.; Quang, Dong-Anh Khuong; Faury, Damien; Majewski, Jacek; Jabado, Nada] McGill Univ, Dept Human Genet, Montreal, PQ H3Z 2Z3, Canada.
   [Liu, Xiao-Yang; Jacob, Karine; Fontebasso, Adam M.; Quang, Dong-Anh Khuong; Faury, Damien; Majewski, Jacek; Jabado, Nada] McGill Univ, Dept Expt Med, Montreal, PQ H3Z 2Z3, Canada.
   [Schwartzentruber, Jeremy; Lepage, Pierre; Montpetit, Alexandre] McGill Univ, Montreal, PQ H3A 1A4, Canada.
   [Schwartzentruber, Jeremy; Lepage, Pierre; Montpetit, Alexandre] Genome Quebec Innovat Ctr, Montreal, PQ H3A 1A4, Canada.
   [Korshunov, Andrey; von Deimling, Andreas] German Canc Res Ctr, Clin Cooperat Unit Neuropathol, D-69120 Heidelberg, Germany.
   [Jones, David T. W.; Pfaff, Elke; Sturm, Dominik; Kool, Marcel; Witt, Hendrik; Pfister, Stefan M.] German Canc Res Ctr, Divis Pediat Neurooncol, D-69120 Heidelberg, Germany.
   [Toenjes, Martje; Hovestadt, Volker; Zapatka, Marc; Lichter, Peter] German Canc Res Ctr, Div Mol Genet, D-69120 Heidelberg, Germany.
   [Albrecht, Steffen] McGill Univ, Ctr Hlth, Montreal Childrens Hosp, Dept Pathol, Montreal, PQ H3H 1P3, Canada.
   [Nantel, Andre] Natl Res Council Canada, Biotechnol Res Inst, Montreal, PQ H4P 2R2, Canada.
   [Konermann, Carolin; Lindroth, Anders; Plass, Christoph] German Canc Res Ctr, Div Epigenom & Canc Risk Factors, D-69120 Heidelberg, Germany.
   [Jaeger, Natalie] German Canc Res Ctr, Div Theoret Bioinformat, D-69120 Heidelberg, Germany.
   [Rausch, Tobias; Korbel, Jan O.] European Mol Biol Lab, D-69117 Heidelberg, Germany.
   [Ryzhova, Marina] Burdenko Neurosurg Inst, Dept Neuropathol, Moscow 125047, Russia.
   [Hielscher, Thomas] German Canc Res Ctr, Div Biostat, D-69120 Heidelberg, Germany.
   [Hauser, Peter; Garami, Miklos] Semmelweis Univ, Dept Paediat 2, H-1094 Budapest, Hungary.
   [Klekner, Almos; Bognar, Laszlo] Univ Debrecen, Dept Neurosurg, Med & Hlth Sci Ctr, H-4032 Debrecen, Hungary.
   [Ebinger, Martin] Childrens Univ Hosp, Dept Hematol & Oncol, D-72076 Tubingen, Germany.
   [Schuhmann, Martin U.] Univ Hosp, Dept Neurosurg, D-72076 Tubingen, Germany.
   [Scheurlen, Wolfram] Nuremberg Childrens Hosp, Cnopfsche Kinderklin, D-90419 Nurnberg, Germany.
   [Pekrun, Arnulf] Prof Hess Childrens Hosp, D-28177 Bremen, Germany.
   [Fruehwald, Michael C.] Augsburg Childrens Hosp, Klinikum Augsburg, D-86156 Augsburg, Germany.
   [Roggendorf, Wolfgang] Univ Wurzburg, Inst Pathol, Dept Neuropathol, D-97080 Wurzburg, Germany.
   [Kramm, Christoph] Univ Childrens Hosp, D-06097 Halle, Germany.
   [Duerken, Matthias] Univ Childrens Hosp, D-68167 Mannheim, Germany.
   [Atkinson, Jeffrey] McGill Univ, Montreal Childrens Hosp, Ctr Hlth, Div Neurosurg,Dept Surg, Montreal, PQ H3H 1P3, Canada.
   [Zakrzewska, Magdalena; Liberski, Pawel P.] Med Univ Lodz, Dept Mol Pathol & Neuropathol, PL-92216 Lodz, Poland.
   [Zakrzewski, Krzystof] Polish Mothers Mem Hosp, Res Inst, Dept Neurosurg, PL-93338 Lodz, Poland.
   [Dong, Zhifeng; Siegel, Peter] McGill Univ, Rosalind & Morris Goodman Canc Res Ctr, Montreal, PQ H3A 1A3, Canada.
   [Kulozik, Andreas E.; Witt, Hendrik; Milde, Till; Witt, Olaf; Pfister, Stefan M.] Univ Heidelberg Hosp, Dept Paediat Oncol Hematol & Immunol, D-69120 Heidelberg, Germany.
   [Guha, Abhijit; Zhang, Cindy; Castelo-Branco, Pedro; Tabori, Uri] Univ Toronto, Hosp Sick Children, Arthur & Sonia Labatt Brain Tumor Res Ctr, Res Inst, Toronto, ON M5G 1X8, Canada.
   [Malkin, David; Tabori, Uri] Univ Toronto, Hosp Sick Children, Div Hematol Oncol, Dept Paediat, Toronto, ON M5G 1X8, Canada.
   [Felsberg, Joerg; Reifenberger, Guido] Univ Dusseldorf, Dept Neuropathol, D-40225 Dusseldorf, Germany.
   [von Deimling, Andreas] Univ Heidelberg Hosp, Dept Neuropathol, D-69120 Heidelberg, Germany.
   [Ichimura, Koichi; Collins, V. Peter] Univ Cambridge, Dept Pathol, Div Mol Histopathol, Cambridge CB2 0QQ, England.
   [Milde, Till; Witt, Olaf] German Canc Res Ctr, Clin Cooperat Unit Paediat Oncol, D-69120 Heidelberg, Germany.
   [Jabado, Nada] McGill Univ, Ctr Hlth, Res Inst, Montreal, PQ H3Z 2Z3, Canada.
   [Jabado, Nada] McGill Univ, Dept Paediat, Montreal, PQ H3Z 2Z3, Canada.
C3 McGill University; McGill University; McGill University; Helmholtz Association; German Cancer Research Center (DKFZ); Helmholtz Association; German Cancer Research Center (DKFZ); Helmholtz Association; German Cancer Research Center (DKFZ); McGill University; National Research Council Canada; Helmholtz Association; German Cancer Research Center (DKFZ); Helmholtz Association; German Cancer Research Center (DKFZ); European Molecular Biology Laboratory (EMBL); Burnazyan Federal Medical Biophysical Center; Helmholtz Association; German Cancer Research Center (DKFZ); Semmelweis University; University of Debrecen; Eberhard Karls University of Tubingen; TUBINGEN UNIVERSITY CHILDRENS HOSPITAL; Eberhard Karls University of Tubingen; Eberhard Karls University Hospital; Klinikum Augsburg; University of Wurzburg; Martin Luther University Halle Wittenberg; Ruprecht Karls University Heidelberg; McGill University; Medical University Lodz; Polish Mother's Memorial Hospital - Research Institute; McGill University; Ruprecht Karls University Heidelberg; University of Toronto; Hospital for Sick Children (SickKids); University of Toronto; Hospital for Sick Children (SickKids); Heinrich Heine University Dusseldorf; Ruprecht Karls University Heidelberg; University of Cambridge; Helmholtz Association; German Cancer Research Center (DKFZ); McGill University; McGill University
RP Majewski, J (corresponding author), McGill Univ, Dept Human Genet, Montreal, PQ H3Z 2Z3, Canada.
EM jacek.majewski@mcgill.ca; s.pfister@dkfz-heidelberg.de; nada.jabado@mcgill.ca
FU Cole Foundation; Genome Canada; Canadian Institute for Health Research (CIHR); Genome BC; Genome Quebec; CIHR-ICR (Institute for Cancer Research); C17, through the Genome Canada/CIHR; Hungarian Scientific Research Fund(OTKA) [T-04639]; National Research and Development Fund (NKFP) [1A/002/2004]; German Cancer Aid [109252]; CNS tumour tissue bank [108456]; BMBF; Samantha Dickson Brain Tumour Trust; National Cancer Center Heidelberg; German Cancer Research Center; Foundation of Stars; Sybille Assmus Award for Neurooncology; Fonds de Recherche en Sante du Quebec; The Brain Tumour Charity [10/106] Funding Source: researchfish
NR 35
TC 2043
Z9 2395
U1 6
U2 247
PU NATURE PUBLISHING 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 9
PY 2012
VL 482
IS 7384
BP 226
EP U119
DI 10.1038/nature10833
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 888HI
UT WOS:000299994100040
PM 22855408
DA 2026-03-09
ER

PT J
AU Rohringer, N
   Ryan, D
   London, RA
   Purvis, M
   Albert, F
   Dunn, J
   Bozek, JD
   Bostedt, C
   Graf, A
   Hill, R
   Hau-Riege, SP
   Rocca, JJ
AF Rohringer, Nina
   Ryan, Duncan
   London, Richard A.
   Purvis, Michael
   Albert, Felicie
   Dunn, James
   Bozek, John D.
   Bostedt, Christoph
   Graf, Alexander
   Hill, Randal
   Hau-Riege, Stefan P.
   Rocca, Jorge J.
TI Atomic inner-shell X-ray laser at 1.46 nanometres pumped by an X-ray free-electron laser
SO NATURE
LA English
DT Article
ID radiation; operation; amplifier
AB Since the invention of the laser more than 50 years ago, scientists have striven to achieve amplification on atomic transitions of increasingly shorter wavelength(1-7). The introduction of X-ray free-electron lasers(8-10) makes it possible to pump new atomic X-ray lasers(11-13) with ultrashort pulse duration, extreme spectral brightness and full temporal coherence. Here we describe the implementation of an X-ray laser in the kiloelectronvolt energy regime, based on atomic population inversion and driven by rapid K-shell photo-ionization using pulses from an X-ray free-electron laser. We established a population inversion of the K alpha transition in singly ionized neon(14) at 1.46 nanometres (corresponding to a photon energy of 849 electronvolts) in an elongated plasma column created by irradiation of a gas medium. We observed strong amplified spontaneous emission from the end of the excited plasma. This resulted in femtosecond-duration, high-intensity X-ray pulses of much shorter wavelength and greater brilliance than achieved with previous atomic X-ray lasers. Moreover, this scheme provides greatly increased wavelength stability, monochromaticity and improved temporal coherence by comparison with present-day X-ray free-electron lasers. The atomic X-ray lasers realized here may be useful for high-resolution spectroscopy and nonlinear X-ray studies.
C1 [Ryan, Duncan; Purvis, Michael; Rocca, Jorge J.] Colorado State Univ, Ft Collins, CO 80523 USA.
   [Ryan, Duncan; Purvis, Michael; Rocca, Jorge J.] NSF Engn Res Ctr Extreme Ultraviolet Sci & Techno, Ft Collins, CO 80523 USA.
   [Bozek, John D.; Bostedt, Christoph] SLAC Natl Accelerator Lab, LCLS, Menlo Pk, CA 94025 USA.
   [Rohringer, Nina; London, Richard A.; Albert, Felicie; Dunn, James; Graf, Alexander; Hill, Randal; Hau-Riege, Stefan P.] Lawrence Livermore Natl Lab, Livermore, CA 94551 USA.
C3 Colorado State University System; Colorado State University Fort Collins; National Science Foundation (NSF); Stanford University; United States Department of Energy (DOE); SLAC National Accelerator Laboratory; United States Department of Energy (DOE); Lawrence Livermore National Laboratory
RP Rohringer, N (corresponding author), DESY, Max Planck Adv Study Grp, Ctr Free Electron Laser Sci, Notkestr 85, D-22607 Hamburg, Germany.
EM nina.rohringer@asg.mpg.de
FU US Department of Energy by Lawrence Livermore National Laboratory (LLNL) [DE-AC52-07NA27344]; LLNL's LDRD [09-LW-044]; US Department of Energy Basic Energy Sciences AMOS
NR 30
TC 291
Z9 315
U1 1
U2 128
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JAN 26
PY 2012
VL 481
IS 7382
BP 488
EP 491
DI 10.1038/nature10721
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 881GY
UT WOS:000299471800036
PM 22281598
DA 2026-03-09
ER

PT J
AU Fujiwara, Y
   Dixon, JA
   O'Hara, F
   Funder, ED
   Dixon, DD
   Rodriguez, RA
   Baxter, RD
   Herlé, B
   Sach, N
   Collins, MR
   Ishihara, Y
   Baran, PS
AF Fujiwara, Yuta
   Dixon, Janice A.
   O'Hara, Fionn
   Funder, Erik Daa
   Dixon, Darryl D.
   Rodriguez, Rodrigo A.
   Baxter, Ryan D.
   Herle, Bart
   Sach, Neal
   Collins, Michael R.
   Ishihara, Yoshihiro
   Baran, Phil S.
TI Practical and innate carbon-hydrogen functionalization of heterocycles
SO NATURE
LA English
DT Article
ID aromatic-compounds; trifluoromethylation; aryl; strategy; chemistry; fluorine; reagent; arenes
AB Nitrogen-rich heterocyclic compounds have had a profound effect on human health because these chemical motifs are found in a large number of drugs used to combat a broad range of diseases and pathophysiological conditions. Advances in transition-metal-mediated cross-coupling have simplified the synthesis of such molecules; however, C-H functionalization of medicinally important heterocycles that does not rely on pre-functionalized starting materials is an underdeveloped area(1-9). Unfortunately, the innate properties of heterocycles that make them so desirable for biological applications-such as aqueous solubility and their ability to act as ligands-render them challenging substrates for direct chemical functionalization. Here we report that zinc sulphinate salts can be used to transfer alkyl radicals to heterocycles, allowing for the mild (moderate temperature, 50 degrees C or less), direct and operationally simple formation of medicinally relevant C-C bonds while reacting in a complementary fashion to other innate C-H functionalization methods(2-6) (Minisci, borono-Minisci, electrophilic aromatic substitution, transition-metal-mediated C-H insertion and C-H deprotonation). We prepared a toolkit of these reagents and studied their reactivity across a wide range of heterocycles (natural products, drugs and building blocks) without recourse to protecting-group chemistry. The reagents can even be used in tandem fashion in a single pot in the presence of water and air.
C1 [Fujiwara, Yuta; Dixon, Janice A.; O'Hara, Fionn; Funder, Erik Daa; Dixon, Darryl D.; Rodriguez, Rodrigo A.; Baxter, Ryan D.; Herle, Bart; Sach, Neal; Collins, Michael R.; Ishihara, Yoshihiro; Baran, Phil S.] Scripps Res Inst, Dept Chem, La Jolla, CA 92037 USA.
   [Sach, Neal; Collins, Michael R.] Pfizer Inc, La Jolla Labs, Dept Chem, San Diego, CA 92121 USA.
C3 Scripps Research Institute; Pfizer; Pfizer USA
RP Baran, PS (corresponding author), Scripps Res Inst, Dept Chem, 10550 N Torrey Pines Rd, La Jolla, CA 92037 USA.
EM pbaran@scripps.edu
FU US NIH/NIGMS [GM-073949]; Uehara Memorial Foundation; US-UK Fulbright Commission; Aarhus University; OChem Graduate School; CDNA; CFIN; NABIIT; US NIH; Pfizer Inc.
NR 30
TC 799
Z9 871
U1 3
U2 478
PU NATURE PUBLISHING 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 6
PY 2012
VL 492
IS 7427
BP 95
EP +
DI 10.1038/nature11680
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 048EQ
UT WOS:000311893400052
PM 23201691
DA 2026-03-09
ER

PT J
AU Wilson, TR
   Fridlyand, J
   Yan, YB
   Penuel, E
   Burton, L
   Chan, E
   Peng, J
   Lin, E
   Wang, YL
   Sosman, J
   Ribas, A
   Li, J
   Moffat, J
   Sutherlin, DP
   Koeppen, H
   Merchant, M
   Neve, R
   Settleman, J
AF Wilson, Timothy R.
   Fridlyand, Jane
   Yan, Yibing
   Penuel, Elicia
   Burton, Luciana
   Chan, Emily
   Peng, Jing
   Lin, Eva
   Wang, Yulei
   Sosman, Jeff
   Ribas, Antoni
   Li, Jiang
   Moffat, John
   Sutherlin, Daniel P.
   Koeppen, Hartmut
   Merchant, Mark
   Neve, Richard
   Settleman, Jeff
TI Widespread potential for growth-factor-driven resistance to anticancer kinase inhibitors
SO NATURE
LA English
DT Article
ID receptor tyrosine kinases; cell lung-cancer; acquired-resistance; met amplification; tumor-cells; sensitivity; survival; therapy; heterogeneity; activation
AB Mutationally activated kinases define a clinically validated class of targets for cancer drug therapy(1). However, the efficacy of kinase inhibitors in patients whose tumours harbour such alleles is invariably limited by innate or acquired drug resistance(2,3). The identification of resistance mechanisms has revealed a recurrent theme-the engagement of survival signals redundant to those transduced by the targeted kinase(4). Cancer cells typically express multiple receptor tyrosine kinases (RTKs) that mediate signals that converge on common critical downstream cell-survival effectors-most notably, phosphatidylinositol-3-OH kinase (PI(3)K) and mitogen-activated protein kinase (MAPK)(5). Consequently, an increase in RTK-ligand levels, through autocrine tumour-cell production, paracrine contribution from tumour stroma(6) or systemic production, could confer resistance to inhibitors of an oncogenic kinase with a similar signalling output. Here, using a panel of kinase-'addicted' human cancer cell lines, we found that most cells can be rescued from drug sensitivity by simply exposing them to one or more RTK ligands. Among the findings with clinical implications was the observation that hepatocyte growth factor(HGF) confers resistance to the BRAF inhibitor PLX4032 (vemurafenib) in BRAF-mutant melanoma cells. These observations highlight the extensive redundancy of RTK-transduced signalling in cancer cells and the potentially broad role of widely expressed RTK ligands in innate and acquired resistance to drugs targeting oncogenic kinases.
C1 [Wilson, Timothy R.; Chan, Emily; Peng, Jing; Lin, Eva; Merchant, Mark; Neve, Richard; Settleman, Jeff] Genentech Inc, Res Oncol, San Francisco, CA 94080 USA.
   [Fridlyand, Jane] Genentech Inc, Biostatast, San Francisco, CA 94080 USA.
   [Yan, Yibing; Penuel, Elicia; Burton, Luciana; Wang, Yulei] Genentech Inc, Dev Sci, San Francisco, CA 94080 USA.
   [Sosman, Jeff] Vanderbilt Univ, Med Ctr, Div Hematol Oncol, Nashville, TN 37232 USA.
   [Ribas, Antoni] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA.
   [Li, Jiang] Roche Nutley, Med Dev Biometr Biostat, Nutley, NJ 07110 USA.
   [Moffat, John] Genentech Inc, Biochem & Cellular Pharmacol, San Francisco, CA 94080 USA.
   [Sutherlin, Daniel P.] Genentech Inc, Discovery Chem, San Francisco, CA 94080 USA.
   [Koeppen, Hartmut] Genentech Inc, Res Pathol, San Francisco, CA 94080 USA.
C3 Roche Holding; Roche Holding USA; Genentech; Roche Holding; Roche Holding USA; Genentech; Roche Holding; Genentech; Roche Holding USA; Vanderbilt University; University of California System; University of California Los Angeles; UCLA Jonsson Comprehensive Cancer Center; Roche Holding; Genentech; Roche Holding USA; Roche Holding; Roche Holding USA; Genentech; Roche Holding; Genentech; Roche Holding USA
RP Settleman, J (corresponding author), Genentech Inc, Res Oncol, 1 DNA Way, San Francisco, CA 94080 USA.
EM settleman.jeffrey@gene.com
FU NCI NIH HHS [K24 CA097588] Funding Source: Medline
NR 29
TC 957
Z9 1117
U1 0
U2 129
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUL 26
PY 2012
VL 487
IS 7408
BP 505
EP U1652
DI 10.1038/nature11249
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 979KD
UT WOS:000306815300043
PM 22763448
DA 2026-03-09
ER

PT J
AU Zhang, JH
   Benavente, CA
   McEvoy, J
   Flores-Otero, J
   Ding, L
   Chen, X
   Ulyanov, A
   Wu, G
   Wilson, M
   Wang, JM
   Brennan, R
   Rusch, M
   Manning, AL
   Ma, J
   Easton, J
   Shurtleff, S
   Mullighan, C
   Pounds, S
   Mukatira, S
   Gupta, P
   Neale, G
   Zhao, D
   Lu, C
   Fulton, RS
   Fulton, LL
   Hong, X
   Dooling, DJ
   Ochoa, K
   Naeve, C
   Dyson, NJ
   Mardis, ER
   Bahrami, A
   Ellison, D
   Wilson, RK
   Downing, JR
   Dyer, MA
AF Zhang, Jinghui
   Benavente, Claudia A.
   McEvoy, Justina
   Flores-Otero, Jacqueline
   Ding, Li
   Chen, Xiang
   Ulyanov, Anatoly
   Wu, Gang
   Wilson, Matthew
   Wang, Jianmin
   Brennan, Rachel
   Rusch, Michael
   Manning, Amity L.
   Ma, Jing
   Easton, John
   Shurtleff, Sheila
   Mullighan, Charles
   Pounds, Stanley
   Mukatira, Suraj
   Gupta, Pankaj
   Neale, Geoff
   Zhao, David
   Lu, Charles
   Fulton, Robert S.
   Fulton, Lucinda L.
   Hong, Xin
   Dooling, David J.
   Ochoa, Kerri
   Naeve, Clayton
   Dyson, Nicholas J.
   Mardis, Elaine R.
   Bahrami, Armita
   Ellison, David
   Wilson, Richard K.
   Downing, James R.
   Dyer, Michael A.
TI A novel retinoblastoma therapy from genomic and epigenetic analyses
SO NATURE
LA English
DT Article
ID tyrosine kinase; syk inhibitor; cancer; aneuploidy; growth; cells; tumor; mcl-1; gene
AB Retinoblastoma is an aggressive childhood cancer of the developing retina that is initiated by the biallelic loss of RB1. Tumours progress very quickly following RB1 inactivation but the underlying mechanism is not known. Here we show that the retinoblastoma genome is stable, but that multiple cancer pathways can be epigenetically deregulated. To identify the mutations that cooperate with RB1 loss, we performed whole-genome sequencing of retinoblastomas. The overall mutational rate was very low; RB1 was the only known cancer gene mutated. We then evaluated the role of RB1 in genome stability and considered non-genetic mechanisms of cancer pathway deregulation. For example, the proto-oncogene SYK is upregulated in retinoblastoma and is required for tumour cell survival. Targeting SYK with a small-molecule inhibitor induced retinoblastoma tumour cell death in vitro and in vivo. Thus, retinoblastomas may develop quickly as a result of the epigenetic deregulation of key cancer pathways as a direct or indirect result of RB1 loss.
C1 [Benavente, Claudia A.; McEvoy, Justina; Flores-Otero, Jacqueline; Brennan, Rachel; Dyer, Michael A.] St Jude Childrens Res Hosp, Dept Dev Neurobiol, Memphis, TN 38105 USA.
   [Zhang, Jinghui; Chen, Xiang; Ulyanov, Anatoly; Wu, Gang; Rusch, Michael; Easton, John] St Jude Childrens Res Hosp, Dept Computat Biol & Bioinformat, Memphis, TN 38105 USA.
   [Ding, Li; Lu, Charles; Fulton, Robert S.; Fulton, Lucinda L.; Hong, Xin; Dooling, David J.; Ochoa, Kerri; Mardis, Elaine R.; Wilson, Richard K.] Washington Univ, Sch Med St Louis, Genome Inst, St Louis, MO 63108 USA.
   [Ding, Li; Fulton, Robert S.; Fulton, Lucinda L.; Hong, Xin; Dooling, David J.; Ochoa, Kerri; Mardis, Elaine R.; Wilson, Richard K.] Washington Univ, Sch Med St Louis, Dept Genet, St Louis, MO 63108 USA.
   [Wilson, Matthew; Dyer, Michael A.] Univ Tennessee, Hlth Sci Ctr, Dept Ophthalmol, Memphis, TN 38163 USA.
   [Wilson, Matthew] St Jude Childrens Res Hosp, Dept Surg, Memphis, TN 38105 USA.
   [Wang, Jianmin; Mukatira, Suraj; Gupta, Pankaj; Neale, Geoff] St Jude Childrens Res Hosp, Hartwell Ctr Biotechnol & Bioinformat, Memphis, TN 38105 USA.
   [Manning, Amity L.; Dyson, Nicholas J.] Massachusetts Gen Hosp, Charlestown, MA 02129 USA.
   [Ma, Jing; Shurtleff, Sheila; Mullighan, Charles; Bahrami, Armita; Ellison, David; Downing, James R.] St Jude Childrens Res Hosp, Dept Pathol, Memphis, TN 38105 USA.
   [Pounds, Stanley] St Jude Childrens Res Hosp, Dept Biostat, Memphis, TN 38105 USA.
   [Zhao, David; Naeve, Clayton] St Jude Childrens Res Hosp, Dept Informat Sci, Memphis, TN 38105 USA.
   [Mardis, Elaine R.] Washington Univ, Sch Med St Louis, Siteman Canc Ctr, St Louis, MO 63108 USA.
   [Wilson, Richard K.] Washington Univ, Sch Med St Louis, Dept Med, St Louis, MO 63108 USA.
   [Dyer, Michael A.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA.
C3 St Jude Children's Research Hospital; St Jude Children's Research Hospital; Saint Louis University; Washington University (WUSTL); Washington University (WUSTL); Saint Louis University; University of Tennessee System; University of Tennessee Health Science Center; St Jude Children's Research Hospital; St Jude Children's Research Hospital; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; St Jude Children's Research Hospital; St Jude Children's Research Hospital; St Jude Children's Research Hospital; Siteman Cancer Center; Washington University (WUSTL); Saint Louis University; Saint Louis University; Washington University (WUSTL); Howard Hughes Medical Institute
RP Dyer, MA (corresponding author), St Jude Childrens Res Hosp, Dept Dev Neurobiol, 332 N Lauderdale St, Memphis, TN 38105 USA.
EM rwilson@wustl.edu; james.downing@stjude.org; michael.dyer@stjude.org
FU St Jude Children's Research Hospital - Washington University; St Jude Children's Research Hospital; NCI [CA21765]; NIH [EY014867, EY018599, GM81607, CA64402]; American Cancer Society; Research to Prevent Blindness Foundation; American Lebanese Syrian Associated Charities; MGH Cancer Center Saltonstall Foundation; AstraZeneca; National Cancer Institute [P30CA021765] Funding Source: NIH RePORTER
NR 32
TC 401
Z9 478
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 JAN 19
PY 2012
VL 481
IS 7381
BP 329
EP 334
DI 10.1038/nature10733
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 877VK
UT WOS:000299210600035
PM 22237022
DA 2026-03-09
ER

PT J
AU Harper, J
   Humphrey, N
   Pfeffer, WT
   Brown, J
   Fettweis, X
AF Harper, J.
   Humphrey, N.
   Pfeffer, W. T.
   Brown, J.
   Fettweis, X.
TI Greenland ice-sheet contribution to sea-level rise buffered by meltwater storage in firn
SO NATURE
LA English
DT Article
ID mass-balance; accumulation; model; parameterizations; retention; runoff; melt
AB Surface melt on the Greenland ice sheet has shown increasing trends in areal extent and duration since the beginning of the satellite era(1-3). Records for melt were broken in 2005(4), 2007(5), 2010(6) and 2012(7). Much of the increased surface melt is occurring in the percolation zone, a region of the accumulation area that is perennially covered by snow and firn (partly compacted snow). The fate of melt water in the percolation zone is poorly constrained: some may travel away from its point of origin and eventually influence the ice sheet's flow dynamics and mass balance and the global sea level, whereas some may simply infiltrate into cold snow or firn and refreeze with none of these effects. Here we quantify the existing water storage capacity of the percolation zone of the Greenland ice sheet and show the potential for hundreds of gigatonnes of meltwater storage. We collected in situ observations of firn structure and meltwater retention along a roughly 85-kilometre-long transect of the melting accumulation area. Our data show that repeated infiltration events in which melt water penetrates deeply(more than 10 metres) eventually fill all pore space with water. As future surface melt intensifies under Arctic warming, a fraction of melt water that would otherwise contribute to sea-level rise will fill existing pore space of the percolation zone. We estimate the lower and upper bounds of this storage sink to be 322 +/- 44 gigatonnes and 1,289(-252)(+388) gigatonnes, respectively. Furthermore, we find that decades are required to fill this pore space under a range of plausible future climate conditions. Hence, routing of surface melt water into filling the pore space of the firn column will delay expansion of the area contributing to sea-level rise, although once the pore space is filled it cannot quickly be regenerated.
C1 [Harper, J.; Brown, J.] Univ Montana, Missoula, MT 59812 USA.
   [Humphrey, N.] Univ Wyoming, Laramie, WY 82071 USA.
   [Pfeffer, W. T.] Univ Colorado, Inst Arctic & Alpine Res, Boulder, CO 80309 USA.
   [Fettweis, X.] Univ Liege, B-114000 Liege, Belgium.
C3 University of Montana System; University of Montana; University of Wyoming; University of Colorado System; University of Colorado Boulder; University of Liege
RP Harper, J (corresponding author), Univ Montana, Missoula, MT 59812 USA.
EM joel@mso.umt.edu
FU US National Science Foundation Office of Polar Programs, Arctic Natural Sciences [0612506, 0612374, 0612351]; Directorate For Geosciences; Division Of Polar Programs [0612351] Funding Source: National Science Foundation; Office of Polar Programs (OPP); Directorate For Geosciences [0612374, 0612506] Funding Source: National Science Foundation
NR 28
TC 182
Z9 226
U1 1
U2 91
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD NOV 8
PY 2012
VL 491
IS 7423
BP 240
EP 243
DI 10.1038/nature11566
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 033DP
UT WOS:000310774300041
PM 23135470
DA 2026-03-09
ER

PT J
AU Zheng, W
   Postman, M
   Zitrin, A
   Moustakas, J
   Shu, XW
   Jouvel, S
   Host, O
   Molino, A
   Bradley, L
   Coe, D
   Moustakas, LA
   Carrasco, M
   Ford, H
   Benítez, N
   Lauer, TR
   Seitz, S
   Bouwens, R
   Koekemoer, A
   Medezinski, E
   Bartelmann, M
   Broadhurst, T
   Donahue, M
   Grillo, C
   Infante, L
   Jha, SW
   Kelson, DD
   Lahav, O
   Lemze, D
   Melchior, P
   Meneghetti, M
   Merten, J
   Nonino, M
   Ogaz, S
   Rosati, P
   Umetsu, K
   van der Wel, A
AF Zheng, Wei
   Postman, Marc
   Zitrin, Adi
   Moustakas, John
   Shu, Xinwen
   Jouvel, Stephanie
   Host, Ole
   Molino, Alberto
   Bradley, Larry
   Coe, Dan
   Moustakas, Leonidas A.
   Carrasco, Mauricio
   Ford, Holland
   Benitez, Narciso
   Lauer, Tod R.
   Seitz, Stella
   Bouwens, Rychard
   Koekemoer, Anton
   Medezinski, Elinor
   Bartelmann, Matthias
   Broadhurst, Tom
   Donahue, Megan
   Grillo, Claudio
   Infante, Leopoldo
   Jha, Saurabh W.
   Kelson, Daniel D.
   Lahav, Ofer
   Lemze, Doron
   Melchior, Peter
   Meneghetti, Massimo
   Merten, Julian
   Nonino, Mario
   Ogaz, Sara
   Rosati, Piero
   Umetsu, Keiichi
   van der Wel, Arjen
TI A magnified young galaxy from about 500 million years after the Big Bang
SO NATURE
LA English
DT Article
ID similar-to 7; stellar population synthesis; deep survey; cluster; bright; discovery; hubble; macs; reionization; calibration
AB Re-ionization of the intergalactic medium occurred in the early Universe at redshift z approximate to 6-11, following the formation of the first generation of stars(1). Those young galaxies (where the bulk of stars formed) at a cosmic age of less than about 500 million years (z less than or similar to 10) remain largely unexplored because they are at or beyond the sensitivity limits of existing large telescopes. Understanding the properties of these galaxies is critical to identifying the source of the radiation that re-ionized the intergalactic medium. Gravitational lensing by galaxy clusters allows the detection of high-redshift galaxies fainter than what otherwise could be found in the deepest images of the sky(2). Here we report multiband observations of the cluster MACS J1149+2223 that have revealed (with high probability) a gravitationally magnified galaxy from the early Universe, at a redshift of z = 9.6 +/- 0.2 (that is, a cosmic age of 490 +/- 15 million years, or 3.6 per cent of the age of the Universe). We estimate that it formed less than 200 million years after the Big Bang (at the 95 per cent confidence level), implying a formation redshift of less than or similar to 14. Given the small sky area that our observations cover, faint galaxies seem to be abundant at such a young cosmic age, suggesting that they may be the dominant source for the early re-ionization of the intergalactic medium.
C1 [Zheng, Wei; Ford, Holland; Medezinski, Elinor; Lemze, Doron] Johns Hopkins Univ, Dept Phys & Astron, Baltimore, MD 21218 USA.
   [Postman, Marc; Bradley, Larry; Coe, Dan; Koekemoer, Anton; Ogaz, Sara] Space Telescope Sci Inst, Baltimore, MD 21218 USA.
   [Zitrin, Adi; Bartelmann, Matthias] Heidelberg Univ, Inst Theoret Astrophys, D-69120 Heidelberg, Germany.
   [Moustakas, John] Siena Coll, Dept Phys & Astron, Loudonville, NY 12211 USA.
   [Shu, Xinwen] Univ Sci & Technol China, Dept Astron, Hefei 230026, Anhui, Peoples R China.
   [Jouvel, Stephanie; Host, Ole; Lahav, Ofer] UCL, Dept Phys & Astron, London WC1E 6BT, England.
   [Jouvel, Stephanie] Inst Ciencies Espai, Bellaterra 08193, Spain.
   [Molino, Alberto; Benitez, Narciso] Inst Astrofis Andalucia, E-18008 Granada, Spain.
   [Moustakas, Leonidas A.; Merten, Julian] CALTECH, Jet Prop Lab, Pasadena, CA 91109 USA.
   [Carrasco, Mauricio; Infante, Leopoldo] Pontificia Univ Catolica Chile, Dept Astron & Astrofis, Santiago 22, Chile.
   [Lauer, Tod R.] Natl Opt Astron Observ, Tucson, AZ 85726 USA.
   [Seitz, Stella] Univ Sternwarte Munchen, D-81679 Munich, Germany.
   [Bouwens, Rychard] Leiden Univ, Leiden Observ, NL-2300 RA Leiden, Netherlands.
   [Broadhurst, Tom] Univ Basque Country, Dept Theoret Phys, Bilbao 48080, Spain.
   [Broadhurst, Tom] Basque Fdn Sci, Ikerbasque, Bilbao 48011, Spain.
   [Donahue, Megan] Michigan State Univ, Dept Phys & Astron, E Lansing, MI 48824 USA.
   [Grillo, Claudio] Univ Copenhagen, Dark Cosmol Ctr, Niels Bohr Inst, DK-2100 Copenhagen, Denmark.
   [Jha, Saurabh W.] Rutgers State Univ, Dept Phys & Astron, Piscataway, NJ 08854 USA.
   [Kelson, Daniel D.] Observ Carnegie Inst Sci, Pasadena, CA 91101 USA.
   [Melchior, Peter] Ohio State Univ, Dept Phys, Columbus, OH 43210 USA.
   [Nonino, Mario] INAF Osservatorio Astron Trieste, I-40131 Trieste, Italy.
   [Meneghetti, Massimo] INAF Osservatorio Astron Bologna, I-40127 Bologna, Italy.
   [Rosati, Piero] European So Observ, D-85748 Garching, Germany.
   [Umetsu, Keiichi] Acad Sinica, Inst Astron & Astrophys, Taipei 10617, Taiwan.
   [van der Wel, Arjen] Max Planck Inst Astron, D-69117 Heidelberg, Germany.
C3 Johns Hopkins University; Space Telescope Science Institute; Ruprecht Karls University Heidelberg; Chinese Academy of Sciences; University of Science & Technology of China, CAS; University of London; University College London; Institut d'Estudis Espacials de Catalunya (IEEC); Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Instituto de Ciencias del Espacio (ICE); Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Instituto de Astrofisica de Andalucia (IAA); National Aeronautics & Space Administration (NASA); NASA Jet Propulsion Laboratory (JPL); California Institute of Technology; Pontificia Universidad Catolica de Chile; National Optical Astronomy Observatory; University of Munich; Leiden University; Leiden University - Excl LUMC; University of Basque Country; Basque Foundation for Science; Michigan State University; University of Copenhagen; Niels Bohr Institute; Rutgers University System; Rutgers University New Brunswick; Carnegie Institution for Science; University System of Ohio; Ohio State University; Istituto Nazionale Astrofisica (INAF); Istituto Nazionale Astrofisica (INAF); European Southern Observatory; Academia Sinica - Taiwan; Max Planck Society
RP Zheng, W (corresponding author), Johns Hopkins Univ, Dept Phys & Astron, Baltimore, MD 21218 USA.
EM zheng@pha.jhu.edu
FU NASA [NAS 5-26555]; NSF [AST-0908246]; Baden Wurttemberg Stiftung; Science and Technology Facilities Council [ST/F001991/1, ST/J001511/1] Funding Source: researchfish; STFC [ST/J001511/1, ST/F001991/1] Funding Source: UKRI
NR 30
TC 265
Z9 289
U1 0
U2 54
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD SEP 20
PY 2012
VL 489
IS 7416
BP 406
EP 408
DI 10.1038/nature11446
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 007AK
UT WOS:000308860900039
PM 22996554
DA 2026-03-09
ER

PT J
AU Griffith, CA
   Lora, JM
   Turner, J
   Penteado, PF
   Brown, RH
   Tomasko, MG
   Doose, L
   See, C
AF Griffith, Caitlin A.
   Lora, Juan M.
   Turner, Jake
   Penteado, Paulo F.
   Brown, Robert H.
   Tomasko, Martin G.
   Doose, Lyn
   See, Charles
TI Possible tropical lakes on Titan from observations of dark terrain
SO NATURE
LA English
DT Article
ID huygens probe; cassini radar; atmosphere; model; clouds; dunes
AB Titan has clouds, rain and lakes-like Earth-but composed of methane rather than water. Unlike Earth, most of the condensable methane (the equivalent of 5 m depth globally averaged(1)) lies in the atmosphere. Liquid detected on the surface (about 2 m deep) has been found by radar images only poleward of 50 degrees latitude(2,3), while dune fields pervade the tropics(4). General circulation models explain this dichotomy, predicting that methane efficiently migrates to the poles from these lower latitudes(5-7). Here we report an analysis of near-infrared spectral images(8) of the region between 20 degrees N and 20 degrees S latitude. The data reveal that the lowest fluxes in seven wavelength bands that probe Titan's surface occur in an oval region of about 60 x 40 km(2), which has been observed repeatedly since 2004. Radiative transfer analyses demonstrate that the resulting spectrum is consistent with a black surface, indicative of liquid methane on the surface. Enduring low-latitude lakes are best explained as supplied by subterranean sources (within the last 10,000 years), which may be responsible for Titan's methane, the continual photochemical depletion of which furnishes Titan's organic chemistry(9).
C1 [Griffith, Caitlin A.; Lora, Juan M.; Turner, Jake; Brown, Robert H.; Tomasko, Martin G.; Doose, Lyn; See, Charles] Univ Arizona, Lunar & Planetary Lab, Tucson, AZ 85721 USA.
   [Penteado, Paulo F.] Univ Sao Paulo, IAG, BR-05508090 Sao Paulo, Brazil.
C3 University of Arizona; Universidade de Sao Paulo
RP Griffith, CA (corresponding author), Univ Arizona, Lunar & Planetary Lab, Tucson, AZ 85721 USA.
EM griffith@lpl.arizona.edu
FU NASA
NR 30
TC 46
Z9 61
U1 0
U2 31
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 14
PY 2012
VL 486
IS 7402
BP 237
EP 239
DI 10.1038/nature11165
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 957UH
UT WOS:000305189000030
PM 22699614
DA 2026-03-09
ER

