PT J
AU Shen, J
   Xia, WY
   Khotskaya, YB
   Huo, LF
   Nakanishi, K
   Lim, SO
   Du, Y
   Wang, Y
   Chang, WC
   Chen, CH
   Hsu, JL
   Wu, Y
   Lam, YC
   James, BP
   Liu, XP
   Liu, CG
   Patel, DJ
   Hung, MC
AF Shen, Jia
   Xia, Weiya
   Khotskaya, Yekaterina B.
   Huo, Longfei
   Nakanishi, Kotaro
   Lim, Seung-Oe
   Du, Yi
   Wang, Yan
   Chang, Wei-Chao
   Chen, Chung-Hsuan
   Hsu, Jennifer L.
   Wu, Yun
   Lam, Yung Carmen
   James, Brian P.
   Liu, Xiuping
   Liu, Chang-Gong
   Patel, Dinshaw J.
   Hung, Mien-Chie
TI EGFR modulates microRNA maturation in response to hypoxia through phosphorylation of AGO2
SO NATURE
LA English
DT Article
ID proteins; endocytosis; complex; cancer
AB MicroRNAs (miRNAs) are generated by two-step processing to yield small RNAs that negatively regulate target gene expression at the post-transcriptional level(1). Deregulation of miRNAs has been linked to diverse pathological processes, including cancer(2,3). Recent studies have also implicated miRNAs in the regulation of cellular response to a spectrum of stresses(4), such as hypoxia, which is frequently encountered in the poorly angiogenic core of a solid tumour(5). However, the upstream regulators of miRNA biogenesis machineries remain obscure, raising the question of how tumour cells efficiently coordinate and impose specificity on miRNA expression and function in response to stresses. Here we show that epidermal growth factor receptor (EGFR), which is the product of a well-characterized oncogene in human cancers, suppresses the maturation of specific tumour-suppressor-like miRNAs in response to hypoxic stress through phosphorylation of argonaute 2 (AGO2) at Tyr 393. The association between EGFR and AGO2 is enhanced by hypoxia, leading to elevated AGO2-Y393 phosphorylation, which in turn reduces the binding of Dicer to AGO2 and inhibits miRNA processing from precursor miRNAs to mature miRNAs. We also identify a long-loop structure in precursor miRNAs as a critical regulatory element in phospho-Y393-AGO2-mediated miRNA maturation. Furthermore, AGO2-Y393 phosphorylation mediates EGFR-enhanced cell survival and invasiveness under hypoxia, and correlates with poorer overall survival in breast cancer patients. Our study reveals a previously unrecognized function of EGFR in miRNA maturation and demonstrates how EGFR is likely to function as a regulator of AGO2 through novel post-translational modification. These findings suggest that modulation of miRNA biogenesis is important for stress response in tumour cells and has potential clinical implications.
C1 [Shen, Jia; Xia, Weiya; Khotskaya, Yekaterina B.; Huo, Longfei; Lim, Seung-Oe; Du, Yi; Wang, Yan; Hsu, Jennifer L.; Lam, Yung Carmen; Hung, Mien-Chie] Univ Texas MD Anderson Canc Ctr, Dept Mol & Cellular Oncol, Houston, TX 77030 USA.
   [Shen, Jia; Du, Yi; Hung, Mien-Chie] Univ Texas Grad Sch Biomed Sci Houston, Houston, TX 77030 USA.
   [Nakanishi, Kotaro; Patel, Dinshaw J.] Mem Sloan Kettering Canc Ctr, Struct Biol Program, New York, NY 10065 USA.
   [Chang, Wei-Chao; Hsu, Jennifer L.; Hung, Mien-Chie] China Med Univ, Ctr Mol Med, Taichung 402, Taiwan.
   [Chang, Wei-Chao; Hsu, Jennifer L.; Hung, Mien-Chie] China Med Univ, Grad Inst Canc Biol, Taichung 402, Taiwan.
   [Chang, Wei-Chao; Chen, Chung-Hsuan] Acad Sinica, Genom Res Ctr, Taipei 105, Taiwan.
   [Hsu, Jennifer L.; Hung, Mien-Chie] Asia Univ, Taichung 413, Taiwan.
   [Wu, Yun] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA.
   [James, Brian P.; Liu, Xiuping; Liu, Chang-Gong] Univ Texas MD Anderson Canc Ctr, Dept Expt Therapeut, Houston, TX 77030 USA.
C3 University of Texas System; UTMD Anderson Cancer Center; University of Texas System; University of Texas Health Science Center Houston; University of Texas Graduate School of Biomedical Sciences; Memorial Sloan Kettering Cancer Center; China Medical University Taiwan; China Medical University Taiwan; Academia Sinica - Taiwan; Asia University Taiwan; University of Texas System; UTMD Anderson Cancer Center; University of Texas System; UTMD Anderson Cancer Center
RP Hung, MC (corresponding author), Univ Texas MD Anderson Canc Ctr, Dept Mol & Cellular Oncol, 1515 Holcombe Blvd, Houston, TX 77030 USA.
EM mhung@mdanderson.org
FU US National Institutes of Health [CA109311, CA099031, CA16672]; US National Breast Cancer Foundation; Center for Biological Pathway at the UT MD Anderson Cancer Center, S. G. Komen [SAC110016]; Sister Institution Fund of China Medical University and Hospital; UT MD Anderson Cancer Center; Cancer Research Center of Excellence, Taiwan [D0H102-TD-C-111-005]; Private University grant, Taiwan [NSC99-2632-B-039-001-MY3]; Program for Stem Cell and Regenerative Medicine Frontier Research, Taiwan [NSC101-2321-B-039-001]; National Cancer Institute [P30CA016672, P30CA008748] Funding Source: NIH RePORTER
NR 27
TC 304
Z9 350
U1 0
U2 147
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 16
PY 2013
VL 497
IS 7449
BP 383
EP 387
DI 10.1038/nature12080
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 144PN
UT WOS:000318952000041
PM 23636329
DA 2026-03-09
ER

PT J
AU Kim, C
   Wong, J
   Wen, JY
   Wang, SR
   Wang, C
   Spiering, S
   Kan, NG
   Forcales, S
   Puri, PL
   Leone, TC
   Marine, JE
   Calkins, H
   Kelly, DP
   Judge, DP
   Chen, HSV
AF Kim, Changsung
   Wong, Johnson
   Wen, Jianyan
   Wang, Shirong
   Wang, Cheng
   Spiering, Sean
   Kan, Natalia G.
   Forcales, Sonia
   Puri, Pier Lorenzo
   Leone, Teresa C.
   Marine, Joseph E.
   Calkins, Hugh
   Kelly, Daniel P.
   Judge, Daniel P.