PT J
AU Kobayashi, Y
   Kumakura, K
   Akasaka, T
   Makimoto, T
AF Kobayashi, Yasuyuki
   Kumakura, Kazuhide
   Akasaka, Tetsuya
   Makimoto, Toshiki
TI Layered boron nitride as a release layer for mechanical transfer of GaN-based devices
SO NATURE
LA English
DT Article
ID laser lift-off; epitaxial-growth; thin-films; bn
AB Nitride semiconductors are the materials of choice for a variety of device applications, notably optoelectronics(1,2) and high-frequency/high-power electronics(3). One important practical goal is to realize such devices on large, flexible and affordable substrates, on which direct growth of nitride semiconductors of sufficient quality is problematic. Several techniques-such as laser lift-off(4,5)-have been investigated to enable the transfer of nitride devices from one substrate to another, but existing methods still have some important disadvantages. Here we demonstrate that hexagonal boron nitride (h-BN) can form a release layer that enables the mechanical transfer of gallium nitride (GaN)-based device structures onto foreign substrates. The h-BN layer serves two purposes: it acts as a buffer layer for the growth of high-quality GaN-based semiconductors, and provides a shear plane that makes it straightforward to release the resulting devices. We illustrate the potential versatility of this approach by using h-BN-buffered sapphire substrates to grow an AlGaN/GaN heterostructure with electron mobility of 1,100 cm(2) V-1 s(-1), an InGaN/GaN multiple-quantum-well structure, and a multiple-quantum-well light-emitting diode. These device structures, ranging in area from five millimetres square to two centimetres square, are then mechanically released from the sapphire substrates and successfully transferred onto other substrates.
C1 [Kobayashi, Yasuyuki; Kumakura, Kazuhide; Akasaka, Tetsuya; Makimoto, Toshiki] Nippon Telegraph & Tel Corp 3 1, NTT Basic Res Labs, Atsugi, Kanagawa 2430198, Japan.
C3 NTT, Inc
RP Kobayashi, Y (corresponding author), Nippon Telegraph & Tel Corp 3 1, NTT Basic Res Labs, Atsugi, Kanagawa 2430198, Japan.
EM kobayashi.yasuyuki@lab.ntt.co.jp
NR 28
TC 402
Z9 446
U1 7
U2 615
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 12
PY 2012
VL 484
IS 7393
BP 223
EP 227
DI 10.1038/nature10970
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 930OV
UT WOS:000303149900031
PM 22498627
DA 2026-03-09
ER

PT J
AU Amole, C
   Ashkezari, MD
   Baquero-Ruiz, M
   Bertsche, W
   Bowe, PD
   Butler, E
   Capra, A
   Cesar, CL
   Charlton, M
   Deller, A
   Donnan, PH
   Eriksson, S
   Fajans, J
   Friesen, T
   Fujiwara, MC
   Gill, DR
   Gutierrez, A
   Hangst, JS
   Hardy, WN
   Hayden, ME
   Humphries, AJ
   Isaac, CA
   Jonsell, S
   Kurchaninov, L
   Little, A
   Madsen, N
   McKenna, JTK
   Menary, S
   Napoli, SC
   Nolan, P
   Olchanski, K
   Olin, A
   Pusa, P
   Rasmussen, CO
   Robicheaux, F
   Sarid, E
   Shields, CR
   Silveira, DM
   Stracka, S
   So, C
   Thompson, RI
   van der Werf, DP
   Wurtele, JS
AF Amole, C.
   Ashkezari, M. D.
   Baquero-Ruiz, M.
   Bertsche, W.
   Bowe, P. D.
   Butler, E.
   Capra, A.
   Cesar, C. L.
   Charlton, M.
   Deller, A.
   Donnan, P. H.
   Eriksson, S.
   Fajans, J.
   Friesen, T.
   Fujiwara, M. C.
   Gill, D. R.
   Gutierrez, A.
   Hangst, J. S.
   Hardy, W. N.
   Hayden, M. E.
   Humphries, A. J.
   Isaac, C. A.
   Jonsell, S.
   Kurchaninov, L.
   Little, A.
   Madsen, N.
   McKenna, J. T. K.
   Menary, S.
   Napoli, S. C.
   Nolan, P.
   Olchanski, K.
   Olin, A.
   Pusa, P.
   Rasmussen, C. O.
   Robicheaux, F.
   Sarid, E.
   Shields, C. R.
   Silveira, D. M.
   Stracka, S.
   So, C.
   Thompson, R. I.
   van der Werf, D. P.
   Wurtele, J. S.
TI Resonant quantum transitions in trapped antihydrogen atoms
SO NATURE
LA English
DT Article
ID magnetic trap; confinement
AB The hydrogen atom is one of the most important and influential model systems in modern physics. Attempts to understand its spectrum are inextricably linked to the early history and development of quantum mechanics. The hydrogen atom's stature lies in its simplicity and in the accuracy with which its spectrum can be measured(1) and compared to theory. Today its spectrum remains a valuable tool for determining the values of fundamental constants and for challenging the limits of modern physics, including the validity of quantum electrodynamics and-by comparison with measurements on its antimatter counterpart, antihydrogen-the validity of CPT (charge conjugation, parity and time reversal) symmetry. Here we report spectroscopy of a pure antimatter atom, demonstrating resonant quantum transitions in antihydrogen. We have manipulated the internal spin state(2,3) of antihydrogen atoms so as to induce magnetic resonance transitions between hyperfine levels of the positronic ground state. We used resonant microwave radiation to flip the spin of the positron in antihydrogen atoms that were magnetically trapped(4-6) in the ALPHA apparatus. The spin flip causes trapped anti-atoms to be ejected from the trap. We look for evidence of resonant interaction by comparing the survival rate of trapped atoms irradiated with microwaves on-resonance to that of atoms subjected to microwaves that are off-resonance. In one variant of the experiment, we detect 23 atoms that survive in 110 trapping attempts with microwaves off-resonance (0.21 per attempt), and only two atoms that survive in 103 attempts with microwaves on-resonance (0.02 per attempt). We also describe the direct detection of the annihilation of antihydrogen atoms ejected by the microwaves.
C1 [Bowe, P. D.; Hangst, J. S.; Rasmussen, C. O.] Aarhus Univ, Dept Phys & Astron, DK-8000 Aarhus C, Denmark.
   [Amole, C.; Capra, A.; Menary, S.] York Univ, Dept Phys & Astron, Toronto, ON M3J 1P3, Canada.
   [Ashkezari, M. D.; Hayden, M. E.] Simon Fraser Univ, Dept Phys, Burnaby, BC V5A 1S6, Canada.
   [Baquero-Ruiz, M.; Fajans, J.; Little, A.; So, C.; Wurtele, J. S.] Univ Calif Berkeley, Dept Phys, Berkeley, CA 94720 USA.
   [Bertsche, W.; Charlton, M.; Deller, A.; Eriksson, S.; Humphries, A. J.; Isaac, C. A.; Madsen, N.; Napoli, S. C.; Shields, C. R.; van der Werf, D. P.] Swansea Univ, Dept Phys, Swansea SA2 8PP, W Glam, Wales.
   [Bertsche, W.] Univ Manchester, Sch Phys & Astron, Manchester M13 9PL, Lancs, England.
   [Bertsche, W.] Cockcroft Inst, Warrington WA4 4AD, Cheshire, England.
   [Butler, E.] CERN, Dept PH, CH-1211 Geneva 23, Switzerland.
   [Cesar, C. L.] Univ Fed Rio de Janeiro, Inst Fis, BR-21941972 Rio De Janeiro, Brazil.
   [Donnan, P. H.; Robicheaux, F.] Auburn Univ, Dept Phys, Auburn, AL 36849 USA.
   [Fajans, J.; Wurtele, J. S.] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Berkeley, CA 94720 USA.
   [Friesen, T.; Fujiwara, M. C.; Thompson, R. I.] Univ Calgary, Dept Phys & Astron, Calgary, AB T2N 1N4, Canada.
   [Fujiwara, M. C.; Gill, D. R.; Kurchaninov, L.; Olchanski, K.; Olin, A.; Stracka, S.] TRIUMF, Vancouver, BC V6T 2A3, Canada.
   [Gutierrez, A.; Hardy, W. N.] Univ British Columbia, Dept Geophys & Astron, Vancouver, BC V6T 1Z1, Canada.
   [Hardy, W. N.] Canadian Inst Adv Res, Toronto, ON M5G 1Z8, Canada.
   [Jonsell, S.] Stockholm Univ, Dept Phys, SE-10691 Stockholm, Sweden.
   [McKenna, J. T. K.; Nolan, P.; Pusa, P.] Univ Liverpool, Dept Phys, Liverpool L69 7ZE, Merseyside, England.
   [Olin, A.] Univ Victoria, Dept Phys & Astron, Victoria, BC V8W 3P6, Canada.
   [Sarid, E.] Nucl Res Ctr Negev, Dept Phys, IL-84190 Beer Sheva, Israel.
   [Silveira, D. M.] RIKEN, Atom Phys Lab, Wako, Saitama 3510198, Japan.
C3 Aarhus University; York University - Canada; Simon Fraser University; University of California System; University of California Berkeley; Swansea University; University of Manchester; STFC Daresbury Laboratory; European Organization for Nuclear Research (CERN); Universidade Federal do Rio de Janeiro; Auburn University System; Auburn University; United States Department of Energy (DOE); Lawrence Berkeley National Laboratory; University of California System; University of California Berkeley; University of Calgary; University of British Columbia; University of British Columbia; Canadian Institute for Advanced Research (CIFAR); Stockholm University; University of Liverpool; University of Victoria; RIKEN
RP Hangst, JS (corresponding author), Aarhus Univ, Dept Phys & Astron, DK-8000 Aarhus C, Denmark.
EM hangst@phys.au.dk; mhayden@sfu.ca
FU CNPq (Brazil); FINEP/RENAFAE (Brazil); ISF (Israel); MEXT (Japan); FNU (Denmark); VR (Sweden); NSERC (Canada); NRC/TRIUMF (Canada); AITF (Canada); FQRNT (Canada); DOE (USA); NSF (USA); EPSRC (UK); Royal Society (UK); Leverhulme Trust (UK); CERN; EPSRC [EP/H026932/1, EP/F019785/1, EP/E048951/1, EP/H02431X/1] Funding Source: UKRI; STFC [ST/G008248/1] Funding Source: UKRI; Engineering and Physical Sciences Research Council [EP/E048951/1, EP/F019785/1, EP/H026932/1, EP/H02431X/1] Funding Source: researchfish; Science and Technology Facilities Council [ST/G008248/1] Funding Source: researchfish; Direct For Mathematical & Physical Scien; Division Of Physics [0903811] Funding Source: National Science Foundation
NR 21
TC 126
Z9 140
U1 0
U2 63
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 22
PY 2012
VL 483
IS 7390
BP 439
EP U86
DI 10.1038/nature10942
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 912CC
UT WOS:000301771200037
PM 22398451
DA 2026-03-09
ER

PT J
AU Wadham, JL
   Arndt, S
   Tulaczyk, S
   Stibal, M
   Tranter, M
   Telling, J
   Lis, GP
   Lawson, E
   Ridgwell, A
   Dubnick, A
   Sharp, MJ
   Anesio, AM
   Butler, CEH
AF Wadham, J. L.
   Arndt, S.
   Tulaczyk, S.
   Stibal, M.
   Tranter, M.
   Telling, J.
   Lis, G. P.
   Lawson, E.
   Ridgwell, A.
   Dubnick, A.
   Sharp, M. J.
   Anesio, A. M.
   Butler, C. E. H.
TI Potential methane reservoirs beneath Antarctica
SO NATURE
LA English
DT Article
ID gas-hydrate; production-rates; cascadia margin; ice-sheet; sediments; deep; lake; geochemistry; populations; diagenesis
AB Once thought to be devoid of life, the ice-covered parts of Antarctica are now known to be a reservoir of metabolically active microbial cells and organic carbon(1). The potential for methanogenic archaea to support the degradation of organic carbon to methane beneath the ice, however, has not yet been evaluated. Large sedimentary basins containing marine sequences up to 14 kilometres thick(2) and an estimated 21,000 petagrams (1 Pg equals 10(15) g) of organic carbon are buried beneath the Antarctic Ice Sheet. No data exist for rates of methanogenesis in sub-Antarctic marine sediments. Here we present experimental data from other subglacial environments that demonstrate the potential for overridden organic matter beneath glacial systems to produce methane. We also numerically simulate the accumulation of methane in Antarctic sedimentary basins using an established one-dimensional hydrate model(3) and show that pressure/temperature conditions favour methane hydrate formation down to sediment depths of about 300 metres in West Antarctica and 700 metres in East Antarctica. Our results demonstrate the potential for methane hydrate accumulation in Antarctic sedimentary basins, where the total inventory depends on rates of organic carbon degradation and conditions at the ice-sheet bed. We calculate that the sub-Antarctic hydrate inventory could be of the same order of magnitude as that of recent estimates made for Arctic permafrost. Our findings suggest that the Antarctic Ice Sheet may be a neglected but important component of the global methane budget, with the potential to act as a positive feedback on climate warming during ice-sheet wastage.
C1 [Wadham, J. L.; Arndt, S.; Stibal, M.; Tranter, M.; Telling, J.; Lis, G. P.; Lawson, E.; Ridgwell, A.; Anesio, A. M.; Butler, C. E. H.] Univ Bristol, Sch Geog Sci, Bristol BS8 1SS, Avon, England.
   [Arndt, S.] Univ Utrecht, Dept Earth Sci Geochem, NL-3508 Utrecht, Netherlands.
   [Tulaczyk, S.; Sharp, M. J.] Univ Calif Santa Cruz, Dept Earth & Planetary Sci, Santa Cruz, CA 95064 USA.
   [Dubnick, A.] Univ Alberta, Dept Earth & Atmospher Sci, Edmonton, AB T6G 2E3, Canada.
C3 University of Bristol; Utrecht University; University of California System; University of California Santa Cruz; University of Alberta
RP Wadham, JL (corresponding author), Univ Bristol, Sch Geog Sci, Bristol BS8 1SS, Avon, England.
EM j.l.wadham@bris.ac.uk
FU Natural Environment Research Council (UK-NERC) [NE/E004016/1]; National Science Foundation WISSARD project [NSF-AISS 0839142]; Leverhulme Trust via a Phillip Leverhulme award; Netherlands Organisation for Scientific Research (NWO); NSERC; Antarctica New Zealand; Polar Continental Shelf Project; NSERC Undergraduate Student Research Award; US National Science Foundation; Directorate For Geosciences [0839142, 0838947] Funding Source: National Science Foundation; Office of Polar Programs (OPP) [0838947, 0839142] Funding Source: National Science Foundation; NERC [NE/I021322/1, NE/E004016/1] Funding Source: UKRI; Natural Environment Research Council [NE/E004016/1, NE/I021322/1] Funding Source: researchfish
NR 32
TC 153
Z9 178
U1 0
U2 258
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD AUG 30
PY 2012
VL 488
IS 7413
BP 633
EP 637
DI 10.1038/nature11374
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 996NC
UT WOS:000308095100051
PM 22932387
DA 2026-03-09
ER

PT J
AU Kohstall, C
   Zaccanti, M
   Jag, M
   Trenkwalder, A
   Massignan, P
   Bruun, GM
   Schreck, F
   Grimm, R
AF Kohstall, C.
   Zaccanti, M.
   Jag, M.
   Trenkwalder, A.
   Massignan, P.
   Bruun, G. M.
   Schreck, F.
   Grimm, R.
TI Metastability and coherence of repulsive polarons in a strongly interacting Fermi mixture
SO NATURE
LA English
DT Article
ID ultracold gases; ferromagnetism; atoms
AB Ultracold Fermi gases with tunable interactions provide a test bed for exploring the many-body physics of strongly interacting quantum systems(1-4). Over the past decade, experiments have investigated many intriguing phenomena, and precise measurements of ground-state properties have provided benchmarks for the development of theoretical descriptions. Metastable states in Fermi gases with strong repulsive interactions(5-11) represent an exciting area of development. The realization of such systems is challenging, because a strong repulsive interaction in an atomic quantum gas implies the existence of a weakly bound molecular state, which makes the system intrinsically unstable against decay. Here we use radio-frequency spectroscopy to measure the complete excitation spectrum of fermionic K-40 impurities resonantly interacting with a Fermi sea of Li-6 atoms. In particular, we show that a well-defined quasiparticle exists for strongly repulsive interactions. We measure the energy and the lifetime of this 'repulsive polaron'(9,12,13), and probe its coherence properties by measuring the quasiparticle residue. The results are well described by a theoretical approach that takes into account the finite effective range of the interaction in our system. We find that when the effective range is of the order of the interparticle spacing, there is a substantial increase in the lifetime of the quasiparticles. The existence of such a long-lived, metastable many-body state offers intriguing prospects for the creation of exotic quantum phases in ultracold, repulsively interacting Fermi gases.
C1 [Kohstall, C.; Zaccanti, M.; Jag, M.; Trenkwalder, A.; Schreck, F.; Grimm, R.] Austrian Acad Sci, Inst Quantenopt & Quanteninformat, A-6020 Innsbruck, Austria.
   [Kohstall, C.; Jag, M.; Grimm, R.] Univ Innsbruck, Inst Expt Phys, A-6020 Innsbruck, Austria.
   [Kohstall, C.; Jag, M.; Grimm, R.] Univ Innsbruck, Zentrum Quantenphys, A-6020 Innsbruck, Austria.
   [Massignan, P.] Inst Ciencies Foton, Castelldefels 08860, Barcelona, Spain.
   [Bruun, G. M.] Univ Aarhus, Dept Phys & Astron, DK-8000 Aarhus C, Denmark.
C3 Austrian Academy of Sciences; University of Innsbruck; University of Innsbruck; Barcelona Institute of Science & Technology; Universitat Politecnica de Catalunya; Institut de Ciencies Fotoniques (ICFO); Aarhus University
RP Zaccanti, M (corresponding author), Austrian Acad Sci, Inst Quantenopt & Quanteninformat, A-6020 Innsbruck, Austria.
EM matteo.zaccanti@oeaw.ac.at
FU Austrian Science Fund FWF through the SFB FoQuS; Lise Meitner programme of the FWF; ERC
NR 34
TC 415
Z9 446
U1 1
U2 61
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 31
PY 2012
VL 485
IS 7400
BP 615
EP +
DI 10.1038/nature11065
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 949WP
UT WOS:000304608000042
PM 22660321
DA 2026-03-09
ER

PT J
AU Hashimoto, T
   Perlot, T
   Rehman, A
   Trichereau, J
   Ishiguro, H
   Paolino, M
   Sigl, V
   Hanada, T
   Hanada, R
   Lipinski, S
   Wild, B
   Camargo, SMR
   Singer, D
   Richter, A
   Kuba, K
   Fukamizu, A
   Schreiber, S
   Clevers, H
   Verrey, F
   Rosenstiel, P
   Penninger, JM
AF Hashimoto, Tatsuo
   Perlot, Thomas
   Rehman, Ateequr
   Trichereau, Jean
   Ishiguro, Hiroaki
   Paolino, Magdalena
   Sigl, Verena
   Hanada, Toshikatsu
   Hanada, Reiko
   Lipinski, Simone
   Wild, Birgit
   Camargo, Simone M. R.
   Singer, Dustin
   Richter, Andreas
   Kuba, Keiji
   Fukamizu, Akiyoshi
   Schreiber, Stefan
   Clevers, Hans
   Verrey, Francois
   Rosenstiel, Philip
   Penninger, Josef M.
TI ACE2 links amino acid malnutrition to microbial ecology and intestinal inflammation
SO NATURE
LA English
DT Article
ID angiotensin-converting-enzyme; mammalian target; hartnup disorder; crohns-disease; blood-pressure; in-vivo; mice; colitis; carboxypeptidase; rapamycin
AB Malnutrition affects up to one billion people in the world and is a major cause of mortality(1,2). In many cases, malnutrition is associated with diarrhoea and intestinal inflammation, further contributing to morbidity and death(2). The mechanisms by which unbalanced dietary nutrients affect intestinal homeostasis are largely unknown. Here we report that deficiency in murine angiotensin I converting enzyme (peptidyl-dipeptidase A) 2 (Ace2), which encodes a key regulatory enzyme of the renin-angiotensin system (RAS), results in highly increased susceptibility to intestinal inflammation induced by epithelial damage. The RAS is known to be involved in acute lung failure(3), cardiovascular functions(4) and SARS infections(5). Mechanistically, ACE2 has a RAS-independent function, regulating intestinal amino acid homeostasis, expression of antimicrobial peptides, and the ecology of the gut microbiome. Transplantation of the altered microbiota from Ace2 mutant mice into germ-free wild-type hosts was able to transmit the increased propensity to develop severe colitis. ACE2-dependent changes in epithelial immunity and the gut microbiota can be directly regulated by the dietary amino acid tryptophan. Our results identify ACE2 as a key regulator of dietary amino acid homeostasis, innate immunity, gut microbial ecology, and transmissible susceptibility to colitis. These results provide a molecular explanation for how amino acid malnutrition can cause intestinal inflammation and diarrhoea.
C1 [Hashimoto, Tatsuo; Perlot, Thomas; Trichereau, Jean; Paolino, Magdalena; Sigl, Verena; Hanada, Toshikatsu; Hanada, Reiko; Penninger, Josef M.] Austrian Acad Sci, Inst Mol Biotechnol, IMBA, A-1030 Vienna, Austria.
   [Hashimoto, Tatsuo; Ishiguro, Hiroaki] Yokohama City Univ, Grad Sch Med, Dept Med Sci & Cardiorenal Med, Yokohama, Kanagawa 2360004, Japan.
   [Hashimoto, Tatsuo; Ishiguro, Hiroaki] Sch Med, Yokohama, Kanagawa 2360004, Japan.
   [Rehman, Ateequr; Lipinski, Simone; Schreiber, Stefan; Rosenstiel, Philip] Univ Kiel, Inst Clin Mol Biol, D-24105 Kiel, Germany.
   [Wild, Birgit; Richter, Andreas] Univ Vienna, Ctr Ecol, Dept Chem Ecol & Ecosyst Res, A-1090 Vienna, Austria.
   [Camargo, Simone M. R.; Singer, Dustin; Verrey, Francois] Univ Zurich, Inst Physiol, CH-8057 Zurich, Switzerland.
   [Camargo, Simone M. R.; Singer, Dustin; Verrey, Francois] Univ Zurich, Ctr Integrat Human Physiol, CH-8057 Zurich, Switzerland.
   [Kuba, Keiji] Akita Univ, Grad Sch Med, Dept Biol Informat & Expt Therapeut, Akita 0108543, Japan.
   [Fukamizu, Akiyoshi] Univ Tsukuba, Grad Sch Life & Environm Sci, Tsukuba, Ibaraki 3058577, Japan.
   [Clevers, Hans] Royal Netherlands Acad Arts & Sci, Hubrecht Inst, NL-3584 CT Utrecht, Netherlands.
   [Clevers, Hans] Univ Med Ctr Utrecht, NL-3584 CT Utrecht, Netherlands.
C3 Vienna Biocenter (VBC); Institute of Molecular Biotechnology (IMBA); Austrian Academy of Sciences; Yokohama City University; University of Kiel; University of Vienna; University of Zurich; University of Zurich; Zurich Center Integrative Human Physiology (ZIHP); Akita University; University of Tsukuba; Royal Netherlands Academy of Arts & Sciences; Hubrecht Institute (KNAW); Utrecht University; Utrecht University Medical Center
RP Penninger, JM (corresponding author), Austrian Acad Sci, Inst Mol Biotechnol, IMBA, A-1030 Vienna, Austria.
EM p.rosenstiel@mucosa.de; josef.penninger@imba.oeaw.ac.at
FU European Respiratory Society; EuGeneHeart; SENSHIN; Marie Curie IIF; IMBA; Austrian Ministry of Sciences; Austrian Academy of Sciences; GEN-AU (AustroMouse); EU ERC; EU network grants EuGeneHeart, ApoSys and INFLA-Care; BMBF Network 'Systematic genomics of chronic inflammation'; DFG Cluster of Excellence Inflammation at Interfaces [SPP1399, SFB877]; DFG [RO1394]
NR 43
TC 1008
Z9 1166
U1 1
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 JUL 26
PY 2012
VL 487
IS 7408
BP 477
EP U89
DI 10.1038/nature11228
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 979KD
UT WOS:000306815300037
PM 22837003
DA 2026-03-09
ER

PT J
AU Gregori, G
   Ravasio, A
   Murphy, CD
   Schaar, K
   Baird, A
   Bell, AR
   Benuzzi-Mounaix, A
   Bingham, R
   Constantin, C
   Drake, RP
   Edwards, M
   Everson, ET
   Gregory, CD
   Kuramitsu, Y
   Lau, W
   Mithen, J
   Niemann, C
   Park, HS
   Remington, BA
   Reville, B
   Robinson, APL
   Ryutov, DD
   Sakawa, Y
   Yang, S
   Woolsey, NC
   Koenig, M
   Miniati, F
AF Gregori, G.
   Ravasio, A.
   Murphy, C. D.
   Schaar, K.
   Baird, A.
   Bell, A. R.
   Benuzzi-Mounaix, A.
   Bingham, R.
   Constantin, C.
   Drake, R. P.
   Edwards, M.
   Everson, E. T.
   Gregory, C. D.
   Kuramitsu, Y.
   Lau, W.
   Mithen, J.
   Niemann, C.
   Park, H. -S.
   Remington, B. A.
   Reville, B.
   Robinson, A. P. L.
   Ryutov, D. D.
   Sakawa, Y.
   Yang, S.
   Woolsey, N. C.
   Koenig, M.
   Miniati, F.
TI Generation of scaled protogalactic seed magnetic fields in laser-produced shock waves
SO NATURE
LA English
DT Article
ID experimental astrophysics; laboratory simulations; turbulence; magnetohydrodynamics; galaxy; criteria
AB The standard model for the origin of galactic magnetic fields is through the amplification of seed fields via dynamo or turbulent processes to the level consistent with present observations(1-3). Although other mechanisms may also operate(4,5), currents from misaligned pressure and temperature gradients (the Biermann battery process) inevitably accompany the formation of galaxies in the absence of a primordial field. Driven by geometrical asymmetries in shocks(6) associated with the collapse of protogalactic structures, the Biermann battery is believed to generate tiny seed fields to a level of about 10(-21) gauss (refs 7, 8). With the advent of high-power laser systems in the past two decades, a new area of research has opened in which, using simple scaling relations(9,10), astrophysical environments can effectively be reproduced in the laboratory(11,12). Here we report the results of an experiment that produced seed magnetic fields by the Biermann battery effect. We show that these results can be scaled to the intergalactic medium, where turbulence, acting on timescales of around 700 million years, can amplify the seed fields(13,14) sufficiently to affect galaxy evolution.
C1 [Gregori, G.; Murphy, C. D.; Schaar, K.; Baird, A.; Bell, A. R.; Edwards, M.; Lau, W.; Mithen, J.; Reville, B.; Yang, S.] Univ Oxford, Dept Phys, Oxford OX1 3PU, England.
   [Gregori, G.; Bingham, R.; Robinson, A. P. L.] Rutherford Appleton Lab, Didcot OX11 0QX, Oxon, England.
   [Ravasio, A.; Benuzzi-Mounaix, A.; Koenig, M.] Univ Paris 06, Lab Utilisat Lasers Intenses, CNRS CEA, Ecole Polytech,UMR7605, F-91128 Palaiseau, France.
   [Bingham, R.] Univ Strathclyde, Dept Phys, Glasgow G4 0NG, Lanark, Scotland.
   [Constantin, C.; Everson, E. T.; Niemann, C.] Univ Calif Los Angeles, Los Angeles, CA 90095 USA.
   [Drake, R. P.] Univ Michigan, Dept Atmospher Ocean & Space Sci, Ann Arbor, MI 48103 USA.
   [Gregory, C. D.; Woolsey, N. C.] Univ York, Dept Phys, York YO10 5DD, N Yorkshire, England.
   [Kuramitsu, Y.; Sakawa, Y.] Osaka Univ, Inst Laser Engn, Suita, Osaka 5650871, Japan.
   [Park, H. -S.; Remington, B. A.; Ryutov, D. D.] Lawrence Livermore Natl Lab, Livermore, CA 94551 USA.
   [Miniati, F.] ETH, Dept Phys, CH-8093 Zurich, Switzerland.
C3 University of Oxford; UK Research & Innovation (UKRI); Science & Technology Facilities Council (STFC); STFC Rutherford Appleton Laboratory; Institut Polytechnique de Paris; Ecole Polytechnique; CEA; Centre National de la Recherche Scientifique (CNRS); Sorbonne Universite; CNRS - Institute of Physics (INP); University of Strathclyde; University of California System; University of California Los Angeles; University of Michigan System; University of Michigan; University of York - UK; University of Osaka; United States Department of Energy (DOE); Lawrence Livermore National Laboratory; Swiss Federal Institutes of Technology Domain; ETH Zurich
RP Gregori, G (corresponding author), Univ Oxford, Dept Phys, Parks Rd, Oxford OX1 3PU, England.
EM g.gregori1@physics.ox.ac.uk; fm@phys.ethz.ch
FU European Research Council under the European Community; EU
NR 26
TC 119
Z9 135
U1 2
U2 93
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JAN 26
PY 2012
VL 481
IS 7382
BP 480
EP 483
DI 10.1038/nature10747
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 881GY
UT WOS:000299471800034
PM 22281596
DA 2026-03-09
ER

PT J
AU O'Roak, BJ
   Vives, L
   Girirajan, S
   Karakoc, E
   Krumm, N
   Coe, BP
   Levy, R
   Ko, A
   Lee, C
   Smith, JD
   Turner, EH
   Stanaway, IB
   Vernot, B
   Malig, M
   Baker, C
   Reilly, B
   Akey, JM
   Borenstein, E
   Rieder, MJ
   Nickerson, DA
   Bernier, R
   Shendure, J
   Eichler, EE
AF O'Roak, Brian J.
   Vives, Laura
   Girirajan, Santhosh
   Karakoc, Emre
   Krumm, Niklas
   Coe, Bradley P.
   Levy, Roie
   Ko, Arthur
   Lee, Choli
   Smith, Joshua D.
   Turner, Emily H.
   Stanaway, Ian B.
   Vernot, Benjamin
   Malig, Maika
   Baker, Carl
   Reilly, Beau
   Akey, Joshua M.
   Borenstein, Elhanan
   Rieder, Mark J.
   Nickerson, Deborah A.
   Bernier, Raphael
   Shendure, Jay
   Eichler, Evan E.
TI Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations
SO NATURE
LA English
DT Article
ID genome-wide association; copy-number variation; spectrum; chd8; integration; strategy; region; genes; nimh; cnvs
AB It is well established that autism spectrum disorders (ASD) have a strong genetic component; however, for at least 70% of cases, the underlying genetic cause is unknown(1). Under the hypothesis that de novo mutations underlie a substantial fraction of the risk for developing ASD in families with no previous history of ASD or related phenotypes-so-called sporadic or simplex families(2,3)-we sequenced all coding regions of the genome (the exome) for parent-child trios exhibiting sporadic ASD, including 189 new trios and 20 that were previously reported(4). Additionally, we also sequenced the exomes of 50 unaffected siblings corresponding to these new (n = 531) and previously reported trios (n = 19)(4), for a total of 677 individual exomes from 209 families. Here we show that de novo point mutations are overwhelmingly paternal in origin (4:1 bias) and positively correlated with paternal age, consistent with the modest increased risk for children of older fathers to develop ASD(5). Moreover, 39% (49 of 126) of the most severe or disruptive de novo mutations map to a highly interconnected beta-catenin/chromatin remodelling protein network ranked significantly for autism candidate genes. In proband exomes, recurrent protein-altering mutations were observed in two genes: CHD8 and NTNG1. Mutation screening of six candidate genes in 1,703 ASD probands identified additional de novo, protein-altering mutations in GRIN2B, LAMC3 and SCN1A. Combined with copy number variant (CNV) data, these results indicate extreme locus heterogeneity but also provide a target for future discovery, diagnostics and therapeutics.
C1 [O'Roak, Brian J.; Vives, Laura; Girirajan, Santhosh; Karakoc, Emre; Krumm, Niklas; Coe, Bradley P.; Levy, Roie; Ko, Arthur; Lee, Choli; Smith, Joshua D.; Turner, Emily H.; Stanaway, Ian B.; Vernot, Benjamin; Malig, Maika; Baker, Carl; Akey, Joshua M.; Borenstein, Elhanan; Rieder, Mark J.; Nickerson, Deborah A.; Shendure, Jay; Eichler, Evan E.] Univ Washington, Sch Med, Dept Genome Sci, Seattle, WA 98195 USA.
   [Reilly, Beau; Bernier, Raphael] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA.
   [Borenstein, Elhanan] Univ Washington, Dept Comp Sci & Engn, Seattle, WA 98195 USA.
   [Borenstein, Elhanan] Santa Fe Inst, Santa Fe, NM 87501 USA.
   [Eichler, Evan E.] 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; The Santa Fe Institute; University of Washington; University of Washington Seattle; Howard Hughes Medical Institute
RP Eichler, EE (corresponding author), Univ Washington, Sch Med, Dept Genome Sci, Seattle, WA 98195 USA.
EM shendure@uw.edu; eee@gs.washington.edu
FU Simons Foundation Autism Research Initiative (SFARI) [137578, 191889]; NIH [HD065285]
NR 46
TC 1678
Z9 2023
U1 4
U2 288
PU NATURE PUBLISHING 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 10
PY 2012
VL 485
IS 7397
BP 246
EP U136
DI 10.1038/nature10989
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 939HJ
UT WOS:000303799800043
PM 22495309
DA 2026-03-09
ER

PT J
AU Jetz, W
   Thomas, GH
   Joy, JB
   Hartmann, K
   Mooers, AO
AF Jetz, W.
   Thomas, G. H.
   Joy, J. B.
   Hartmann, K.
   Mooers, A. O.
TI The global diversity of birds in space and time
SO NATURE
LA English
DT Article
ID molecular phylogeny; diversification rates; north-american; fossil record; evolution; radiations; patterns; history; biogeography; extinction
AB Current global patterns of biodiversity result from processes that operate over both space and time and thus require an integrated macroecological and macroevolutionary perspective(1-4). Molecular time trees have advanced our understanding of the tempo and mode of diversification(5-7) and have identified remarkable adaptive radiations across the tree of life(8-10). However, incomplete joint phylogenetic and geographic sampling has limited broad-scale inference. Thus, the relative prevalence of rapid radiations and the importance of their geographic settings in shaping global biodiversity patterns remain unclear. Here we present, analyse and map the first complete dated phylogeny of all 9,993 extant species of birds, a widely studied group showing many unique adaptations. We find that birds have undergone a strong increase in diversification rate from about 50 million years ago to the near present. This acceleration is due to a number of significant rate increases, both within songbirds and within other young and mostly temperate radiations including the waterfowl, gulls and woodpeckers. Importantly, species characterized with very high past diversification rates are interspersed throughout the avian tree and across geographic space. Geographically, the major differences in diversification rates are hemispheric rather than latitudinal, with bird assemblages in Asia, North America and southern South America containing a disproportionate number of species from recent rapid radiations. The contribution of rapidly radiating lineages to both temporal diversification dynamics and spatial distributions of species diversity illustrates the benefits of an inclusive geographical and taxonomical perspective. Overall, whereas constituent clades may exhibit slowdowns(10,11), the adaptive zone into which modern birds have diversified since the Cretaceous may still offer opportunities for diversification.
C1 [Jetz, W.] Yale Univ, Dept Ecol & Evolutionary Biol, New Haven, CT 06520 USA.
   [Thomas, G. H.] Univ Sheffield, Dept Anim & Plant Sci, Sheffield S10 2TN, S Yorkshire, England.
   [Joy, J. B.; Mooers, A. O.] Simon Fraser Univ, Dept Biol Sci, Burnaby, BC V5A 1S6, Canada.
   [Hartmann, K.] Univ Tasmania, Inst Marine & Antarctic Studies, Hobart, Tas 7001, Australia.
C3 Yale University; University of Sheffield; Simon Fraser University; University of Tasmania
RP Jetz, W (corresponding author), Yale Univ, Dept Ecol & Evolutionary Biol, 165 Prospect St, New Haven, CT 06520 USA.
EM walter.jetz@yale.edu; amooers@sfu.ca
FU NSF [DBI 0960550, DEB 1026764]; NASA [NNX11AP72G]; Natural Environment Research Council [NE/G012938/1]; NERC (Centre for Population Biology); NSERC Canada; Wissenschaftskolleg zu Berlin; Yale Institute for Biospheric Sciences; Simon Fraser University; NERC [NE/G012938/2, NE/G012938/1] Funding Source: UKRI; Direct For Biological Sciences; Div Of Biological Infrastructure [0960550] Funding Source: National Science Foundation; Direct For Biological Sciences; Div Of Biological Infrastructure [0960549] Funding Source: National Science Foundation; Division Of Environmental Biology; Direct For Biological Sciences [1026764] Funding Source: National Science Foundation; Natural Environment Research Council [NE/G012938/1, NE/G012938/2] Funding Source: researchfish
NR 30
TC 2932
Z9 3259
U1 19
U2 1289
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD NOV 15
PY 2012
VL 491
IS 7424
BP 444
EP 448
DI 10.1038/nature11631
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 036MY
UT WOS:000311031600046
PM 23123857
DA 2026-03-09
ER

PT J
AU Sheffield, J
   Wood, EF
   Roderick, ML
AF Sheffield, Justin
   Wood, Eric F.
   Roderick, Michael L.
TI Little change in global drought over the past 60 years
SO NATURE
LA English
DT Article
ID pan evaporation; severity index; soil-moisture; climate; precipitation; dataset; water
AB Drought is expected to increase in frequency and severity in the future as a result of climate change, mainly as a consequence of decreases in regional precipitation but also because of increasing evaporation driven by global warming(1-3). Previous assessments of historic changes in drought over the late twentieth and early twenty-first centuries indicate that this may already be happening globally. In particular, calculations of the Palmer Drought Severity Index (PDSI) show a decrease in moisture globally since the 1970s with a commensurate increase in the area in drought that is attributed, in part, to global warming(4,5). The simplicity of the PDSI, which is calculated from a simple water-balance model forced by monthly precipitation and temperature data, makes it an attractive tool in large-scale drought assessments, but may give biased results in the context of climate change(6). Here we show that the previously reported increase in global drought is overestimated because the PDSI uses a simplified model of potential evaporation(7) that responds only to changes in temperature and thus responds incorrectly to global warming in recent decades. More realistic calculations, based on the underlying physical principles(8) that take into account changes in available energy, humidity and wind speed, suggest that there has been little change in drought over the past 60 years. The results have implications for how we interpret the impact of global warming on the hydrological cycle and its extremes, and may help to explain why palaeoclimate drought reconstructions based on tree-ring data diverge from the PDSI-based drought record in recent years(9,10).
C1 [Sheffield, Justin; Wood, Eric F.] Princeton Univ, Dept Civil & Environm Engn, Princeton, NJ 08544 USA.
   [Roderick, Michael L.] Australian Natl Univ, Res Sch Earth Sci, Australian Res Council Ctr Excellence Climate Sys, Canberra, ACT 0200, Australia.
   [Roderick, Michael L.] Australian Natl Univ, Res Sch Biol, Australian Res Council Ctr Excellence Climate Sys, Canberra, ACT 0200, Australia.
C3 Princeton University; Australian National University; Australian National University
RP Sheffield, J (corresponding author), Princeton Univ, Dept Civil & Environm Engn, Princeton, NJ 08544 USA.
EM justin@princeton.edu
FU US National Oceanic and Atmospheric Agency [NA10OAR4310130, NA11OAR4310097]; NASA [NNX08AN40A]; Australian Research Council [DP0879763, DP110105376, CE11E0098]; Australian Research Council [DP0879763] Funding Source: Australian Research Council
NR 47
TC 1598
Z9 1796
U1 25
U2 1003
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 15
PY 2012
VL 491
IS 7424
BP 435
EP +
DI 10.1038/nature11575
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 036MY
UT WOS:000311031600044
PM 23151587
DA 2026-03-09
ER

PT J
AU Rollauer, SE
   Tarry, MJ
   Graham, JE
   Jääskeläinen, M
   Jäger, F
   Johnson, S
   Krehenbrink, M
   Liu, SM
   Lukey, MJ
   Marcoux, J
   McDowell, MA
   Rodriguez, F
   Roversi, P
   Stansfeld, PJ
   Robinson, CV
   Sansom, MSP
   Palmer, T
   Högbom, M
   Berks, BC
   Lea, SM
AF Rollauer, Sarah E.
   Tarry, Michael J.
   Graham, James E.
   Jaaskelainen, Mari
   Jaeger, Franziska
   Johnson, Steven
   Krehenbrink, Martin
   Liu, Sai-Man
   Lukey, Michael J.
   Marcoux, Julien
   McDowell, Melanie A.
   Rodriguez, Fernanda
   Roversi, Pietro
   Stansfeld, Phillip J.
   Robinson, Carol V.
   Sansom, Mark S. P.
   Palmer, Tracy
   Hogbom, Martin
   Berks, Ben C.
   Lea, Susan M.
TI Structure of the TatC core of the twin-arginine protein transport system
SO NATURE
LA English
DT Article
ID sec-independent protein; cysteine scanning mutagenesis; signal peptide; translocase component; pathway; topology; binding; form; complexes; efficient
AB The twin-arginine translocation (Tat) pathway is one of two general protein transport systems found in the prokaryotic cytoplasmic membrane and is conserved in the thylakoid membrane of plant chloroplasts. The defining, and highly unusual, property of the Tat pathway is that it transports folded proteins, a task that must be achieved without allowing appreciable ion leakage across the membrane. The integral membrane TatC protein is the central component of the Tat pathway. TatC captures substrate proteins by binding their signal peptides. TatC then recruits TatA family proteins to form the active translocation complex. Here we report the crystal structure of TatC from the hyperthermophilic bacterium Aquifex aeolicus. This structure provides a molecular description of the core of the Tat translocation system and a framework for understanding the unique Tat transport mechanism.
C1 [Rollauer, Sarah E.; Graham, James E.; Krehenbrink, Martin; Liu, Sai-Man; Lukey, Michael J.; Rodriguez, Fernanda; Stansfeld, Phillip J.; Sansom, Mark S. P.; Berks, Ben C.] Univ Oxford, Dept Biochem, Oxford OX1 3QU, England.
   [Rollauer, Sarah E.; Graham, James E.; Johnson, Steven; Liu, Sai-Man; Lukey, Michael J.; McDowell, Melanie A.; Roversi, Pietro; Lea, Susan M.] Univ Oxford, Sir William Dunn Sch Pathol, Oxford OX1 3RE, England.
   [Tarry, Michael J.; Jaaskelainen, Mari; Hogbom, Martin] Stockholm Univ, Dept Biochem & Biophys, Stockholm Ctr Biomembrane Res, S-10691 Stockholm, Sweden.
   [Jaeger, Franziska; Palmer, Tracy] Univ Dundee, Div Mol Microbiol, Coll Life Sci, Dundee DD1 5EH, Scotland.
   [Marcoux, Julien; Robinson, Carol V.] Univ Oxford, Dept Chem, Phys & Theoret Chem Lab, Oxford OX1 3QZ, England.
C3 University of Oxford; University of Oxford; Stockholm University; University of Dundee; University of Oxford
RP Berks, BC (corresponding author), Univ Oxford, Dept Biochem, S Parks Rd, Oxford OX1 3QU, England.
EM ben.berks@bioch.ox.ac.uk; susan.lea@path.ox.ac.uk
FU Wellcome Trust [083599, 092970MA]; Swedish Foundation for Strategic Research; Swedish Research Council [2010-5061]; E.P. Abrahams Cephalosporin Trust; Biotechnology and Biological Sciences Research Council [BB/E023347/1, BB/1019855/1]; Medical Research Council [G1001640, G0900888]; European Research Council; James Martin 21st Century School Vaccine Design Institute; BBSRC [BB/E023347/1, BB/F02150X/1, BB/H000267/1, BB/I019855/1] Funding Source: UKRI; MRC [G1001640] Funding Source: UKRI; Biotechnology and Biological Sciences Research Council [BB/F02150X/1, BB/E023347/1, BB/H000267/1, B19456, BB/I019855/1, BEP17032, BBS/B/16011] Funding Source: researchfish; Medical Research Council [G1001640, G0900888] Funding Source: researchfish
NR 63
TC 143
Z9 171
U1 1
U2 118
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 13
PY 2012
VL 492
IS 7428
BP 210
EP +
DI 10.1038/nature11683
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 053GM
UT WOS:000312259300033
PM 23201679
DA 2026-03-09
ER

PT J
AU Wang, R
   Dearing, JA
   Langdon, PG
   Zhang, EL
   Yang, XD
   Dakos, V
   Scheffer, M
AF Wang, Rong
   Dearing, John A.
   Langdon, Peter G.
   Zhang, Enlou
   Yang, Xiangdong
   Dakos, Vasilis
   Scheffer, Marten
TI Flickering gives early warning signals of a critical transition to a eutrophic lake state
SO NATURE
LA English
DT Article
ID ecosystem services; regime shifts; climate-change; tipping point; resilience; systems; science; time
AB There is a recognized need to anticipate tipping points, or critical transitions, in social-ecological systems(1,2). Studies of mathematical(3-5) and experimental(6-9) systems have shown that systems may 'wobble' before a critical transition. Such early warning signals(10) may be due to the phenomenon of critical slowing down, which causes a system to recover slowly from small impacts, or to a flickering phenomenon, which causes a system to switch back and forth between alternative states in response to relatively large impacts. Such signals for transitions in social-ecological systems have rarely been observed(11), not the least because high-resolution time series are normally required. Here we combine empirical data from a lake-catchment system with a mathematical model and show that flickering can be detected from sparse data. We show how rising variance coupled to decreasing autocorrelation and skewness started 10-30 years before the transition to eutrophic lake conditions in both the empirical records and the model output, a finding that is consistent with flickering rather than critical slowing down(4,12). Our results suggest that if environmental regimes are sufficiently affected by large external impacts that flickering is induced, then early warning signals of transitions in modern social-ecological systems may be stronger, and hence easier to identify, than previously thought.
C1 [Wang, Rong; Dearing, John A.; Langdon, Peter G.] Univ Southampton, Palaeoecol Lab, Southampton SO17 1BJ, Hants, England.
   [Wang, Rong; Zhang, Enlou; Yang, Xiangdong] Chinese Acad Sci, Nanjing Inst Geog & Limnol, State Key Lab Lake Sci & Environm, Nanjing 210008, Jiangsu, Peoples R China.
   [Dakos, Vasilis; Scheffer, Marten] Wageningen Univ, Dept Aquat Ecol & Water Qual Management, NL-6700 AA Wageningen, Netherlands.
   [Dakos, Vasilis] CSIC, Estn Biol Donana, Integrat Ecol Grp, E-41092 Seville, Spain.
C3 University of Southampton; Chinese Academy of Sciences; Nanjing Institute of Geography & Limnology, CAS; Wageningen University & Research; Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Estacion Biologica de Donana (EBD)
RP Dearing, JA (corresponding author), Univ Southampton, Palaeoecol Lab, Southampton SO17 1BJ, Hants, England.
EM j.dearing@soton.ac.uk
FU UK Overseas Research Students Awards; Great Britain-China Educational Trust; University of Southampton; National Basic Research Program of China (973 program) [2012CB956104]; NWO-Rubicon; EU Marie Curie fellowship; Spinoza (NWO) Award; European Research Council; Direct For Social, Behav & Economic Scie; Division Of Behavioral and Cognitive Sci [1134890] Funding Source: National Science Foundation
NR 27
TC 402
Z9 470
U1 19
U2 622
PU NATURE PUBLISHING 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 20
PY 2012
VL 492
IS 7429
BP 419
EP 422
DI 10.1038/nature11655
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 056KQ
UT WOS:000312488200054
PM 23160492
DA 2026-03-09
ER

PT J
AU Bingham, RG
   Ferraccioli, F
   King, EC
   Larter, RD
   Pritchard, HD
   Smith, AM
   Vaughan, DG
AF Bingham, Robert G.
   Ferraccioli, Fausto
   King, Edward C.
   Larter, Robert D.
   Pritchard, Hamish D.
   Smith, Andrew M.
   Vaughan, David G.
TI Inland thinning of West Antarctic Ice Sheet steered along subglacial rifts
SO NATURE
LA English
DT Article
ID crustal structure; land; sea; anomaly; dynamics; region; basin
AB Current ice loss from the West Antarctic Ice Sheet (WAIS) accounts for about ten per cent of observed global sea-level rise(1). Losses are dominated by dynamic thinning, in which forcings by oceanic or atmospheric perturbations to the ice margin lead to an accelerated thinning of ice along the coastline(2-5). Although central to improving projections of future ice-sheet contributions to global sea-level rise, the incorporation of dynamic thinning into models has been restricted by lack of knowledge of basal topography and subglacial geology so that the rate and ultimate extent of potential WAIS retreat remains difficult to quantify. Here we report the discovery of a subglacial basin under Ferrigno Ice Stream up to 1.5 kilometres deep that connects the ice-sheet interior to the Bellingshausen Sea margin, and whose existence profoundly affects ice loss. We use a suite of ice-penetrating radar, magnetic and gravity measurements to propose a rift origin for the basin in association with the wider development of the West Antarctic rift system. The Ferrigno rift, overdeepened by glacial erosion, is a conduit which fed a major palaeo-ice stream on the adjacent continental shelf during glacial maxima(6). The palaeo-ice stream, in turn, eroded the 'Belgica' trough, which today routes warm open-ocean water back to the ice front(7) to reinforce dynamic thinning. We show that dynamic thinning from both the Bellingshausen and Amundsen Sea region is being steered back to the ice-sheet interior along rift basins. We conclude that rift basins that cut across the WAIS margin can rapidly transmit coastally perturbed change inland, thereby promoting ice-sheet instability.
C1 [Bingham, Robert G.] Univ Aberdeen, Sch Geosci, Aberdeen AB24 3UF, Scotland.
   [Ferraccioli, Fausto; King, Edward C.; Larter, Robert D.; Pritchard, Hamish D.; Smith, Andrew M.; Vaughan, David G.] British Antarctic Survey, Cambridge CB3 0ET, England.
C3 University of Aberdeen; UK Research & Innovation (UKRI); Natural Environment Research Council (NERC); NERC British Antarctic Survey
RP Bingham, RG (corresponding author), Univ Aberdeen, Sch Geosci, Elphinstone Rd, Aberdeen AB24 3UF, Scotland.
EM r.bingham@abdn.ac.uk
FU Natural Environment Research Council [NERC/AFI/CGS/11/60]; British Antarctic Survey research programme Polar Science for Planet Earth; NERC [bas0100026, bas0100027] Funding Source: UKRI; Natural Environment Research Council [bas0100027, bas0100026] Funding Source: researchfish
NR 30
TC 78
Z9 89
U1 2
U2 66
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 26
PY 2012
VL 487
IS 7408
BP 468
EP 471
DI 10.1038/nature11292
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 979KD
UT WOS:000306815300035
PM 22837002
DA 2026-03-09
ER

PT J
AU Diochot, S
   Baron, A
   Salinas, M
   Douguet, D
   Scarzello, S
   Dabert-Gay, AS
   Debayle, D
   Friend, V
   Alloui, A
   Lazdunski, M
   Lingueglia, E
AF Diochot, Sylvie
   Baron, Anne
   Salinas, Miguel
   Douguet, Dominique
   Scarzello, Sabine
   Dabert-Gay, Anne-Sophie
   Debayle, Delphine
   Friend, Valerie
   Alloui, Abdelkrim
   Lazdunski, Michel
   Lingueglia, Eric
TI Black mamba venom peptides target acid-sensing ion channels to abolish pain
SO NATURE
LA English
DT Article
ID activated currents; asic3; mechanisms; evolution; alignment; toxins
AB Polypeptide toxins have played a central part in understanding physiological and physiopathological functions of ion channels(1,2). In the field of pain, they led to important advances in basic research(3-6) and even to clinical applications(7,8). Acid-sensing ion channels (ASICs) are generally considered principal players in the pain pathway(9), including in humans(10). A snake toxin activating peripheral ASICs in nociceptive neurons has been recently shown to evoke pain(11). Here we show that a new class of three-finger peptides from another snake, the black mamba, is able to abolish pain through inhibition of ASICs expressed either in central or peripheral neurons. These peptides, which we call mambalgins, are not toxic in mice but show a potent analgesic effect upon central and peripheral injection that can be as strong as morphine. This effect is, however, resistant to naloxone, and mambalgins cause much less tolerance than morphine and no respiratory distress. Pharmacological inhibition by mambalgins combined with the use of knockdown and knockout animals indicates that blockade of heteromeric channels made of ASIC1a and ASIC2a subunits in central neurons and of ASIC1b-containing channels in nociceptors is involved in the analgesic effect of mambalgins. These findings identify new potential therapeutic targets for pain and introduce natural peptides that block them to produce a potent analgesia.
C1 [Diochot, Sylvie; Baron, Anne; Salinas, Miguel; Douguet, Dominique; Scarzello, Sabine; Dabert-Gay, Anne-Sophie; Debayle, Delphine; Friend, Valerie; Lazdunski, Michel; Lingueglia, Eric] CNRS, Inst Pharmacol Mol & Cellulaire, UMR 7275, F-06560 Valbonne, France.
   [Diochot, Sylvie; Baron, Anne; Salinas, Miguel; Douguet, Dominique; Scarzello, Sabine; Dabert-Gay, Anne-Sophie; Debayle, Delphine; Friend, Valerie; Lazdunski, Michel; Lingueglia, Eric] Univ Nice Sophia Antipolis, F-06560 Valbonne, France.
   [Diochot, Sylvie; Baron, Anne; Salinas, Miguel; Friend, Valerie; Lingueglia, Eric] LabEx Ion Channel Sci & Therapeut, F-06560 Valbonne, France.
   [Alloui, Abdelkrim] Univ Auvergne, Clermont Univ, NEURO DOL, F-63000 Clermont Ferrand, France.
   [Alloui, Abdelkrim] INSERM, U1107, F-63001 Clermont Ferrand, France.
C3 Universite Cote d'Azur; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB); Universite Cote d'Azur; Universite Clermont Auvergne (UCA); Institut National de la Sante et de la Recherche Medicale (Inserm)
RP Baron, A (corresponding author), CNRS, Inst Pharmacol Mol & Cellulaire, UMR 7275, 660 Route Lucioles, F-06560 Valbonne, France.
EM baron@ipmc.cnrs.fr; lingueglia@ipmc.cnrs.fr
FU Fondation pour la Recherche Medicale; Association Francaise contre les Myopathies; Agence Nationale de la Recherche; EMMAservice under European Union of the EC FP7 Capacities Specific Programme [227490]
NR 43
TC 336
Z9 375
U1 0
U2 180
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 25
PY 2012
VL 490
IS 7421
BP 552
EP +
DI 10.1038/nature11494
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 025NK
UT WOS:000310196200045
PM 23034652
DA 2026-03-09
ER

PT J
AU DuPage, M
   Mazumdar, C
   Schmidt, LM
   Cheung, AF
   Jacks, T
AF DuPage, Michel
   Mazumdar, Claire
   Schmidt, Leah M.
   Cheung, Ann F.
   Jacks, Tyler
TI Expression of tumour-specific antigens underlies cancer immunoediting
SO NATURE
LA English
DT Article
ID mouse model; immunosurveillance; immunity; rejection; variants; escape; cells
AB Cancer immunoediting is a process by which immune cells, particularly lymphocytes of the adaptive immune system, protect the host from the development of cancer and alter tumour progression by driving the outgrowth of tumour cells with decreased sensitivity to immune attack(1,2). Carcinogen-induced mouse models of cancer have shown that primary tumour susceptibility is thereby enhanced in immune-compromised mice, whereas the capacity for such tumours to grow after transplantation into wild-type mice is reduced(2,3). However, many questions about the process of cancer immunoediting remain unanswered, in part because of the known antigenic complexity and heterogeneity of carcinogen-induced tumours(4). Here we adapted a genetically engineered, autochthonous mouse model of sarcomagenesis to investigate the process of cancer immunoediting. This system allows us to monitor the onset and growth of immunogenic and non-immunogenic tumours induced in situ that harbour identical genetic and histopathological characteristics. By comparing the development of such tumours in immune-competent mice with their development in mice with broad immunodeficiency or specific antigenic tolerance, we show that recognition of tumour-specific antigens by lymphocytes is critical for immunoediting against sarcomas. Furthermore, primary sarcomas were edited to become less immunogenic through the selective outgrowth of cells that were able to escape T lymphocyte attack. Loss of tumour antigen expression or presentation on major histocompatibility complex I was necessary and sufficient for this immunoediting process to occur. These results highlight the importance of tumour-specific-antigen expression in immune surveillance, and potentially, immunotherapy.
C1 [DuPage, Michel; Mazumdar, Claire; Schmidt, Leah M.; Cheung, Ann F.; Jacks, Tyler] MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA.
   [DuPage, Michel; Mazumdar, Claire; Schmidt, Leah M.; Cheung, Ann F.; Jacks, Tyler] MIT, Dept Biol, Cambridge, MA 02139 USA.
   [Jacks, Tyler] MIT, Howard Hughes Med Inst, Cambridge, MA 02139 USA.
C3 Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); Howard Hughes Medical Institute
RP Jacks, T (corresponding author), MIT, Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
EM tjacks@mit.edu
FU NIH [1 U54 CA126515-01]; Cancer Center from National Cancer Institute [P30-CA14051]; John D. Proctor Foundation; National Cancer Institute [P30CA014051] Funding Source: NIH RePORTER
NR 27
TC 422
Z9 542
U1 1
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 FEB 16
PY 2012
VL 482
IS 7385
BP 405
EP U1512
DI 10.1038/nature10803
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 892LG
UT WOS:000300287100047
PM 22318517
DA 2026-03-09
ER

PT J
AU Dunne, J
   Evershed, RP
   Salque, M
   Cramp, L
   Bruni, S
   Ryan, K
   Biagetti, S
   di Lernia, S
AF Dunne, Julie
   Evershed, Richard P.
   Salque, Melanie
   Cramp, Lucy
   Bruni, Silvia
   Ryan, Kathleen
   Biagetti, Stefano
   di Lernia, Savino
TI First dairying in green Saharan Africa in the fifth millennium BC
SO NATURE
LA English
DT Article
ID lactase-persistence phenotype; organic residue analysis; archaeological pottery; cattle; libya; milk; date
AB In the prehistoric green Sahara of Holocene North Africa-in contrast to the Neolithic of Europe and Eurasia-a reliance on cattle, sheep and goats emerged as a stable and widespread way of life, long before the first evidence for domesticated plants or settled village farming communities(1-3). The remarkable rock art found widely across the region depicts cattle herding among early Saharan pastoral groups, and includes rare scenes of milking; however, these images can rarely be reliably dated(4). Although the faunal evidence provides further confirmation of the importance of cattle and other domesticates(5), the scarcity of cattle bones makes it impossible to ascertain herd structures via kill-off patterns, thereby precluding interpretations of whether dairying was practiced. Because pottery production begins early in northern Africa(6) the potential exists to investigate diet and subsistence practices using molecular and isotopic analyses of absorbed food residues(7). This approach has been successful in determining the chronology of dairying beginning in the 'Fertile Crescent' of the Near East and its spread across Europe(8-11). Here we report the first unequivocal chemical evidence, based on the delta C-13 and Delta C-13 values of the major alkanoic acids of milk fat, for the adoption of dairying practices by prehistoric Saharan African people in the fifth millennium BC. Interpretations are supported by a new database of modern ruminant animal fats collected from Africa. These findings confirm the importance of 'lifetime products', such as milk, in early Saharan pastoralism, and provide an evolutionary context for the emergence of lactase persistence in Africa.
C1 [Dunne, Julie; Evershed, Richard P.; Salque, Melanie; Cramp, Lucy] Univ Bristol, Sch Chem, Organ Geochem Unit, Bristol BS8 1TS, Avon, England.
   [Bruni, Silvia] Univ Milan, Dipartimento Chim Inorgan Metallorgan & Analit La, I-20133 Milan, Italy.
   [Ryan, Kathleen] Univ Penn, African Sect, Museum Archaeol & Anthropol, Philadelphia, PA 19104 USA.
   [Biagetti, Stefano; di Lernia, Savino] Univ Roma La Sapienza, Dipartimento Sci Antichita, I-00185 Rome, Italy.
   [di Lernia, Savino] Univ Witwatersrand, Sch Geog Archaeology& Environm Sci, ZA-2050 Wits, South Africa.
C3 University of Bristol; University of Milan; University of Pennsylvania; Sapienza University Rome; University of Witwatersrand
RP Evershed, RP (corresponding author), Univ Bristol, Sch Chem, Organ Geochem Unit, Cantocks Close, Bristol BS8 1TS, Avon, England.
EM r.p.evershed@bristol.ac.uk; Savino.Dilernia@uniroma1.it
FU UK Natural Environment Research Council; Sapienza, University of Rome (Grandi Scavi di Ateneo); Minister of Foreign Affairs (DGSP); USA National Science Foundation; Royal Society
NR 30
TC 293
Z9 323
U1 4
U2 134
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUN 21
PY 2012
VL 486
IS 7403
BP 390
EP 394
DI 10.1038/nature11186
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 961LV
UT WOS:000305466800041
PM 22722200
DA 2026-03-09
ER

PT J
AU Rich, RM
   Collins, MLM
   Black, CM
   Longstaff, FA
   Koch, A
   Benson, A
   Reitzel, DB
AF Rich, R. M.
   Collins, M. L. M.
   Black, C. M.
   Longstaff, F. A.
   Koch, A.
   Benson, A.
   Reitzel, D. B.
TI A tidally distorted dwarf galaxy near NGC 4449
SO NATURE
LA English
DT Article
ID tails; evolution; cluster
AB NGC 4449 is a nearby Magellanic irregular starburst galaxy(1) with a B-band absolute magnitude of -18 and a prominent, massive, intermediate-age nucleus(2) at a distance from Earth of 3.8 megaparsecs (ref. 3). It is wreathed in an extraordinary neutral hydrogen (H I) complex, which includes rings, shells and a counter-rotating core, spanning similar to 90 kiloparsecs (kpc; refs 1, 4). NGC 4449 is relatively isolated(5), although an interaction with its nearest known companion-the galaxy DDO 125, some 40 kpc to the south-has been proposed as being responsible for the complexity of its HI structure(6). Here we report the presence of a dwarf galaxy companion to NGC 4449, namely NGC 4449B. This companion has a V-band absolute magnitude of -13.4 and a half-light radius of 2.7 kpc, with a full extent of around 8 kpc. It is in a transient stage of tidal disruption, similar to that of the Sagittarius dwarf(7) near the Milky Way. NGC 4449B exhibits a striking S-shaped morphology that has been predicted for disrupting galaxies(7,8) but has hitherto been seen only in a dissolving globular cluster(9). We also detect an additional arc or disk ripple embedded in a two-component stellar halo, including a component extending twice as far as previously known, to about 20 kpc from the galaxy's centre.
C1 [Rich, R. M.; Black, C. M.; Reitzel, D. B.] Univ Calif Los Angeles, Dept Phys & Astron, Los Angeles, CA 90095 USA.
   [Rich, R. M.; Longstaff, F. A.] Polaris Observ Assoc, Frazier Pk, CA 93225 USA.
   [Collins, M. L. M.] Max Planck Inst Astron, D-69117 Heidelberg, Germany.
   [Longstaff, F. A.] Univ Calif Los Angeles, Anderson Sch Management, Los Angeles, CA 90095 USA.
   [Koch, A.] Heidelberg Univ, Zentrum Astronomieder, D-69117 Heidelberg, Germany.
   [Benson, A.] CALTECH, Dept Astron, Pasadena, CA 91125 USA.
   [Reitzel, D. B.] Griffith Observ, Los Angeles, CA 90027 USA.
C3 University of California System; University of California Los Angeles; Max Planck Society; University of California System; University of California Los Angeles; Ruprecht Karls University Heidelberg; California Institute of Technology
RP Rich, RM (corresponding author), Univ Calif Los Angeles, Dept Phys & Astron, 430 Portola Plaza,Box 951547, Los Angeles, CA 90095 USA.
EM rmr@astro.ucla.edu
FU National Science Foundation
NR 18
TC 78
Z9 86
U1 0
U2 2
PU NATURE PUBLISHING 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 9
PY 2012
VL 482
IS 7384
BP 192
EP U78
DI 10.1038/nature10837
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 888HI
UT WOS:000299994100032
PM 22318602
DA 2026-03-09
ER

PT J
AU Puig, P
   Canals, M
   Company, JB
   Martín, J
   Amblas, D
   Lastras, G
   Palanques, A
   Calafat, AM
AF Puig, Pere
   Canals, Miquel
   Company, Joan B.
   Martin, Jacobo
   Amblas, David
   Lastras, Galderic
   Palanques, Albert
   Calafat, Antoni M.
TI Ploughing the deep sea floor
SO NATURE
LA English
DT Article
ID mobile-fishing-gear; continental shelves; submarine canyons; transport; currents; geology; impact; resuspension; ecosystems; slopes
AB Bottom trawling is a non-selective commercial fishing technique whereby heavy nets and gear are pulled along the sea floor. The direct impact of this technique on fish populations(1,2) and benthic communities(3,4) has received much attention, but trawling can also modify the physical properties of seafloor sediments, water-sediment chemical exchanges and sediment fluxes(5,6). Most of the studies addressing the physical disturbances of trawl gear on the seabed have been undertaken in coastal and shelf environments(7,8), however, where the capacity of trawling to modify the seafloor morphology coexists with high-energy natural processes driving sediment erosion, transport and deposition(9). Here we show that on upper continental slopes, the reworking of the deep sea floor by trawling gradually modifies the shape of the submarine landscape over large spatial scales. We found that trawling-induced sediment displacement and removal from fishing grounds causes the morphology of the deep sea floor to become smoother over time, reducing its original complexity as shown by high-resolution seafloor relief maps. Our results suggest that in recent decades, following the industrialization of fishing fleets, bottom trawling has become an important driver of deep seascape evolution. Given the global dimension of this type of fishery, we anticipate that the morphology of the upper continental slope in many parts of the world's oceans could be altered by intensive bottom trawling, producing comparable effects on the deep sea floor to those generated by agricultural ploughing on land.
C1 [Puig, Pere; Company, Joan B.; Martin, Jacobo; Palanques, Albert] CSIC, Inst Marine Sci, E-08003 Barcelona, Spain.
   [Canals, Miquel; Amblas, David; Lastras, Galderic; Calafat, Antoni M.] Univ Barcelona, CRG Marine Geosci, E-08028 Barcelona, Spain.
C3 Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Centro Mediterraneo de Investigaciones Marinas y Ambientales (CMIMA); CSIC - Instituto de Ciencias del Mar (ICM); University of Barcelona
RP Puig, P (corresponding author), CSIC, Inst Marine Sci, E-08003 Barcelona, Spain.
EM ppuig@icm.csic.es
FU HERMIONE [226354, CTM2010-11084-E]; DOS MARES [CTM2010-21810-C03]; OASIS DEL MAR-Obra Social "la Caixa"; GRACCIE-CONSOLIDER [CSD2007-00067]; REDECO [CTM2008-04973-E]; Catalan Government Grups de Recerca Consolidats grants [SGR 899, 1305]; Spanish General Secretariat of Maritime Fishing (SEGEMAR); Consejo Superior de Investigaciones Cientificas; European Social Fund
NR 32
TC 334
Z9 354
U1 1
U2 271
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 13
PY 2012
VL 489
IS 7415
BP 286
EP +
DI 10.1038/nature11410
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 003UC
UT WOS:000308635900040
PM 22951970
DA 2026-03-09
ER

PT J
AU Uniacke, J
   Holterman, CE
   Lachance, G
   Franovic, A
   Jacob, MD
   Fabian, MR
   Payette, J
   Holcik, M
   Pause, A
   Lee, S
AF Uniacke, James
   Holterman, Chet E.
   Lachance, Gabriel
   Franovic, Aleksandra
   Jacob, Mathieu D.
   Fabian, Marc R.
   Payette, Josianne
   Holcik, Martin
   Pause, Arnim
   Lee, Stephen
TI An oxygen-regulated switch in the protein synthesis machinery
SO NATURE
LA English
DT Article
ID messenger-rna translation; binding protein; hif-alpha; hypoxia; cancer; mechanisms; stress; growth; hydroxylation; expression
AB Protein synthesis involves the translation of ribonucleic acid information into proteins, the building blocks of life. The initial step of protein synthesis is the binding of the eukaryotic translation initiation factor 4E (eIF4E) to the 7-methylguanosine (m(7)-GpppG) 5' cap of messenger RNAs1,2. Low oxygen tension (hypoxia) represses cap-mediated translation by sequestering eIF4E through mammalian target of rapamycin (mTOR)dependent mechanisms(3-6). Although the internal ribosome entry site is an alternative translation initiation mechanism, this pathway alone cannot account for the translational capacity of hypoxic cells(7,8). This raises a fundamental question in biology as to how proteins are synthesized in periods of oxygen scarcity and eIF4E inhibition(9). Here we describe an oxygen-regulated translation initiation complex that mediates selective cap-dependent protein synthesis. We show that hypoxia stimulates the formation of a complex that includes the oxygen-regulated hypoxia-inducible factor 2 alpha (HIF-2 alpha), the RNA-binding protein RBM4 and the cap-binding eIF4E2, an eIF4E homologue. Photoactivatable ribonucleoside-enhanced crosslinking and immunoprecipitation (PAR-CLIP)(10) analysis identified an RNA hypoxia response element (rHRE) that recruits this complex to a wide array of mRNAs, including that encoding the epidermal growth factor receptor. Once assembled at the rHRE, the HIF-2 alpha-RBM4-eIF4E2 complex captures the 5' cap and targets mRNAs to polysomes for active translation, thereby evading hypoxia-induced repression of protein synthesis. These findings demonstrate that cells have evolved a program by which oxygen tension switches the basic translation initiation machinery.
C1 [Uniacke, James; Holterman, Chet E.; Lachance, Gabriel; Franovic, Aleksandra; Jacob, Mathieu D.; Payette, Josianne; Lee, Stephen] Univ Ottawa, Fac Med, Dept Cellular & Mol Med, Ottawa, ON K1H 8M5, Canada.
   [Fabian, Marc R.; Pause, Arnim] McGill Univ, Dept Biochem, Goodman Canc Res Ctr, Montreal, PQ H3G 1Y6, Canada.
   [Holcik, Martin] Childrens Hosp Eastern Ontario, Res Inst, Apoptosis Res Ctr, Ottawa, ON K1H 8L1, Canada.
C3 University of Ottawa; McGill University; University of Ottawa; Children's Hospital of Eastern Ontario
RP Lee, S (corresponding author), Univ Ottawa, Fac Med, Dept Cellular & Mol Med, Ottawa, ON K1H 8M5, Canada.
EM slee@uottawa.ca
FU Canadian Institutes of Health Research; Terry Fox Foundation (Canadian Cancer Society) [700014]; Terry Fox Foundation; Canadian Cancer Society
NR 32
TC 264
Z9 299
U1 0
U2 68
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD JUN 7
PY 2012
VL 486
IS 7401
BP 126
EP U154
DI 10.1038/nature11055
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 953GD
UT WOS:000304854000041
PM 22678294
DA 2026-03-09
ER

PT J
AU Landis, SC
   Amara, SG
   Asadullah, K
   Austin, CP
   Blumenstein, R
   Bradley, EW
   Crystal, RG
   Darnell, RB
   Ferrante, RJ
   Fillit, H
   Finkelstein, R
   Fisher, M
   Gendelman, HE
   Golub, RM
   Goudreau, JL
   Gross, RA
   Gubitz, AK
   Hesterlee, SE
   Howells, DW
   Huguenard, J
   Kelner, K
   Koroshetz, W
   Krainc, D
   Lazic, SE
   Levine, MS
   Macleod, MR
   McCall, JM
   Moxley, RT
   Narasimhan, K
   Noble, LJ
   Perrin, S
   Porter, JD
   Steward, O
   Unger, E
   Utz, U
   Silberberg, SD
AF Landis, Story C.
   Amara, Susan G.
   Asadullah, Khusru
   Austin, Chris P.
   Blumenstein, Robi
   Bradley, Eileen W.
   Crystal, Ronald G.
   Darnell, Robert B.
   Ferrante, Robert J.
   Fillit, Howard
   Finkelstein, Robert
   Fisher, Marc
   Gendelman, Howard E.
   Golub, Robert M.
   Goudreau, John L.
   Gross, Robert A.
   Gubitz, Amelie K.
   Hesterlee, Sharon E.
   Howells, David W.
   Huguenard, John
   Kelner, Katrina
   Koroshetz, Walter
   Krainc, Dimitri
   Lazic, Stanley E.
   Levine, Michael S.
   Macleod, Malcolm R.
   McCall, John M.
   Moxley, Richard T., III
   Narasimhan, Kalyani
   Noble, Linda J.
   Perrin, Steve
   Porter, John D.
   Steward, Oswald
   Unger, Ellis
   Utz, Ursula
   Silberberg, Shai D.
TI A call for transparent reporting to optimize the predictive value of preclinical research
SO NATURE
LA English
DT Article
ID randomized controlled-trials; empirical-evidence; statistical-analysis; clinical-trials; animal research; quality; design; efficacy; bias; publication
AB The US National Institute of Neurological Disorders and Stroke convened major stakeholders in June 2012 to discuss how to improve the methodological reporting of animal studies in grant applications and publications. The main workshop recommendation is that at a minimum studies should report on sample-size estimation, whether and how animals were randomized, whether investigators were blind to the treatment, and the handling of data. We recognize that achieving a meaningful improvement in the quality of reporting will require a concerted effort by investigators, reviewers, funding agencies and journal editors. Requiring better reporting of animal studies will raise awareness of the importance of rigorous study design to accelerate scientific progress.
C1 [Landis, Story C.; Finkelstein, Robert; Gubitz, Amelie K.; Koroshetz, Walter; Porter, John D.; Utz, Ursula; Silberberg, Shai D.] Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD 20892 USA.
   [Amara, Susan G.] Univ Pittsburgh, Sch Med, Dept Neurobiol, Pittsburgh, PA 15213 USA.
   [Asadullah, Khusru] Bayer HealthCare, D-13342 Berlin, Germany.
   [Austin, Chris P.] NIH, Natl Ctr Adv Translat Sci, Rockville, MD 20854 USA.
   [Blumenstein, Robi] CHDI Management CHDI Fdn, New York, NY 10001 USA.
   [Bradley, Eileen W.] NIH, Ctr Review, Bethesda, MD 20892 USA.
   [Crystal, Ronald G.] Weill Cornell Med Coll, Dept Genet Med, New York, NY 10021 USA.
   [Darnell, Robert B.] Rockefeller Univ, Howard Hughes Med Inst, New York, NY 10065 USA.
   [Ferrante, Robert J.] Univ Pittsburgh, Dept Neurol Surg, Pittsburgh, PA 15213 USA.
   [Fillit, Howard] Alzheimers Drug Discovery Fdn, New York, NY 10019 USA.
   [Fisher, Marc] Univ Massachusetts, Sch Med, Dept Neurol, Worcester, MA 01545 USA.
   [Gendelman, Howard E.] Univ Nebraska Med Ctr, Dept Pharmacol & Expt Neurosci, Omaha, NE 68198 USA.
   [Golub, Robert M.] JAMA, Chicago, IL 60654 USA.
   [Goudreau, John L.] Michigan State Univ, Dept Neurol, E Lansing, MI 48824 USA.
   [Gross, Robert A.] Univ Rochester, Med Ctr, Dept Neurol, Rochester, NY 14642 USA.
   [Hesterlee, Sharon E.] Parent Project Muscular Dystrophy, Hackensack, NJ 07601 USA.
   [Howells, David W.] Univ Melbourne, Florey Inst Neurosci & Mental Hlth, Heidelberg, Vic 3081, Australia.
   [Huguenard, John] Stanford Univ, Stanford, CA 94305 USA.
   [Kelner, Katrina] AAAS, Washington, DC USA.
   [Krainc, Dimitri] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
   [Lazic, Stanley E.] F Hoffmann La Roche & Co Ltd, CH-4070 Basel, Switzerland.
   [Levine, Michael S.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA.
   [Macleod, Malcolm R.] Univ Edinburgh, Western Gen Hosp, Dept Clin Neurosci, Edinburgh EH4 2XU, Midlothian, Scotland.
   [Moxley, Richard T., III] Univ Rochester, Med Ctr, Sch Med & Dent, Rochester, NY 14642 USA.
   [McCall, John M.] PharMac LLC, Boca Grande, FL 33921 USA.
   [Narasimhan, Kalyani] Nat Neurosci, New York, NY 10013 USA.
   [Noble, Linda J.] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 94143 USA.
   [Perrin, Steve] ALS Therapy Dev Inst, Cambridge, MA 02139 USA.
   [Steward, Oswald] Univ Calif Irvine, Reeve Irvine Res Ctr, Irvine, CA 92697 USA.
   [Unger, Ellis] US FDA, Off New Drugs, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA.
C3 National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS); Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh; Bayer AG; Bayer Healthcare Pharmaceuticals; National Institutes of Health (NIH) - USA; NIH National Center for Advancing Translational Sciences (NCATS); National Institutes of Health (NIH) - USA; Cornell University; Weill Cornell Medicine; Howard Hughes Medical Institute; Rockefeller University; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh; University of Massachusetts System; University of Massachusetts Worcester; University of Nebraska System; University of Nebraska Medical Center; Michigan State University; University of Rochester; Florey Institute of Neuroscience & Mental Health; University of Melbourne; Stanford University; Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Massachusetts General Hospital; Roche Holding; University of California System; University of California Los Angeles; University of Edinburgh; University of Rochester; University of California System; University of California San Francisco; University of California System; University of California Irvine; US Food & Drug Administration (FDA)
RP Silberberg, SD (corresponding author), Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD 20892 USA.
EM silberbs@ninds.nih.gov
FU NINDS; National Institute of Mental Health [ZIAMH002946, P30MH062261] Funding Source: NIH RePORTER; National Institute of Neurological Disorders and Stroke [R01NS034774] Funding Source: NIH RePORTER; National Institute on Aging; National Institute of General Medical Sciences; National Institute of Mental Health [T32MH020016] Funding Source: NIH RePORTER
NR 64
TC 927
Z9 1041
U1 1
U2 130
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 11
PY 2012
VL 490
IS 7419
BP 187
EP 191
DI 10.1038/nature11556
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 019IY
UT WOS:000309733300036
PM 23060188
DA 2026-03-09
ER

PT J
AU Kozorovitskiy, Y
   Saunders, A
   Johnson, CA
   Lowell, BB
   Sabatini, BL
AF Kozorovitskiy, Yevgenia
   Saunders, Arpiar
   Johnson, Caroline A.
   Lowell, Bradford B.
   Sabatini, Bernardo L.
TI Recurrent network activity drives striatal synaptogenesis
SO NATURE
LA English
DT Article
ID medium spiny neurons; basal ganglia; dendritic spines; cortex; organization; gaba; pathways; circuits; input; light
AB Neural activity during development critically shapes postnatal wiring of the mammalian brain. This is best illustrated by the sensory systems, in which the patterned feed-forward excitation provided by sensory organs and experience drives the formation of mature topographic circuits capable of extracting specific features of sensory stimuli(1,2). In contrast, little is known about the role of early activity in the development of the basal ganglia, a phylogenetically ancient group of nuclei fundamentally important for complex motor action and reward-based learning(3,4). These nuclei lack direct sensory input and are only loosely topographically organized(5,6), forming interlocking feed-forward and feed-back inhibitory circuits without laminar structure. Here we use transgenic mice and viral gene transfer methods to modulate neurotransmitter release and neuronal activity in vivo in the developing striatum. We find that the balance of activity between the two inhibitory and antagonist pathways in the striatum regulates excitatory innervation of the basal ganglia during development. These effects indicate that the propagation of activity through a multi-stage network regulates the wiring of the basal ganglia, revealing an important role of positive feedback in driving network maturation.
C1 [Kozorovitskiy, Yevgenia; Saunders, Arpiar; Johnson, Caroline A.; Sabatini, Bernardo L.] Harvard Univ, Sch Med, Howard Hughes Med Inst, Dept Neurobiol, Boston, MA 02115 USA.
   [Lowell, Bradford B.] Beth Israel Deaconess Med Ctr, Div Endocrinol, Boston, MA 02215 USA.
C3 Harvard University; Harvard Medical School; Howard Hughes Medical Institute; Harvard University; Harvard University Medical Affiliates; Beth Israel Deaconess Medical Center
RP Sabatini, BL (corresponding author), Harvard Univ, Sch Med, Howard Hughes Med Inst, Dept Neurobiol, 220 Longwood Ave, Boston, MA 02115 USA.
EM bsabatini@hms.harvard.edu
FU NINDS [NS046579]; W.F. Milton Fund Award; Leonard and Isabelle Goldenson Research Fellowship; NIH [F31 NS074842]; Shapiro predoctoral fellowship; National Institute of Diabetes and Digestive and Kidney Diseases [R01DK089044] Funding Source: NIH RePORTER; National Institute of Mental Health; National Institute of Neurological Disorders and Stroke; National Institute on Alcohol Abuse and Alcoholism [T32MH020017] Funding Source: NIH RePORTER
NR 30
TC 136
Z9 169
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 MAY 31
PY 2012
VL 485
IS 7400
BP 646
EP +
DI 10.1038/nature11052
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 949WP
UT WOS:000304608000049
PM 22660328
DA 2026-03-09
ER