   Chen, Huei-Sheng Vincent
TI Studying arrhythmogenic right ventricular dysplasia with patient-specific iPSCs
SO NATURE
LA English
DT Article
ID pluripotent stem-cells; differentiation; mechanisms; disease; metabolism; models; heart; gamma
AB Cellular reprogramming of somatic cells to patient-specific induced pluripotent stem cells.(iPSCs) enables in vitro modelling of human genetic disorders for pathogenic investigations and therapeutic screens(1-7). However, using iPSC-derived cardiomyocytes (iPSC-CMs) to model an adult-onset heart disease remains challenging owing to the uncertainty regarding the ability of relatively immature iPSC-CMs to fully recapitulate adult disease phenotypes. Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is an inherited heart disease characterized by pathological fatty infiltration and cardiomyocyte loss predominantly in the right ventricles(8), which is associated with life-threatening ventricular arrhythmias. Over 50% of affected individuals have desmosome gene mutations, most commonly in PKP2, encoding plakophilin-2 (ref. 9). The median age at presentation of ARVD/C is 26 years(8). We used previously published methods(1,10) to generate iPSC lines from fibroblasts of two patients with ARVD/C and PKP2 mutations(11,12). Mutant PKP2 iPSC-CMs demonstrate abnormal plakoglobin nuclear translocation and decreased beta-catenin activity(13) in cardiogenic conditions; yet, these abnormal features are insufficient to reproduce the pathological phenotypes of ARVD/C in standard cardiogenic conditions. Here we show that induction of adult-like metabolic energetics from an embryonic/glycolytic state and abnormal peroxisome proliferator-activated receptor gamma (PPAR-gamma) activation underlie the pathogenesis of ARVD/C. By co-activating normal PPAR-alpha-dependent metabolism and abnormal PPAR-gamma pathway in beating embryoid bodies (EBs) with defined media, we established an efficient ARVD/C in vitro model within 2 months. This model manifests exaggerated lipogenesis and apoptosis in mutant PKP2 iPSC-CMs. iPSC-CMs with a homozygous PKP2 mutation also had calcium-handling deficits. Our study is the first to demonstrate that induction of adult-like metabolism has a critical role in establishing an adult-onset disease model using patient-specific iPSCs. Using this model, we revealed crucial pathogenic insights that metabolic derangement in adult-like metabolic milieu underlies ARVD/C pathologies, enabling us to propose novel disease-modifying therapeutic strategies.
C1 [Kim, Changsung; Wong, Johnson; Wen, Jianyan; Wang, Shirong; Wang, Cheng; Chen, Huei-Sheng Vincent] Sanford Burnham Med Res Inst, Del E Webb Neurosci Aging & Stem Cell Res Ctr, La Jolla, CA 92037 USA.
   [Wen, Jianyan] China Japan Friendship Hosp, Dept Cardiovasc Surg, Beijing 100029, Peoples R China.
   [Spiering, Sean; Kan, Natalia G.; Forcales, Sonia; Puri, Pier Lorenzo] Sanford Burnham Med Res Inst, Muscle Regenerat & Dev Program, La Jolla, CA 92037 USA.
   [Puri, Pier Lorenzo] IRCCS Fdn Santa Lucia, Dulbecco Telethon Inst, I-00179 Rome, Italy.
   [Leone, Teresa C.; Kelly, Daniel P.] Sanford Burnham Med Res Inst, Diabet & Obes Res Ctr, Orlando, FL 32827 USA.
   [Marine, Joseph E.; Calkins, Hugh; Judge, Daniel P.] Johns Hopkins Univ, Sch Med, Dept Med Cardiol, Baltimore, MD 21287 USA.
   [Chen, Huei-Sheng Vincent] Univ Calif San Diego, Dept Med Cardiol, San Diego, CA 92103 USA.
C3 Sanford Burnham Prebys Medical Discovery Institute; China-Japan Friendship Hospital; Sanford Burnham Prebys Medical Discovery Institute; IRCCS Santa Lucia; Fondazione Telethon; Dulbecco Telethon Institute (DTI); Sanford Burnham Prebys Medical Discovery Institute; Johns Hopkins University; University of California System; University of California San Diego
RP Chen, HSV (corresponding author), Sanford Burnham Med Res Inst, Del E Webb Neurosci Aging & Stem Cell Res Ctr, La Jolla, CA 92037 USA.
EM hsv_chen@burnham.org
FU Scripps Research Institute; NIH [RO1 HL058493, RO1 HL101189, RO1 AR056712, RO1 AR052779, RO1 HL105194]; California Institute of Regenerative Medicine (CIRM) [RS1-00171-1, RB2-01512, RB4-06276]; Fondazione Telethon Funding Source: Custom; National Heart Lung and Blood Institute [R01HL058493] Funding Source: NIH RePORTER; National Institute of Arthritis and Musculoskeletal and Skin Diseases [R01AR056712] Funding Source: NIH RePORTER
NR 30
TC 422
Z9 496
U1 0
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 FEB 7
PY 2013
VL 494
IS 7435
BP 105
EP 110
DI 10.1038/nature11799
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 087DJ
UT WOS:000314741200043
PM 23354045
DA 2026-03-09
ER

PT J
AU Senyo, SE
   Steinhauser, ML
   Pizzimenti, CL
   Yang, VK
   Cai, L
   Wang, M
   Wu, TD
   Guerquin-Kern, JL
   Lechene, CP
   Lee, RT
AF Senyo, Samuel E.
   Steinhauser, Matthew L.
   Pizzimenti, Christie L.
   Yang, Vicky K.
   Cai, Lei
   Wang, Mei
   Wu, Ting-Di
   Guerquin-Kern, Jean-Luc
   Lechene, Claude P.
   Lee, Richard T.
TI Mammalian heart renewal by pre-existing cardiomyocytes
SO NATURE
LA English
DT Article
ID stem-cells; mouse; regeneration; turnover
AB Although recent studies have revealed that heart cells are generated in adult mammals, the frequency of generation and the source of new heart cells are not yet known. Some studies suggest a high rate of stem cell activity with differentiation of progenitors to cardiomyocytes(1). Other studies suggest that new cardiomyocytes are born at a very low rate(2-4), and that they may be derived from the division of pre-existing cardiomyocytes. Here we show, by combining two different pulse-chase approaches-genetic fate-mapping with stable isotope labelling, and multi-isotope imaging mass spectrometry-that the genesis of cardiomyocytes occurs at a low rate by the division of pre-existing cardiomyocytes during normal ageing, a process that increases adjacent to areas of myocardial injury. We found that cell cycle activity during normal ageing and after injury led to polyploidy and multinucleation, but also to new diploid, mononucleate cardiomyocytes. These data reveal pre-existing cardiomyocytes as the dominant source of cardiomyocyte replacement in normal mammalian myocardial homeostasis as well as after myocardial injury.
C1 [Senyo, Samuel E.; Steinhauser, Matthew L.; Pizzimenti, Christie L.; Yang, Vicky K.; Cai, Lei; Lee, Richard T.] Brigham & Womens Hosp, Dept Med, Div Cardiovasc, Cambridge, MA 02139 USA.
   [Senyo, Samuel E.; Steinhauser, Matthew L.; Pizzimenti, Christie L.; Yang, Vicky K.; Cai, Lei; Wang, Mei; Lechene, Claude P.; Lee, Richard T.] Harvard Univ, Sch Med, Cambridge, MA 02139 USA.
   [Wu, Ting-Di; Guerquin-Kern, Jean-Luc] INSERM, U759, F-91405 Orsay, France.
   [Wu, Ting-Di; Guerquin-Kern, Jean-Luc] Inst Curie, Lab Microscopie Ion, F-91405 Orsay, France.