PT J
AU Ellis, MJ
   Ding, L
   Shen, D
   Luo, JQ
   Suman, VJ
   Wallis, JW
   Van Tine, BA
   Hoog, J
   Goiffon, RJ
   Goldstein, TC
   Ng, S
   Lin, L
   Crowder, R
   Snider, J
   Ballman, K
   Weber, J
   Chen, K
   Koboldt, DC
   Kandoth, C
   Schierding, WS
   McMichael, JF
   Miller, CA
   Lu, C
   Harris, CC
   McLellan, MD
   Wendl, MC
   DeSchryver, K
   Allred, DC
   Esserman, L
   Unzeitig, G
   Margenthaler, J
   Babiera, GV
   Marcom, PK
   Guenther, JM
   Leitch, M
   Hunt, K
   Olson, J
   Tao, Y
   Maher, CA
   Fulton, LL
   Fulton, RS
   Harrison, M
   Oberkfell, B
   Du, FY
   Demeter, R
   Vickery, TL
   Elhammali, A
   Piwnica-Worms, H
   McDonald, S
   Watson, M
   Dooling, DJ
   Ota, D
   Chang, LW
   Bose, R
   Ley, TJ
   Piwnica-Worms, D
   Stuart, JM
   Wilson, RK
   Mardis, ER
AF Ellis, Matthew J.
   Ding, Li
   Shen, Dong
   Luo, Jingqin
   Suman, Vera J.
   Wallis, John W.
   Van Tine, Brian A.
   Hoog, Jeremy
   Goiffon, Reece J.
   Goldstein, Theodore C.
   Ng, Sam
   Lin, Li
   Crowder, Robert
   Snider, Jacqueline
   Ballman, Karla
   Weber, Jason
   Chen, Ken
   Koboldt, Daniel C.
   Kandoth, Cyriac
   Schierding, William S.
   McMichael, Joshua F.
   Miller, Christopher A.
   Lu, Charles
   Harris, Christopher C.
   McLellan, Michael D.
   Wendl, Michael C.
   DeSchryver, Katherine
   Allred, D. Craig
   Esserman, Laura
   Unzeitig, Gary
   Margenthaler, Julie
   Babiera, G. V.
   Marcom, P. Kelly
   Guenther, J. M.
   Leitch, Marilyn
   Hunt, Kelly
   Olson, John
   Tao, Yu
   Maher, Christopher A.
   Fulton, Lucinda L.
   Fulton, Robert S.
   Harrison, Michelle
   Oberkfell, Ben
   Du, Feiyu
   Demeter, Ryan
   Vickery, Tammi L.
   Elhammali, Adnan
   Piwnica-Worms, Helen
   McDonald, Sandra
   Watson, Mark
   Dooling, David J.
   Ota, David
   Chang, Li-Wei
   Bose, Ron
   Ley, Timothy J.
   Piwnica-Worms, David
   Stuart, Joshua M.
   Wilson, Richard K.
   Mardis, Elaine R.
TI Whole-genome analysis informs breast cancer response to aromatase inhibition
SO NATURE
LA English
DT Article
ID myeloid-leukemia genome; cell lung-cancer; endocrine therapy; suppressor gene; mutation; pathway; phosphorylation; mechanisms; carcinoma; outcm
AB To correlate the variable clinical features of oestrogen-receptor-positive breast cancer with somatic alterations, we studied pretreatment tumour biopsies accrued from patients in two studies of neoadjuvant aromatase inhibitor therapy by massively parallel sequencing and analysis. Eighteen significantly mutated genes were identified, including five genes (RUNX1, CBFB, MYH9, MLL3 and SF3B1) previously linked to haematopoietic disorders. Mutant MAP3K1 was associated with luminal A status, low-grade histology and low proliferation rates, whereas mutant TP53 was associated with the opposite pattern. Moreover, mutant GATA3 correlated with suppression of proliferation upon aromatase inhibitor treatment. Pathway analysis demonstrated that mutations in MAP2K4, a MAP3K1 substrate, produced similar perturbations as MAP3K1 loss. Distinct phenotypes in oestrogen-receptor-positive breast cancer are associated with specific patterns of somatic mutations that map into cellular pathways linked to tumour biology, but most recurrent mutations are relatively infrequent. Prospective clinical trials based on these findings will require comprehensive genome sequencing.
C1 [Ellis, Matthew J.; Van Tine, Brian A.; Hoog, Jeremy; Lin, Li; Crowder, Robert; Snider, Jacqueline; Weber, Jason; DeSchryver, Katherine; Maher, Christopher A.; Ley, Timothy J.] Washington Univ, Dept Internal Med, Div Oncol, St Louis, MO 63110 USA.
   [Ellis, Matthew J.; Margenthaler, Julie; McDonald, Sandra; Bose, Ron; Ley, Timothy J.; Wilson, Richard K.; Mardis, Elaine R.] Washington Univ, Siteman Canc Ctr, St Louis, MO 63110 USA.
   [Ellis, Matthew J.; Luo, Jingqin; Allred, D. Craig; Chang, Li-Wei; Bose, Ron] Washington Univ, Breast Canc Program, St Louis, MO 63110 USA.
   [Ding, Li; Shen, Dong; Wallis, John W.; Koboldt, Daniel C.; Kandoth, Cyriac; Schierding, William S.; McMichael, Joshua F.; Miller, Christopher A.; Lu, Charles; Harris, Christopher C.; McLellan, Michael D.; Wendl, Michael C.; Maher, Christopher A.; Fulton, Lucinda L.; Fulton, Robert S.; Harrison, Michelle; Oberkfell, Ben; Du, Feiyu; Demeter, Ryan; Vickery, Tammi L.; Dooling, David J.; Ley, Timothy J.; Wilson, Richard K.; Mardis, Elaine R.] Washington Univ, Genome Inst, St Louis, MO 63108 USA.
   [Ding, Li; Shen, Dong; Wallis, John W.; Koboldt, Daniel C.; Kandoth, Cyriac; Schierding, William S.; McMichael, Joshua F.; Miller, Christopher A.; Lu, Charles; Harris, Christopher C.; McLellan, Michael D.; Wendl, Michael C.; Fulton, Lucinda L.; Fulton, Robert S.; Harrison, Michelle; Oberkfell, Ben; Du, Feiyu; Demeter, Ryan; Vickery, Tammi L.; Dooling, David J.; Wilson, Richard K.; Mardis, Elaine R.] Washington Univ, Dept Genet, St Louis, MO 63108 USA.
   [Luo, Jingqin; Tao, Yu; Watson, Mark] Washington Univ, Div Biostat, St Louis, MO 63110 USA.
   [Suman, Vera J.; Ballman, Karla] Mayo Clin, ACOSOG Stat Ctr, Rochester, MN 55905 USA.
   [Goiffon, Reece J.; Weber, Jason; Elhammali, Adnan; Piwnica-Worms, Helen; Piwnica-Worms, David] Washington Univ, BRIGHT Inst, Sch Med, St Louis, MO 63110 USA.
   [Goiffon, Reece J.; Elhammali, Adnan; Piwnica-Worms, David] Washington Univ, Mol Imaging Ctr, St Louis, MO 63110 USA.
   [Goiffon, Reece J.; Elhammali, Adnan; Piwnica-Worms, David] Washington Univ, Malinckrodt Inst Radiol, St Louis, MO 63110 USA.
   [Goldstein, Theodore C.; Ng, Sam; Stuart, Joshua M.] Univ Calif Santa Cruz, Dept Biomol Engn, Santa Cruz, CA 95064 USA.
   [Weber, Jason] Washington Univ, Dept Cell Biol & Physiol, St Louis, MO 63110 USA.
   [Chen, Ken; Babiera, G. V.; Hunt, Kelly] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
   [Allred, D. Craig; Watson, Mark; Chang, Li-Wei] Washington Univ, Dept Pathol & Immunol, St Louis, MO 63110 USA.
   [Esserman, Laura] Univ Calif San Francisco, Helen Diller Canc Ctr, San Francisco, CA 94143 USA.
   [Unzeitig, Gary] Doctors Hosp Laredo, Laredo, TX 78045 USA.
   [Marcom, P. Kelly; Olson, John] Duke Univ, Ctr Canc, Durham, NC 27705 USA.
   [Guenther, J. M.] Good Samaritan Hosp, Cincinnati, OH 45406 USA.
   [Leitch, Marilyn] Univ Texas SW, Simmons Canc Ctr, Dallas, TX 75390 USA.
   [Piwnica-Worms, Helen] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA.
   [McDonald, Sandra; Watson, Mark] Washington Univ, ACOSOG Cent Specimen Bank, St Louis, MO 63110 USA.
   [Ota, David] Duke Univ, ACOSOG Operat Ctr, Durham, NC 27705 USA.
   [Piwnica-Worms, David] Washington Univ, Dept Dev Biol, St Louis, MO 63110 USA.
C3 Washington University (WUSTL); Siteman Cancer Center; Washington University (WUSTL); Washington University (WUSTL); Washington University (WUSTL); Washington University (WUSTL); Washington University (WUSTL); Mayo Clinic; Washington University (WUSTL); Washington University (WUSTL); Washington University (WUSTL); University of California System; University of California Santa Cruz; Washington University (WUSTL); University of Texas System; UTMD Anderson Cancer Center; Washington University (WUSTL); University of California System; University of California San Francisco; UCSF Medical Center; UCSF Helen Diller Family Comprehensive Cancer Center; Duke University; Good Samaritan Hospital - Cincinnati; University of Texas System; University of Texas Southwestern Medical Center; Howard Hughes Medical Institute; Washington University (WUSTL); Duke University; Washington University (WUSTL)
RP Ellis, MJ (corresponding author), Washington Univ, Dept Internal Med, Div Oncol, St Louis, MO 63110 USA.
FU National Human Genome Research Institute (NHGRI) [U54 HG003079]; National Cancer Institute [NCI R01 CA095614, NCI U01 CA114722]; Susan G. Komen Breast Cancer Foundation [BCTR0707808]; Fashion Footwear Charitable Foundation, Inc. [NCI U10 CA076001]; Breast Cancer Research Foundation; Novartis; Pfizer; Center grant [NCI P50 CA94056]; NCI core grant [NCI 3P50 CA68438]; Direct For Biological Sciences [0845783] Funding Source: National Science Foundation; Div Of Biological Infrastructure [0845783] Funding Source: National Science Foundation; National Cancer Institute [P30CA016672, P30CA091842] Funding Source: NIH RePORTER
NR 45
TC 834
Z9 976
U1 0
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 JUN 21
PY 2012
VL 486
IS 7403
BP 353
EP 360
DI 10.1038/nature11143
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 961LV
UT WOS:000305466800034
PM 22722193
DA 2026-03-09
ER

PT J
AU Andersson, LS
   Larhammar, M
   Memic, F
   Wootz, H
   Schwochow, D
   Rubin, CJ
   Patra, K
   Arnason, T
   Wellbring, L
   Hjälm, G
   Imsland, F
   Petersen, JL
   McCue, ME
   Mickelson, JR
   Cothran, G
   Ahituv, N
   Roepstorff, L
   Mikko, S
   Vallstedt, A
   Lindgren, G
   Andersson, L
   Kullander, K
AF Andersson, Lisa S.
   Larhammar, Martin
   Memic, Fatima
   Wootz, Hanna
   Schwochow, Doreen
   Rubin, Carl-Johan
   Patra, Kalicharan
   Arnason, Thorvaldur
   Wellbring, Lisbeth
   Hjalm, Goran
   Imsland, Freyja
   Petersen, Jessica L.
   McCue, Molly E.
   Mickelson, James R.
   Cothran, Gus
   Ahituv, Nadav
   Roepstorff, Lars
   Mikko, Sofia
   Vallstedt, Anna
   Lindgren, Gabriella
   Andersson, Leif
   Kullander, Klas
TI Mutations in DMRT3 affect locomotion in horses and spinal circuit function in mice
SO NATURE
LA English
DT Article
ID lamina-viii interneurons; pattern generation; cord; networks; differentiation; pathways; walking; genes; cat
AB Locomotion in mammals relies on a central pattern-generating circuitry of spinal interneurons established during development that coordinates limb movement(1). These networks produce left-right alternation of limbs as well as coordinated activation of flexor and extensor muscles(2). Here we show that a premature stop codon in the DMRT3 gene has a major effect on the pattern of locomotion in horses. The mutation is permissive for the ability to perform alternate gaits and has a favourable effect on harness racing performance. Examination of wild-type and Dmrt3-null mice demonstrates that Dmrt3 is expressed in the dI6 subdivision of spinal cord neurons, takes part in neuronal specification within this subdivision, and is critical for the normal development of a coordinated locomotor network controlling limb movements. Our discovery positions Dmrt3 in a pivotal role for configuring the spinal circuits controlling stride in vertebrates. The DMRT3 mutation has had a major effect on the diversification of the domestic horse, as the altered gait characteristics of a number of breeds apparently require this mutation.
C1 [Andersson, Lisa S.; Schwochow, Doreen; Wellbring, Lisbeth; Mikko, Sofia; Lindgren, Gabriella; Andersson, Leif] Swedish Univ Agr Sci, Dept Anim Breeding & Genet, SE-75124 Uppsala, Sweden.
   [Larhammar, Martin; Memic, Fatima; Wootz, Hanna; Patra, Kalicharan; Vallstedt, Anna; Kullander, Klas] Uppsala Univ, Dept Neurosci, SE-75124 Uppsala, Sweden.
   [Rubin, Carl-Johan; Hjalm, Goran; Imsland, Freyja; Andersson, Leif] Uppsala Univ, Dept Med Biochem & Microbiol, SE-75123 Uppsala, Sweden.
   [Arnason, Thorvaldur] Agr Univ Iceland, Fac Land & Anim Resources, IS-311 Borgarnes, Iceland.
   [Petersen, Jessica L.; McCue, Molly E.; Mickelson, James R.] Univ Minnesota, Coll Vet Med, St Paul, MN 55108 USA.
   [Cothran, Gus] Texas A&M Univ, Coll Vet Med & Biomed Sci, Dept Vet Integrat Biosci, College Stn, TX 77483 USA.
   [Ahituv, Nadav] Univ Calif San Francisco, Dept Bioengn & Therapeut Sci, San Francisco, CA 94143 USA.
   [Ahituv, Nadav] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA.
   [Roepstorff, Lars] Swedish Univ Agr Sci, Unit Equine Studies, SE-75007 Uppsala, Sweden.
C3 Swedish University of Agricultural Sciences; Uppsala University; Uppsala University; University of Minnesota System; University of Minnesota Twin Cities; Texas A&M University System; Texas A&M University College Station; University of California System; University of California San Francisco; University of California System; University of California San Francisco; Swedish University of Agricultural Sciences
RP Andersson, LS (corresponding author), Swedish Univ Agr Sci, Dept Anim Breeding & Genet, SE-75124 Uppsala, Sweden.
EM leif.andersson@imbim.uu.se
FU Swedish Foundation for Strategic Research; Swedish Research Council Formas [221-2009-1631]; Swedish Research Council Medicine and Health [2007-3630/4479, 2010-4394]; Swedish Society for Medical Research; National Institute of Child Health & Human Development [R01HD059862]; Swedish Brain Foundation; Uppsala University and Hospital, SciLife Lab - Uppsala and the Swedish Research Council [80576801, 70374401]; Knut and Alice Wallenberg Foundation
NR 27
TC 315
Z9 386
U1 0
U2 120
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD AUG 30
PY 2012
VL 488
IS 7413
BP 642
EP 646
DI 10.1038/nature11399
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 996NC
UT WOS:000308095100053
PM 22932389
DA 2026-03-09
ER

PT J
AU Köhler, M
   Marín-Moratalla, N
   Jordana, X
   Aanes, R
AF Koehler, Meike
   Marin-Moratalla, Nekane
   Jordana, Xavier
   Aanes, Ronny
TI Seasonal bone growth and physiology in endotherms shed light on dinosaur physiology
SO NATURE
LA English
DT Article
ID amprinos rule; reindeer; deer; hypometabolism; histology; hormones; food
AB Cyclical growth leaves marks in bone tissue that are in the forefront of discussions about physiologies of extinct vertebrates(1). Ectotherms show pronounced annual cycles of growth arrest that correlate with a decrease in body temperature and metabolic rate; endotherms are assumed to grow continuously until they attain maturity because of their constant high body temperature and sustained metabolic rate(1,2). This apparent dichotomy has driven the argument that zonal bone denotes ectotherm-like physiologies, thus fuelling the controversy on dinosaur thermophysiology and the evolution of endothermy in birds and mammal-like reptiles(1-4). Here we show, from a comprehensive global study of wild ruminants from tropical to polar environments, that cyclical growth is a universal trait of homoeothermic endotherms. Growth is arrested during the unfavourable season concurrently with decreases in body temperature, metabolic rate and bone-growth-mediating plasma insulin-like growth factor-1 levels, forming part of a plesiomorphic thermometabolic strategy for energy conservation. Conversely, bouts of intense tissue growth coincide with peak metabolic rates and correlated hormonal changes at the beginning of the favourable season, indicating an increased efficiency in acquiring and using seasonal resources. Our study supplies the strongest evidence so far that homeothermic endotherms arrest growth seasonally, which precludes the use of lines of arrested growth as an argument in support of ectothermy. However, high growth rates are a distinctive trait of mammals, suggesting the capacity for endogenous heat generation. The ruminant annual cycle provides an extant model on which to base inferences regarding the thermophysiology of dinosaurs and other extinct taxa.
C1 [Koehler, Meike] Univ Autonoma Barcelona, ICREA, Inst Catala Paleontol Miquel Crusafont, Bellaterra 08193, Spain.
   [Aanes, Ronny] Norwegian Polar Res Inst, Fram Ctr, NO-9296 Tromso, Norway.
   [Aanes, Ronny] Norwegian Directorate Nat Management, NO-7047 Trondheim, Norway.
C3 Institut Catala de Paleontologia Miquel Crusafont (ICP); ICREA; Autonomous University of Barcelona; Norwegian Polar Institute
RP Köhler, M (corresponding author), Univ Autonoma Barcelona, ICREA, Inst Catala Paleontol Miquel Crusafont, Bellaterra 08193, Spain.
EM meike.kohler@icp.cat
FU Spanish Ministry of Science and Innovation [CGL2008-06204/BTE, CGL2011-24685, BES-2009-02641, JCI-2010-08157]; Norwegian Research Council [NORKLIMA 178561/S30]; ICREA Funding Source: Custom
NR 30
TC 199
Z9 226
U1 3
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 JUL 19
PY 2012
VL 487
IS 7407
BP 358
EP 361
DI 10.1038/nature11264
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 975JB
UT WOS:000306506500041
PM 22763443
DA 2026-03-09
ER

PT J
AU Costelloe, T
   Louge, R
   Tomimatsu, N
   Mukherjee, B
   Martini, E
   Khadaroo, B
   Dubois, K
   Wiegant, WW
   Thierry, A
   Burma, S
   van Attikum, H
   Llorente, B
AF Costelloe, Thomas
   Louge, Raphael
   Tomimatsu, Nozomi
   Mukherjee, Bipasha
   Martini, Emmanuelle
   Khadaroo, Basheer
   Dubois, Kenny
   Wiegant, Wouter W.
   Thierry, Agnes
   Burma, Sandeep
   van Attikum, Haico
   Llorente, Bertrand
TI The yeast Fun30 and human SMARCAD1 chromatin remodellers promote DNA end resection
SO NATURE
LA English
DT Article
ID double-strand breaks; saccharomyces-cerevisiae; distinct roles; damage; exo1; repair; recombination; mutants; genes; sgs1
AB Several homology-dependent pathways can repair potentially lethal DNA double-strand breaks (DSBs). The first step common to all homologous recombination reactions is the 5'-3' degradation of DSB ends that yields the 39 single-stranded DNA required for the loading of checkpoint and recombination proteins. In yeast, the Mre11-Rad50-Xrs2 complex (Xrs2 is known as NBN or NBS1 in humans) and Sae2 (known as RBBP8 or CTIP in humans) initiate end resection, whereas long-range resection depends on the exonuclease Exo1, or the helicase-topoisomerase complex Sgs1-Top3-Rmi1 together with the endonuclease Dna2 (refs 1-6). DSBs occur in the context of chromatin, but how the resection machinery navigates through nucleosomal DNA is a process that is not well understood(7). Here we show that the yeast Saccharomyces cerevisiae Fun30 protein and its human counterpart SMARCAD1 (ref. 8), two poorly characterized ATP-dependent chromatin remodellers of the Snf2 ATPase family, are directly involved in the DSB response. Fun30 physically associates with DSB ends and directly promotes both Exo1- and Sgs1-dependent end resection through a mechanism involving its ATPase activity. The function of Fun30 in resection facilitates the repair of camptothecin-induced DNA lesions, although it becomes dispensable when Exo1 is ectopically overexpressed. Interestingly, SMARCAD1 is also recruited to DSBs, and the kinetics of recruitment is similar to that of EXO1. The loss of SMARCAD1 impairs end resection and recombinational DNA repair, and renders cells hypersensitive to DNA damage resulting from camptothecin or poly(ADP-ribose) polymerase inhibitor treatments. These findings unveil an evolutionarily conserved role for the Fun30 and SMARCAD1 chromatin remodellers in controlling end resection, homologous recombination and genome stability in the context of chromatin.
C1 [Louge, Raphael; Khadaroo, Basheer; Dubois, Kenny; Llorente, Bertrand] Ctr Rech Cancerol Marseille, CNRS, Unite Mixte Rech 7258, F-13009 Marseille, France.
   [Costelloe, Thomas; Wiegant, Wouter W.; van Attikum, Haico] Leiden Univ, Med Ctr, Dept Toxicogenet, NL-2333 ZC Leiden, Netherlands.
   [Louge, Raphael; Khadaroo, Basheer; Dubois, Kenny; Llorente, Bertrand] Aix Marseille Univ, Unite Mixte Rech 7258, F-13284 Marseille, France.
   [Tomimatsu, Nozomi; Mukherjee, Bipasha; Burma, Sandeep] Univ Texas SW Med Ctr Dallas, Dept Radiat Oncol, Div Mol Radiat Biol, Dallas, TX 75390 USA.
   [Martini, Emmanuelle] CEA DSV Inst Radiobiol Cellulaire & Mol, F-92265 Fontenay Aux Roses, France.
   [Thierry, Agnes] Inst Pasteur, CNRS, Unite Genet Mol Levures, F-75724 Paris 15, France.
   [Thierry, Agnes] Univ Paris 06, F-75724 Paris 15, France.
C3 Centre National de la Recherche Scientifique (CNRS); Aix-Marseille Universite; Institut National de la Sante et de la Recherche Medicale (Inserm); Leiden University - Excl LUMC; Leiden University; Leiden University Medical Center (LUMC); Aix-Marseille Universite; University of Texas System; University of Texas Southwestern Medical Center; Pasteur Network; Universite Paris Cite; Institut Pasteur Paris; Centre National de la Recherche Scientifique (CNRS); Sorbonne Universite
RP Llorente, B (corresponding author), Ctr Rech Cancerol Marseille, CNRS, Unite Mixte Rech 7258, F-13009 Marseille, France.
EM h.van.attikum@lumc.nl; bllorente@ifr88.cnrs-mrs.fr
FU National Institutes of Health [RO1 CA149461]; National Aeronautics and Space Administration [NNX10AE08G]; Cancer Prevention and Research Institute of Texas [RP100644]; Netherlands Organization for Scientific Research (NWO-VIDI grant); Human Frontiers Science Program(HFSP-CDA grant); CNRS (ATIP); Agence Nationale de la Recherche [ANR-10-BLAN-1606-03]; Agence Nationale de la Recherche (ANR) [ANR-10-BLAN-1606] Funding Source: Agence Nationale de la Recherche (ANR)
NR 38
TC 210
Z9 249
U1 1
U2 30
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 27
PY 2012
VL 489
IS 7417
BP 581
EP +
DI 10.1038/nature11353
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 046RG
UT WOS:000311781500007
PM 22960744
DA 2026-03-09
ER

PT J
AU Kumar, SV
   Lucyshyn, D
   Jaeger, KE
   Alós, E
   Alvey, E
   Harberd, NP
   Wigge, PA
AF Kumar, S. Vinod
   Lucyshyn, Doris
   Jaeger, Katja E.
   Alos, Enriqueta
   Alvey, Elizabeth
   Harberd, Nicholas P.
   Wigge, Philip A.
TI Transcription factor PIF4 controls the thermosensory activation of flowering
SO NATURE
LA English
DT Article
ID arabidopsis-thaliana; locus-t; high-temperature; gibberellin; growth; time; constans; light; expression; plants
AB Plant growth and development are strongly affected by small differences in temperature(1). Current climate change has already altered global plant phenology and distribution(2,3), and projected increases in temperature pose a significant challenge to agriculture(4). Despite the important role of temperature on plant development, the underlying pathways are unknown. It has previously been shown that thermal acceleration of flowering is dependent on the florigen, FLOWERING LOCUS T (FT)(5,6). How this occurs is, however, not understood, because the major pathway known to upregulate FT, the photoperiod pathway, is not required for thermal acceleration of flowering(6). Here we demonstrate a direct mechanism by which increasing temperature causes the bHLH transcription factor PHYTOCHROME INTERACTING FACTOR4 (PIF4) to activate FT. Our findings provide a new understanding of how plants control their timing of reproduction in response to temperature. Flowering time is an important trait in crops as well as affecting the life cycles of pollinator species. A molecular understanding of how temperature affects flowering will be important for mitigating the effects of climate change.
C1 [Kumar, S. Vinod; Lucyshyn, Doris; Jaeger, Katja E.; Alos, Enriqueta; Alvey, Elizabeth; Harberd, Nicholas P.; Wigge, Philip A.] John Innes Ctr Plant Sci Res, Dept Cell & Dev Biol, Norwich NR4 7UH, Norfolk, England.
   [Harberd, Nicholas P.] Univ Oxford, Dept Plant Sci, Oxford OX1 3RB, England.
C3 UK Research & Innovation (UKRI); Biotechnology and Biological Sciences Research Council (BBSRC); John Innes Centre; University of Oxford
RP Wigge, PA (corresponding author), Univ Cambridge, Sainsbury Lab, Bateman St, Cambridge CB2 1LR, England.
EM philip.wigge@slcu.cam.ac.uk
FU King Abdullah University of Science and Technology [KUK-I1-002-03]; Biotechnology and Biological Sciences Research Council (BBSRC) [BB/I019022/1, BB/D0100470/1]; Erwin Schroedinger Fellowship from the Austrian Science Fund FWF; John Innes Centre; European Research Council (ERC) [243140]; BBSRC [BBS/E/J/000CA346, BBS/E/J/000C0656, BBS/E/J/000CA402, BB/I019022/1] Funding Source: UKRI; Biotechnology and Biological Sciences Research Council [BBS/E/J/000C0656, BBS/E/J/000CA402, BBS/E/J/00000583, P19972, BBS/E/J/000CA346, BBS/E/J/00000610, BBS/E/J/000C0636, BB/I019022/1] Funding Source: researchfish; European Research Council (ERC) [243140] Funding Source: European Research Council (ERC)
NR 26
TC 618
Z9 718
U1 12
U2 437
PU NATURE PUBLISHING 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 12
PY 2012
VL 484
IS 7393
BP 242
EP U127
DI 10.1038/nature10928
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 930OV
UT WOS:000303149900035
PM 22437497
DA 2026-03-09
ER

PT J
AU Halfmann, R
   Jarosz, DF
   Jones, SK
   Chang, A
   Lancaster, AK
   Lindquist, S
AF Halfmann, Randal
   Jarosz, Daniel F.
   Jones, Sandra K.
   Chang, Amelia
   Lancaster, Alex K.
   Lindquist, Susan
TI Prions are a common mechanism for phenotypic inheritance in wild yeasts
SO NATURE
LA English
DT Article
ID genetic-variation; evolvability property; evolution; stress; chaperone; psi+; resistance; hsp104; hsp70
AB The self-templating conformations of yeast prion proteins act as epigenetic elements of inheritance. Yeast prions might provide a mechanism for generating heritable phenotypic diversity that promotes survival in fluctuating environments and the evolution of new traits. However, this hypothesis is highly controversial. Prions that create new traits have not been found in wild strains, leading to the perception that they are rare 'diseases' of laboratory cultivation. Here we biochemically test approximately 700 wild strains of Saccharomyces for [PSI+] or [MOT3(+)], and find these prions in many. They conferred diverse phenotypes that were frequently beneficial under selective conditions. Simple meiotic re-assortment of the variation harboured within a strain readily fixed one such trait, making it robust and prion-independent. Finally, we genetically screened for unknown prion elements. Fully one-third of wild strains harboured them. These, too, created diverse, often beneficial phenotypes. Thus, prions broadly govern heritable traits in nature, in a manner that could profoundly expand adaptive opportunities.
C1 [Halfmann, Randal; Jarosz, Daniel F.; Jones, Sandra K.; Chang, Amelia; Lancaster, Alex K.; Lindquist, Susan] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA.
   [Halfmann, Randal; Chang, Amelia; Lindquist, Susan] MIT, Dept Biol, Cambridge, MA 02139 USA.
   [Lindquist, Susan] MIT, Howard Hughes Med Inst, Cambridge, MA 02139 USA.
C3 Massachusetts Institute of Technology (MIT); Whitehead Institute; Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); Howard Hughes Medical Institute
RP Lindquist, S (corresponding author), Whitehead Inst Biomed Res, 9 Cambridge Ctr, Cambridge, MA 02142 USA.
EM Lindquist_admin@wi.mit.edu
FU G. Harold and Leila Y. Mathers Foundation; HHMI; NIH [K99 GM098600]
NR 46
TC 324
Z9 405
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 FEB 16
PY 2012
VL 482
IS 7385
BP 363
EP U1507
DI 10.1038/nature10875
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 892LG
UT WOS:000300287100038
PM 22337056
DA 2026-03-09
ER

PT J
AU van der Harst, P
   Zhang, WH
   Leach, IM
   Rendon, A
   Verweij, N
   Sehmi, J
   Paul, DS
   Elling, U
   Allayee, H
   Li, XZ
   Radhakrishnan, A
   Tan, ST
   Voss, K
   Weichenberger, CX
   Albers, CA
   Al-Hussani, A
   Asselbergs, FW
   Ciullo, M
   Danjou, F
   Dina, C
   Esko, T
   Evans, DM
   Franke, L
   Goegele, M
   Hartiala, J
   Hersch, M
   Holm, H
   Hottenga, JJ
   Kanoni, S
   Kleber, ME
   Lagou, V
   Langenberg, C
   Lopez, LM
   Lyytikäinen, LP
   Melander, O
   Murgia, F
   Nolte, IM
   O'Reilly, PF
   Padmanabhan, S
   Parsa, A
   Pirastu, N
   Porcu, E
   Portas, L
   Prokopenko, I
   Ried, JS
   Shin, SY
   Tang, CS
   Teumer, A
   Traglia, M
   Ulivi, S
   Westra, HJ
   Yang, J
   Zhao, JH
   Anni, F
   Abdellaoui, A
   Attwood, A
   Balkau, B
   Bandinelli, S
   Bastardot, F
   Benyamin, B
   Boehm, BO
   Cookson, WO
   Das, D
   de Bakker, PIW
   de Boer, RA
   de Geus, EJC
   de Moor, MH
   Dimitriou, M
   Domingues, FS
   Döring, A
   Engström, G
   Eyjolfsson, GI
   Ferrucci, L
   Fischer, K
   Galanello, R
   Garner, SF
   Genser, B
   Gibson, QD
   Girotto, G
   Gudbjartsson, DF
   Harris, SE
   Hartikainen, AL
   Hastie, CE
   Hedblad, B
   Illig, T
   Jolley, J
   Kähönen, M
   Kema, IP
   Kemp, JP
   Liang, LM
   Lloyd-Jones, H
   Loos, RJF
   Meacham, S
   Medland, SE
   Meisinger, C
   Memari, Y
   Mihailov, E
   Miller, K
   Moffatt, MF
   Nauck, M
   Novatchkova, M
   Nutile, T
   Olafsson, I
   Onundarson, PT
   Parracciani, D
   Penninx, BW
   Perseu, L
   Piga, A
   Pistis, G
   Pouta, A
   Puc, U
   Raitakari, O
   Ring, SM
   Robino, A
   Ruggiero, D
   Ruokonen, A
   Saint-Pierre, A
   Sala, C
   Salumets, A
   Sambrook, J
   Schepers, H
   Schmidt, CO
   Silljé, HHW
   Sladek, R
   Smit, JH
   Starr, JM
   Stephens, J
   Sulem, P
   Tanaka, T
   Thorsteinsdottir, U
   Tragante, V
   van Gilst, WH
   van Pelt, LJ
   van Veldhuisen, DJ
   Völker, U
   Whitfield, JB
   Willemsen, G
   Winkelmann, BR
   Wirnsberger, G
   Algra, A
   Cucca, F
   d'Adamo, AP
   Danesh, J
   Deary, IJ
   Dominiczak, AF
   Elliott, P
   Fortina, P
   Froguel, P
   Gasparini, P
   Greinacher, A
   Hazen, SL
   Jarvelin, MR
   Khaw, KT
   Lehtimäki, T
   Maerz, W
   Martin, NG
   Metspalu, A
   Mitchell, BD
   Montgomery, GW
   Moore, C
   Navis, G
   Pirastu, M
   Pramstaller, PP
   Ramirez-Solis, R
   Schadt, E
   Scott, J
   Shuldiner, AR
   Smith, GD
   Smith, JG
   Snieder, H
   Sorice, R
   Spector, TD
   Stefansson, K
   Stumvoll, M
   Tang, WHW
   Toniolo, D
   Tönjes, A
   Visscher, PM
   Vollenweider, P
   Wareham, NJ
   Wolffenbuttel, BHR
   Boomsma, DI
   Beckmann, JS
   Dedoussis, GV
   Deloukas, P
   Ferreira, MA
   Sanna, S
   Uda, M
   Hicks, AA
   Penninger, JM
   Gieger, C
   Kooner, JS
   Ouwehand, WH
   Soranzo, N
   Chambers, JC
AF van der Harst, Pim
   Zhang, Weihua
   Leach, Irene Mateo
   Rendon, Augusto
   Verweij, Niek
   Sehmi, Joban
   Paul, Dirk S.
   Elling, Ulrich
   Allayee, Hooman
   Li, Xinzhong
   Radhakrishnan, Aparna
   Tan, Sian-Tsung
   Voss, Katrin
   Weichenberger, Christian X.
   Albers, Cornelis A.
   Al-Hussani, Abtehale
   Asselbergs, Folkert W.
   Ciullo, Marina
   Danjou, Fabrice
   Dina, Christian
   Esko, Tonu
   Evans, David M.
   Franke, Lude
   Goegele, Martin
   Hartiala, Jaana
   Hersch, Micha
   Holm, Hilma
   Hottenga, Jouke-Jan
   Kanoni, Stavroula
   Kleber, Marcus E.
   Lagou, Vasiliki
   Langenberg, Claudia
   Lopez, Lorna M.
   Lyytikainen, Leo-Pekka
   Melander, Olle
   Murgia, Federico
   Nolte, Ilja M.
   O'Reilly, Paul F.
   Padmanabhan, Sandosh
   Parsa, Afshin
   Pirastu, Nicola
   Porcu, Eleonora
   Portas, Laura
   Prokopenko, Inga
   Ried, Janina S.
   Shin, So-Youn
   Tang, Clara S.
   Teumer, Alexander
   Traglia, Michela
   Ulivi, Sheila
   Westra, Harm-Jan
   Yang, Jian
   Zhao, Jing Hua
   Anni, Franco
   Abdellaoui, Abdel
   Attwood, Antony
   Balkau, Beverley
   Bandinelli, Stefania
   Bastardot, Francois
   Benyamin, Beben
   Boehm, Bernhard O.
   Cookson, William O.
   Das, Debashish
   de Bakker, Paul I. W.
   de Boer, Rudolf A.
   de Geus, Eco J. C.
   de Moor, Marleen H.
   Dimitriou, Maria
   Domingues, Francisco S.
   Doering, Angela
   Engstrom, Gunnar
   Eyjolfsson, Gudmundur Ingi
   Ferrucci, Luigi
   Fischer, Krista
   Galanello, Renzo
   Garner, Stephen F.
   Genser, Bernd
   Gibson, Quince D.
   Girotto, Giorgia
   Gudbjartsson, Daniel Fannar
   Harris, Sarah E.
   Hartikainen, Anna-Liisa
   Hastie, Claire E.
   Hedblad, Bo
   Illig, Thomas
   Jolley, Jennifer
   Kahonen, Mika
   Kema, Ido P.
   Kemp, John P.
   Liang, Liming
   Lloyd-Jones, Heather
   Loos, Ruth J. F.
   Meacham, Stuart
   Medland, Sarah E.
   Meisinger, Christa
   Memari, Yasin
   Mihailov, Evelin
   Miller, Kathy
   Moffatt, Miriam F.
   Nauck, Matthias
   Novatchkova, Maria
   Nutile, Teresa
   Olafsson, Isleifur
   Onundarson, Pall T.
   Parracciani, Debora
   Penninx, Brenda W.
   Perseu, Lucia
   Piga, Antonio
   Pistis, Giorgio
   Pouta, Anneli
   Puc, Ursula
   Raitakari, Olli
   Ring, Susan M.
   Robino, Antonietta
   Ruggiero, Daniela
   Ruokonen, Aimo
   Saint-Pierre, Aude
   Sala, Cinzia
   Salumets, Andres
   Sambrook, Jennifer
   Schepers, Hein
   Schmidt, Carsten Oliver
   Sillje, Herman H. W.
   Sladek, Rob
   Smit, Johannes H.
   Starr, John M.
   Stephens, Jonathan
   Sulem, Patrick
   Tanaka, Toshiko
   Thorsteinsdottir, Unnur
   Tragante, Vinicius
   van Gilst, Wiek H.
   van Pelt, L. Joost
   van Veldhuisen, Dirk J.
   Voelker, Uwe
   Whitfield, John B.
   Willemsen, Gonneke
   Winkelmann, Bernhard R.
   Wirnsberger, Gerald
   Algra, Ale
   Cucca, Francesco
   d'Adamo, Adamo Pio
   Danesh, John
   Deary, Ian J.
   Dominiczak, Anna F.
   Elliott, Paul
   Fortina, Paolo
   Froguel, Philippe
   Gasparini, Paolo
   Greinacher, Andreas
   Hazen, Stanley L.
   Jarvelin, Marjo-Riitta
   Khaw, Kay Tee
   Lehtimaki, Terho
   Maerz, Winfried
   Martin, Nicholas G.
   Metspalu, Andres
   Mitchell, Braxton D.
   Montgomery, Grant W.
   Moore, Carmel
   Navis, Gerjan
   Pirastu, Mario
   Pramstaller, Peter P.
   Ramirez-Solis, Ramiro
   Schadt, Eric
   Scott, James
   Shuldiner, Alan R.
   Smith, George Davey
   Smith, J. Gustav
   Snieder, Harold
   Sorice, Rossella
   Spector, Tim D.
   Stefansson, Kari
   Stumvoll, Michael
   Tang, W. H. Wilson
   Toniolo, Daniela
   Toenjes, Anke
   Visscher, Peter M.
   Vollenweider, Peter
   Wareham, Nicholas J.
   Wolffenbuttel, Bruce H. R.
   Boomsma, Dorret I.
   Beckmann, Jacques S.
   Dedoussis, George V.
   Deloukas, Panos
   Ferreira, Manuel A.
   Sanna, Serena
   Uda, Manuela
   Hicks, Andrew A.
   Penninger, Josef Martin
   Gieger, Christian
   Kooner, Jaspal S.
   Ouwehand, Willem H.
   Soranzo, Nicole
   Chambers, John C.
TI Seventy-five genetic loci influencing the human red blood cell
SO NATURE
LA English
DT Article
ID genome-wide association; hemoglobin levels; variants; expression; protein; cohort; domain; level; mouse; stem
AB Anaemia is a chief determinant of global ill health, contributing to cognitive impairment, growth retardation and impaired physical capacity. To understand further the genetic factors influencing red blood cells, we carried out a genome-wide association study of haemoglobin concentration and related parameters in up to 135,367 individuals. Here we identify 75 independent genetic loci associated with one or more red blood cell phenotypes at P < 10(-8), which together explain 4-9% of the phenotypic variance per trait. Using expression quantitative trait loci and bioinformatic strategies, we identify 121 candidate genes enriched in functions relevant to red blood cell biology. The candidate genes are expressed preferentially in red blood cell precursors, and 43 have haematopoietic phenotypes in Mus musculus or Drosophila melanogaster. Through open-chromatin and coding-variant analyses we identify potential causal genetic variants at 41 loci. Our findings provide extensive new insights into genetic mechanisms and biological pathways controlling red blood cell formation and function.
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   [Pramstaller, Peter P.] Med Univ Lubeck, Dept Neurol, D-23538 Lubeck, Germany.
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   [Smith, J. Gustav] Lund Univ, Dept Cardiol, S-22185 Lund, Sweden.
   [Spector, Tim D.] Kings Coll London, Dept Twin Res & Genet Epidemiol, London SE1 7EH, England.
   [Stumvoll, Michael; Toenjes, Anke] Univ Leipzig, Dept Med, D-04103 Leipzig, Germany.
   [Stumvoll, Michael; Toenjes, Anke] Univ Leipzig, IFB Adipos Dis, D-04103 Leipzig, Germany.
   [Toniolo, Daniela] CNR, Inst Mol Genet, I-27100 Pavia, Italy.
   [Wolffenbuttel, Bruce H. R.] Univ Groningen, Univ Med Ctr Groningen, Dept Endocrinol, NL-9700 RB Groningen, Netherlands.
   [Beckmann, Jacques S.] CHU Vaudois, Serv Med Genet, CH-1011 Lausanne, Switzerland.
   [Kooner, Jaspal S.; Chambers, John C.] Imperial Coll Healthcare NHS Trust, London W12 0HS, England.
C3 Imperial College London; University of Groningen; University of Groningen; University of Cambridge; MRC Biostatistics Unit; University of Cambridge; University of Cambridge; Imperial College London; Wellcome Trust Sanger Institute; Austrian Academy of Sciences; Vienna Biocenter (VBC); Institute of Molecular Biotechnology (IMBA); University of Southern California; Imperial College London; Royal Brompton & Harefield NHS Foundation Trust; Imperial College London; European Academy of Bozen-Bolzano; Utrecht University; Utrecht University Medical Center; Utrecht University; Utrecht University Medical Center; Utrecht University; Utrecht University Medical Center; Consiglio Nazionale delle Ricerche (CNR); Istituto di Genetica e Biofisica Adriano Buzzati-Traverso (IGB-CNR); University of Cagliari; Institut National de la Sante et de la Recherche Medicale (Inserm); Centre National de la Recherche Scientifique (CNRS); Nantes Universite; University of Tartu; University of Tartu; University of Bristol; University of Lausanne; Swiss Institute of Bioinformatics; Decode Genetics; Vrije Universiteit Amsterdam; Ruprecht Karls University Heidelberg; University of Oxford; University of Oxford; Wellcome Centre for Human Genetics; University of Cambridge; Cambridge University Hospitals NHS Foundation Trust; Addenbrooke's Hospital; University of Edinburgh; University of Edinburgh; Tampere University; Tampere University Hospital; Tampere University; Lund University; Consiglio Nazionale delle Ricerche (CNR); University of Groningen; University of Glasgow; University System of Maryland; University of Maryland Baltimore; University of Trieste; IRCCS Burlo Garofolo; University of Cagliari; Consiglio Nazionale delle Ricerche (CNR); Istituto di Ricerca Genetica e Biomedica (IRGB-CNR); Helmholtz Association; Helmholtz-Center Munich - German Research Center for Environmental Health; QIMR Berghofer Medical Research Institute; Universitat Greifswald; Greifswald Medical School; Vita-Salute San Raffaele University; IRCCS Ospedale San Raffaele; Princess Alexandra Hospital; University of Queensland; Universite Paris Saclay; Institut National de la Sante et de la Recherche Medicale (Inserm); Institut National de la Sante et de la Recherche Medicale (Inserm); Universite Paris Saclay; Azienda Sanitaria di Firenze; University of Lausanne; University of Queensland; Ulm University; University of London; University College London; Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Harokopio University Athens; Helmholtz Association; Helmholtz-Center Munich - German Research Center for Environmental Health; Helmholtz Association; Helmholtz-Center Munich - German Research Center for Environmental Health; National Institutes of Health (NIH) - USA; NIH National Institute on Aging (NIA); Universidade Federal da Bahia; University of Edinburgh; University of Oulu; Helmholtz Association; Helmholtz-Center Munich - German Research Center for Environmental Health; Hannover Medical School; Tampere University; Tampere University Hospital; Tampere University; University of Groningen; Harvard University; Harvard T.H. Chan School of Public Health; University of London; King's College London; Universitat Greifswald; Greifswald Medical School; Landspitali National University Hospital; University of Iceland; Landspitali National University Hospital; Landspitali National University Hospital; Vrije Universiteit Amsterdam; Amsterdam University Medical Center; University of Groningen; Leiden University; Leiden University Medical Center (LUMC); Leiden University - Excl LUMC; University of Turin; University of Turin; University of Oulu; Finland National Institute for Health & Welfare; University of Turku; University of Turku; University of Bristol; University of Oulu; University of Tartu; University of Groningen; University of Groningen; Universitat Greifswald; Greifswald Medical School; McGill University; McGill University; University of Edinburgh; Utrecht University; Utrecht University Medical Center; University of Sassari; University of Cambridge; Imperial College London; Thomas Jefferson University; Sapienza University Rome; Pasteur Network; Universite de Lille; Institut Pasteur Lille; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB); Imperial College London; Universitat Greifswald; Greifswald Medical School; Cleveland Clinic Foundation; Finland National Institute for Health & Welfare; University of Oulu; University of Cambridge; Cambridge University Hospitals NHS Foundation Trust; Addenbrooke's Hospital; SYNLAB Group; University of Groningen; Krankenhaus Bozen; University of Lubeck; Icahn School of Medicine at Mount Sinai; Geriatric Research Education & Clinical Center; US Department of Veterans Affairs; Veterans Health Administration (VHA); Lund University; University of London; King's College London; Leipzig University; Leipzig University; Consiglio Nazionale delle Ricerche (CNR); Istituto di Genetica Molecolare (IGM-CNR); University of Groningen; University of Lausanne; Centre Hospitalier Universitaire Vaudois (CHUV); Imperial College London
RP Chambers, JC (corresponding author), Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Biostat, London W2 1PG, England.
EM p.van.der.harst@umcg.nl; christian.gieger@helmholtz-muenchen.de; j.kooner@ic.ac.uk; who1000@cam.ac.uk; ns6@sanger.ac.uk; john.chambers@ic.ac.uk
FU MRC [G0600705, G0801056, G1002084, MC_U106188470, G0700704] Funding Source: UKRI; Austrian Science Fund FWF [I 434] Funding Source: Medline; British Heart Foundation [RG/09/012/28096, RG/08/014/24067] Funding Source: Medline; Cancer Research UK [14136] Funding Source: Medline; Chief Scientist Office [ETM/55, CZB/4/505] Funding Source: Medline; Medical Research Council [G9815508, G0700704, G0801056, G1002084, G0401527, MC_U106179471, MC_U106188470, G1000143, G0600705] Funding Source: Medline; NCATS NIH HHS [UL1 TR000439] Funding Source: Medline; NCI NIH HHS [R01 CA165001] Funding Source: Medline; NCRR NIH HHS [K12 RR023250, U54 RR020278, UL1 RR025005] Funding Source: Medline; NHGRI NIH HHS [U01 HG004402] Funding Source: Medline; NHLBI NIH HHS [P01 HL098055, HHSN268201100005G, R01 HL103931, HHSN268201100007I, HHSN268201100005I, HHSN268201100010C, R01 HL088119, R01 HL087641, R01 HL087679, HHSN268201100009I, HHSN268201100012C, HHSN268201100009C, R01 HL059367, U01 HL072515, P20 HL113452, HHSN268201100008I, R01 HL103866, HHSN268201100008C, P01 HL076491, R01 HL086694, HHSN268201100011C, HHSN268201100006C, HHSN268201100011I, U01 HL084756, HHSN268201100007C, HHSN268201100005C] Funding Source: Medline; NIA NIH HHS [R01 AG018728, N01 AG012109] Funding Source: Medline; NICHD NIH HHS [R01 HD042157] Funding Source: Medline; NIDA NIH HHS [HHSN271201100005C] Funding Source: Medline; NIDDK NIH HHS [P30 DK072488] Funding Source: Medline; NIGMS NIH HHS [R01 GM053275, U01 GM074518] Funding Source: Medline; NIMH NIH HHS [U24 MH068457, RL1 MH083268, R01 MH081802] Funding Source: Medline; NLM NIH HHS [R01 LM010098] Funding Source: Medline; Wellcome Trust [092731, 097117] Funding Source: Medline; Department of Health [RP-PG-0310-1002] Funding Source: Medline; National Heart Lung and Blood Institute [R01HL059367, R01HL086694] Funding Source: NIH RePORTER; National Heart Lung and Blood Institute; NIH Office of the Director [R01HL103866] Funding Source: NIH RePORTER; National Institute of Mental Health [U24MH068457] Funding Source: NIH RePORTER; National Library of Medicine [R01LM010098] Funding Source: NIH RePORTER; Austrian Science Fund (FWF) [I 434] Funding Source: researchfish; British Heart Foundation [RG/09/012/28096, RG/08/014/24067] Funding Source: researchfish; Cancer Research UK [14136] Funding Source: researchfish; Chief Scientist Office [CZB/4/505, ETM/55] Funding Source: researchfish; Medical Research Council [G0801056, G0401527, G1000143, MC_U106188470, G1002084, G0700704B, G0600705, G9815508, G0801056B, MC_U106179471, G0700704] Funding Source: researchfish; National Institute for Health Research [NF-SI-0611-10136, NF-SI-0611-10275, RP-PG-0310-1002] Funding Source: researchfish; Wellcome Trust [096964/Z/11/Z] Funding Source: researchfish
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NR 47
TC 258
Z9 284
U1 0
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 20
PY 2012
VL 492
IS 7429
BP 369
EP +
DI 10.1038/nature11677
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 056KQ
UT WOS:000312488200044
PM 23222517
DA 2026-03-09
ER

PT J
AU Robinson, G
   Parker, M
   Kranenburg, TA
   Lu, C
   Chen, X
   Ding, L
   Phoenix, TN
   Hedlund, E
   Wei, L
   Zhu, XY
   Chalhoub, N
   Baker, SJ
   Huether, R
   Kriwacki, R
   Curley, N
   Thiruvenkatam, R
   Wang, JM
   Wu, G
   Rusch, M
   Hong, X
   Becksfort, J
   Gupta, P
   Ma, J
   Easton, J
   Vadodaria, B
   Onar-Thomas, A
   Lin, T
   Li, SY
   Pounds, S
   Paugh, S
   Zhao, D
   Kawauchi, D
   Roussel, MF
   Finkelstein, D
   Ellison, DW
   Lau, CC
   Bouffet, E
   Hassall, T
   Gururangan, S
   Cohn, R
   Fulton, RS
   Fulton, LL
   Dooling, DJ
   Ochoa, K
   Gajjar, A
   Mardis, ER
   Wilson, RK
   Downing, JR
   Zhang, JH
   Gilbertson, RJ
AF Robinson, Giles
   Parker, Matthew
   Kranenburg, Tanya A.
   Lu, Charles
   Chen, Xiang
   Ding, Li
   Phoenix, Timothy N.
   Hedlund, Erin
   Wei, Lei
   Zhu, Xiaoyan
   Chalhoub, Nader
   Baker, Suzanne J.
   Huether, Robert
   Kriwacki, Richard
   Curley, Natasha
   Thiruvenkatam, Radhika
   Wang, Jianmin
   Wu, Gang
   Rusch, Michael
   Hong, Xin
   Becksfort, Jared
   Gupta, Pankaj
   Ma, Jing
   Easton, John
   Vadodaria, Bhavin
   Onar-Thomas, Arzu
   Lin, Tong
   Li, Shaoyi
   Pounds, Stanley
   Paugh, Steven
   Zhao, David
   Kawauchi, Daisuke
   Roussel, Martine F.
   Finkelstein, David
   Ellison, David W.
   Lau, Ching C.
   Bouffet, Eric
   Hassall, Tim
   Gururangan, Sridharan
   Cohn, Richard
   Fulton, Robert S.
   Fulton, Lucinda L.
   Dooling, David J.
   Ochoa, Kerri
   Gajjar, Amar
   Mardis, Elaine R.
   Wilson, Richard K.
   Downing, James R.
   Zhang, Jinghui
   Gilbertson, Richard J.
TI Novel mutations target distinct subgroups of medulloblastoma
SO NATURE
LA English
DT Article
ID box rna helicase; e-cadherin gene; beta-catenin; somatic mutations; breast-cancer; stem-cells; drosophila; ezh2; transactivation; methylation
AB Medulloblastoma is a malignant childhood brain tumour comprising four discrete subgroups. Here, to identify mutations that drive medulloblastoma, we sequenced the entire genomes of 37 tumours and matched normal blood. One-hundred and thirty-six genes harbouring somatic mutations in this discovery set were sequenced in an additional 56 medulloblastomas. Recurrent mutations were detected in 41 genes not yet implicated in medulloblastoma; several target distinct components of the epigenetic machinery in different disease subgroups, such as regulators of H3K27 and H3K4 trimethylation in subgroups 3 and 4 (for example, KDM6A and ZMYM3), and CTNNB1-associated chromatin re-modellers in WNT-subgroup tumours (for example, SMARCA4 and CREBBP). Modelling of mutations in mouse lower rhombic lip progenitors that generate WNT-subgroup tumours identified genes that maintain this cell lineage (DDX3X), as well as mutated genes that initiate (CDH1) or cooperate (PIK3CA) in tumorigenesis. These data provide important new insights into the pathogenesis of medulloblastoma subgroups and highlight targets for therapeutic development.
C1 [Robinson, Giles; Parker, Matthew; Kranenburg, Tanya A.; Lu, Charles; Chen, Xiang; Ding, Li; Phoenix, Timothy N.; Hedlund, Erin; Wei, Lei; Zhu, Xiaoyan; Chalhoub, Nader; Baker, Suzanne J.; Huether, Robert; Kriwacki, Richard; Curley, Natasha; Thiruvenkatam, Radhika; Wang, Jianmin; Wu, Gang; Rusch, Michael; Hong, Xin; Becksfort, Jared; Gupta, Pankaj; Ma, Jing; Easton, John; Vadodaria, Bhavin; Onar-Thomas, Arzu; Lin, Tong; Li, Shaoyi; Pounds, Stanley; Paugh, Steven; Zhao, David; Kawauchi, Daisuke; Roussel, Martine F.; Finkelstein, David; Ellison, David W.; Lau, Ching C.; Bouffet, Eric; Hassall, Tim; Gururangan, Sridharan; Cohn, Richard; Fulton, Robert S.; Fulton, Lucinda L.; Dooling, David J.; Ochoa, Kerri; Gajjar, Amar; Mardis, Elaine R.; Wilson, Richard K.; Downing, James R.; Zhang, Jinghui; Gilbertson, Richard J.] Washington Univ, St Jude Childrens Res Hosp, Pediat Canc Genome Project, Memphis, TN 38105 USA.
   [Robinson, Giles; Kranenburg, Tanya A.; Phoenix, Timothy N.; Zhu, Xiaoyan; Chalhoub, Nader; Baker, Suzanne J.; Curley, Natasha; Thiruvenkatam, Radhika; Gilbertson, Richard J.] St Jude Childrens Hosp, Dept Dev Neurobiol, Memphis, TN 38105 USA.
   [Robinson, Giles; Gajjar, Amar; Gilbertson, Richard J.] St Jude Childrens Hosp, Dept Oncol, Memphis, TN 38105 USA.
   [Parker, Matthew; Chen, Xiang; Hedlund, Erin; Wei, Lei; Huether, Robert; Wu, Gang; Rusch, Michael; Easton, John; Vadodaria, Bhavin; Finkelstein, David; Zhang, Jinghui] St Jude Childrens Hosp, Dept Computat Biol & Bioinformat, Memphis, TN 38105 USA.
   [Lu, Charles; Ding, Li; Hong, Xin; Fulton, Robert S.; Fulton, Lucinda L.; Dooling, David J.; Ochoa, Kerri; Mardis, Elaine R.; Wilson, Richard K.] Washington Univ, Sch Med, Genome Inst, St Louis, MO 63108 USA.
   [Ding, Li; Fulton, Robert S.; Fulton, Lucinda L.; Dooling, David J.; Ochoa, Kerri; Mardis, Elaine R.; Wilson, Richard K.] Washington Univ, Sch Med, Dept Genet, St Louis, MO 63108 USA.
   [Wei, Lei; Ma, Jing; Ellison, David W.; Downing, James R.] St Jude Childrens Hosp, Dept Pathol, Memphis, TN 38105 USA.
   [Huether, Robert; Kriwacki, Richard] St Jude Childrens Hosp, Dept Biol Struct, Memphis, TN 38105 USA.
   [Wang, Jianmin; Becksfort, Jared; Gupta, Pankaj; Zhao, David] St Jude Childrens Hosp, Dept Informat Sci, Memphis, TN 38105 USA.
   [Onar-Thomas, Arzu; Lin, Tong; Li, Shaoyi; Pounds, Stanley] St Jude Childrens Hosp, Dept Biostat, Memphis, TN 38105 USA.
   [Paugh, Steven] St Jude Childrens Hosp, Dept Pharmaceut Sci, Memphis, TN 38105 USA.
   [Kawauchi, Daisuke; Roussel, Martine F.] St Jude Childrens Hosp, Dept Tumour Biol & Genet, Memphis, TN 38105 USA.
   [Lau, Ching C.] Texas Childrens Canc & Hematol Ctr, Houston, TX 77030 USA.
   [Bouffet, Eric] Hosp Sick Children, Toronto, ON M5G 1X8, Canada.
   [Hassall, Tim] Royal Childrens Hosp, Parkville, Vic 3052, Australia.
   [Gururangan, Sridharan] Duke Univ, Med Ctr, Durham, NC 27710 USA.
   [Cohn, Richard] Univ New S Wales, Sch Womens & Childrens Hlth, Kensington, NSW 2052, Australia.
   [Mardis, Elaine R.] Washington Univ, Sch Med, Siteman Canc Ctr, St Louis, MO 63108 USA.
   [Wilson, Richard K.] Washington Univ, Sch Med, Dept Med, 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; Washington University (WUSTL); Washington University (WUSTL); 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 Tennessee System; University of Tennessee Health Science Center; St Jude Children's Research Hospital; Texas Children's Cancer Center; University of Toronto; Hospital for Sick Children (SickKids); Royal Children's Hospital Melbourne; Duke University; University of New South Wales Sydney; Washington University (WUSTL); Siteman Cancer Center; Washington University (WUSTL)
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; 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); Musicians against Childhood Cancer (MACC); Noyes Brain Tumour Foundation; American Lebanese Syrian Associated Charities (ALSAC); National Cancer Institute [P30CA021765, P01CA096832] Funding Source: NIH RePORTER
NR 50
TC 696
Z9 819
U1 1
U2 65
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD AUG 2
PY 2012
VL 488
IS 7409
BP 43
EP 48
DI 10.1038/nature11213
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 981ZE
UT WOS:000307010700029
PM 22722829
DA 2026-03-09
ER

PT J
AU Chen, JN
   Badioli, M
   Alonso-González, P
   Thongrattanasiri, S
   Huth, F
   Osmond, J
   Spasenovic, M
   Centeno, A
   Pesquera, A
   Godignon, P
   Elorza, AZ
   Camara, N
   de Abajo, FJG
   Hillenbrand, R
   Koppens, FHL
AF Chen, Jianing
   Badioli, Michela
   Alonso-Gonzalez, Pablo
   Thongrattanasiri, Sukosin
   Huth, Florian
   Osmond, Johann
   Spasenovic, Marko
   Centeno, Alba
   Pesquera, Amaia
   Godignon, Philippe
   Zurutuza Elorza, Amaia
   Camara, Nicolas
   Javier Garcia de Abajo, F.
   Hillenbrand, Rainer
   Koppens, Frank H. L.
TI Optical nano-imaging of gate-tunable graphene plasmons
SO NATURE
LA English
DT Article
ID scattering; dynamics; scale
AB The ability to manipulate optical fields and the energy flow of light is central to modern information and communication technologies, as well as quantum information processing schemes. However, because photons do not possess charge, a way of controlling them efficiently by electrical means has so far proved elusive. A promising way to achieve electric control of light could be through plasmon polaritons-coupled excitations of photons and charge carriers-in graphene(1-5). In this two-dimensional sheet of carbon atoms(6), it is expected that plasmon polaritons and their associated optical fields can readily be tuned electrically by varying the graphene carrier density. Although evidence of optical graphene plasmon resonances has recently been obtained spectroscopically(7,8), no experiments so far have directly resolved propagating plasmons in real space. Here we launch and detect propagating optical plasmons in tapered graphene nanostructures using near-field scattering microscopy with infrared excitation light(9-11). We provide real-space images of plasmon fields, and find that the extracted plasmon wavelength is very short-more than 40 times smaller than the wavelength of illumination. We exploit this strong optical field confinement to turn a graphene nanostructure into a tunable resonant plasmonic cavity with extremely small mode volume. The cavity resonance is controlled in situ by gating the graphene, and in particular, complete switching on and off of the plasmon modes is demonstrated, thus paving the way towards graphene-based optical transistors. This successful alliance between nanoelectronics and nano-optics enables the development of active subwavelength-scale optics and a plethora of nano-optoelectronic devices and functionalities, such as tunable metamaterials(12), nanoscale optical processing, and strongly enhanced light-matter interactions for quantum devices(13) and biosensing applications.
C1 [Thongrattanasiri, Sukosin; Javier Garcia de Abajo, F.] CSIC, Inst Quim Fis Rocasolano, E-28006 Madrid, Spain.
   [Chen, Jianing; Alonso-Gonzalez, Pablo; Huth, Florian; Hillenbrand, Rainer] CIC nanoGUNE Consolider, Donostia San Sebastian 20018, Spain.
   [Chen, Jianing] Ctr Fis Mat CSIC UPV EHU, Donostia San Sebastian 20018, Spain.
   [Chen, Jianing] DIPC, Donostia San Sebastian 20018, Spain.
   [Badioli, Michela; Osmond, Johann; Spasenovic, Marko; Koppens, Frank H. L.] ICFO Inst Ciencies Foton, Barcelona 08860, Spain.
   [Huth, Florian] Neaspec GmbH, D-82152 Munich, Germany.
   [Centeno, Alba; Pesquera, Amaia; Zurutuza Elorza, Amaia] Graphenea SA, Donostia San Sebastian 20018, Spain.
   [Godignon, Philippe] CSIC, IMB, CNM, Barcelona 08193, Spain.
   [Camara, Nicolas] Univ Tours, CNRS, UMR 7347, GREMAN, F-37071 Tours 2, France.
   [Hillenbrand, Rainer] Basque Fdn Sci, IKERBASQUE, Bilbao 48011, Spain.
C3 Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Instituto de Quimica Fisica Blas Cabrera (IQF-CSIC); University of Basque Country; Barcelona Institute of Science & Technology; Universitat Politecnica de Catalunya; Institut de Ciencies Fotoniques (ICFO); Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Centro Nacional de Microelectronica (CNM); CSIC - Instituto de Microelectronica de Barcelona (IMB-CNM); Universite de Tours; Centre National de la Recherche Scientifique (CNRS); Basque Foundation for Science
RP de Abajo, FJG (corresponding author), CSIC, Inst Quim Fis Rocasolano, Serrano 119, E-28006 Madrid, Spain.
EM J.G.deAbajo@csic.es; r.hillenbrand@nanogune.eu; frank.koppens@icfo.es
FU Fundacicio Cellex Barcelona; Spanish MICINN [MAT2010-14885, Consolider NanoLight.es]; European FP7 projects [FP7-HEALTH-F5-2009-241818-NANOANTENNA, FP7-ICT-2009-4-248909-LIMA, FP7-ICT-2009-4-248855-N4E]; ERC [258461]; European Research Council (ERC) [258461] Funding Source: European Research Council (ERC)
NR 29
TC 1817
Z9 2017
U1 16
U2 1645
PU NATURE PUBLISHING 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 5
PY 2012
VL 487
IS 7405
BP 77
EP 81
DI 10.1038/nature11254
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 968LM
UT WOS:000305982900053
PM 22722861
DA 2026-03-09
ER

PT J
AU Ackman, JB
   Burbridge, TJ
   Crair, MC
AF Ackman, James B.
   Burbridge, Timothy J.
   Crair, Michael C.
TI Retinal waves coordinate patterned activity throughout the developing visual system
SO NATURE
LA English
DT Article
ID retinotopic map refinement; eye-specific segregation; ganglion-cells; activity transients; direction selectivity; action-potentials; ocular dominance; instructive role; mouse; columns
AB The morphological and functional development of the vertebrate nervous system is initially governed by genetic factors and subsequently refined by neuronal activity. However, fundamental features of the nervous system emerge before sensory experience is possible. Thus, activity-dependent development occurring before the onset of experience must be driven by spontaneous activity, but the origin and nature of activity in vivo remains largely untested. Here we use optical methods to show in live neonatal mice that waves of spontaneous retinal activity are present and propagate throughout the entire visual system before eye opening. This patterned activity encompassed the visual field, relied on cholinergic neurotransmission, preferentially initiated in the binocular retina and exhibited spatiotemporal correlations between the two hemispheres. Retinal waves were the primary source of activity in the midbrain and primary visual cortex, but only modulated ongoing activity in secondary visual areas. Thus, spontaneous retinal activity is transmitted through the entire visual system and carries patterned information capable of guiding the activity-dependent development of complex intra-and inter-hemispheric circuits before the onset of vision.
C1 [Ackman, James B.; Burbridge, Timothy J.; Crair, Michael C.] Yale Univ, Sch Med, Dept Neurobiol, New Haven, CT 06510 USA.
C3 Yale University
RP Crair, MC (corresponding author), Yale Univ, Sch Med, Dept Neurobiol, 333 Cedar St, New Haven, CT 06510 USA.
EM michael.crair@yale.edu
FU US National Institutes of Health (NIH) [P30 EY000785, R01 EY015788, T32 NS007224, T15 LM070506, T32 EY017353]; family of William Ziegler III; National Eye Institute [T32EY022312, R01EY015788] Funding Source: NIH RePORTER; National Institute of Neurological Disorders and Stroke [T32NS007224] Funding Source: NIH RePORTER
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NR 59
TC 372
Z9 440
U1 1
U2 67
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 11
PY 2012
VL 490
IS 7419
BP 219
EP +
DI 10.1038/nature11529
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 019IY
UT WOS:000309733300041
PM 23060192
DA 2026-03-09
ER

PT J
AU Song, KH
   Nam, YJ
   Luo, X
   Qi, XX
   Tan, W
   Huang, GN
   Acharya, A
   Smith, CL
   Tallquist, MD
   Neilson, EG
   Hill, JA
   Bassel-Duby, R
   Olson, EN
AF Song, Kunhua
   Nam, Young-Jae
   Luo, Xiang
   Qi, Xiaoxia
   Tan, Wei
   Huang, Guo N.
   Acharya, Asha
   Smith, Christopher L.
   Tallquist, Michelle D.
   Neilson, Eric G.
   Hill, Joseph A.
   Bassel-Duby, Rhonda
   Olson, Eric N.
TI Heart repair by reprogramming non-myocytes with cardiac transcription factors
SO NATURE
LA English
DT Article
ID fibroblasts; expression; disease; adult; cells; cardiomyocytes; generation; regulator; therapy; neurons
AB The adult mammalian heart possesses little regenerative potential following injury. Fibrosis due to activation of cardiac fibroblasts impedes cardiac regeneration and contributes to loss of contractile function, pathological remodelling and susceptibility to arrhythmias. Cardiac fibroblasts account for a majority of cells in the heart and represent a potential cellular source for restoration of cardiac function following injury through phenotypic reprogramming to a myocardial cell fate. Here we show that four transcription factors, GATA4, HAND2, MEF2C and TBX5, can cooperatively reprogram adult mouse tail-tip and cardiac fibroblasts into beating cardiac-like myocytes in vitro. Forced expression of these factors in dividing non-cardiomyocytes in mice reprograms these cells into functional cardiac-like myocytes, improves cardiac function and reduces adverse ventricular remodelling following myocardial infarction. Our results suggest a strategy for cardiac repair through reprogramming fibroblasts resident in the heart with cardiogenic transcription factors or other molecules.
C1 [Song, Kunhua; Nam, Young-Jae; Qi, Xiaoxia; Huang, Guo N.; Acharya, Asha; Smith, Christopher L.; Tallquist, Michelle D.; Hill, Joseph A.; Bassel-Duby, Rhonda; Olson, Eric N.] Univ Texas SW Med Ctr Dallas, Dept Mol Biol, Dallas, TX 75390 USA.
   [Nam, Young-Jae; Luo, Xiang; Tan, Wei; Hill, Joseph A.] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Dallas, TX 75390 USA.
   [Neilson, Eric G.] Vanderbilt Univ, Sch Med, Dept Med, Nashville, TN 37232 USA.
C3 University of Texas System; University of Texas Southwestern Medical Center; University of Texas System; University of Texas Southwestern Medical Center; Vanderbilt University
RP Olson, EN (corresponding author), Univ Texas SW Med Ctr Dallas, Dept Mol Biol, 5323 Harry Hines Blvd, Dallas, TX 75390 USA.
EM eric.olson@utsouthwestern.edu
FU NIH; Donald W. Reynolds Center for Clinical Cardiovascular Research; Robert A. Welch Foundation [I-0025]; Leducq Fondation-Transatlantic Network of Excellence in Cardiovascular Research; American Heart Association-Jon Holden DeHaan Foundation; Cancer Prevention & Research Institute of Texas (CPRIT)
NR 41
TC 925
Z9 1119
U1 1
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 31
PY 2012
VL 485
IS 7400
BP 599
EP +
DI 10.1038/nature11139
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 949WP
UT WOS:000304608000039
PM 22660318
DA 2026-03-09
ER

PT J
AU Kruse, AC
   Hu, JX
   Pan, AC
   Arlow, DH
   Rosenbaum, DM
   Rosemond, E
   Green, HF
   Liu, T
   Chae, PS
   Dror, RO
   Shaw, DE
   Weis, WI
   Wess, J
   Kobilka, BK
AF Kruse, Andrew C.
   Hu, Jianxin
   Pan, Albert C.
   Arlow, Daniel H.
   Rosenbaum, Daniel M.
   Rosemond, Erica
   Green, Hillary F.
   Liu, Tong
   Chae, Pil Seok
   Dror, Ron O.
   Shaw, David E.
   Weis, William I.
   Wess, Juergen
   Kobilka, Brian K.
TI Structure and dynamics of the M3 muscarinic acetylcholine receptor
SO NATURE
LA English
DT Article
ID conformational-changes; molecular-dynamics; force-field; amino-acid; binding; identification; activation; site; selectivity; validation
AB Acetylcholine, the first neurotransmitter to be identified(1), exerts many of its physiological actions via activation of a family of G-protein-coupled receptors (GPCRs) known as muscarinic acetylcholine receptors (mAChRs). Although the five mAChR subtypes (M1-M5) share a high degree of sequence homology, they show pronounced differences in G-protein coupling preference and the physiological responses they mediate(2-4). Unfortunately, despite decades of effort, no therapeutic agents endowed with clear mAChR subtype selectivity have been developed to exploit these differences(5,6). We describe here the structure of the G(q/11)-coupled M3 mAChR ('M3 receptor', from rat) bound to the bronchodilator drug tiotropium and identify the binding mode for this clinically important drug. This structure, together with that of the G(i/o)-coupled M2 receptor(7), offers possibilities for the design of mAChR subtype-selective ligands. Importantly, the M3 receptor structure allows a structural comparison between two members of a mammalian GPCR subfamily displaying different G-protein coupling selectivities. Furthermore, molecular dynamics simulations suggest that tiotropium binds transiently to an allosteric site en route to the binding pocket of both receptors. These simulations offer a structural view of an allosteric binding mode for an orthosteric GPCR ligand and provide additional opportunities for the design of ligands with different affinities or binding kinetics for different mAChR subtypes. Our findings not only offer insights into the structure and function of one of the most important GPCR families, but may also facilitate the design of improved therapeutics targeting these critical receptors.
C1 [Kruse, Andrew C.; Weis, William I.; Kobilka, Brian K.] Stanford Univ, Sch Med, Dept Mol & Cellular Physiol, Stanford, CA 94305 USA.
   [Hu, Jianxin; Rosemond, Erica; Liu, Tong; Wess, Juergen] NIDDK, Mol Signaling Sect, Bioorgan Chem Lab, Bethesda, MD 20892 USA.
   [Pan, Albert C.; Arlow, Daniel H.; Green, Hillary F.; Dror, Ron O.; Shaw, David E.] DE Shaw Res, New York, NY 10036 USA.
   [Rosenbaum, Daniel M.] Univ Texas SW Med Ctr Dallas, Dept Biochem, Dallas, TX 75390 USA.
   [Chae, Pil Seok] Hanyang Univ, Dept Bionano Engn, Ansan 426791, South Korea.
   [Weis, William I.] Stanford Univ, Sch Med, Dept Biol Struct, Stanford, CA 94305 USA.
C3 Stanford University; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK); D. E. Shaw Research; University of Texas System; University of Texas Southwestern Medical Center; Hanyang University; Stanford University
RP Kobilka, BK (corresponding author), Stanford Univ, Sch Med, Dept Mol & Cellular Physiol, 279 Campus Dr, Stanford, CA 94305 USA.
EM jwess@helix.nih.gov; kobilka@stanford.edu
FU National Institutes of Health [NS028471, GM56169]; Mathers Foundation; National Science Foundation; NIDDK, NIH, US Department of Health and Human Services; National Institute of Diabetes and Digestive and Kidney Diseases [ZIADK031129] Funding Source: NIH RePORTER; National Institute of General Medical Sciences [R01GM083118] Funding Source: NIH RePORTER; National Institute of Neurological Disorders and Stroke [R01NS028471] Funding Source: NIH RePORTER
NR 58
TC 676
Z9 757
U1 4
U2 300
PU NATURE PUBLISHING 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 23
PY 2012
VL 482
IS 7386
BP 552
EP 556
DI 10.1038/nature10867
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 898VM
UT WOS:000300770500056
PM 22358844
DA 2026-03-09
ER