   [Wang, Mei; Lechene, Claude P.] Natl Resource Imaging Mass Spectrometry, Cambridge, MA 02139 USA.
   [Wang, Mei; Lechene, Claude P.] Brigham & Womens Hosp, Dept Med, Div Genet, Cambridge, MA 02139 USA.
   [Lee, Richard T.] Harvard Stem Cell Inst, Cambridge, MA 02139 USA.
C3 Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard University; Universite PSL; UNICANCER; Institut Curie; Institut National de la Sante et de la Recherche Medicale (Inserm); UNICANCER; Universite PSL; Institut Curie; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard University
RP Lee, RT (corresponding author), Brigham & Womens Hosp, Dept Med, Div Cardiovasc, Cambridge, MA 02139 USA.
EM rlee@partners.org
FU National Institutes of Health (NIH) [F32 HL108570, K08 DK090147, EB001974, AG034641, AG032977, AG040019]; American Heart Association (AHA FTF); Future Leaders in Cardiovascular Medicine; Watkins Cardiovascular Leadership Award; Ellison Medical Foundation [AG-SS-2215-08]; Harvard Stem Cell Institute
CR ADLER CP, 1986, J MOL CELL CARDIOL, V18, P39, DOI 10.1016/S0022-2828(86)80981-6
   Beltrami AP, 2003, CELL, V114, P763, DOI 10.1016/S0092-8674(03)00687-1
   Bergmann O, 2011, EXP CELL RES, V317, P188, DOI 10.1016/j.yexcr.2010.08.017
   Bergmann O, 2009, SCIENCE, V324, P98, DOI 10.1126/science.1164680
   Dong F, 2012, CIRCULATION, V126, P314, DOI 10.1161/CIRCULATIONAHA.111.082453
   Hosoda T, 2011, J THROMB HAEMOST, V9, P151, DOI 10.1111/j.1538-7836.2011.04363.x
   Hosoda T, 2009, P NATL ACAD SCI USA, V106, P17169, DOI 10.1073/pnas.0903089106
   Hsieh PCH, 2007, NAT MED, V13, P970, DOI 10.1038/nm1618
   Hu VW, 2002, FASEB J, V16, P1456, DOI 10.1096/fj.02-0142fje
   Jopling C, 2010, NATURE, V464, P606, DOI 10.1038/nature08899
   Kajstura J, 2010, CIRC RES, V107, P1374, DOI 10.1161/CIRCRESAHA.110.231498
   Katzberg AA, 1977, AM J ANAT, V149, P489
   Kikuchi K, 2010, NATURE, V464, P601, DOI 10.1038/nature08804
   KLEIN PD, 1986, J CLIN PHARMACOL, V26, P378, DOI 10.1002/j.1552-4604.1986.tb03544.x
   Laflamme MA, 2005, NAT BIOTECHNOL, V23, P845, DOI 10.1038/nbt1117
   Laflamme MA, 2011, NATURE, V473, P326, DOI 10.1038/nature10147
   Lechene Claude, 2006, J BIOL, V5, P20, DOI 10.1186/jbiol42
   Li FQ, 1996, J MOL CELL CARDIOL, V28, P1737, DOI 10.1006/jmcc.1996.0163
   Loffredo FS, 2011, CELL STEM CELL, V8, P389, DOI 10.1016/j.stem.2011.02.002
   Nikolova V, 2004, J CLIN INVEST, V113, P357, DOI 10.1172/JCI200419448
   Orlic D, 2001, NATURE, V410, P701, DOI 10.1038/35070587
   Porrello ER, 2011, SCIENCE, V331, P1078, DOI 10.1126/science.1200708
   Soonpaa MH, 1997, AM J PHYSIOL-HEART C, V272, PH220, DOI 10.1152/ajpheart.1997.272.1.H220
   Steinhauser ML, 2012, NATURE, V481, P516, DOI 10.1038/nature10734
   Walsh S, 2010, CARDIOVASC RES, V86, P365, DOI 10.1093/cvr/cvq005
   Wilson A, 2008, CELL, V135, P1118, DOI 10.1016/j.cell.2008.10.048
   Zhang DS, 2012, NATURE, V481, P520, DOI 10.1038/nature10745
NR 27
TC 1083
Z9 1308
U1 1
U2 231
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 17
PY 2013
VL 493
IS 7432
BP 433
EP U186
DI 10.1038/nature11682
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 071TA
UT WOS:000313615900058
PM 23222518
DA 2026-03-09
ER

PT J
AU Klein, CA
AF Klein, Christoph A.
TI Selection and adaptation during metastatic cancer progression
SO NATURE
LA English
DT Article
ID disseminated tumor-cells; primary colorectal cancers; breast-cancer; bone-marrow; clonal evolution; in-situ; adhesion molecule; genomic analysis; genetic-analysis; diversity
AB Cancer is often regarded as a process of asexual evolution driven by genomic and genetic instability. Mutation, selection and adaptation are by convention thought to occur primarily within, and to a lesser degree outside, the primary tumour. However, disseminated cancer cells that remain after 'curative' surgery exhibit extreme genomic heterogeneity before the manifestation of metastasis. This heterogeneity is later reduced by selected clonal expansion, suggesting that the disseminated cells had yet to acquire key traits of fully malignant cells. Abrogation of the cells' progression outside the primary tumour implies new challenges and opportunities for diagnosis and adjuvant therapies.
C1 [Klein, Christoph A.] Univ Regensburg, D-93053 Regensburg, Germany.
   [Klein, Christoph A.] Fraunhofer Inst Toxicol & Expt Med, Personalized Tumor Therapy Project Grp, Regensburg, Germany.
C3 University of Regensburg; Fraunhofer Gesellschaft; Fraunhofer Germany; Fraunhofer Toxicology & Experimental Medicine
RP Klein, CA (corresponding author), Univ Regensburg, D-93053 Regensburg, Germany.
EM christoph.klein@ukr.de
NR 104
TC 224
Z9 254
U1 0
U2 80
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 19
PY 2013
VL 501
IS 7467
BP 365
EP 372
DI 10.1038/nature12628
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 219XT
UT WOS:000324545700035
PM 24048069
DA 2026-03-09
ER

PT J
AU Hedman, MM
   Gosmeyer, CM
   Nicholson, PD
   Sotin, C
   Brown, RH
   Clark, RN
   Baines, KH
   Buratti, BJ
   Showalter, MR
AF Hedman, M. M.
   Gosmeyer, C. M.
   Nicholson, P. D.
   Sotin, C.
   Brown, R. H.
   Clark, R. N.
   Baines, K. H.
   Buratti, B. J.
   Showalter, M. R.