PT J
AU Jostins, L
   Ripke, S
   Weersma, RK
   Duerr, RH
   McGovern, DP
   Hui, KY
   Lee, JC
   Schumm, LP
   Sharma, Y
   Anderson, CA
   Essers, J
   Mitrovic, M
   Ning, K
   Cleynen, I
   Theatre, E
   Spain, SL
   Raychaudhuri, S
   Goyette, P
   Wei, Z
   Abraham, C
   Achkar, JP
   Ahmad, T
   Amininejad, L
   Ananthakrishnan, AN
   Andersen, V
   Andrews, JM
   Baidoo, L
   Balschun, T
   Bampton, PA
   Bitton, A
   Boucher, G
   Brand, S
   Büning, C
   Cohain, A
   Cichon, S
   D'Amato, M
   De Jong, D
   Devaney, KL
   Dubinsky, M
   Edwards, C
   Ellinghaus, D
   Ferguson, LR
   Franchimont, D
   Fransen, K
   Gearry, R
   Georges, M
   Gieger, C
   Glas, J
   Haritunians, T
   Hart, A
   Hawkey, C
   Hedl, M
   Hu, XL
   Karlsen, TH
   Kupcinskas, L
   Kugathasan, S
   Latiano, A
   Laukens, D
   Lawrance, IC
   Lees, CW
   Louis, E
   Mahy, G
   Mansfield, J
   Morgan, AR
   Mowat, C
   Newman, W
   Palmieri, O
   Ponsioen, CY
   Potocnik, U
   Prescott, NJ
   Regueiro, M
   Rotter, JI
   Russell, RK
   Sanderson, JD
   Sans, M
   Satsangi, J
   Schreiber, S
   Simms, LA
   Sventoraityte, J
   Targan, SR
   Taylor, KD
   Tremelling, M
   Verspaget, HW
   De Vos, M
   Wijmenga, C
   Wilson, DC
   Winkelmann, J
   Xavier, RJ
   Zeissig, S
   Zhang, B
   Zhang, CK
   Zhao, HY
   Silverberg, MS
   Annese, V
   Hakonarson, H
   Brant, SR
   Radford-Smith, G
   Mathew, CG
   Rioux, JD
   Schadt, EE
   Daly, MJ
   Franke, A
   Parkes, M
   Vermeire, S
   Barrett, JC
   Cho, JH
AF Jostins, Luke
   Ripke, Stephan
   Weersma, Rinse K.
   Duerr, Richard H.
   McGovern, Dermot P.
   Hui, Ken Y.
   Lee, James C.
   Schumm, L. Philip
   Sharma, Yashoda
   Anderson, Carl A.
   Essers, Jonah
   Mitrovic, Mitja
   Ning, Kaida
   Cleynen, Isabelle
   Theatre, Emilie
   Spain, Sarah L.
   Raychaudhuri, Soumya
   Goyette, Philippe
   Wei, Zhi
   Abraham, Clara
   Achkar, Jean-Paul
   Ahmad, Tariq
   Amininejad, Leila
   Ananthakrishnan, Ashwin N.
   Andersen, Vibeke
   Andrews, Jane M.
   Baidoo, Leonard
   Balschun, Tobias
   Bampton, Peter A.
   Bitton, Alain
   Boucher, Gabrielle
   Brand, Stephan
   Buening, Carsten
   Cohain, Ariella
   Cichon, Sven
   D'Amato, Mauro
   De Jong, Dirk
   Devaney, Kathy L.
   Dubinsky, Marla
   Edwards, Cathryn
   Ellinghaus, David
   Ferguson, Lynnette R.
   Franchimont, Denis
   Fransen, Karin
   Gearry, Richard
   Georges, Michel
   Gieger, Christian
   Glas, Juergen
   Haritunians, Talin
   Hart, Ailsa
   Hawkey, Chris
   Hedl, Matija
   Hu, Xinli
   Karlsen, Tom H.
   Kupcinskas, Limas
   Kugathasan, Subra
   Latiano, Anna
   Laukens, Debby
   Lawrance, Ian C.
   Lees, Charlie W.
   Louis, Edouard
   Mahy, Gillian
   Mansfield, John
   Morgan, Angharad R.
   Mowat, Craig
   Newman, William
   Palmieri, Orazio
   Ponsioen, Cyriel Y.
   Potocnik, Uros
   Prescott, Natalie J.
   Regueiro, Miguel
   Rotter, Jerome I.
   Russell, Richard K.
   Sanderson, Jeremy D.
   Sans, Miquel
   Satsangi, Jack
   Schreiber, Stefan
   Simms, Lisa A.
   Sventoraityte, Jurgita
   Targan, Stephan R.
   Taylor, Kent D.
   Tremelling, Mark
   Verspaget, Hein W.
   De Vos, Martine
   Wijmenga, Cisca
   Wilson, David C.
   Winkelmann, Juliane
   Xavier, Ramnik J.
   Zeissig, Sebastian
   Zhang, Bin
   Zhang, Clarence K.
   Zhao, Hongyu
   Silverberg, Mark S.
   Annese, Vito
   Hakonarson, Hakon
   Brant, Steven R.
   Radford-Smith, Graham
   Mathew, Christopher G.
   Rioux, John D.
   Schadt, Eric E.
   Daly, Mark J.
   Franke, Andre
   Parkes, Miles
   Vermeire, Severine
   Barrett, Jeffrey C.
   Cho, Judy H.
TI Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease
SO NATURE
LA English
DT Article
ID hyper-ige syndrome; risk loci; susceptibility; expression; metaanalysis; tuberculosis; mutations; network; number
AB Crohn's disease and ulcerative colitis, the two common forms of inflammatory bowel disease (IBD), affect over 2.5 million people of European ancestry, with rising prevalence in other populations(1). Genome-wide association studies and subsequent meta-analyses of these two diseases(2,3) as separate phenotypes have implicated previously unsuspected mechanisms, such as autophagy(4), in their pathogenesis and showed that some IBD loci are shared with other inflammatory diseases(5). Here we expand on the knowledge of relevant pathways by undertaking a meta-analysis of Crohn's disease and ulcerative colitis genome-wide association scans, followed by extensive validation of significant findings, with a combined total of more than 75,000 cases and controls. We identify 71 new associations, for a total of 163 IBD loci, that meet genome-wide significance thresholds. Most loci contribute to both phenotypes, and both directional (consistently favouring one allele over the course of human history) and balancing (favouring the retention of both alleles within populations) selection effects are evident. Many IBD loci are also implicated in other immune-mediated disorders, most notably with ankylosing spondylitis and psoriasis. We also observe considerable overlap between susceptibility loci for IBD and mycobacterial infection. Gene co-expression network analysis emphasizes this relationship, with pathways shared between host responses to mycobacteria and those predisposing to IBD.
C1 [Hui, Ken Y.; Cho, Judy H.] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06520 USA.
   [Jostins, Luke; Anderson, Carl A.; Barrett, Jeffrey C.] Wellcome Trust Sanger Inst, Cambridge CB10 1HH, England.
   [Ripke, Stephan; Daly, Mark J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA.
   [Ripke, Stephan; Daly, Mark J.] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.
   [Weersma, Rinse K.; De Jong, Dirk] Univ Groningen, Dept Gastroenterol & Hepatol, NL-9700 RB Groningen, Netherlands.
   [Mitrovic, Mitja] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, NL-9700 RB Groningen, Netherlands.
   [Duerr, Richard H.; Baidoo, Leonard; Fransen, Karin; Regueiro, Miguel] Univ Pittsburgh, Sch Med, Dept Med, Div Gastroenterol Hepatol & Nutr, Pittsburgh, PA 15261 USA.
   [Duerr, Richard H.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Human Genet, Pittsburgh, PA 15261 USA.
   [McGovern, Dermot P.; Targan, Stephan R.; Taylor, Kent D.] F Widjaja Fdn Inflammatory Bowel, Los Angeles, CA 90048 USA.
   [McGovern, Dermot P.; Targan, Stephan R.; Taylor, Kent D.] Immunobiol Res Inst, Los Angeles, CA 90048 USA.
   [McGovern, Dermot P.; Haritunians, Talin; Rotter, Jerome I.; Taylor, Kent D.] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA.
   [Lee, James C.; Parkes, Miles] Univ Cambridge, Addenbrookes Hosp, Inflammatory Bowel Dis Res Grp, Cambridge CB2 0QQ, England.
   [Schumm, L. Philip] Univ Chicago, Dept Hlth Studies, Chicago, IL 60637 USA.
   [Sharma, Yashoda; Ning, Kaida; Abraham, Clara; Hedl, Matija; Cho, Judy H.] Yale Univ, Sch Med, Dept Internal Med, Sect Digest Dis, New Haven, CT 06520 USA.
   [Essers, Jonah] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
   [Mitrovic, Mitja; Potocnik, Uros] Univ Maribor, Fac Med, Ctr Human Mol Genet & Pharmacogen, SLO-2000 Maribor, Slovenia.
   [Cleynen, Isabelle; Vermeire, Severine] Katholieke Univ Leuven, Gastroenterol Sect, Dept Clin & Expt Med, B-3000 Louvain, Belgium.
   [Theatre, Emilie; Georges, Michel] Univ Liege, Grp Interdisciplinaire Genoprote Appl GIGA R, Unit Anim Genom, B-4000 Liege, Belgium.
   [Theatre, Emilie; Georges, Michel] Univ Liege, Fac Vet Med, B-4000 Liege, Belgium.
   [Theatre, Emilie; Louis, Edouard] Univ Liege, Ctr Hosp Univ, Div Gastroenterol, B-4000 Liege, Belgium.
   [Spain, Sarah L.; Prescott, Natalie J.; Mathew, Christopher G.] Kings Coll London, Dept Med & Mol Genet, Div Genet & Mol Med, Sch Med,Guys Hosp, London SE1 9RT, England.
   [Raychaudhuri, Soumya; Hu, Xinli] Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA.
   [Raychaudhuri, Soumya] Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA.
   [Raychaudhuri, Soumya] Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA.
   [Goyette, Philippe; Boucher, Gabrielle; Rioux, John D.] Univ Montreal, Montreal, PQ H1T 1C8, Canada.
   [Goyette, Philippe; Boucher, Gabrielle; Rioux, John D.] Montreal Heart Inst, Res Ctr, Montreal, PQ H1T 1C8, Canada.
   [Wei, Zhi] New Jersey Inst Technol, Dept Comp Sci, Newark, NJ 07102 USA.
   [Achkar, Jean-Paul] Cleveland Clin, Dept Gastroenterol & Hepatol, Inst Digest Dis, Cleveland, OH 44195 USA.
   [Achkar, Jean-Paul] Cleveland Clin, Lerner Res Inst, Dept Pathobiol, Cleveland, OH 44195 USA.
   [Ahmad, Tariq] Peninsula Coll Med & Dent, Exeter EX1 2LU, Devon, England.
   [Amininejad, Leila; Franchimont, Denis] Free Univ Brussels, Erasmus Hosp, Dept Gastroenterol, B-1070 Brussels, Belgium.
   [Ananthakrishnan, Ashwin N.; Devaney, Kathy L.; Xavier, Ramnik J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gastroenterol Unit, Boston, MA 02114 USA.
   [Andersen, Vibeke] Viborg Reg Hosp, Dept Med, DK-8800 Viborg, Denmark.
   [Andrews, Jane M.] Royal Adelaide Hosp, Dept Gastroenterol & Hepatol, Inflammatory Bowel Dis Serv, Adelaide, SA 5000, Australia.
   [Andrews, Jane M.] Univ Adelaide, Sch Med, Adelaide, SA 5000, Australia.
   [Balschun, Tobias; Ellinghaus, David; Schreiber, Stefan; Franke, Andre] Univ Kiel, Inst Clin Chem, D-24105 Kiel, Germany.
   [Bampton, Peter A.] Flinders Med Ctr, Dept Gastroenterol & Hepatol, Adelaide, SA 5000, Australia.
   [Bampton, Peter A.] Flinders Univ S Australia, Sch Med, Adelaide, SA 5000, Australia.
   [Bitton, Alain; Glas, Juergen] McGill Univ, Ctr Hlth, Div Gastroenterol, Royal Victoria Hosp, Montreal, PQ H3A 1A1, Canada.
   [Brand, Stephan] Univ Munich, Univ Hosp Munich Grosshadern, Dept Med 2, D-80336 Munich, Germany.
   [Buening, Carsten] Univ Med Berlin, Charite, Dept Gastroenterol, D-10117 Berlin, Germany.
   [Cohain, Ariella; Zhang, Bin; Schadt, Eric E.] Mt Sinai Sch Med, Dept Genet & Genom Sci, New York, NY 10029 USA.
   [Cichon, Sven] Univ Hosp Bonn, Life & Brain Ctr, Dept Genom, D-53012 Bonn, Germany.
   [D'Amato, Mauro] Karolinska Inst, Dept Biosci & Nutr, S-14183 Stockholm, Sweden.
   [Dubinsky, Marla] Cedars Sinai Med Ctr, Dept Pediat, Los Angeles, CA 90048 USA.
   [Edwards, Cathryn] Torbay Hosp, Dept Gastroenterol, Torquay TQ2 7AA, Devon, England.
   [Ferguson, Lynnette R.; Morgan, Angharad R.] Univ Auckland, Fac Med & Hlth Sci, Sch Med Sci, Auckland 1142, New Zealand.
   [Fransen, Karin; Wijmenga, Cisca] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, NL-9700 RB Groningen T, Netherlands.
   [Gearry, Richard] Univ Otago, Dept Med, Christchurch 8140, New Zealand.
   [Gearry, Richard] Christchurch Hosp, Dept Gastroenterol, Christchurch 8011, New Zealand.
   [Gieger, Christian] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Genet Epidemiol, D-85764 Neuherberg, Germany.
   [Hart, Ailsa] St Marks Hosp, Harrow HA1 3UJ, Middx, England.
   [Hawkey, Chris] QueensMed Ctr, Nottingham Digest Dis Ctr, Nottingham NG7 1AW, England.
   [Karlsen, Tom H.] Natl Hosp Norway, Oslo Univ Hosp, Internal Med Res Inst, N-0424 Oslo, Norway.
   [Kupcinskas, Limas; Sventoraityte, Jurgita] Kaunas Univ Med, Dept Gastroenterol, LT-44307 Kaunas, Lithuania.
   [Kugathasan, Subra] Emory Univ, Sch Med, Dept Pediat, Atlanta, GA 30322 USA.
   [Latiano, Anna; Palmieri, Orazio; Annese, Vito] Ist Ricovero & Cura Carattere Sci Casa Sollievo S, Gastroenterol Unit, I-71013 San Giovanni Rotondo, Italy.
   [Laukens, Debby; De Vos, Martine] Ghent Univ Hosp, Dept Gastroenterol & Hepatol, B-9000 Ghent, Belgium.
   [Lawrance, Ian C.] Univ Western Australia, Sch Med & Pharmacol, Fremantle, WA 6009, Australia.
   [Lees, Charlie W.; Satsangi, Jack] Univ Edinburgh, Western Gen Hosp, Mol Med Ctr, Gastrointestinal Unit, Edinburgh EH4 2XU, Midlothian, Scotland.
   [Mahy, Gillian] Townsville Hosp, Dept Gastroenterol, Townsville, Qld 4810, Australia.
   [Mansfield, John] Newcastle Univ, Inst Human Genet, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.
   [Mowat, Craig] Univ Dundee, Ninewells Hosp & Med Sch, Dept Med, Dundee DD1 9SY, Scotland.
   [Newman, William] Univ Manchester, MAHSC, Manchester M13 9PL, Lancs, England.
   [Ponsioen, Cyriel Y.] Univ Amsterdam, Acad Med Ctr, Dept Gastroenterol, NL-1105 AZ Amsterdam, Netherlands.
   [Potocnik, Uros] Univ Maribor, Fac Chem & Chem Engn, SLO-2000 Maribor, Slovenia.
   [Russell, Richard K.; Wilson, David C.] Royal Hosp Sick Children, Glasgow G3 8SJ, Lanark, Scotland.
   [Sanderson, Jeremy D.] Guys & St Thomas NHS Fdn Trust, St Thomas Hosp, Dept Gastroenterol, London SE1 7EH, England.
   [Sans, Miquel] Hosp Clin Barcelona, Inst Invest Biomed August Pi & Sunyer IDIBAPS, Dept Gastroenterol, Barcelona, Spain.
   [Sans, Miquel] CIBER EHD, Barcelona 08036, Spain.
   [Schreiber, Stefan; Zeissig, Sebastian] Univ Kiel, Dept Gen Internal Med, D-24118 Kiel, Germany.
   [Simms, Lisa A.; Radford-Smith, Graham] Queensland Inst Med Res, Brisbane, Qld 4029, Australia.
   [Tremelling, Mark] Norfolk & Norwich Univ Hosp, Norwich NR4 7UY, Norfolk, England.
   [Verspaget, Hein W.] Leiden Univ, Med Ctr, Dept Gastroenterol, NL-2333 ZA Leiden, Netherlands.
   [Wilson, David C.] Univ Edinburgh, Edinburgh EH9 1UW, Midlothian, Scotland.
   [Winkelmann, Juliane] Tech Univ Munich, Inst Human Genet, D-80336 Munich, Germany.
   [Winkelmann, Juliane] Tech Univ Munich, Dept Neurol, D-80336 Munich, Germany.
   [Xavier, Ramnik J.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA.
   [Zhang, Clarence K.; Zhao, Hongyu] Yale Univ, Sch Publ Hlth, Dept Biostat, New Haven, CT 06520 USA.
   [Silverberg, Mark S.] Univ Toronto, Mt Sinai Hosp, Ctr Inflammatory Bowel Dis, Toronto, ON M5G 1X5, Canada.
   [Annese, Vito] Azienda Osped Univ AOU Careggi, Unit Gastroenterol SOD2, I-50134 Florence, Italy.
   [Hakonarson, Hakon] Childrens Hosp Philadelphia, Ctr Appl Genom, Philadelphia, PA 19104 USA.
   [Hakonarson, Hakon] Childrens Hosp Philadelphia, Ctr Pediat Inflammatory Bowel Dis, Dept Pediat, Philadelphia, PA 19104 USA.
   [Brant, Steven R.] Johns Hopkins Univ, Sch Med, Dept Med, Meyerhoff Inflammatory Bowel Dis Ctr, Baltimore, MD 21205 USA.
   [Brant, Steven R.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA.
   [Radford-Smith, Graham] Royal Brisbane & Womens Hosp, Dept Gastroenterol, Brisbane, Qld 4029, Australia.
   [Radford-Smith, Graham] Univ Queensland, Sch Med, Brisbane, Qld 4029, Australia.
   [Vermeire, Severine] Univ Hosp Leuven, Dept Gastroenterol, B-3000 Louvain, Belgium.
C3 Yale University; Wellcome Trust Sanger Institute; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard Medical School; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; University of Groningen; University of Groningen; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh; Cedars Sinai Medical Center; University of Cambridge; Cambridge University Hospitals NHS Foundation Trust; Addenbrooke's Hospital; University of Chicago; Yale University; Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Massachusetts General Hospital; University of Maribor; KU Leuven; University of Liege; University of Liege; University of Liege; Guy's & St Thomas' NHS Foundation Trust; University of London; King's College London; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Universite de Montreal; Universite de Montreal; New Jersey Institute of Technology; Cleveland Clinic Foundation; Cleveland Clinic Foundation; University of Exeter; University of Plymouth; Universite Libre de Bruxelles; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard Medical School; Aarhus University; Viborg City Hospital; Royal Adelaide Hospital; Adelaide University; University of Adelaide; University of Kiel; Flinders Medical Centre; Flinders University; Royal Victoria Hospital; McGill University; University of Munich; Free University of Berlin; Humboldt University of Berlin; Charite Universitatsmedizin Berlin; Icahn School of Medicine at Mount Sinai; University of Bonn; Karolinska Institutet; Cedars Sinai Medical Center; University of Auckland; University of Groningen; University of Otago; Christchurch Hospital New Zealand; Helmholtz Association; Helmholtz-Center Munich - German Research Center for Environmental Health; Imperial College London; University of Nottingham; University of Oslo; National Hospital Norway; Lithuanian University of Health Sciences; Emory University; Ghent University; Ghent University Hospital; University of Western Australia; University of Edinburgh; Queensland Health; Townsville Hospital; Newcastle University - UK; University of Dundee; University of Manchester; University of Amsterdam; Academic Medical Center Amsterdam; University of Maribor; University of Glasgow; Guy's & St Thomas' NHS Foundation Trust; University of Barcelona; Hospital Clinic de Barcelona; IDIBAPS; CIBER - Centro de Investigacion Biomedica en Red; CIBEREHD; University of Kiel; QIMR Berghofer Medical Research Institute; Norfolk & Norwich University Hospitals NHS Foundation Trust; Norfolk & Norwich University Hospital; Leiden University - Excl LUMC; Leiden University; Leiden University Medical Center (LUMC); University of Edinburgh; Technical University of Munich; Technical University of Munich; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Yale University; University of Toronto; Sinai Health System Toronto; University of Florence; Azienda Ospedaliero Universitaria Careggi; University of Pennsylvania; Pennsylvania Medicine; Childrens Hospital of Philadelphia; University of Pennsylvania; Pennsylvania Medicine; Childrens Hospital of Philadelphia; Johns Hopkins University; Johns Hopkins University; Johns Hopkins Bloomberg School of Public Health; Royal Brisbane & Women's Hospital; University of Queensland; KU Leuven; University Hospital Leuven
RP Cho, JH (corresponding author), Yale Univ, Sch Med, Dept Genet, New Haven, CT 06520 USA.
EM judy.cho@yale.edu
FU National Association for Colitis and Crohn's disease; Wellcome Trust [098051, 083948/Z/07/Z, 085475/B/08/Z, 085475/Z/08/Z]; Medical Research Council UK; Catherine McEwan Foundation; NHS Research Scotland career fellowship; Peninsula College of Medicine and Dentistry, Exeter; National Institute for Health Research, through the Comprehensive Local Research Network; Biomedical ResearchCentre; Saint Thomas' NationalHealth Service Trust; King's College London; Addenbrooke's Hospital, University of Cambridge School of Clinical Medicine; University of Manchester; Central Manchester Foundation Trust; Medical Research Council [G0000934]; Wellcome Trust grant [068545/Z/02]; UK National Blood Service; National Institute of Diabetes, Digestive and Kidney diseases (NIDDK) IBD Genetics Consortium; National Institutes of Health (NIH) [MSTP TG T32GM07205]; USPHS [PO1DK046763]; Cedars-Sinai F. Widjaja Inflammatory Bowel and Immunobiology Research Institute Research Funds; National Center for Research Resources (NCRR) [M01-RR00425]; UCLA/Cedars-Sinai/Harbor/Drew Clinical and Translational Science Institute (CTSI) [UL1 TR000124-01]; Southern California Diabetes and Endocrinology Research Grant (DERC) [DK063491]; Helmsley Foundation; Crohn's and Colitis Foundation of America; Netherlands Organization for Scientific Research [90.700.281, 918.66.620]; Celiac Disease Consortium [BSIK03009]; German Ministry of Education and Research through the National Genome Research Network; Popgen biobank, through the Deutsche Forschungsgemeinschaft (DFG) cluster of excellence ` Inflammation at Interfaces'; DFG [FR 2821/2-1, BR 1912/6-1]; Else Kroner-Fresenius-Stiftung (Else Kroner-Exzellenzstipendium); Italian Society for Paediatric Gastroenterology, Hepatology and Nutrition; Italian Ministry of Health [GR-2008-1144485]; Swedish Society of Medicine; Ihre Foundation; Orebro University Hospital Research Foundation; Karolinska Institutet; Swedish National Program for IBD Genetics; Swedish Organization for IBD; Swedish Medical Research Council; Royal Brisbane and Women's Hospital Foundation; National Health and Medical Research Council, Australia; European Community (5th PCRDT); NIDDK, National Institute of Allergy and Infectious Diseases (NIAID); National Human Genome Research Institute (NHGRI); National Institute of Child Health and Human Development (NICHD); Juvenile Diabetes Research Foundation (JDRF); Helmholtz Zentrum Munchen-German Research Center for Environmental Health; German Federal Ministry of Education and Research (BMBF); State of Bavaria;  [DK062431];  [DK062422];  [DK062420];  [DK062432];  [DK062423];  [DK062413];  [DK076984];  [DK084554];  [DK062429];  [DK062429-S1];  [CA141743];  [DK83756];  [AI062773];  [DK043351];  [U01 DK062418]; MRC [G0600329, G1002033, G0800675, G0800759] Funding Source: UKRI; Chief Scientist Office [ETM/75, CZB/4/540, ETM/137] Funding Source: researchfish; Crohn&apos;s and Colitis UK [M11-1] Funding Source: researchfish; Medical Research Council [G1002033, G0800675, G0600329, G0800759] Funding Source: researchfish; National Institute for Health Research [NF-SI-0611-10219, NF-SI-0508-10299] Funding Source: researchfish; Versus Arthritis; Cancer Research UK [18475] Funding Source: researchfish; National Institute of Diabetes and Digestive and Kidney Diseases [U01DK062432, U01DK062422, U01DK062431, U01DK062413, U01DK062420, P30DK063491, U01DK062423, P30DK043351] Funding Source: NIH RePORTER
NR 30
TC 3744
Z9 4326
U1 17
U2 942
PU NATURE PUBLISHING 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 1
PY 2012
VL 491
IS 7422
BP 119
EP 124
DI 10.1038/nature11582
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 028PM
UT WOS:000310434500042
PM 23128233
DA 2026-03-09
ER

PT J
AU LaRiviere, JP
   Ravelo, AC
   Crimmins, A
   Dekens, PS
   Ford, HL
   Lyle, M
   Wara, MW
AF LaRiviere, Jonathan P.
   Ravelo, A. Christina
   Crimmins, Allison
   Dekens, Petra S.
   Ford, Heather L.
   Lyle, Mitch
   Wara, Michael W.
TI Late Miocene decoupling of oceanic warmth and atmospheric carbon dioxide forcing
SO NATURE
LA English
DT Article
ID panamanian seaway closure; permanent el-nino; glaciation; middle; depth; pool; ma
AB Deep-time palaeoclimate studies are vitally important for developing a complete understanding of climate responses to changes in the atmospheric carbon dioxide concentration (that is, the atmospheric partial pressure of CO2, p(CO2))(1). Although past studies have explored these responses during portions of the Cenozoic era (the most recent 65.5 million years (Myr) of Earth history), comparatively little is known about the climate of the late Miocene (similar to 12-5 Myr ago), an interval with p(CO2) values of only 200-350 parts per million by volume but nearly ice-free conditions in the Northern Hemisphere(2,3) and warmer-than-modern temperatures on the continents(4). Here we present quantitative geochemical sea surface temperature estimates from the Miocene mid-latitude North Pacific Ocean, and show that oceanic warmth persisted throughout the interval of low p(CO2) similar to 12-5 Myr ago. We also present new stable isotope measurements from the western equatorial Pacific that, in conjunction with previously published data(5-10), reveal a long-term trend of thermocline shoaling in the equatorial Pacific since similar to 13 Myr ago. We propose that a relatively deep global thermocline, reductions in low-latitude gradients in sea surface temperature, and cloud and water vapour feedbacks may help to explain the warmth of the late Miocene. Additional shoaling of the thermocline after 5 Myr ago probably explains the stronger coupling between p(CO2), sea surface temperatures and climate that is characteristic of the more recent Pliocene and Pleistocene epochs(11,12).
C1 [LaRiviere, Jonathan P.; Ravelo, A. Christina; Crimmins, Allison; Dekens, Petra S.; Ford, Heather L.; Wara, Michael W.] Univ Calif Santa Cruz, Ocean Sci Dept, Santa Cruz, CA 95064 USA.
   [Lyle, Mitch] Texas A&M Univ, Dept Oceanog, College Stn, TX 77843 USA.
C3 University of California System; University of California Santa Cruz; Texas A&M University System; Texas A&M University College Station
RP LaRiviere, JP (corresponding author), Univ Calif Santa Cruz, Ocean Sci Dept, Santa Cruz, CA 95064 USA.
EM jlarivie@ucsc.edu
FU NSF [OCE0902047]; Directorate For Geosciences [0824978] Funding Source: National Science Foundation; Division Of Earth Sciences [0824978] Funding Source: National Science Foundation; Division Of Ocean Sciences; Directorate For Geosciences [0902047] Funding Source: National Science Foundation
NR 31
TC 175
Z9 206
U1 3
U2 153
PU NATURE PUBLISHING 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 7
PY 2012
VL 486
IS 7401
BP 97
EP 100
DI 10.1038/nature11200
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 953GD
UT WOS:000304854000034
PM 22678287
DA 2026-03-09
ER

PT J
AU Montaño, SP
   Pigli, YZ
   Rice, PA
AF Montano, Sherwin P.
   Pigli, Ying Z.
   Rice, Phoebe A.
TI The Mu transpososome structure sheds light on DDE recombinase evolution
SO NATURE
LA English
DT Article
ID in-vitro transposition; dna-binding domain; bacteriophage-mu; phage-mu; strand transfer; crystal-structure; complex; protein; clpx; integration
AB Studies of bacteriophage Mu transposition paved the way for understanding retroviral integration and V(D)J recombination as well as many other DNA transposition reactions. Here we report the structure of the Mu transpososome-Mu transposase (MuA) in complex with bacteriophage DNA ends and target DNA-determined from data that extend anisotropically to 5.2 angstrom, 5.2 angstrom and 3.7 angstrom resolution, in conjunction with previously determined structures of individual domains. The highly intertwined structure illustrates why chemical activity depends on formation of the synaptic complex, and reveals that individual domains have different roles when bound to different sites. The structure also provides explanations for the increased stability of the final product complex and for its preferential recognition by the ATP-dependent unfoldase ClpX. Although MuA and many other recombinases share a structurally conserved 'DDE' catalytic domain, comparisons among the limited set of available complex structures indicate that some conserved features, such as catalysis in trans and target DNA bending, arose through convergent evolution because they are important for function.
C1 [Montano, Sherwin P.; Pigli, Ying Z.; Rice, Phoebe A.] Univ Chicago, Dept Biochem & Mol Biol, Chicago, IL 60637 USA.
C3 University of Chicago
RP Rice, PA (corresponding author), Univ Chicago, Dept Biochem & Mol Biol, 920 E 58Th St, Chicago, IL 60637 USA.
EM PRice@uchicago.edu
FU NIH [GM086826]
NR 63
TC 104
Z9 122
U1 0
U2 25
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 15
PY 2012
VL 491
IS 7424
BP 413
EP +
DI 10.1038/nature11602
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 036MY
UT WOS:000311031600039
PM 23135398
DA 2026-03-09
ER

PT J
AU Wang, YG
   Li, G
   Goode, J
   Paz, JC
   Ouyang, KF
   Screaton, R
   Fischer, WH
   Chen, J
   Tabas, I
   Montminy, M
AF Wang, Yiguo
   Li, Gang
   Goode, Jason
   Paz, Jose C.
   Ouyang, Kunfu
   Screaton, Robert
   Fischer, Wolfgang H.
   Chen, Ju
   Tabas, Ira
   Montminy, Marc
TI Inositol-1,4,5-trisphosphate receptor regulates hepatic gluconeogenesis in fasting and diabetes
SO NATURE
LA English
DT Article
ID inositol 1,4,5-trisphosphate receptors; dependent protein-kinase; modulates gluconeogenesis; coactivator pgc-1; creb; calcium; phosphorylation; torc2; hepatocytes; release
AB In the fasted state, increases in circulating glucagon promote hepatic glucose production through induction of the gluconeogenic program. Triggering of the cyclic AMP pathway increases gluconeogenic gene expression via the de-phosphorylation of the CREB co-activator CRTC2 (ref. 1). Glucagon promotes CRTC2 dephosphorylation in part through the protein kinase A (PKA)-mediated inhibition of the CRTC2 kinase SIK2. A number of Ser/Thr phosphatases seem to be capable of dephosphorylating CRTC2 (refs 2, 3), but the mechanisms by which hormonal cues regulate these enzymes remain unclear. Here we show in mice that glucagon stimulates CRTC2 dephosphorylation in hepatocytes by mobilizing intracellular calcium stores and activating the calcium/calmodulin-dependent Ser/Thr-phosphatase calcineurin (also known as PP3CA). Glucagon increased cytosolic calcium concentration through the PKA-mediated phosphorylation of inositol-1,4,5-trisphosphate receptors (InsP(3)Rs), which associate with CRTC2. After their activation, InsP(3)Rs enhanced gluconeogenic gene expression by promoting the calcineurin-mediated dephosphorylation of CRTC2. During feeding, increases in insulin signalling reduced CRTC2 activity via the AKT-mediated inactivation of InsP(3)Rs. InsP(3)R activity was increased in diabetes, leading to upregulation of the gluconeogenic program. As hepatic downregulation of InsP(3)Rs and calcineurin improved circulating glucose levels in insulin resistance, these results demonstrate how interactions between cAMP and calcium pathways at the level of the InsP(3)R modulate hepatic glucose production under fasting conditions and in diabetes.
C1 [Wang, Yiguo; Goode, Jason; Paz, Jose C.; Fischer, Wolfgang H.; Montminy, Marc] Salk Inst Biol Studies, Clayton Fdn Labs Peptide Biol, La Jolla, CA 92037 USA.
   [Li, Gang; Tabas, Ira] Columbia Univ, Dept Med, New York, NY 10032 USA.
   [Ouyang, Kunfu; Chen, Ju] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA.
   [Screaton, Robert] Univ Ottawa, Eastern Ontario Res Inst, Childrens Hosp, Ottawa, ON K1H 8L1, Canada.
   [Screaton, Robert] Univ Ottawa, Dept Pediat, Ottawa, ON K1H 8L1, Canada.
   [Screaton, Robert] Univ Ottawa, Dept Cellular & Mol Med, Ottawa, ON K1H 8L1, Canada.
   [Tabas, Ira] Columbia Univ, Dept Physiol & Cellular Biophys, New York, NY 10032 USA.
   [Tabas, Ira] Columbia Univ, Dept Pathol & Cell Biol, New York, NY 10032 USA.
C3 Salk Institute; Columbia University; University of California System; University of California San Diego; University of Ottawa; Children's Hospital of Eastern Ontario; University of Ottawa; University of Ottawa; Columbia University; Columbia University
RP Montminy, M (corresponding author), Salk Inst Biol Studies, Clayton Fdn Labs Peptide Biol, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA.
EM montminy@salk.edu
FU National Institutes of Health [R01-DK049777, R01-DK083834, R01-DK091618, HL087123]; Kieckhefer Foundation; Clayton Foundation for Medical Research; Leona M. and Harry B. Helmsley Charitable Trust; National Heart Lung and Blood Institute [P01HL087123] Funding Source: NIH RePORTER; National Institute of Diabetes and Digestive and Kidney Diseases [R01DK083834] Funding Source: NIH RePORTER; National Institute of General Medical Sciences [T32GM008666] Funding Source: NIH RePORTER
NR 21
TC 174
Z9 207
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 MAY 3
PY 2012
VL 485
IS 7396
BP 128
EP U166
DI 10.1038/nature10988
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 934NV
UT WOS:000303451900048
PM 22495310
DA 2026-03-09
ER

PT J
AU Josefowicz, SZ
   Niec, RE
   Kim, HY
   Treuting, P
   Chinen, T
   Zheng, Y
   Umetsu, DT
   Rudensky, AY
AF Josefowicz, Steven Z.
   Niec, Rachel E.
   Kim, Hye Young
   Treuting, Piper
   Chinen, Takatoshi
   Zheng, Ye
   Umetsu, Dale T.
   Rudensky, Alexander Y.
TI Extrathymically generated regulatory T cells control mucosal TH2 inflammation
SO NATURE
LA English
DT Article
ID foxp3 gene; induction; lineage; homeostasis; expression; responses; smad3; fate
AB A balance between pro- and anti-inflammatory mechanisms at mucosal interfaces, which are sites of constitutive exposure to microbes and non-microbial foreign substances, allows for efficient protection against pathogens yet prevents adverse inflammatory responses associated with allergy, asthma and intestinal inflammation(1). Regulatory T (T-reg) cells prevent systemic and tissue-specific autoimmunity and inflammatory lesions at mucosal interfaces. These cells are generated in the thymus (tT(reg) cells) and in the periphery (induced (i)T-reg cells), and their dual origin implies a division of labour between tT(reg) and iT(reg) cells in immune homeostasis. Here we show that a highly selective blockage in differentiation of iT(reg) cells in mice did not lead to unprovoked multi-organ autoimmunity, exacerbation of induced tissue-specific autoimmune pathology, or increased pro-inflammatory responses of T helper 1 (T(H)1) and T(H)17 cells. However, mice deficient in iT(reg) cells spontaneously developed pronounced T(H)2-type pathologies at mucosal sites-in the gastrointestinal tract and lungs-with hallmarks of allergic inflammation and asthma. Furthermore, iT(reg)-cell deficiency altered gut microbial communities. These results suggest that whereas T-reg cells generated in the thymus appear sufficient for control of systemic and tissue-specific autoimmunity, extrathymic differentiation of T-reg cells affects commensal microbiota composition and serves a distinct, essential function in restraint of allergic-type inflammation at mucosal interfaces.
C1 [Josefowicz, Steven Z.; Niec, Rachel E.; Chinen, Takatoshi; Rudensky, Alexander Y.] Howard Hughes Med Inst, New York, NY 10021 USA.
   [Josefowicz, Steven Z.; Niec, Rachel E.; Chinen, Takatoshi; Rudensky, Alexander Y.] Sloan Kettering Inst, Program Immunol, New York, NY 10021 USA.
   [Josefowicz, Steven Z.] Rockefeller Univ, Lab Chromatin Biol & Epigenet, New York, NY 10065 USA.
   [Kim, Hye Young; Umetsu, Dale T.] Harvard Univ, Childrens Hosp, Sch Med, Div Immunol, Boston, MA 02115 USA.
   [Treuting, Piper] Univ Washington, Sch Med, Dept Comparat Med, Seattle, WA 98195 USA.
   [Chinen, Takatoshi] Keio Univ, Dept Microbiol & Immunol, Sch Med, Tokyo 1608582, Japan.
   [Zheng, Ye] Salk Inst Biol Studies, Nomis Fdn Labs Immunobiol & Microbial Pathogenesi, La Jolla, CA 92037 USA.
C3 Howard Hughes Medical Institute; Memorial Sloan Kettering Cancer Center; Rockefeller University; Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Boston Children's Hospital; University of Washington; University of Washington Seattle; Keio University; Salk Institute
RP Rudensky, AY (corresponding author), Howard Hughes Med Inst, New York, NY 10021 USA.
EM rudenska@mskcc.org
FU NIH MSTP [GM07739]; NINDS [1F31NS073203-01]; Department of Microbiology and Immunology, Keio University School of Medicine; NIH [R37 AI034206]
NR 39
TC 686
Z9 840
U1 0
U2 91
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 16
PY 2012
VL 482
IS 7385
BP 395
EP U1510
DI 10.1038/nature10772
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 892LG
UT WOS:000300287100045
PM 22318520
DA 2026-03-09
ER

PT J
AU Chen, XF
   Cui, DD
   Papusha, A
   Zhang, XT
   Chu, CD
   Tang, JW
   Chen, KF
   Pan, XW
   Ira, G
AF Chen, Xuefeng
   Cui, Dandan
   Papusha, Alma
   Zhang, Xiaotian
   Chu, Chia-Dwo
   Tang, Jiangwu
   Chen, Kaifu
   Pan, Xuewen
   Ira, Grzegorz
TI The Fun30 nucleosome remodeller promotes resection of DNA double-strand break ends
SO NATURE
LA English
DT Article
ID saccharomyces-cerevisiae; homologous recombination; checkpoint activation; h2a phosphorylation; budding yeast; repair; chromatin; helicase; sgs1; mre11-rad50-xrs2
AB Chromosomal double-strand breaks (DSBs) are resected by 5' nucleases to form 3' single-stranded DNA substrates for binding by homologous recombination and DNA damage checkpoint proteins. Two redundant pathways of extensive resection have been described both in cells(1-3) and in vitro(4-6), one relying on Exo1 exonuclease and the other on Sgs1 helicase and Dna2 nuclease. However, it remains unknown how resection proceeds within the context of chromatin, where histones and histone-bound proteins represent barriers for resection enzymes. Here we identify the yeast nucleosome-remodelling enzyme Fun30 as a factor promoting DSB end resection. Fun30 is the major nucleosome remodeller promoting extensive Exo1- and Sgs1-dependent resection of DSBs. The RSC and INO80 chromatin-remodelling complexes and Fun30 have redundant roles in resection adjacent to DSB ends. ATPase and helicase domains of Fun30, which are needed for nucleosome remodelling(7), are also required for resection. Fun30 is robustly recruited to DNA breaks and spreads along the DSB coincident with resection. Fun30 becomes less important for resection in the absence of the histone-bound Rad9 checkpoint adaptor protein known to block 5' strand processing(8) and in the absence of either histone H3 K79 methylation or gamma-H2A, which mediate recruitment of Rad9 (refs 9, 10). Together these data suggest that Fun30 helps to overcome the inhibitory effect of Rad9 on DNA resection.
C1 [Cui, Dandan; Tang, Jiangwu; Chen, Kaifu; Pan, Xuewen] Baylor Coll Med, Verna & Marrs McLean Dept Biochem & Mol Biol, Houston, TX 77030 USA.
   [Chen, Xuefeng; Papusha, Alma; Zhang, Xiaotian; Chu, Chia-Dwo; Ira, Grzegorz] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA.
C3 Baylor College of Medicine; Baylor College of Medicine
RP Pan, XW (corresponding author), Baylor Coll Med, Verna & Marrs McLean Dept Biochem & Mol Biol, 1 Baylor Plaza, Houston, TX 77030 USA.
EM xuewenp@bcm.edu; gira@bcm.edu
FU National Institutes of Health [GM080600, HG004840]; National Institute of General Medical Sciences [R01GM080600] Funding Source: NIH RePORTER
NR 34
TC 196
Z9 241
U1 0
U2 35
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD SEP 27
PY 2012
VL 489
IS 7417
BP 576
EP +
DI 10.1038/nature11355
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 046RG
UT WOS:000311781500006
PM 22960743
DA 2026-03-09
ER

PT J
AU Kuzyk, A
   Schreiber, R
   Fan, ZY
   Pardatscher, G
   Roller, EM
   Högele, A
   Simmel, FC
   Govorov, AO
   Liedl, T
AF Kuzyk, Anton
   Schreiber, Robert
   Fan, Zhiyuan
   Pardatscher, Guenther
   Roller, Eva-Maria
   Hoegele, Alexander
   Simmel, Friedrich C.
   Govorov, Alexander O.
   Liedl, Tim
TI DNA-based self-assembly of chiral plasmonic nanostructures with tailored optical response
SO NATURE
LA English
DT Article
ID metal nanoparticle assembly; circular-dichroism; shapes; superstructures; origami
AB Matter structured on a length scale comparable to or smaller than the wavelength of light can exhibit unusual optical properties(1). Particularly promising components for such materials are metal nanostructures, where structural alterations provide a straightforward means of tailoring their surface plasmon resonances and hence their interaction with light(2,3). But the top-down fabrication of plasmonic materials with controlled optical responses in the visible spectral range remains challenging, because lithographic methods are limited in resolution and in their ability to generate genuinely three-dimensional architectures(4,5). Molecular self-assembly(6,7) provides an alternative bottom-up fabrication route not restricted by these limitations, and DNA-and peptide-directed assembly have proved to be viable methods for the controlled arrangement of metal nanoparticles in complex and also chiral geometries(8-14). Here we show that DNA origami(15,16) enables the high-yield production of plasmonic structures that contain nanoparticles arranged in nanometre-scale helices. We find, in agreement with theoretical predictions(17), that the structures in solution exhibit defined circular dichroism and optical rotatory dispersion effects at visible wavelengths that originate from the collective plasmon-plasmon interactions of the nanoparticles positioned with an accuracy better than two nanometres. Circular dichroism effects in the visible part of the spectrum have been achieved by exploiting the chiral morphology of organic molecules and the plasmonic properties of nanoparticles(18-20), or even without precise control over the spatial configuration of the nanoparticles(12,21,22). In contrast, the optical response of our nanoparticle assemblies is rationally designed and tunable in handedness, colour and intensity-in accordance with our theoretical model.
C1 [Schreiber, Robert; Roller, Eva-Maria; Hoegele, Alexander; Liedl, Tim] Univ Munich, Fak Phys, D-80539 Munich, Germany.
   [Schreiber, Robert; Roller, Eva-Maria; Hoegele, Alexander; Liedl, Tim] Univ Munich, Ctr Nanosci, D-80539 Munich, Germany.
   [Kuzyk, Anton; Pardatscher, Guenther; Simmel, Friedrich C.] Tech Univ Munich, Phys Dept, D-85748 Garching, Germany.
   [Kuzyk, Anton; Pardatscher, Guenther; Simmel, Friedrich C.] Tech Univ Munich, ZNN WSI, D-85748 Garching, Germany.
   [Fan, Zhiyuan; Govorov, Alexander O.] Ohio Univ, Dept Phys & Astron, Athens, OH 45701 USA.
C3 University of Munich; University of Munich; Technical University of Munich; Technical University of Munich; University System of Ohio; Ohio University
RP Liedl, T (corresponding author), Univ Munich, Fak Phys, Geschwister Scholl Pl 1, D-80539 Munich, Germany.
EM tim.liedl@lmu.de
FU Volkswagen Foundation; DFG Cluster of Excellence NIM (Nanosystems Initiative Munich); NSF (USA); Div Of Chem, Bioeng, Env, & Transp Sys; Directorate For Engineering [0933415] Funding Source: National Science Foundation
NR 30
TC 1923
Z9 2178
U1 31
U2 2170
PU NATURE PUBLISHING 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 15
PY 2012
VL 483
IS 7389
BP 311
EP 314
DI 10.1038/nature10889
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 908HP
UT WOS:000301481800044
PM 22422265
DA 2026-03-09
ER

PT J
AU Mesgarani, N
   Chang, EF
AF Mesgarani, Nima
   Chang, Edward F.
TI Selective cortical representation of attended speaker in multi-talker speech perception
SO NATURE
LA English
DT Article
AB Humans possess a remarkable ability to attend to a single speaker's voice in a multi-talker background(1-3). How the auditory system manages to extract intelligible speech under such acoustically complex and adverse listening conditions is not known, and, indeed, it is not clear how attended speech is internally represented(4,5). Here, using multi-electrode surface recordings from the cortex of subjects engaged in a listening task with two simultaneous speakers, we demonstrate that population responses in non-primary human auditory cortex encode critical features of attended speech: speech spectrograms reconstructed based on cortical responses to the mixture of speakers reveal the salient spectral and temporal features of the attended speaker, as if subjects were listening to that speaker alone. A simple classifier trained solely on examples of single speakers can decode both attended words and speaker identity. We find that task performance is well predicted by a rapid increase in attention-modulated neural selectivity across both single-electrode and population-level cortical responses. These findings demonstrate that the cortical representation of speech does not merely reflect the external acoustic environment, but instead gives rise to the perceptual aspects relevant for the listener's intended goal.
C1 [Mesgarani, Nima; Chang, Edward F.] Univ Calif San Francisco, UCSF Ctr Integrat Neurosci, Dept Neurol Surg, San Francisco, CA 94143 USA.
   [Mesgarani, Nima; Chang, Edward F.] Univ Calif San Francisco, UCSF Ctr Integrat Neurosci, Dept Physiol, 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 Chang, EF (corresponding author), Univ Calif San Francisco, UCSF Ctr Integrat Neurosci, Dept Neurol Surg, San Francisco, CA 94143 USA.
EM changed@neurosurg.ucsf.edu
FU National Institutes of Health [R00-NS065120, DP2-OD00862, R01-DC012379]; Ester A. and Joseph Klingenstein Foundation; National Institute on Deafness and Other Communication Disorders [R01DC012379] Funding Source: NIH RePORTER
NR 29
TC 731
Z9 874
U1 3
U2 171
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 10
PY 2012
VL 485
IS 7397
BP 233
EP U118
DI 10.1038/nature11020
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 939HJ
UT WOS:000303799800040
PM 22522927
DA 2026-03-09
ER