TI An observed correlation between plume activity and tidal stresses on Enceladus
SO NATURE
LA English
DT Article
ID water reservoir; cassini iss; south-pole; e-ring; spectrometer; eruptions; origin; vims; mass
AB Saturn's moon Enceladus emits a plume of water vapour and micrometre-sized ice particles from a series of warm fissures located near its south pole(1-10). This geological activity could be powered or controlled by variations in the tidal stresses experienced by Enceladus as it moves around its slightly eccentric orbit. The specific mechanisms by which these varying stresses are converted into heat, however, are still being debated(11-16). Furthermore, it has proved difficult to find a clear correlation between the predicted tidal forces and measured temporal variations in the plume's gas content(17-19) or the particle flux from individual sources(20,21). Here we report that the plume's horizontally integrated brightness is several times greater when Enceladus is near the point in its eccentric orbit where it is furthest from Saturn (apocentre) than it is when near the point of closest approach to the planet (pericentre). More material therefore seems to be escaping from beneath Enceladus' surface at times when geophysical models predict its fissures should be under tension(12,15,16) and therefore may be wider open.
C1 [Hedman, M. M.; Nicholson, P. D.] Cornell Univ, Ctr Radiophys & Space Res, Ithaca, NY 14853 USA.
   [Gosmeyer, C. M.] Indiana Univ, Dept Astron, Bloomington, IN 47405 USA.
   [Sotin, C.; Baines, K. H.; Buratti, B. J.] CALTECH, Jet Prop Lab, Pasadena, CA 91109 USA.
   [Brown, R. H.] Univ Arizona, Dept Planetary Sci, Lunar & Planetary Lab, Tucson, AZ 85721 USA.
   [Clark, R. N.] US Geol Survey, Denver Fed Ctr, Denver, CO 80225 USA.
   [Showalter, M. R.] SETI Inst, Mountain View, CA 94043 USA.
C3 Cornell University; Indiana University System; Indiana University Bloomington; National Aeronautics & Space Administration (NASA); NASA Jet Propulsion Laboratory (JPL); California Institute of Technology; University of Arizona; United States Department of the Interior; United States Geological Survey; SETI Institute
RP Hedman, MM (corresponding author), Cornell Univ, Ctr Radiophys & Space Res, Ithaca, NY 14853 USA.
EM mmhedman@astro.cornell.edu
FU VIMS team; Cassini project; NASA [NNX12AC29G]; Cornell University; NASA [NNX12AC29G, 52379] Funding Source: Federal RePORTER
NR 23
TC 132
Z9 149
U1 0
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 AUG 8
PY 2013
VL 500
IS 7461
BP 182
EP 184
DI 10.1038/nature12371
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 197CH
UT WOS:000322825500029
PM 23903658
DA 2026-03-09
ER

PT J
AU Kunisaki, Y
   Bruns, I
   Scheiermann, C
   Ahmed, J
   Pinho, S
   Zhang, DC
   Mizoguchi, T
   Wei, QZ
   Lucas, D
   Ito, K
   Mar, JC
   Bergman, A
   Frenette, PS
AF Kunisaki, Yuya
   Bruns, Ingmar
   Scheiermann, Christoph
   Ahmed, Jalal
   Pinho, Sandra
   Zhang, Dachuan
   Mizoguchi, Toshihide
   Wei, Qiaozhi
   Lucas, Daniel
   Ito, Keisuke
   Mar, Jessica C.
   Bergman, Aviv
   Frenette, Paul S.
TI Arteriolar niches maintain haematopoietic stem cell quiescence
SO NATURE
LA English
DT Article
ID self-renewal; progenitor cells; expression; microdomains; osteopontin; component; dormancy; pool
AB Cell cycle quiescence is a critical feature contributing to haematopoietic stem cell (HSC) maintenance. Although various candidate stromal cells have been identified as potential HSC niches, the spatial localization of quiescent HSCs in the bone marrow remains unclear. Here, using a novel approach that combines whole-mount confocal immunofluorescence imaging techniques and computational modelling to analyse significant three-dimensional associations in the mouse bone marrow among vascular structures, stromal cells and HSCs, we show that quiescent HSCs associate specifically with small arterioles that are preferentially found in endosteal bone marrow. These arterioles are ensheathed exclusively by rare NG2 (also known as CSPG4)(+) pericytes, distinct from sinusoid-associated leptin receptor (LEPR)(+) cells. Pharmacological or genetic activation of the HSC cell cycle alters the distribution of HSCs from NG2(+) periarteriolar niches to LEPR+ perisinusoidal niches. Conditional depletion of NG2(+) cells induces HSC cycling and reduces functional long-term repopulating HSCs in the bone marrow. These results thus indicate that arteriolar niches are indispensable for maintaining HSC quiescence.
C1 [Kunisaki, Yuya; Bruns, Ingmar; Scheiermann, Christoph; Ahmed, Jalal; Pinho, Sandra; Zhang, Dachuan; Mizoguchi, Toshihide; Wei, Qiaozhi; Lucas, Daniel; Ito, Keisuke; Frenette, Paul S.] Albert Einstein Coll Med, Ruth L & David S Gottesman Inst Stem Cell & Regen, Bronx, NY 10461 USA.
   [Kunisaki, Yuya; Bruns, Ingmar; Scheiermann, Christoph; Pinho, Sandra; Zhang, Dachuan; Mizoguchi, Toshihide; Wei, Qiaozhi; Ito, Keisuke; Frenette, Paul S.] Albert Einstein Coll Med, Dept Cell Biol, Bronx, NY 10461 USA.
   [Bruns, Ingmar] Univ Dusseldorf, Dept Hematol Oncol & Clin Immunol, D-40225 Dusseldorf, Germany.
   [Ahmed, Jalal] Mt Sinai Sch Med, New York, NY 10029 USA.
   [Lucas, Daniel; Ito, Keisuke; Frenette, Paul S.] Albert Einstein Coll Med, Dept Med, Bronx, NY 10461 USA.
   [Mar, Jessica C.; Bergman, Aviv] Albert Einstein Coll Med, Dept Syst & Computat Biol, Bronx, NY 10461 USA.
   [Mar, Jessica C.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10461 USA.
C3 Montefiore Medical Center; Albert Einstein College of Medicine; Yeshiva University; Yeshiva University; Montefiore Medical Center; Albert Einstein College of Medicine; Heinrich Heine University Dusseldorf; Icahn School of Medicine at Mount Sinai; Montefiore Medical Center; Albert Einstein College of Medicine; Yeshiva University; Yeshiva University; Montefiore Medical Center; Albert Einstein College of Medicine; Yeshiva University; Montefiore Medical Center; Albert Einstein College of Medicine
RP Frenette, PS (corresponding author), Albert Einstein Coll Med, Ruth L & David S Gottesman Inst Stem Cell & Regen, Bronx, NY 10461 USA.
EM paul.frenette@einstein.yu.edu
FU New York Stem Cell Foundation-Druckenmiller Fellowship; German Research Foundation (DFG) (Emmy-Noether-Program); National Institutes of Health (R01 grants) [DK056638, HL069438, HL097700];  [T32 063754]; National Heart Lung and Blood Institute [R01HL069438] Funding Source: NIH RePORTER; National Institute of Diabetes and Digestive and Kidney Diseases [R01DK056638, R01DK098263] Funding Source: NIH RePORTER
NR 48
TC 955
Z9 1088
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 OCT 31
PY 2013
VL 502
IS 7473
BP 637
EP +
DI 10.1038/nature12612
PG 21
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 243CC
UT WOS:000326293200038
PM 24107994
DA 2026-03-09
ER

PT J
AU Diard, M
   Garcia, V
   Maier, L
   Remus-Emsermann, MNP
   Regoes, RR
   Ackermann, M
   Hardt, WD
AF Diard, Mederic
   Garcia, Victor
   Maier, Lisa
   Remus-Emsermann, Mitja N. P.