PT J
AU Hawrylycz, MJ
   Lein, ES
   Guillozet-Bongaarts, AL
   Shen, EH
   Ng, L
   Miller, JA
   van de Lagemaat, LN
   Smith, KA
   Ebbert, A
   Riley, ZL
   Abajian, C
   Beckmann, CF
   Bernard, A
   Bertagnolli, D
   Boe, AF
   Cartagena, PM
   Chakravarty, MM
   Chapin, M
   Chong, J
   Dalley, RA
   Daly, BD
   Dang, C
   Datta, S
   Dee, N
   Dolbeare, TA
   Faber, V
   Feng, D
   Fowler, DR
   Goldy, J
   Gregor, BW
   Haradon, Z
   Haynor, DR
   Hohmann, JG
   Horvath, S
   Howard, RE
   Jeromin, A
   Jochim, JM
   Kinnunen, M
   Lau, C
   Lazarz, ET
   Lee, C
   Lemon, TA
   Li, L
   Li, Y
   Morris, JA
   Overly, CC
   Parker, PD
   Parry, SE
   Reding, M
   Royall, JJ
   Schulkin, J
   Sequeira, PA
   Slaughterbeck, CR
   Smith, SC
   Sodt, AJ
   Sunkin, SM
   Swanson, BE
   Vawter, MP
   Williams, D
   Wohnoutka, P
   Zielke, HR
   Geschwind, DH
   Hof, PR
   Smith, SM
   Koch, C
   Grant, SGN
   Jones, AR
AF Hawrylycz, Michael J.
   Lein, Ed S.
   Guillozet-Bongaarts, Angela L.
   Shen, Elaine H.
   Ng, Lydia
   Miller, Jeremy A.
   van de lagemaat, Louie N.
   Smith, Kimberly A.
   Ebbert, Amanda
   Riley, Zackery L.
   Abajian, Chris
   Beckmann, Christian F.
   Bernard, Amy
   Bertagnolli, Darren
   Boe, Andrew F.
   Cartagena, Preston M.
   Chakravarty, M. Mallar
   Chapin, Mike
   Chong, Jimmy
   Dalley, Rachel A.
   Daly, Barry David
   Dang, Chinh
   Datta, Suvro
   Dee, Nick
   Dolbeare, Tim A.
   Faber, Vance
   Feng, David
   Fowler, David R.
   Goldy, Jeff
   Gregor, Benjamin W.
   Haradon, Zeb
   Haynor, David R.
   Hohmann, John G.
   Horvath, Steve
   Howard, Robert E.
   Jeromin, Andreas
   Jochim, Jayson M.
   Kinnunen, Marty
   Lau, Christopher
   Lazarz, Evan T.
   Lee, Changkyu
   Lemon, Tracy A.
   Li, Ling
   Li, Yang
   Morris, John A.
   Overly, Caroline C.
   Parker, Patrick D.
   Parry, Sheana E.
   Reding, Melissa
   Royall, Joshua J.
   Schulkin, Jay
   Sequeira, Pedro Adolfo
   Slaughterbeck, Clifford R.
   Smith, Simon C.
   Sodt, Andy J.
   Sunkin, Susan M.
   Swanson, Beryl E.
   Vawter, Marquis P.
   Williams, Derric
   Wohnoutka, Paul
   Zielke, H. Ronald
   Geschwind, Daniel H.
   Hof, Patrick R.
   Smith, Stephen M.
   Koch, Christof
   Grant, Seth G. N.
   Jones, Allan R.
TI An anatomically comprehensive atlas of the adult human brain transcriptome
SO NATURE
LA English
DT Article
ID lists
AB Neuroanatomically precise, genome-wide maps of transcript distributions are critical resources to complement genomic sequence data and to correlate functional and genetic brain architecture. Here we describe the generation and analysis of a transcriptional atlas of the adult human brain, comprising extensive histological analysis and comprehensive microarray profiling of similar to 900 neuroanatomically precise subdivisions in two individuals. Transcriptional regulation varies enormously by anatomical location, with different regions and their constituent cell types displaying robust molecular signatures that are highly conserved between individuals. Analysis of differential gene expression and gene co-expression relationships demonstrates that brain-wide variation strongly reflects the distributions of major cell classes such as neurons, oligodendrocytes, astrocytes and microglia. Local neighbourhood relationships between fine anatomical subdivisions are associated with discrete neuronal subtypes and genes involved with synaptic transmission. The neocortex displays a relatively homogeneous transcriptional pattern, but with distinct features associated selectively with primary sensorimotor cortices and with enriched frontal lobe expression. Notably, the spatial topography of the neocortex is strongly reflected in its molecular topography-the closer two cortical regions, the more similar their transcriptomes. This freely accessible online data resource forms a high-resolution transcriptional baseline for neurogenetic studies of normal and abnormal human brain function.
C1 [Hawrylycz, Michael J.; Lein, Ed S.; Guillozet-Bongaarts, Angela L.; Shen, Elaine H.; Ng, Lydia; Miller, Jeremy A.; Smith, Kimberly A.; Ebbert, Amanda; Riley, Zackery L.; Abajian, Chris; Bernard, Amy; Bertagnolli, Darren; Boe, Andrew F.; Chakravarty, M. Mallar; Chapin, Mike; Chong, Jimmy; Dalley, Rachel A.; Dang, Chinh; Datta, Suvro; Dee, Nick; Dolbeare, Tim A.; Faber, Vance; Feng, David; Goldy, Jeff; Gregor, Benjamin W.; Haradon, Zeb; Hohmann, John G.; Howard, Robert E.; Jochim, Jayson M.; Kinnunen, Marty; Lau, Christopher; Lazarz, Evan T.; Lee, Changkyu; Lemon, Tracy A.; Li, Yang; Morris, John A.; Overly, Caroline C.; Parker, Patrick D.; Parry, Sheana E.; Reding, Melissa; Royall, Joshua J.; Slaughterbeck, Clifford R.; Sodt, Andy J.; Sunkin, Susan M.; Swanson, Beryl E.; Williams, Derric; Wohnoutka, Paul; Koch, Christof; Jones, Allan R.] Allen Inst Brain Sci, Seattle, WA 98103 USA.
   [van de lagemaat, Louie N.; Grant, Seth G. N.] Univ Edinburgh, Genes Cognit Programme, Edinburgh EH16 4SB, Midlothian, Scotland.
   [Beckmann, Christian F.] Univ Twente, MIRA Inst, Nijmegen, Netherlands.
   [Beckmann, Christian F.] Radboud Univ Nijmegen, Donders Inst, NL-6525 ED Nijmegen, Netherlands.
   [Cartagena, Preston M.] Univ Calif Irvine, Dept Psychiat & Human Behav, Irvine, CA 92697 USA.
   [Chakravarty, M. Mallar] Ctr Addict & Mental Hlth Toronto, Kimel Family Translat Imaging Genet Lab, Toronto, ON M5S 2S1, Canada.
   [Daly, Barry David] Univ Maryland, Sch Med, Dept Diagnost Radiol, Med Ctr, Baltimore, MD 21201 USA.
   [Fowler, David R.] Univ Maryland, Dept Pathol, Sch Med, Baltimore, MD 21201 USA.
   [Haynor, David R.] Univ Washington, Dept Radiol, Seattle, WA 98195 USA.
   [Horvath, Steve] Univ Calif Los Angeles, David Geffen Sch Med, Dept Human Genet, Gonda Res Ctr, Los Angeles, CA 90095 USA.
   [Jeromin, Andreas] Banyan Biomarkers Inc, Alachua, FL 32615 USA.
   [Li, Ling] Off Chief Med Examiner, Baltimore, MD USA.
   [Li, Ling] Univ Maryland, Dept Pediat, Baltimore, MD 21201 USA.
   [Schulkin, Jay] Georgetown Univ, Sch Med, Dept Neurosci, Washington, DC 20007 USA.
   [Sequeira, Pedro Adolfo; Vawter, Marquis P.] Univ Calif Irvine, Funct Genom Lab, Dept Psychiat & Human Behav, Sch Med, Irvine, CA 92697 USA.
   [Smith, Simon C.] Histion LLC, Everett, WA 98204 USA.
   [Zielke, H. Ronald] Univ Maryland, Eunice Kennedy Shriver NICHD Brain & Tissue Bank, Baltimore, MD 21201 USA.
   [Geschwind, Daniel H.] Univ Calif Los Angeles, David Geffen Sch Med, Program Neurogenet, Dept Neurol, Los Angeles, CA 90095 USA.
   [Geschwind, Daniel H.] Univ Calif Los Angeles, David Geffen Sch Med, Semel Inst, Los Angeles, CA 90095 USA.
   [Hof, Patrick R.] Mt Sinai Sch Med, Fishberg Dept Neurosci, New York, NY 10029 USA.
   [Hof, Patrick R.] Mt Sinai Sch Med, Friedman Brain Inst, New York, NY 10029 USA.
   [Smith, Stephen M.] Univ Oxford, FMRIB, Oxford OX3 9DU, England.
   [Koch, Christof] CALTECH, Pasadena, CA 91125 USA.
C3 Allen Institute for Brain Science; University of Edinburgh; Radboud University Nijmegen; University of California System; University of California Irvine; University of Toronto; Centre for Addiction & Mental Health - Canada; University System of Maryland; University of Maryland Baltimore; University System of Maryland; University of Maryland Baltimore; University of Washington; University of Washington Seattle; University of California System; University of California Los Angeles; University of California Los Angeles Medical Center; David Geffen School of Medicine at UCLA; Banyan Biomarkers Inc.; University System of Maryland; University of Maryland Baltimore; Georgetown University; University of California System; University of California Irvine; National Institutes of Health (NIH) - USA; NIH Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD); University System of Maryland; University of Maryland Baltimore; 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; Icahn School of Medicine at Mount Sinai; Icahn School of Medicine at Mount Sinai; University of Oxford; California Institute of Technology
RP Hawrylycz, MJ (corresponding author), Allen Inst Brain Sci, Seattle, WA 98103 USA.
EM mikeh@alleninstitute.org
FU Department of Health and Human Services Health Resources and Services Administration Awards [1C76HF15069-01-00, 1 1C76HF19619-01-00]; MRCD; Wellcome Trust; European Union Seventh Framework Programme [241498 EUROSPIN, 242167 SynSys, 241995 GENCODYS]; MRC [G0700399, G0802238] Funding Source: UKRI; Medical Research Council [G0802238, G0700399] Funding Source: researchfish
NR 35
TC 2212
Z9 2504
U1 8
U2 259
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 20
PY 2012
VL 489
IS 7416
BP 391
EP 399
DI 10.1038/nature11405
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 007AK
UT WOS:000308860900037
PM 22996553
DA 2026-03-09
ER

PT J
AU Barbez, E
   Kubes, M
   Rolcík, J
   Béziat, C
   Pencík, A
   Wang, BJ
   Rosquete, MR
   Zhu, JS
   Dobrev, PI
   Lee, Y
   Zazímalovà, E
   Petrásek, J
   Geisler, M
   Friml, J
   Kleine-Vehn, J
AF Barbez, Elke
   Kubes, Martin
   Rolcik, Jakub
   Beziat, Chloe
   Pencik, Ales
   Wang, Bangjun
   Rosquete, Michel Ruiz
   Zhu, Jinsheng
   Dobrev, Petre I.
   Lee, Yuree
   Zazimalova, Eva
   Petrasek, Jan
   Geisler, Markus
   Friml, Jiri
   Kleine-Vehn, Juergen
TI A novel putative auxin carrier family regulates intracellular auxin homeostasis in plants
SO NATURE
LA English
DT Article
ID solid-phase extraction; tobacco cells; abscisic-acid; arabidopsis; efflux; transport; proteins; biosynthesis; localization; purification
AB The phytohormone auxin acts as a prominent signal, providing, by its local accumulation or depletion in selected cells, a spatial and temporal reference for changes in the developmental program(1-7). The distribution of auxin depends on both auxin metabolism (biosynthesis, conjugation and degradation)(8-10) and cellular auxin transport(11-15). We identified in silico a novel putative auxin transport facilitator family, called PIN-LIKES (PILS). Here we illustrate that PILS proteins are required for auxin-dependent regulation of plant growth by determining the cellular sensitivity to auxin. PILS proteins regulate intracellular auxin accumulation at the endoplasmic reticulum and thus auxin availability for nuclear auxin signalling. PILS activity affects the level of endogenous auxin indole-3-acetic acid (IAA), presumably via intracellular accumulation and metabolism. Our findings reveal that the transport machinery to compartmentalize auxin within the cell is of an unexpected molecular complexity and demonstrate this compartmentalization to be functionally important for a number of developmental processes.
C1 [Barbez, Elke; Beziat, Chloe; Rosquete, Michel Ruiz; Friml, Jiri; Kleine-Vehn, Juergen] Univ Ghent VIB, Dept Plant Syst Biol, B-9052 Ghent, Belgium.
   [Barbez, Elke; Beziat, Chloe; Rosquete, Michel Ruiz; Friml, Jiri; Kleine-Vehn, Juergen] Univ Ghent, Dept Plant Biotechnol & Bioinformat, B-9052 Ghent, Belgium.
   [Barbez, Elke; Beziat, Chloe; Rosquete, Michel Ruiz; Kleine-Vehn, Juergen] Univ Nat Resources & Life Siences BOKU, Dept Appl Genet & Cell Biol, A-1190 Vienna, Austria.
   [Kubes, Martin; Dobrev, Petre I.; Zazimalova, Eva; Petrasek, Jan] Acad Sci Czech Republ, Inst Expt Bot, CR-16502 Prague 6, Czech Republic.
   [Rolcik, Jakub] Palacky Univ, Fac Sci, Lab Growth Regulators, Olomouc 78371, Czech Republic.
   [Rolcik, Jakub] Inst Expt Bot AS CR, Olomouc 78371, Czech Republic.
   [Pencik, Ales] Palacky Univ, Fac Sci, Dept Growth Regulators, Ctr Reg Hana Biotechnol & Agr Res, Olomouc 78371, Czech Republic.
   [Wang, Bangjun; Zhu, Jinsheng; Geisler, Markus] Univ Fribourg, Dept Biol Plant Biol, CH-1700 Fribourg, Switzerland.
   [Lee, Yuree] Univ Lausanne, Dept Plant Mol Biol, CH-1015 Lausanne, Switzerland.
C3 Ghent University; Flanders Institute for Biotechnology (VIB); Ghent University; Czech Academy of Sciences; Institute of Experimental Botany of the Czech Academy of Sciences; Palacky University Olomouc; Czech Academy of Sciences; Institute of Experimental Botany of the Czech Academy of Sciences; Palacky University Olomouc; University of Fribourg; University of Lausanne
RP Kleine-Vehn, J (corresponding author), Univ Ghent VIB, Dept Plant Syst Biol, B-9052 Ghent, Belgium.
EM juergen.kleine-vehn@boku.ac.at
FU Vienna Science and Technology Fund (WWTF); Agency for Innovation by Science and Technology (IWT); Research Foundation-Flanders; Swiss National Funds; Ministry of Education, Youth and Sports of the Czech Republic [LC06034]; Grant Agency of the Czech Republic [P305/11/2476, P305/11/0797]
NR 35
TC 311
Z9 368
U1 6
U2 251
PU NATURE PUBLISHING 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 3
PY 2012
VL 485
IS 7396
BP 119
EP U155
DI 10.1038/nature11001
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 934NV
UT WOS:000303451900046
PM 22504182
DA 2026-03-09
ER

PT J
AU Won, H
   Lee, HR
   Gee, HY
   Mah, W
   Kim, JI
   Lee, J
   Ha, S
   Chung, C
   Jung, ES
   Cho, YS
   Park, SG
   Lee, JS
   Lee, K
   Kim, D
   Bae, YC
   Kaang, BK
   Lee, MG
   Kim, E
AF Won, Hyejung
   Lee, Hye-Ryeon
   Gee, Heon Yung
   Mah, Won
   Kim, Jae-Ick
   Lee, Jiseok
   Ha, Seungmin
   Chung, Changuk
   Jung, Eun Suk
   Cho, Yi Sul
   Park, Sae-Geun
   Lee, Jung-Soo
   Lee, Kyungmin
   Kim, Daesoo
   Bae, Yong Chul
   Kaang, Bong-Kiun
   Lee, Min Goo
   Kim, Eunjoon
TI Autistic-like social behaviour in Shank2-mutant mice improved by restoring NMDA receptor function
SO NATURE
LA English
DT Article
ID metabotropic glutamate receptors; positive allosteric modulator; postsynaptic density; synaptic plasticity; spectrum disorder; shank3; proteins; communication; trafficking; dysfunction
AB Autism spectrum disorder (ASD) is a group of conditions characterized by impaired social interaction and communication, and restricted and repetitive behaviours. ASD is a highly heritable disorder involving various genetic determinants(1). Shank2 (also known as ProSAP1) is a multi-domain scaffolding protein and signalling adaptor enriched at excitatory neuronal synapses(2-4), and mutations in the human SHANK2 gene have recently been associated with ASD and intellectual disability(5). Although ASD-associated genes are being increasingly identified and studied using various approaches, including mouse genetics(6-16), further efforts are required to delineate important causal mechanisms with the potential for therapeutic application. Here we show that Shank2-mutant (Shank2(-/-)) mice carrying a mutation identical to the ASD-associated microdeletion in the human SHANK2 gene exhibit ASD-like behaviours including reduced social interaction, reduced social communication by ultrasonic vocalizations, and repetitive jumping. These mice show a marked decrease in NMDA (N-methyl-D-aspartate) glutamate receptor (NMDAR) function. Direct stimulation of NMDARs with D-cycloserine, a partial agonist of NMDARs, normalizes NMDAR function and improves social interaction in Shank2(-/-) mice. Furthermore, treatment of Shank2(-/-) mice with a positive allosteric modulator of metabotropic glutamate receptor 5 (mGluR5), which enhances NMDAR function via mGluR5 activation(17), also normalizes NMDAR function and markedly enhances social interaction. These results suggest that reduced NMDAR function may contribute to the development of ASD-like phenotypes in Shank2(-/-) mice, and mGluR modulation of NMDARs offers a potential strategy to treat ASD.
C1 [Lee, Hye-Ryeon; Kim, Jae-Ick; Kaang, Bong-Kiun] Seoul Natl Univ, Natl Creat Res Initiat Ctr Memory, Dept Biol Sci, Coll Nat Sci, Seoul 151747, South Korea.
   [Won, Hyejung; Mah, Won; Lee, Jiseok; Ha, Seungmin; Chung, Changuk; Park, Sae-Geun; Kim, Daesoo; Kim, Eunjoon] Korea Adv Inst Sci & Technol, Dept Biol Sci, Taejon 305701, South Korea.
   [Won, Hyejung; Mah, Won; Lee, Jiseok; Ha, Seungmin; Chung, Changuk; Kim, Eunjoon] Korea Adv Inst Sci & Technol, Natl Creat Res Initiat Ctr Synaptogenesis, Taejon 305701, South Korea.
   [Gee, Heon Yung; Jung, Eun Suk; Lee, Jung-Soo; Lee, Min Goo] Yonsei Univ, Dept Pharmacol, Brain Korea Project Med Sci 21, Severance Biomed Sci Inst,Coll Med, Seoul 120752, South Korea.
   [Cho, Yi Sul; Bae, Yong Chul] Kyungpook Natl Univ, Dept Oral Anat & Neurobiol, Sch Dent, Taegu 700412, South Korea.
   [Lee, Kyungmin] Kyungpook Natl Univ, Dept Anat, Sch Med, Brain Sci & Engn Inst, Taegu 700412, South Korea.
   [Kaang, Bong-Kiun] Seoul Natl Univ, Dept Brain & Cognit Sci, Seoul 151747, South Korea.
   [Kim, Eunjoon] World Class Univ, Grad Sch Nanosci & Technol, Korea Adv Inst Sci & Technol, Taejon 305701, South Korea.
   [Kim, Eunjoon] Inst for Basic Sci Korea, Ctr Synapt Brain Dysfunct, Taejon 305811, South Korea.
C3 Seoul National University (SNU); Korea Advanced Institute of Science & Technology (KAIST); Korea Advanced Institute of Science & Technology (KAIST); Yonsei University; Yonsei University Health System; Kyungpook National University (KNU); Kyungpook National University (KNU); Seoul National University (SNU); Korea Advanced Institute of Science & Technology (KAIST); Institute for Basic Science - Korea (IBS)
RP Kaang, BK (corresponding author), Seoul Natl Univ, Natl Creat Res Initiat Ctr Memory, Dept Biol Sci, Coll Nat Sci, Gwanangno 599, Seoul 151747, South Korea.
EM kaang@snu.ac.kr; mlee@yuhs.ac; kime@kaist.ac.kr
FU National Creative Research Initiative Program [2007-0054846]; WCU [2007-0054846, R31-2008-000-10071-0]; Institute for Basic Science; National Research Foundation of Korea [2012-0000812, 2011-0028240]; National Leading Research Laboratory [2011-0028772]; BK21 fellowship; TJ Park Doctoral Fellowship; National Junior Research Fellowship
NR 30
TC 564
Z9 663
U1 1
U2 130
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 14
PY 2012
VL 486
IS 7402
BP 261
EP 265
DI 10.1038/nature11208
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 957UH
UT WOS:000305189000036
PM 22699620
DA 2026-03-09
ER

PT J
AU Zhang, JH
   Ding, L
   Holmfeldt, L
   Wu, G
   Heatley, SL
   Payne-Turner, D
   Easton, J
   Chen, X
   Wang, JM
   Rusch, M
   Lu, C
   Chen, SC
   Wei, L
   Collins-Underwood, JR
   Ma, J
   Roberts, KG
   Pounds, SB
   Ulyanov, A
   Becksfort, J
   Gupta, P
   Huether, R
   Kriwacki, RW
   Parker, M
   McGoldrick, DJ
   Zhao, D
   Alford, D
   Espy, S
   Bobba, KC
   Song, GC
   Pei, DQ
   Cheng, C
   Roberts, S
   Barbato, MI
   Campana, D
   Coustan-Smith, E
   Shurtleff, SA
   Raimondi, SC
   Kleppe, M
   Cools, J
   Shimano, KA
   Hermiston, ML
   Doulatov, S
   Eppert, K
   Laurenti, E
   Notta, F
   Dick, JE
   Basso, G
   Hunger, SP
   Loh, ML
   Devidas, M
   Wood, B
   Winter, S
   Dunsmore, KP
   Fulton, RS
   Fulton, LL
   Hong, X
   Harris, CC
   Dooling, DJ
   Ochoa, K
   Johnson, KJ
   Obenauer, JC
   Evans, WE
   Pui, CH
   Naeve, CW
   Ley, TJ
   Mardis, ER
   Wilson, RK
   Downing, JR
   Mullighan, CG
AF Zhang, Jinghui
   Ding, Li
   Holmfeldt, Linda
   Wu, Gang
   Heatley, Sue L.
   Payne-Turner, Debbie
   Easton, John
   Chen, Xiang
   Wang, Jianmin
   Rusch, Michael
   Lu, Charles
   Chen, Shann-Ching
   Wei, Lei
   Collins-Underwood, J. Racquel
   Ma, Jing
   Roberts, Kathryn G.
   Pounds, Stanley B.
   Ulyanov, Anatoly
   Becksfort, Jared
   Gupta, Pankaj
   Huether, Robert
   Kriwacki, Richard W.
   Parker, Matthew
   McGoldrick, Daniel J.
   Zhao, David
   Alford, Daniel
   Espy, Stephen
   Bobba, Kiran Chand
   Song, Guangchun
   Pei, Deqing
   Cheng, Cheng
   Roberts, Stefan
   Barbato, Michael I.
   Campana, Dario
   Coustan-Smith, Elaine
   Shurtleff, Sheila A.
   Raimondi, Susana C.
   Kleppe, Maria
   Cools, Jan
   Shimano, Kristin A.
   Hermiston, Michelle L.
   Doulatov, Sergei
   Eppert, Kolja
   Laurenti, Elisa
   Notta, Faiyaz
   Dick, John E.
   Basso, Giuseppe
   Hunger, Stephen P.
   Loh, Mignon L.
   Devidas, Meenakshi
   Wood, Brent
   Winter, Stuart
   Dunsmore, Kimberley P.
   Fulton, Robert S.
   Fulton, Lucinda L.
   Hong, Xin
   Harris, Christopher C.
   Dooling, David J.
   Ochoa, Kerri
   Johnson, Kimberly J.
   Obenauer, John C.
   Evans, William E.
   Pui, Ching-Hon
   Naeve, Clayton W.
   Ley, Timothy J.
   Mardis, Elaine R.
   Wilson, Richard K.
   Downing, James R.
   Mullighan, Charles G.
TI The genetic basis of early T-cell precursor acute lymphoblastic leukaemia
SO NATURE
LA English
DT Article
ID activating flt3 mutations; ras; rearrangement; expression; crlf2; runx1; etv6
AB Early T-cell precursor acute lymphoblastic leukaemia (ETP ALL) is an aggressive malignancy of unknown genetic basis. We performed whole-genome sequencing of 12 ETP ALL cases and assessed the frequency of the identified somatic mutations in 94 T-cell acute lymphoblastic leukaemia cases. ETP ALL was characterized by activating mutations in genes regulating cytokine receptor and RAS signalling (67% of cases; NRAS, KRAS, FLT3, IL7R, JAK3, JAK1, SH2B3 and BRAF), inactivating lesions disrupting haematopoietic development (58%; GATA3, ETV6, RUNX1, IKZF1 and EP300) and histone-modifying genes (48%; EZH2, EED, SUZ12, SETD2 and EP300). We also identified new targets of recurrent mutation including DNM2, ECT2L and RELN. The mutational spectrum is similar to myeloid tumours, and moreover, the global transcriptional profile of ETP ALL was similar to that of normal and myeloid leukaemia haematopoietic stem cells. These findings suggest that addition of myeloid-directed therapies might improve the poor outcome of ETP ALL.
C1 [Holmfeldt, Linda; Heatley, Sue L.; Payne-Turner, Debbie; Chen, Shann-Ching; Wei, Lei; Collins-Underwood, J. Racquel; Ma, Jing; Roberts, Kathryn G.; Song, Guangchun; Shurtleff, Sheila A.; Raimondi, Susana C.; Downing, James R.; Mullighan, Charles G.] St Jude Childrens Res Hosp, Dept Pathol, Memphis, TN 38105 USA.
   [Zhang, Jinghui; Wu, Gang; Chen, Xiang; Rusch, Michael; Ulyanov, Anatoly; Huether, Robert] St Jude Childrens Res Hosp, Dept Computat Biol & Bioinformat, Memphis, TN 38105 USA.
   [Ding, Li; Lu, Charles; Fulton, Robert S.; Fulton, Lucinda L.; Hong, Xin; Harris, Christopher C.; Dooling, David J.; Ochoa, Kerri; Johnson, Kimberly J.; Ley, Timothy J.; Mardis, Elaine R.; Wilson, Richard K.] Washington Univ, Genome Inst, St Louis, MO 63108 USA.
   [Ding, Li; Fulton, Robert S.; Fulton, Lucinda L.; Dooling, David J.; Mardis, Elaine R.; Wilson, Richard K.] Washington Univ, Dept Genet, Sch Med, St Louis, MO 63110 USA.
   [Easton, John; Parker, Matthew; Roberts, Stefan; Barbato, Michael I.] St Jude Childrens Res Hosp, Pediat Canc Genome Project Lab, Memphis, TN 38105 USA.
   [Wang, Jianmin; Becksfort, Jared; Gupta, Pankaj; McGoldrick, Daniel J.; Zhao, David; Alford, Daniel; Espy, Stephen; Bobba, Kiran Chand; Obenauer, John C.; Naeve, Clayton W.] St Jude Childrens Res Hosp, Dept Informat Sci, Memphis, TN 38105 USA.
   [Pounds, Stanley B.; Pei, Deqing; Cheng, Cheng] St Jude Childrens Res Hosp, Dept Biostat, Memphis, TN 38105 USA.
   [Huether, Robert; Kriwacki, Richard W.] St Jude Childrens Res Hosp, Dept Biol Struct, Memphis, TN 38105 USA.
   [Campana, Dario; Coustan-Smith, Elaine; Pui, Ching-Hon] St Jude Childrens Res Hosp, Dept Oncol, Memphis, TN 38105 USA.
   [Kleppe, Maria; Cools, Jan] Katholieke Univ Leuven, Dept Mol & Dev Genet, Ctr Human Genet, VIB, B-3000 Louvain, Belgium.
   [Shimano, Kristin A.; Hermiston, Michelle L.; Loh, Mignon L.] Univ Calif San Francisco, Dept Pediat, Sch Med, San Francisco, CA 94143 USA.
   [Doulatov, Sergei; Eppert, Kolja; Laurenti, Elisa; Notta, Faiyaz; Dick, John E.] Univ Hlth Network, Dept Stem Cell & Dev Biol, Campbell Family Canc Res Inst, Ontario Canc Inst, Toronto, ON M5G 2M9, Canada.
   [Doulatov, Sergei; Eppert, Kolja; Laurenti, Elisa; Notta, Faiyaz] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A8, Canada.
   [Basso, Giuseppe] Univ Padua, Oncohematol Lab, Dept Pediat, I-35122 Padua, Italy.
   [Hunger, Stephen P.] Univ Colorado, Sect Pediat Hematol Oncol Bone Marrow Transplanta, Aurora, CO 80045 USA.
   [Hunger, Stephen P.] Univ Colorado, Ctr Canc & Blood Disorders, Denver Sch Med, Childrens Hosp Colorado, Aurora, CO 80045 USA.
   [Devidas, Meenakshi] Univ Florida, Dept Biostat, Coll Med, Gainesville, FL 32603 USA.
   [Wood, Brent] Seattle Childrens Hosp, Dept Lab Med, Seattle, WA 98105 USA.
   [Winter, Stuart] Univ New Mexico, Albuquerque, NM 87131 USA.
   [Dunsmore, Kimberley P.] Univ Virginia, Charlottesville, VA 22903 USA.
   [Evans, William E.] St Jude Childrens Res Hosp, Dept Pharmaceut Sci, Memphis, TN 38105 USA.
   [Ley, Timothy J.] Washington Univ, Div Oncol, St Louis, MO 63110 USA.
   [Ley, Timothy J.] Washington Univ, Siteman Canc Ctr, St Louis, MO 63110 USA.
C3 St Jude Children's Research Hospital; St Jude Children's Research Hospital; Washington University (WUSTL); Washington University (WUSTL); 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; Flanders Institute for Biotechnology (VIB); KU Leuven; University of California System; University of California San Francisco; University of Toronto; University Health Network Toronto; University of Toronto; University of Padua; University of Colorado System; University of Colorado Anschutz Medical Campus; University of Colorado System; University of Colorado Anschutz Medical Campus; Children's Hospital Colorado; State University System of Florida; University of Florida; Seattle Children's Hospital; University of New Mexico; University of Virginia; University of Tennessee System; University of Tennessee Health Science Center; St Jude Children's Research Hospital; Washington University (WUSTL); Siteman Cancer Center; Washington University (WUSTL)
RP Downing, JR (corresponding author), St Jude Childrens Res Hosp, Dept Pathol, 332 N Lauderdale St, Memphis, TN 38105 USA.
EM james.downing@stjude.org; charles.mullighan@stjude.org
FU St Jude Children's Research Hospital; The Genome Institute and Siteman Cancer Center at Washington University in St Louis; The St Jude Children's Research Hospital-Washington University Pediatric Cancer; ALSAC of St JudeChildren's Research Hospital; Cancer Center [P30CA021765]; Washington University in St Louis [NIHU 01GM92666-PAAR4Kids]; National Human Genome Research Institute (NHGRI) [U54 HG003079]; NCI [CA98543, CA98413, CA114766]; Alex's Lemonade Stand; St. Baldrick's Foundation; Haematology Society of Australasia; New Zealand New Investigator Scholarship; National Cancer Institute [R25CA023944, P30CA021765] Funding Source: NIH RePORTER
NR 43
TC 1315
Z9 1473
U1 3
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 JAN 12
PY 2012
VL 481
IS 7380
BP 157
EP 163
DI 10.1038/nature10725
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 874TO
UT WOS:000298981200029
PM 22237106
DA 2026-03-09
ER

PT J
AU Thompson, AA
   Liu, W
   Chun, E
   Katritch, V
   Wu, HX
   Vardy, E
   Huang, XP
   Trapella, C
   Guerrini, R
   Calo, G
   Roth, BL
   Cherezov, V
   Stevens, RC
AF Thompson, Aaron A.
   Liu, Wei
   Chun, Eugene
   Katritch, Vsevolod
   Wu, Huixian
   Vardy, Eyal
   Huang, Xi-Ping
   Trapella, Claudio
   Guerrini, Remo
   Calo, Girolamo
   Roth, Bryan L.
   Cherezov, Vadim
   Stevens, Raymond C.
TI Structure of the nociceptin/orphanin FQ receptor in complex with a peptide mimetic
SO NATURE
LA English
DT Article
ID orl1 receptor; orphanin-fq; crystallizing membrane; protein; binding; antagonist; agonist; site; identification; mutagenesis
AB Members of the opioid receptor family of G-protein-coupled receptors (GPCRs) are found throughout the peripheral and central nervous system, where they have key roles in nociception and analgesia. Unlike the 'classical' opioid receptors, delta, kappa and mu (delta-OR, kappa-OR and mu-OR), which were delineated by pharmacological criteria in the 1970s and 1980s, the nociceptin/orphanin FQ (N/OFQ) peptide receptor (NOP, also known as ORL-1) was discovered relatively recently by molecular cloning and characterization of an orphan GPCR(1). Although it shares high sequence similarity with classical opioid GPCR subtypes (similar to 60%), NOP has a markedly distinct pharmacology, featuring activation by the endogenous peptide N/OFQ, and unique selectivity for exogenous ligands(2,3). Here we report the crystal structure of human NOP, solved in complex with the peptide mimetic antagonist compound-24 (C-24) (ref. 4), revealing atomic details of ligand-receptor recognition and selectivity. Compound-24 mimics the first four amino-terminal residues of the NOP-selective peptide antagonist UFP-101, a close derivative of N/OFQ, and provides important clues to the binding of these peptides. The X-ray structure also shows substantial conformational differences in the pocket regions between NOP and the classical opioid receptors k (ref. 5) and m (ref. 6), and these are probably due to a small number of residues that vary between these receptors. The NOP-compound-24 structure explains the divergent selectivity profile of NOP and provides a new structural template for the design of NOP ligands.
C1 [Thompson, Aaron A.; Liu, Wei; Chun, Eugene; Katritch, Vsevolod; Wu, Huixian; Cherezov, Vadim; Stevens, Raymond C.] Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA.
   [Vardy, Eyal; Huang, Xi-Ping; Roth, Bryan L.] Univ N Carolina, Chapel Hill Med Sch, Natl Inst Mental Hlth Psychoact Drug Screening Pr, Dept Pharmacol, Chapel Hill, NC 27599 USA.
   [Vardy, Eyal; Huang, Xi-Ping; Roth, Bryan L.] Univ N Carolina, Chapel Hill Med Sch, Div Chem Biol & Med Chem, Chapel Hill, NC 27599 USA.
   [Trapella, Claudio; Guerrini, Remo] Univ Ferrara, Dept Pharmaceut Sci, I-44121 Ferrara, Italy.
   [Trapella, Claudio; Guerrini, Remo] Univ Ferrara, LTTA, I-44121 Ferrara, Italy.
   [Calo, Girolamo] Univ Ferrara, Pharmacol Sect, Dept Expt & Clin Med, I-44121 Ferrara, Italy.
   [Calo, Girolamo] Univ Ferrara, Natl Inst Neurosci, I-44121 Ferrara, Italy.
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; University of North Carolina Chapel Hill; University of Ferrara; University of Ferrara; University of Ferrara; University of Ferrara
RP Stevens, RC (corresponding author), Scripps Res Inst, Dept Mol Biol, 10666 N Torrey Pines Rd, La Jolla, CA 92037 USA.
EM stevens@scripps.edu
FU PSI:Biology [U54 GM094618]; NIH [P50 GM073197, R01 DA017204, R01 DA27170]; NIMH; Michael Hooker Chair of Pharmacology; University of Ferrara (FAR); Italian Ministry of University (FIRB); National Cancer Institute [Y1-CO-1020]; National Institute of General Medical Sciences [Y1-GM-1104]
NR 41
TC 408
Z9 473
U1 1
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 MAY 17
PY 2012
VL 485
IS 7398
BP 395
EP U150
DI 10.1038/nature11085
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 943CW
UT WOS:000304099100048
PM 22596163
DA 2026-03-09
ER

PT J
AU Farago, M
   Rosenbluh, C
   Tevlin, M
   Fraenkel, S
   Schlesinger, S
   Masika, H
   Gouzman, M
   Teng, G
   Schatz, D
   Rais, Y
   Hanna, JH
   Mildner, A
   Jung, S
   Mostoslavsky, G
   Cedar, H
   Bergman, Y
AF Farago, Marganit
   Rosenbluh, Chaggai
   Tevlin, Maya
   Fraenkel, Shira
   Schlesinger, Sharon
   Masika, Hagit
   Gouzman, Masha
   Teng, Grace
   Schatz, David
   Rais, Yoach
   Hanna, Jacob H.
   Mildner, Alexander
   Jung, Steffen
   Mostoslavsky, Gustavo
   Cedar, Howard
   Bergman, Yehudit
TI Clonal allelic predetermination of immunoglobulin-κ rearrangement
SO NATURE
LA English
DT Article
ID b-cell development; asynchronous replication; in-vitro; mature b; genes; expression; transcription; inactivation; lysine-4; mice
AB Although most genes are expressed biallelically, a number of key genomic sites-including immune and olfactory receptor regions-are controlled monoallelically in a stochastic manner, with some cells expressing the maternal allele and others the paternal allele in the target tissue(1,2). Very little is known about how this phenomenon is regulated and programmed during development. Here, using mouse immunoglobulin-kappa (Ig kappa) as a model system, we demonstrate that although individual haematopoietic stem cells are characterized by allelic plasticity, early lymphoid lineage cells become committed to the choice of a single allele, and this decision is then stably maintained in a clonal manner that predetermines monoallelic rearrangement in B cells. This is accompanied at the molecular level by underlying allelic changes in asynchronous replication timing patterns at the kappa locus. These experiments may serve to define a new concept of stem cell plasticity.
C1 [Farago, Marganit; Rosenbluh, Chaggai; Tevlin, Maya; Fraenkel, Shira; Schlesinger, Sharon; Masika, Hagit; Gouzman, Masha; Cedar, Howard; Bergman, Yehudit] Hebrew Univ Jerusalem, Sch Med, Inst Med Res Israel Canada, Dept Dev Biol & Canc Res, IL-91120 Jerusalem, Israel.
   [Teng, Grace; Schatz, David] Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT 06520 USA.
   [Schatz, David] Yale Univ, Sch Med, Howard Hughes Med Inst, New Haven, CT 06520 USA.
   [Rais, Yoach; Hanna, Jacob H.] Weizmann Inst Sci, Dept Mol Genet, IL-76100 Rehovot, Israel.
   [Mildner, Alexander; Jung, Steffen] Weizmann Inst Sci, Dept Immunol, IL-76100 Rehovot, Israel.
   [Mostoslavsky, Gustavo] Boston Univ, Sch Med, Ctr Regenerat Med CReM, Dept Med, Boston, MA 02118 USA.
C3 Hebrew University of Jerusalem; Yale University; Howard Hughes Medical Institute; Yale University; Weizmann Institute of Science; Weizmann Institute of Science; Boston University
RP Cedar, H (corresponding author), Hebrew Univ Jerusalem, Sch Med, Inst Med Res Israel Canada, Dept Dev Biol & Canc Res, POB 12272, IL-91120 Jerusalem, Israel.
EM cedar@mail.huji.ac.il; Yehudit.Bergman@huji.ac.il
FU Israel Academy of Sciences; National Institutes of Health; Israel Cancer Research Foundation; European Community
NR 36
TC 36
Z9 50
U1 0
U2 14
PU NATURE PUBLISHING 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 25
PY 2012
VL 490
IS 7421
BP 561
EP +
DI 10.1038/nature11496
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 025NK
UT WOS:000310196200047
PM 23023124
DA 2026-03-09
ER

PT J
AU Mitchell, RN
   Kilian, TM
   Evans, DAD
AF Mitchell, Ross N.
   Kilian, Taylor M.
   Evans, David A. D.
TI Supercontinent cycles and the calculation of absolute palaeolongitude in deep time
SO NATURE
LA English
DT Article
ID true polar wander; rodinia; core; tectonics; gondwana; rotation
AB Traditional models of the supercontinent cycle predict that the next supercontinent-'Amasia'-will form either where Pangaea rifted (the 'introversion'(1) model) or on the opposite side of the world (the 'extroversion'(2-4) models). Here, by contrast, we develop an 'orthoversion'(5) model whereby a succeeding supercontinent forms 90 degrees away, within the great circle of subduction encircling its relict predecessor. A supercontinent aggregates over a mantle downwelling but then influences global-scale mantle convection to create an upwelling under the landmass(6). We calculate the minimum moment of inertia about which oscillatory true polar wander occurs owing to the prolate shape of the non-hydrostatic Earth(5,7). By fitting great circles to each supercontinent's true polar wander legacy, we determine that the arc distances between successive supercontinent centres (the axes of the respective minimum moments of inertia) are 88 degrees for Nuna to Rodinia and 87 degrees for Rodinia to Pangaea-as predicted by the orthoversion model. Supercontinent centres can be located back into Precambrian time, providing fixed points for the calculation of absolute palaeolongitude over billion-year timescales. Palaeogeographic reconstructions additionally constrained in palaeolongitude will provide increasingly accurate estimates of ancient plate motions and palaeobiogeographic affinities.
C1 [Mitchell, Ross N.; Kilian, Taylor M.; Evans, David A. D.] Yale Univ, New Haven, CT 06511 USA.
C3 Yale University
RP Mitchell, RN (corresponding author), Yale Univ, 210 Whitney Ave, New Haven, CT 06511 USA.
EM ross.mitchell@yale.edu
FU NSF; Directorate For Geosciences; Division Of Earth Sciences [1019739] Funding Source: National Science Foundation; Division Of Earth Sciences; Directorate For Geosciences [1114432] Funding Source: National Science Foundation
NR 41
TC 143
Z9 174
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 FEB 9
PY 2012
VL 482
IS 7384
BP 208
EP U96
DI 10.1038/nature10800
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 888HI
UT WOS:000299994100036
PM 22318605
DA 2026-03-09
ER