   Regoes, Roland R.
   Ackermann, Martin
   Hardt, Wolf-Dietrich
TI Stabilization of cooperative virulence by the expression of an avirulent phenotype
SO NATURE
LA English
DT Article
ID enterica serovar typhimurium; iii secretion system; bacterial virulence; multiple infection; social evolution; dynamics; pathogenicity; populations; microbiota
AB Pathogens often infect hosts through collective actions: they secrete growth-promoting compounds or virulence factors, or evoke host reactions that fuel the colonization of the host. Such behaviours are vulnerable to the rise of mutants that benefit from the collective action without contributing to it; how these behaviours can be evolutionarily stable is not well understood(1). We address this question using the intestinal pathogen Salmonella enterica serovar Typhimurium (hereafter termed S. typhimurium), which manipulates its host to induce inflammation, and thereby outcompetes the commensal microbiota(2,3). Notably, the virulence factors needed for host manipulation are expressed in a bistable fashion, leading to a slow-growing subpopulation that expresses virulence genes, and a fast-growing subpopulation that is phenotypically avirulent(4,5). Here we show that the expression of the genetically identical but phenotypically avirulent subpopulation is essential for the evolutionary stability of virulence in this pathogen. Using a combination of mathematical modelling, experimental evolution and competition experiments we found that within-host evolution leads to the emergence of mutants that are genetically avirulent and fast-growing. These mutants are defectors that exploit inflammation without contributing to it. In infection experiments initiated with wild-type S. typhimurium, defectors increase only slowly in frequency. In a genetically modified S. typhimurium strain in which the phenotypically avirulent subpopulation is reduced in size, defectors rise more rapidly, inflammation ceases prematurely, and S. typhimurium is quickly cleared from the gut. Our results establish that host manipulation by S. typhimurium is a cooperative trait that is vulnerable to the rise of avirulent defectors; the expression of a phenotypically avirulent subpopulation that grows as fast as defectors slows down this process, and thereby promotes the evolutionary stability of virulence. This points to a key role of bistable virulence gene expression in stabilizing cooperative virulence and may lead the way to new approaches, for controlling pathogens.
C1 [Diard, Mederic; Maier, Lisa; Remus-Emsermann, Mitja N. P.; Hardt, Wolf-Dietrich] ETH, Inst Microbiol, CH-8093 Zurich, Switzerland.
   [Garcia, Victor; Regoes, Roland R.] ETH, Inst Integrat Biol, CH-8092 Zurich, Switzerland.
   [Ackermann, Martin] Swiss Fed Inst Technol, Dept Environm Syst Sci, CH-8600 Dubendorf, Switzerland.
   [Ackermann, Martin] Dept Environm Microbiol Eawag, CH-8600 Dubendorf, Switzerland.
C3 Swiss Federal Institutes of Technology Domain; ETH Zurich; Swiss Federal Institutes of Technology Domain; ETH Zurich; Swiss Federal Institutes of Technology Domain; ETH Zurich
RP Regoes, RR (corresponding author), ETH, Inst Integrat Biol, Univ Str 16, CH-8092 Zurich, Switzerland.
EM roland.regoes@env.ethz.ch; martin.ackermann@env.ethz.ch; wolf-dietrich.hardt@micro.biol.ethz.ch
FU Fondation pour la Recherche Medicale; Swiss National Science Foundation
NR 24
TC 261
Z9 297
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 21
PY 2013
VL 494
IS 7437
BP 353
EP 356
DI 10.1038/nature11913
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 095CS
UT WOS:000315312900038
PM 23426324
DA 2026-03-09
ER

PT J
AU Benner, EJ
   Luciano, D
   Jo, R
   Abdi, K
   Paez-Gonzalez, P
   Sheng, HX
   Warner, DS
   Liu, CL
   Eroglu, C
   Kuo, CT
AF Benner, Eric J.
   Luciano, Dominic
   Jo, Rebecca
   Abdi, Khadar
   Paez-Gonzalez, Patricia
   Sheng, Huaxin
   Warner, David S.
   Liu, Chunlei
   Eroglu, Cagla
   Kuo, Chay T.
TI Protective astrogenesis from the SVZ niche after injury is controlled by Notch modulator Thbs4
SO NATURE
LA English
DT Article
ID adult subventricular zone; cerebral-ischemia; stem-cell; astrocytes; thrombospondin-4; gliogenesis; neuroblasts; recovery; reveals; repair
AB Postnatal/adult neural stem cells (NSCs) within the rodent subventricular zone (SVZ; also called subependymal zone) generate doublecortin (Dcx)(+) neuroblasts that migrate and integrate into olfactory bulb circuitry(1,2). Continuous production of neuroblasts is controlled by the SVZ microenvironmental niche(3,4). It is generally thought that enhancing the neurogenic activities of endogenous NSCs may provide needed therapeutic options for disease states and after brain injury. However, SVZ NSCs can also differentiate into astrocytes. It remains unclear whether there are conditions that favour astrogenesis over neurogenesis in the SVZ niche, and whether astrocytes produced there have different properties compared with astrocytes produced elsewhere in the brain(5). Here we show in mice that SVZ-generated astrocytes express high levels of thrombospondin 4 (Thbs4)(6,7), a secreted homopentameric glycoprotein, in contrast to cortical astrocytes, which express low levels of Thbs4. We found that localized photothrombotic/ischaemic cortical injury initiates a marked increase in Thbs4(hi) astrocyte production from the postnatal SVZ niche. Tamoxifen-inducible nestin-creER(tm)4 lineage tracing demonstrated that it is these SVZ-generated Thbs4(hi) astrocytes, and not Dcx(+) neuroblasts, that home-in on the injured cortex. This robust post-injury astrogenic response required SVZ Notch activation modulated by Thbs4 via direct Notch1 receptor binding and endocytosis to activate downstream signals, including increased Nfia transcription factor expression important for glia production(8). Consequently, Thbs4 homozygous knockout mice (Thbs4(KO/KO)) showed severe defects in cortical-injury-induced SVZ astrogenesis, instead producing cells expressing Dcx migrating from SVZ to the injury sites. These alterations in cellular responses resulted in abnormal glial scar formation after injury, and significantly increased microvascular haemorrhage into the brain parenchyma of Thbs4(KO/KO) mice. Taken together, these findings have important implications for post-injury applications of endogenous and transplanted NSCs in the therapeutic setting, as well as disease states where Thbs family members have important roles(9,10).
C1 [Benner, Eric J.; Jo, Rebecca; Kuo, Chay T.] Duke Univ, Sch Med, Dept Pediat, George & Jean Brumley Neonatal Perinatal Res Inst, Durham, NC 27710 USA.
   [Luciano, Dominic; Jo, Rebecca; Abdi, Khadar; Paez-Gonzalez, Patricia; Eroglu, Cagla; Kuo, Chay T.] Duke Univ, Sch Med, Dept Cell Biol, Durham, NC 27710 USA.
   [Luciano, Dominic; Eroglu, Cagla; Kuo, Chay T.] Duke Univ, Sch Med, Dept Neurobiol, Durham, NC 27710 USA.
   [Sheng, Huaxin; Warner, David S.] Duke Univ, Sch Med, Dept Anesthesiol, Durham, NC 27710 USA.
   [Liu, Chunlei] Duke Univ, Sch Med, Dept Radiol, Brain Imaging & Anal Ctr, Durham, NC 27710 USA.
   [Liu, Chunlei] Duke Univ, Sch Med, Dept Radiol, Durham, NC 27710 USA.
   [Eroglu, Cagla; Kuo, Chay T.] Duke Univ, Sch Med, Duke Inst Brain Sci, Durham, NC 27710 USA.
   [Kuo, Chay T.] Duke Univ, Sch Med, Preston Robert Tisch Brain Tumor Ctr, Durham, NC 27710 USA.
C3 Duke University; Duke University; Duke University; Duke University; Duke University; Duke University; Duke University; Duke University
RP Kuo, CT (corresponding author), Duke Univ, Sch Med, Dept Pediat, George & Jean Brumley Neonatal Perinatal Res Inst, Durham, NC 27710 USA.
EM chay.kuo@duke.edu
FU National Biomedical Technology Resource Center [P41 RR005959, P41 EB015897]; George and Jean Brumley Endowment; Sontag Foundation; David and Lucile Packard Foundation; March of Dimes; NIH [1 DP2 OD004453-01]
NR 39
TC 227
Z9 285
U1 2
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 MAY 16
PY 2013
VL 497
IS 7449
BP 369
EP +
DI 10.1038/nature12069
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 144PN
UT WOS:000318952000038
PM 23615612
DA 2026-03-09
ER

PT J
AU Chandra, P
   Coleman, P
   Flint, R
AF Chandra, Premala
   Coleman, Piers
   Flint, Rebecca
TI Hastatic order in the heavy-fermion compound URu2Si2
SO NATURE
LA English
DT Article
ID hidden-order; magnetic-property; field; system; state; superconductivity; excitations; transition; lattice; phase
AB The development of collective long-range order by means of phase transitions occurs by the spontaneous breaking of fundamental symmetries. Magnetism is a consequence of broken time-reversal symmetry, whereas superfluidity results from broken gauge invariance. The broken symmetry that develops below 17.5 kelvin in the heavy-fermion compound URu2Si2 has long eluded such identification. Here we show that the recent observation of Ising quasiparticles in URu2Si2 results from a spinor order parameter that breaks double time-reversal symmetry, mixing states of integer and half-integer spin. Such 'hastatic' order hybridizes uranium-atom conduction electrons with Ising 5f(2) states to produce Ising quasiparticles; it accounts for the large entropy of condensation and the magnetic anomaly observed in torque magnetometry. Hastatic order predicts a tiny transverse moment in the conduction-electron 'sea', a colossal Ising anisotropy in the nonlinear susceptibility anomaly and a resonant, energy-dependent nematicity in the tunnelling density of states.
C1 [Chandra, Premala; Coleman, Piers] Rutgers State Univ, Dept Phys & Astron, Ctr Mat Theory, Piscataway, NJ 08854 USA.
   [Coleman, Piers] Univ London, Dept Phys, Egham TW20 0EX, Surrey, England.
   [Flint, Rebecca] MIT, Dept Phys, Cambridge, MA 02139 USA.
C3 Rutgers University System; Rutgers University New Brunswick; University of London; Royal Holloway University London; Massachusetts Institute of Technology (MIT)
RP Coleman, P (corresponding author), Rutgers State Univ, Dept Phys & Astron, Ctr Mat Theory, 136 Frelinghuysen Rd, Piscataway, NJ 08854 USA.
EM coleman@physics.rutgers.edu
FU Simons Foundation; US National Science Foundation [DMR 0907179, 1066293]; US National Science Foundation I2CAM International Materials Institute [DMR-0844115]; Direct For Mathematical & Physical Scien; Division Of Materials Research [0907179] Funding Source: National Science Foundation
NR 49
TC 116
Z9 130
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 JAN 31
PY 2013
VL 493
IS 7434
BP 621
EP 626
DI 10.1038/nature11820
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 080CU
UT WOS:000314219600046
PM 23364741
DA 2026-03-09
ER

PT J
AU Prokopenko, MG
   Hirst, MB
   De Brabandere, L
   Lawrence, DJP
   Berelson, WM
   Granger, J
   Chang, BX
   Dawson, S
   Crane, EJ
   Chong, L
   Thamdrup, B
   Townsend-Small, A
   Sigman, DM
AF Prokopenko, M. G.
   Hirst, M. B.
   De Brabandere, L.
   Lawrence, D. J. P.
   Berelson, W. M.
   Granger, J.
   Chang, B. X.
   Dawson, S.
   Crane, E. J., III
   Chong, L.
   Thamdrup, B.
   Townsend-Small, A.
   Sigman, D. M.
TI Nitrogen losses in anoxicmarine sediments driven by Thioploca-anammox bacterial consortia
SO NATURE
LA English
DT Article
ID continental-margin; methane oxidation; sulfur bacteria; north pacific; fresh-water; marine; denitrification; nitrate; diagenesis; carbon
AB Ninety per cent of marine organic matter burial occurs in continental margin sediments, where a substantial fraction of organic carbon escapes oxidation and enters long-term geologic storage within sedimentary rocks. In such environments, microbial metabolism is limited by the diffusive supply of electron acceptors. One strategy to optimize energy yields in a resource-limited habitat is symbiotic metabolite exchange among microbial associations(1,2). Thermodynamic and geochemical considerations indicate that microbial cometabolisms are likely to play a critical part in sedimentary organic carbon cycling(3-5). Yet only one association, between methanotrophic archaea and sulphate-reducing bacteria, has been demonstrated in marine sedimentsin situ(6,7), and little is known of the role of microbial symbiotic interactions in other sedimentary biogeochemical cycles(8). Here we report in situ molecular and incubation-based evidence for a novel symbiotic consortium between two chemolithotrophic bacteria-anaerobic ammonium-oxidizing (anammox) bacteria and the nitrate-sequestering sulphur-oxidizing Thioploca species-in anoxic sediments of the Soledad basin at the Mexican Pacific margin. A mass balance of benthic solute fluxes and the corresponding nitrogen isotope composition of nitrate and ammonium fluxes indicate that anammox bacteria rely on Thioploca species for the supply of metabolic substrates and account for about 57 +/- 21 per cent of the total benthic N-2 production. We show that Thioploca-anammox symbiosis intensifies benthic fixed nitrogen losses in anoxic sediments, bypassing diffusion-imposed limitations by efficiently coupling the carbon, nitrogen and sulphur cycles.
C1 [Prokopenko, M. G.] Pomona Coll, Dept Geol, Claremont, CA 91711 USA.
   [Prokopenko, M. G.; Berelson, W. M.; Chong, L.] Univ So Calif, Dept Earth Sci, Los Angeles, CA 90089 USA.
   [Hirst, M. B.; Dawson, S.] Univ Calif Davis, Dept Microbiol & Mol Genet, Davis, CA 95616 USA.