PT J
AU Coste, B
   Xiao, BL
   Santos, JS
   Syeda, R
   Grandl, J
   Spencer, KS
   Kim, SE
   Schmidt, M
   Mathur, J
   Dubin, AE
   Montal, M
   Patapoutian, A
AF Coste, Bertrand
   Xiao, Bailong
   Santos, Jose S.
   Syeda, Ruhma
   Grandl, Joerg
   Spencer, Kathryn S.
   Kim, Sung Eun
   Schmidt, Manuela
   Mathur, Jayanti
   Dubin, Adrienne E.
   Montal, Mauricio
   Patapoutian, Ardem
TI Piezo proteins are pore-forming subunits of mechanically activated channels
SO NATURE
LA English
DT Article
ID voltage sensor; mechanotransduction; transduction; neurons; hearing; toxin
AB Mechanotransduction has an important role in physiology. Biological processes including sensing touch and sound waves require as-yet-unidentified cation channels that detect pressure. Mouse Piezo1 (MmPiezo1) and MmPiezo2 (also called Fam38a and Fam38b, respectively) induce mechanically activated cationic currents in cells; however, it is unknown whether Piezo proteins are pore-forming ion channels or modulate ion channels. Here we show that Drosophila melanogaster Piezo (DmPiezo, also called CG8486) also induces mechanically activated currents in cells, but through channels with remarkably distinct pore properties including sensitivity to the pore blocker ruthenium red and single channel conductances. MmPiezo1 assembles as a similar to 1.2-million-dalton homo-oligomer, with no evidence of other proteins in this complex. Purified MmPiezo1 reconstituted into asymmetric lipid bilayers and liposomes forms ruthenium-red-sensitive ion channels. These data demonstrate that Piezo proteins are an evolutionarily conserved ion channel family involved in mechanotransduction.
C1 [Coste, Bertrand; Xiao, Bailong; Grandl, Joerg; Spencer, Kathryn S.; Kim, Sung Eun; Schmidt, Manuela; Dubin, Adrienne E.; Patapoutian, Ardem] Scripps Res Inst, Dept Cell Biol, Dorris Neurosci Ctr, La Jolla, CA 92037 USA.
   [Santos, Jose S.; Syeda, Ruhma; Montal, Mauricio] Univ Calif San Diego, Div Biol Sci, Neurobiol Sect, La Jolla, CA 92093 USA.
   [Mathur, Jayanti; Patapoutian, Ardem] Novartis Res Fdn, Genom Inst, San Diego, CA 92121 USA.
C3 Scripps Research Institute; University of California System; University of California San Diego; Novartis; Novartis USA
RP Patapoutian, A (corresponding author), Scripps Res Inst, Dept Cell Biol, Dorris Neurosci Ctr, La Jolla, CA 92037 USA.
EM mmontal@ucsd.edu; apatapou@gnf.org
FU National Institutes of Dental and Craniofacial Research, Neurological Disorders, General Medical Sciences; Genomics Institute of the Novartis Research Foundation; American Heart Association; NIH
NR 34
TC 887
Z9 1083
U1 6
U2 454
PU NATURE PUBLISHING 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 8
PY 2012
VL 483
IS 7388
BP 176
EP U72
DI 10.1038/nature10812
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 904DT
UT WOS:000301174900030
PM 22343900
DA 2026-03-09
ER

PT J
AU Schmeisser, MJ
   Ey, E
   Wegener, S
   Bockmann, J
   Stempel, AV
   Kuebler, A
   Janssen, AL
   Udvardi, PT
   Shiban, E
   Spilker, C
   Balschun, D
   Skryabin, BV
   Dieck, ST
   Smalla, KH
   Montag, D
   Leblond, CS
   Faure, P
   Torquet, N
   Le Sourd, AM
   Toro, R
   Grabrucker, AM
   Shoichet, SA
   Schmitz, D
   Kreutz, MR
   Bourgeron, T
   Gundelfinger, ED
   Boeckers, TM
AF Schmeisser, Michael J.
   Ey, Elodie
   Wegener, Stephanie
   Bockmann, Juergen
   Stempel, A. Vanessa
   Kuebler, Angelika
   Janssen, Anna-Lena
   Udvardi, Patrick T.
   Shiban, Ehab
   Spilker, Christina
   Balschun, Detlef
   Skryabin, Boris V.
   Dieck, Susanne Tom
   Smalla, Karl-Heinz
   Montag, Dirk
   Leblond, Claire S.
   Faure, Philippe
   Torquet, Nicolas
   Le Sourd, Anne-Marie
   Toro, Roberto
   Grabrucker, Andreas M.
   Shoichet, Sarah A.
   Schmitz, Dietmar
   Kreutz, Michael R.
   Bourgeron, Thomas
   Gundelfinger, Eckart D.
   Boeckers, Tobias M.
TI Autistic-like behaviours and hyperactivity in mice lacking ProSAP1/Shank2
SO NATURE
LA English
DT Article
ID spectrum disorder; synaptic-transmission; postsynaptic density; mutations; shank3; gene
AB Autism spectrum disorders comprise a range of neurodevelopmental disorders characterized by deficits in social interaction and communication, and by repetitive behaviour(1). Mutations in synaptic proteins such as neuroligins(2,3), neurexins(4), GKAPs/SAPAPs(5) and ProSAPs/Shanks(6-10) were identified in patients with autism spectrum disorder, but the causative mechanisms remain largely unknown. ProSAPs/Shanks build large homo-and heteromeric protein complexes at excitatory synapses and organize the complex protein machinery of the postsynaptic density in a laminar fashion(11,12). Here we demonstrate that genetic deletion of ProSAP1/Shank2 results in an early, brain-region-specific upregulation of ionotropic glutamate receptors at the synapse and increased levels of ProSAP2/Shank3. Moreover, ProSAP1/Shank2(-/-) mutants exhibit fewer dendritic spines and show reduced basal synaptic transmission, a reduced frequency of miniature excitatory postsynaptic currents and enhanced N-methyl-D-aspartate receptor-mediated excitatory currents at the physiological level. Mutants are extremely hyperactive and display profound autistic-like behavioural alterations including repetitive grooming as well as abnormalities in vocal and social behaviours. By comparing the data on ProSAP1/Shank2(-/-) mutants with ProSAP2/Shank3 alpha beta(-/-) mice, we show that different abnormalities in synaptic glutamate receptor expression can cause alterations in social interactions and communication. Accordingly, we propose that appropriate therapies for autism spectrum disorders are to be carefully matched to the underlying synaptopathic phenotype.
C1 [Schmeisser, Michael J.; Bockmann, Juergen; Kuebler, Angelika; Janssen, Anna-Lena; Udvardi, Patrick T.; Shiban, Ehab; Grabrucker, Andreas M.; Boeckers, Tobias M.] Univ Ulm, Inst Anat & Cell Biol, D-89081 Ulm, Germany.
   [Ey, Elodie; Leblond, Claire S.; Torquet, Nicolas; Le Sourd, Anne-Marie; Toro, Roberto; Bourgeron, Thomas] Inst Pasteur, CNRS, URA Genes Synapses & Cognit 2182, F-75724 Paris 15, France.
   [Ey, Elodie; Leblond, Claire S.; Torquet, Nicolas; Le Sourd, Anne-Marie; Toro, Roberto; Bourgeron, Thomas] Univ Paris Diderot, Sorbonne Paris Cite, F-75013 Paris, France.
   [Wegener, Stephanie; Stempel, A. Vanessa; Shoichet, Sarah A.; Schmitz, Dietmar] Charite, Neurosci Res Ctr, D-10117 Berlin, Germany.
   [Spilker, Christina; Kreutz, Michael R.] Leibniz Inst Neurobiol, PG Neuroplast, D-39118 Magdeburg, Germany.
   [Balschun, Detlef] Catholic Univ Louvain, Lab Biol Psychol, Dept Psychol, B-3000 Louvain, Belgium.
   [Skryabin, Boris V.] Univ Munster, Inst Expt Pathol ZMBE, D-48149 Munster, Germany.
   [Skryabin, Boris V.] Univ Munster, Interdisciplinary Ctr Clin Res IZKF, D-48149 Munster, Germany.
   [Dieck, Susanne Tom] Max Planck Inst Brain Res, Dept Synapt Plast, D-60528 Frankfurt, Germany.
   [Smalla, Karl-Heinz; Gundelfinger, Eckart D.] Leibniz Inst Neurobiol, Dept Neurochem, D-39118 Magdeburg, Germany.
   [Montag, Dirk] Leibniz Inst Neurobiol, Neurogenet Special Lab, D-39118 Magdeburg, Germany.
   [Faure, Philippe] Univ Paris 06, CNRS, UMR 7102, F-75005 Paris, France.
C3 Ulm University; Centre National de la Recherche Scientifique (CNRS); Pasteur Network; Universite Paris Cite; Institut Pasteur Paris; Universite Paris Cite; Free University of Berlin; Humboldt University of Berlin; Charite Universitatsmedizin Berlin; Leibniz Association; Leibniz Institut fur Neurobiologie (LIN); Universite Catholique Louvain; University of Munster; University of Munster; Max Planck Society; Leibniz Association; Leibniz Institut fur Neurobiologie (LIN); Leibniz Association; Leibniz Institut fur Neurobiologie (LIN); Sorbonne Universite; Centre National de la Recherche Scientifique (CNRS)
RP Boeckers, TM (corresponding author), Univ Ulm, Inst Anat & Cell Biol, D-89081 Ulm, Germany.
EM tobias.boeckers@uni-ulm.de
FU Baustein 3.2 [L.SBN.0081, L.SBN.0083]; Fondation de France; Agence Nationale de la Recherche (ANR) FLEXNEURIM [ANR09BLAN034003]; Deutsche Forschungsgemeinschaft (DFG) [GRK 1123, EXC 257, SFB 618, SFB 665, SFB 779, Bo 1718/3-1, 1718/4-1, SFB 497/B8]; Bundesministerium fur Bildung und Forschung (BMBF) (BCCN, BFNL); Einstein Foundation; ANR [ANR-08-MNPS-037-01 - SynGen]; Neuron-ERANET [EUHF-AUTISM]; Fondation Orange; Fondation FondaMentale; Bettencourt-Schueller Fondation; CNRS Neuroinformatic; BMBF (EraNET Neuron)
NR 38
TC 510
Z9 596
U1 1
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 JUN 14
PY 2012
VL 486
IS 7402
BP 256
EP +
DI 10.1038/nature11015
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 957UH
UT WOS:000305189000035
PM 22699619
DA 2026-03-09
ER

PT J
AU Shakun, JD
   Clark, PU
   He, F
   Marcott, SA
   Mix, AC
   Liu, ZY
   Otto-Bliesner, B
   Schmittner, A
   Bard, E
AF Shakun, Jeremy D.
   Clark, Peter U.
   He, Feng
   Marcott, Shaun A.
   Mix, Alan C.
   Liu, Zhengyu
   Otto-Bliesner, Bette
   Schmittner, Andreas
   Bard, Edouard
TI Global warming preceded by increasing carbon dioxide concentrations during the last deglaciation
SO NATURE
LA English
DT Article
ID ice core records; atmospheric co2; climate sensitivity; glacial maximum; atlantic; ocean; temperature; calibration; greenland; rise
AB The covariation of carbon dioxide (CO2) concentration and temperature in Antarctic ice-core records suggests a close link between CO2 and climate during the Pleistocene ice ages. The role and relative importance of CO2 in producing these climate changes remains unclear, however, in part because the ice-core deuterium record reflects local rather than global temperature. Here we construct a record of global surface temperature from 80 proxy records and show that temperature is correlated with and generally lags CO2 during the last (that is, the most recent) deglaciation. Differences between the respective temperature changes of the Northern Hemisphere and Southern Hemisphere parallel variations in the strength of the Atlantic meridional overturning circulation recorded in marine sediments. These observations, together with transient global climate model simulations, support the conclusion that an antiphased hemispheric temperature response to ocean circulation changes superimposed on globally in-phase warming driven by increasing CO2 concentrations is an explanation for much of the temperature change at the end of the most recent ice age.
C1 [Shakun, Jeremy D.] Harvard Univ, Dept Earth & Planetary Sci, Cambridge, MA 02138 USA.
   [Shakun, Jeremy D.] Columbia Univ, Lamont Doherty Earth Observ, Palisades, NY 10964 USA.
   [Clark, Peter U.; Marcott, Shaun A.; Mix, Alan C.; Schmittner, Andreas] Oregon State Univ, Coll Earth Ocean & Atmospher Sci, Corvallis, OR 97331 USA.
   [He, Feng; Liu, Zhengyu] Univ Wisconsin, Ctr Climat Res, Madison, WI 53706 USA.
   [Liu, Zhengyu] Univ Wisconsin, Dept Atmospher & Ocean Sci, Madison, WI 53706 USA.
   [Liu, Zhengyu] Peking Univ, Lab Ocean Atmosphere Studies, Beijing 100871, Peoples R China.
   [Otto-Bliesner, Bette] Natl Ctr Atmospher Res, Climate & Global Dynam Div, Boulder, CO 80307 USA.
   [Bard, Edouard] Univ Aix Marseille, CNRS, Coll France, CEREGE, F-13545 Aix En Provence, France.
C3 Harvard University; Columbia University; Oregon State University; University of Wisconsin System; University of Wisconsin Madison; University of Wisconsin System; University of Wisconsin Madison; Peking University; National Center Atmospheric Research (NCAR) - USA; Universite PSL; College de France; Aix-Marseille Universite; Centre National de la Recherche Scientifique (CNRS)
RP Shakun, JD (corresponding author), Harvard Univ, Dept Earth & Planetary Sci, 20 Oxford St, Cambridge, MA 02138 USA.
EM shakun@fas.harvard.edu
FU Office of Science of the Department of Energy [DE-AC05-00OR22725]; NSF [AGS-0602395]; NOAA
NR 54
TC 1115
Z9 1296
U1 18
U2 961
PU NATURE PUBLISHING 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 5
PY 2012
VL 484
IS 7392
BP 49
EP 54
DI 10.1038/nature10915
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 919QN
UT WOS:000302343400032
PM 22481357
DA 2026-03-09
ER

PT J
AU Stadler, D
   Krinner, S
   Meineke, J
   Brantut, JP
   Esslinger, T
AF Stadler, David
   Krinner, Sebastian
   Meineke, Jakob
   Brantut, Jean-Philippe
   Esslinger, Tilman
TI Observing the drop of resistance in the flow of a superfluid Fermi gas
SO NATURE
LA English
DT Article
ID bose-einstein condensate; thermodynamics; vortices
AB The ability of particles to flow with very low resistance is characteristic of superfluid and superconducting states, leading to their discovery in the past century(1,2). Although measuring the particle flow in liquid helium or superconducting materials is essential to identify superfluidity or superconductivity, no analogous measurement has been performed for superfluids based on ultracold Fermi gases. Here we report direct measurements of the conduction properties of strongly interacting fermions, observing the well-known drop in resistance that is associated with the onset of superfluidity. By varying the depth of the trapping potential in a narrow channel connecting two atomic reservoirs, we observed variations of the atomic current over several orders of magnitude. We related the intrinsic conduction properties to the thermodynamic functions in a model-independent way, by making use of high-resolution in situ imaging in combination with current measurements. Our results show that, as in solid-state systems, current and resistance measurements in quantum gases provide a sensitive probe with which to explore many-body physics. Our method is closely analogous to the operation of a solid-state field-effect transistor and could be applied as a probe for optical lattices and disordered systems, paving the way for modelling complex superconducting devices.
C1 [Stadler, David; Krinner, Sebastian; Meineke, Jakob; Brantut, Jean-Philippe; Esslinger, Tilman] ETH, Inst Quantum Elect, CH-8093 Zurich, Switzerland.
C3 Swiss Federal Institutes of Technology Domain; ETH Zurich
RP Brantut, JP (corresponding author), ETH, Inst Quantum Elect, CH-8093 Zurich, Switzerland.
EM brantutj@phys.ethz.ch; esslinger@phys.ethz.ch
FU NCCR MaNEP and QSIT; ERC
NR 31
TC 89
Z9 98
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 NOV 29
PY 2012
VL 491
IS 7426
BP 736
EP +
DI 10.1038/nature11613
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 044FY
UT WOS:000311606000040
PM 23192151
DA 2026-03-09
ER

PT J
AU Maisel, SB
   Höfler, M
   Müller, S
AF Maisel, Sascha B.
   Hoefler, Michaela
   Mueller, Stefan
TI A canonical stability-elasticity relationship verified for one million face-centred-cubic structures
SO NATURE
LA English
DT Article
ID total-energy calculations; roman civilizations; 1st-principles; alloys; etruscan; greek
AB Any thermodynamically stable or metastable phase corresponds to a local minimum of a potentially very complicated energy landscape. But however complex the crystal might be, this energy landscape is of parabolic shape near its minima. Roughly speaking, the depth of this energy well with respect to some reference level determines the thermodynamic stability of the system, and the steepness of the parabola near its minimum determines the system's elastic properties. Although changing alloying elements and their concentrations in a given material to enhance certain properties dates back to the Bronze Age(1,2), the systematic search for desirable properties in metastable atomic configurations at a fixed stoichiometry is a very recent tool in materials design(3). Here we demonstrate, using first-principles studies of four binary alloy systems, that the elastic properties of face-centred-cubic intermetallic compounds obey certain rules. We reach two conclusions based on calculations on a huge subset of the face-centred-cubic configuration space. First, the stiffness and the heat of formation are negatively correlated with a nearly constant Spearman correlation(4) for all concentrations. Second, the averaged stiffness of metastable configurations at a fixed concentration decays linearly with their distance to the ground-state line (the phase diagram of an alloy at zero Kelvin). We hope that our methods will help to simplify the quest for new materials with optimal properties from the vast configuration space available.
C1 [Maisel, Sascha B.; Hoefler, Michaela; Mueller, Stefan] Hamburg Univ Technol, Inst Adv Ceram, D-21073 Hamburg, Germany.
C3 Hamburg University of Technology
RP Maisel, SB (corresponding author), Hamburg Univ Technol, Inst Adv Ceram, Denickestr 15, D-21073 Hamburg, Germany.
EM stefan.mueller@tuhh.de
FU DFG (Deutsche Forschungsgemeinschaft) [Mu1648/5]
NR 25
TC 24
Z9 24
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 NOV 29
PY 2012
VL 491
IS 7426
BP 740
EP +
DI 10.1038/nature11609
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 044FY
UT WOS:000311606000041
PM 23172142
DA 2026-03-09
ER

PT J
AU Dühren-von Minden, M
   Übelhart, R
   Schneider, D
   Wossning, T
   Bach, MP
   Buchner, M
   Hofmann, D
   Surova, E
   Follo, M
   Köhler, F
   Wardemann, H
   Zirlik, K
   Veelken, H
   Jumaa, H
AF Duehren-von Minden, Marcus
   Uebelhart, Rudolf
   Schneider, Dunja
   Wossning, Thomas
   Bach, Martina P.
   Buchner, Maike
   Hofmann, Daniel
   Surova, Elena
   Follo, Marie
   Koehler, Fabian
   Wardemann, Hedda
   Zirlik, Katja
   Veelken, Hendrik
   Jumaa, Hassan
TI Chronic lymphocytic leukaemia is driven by antigen-independent cell-autonomous signalling
SO NATURE
LA English
DT Article
ID b-cells; fostamatinib disodium; receptor; lymphoma; syk; proliferation; inhibition; precursors; expression; cloning
AB B-cell antigen receptor (BCR) expression is an important feature of chronic lymphocytic leukaemia (CLL), one of the most prevalent B-cell neoplasias in Western countries(1). The presence of stereotyped and quasi-identical BCRs in different CLL patients suggests that recognition of specific antigens might drive CLL pathogenesis. Here we show that, in contrast to other B-cell neoplasias, CLL-derived BCRs induce antigen-independent cell-autonomous signalling, which is dependent on the heavy-chain complementarity-determining region (HCDR3) and an internal epitope of the BCR. Indeed, transferring the HCDR3 of a CLL-derived BCR provides autonomous signalling capacity to a non-autonomously active BCR, whereas mutations in the internal epitope abolish this capacity. Because BCR expression was required for the binding of secreted CLL-derived BCRs to target cells, and mutations in the internal epitope reduced this binding, our results indicate a new model for CLL pathogenesis, with cell-autonomous antigen-independent signalling as a crucial pathogenic mechanism.
C1 [Duehren-von Minden, Marcus; Uebelhart, Rudolf; Schneider, Dunja; Wossning, Thomas; Bach, Martina P.; Hofmann, Daniel; Surova, Elena; Koehler, Fabian; Jumaa, Hassan] Univ Freiburg, Ctr Biol Signaling Studies BIOSS, D-79104 Freiburg, Germany.
   [Uebelhart, Rudolf; Surova, Elena] Univ Freiburg, Spemann Grad Sch Biol & Med, D-79104 Freiburg, Germany.
   [Buchner, Maike; Follo, Marie; Zirlik, Katja] Univ Med Ctr Freiburg, Dept Hematol Oncol, D-79106 Freiburg, Germany.
   [Wardemann, Hedda] Max Planck Inst Infect Biol, Max Planck Res Grp Mol Immunol, D-10117 Berlin, Germany.
   [Veelken, Hendrik] Leiden Univ, Med Ctr, Dept Hematol, NL-2333 ZA Leiden, Netherlands.
   [Jumaa, Hassan] Univ Freiburg, Fac Biol, Dept Mol Immunol, D-79108 Freiburg, Germany.
   [Jumaa, Hassan] Max Planck Inst Immunobiol & Epigenet, D-79108 Freiburg, Germany.
C3 University of Freiburg; University of Freiburg; University of Freiburg; Max Planck Society; Leiden University; Leiden University Medical Center (LUMC); Leiden University - Excl LUMC; University of Freiburg; Max Planck Society
RP Jumaa, H (corresponding author), Univ Freiburg, Ctr Biol Signaling Studies BIOSS, D-79104 Freiburg, Germany.
EM jumaa@immunbio.mpg.de
FU Deutsche Krebshilfe [108935]; Deutsche Forschungsgemeinschaft [SFB746, JU463/2-1]; Excellence Initiative of the German Federal and State Governments [GSC-4]; Academy of Finland (AKA) [108935] Funding Source: Academy of Finland (AKA)
NR 28
TC 421
Z9 472
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 SEP 13
PY 2012
VL 489
IS 7415
BP 309
EP +
DI 10.1038/nature11309
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 003UC
UT WOS:000308635900045
PM 22885698
DA 2026-03-09
ER

PT J
AU Kay, JN
   Chu, MW
   Sanes, JR
AF Kay, Jeremy N.
   Chu, Monica W.
   Sanes, Joshua R.
TI MEGF10 and MEGF11 mediate homotypic interactions required for mosaic spacing of retinal neurons
SO NATURE
LA English
DT Article
ID cholinergic amacrine cells; mouse retina; engulfment receptor; horizontal cells; rodent retina; resource; models; dscam
AB In many parts of the nervous system, neuronal somata display orderly spatial arrangements(1). In the retina, neurons of numerous individual subtypes form regular arrays called mosaics: they are less likely to be near neighbours of the same subtype than would occur by chance, resulting in 'exclusion zones' that separate them(1-4). Mosaic arrangements provide a mechanism to distribute each cell type evenly across the retina, ensuring that all parts of the visual field have access to a full set of processing elements(2). Remarkably, mosaics are independent of each other: although a neuron of one subtype is unlikely to be adjacent to another of the same subtype, there is no restriction on its spatial relationship to neighbouring neurons of other subtypes(5). This independence has led to the hypothesis that molecular cues expressed by specific subtypes pattern mosaics by mediating homotypic (within-subtype) short-range repulsive interactions(1,4-9). So far, however, no molecules have been identified that show such activity, so this hypothesis remains untested. Here we demonstrate in mouse that two related transmembrane proteins, MEGF10 and MEGF11, have critical roles in the formation of mosaics by two retinal interneuron subtypes, starburst amacrine cells and horizontal cells. MEGF10 and 11 and their invertebrate relatives Caenorhabditis elegans CED-1 and Drosophila Draper have hitherto been studied primarily as receptors necessary for engulfment of debris following apoptosis or axonal injury(10-14). Our results demonstrate that members of this gene family can also serve as subtype-specific ligands that pattern neuronal arrays.
C1 [Kay, Jeremy N.; Chu, Monica W.; Sanes, Joshua R.] Harvard Univ, Ctr Brain Sci, Cambridge, MA 02138 USA.
   [Kay, Jeremy N.; Chu, Monica W.; Sanes, Joshua R.] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA.
C3 Harvard University; Harvard University
RP Sanes, JR (corresponding author), Harvard Univ, Ctr Brain Sci, 52 Oxford St, Cambridge, MA 02138 USA.
EM sanesj@mcb.harvard.edu
FU National Institutes of Health [NS029169, EY022073]; Life Sciences Research Foundation
NR 35
TC 150
Z9 188
U1 0
U2 16
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 22
PY 2012
VL 483
IS 7390
BP 465
EP U117
DI 10.1038/nature10877
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 912CC
UT WOS:000301771200043
PM 22407321
DA 2026-03-09
ER

PT J
AU Wei, P
   Wong, WW
   Park, JS
   Corcoran, EE
   Peisajovich, SG
   Onuffer, JJ
   Weiss, A
   Lim, WA
AF Wei, Ping
   Wong, Wilson W.
   Park, Jason S.
   Corcoran, Ethan E.
   Peisajovich, Sergio G.
   Onuffer, James J.
   Weiss, Arthur
   Lim, Wendell A.
TI Bacterial virulence proteins as tools to rewire kinase pathways in yeast and immune cells
SO NATURE
LA English
DT Article
ID nf-kappa-b; t-cells; phosphothreonine lyase; tyrosine-phosphatase; synthetic biology; gene-expression; adverse event; activation; yersinia; adaptation
AB Bacterial pathogens have evolved specific effector proteins that, by interfacing with host kinase signalling pathways, provide a mechanism to evade immune responses during infection(1,2). Although these effectors contribute to pathogen virulence, we realized that they might also serve as valuable synthetic biology reagents for engineering cellular behaviour. Here we exploit two effector proteins, the Shigella flexneri OspF protein(3) and Yersinia pestis YopH protein(4), to rewire kinase-mediated responses systematically both in yeast and mammalian immune cells. Bacterial effector proteins can be directed to inhibit specific mitogen-activated protein kinase pathways selectively in yeast by artificially targeting them to pathway-specific complexes. Moreover, we show that unique properties of the effectors generate new pathway behaviours: OspF, which irreversibly inactivates mitogen-activated protein kinases(4), was used to construct a synthetic feedback circuit that shows novel frequency-dependent input filtering. Finally, we show that effectors can be used in T cells, either as feedback modulators to tune the T-cell response amplitude precisely, or as an inducible pause switch that can temporarily disable T-cell activation. These studies demonstrate how pathogens could provide a rich toolkit of parts to engineer cells for therapeutic or biotechnological applications.
C1 [Wei, Ping; Wong, Wilson W.; Park, Jason S.; Peisajovich, Sergio G.; Onuffer, James J.; Lim, Wendell A.] Univ Calif San Francisco, Dept Cellular & Mol Pharmacol, San Francisco, CA 94158 USA.
   [Wei, Ping; Wong, Wilson W.; Park, Jason S.; Corcoran, Ethan E.; Peisajovich, Sergio G.; Weiss, Arthur; Lim, Wendell A.] Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94158 USA.
   [Wong, Wilson W.; Park, Jason S.; Corcoran, Ethan E.; Onuffer, James J.; Weiss, Arthur; Lim, Wendell A.] Univ Calif San Francisco, Cell Prop Lab, San Francisco, CA 94158 USA.
   [Corcoran, Ethan E.; Weiss, Arthur] Univ Calif San Francisco, Dept Med, San Francisco, CA 94158 USA.
C3 University of California System; University of California San Francisco; University of California System; University of California San Francisco; Howard Hughes Medical Institute; University of California System; University of California San Francisco; University of California System; University of California San Francisco
RP Lim, WA (corresponding author), Univ Calif San Francisco, Dept Cellular & Mol Pharmacol, San Francisco, CA 94158 USA.
EM lim@cmp.ucsf.edu
FU American Cancer Society fellowship [PF-09-137-01-TBE]; Li Foundation Fellowship; California Institute for Regenerative Medicine fellowship [TG2-01153]; National Institutes of Health [PN2EY016546, RO1GM055040, RO1GM062583, P50GM081879]; NSF Synthetic Biology and Engineering Research Center; Packard Foundation; Howard Hughes Medical Institute
NR 32
TC 98
Z9 142
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 AUG 16
PY 2012
VL 488
IS 7411
BP 384
EP +
DI 10.1038/nature11259
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 988OS
UT WOS:000307501000043
PM 22820255
DA 2026-03-09
ER

PT J
AU Lekomtsev, S
   Su, KC
   Pye, VE
   Blight, K
   Sundaramoorthy, S
   Takaki, T
   Collinson, LM
   Cherepanov, P
   Divecha, N
   Petronczki, M
AF Lekomtsev, Sergey
   Su, Kuan-Chung
   Pye, Valerie E.
   Blight, Ken
   Sundaramoorthy, Sriramkumar
   Takaki, Tohru
   Collinson, Lucy M.
   Cherepanov, Peter
   Divecha, Nullin
   Petronczki, Mark
TI Centralspindlin links the mitotic spindle to the plasma membrane during cytokinesis
SO NATURE
LA English
DT Article
ID contractile ring; binding domain; rhogef ect2; protein; complex; abscission; gtpase; actin; microtubules; pi(4,5)p-2
AB At the end of cell division, cytokinesis splits the cytoplasm of nascent daughter cells and partitions segregated sister genomes(1,2). To coordinate cell division with chromosome segregation, the mitotic spindle controls cytokinetic events at the cell envelope. The spindle midzone stimulates the actomyosin-driven contraction of the cleavage furrow, which proceeds until the formation of a microtubule-rich intercellular bridge with the midbody at its centre. The midbody directs the final membrane abscission reaction(1,2) and has been proposed to attach the cleavage furrow to the intercellular bridge(3). How the mitotic spindle is connected to the plasma membrane during cytokinesis is not understood. Here we identify a plasma membrane tethering activity in the centralspindlin protein complex, a conserved component of the spindle midzone and midbody(4). We demonstrate that the C1 domain of the centralspindlin subunit MgcRacGAP associates with the plasma membrane by interacting with polyanionic phosphoinositide lipids. Using X-ray crystallography we determine the structure of this atypical C1 domain. Mutations in the hydrophobic cap and in basic residues of the C1 domain of MgcRacGAP prevent association of the protein with the plasma membrane, and abrogate cytokinesis in human and chicken cells. Artificial membrane tethering of centralspindlin restores cell division in the absence of the C1 domain of MgcRacGAP. Although C1 domain function is dispensable for the formation of the midzone and midbody, it promotes contractility and is required for the attachment of the plasma membrane to the midbody, a long-postulated function of this organelle(3). Our analysis suggests that centralspindlin links the mitotic spindle to the plasma membrane to secure the final cut during cytokinesis in animal cells.
C1 [Lekomtsev, Sergey; Su, Kuan-Chung; Sundaramoorthy, Sriramkumar; Takaki, Tohru; Petronczki, Mark] Canc Res UK London Res Inst, Clare Hall Labs, Cell Div, S Mimms EN6 3LD, Herts, England.
   [Lekomtsev, Sergey; Su, Kuan-Chung; Sundaramoorthy, Sriramkumar; Takaki, Tohru; Petronczki, Mark] Canc Res UK London Res Inst, Clare Hall Labs, Aneuploidy Lab, S Mimms EN6 3LD, Herts, England.
   [Pye, Valerie E.; Cherepanov, Peter] Canc Res UK London Res Inst, Clare Hall Labs, Chromatin Struct & Mobile DNA Lab, S Mimms EN6 3LD, Herts, England.
   [Blight, Ken; Collinson, Lucy M.] Canc Res UK London Res Inst, Electron Microscopy Unit, London WC2A 3PX, England.
   [Divecha, Nullin] Univ Manchester, Paterson Inst Canc Res, Inositide Lab, Manchester M20 4BX, Lancs, England.
C3 Cancer Research UK; Cancer Research UK; Cancer Research UK; Cancer Research UK; Paterson Institute for Cancer Research; University of Manchester
RP Petronczki, M (corresponding author), Canc Res UK London Res Inst, Clare Hall Labs, Cell Div, Blanche Lane, S Mimms EN6 3LD, Herts, England.
EM mark.petronczki@cancer.org.uk
FU Cancer Research UK; EMBO; Cancer Research UK [15272] Funding Source: researchfish
NR 44
TC 123
Z9 148
U1 1
U2 37
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 13
PY 2012
VL 492
IS 7428
BP 276
EP +
DI 10.1038/nature11773
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 053GM
UT WOS:000312259300047
PM 23235882
DA 2026-03-09
ER

PT J
AU Peters, SE
   Gaines, RR
AF Peters, Shanan E.
   Gaines, Robert R.
TI Formation of the 'Great Unconformity' as a trigger for the Cambrian explosion
SO NATURE
LA English
DT Article
ID seawater chemistry; fluid inclusions; animals; ocean; geochemistry; minerals; rise
AB The transition between the Proterozoic and Phanerozoic eons, beginning 542 million years (Myr) ago, is distinguished by the diversification of multicellular animals and by their acquisition of mineralized skeletons during the Cambrian period(1). Considerable progress has been made in documenting and more precisely correlating biotic patterns in the Neoproterozoic-Cambrian fossil record with geochemical and physical environmental perturbations(2-5), but the mechanisms responsible for those perturbations remain uncertain(1,2). Here we use new stratigraphic and geochemical data to show that early Palaeozoic marine sediments deposited approximately 540-480 Myr ago record both an expansion in the area of shallow epicontinental seas and anomalous patterns of chemical sedimentation that are indicative of increased oceanic alkalinity and enhanced chemical weathering of continental crust. These geochemical conditions were caused by a protracted period of widespread continental denudation during the Neoproterozoic followed by extensive physical reworking of soil, regolith and basement rock during the first continental-scale marine transgression of the Phanerozoic. The resultant globally occurring stratigraphic surface, which in most regions separates continental crystalline basement rock from much younger Cambrian shallow marine sedimentary deposits, is known as the Great Unconformity(6). Although Darwin and others have interpreted this widespread hiatus in sedimentation on the continents as a failure of the geologic record, this palaeogeomorphic surface represents a unique physical environmental boundary condition that affected seawater chemistry during a time of profound expansion of shallow marine habitats. Thus, the formation of the Great Unconformity may have been an environmental trigger for the evolution of biomineralization and the 'Cambrian explosion' of ecologic and taxonomic diversity following the Neoproterozoic emergence of animals.
C1 [Peters, Shanan E.] Univ Wisconsin, Dept Geosci, Madison, WI 53706 USA.
   [Gaines, Robert R.] Pomona Coll, Dept Geol, Claremont, CA 91711 USA.
C3 University of Wisconsin System; University of Wisconsin Madison; Claremont Colleges; Pomona College
RP Peters, SE (corresponding author), Univ Wisconsin, Dept Geosci, Madison, WI 53706 USA.
EM peters@geology.wisc.edu
FU NSF [EAR-0819931, EAR-1046233, DUE-0942447]; Direct For Education and Human Resources; Division Of Undergraduate Education [0942447] Funding Source: National Science Foundation; Directorate For Geosciences; Division Of Earth Sciences [1046233] Funding Source: National Science Foundation
NR 30
TC 304
Z9 375
U1 2
U2 227
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 
J9 NATURE
JI Nature
PD APR 19
PY 2012
VL 484
IS 7394
BP 363
EP 366
DI 10.1038/nature10969
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 927YM
UT WOS:000302946500030
PM 22517163
DA 2026-03-09
ER

PT J
AU Ritter, S
   Nölleke, C
   Hahn, C
   Reiserer, A
   Neuzner, A
   Uphoff, M
   Mücke, M
   Figueroa, E
   Bochmann, J
   Rempe, G
AF Ritter, Stephan
   Noelleke, Christian
   Hahn, Carolin
   Reiserer, Andreas
   Neuzner, Andreas
   Uphoff, Manuel
   Muecke, Martin
   Figueroa, Eden
   Bochmann, Joerg
   Rempe, Gerhard
TI An elementary quantum network of single atoms in optical cavities
SO NATURE
LA English
DT Article
ID entanglement distribution; linear optics; ensembles; memory; communication; transitions; information; repeaters; interface; distance
AB Quantum networks are distributed quantum many-body systems with tailored topology and controlled information exchange. They are the backbone of distributed quantum computing architectures and quantum communication. Here we present a prototype of such a quantum network based on single atoms embedded in optical cavities. We show that atom-cavity systems form universal nodes capable of sending, receiving, storing and releasing photonic quantum information. Quantum connectivity between nodes is achieved in the conceptually most fundamental way-by the coherent exchange of a single photon. We demonstrate the faithful transfer of an atomic quantum state and the creation of entanglement between two identical nodes in separate laboratories. The non-local state that is created is manipulated by local quantum bit (qubit) rotation. This efficient cavity-based approach to quantum networking is particularly promising because it offers a clear perspective for scalability, thus paving the way towards large-scale quantum networks and their applications.
C1 [Ritter, Stephan; Noelleke, Christian; Hahn, Carolin; Reiserer, Andreas; Neuzner, Andreas; Uphoff, Manuel; Muecke, Martin; Figueroa, Eden; Bochmann, Joerg; Rempe, Gerhard] Max Planck Inst Quantum Opt, D-85748 Garching, Germany.
C3 Max Planck Society
RP Ritter, S (corresponding author), Max Planck Inst Quantum Opt, Hans Kopfermann Str 1, D-85748 Garching, Germany.
EM stephan.ritter@mpq.mpg.de
FU Deutsche Forschungsgemeinschaft (Research Unit 635); European Union; Bundesministerium fur Bildung und Forschung via IKT (QK_QuOReP); Alexander von Humboldt Foundation
NR 38
TC 751
Z9 871
U1 4
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 APR 12
PY 2012
VL 484
IS 7393
BP 195
EP U73
DI 10.1038/nature11023
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 930OV
UT WOS:000303149900026
PM 22498625
DA 2026-03-09
ER

PT J
AU Abitua, PB
   Wagner, E
   Navarrete, IA
   Levine, M
AF Abitua, Philip Barron
   Wagner, Eileen
   Navarrete, Ignacio A.
   Levine, Michael
TI Identification of a rudimentary neural crest in a non-vertebrate chordate
SO NATURE
LA English
DT Article
ID mesodermal tissue; cell fate; lineage; gene; plasticity; induction; evolution; insights; origin; genome
AB Neural crest arises at the neural plate border, expresses a core set of regulatory genes and produces a diverse array of cell types, including ectomesenchyme derivatives that elaborate the vertebrate head(1,2). The evolution of neural crest has been proposed to be a key event leading to the appearance of new cell types that fostered the transition from filter feeding to active predation in ancestral vertebrates(3). However, the origin of neural crest remains controversial, as homologous cell types have not been unambiguously identified in non-vertebrate chordates(1,4). Here we show that the tunicate Ciona intestinalis possesses a cephalic melanocyte lineage (a9.49) similar to neural crest that can be reprogrammed into migrating 'ectomesenchyme' by the targeted misexpression of Twist (also known as twist-like 2). Our results suggest that the neural crest melanocyte regulatory network pre-dated the divergence of tunicates and vertebrates. We propose that the co-option of mesenchyme determinants, such as Twist, into the neural plate ectoderm was crucial to the emergence of the vertebrate 'new head'(3).
C1 [Abitua, Philip Barron; Wagner, Eileen; Navarrete, Ignacio A.; Levine, Michael] Univ Calif Berkeley, Dept Mol & Cell Biol, Ctr Integrat Genom, Div Genet Genom & Dev, Berkeley, CA 94720 USA.
C3 University of California System; University of California Berkeley
RP Levine, M (corresponding author), Univ Calif Berkeley, Dept Mol & Cell Biol, Ctr Integrat Genom, Div Genet Genom & Dev, 229 Stanley Hall, Berkeley, CA 94720 USA.
EM mlevine@berkeley.edu
FU US National Science Foundation; US National Institutes of Health [NS 076542]; National Institute of Neurological Disorders and Stroke [R01NS076542] Funding Source: NIH RePORTER
NR 30
TC 171
Z9 199
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 DEC 6
PY 2012
VL 492
IS 7427
BP 104
EP +
DI 10.1038/nature11589
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 048EQ
UT WOS:000311893400054
PM 23135395
DA 2026-03-09
ER