   [De Brabandere, L.; Thamdrup, B.] Univ Southern Denmark, Dept Biol, Nord Ctr Earth Evolut, DK-5230 Odense M, Denmark.
   [Lawrence, D. J. P.; Crane, E. J., III] Pomona Coll, Dept Biol, Claremont, CA 91711 USA.
   [Granger, J.] Univ Connecticut, Dept Marine Sci, Groton, CT 06340 USA.
   [Chang, B. X.; Sigman, D. M.] Princeton Univ, Dept Geosci, Princeton, NJ 08544 USA.
   [Townsend-Small, A.] Univ Cincinnati, Dept Geol, Cincinnati, OH 45221 USA.
C3 Claremont Colleges; Pomona College; University of Southern California; University of California System; University of California Davis; University of Southern Denmark; Claremont Colleges; Pomona College; University of Connecticut; Princeton University; University System of Ohio; University of Cincinnati
RP Prokopenko, MG (corresponding author), Pomona Coll, Dept Geol, Claremont, CA 91711 USA.
EM prokopen@usc.edu
FU NSF OCE [OCE-0727123]
CR Ashelford KE, 2006, APPL ENVIRON MICROB, V72, P5734, DOI 10.1128/AEM.00556-06
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   Bernhard JM, 2004, GEOLOGIC SOC AM, V379, P35
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   Jensen MM, 2011, ISME J, V5, P1660, DOI 10.1038/ismej.2011.44
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   Kuenen JG, 2008, NAT REV MICROBIOL, V6, P320, DOI 10.1038/nrmicro1857
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NR 43
TC 97
Z9 112
U1 9
U2 398
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 8
PY 2013
VL 500
IS 7461
BP 194
EP +
DI 10.1038/nature12365
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 197CH
UT WOS:000322825500032
PM 23925243
DA 2026-03-09
ER

PT J
AU Xu, T
   Agrawal, A
   Abashin, M
   Chau, KJ
   Lezec, HJ
AF Xu, Ting
   Agrawal, Amit
   Abashin, Maxim
   Chau, Kenneth J.
   Lezec, Henri J.
TI All-angle negative refraction and active flat lensing of ultraviolet light
SO NATURE
LA English
DT Article
ID index
AB Decades ago, Veselago(1) predicted that a material with simultaneously negative electric and magnetic polarization responses would yield a 'left-handed' medium in which light propagates with opposite phase and energy velocities-a condition described by a negative refractive index. He proposed that a flat slab of left-handed material possessing an isotropic refractive index of 21 could act like an imaging lens in free space. Left-handed materials do not occur naturally, and it has only recently become possible to achieve a left-handed response using metamaterials, that is, electromagnetic structures engineered on subwavelength scales to elicit tailored polarization responses. So far, left-handed responses have typically been implemented using resonant metamaterials composed of periodic arrays of unit cells containing inductive-capacitive resonators and conductive wires. Negative refractive indices that are isotropic in two(2) or three(3) dimensions at microwave frequencies have been achieved in resonant metamaterials with centimetre-scale features. Scaling the left-handed response to higher frequencies, such as infrared or visible, has been done by shrinking critical dimensions to submicrometre scales by means of top-down nanofabrication(4). This miniaturization has, however, so far been achieved at the cost of reduced unit-cell symmetry, yielding a refractive index that is negative along only one axis. Moreover, lithographic scaling limits have so far precluded the fabrication of resonant metamaterials with left-handed responses at frequencies beyond the visible(5). Here we report the experimental implementation of a bulk metamaterial with a left-handed response to ultraviolet light. The structure, based on stacked plasmonic waveguides(6), yields an omnidirectional left-handed response for transverse magnetic polarization characterized by a negative refractive index. By engineering the structure to have a refractive index close to -1 over a broad angular range, we achieve Veselago flat lensing, in free space, of arbitrarily shaped, two-dimensional objects beyond the near field. We further demonstrate active, all-optical modulation of the image transferred by the flat lens.
C1 [Xu, Ting; Agrawal, Amit; Abashin, Maxim; Lezec, Henri J.] NIST, Ctr Nanoscale Sci & Technol, Gaithersburg, MD 20899 USA.
   [Xu, Ting; Abashin, Maxim] Univ Maryland, Maryland Nano Ctr, College Pk, MD 20742 USA.
   [Agrawal, Amit] Syracuse Univ, Dept Elect Engn & Comp Sci, Syracuse, NY 13244 USA.
   [Chau, Kenneth J.] Univ British Columbia, Sch Engn, Kelowna, BC V1V 1V7, Canada.
C3 National Institute of Standards & Technology (NIST) - USA; University System of Maryland; University of Maryland College Park; Syracuse University; University of British Columbia
RP Lezec, HJ (corresponding author), NIST, Ctr Nanoscale Sci & Technol, Gaithersburg, MD 20899 USA.
EM hlezec@nist.gov
FU University of Maryland [70NANB10H193]
NR 30
TC 270
Z9 298
U1 1
U2 409
PU NATURE PUBLISHING 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 23
PY 2013
VL 497
IS 7450
BP 470
EP 474
DI 10.1038/nature12158
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 148OG
UT WOS:000319254000043
PM 23698446
DA 2026-03-09
ER

PT J
AU Michalski, JR
   Bleacher, JE
AF Michalski, Joseph R.
   Bleacher, Jacob E.
TI Supervolcanoes within an ancient volcanic province in Arabia Terra, Mars
SO NATURE
LA English
DT Article
ID thermokarst lakes; tharsis region; history; crust; dispersal; meridiani; outcrops; sulfur; lava
AB Several irregularly shaped craters located within Arabia Terra, Mars, represent a new type of highland volcanic construct and together constitute a previously unrecognized Martian igneous province. Similar to terrestrial supervolcanoes, these low-relief paterae possess a range of geomorphic features related to structural collapse, effusive volcanism and explosive eruptions. Extruded lavas contributed to the formation of enigmatic highland ridged plains in Arabia Terra. Outgassed sulphur and erupted fine-grained pyroclastics from these calderas probably fed the formation of altered, layered sedimentary rocks and fretted terrain found throughout the equatorial region. The discovery of a new type of volcanic construct in the Arabia volcanic province fundamentally changes the picture of ancient volcanism and climate evolution on Mars. Other eroded topographic basins in the ancient Martian highlands that have been dismissed as degraded impact craters should be reconsidered as possible volcanic constructs formed in an early phase of widespread, disseminated magmatism on Mars.
C1 [Michalski, Joseph R.] Planetary Sci Inst, Tucson, AZ 85719 USA.
   [Michalski, Joseph R.] Nat Hist Museum, Dept Earth Sci, London SW7 5BD, England.
   [Bleacher, Jacob E.] NASA, Goddard Space Flight Ctr, Greenbelt, MD 20771 USA.
C3 Natural History Museum London; National Aeronautics & Space Administration (NASA); NASA Goddard Space Flight Center
RP Michalski, JR (corresponding author), Planetary Sci Inst, Tucson, AZ 85719 USA.
EM michalski@psi.edu
FU NASA Mars Data Analysis programme
NR 50
TC 79
Z9 92
U1 0
U2 57
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 3
PY 2013
VL 502
IS 7469
BP 47
EP +
DI 10.1038/nature12482
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 227IM
UT WOS:000325106000028
PM 24091975
DA 2026-03-09
ER

PT J
AU Holme, R
   de Viron, O
AF Holme, R.
   de Viron, O.
TI Characterization and implications of intradecadal variations in length of day
SO NATURE
LA English
DT Article
ID electrical-conductivity; magnetic jerk; mantle; rotation; earth; field
AB Variations in Earth's rotation (defined in terms of length of day) arise from external tidal torques, or from an exchange of angular momentum between the solid Earth and its fluid components(1). On short timescales (annual or shorter) the non-tidal component is dominated by the atmosphere, with small contributions from the ocean and hydrological system. On decadal timescales, the dominant contribution is from angular momentum exchange between the solid mantle and fluid outer core. Intradecadal periods have been less clear and have been characterized by signals with a wide range of periods and varying amplitudes, including a peak at about 6 years (refs 2-4). Here, by working in the time domain rather than the frequency domain, we show a clear partition of the non-atmospheric component into only three components: a decadally varying trend, a 5.9-year period oscillation, and jumps at times contemporaneous with geomagnetic jerks. The nature of the jumps in length of day leads to a fundamental change in what class of phenomena may give rise to the jerks, and provides a strong constraint on electrical conductivity of the lower mantle, which can in turn constrain its structure and composition.
C1 [Holme, R.] Univ Liverpool, Sch Environm Sci, Liverpool L69 3GP, Merseyside, England.
   [de Viron, O.] Univ Paris Diderot, Sorbonne Paris Cit, Inst Phys Globe, UMR7154, F-75013 Paris, France.
C3 University of Liverpool; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Earth Sciences & Astronomy (INSU); Universite Paris Cite
RP Holme, R (corresponding author), Univ Liverpool, Sch Environm Sci, Liverpool L69 3GP, Merseyside, England.
EM holme@liv.ac.uk
FU Centre National d'Etudes Spatiales (CNES) through the TOSCA (Terre, Ocean, Surfaces Continentales, Atmosphere) programme; French Institut Universitaire de France; National Oceanographic Partnership Program
NR 27
TC 129
Z9 136
U1 0
U2 43
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 11
PY 2013
VL 499
IS 7457
BP 202
EP +
DI 10.1038/nature12282
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 179YA
UT WOS:000321557600060
PM 23846659
DA 2026-03-09
ER

PT J
AU Dorner, M
   Horwitz, JA
   Donovan, BM
   Labitt, RN
   Budell, WC
   Friling, T
   Vogt, A
   Catanese, MT
   Satoh, T
   Kawai, T
   Akira, S
   Law, M
   Rice, CM
   Ploss, A
AF Dorner, Marcus
   Horwitz, Joshua A.
   Donovan, Bridget M.
   Labitt, Rachael N.
   Budell, William C.
   Friling, Tamar
   Vogt, Alexander
   Catanese, Maria Teresa
   Satoh, Takashi
   Kawai, Taro
   Akira, Shizuo
   Law, Mansun
   Rice, Charles M.
   Ploss, Alexander
TI Completion of the entire hepatitis C virus life cycle in genetically humanized mice
SO NATURE
LA English
DT Article
ID b type-i; targeted disruption; cyclophilin-a; rna; infection; cells; replication; expression; receptor; entry
AB More than 130 million people worldwide chronically infected with hepatitis C virus (HCV) are at risk of developing severe liver disease. Antiviral treatments are only partially effective against HCV infection, and a vaccine is not available. Development of more efficient therapies has been hampered by the lack of a small animal model. Building on the observation that CD81 and occludin (OCLN) comprise the minimal set of human factors required to render mouse cells permissive to HCV entry(1), we previously showed that transient expression of these two human genes is sufficient to allow viral uptake into fully immunocompetent inbred mice(2). Here we demonstrate that transgenic mice stably expressing human CD81 and OCLN also support HCV entry, but innate and adaptive immune responses restrict HCV infection in vivo. Blunting antiviral immunity in genetically humanized mice infected with HCV results in measurable viraemia over several weeks. In mice lacking the essential cellular cofactor cyclophilin A (CypA), HCV RNA replication is markedly diminished, providing genetic evidence that this process is faithfully recapitulated. Using a cell-based fluorescent reporter activated by the NS3-4A protease we visualize HCV infection in single hepatocytes in vivo. Persistently infected mice produce de novo infectious particles, which can be inhibited with directly acting antiviral drug treatment, thereby providing evidence for the completion of the entire HCV life cycle in inbred mice. This genetically humanized mouse model opens new opportunities to dissect genetically HCV infection in vivo and provides an important preclinical platform for testing and prioritizing drug candidates and may also have utility for evaluating vaccine efficacy.
C1 [Dorner, Marcus; Horwitz, Joshua A.; Donovan, Bridget M.; Labitt, Rachael N.; Budell, William C.; Friling, Tamar; Vogt, Alexander; Catanese, Maria Teresa; Rice, Charles M.; Ploss, Alexander] Rockefeller Univ, Ctr Study Hepatitis C, New York, NY 10065 USA.
   [Satoh, Takashi; Kawai, Taro; Akira, Shizuo] Osaka Univ, WPI Immunol Frontier Res Ctr, Lab Host Def, Suita, Osaka 5650871, Japan.
   [Law, Mansun] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA.
C3 Rockefeller University; University of Osaka; Scripps Research Institute
RP Ploss, A (corresponding author), Princeton Univ, Dept Mol Biol, Princeton, NJ 08544 USA.
EM ricec@rockefeller.edu; aploss@princeton.edu
FU National Institute of Diabetes and Digestive and Kidney Diseases [RC1DK087193]; National Institute for Allergy and Infectious Disease [R01AI072613, R01AI099284]; National Cancer Institute [R01CA057973]; The Starr Foundation; Greenberg Medical Research Institute; Richard Salomon Family Foundation; Ronald A. Shellow, M. D. Memorial Fund; MGM Mirage Voice Foundation; German Research Foundation (Deutsche Forschungsgesellschaft); The Rockefeller University Women & Science Fellowship; Infectious Disease Society of America; American Liver Foundation; Grants-in-Aid for Scientific Research [23689030] Funding Source: KAKEN; National Institute of Allergy and Infectious Diseases [R01AI107301] Funding Source: NIH RePORTER
NR 41
TC 185
Z9 218
U1 0
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 SEP 12
PY 2013
VL 501
IS 7466
BP 237
EP +
DI 10.1038/nature12427
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 215XR
UT WOS:000324244900044
PM 23903655
DA 2026-03-09
ER

PT J
AU Paul, S
   Million-Weaver, S
   Chattopadhyay, S
   Sokurenko, E
   Merrikh, H
AF Paul, Sandip
   Million-Weaver, Samuel
   Chattopadhyay, Sujay
   Sokurenko, Evgeni
   Merrikh, Houra
TI Accelerated gene evolution through replication-transcription conflicts
SO NATURE
LA English
DT Article
ID escherichia-coli; fluctuation analysis; dna-replication; leading-strand; lagging-strand; essentiality; organization; mutagenesis; expression; mutations
AB Several mechanisms that increase the rate of mutagenesis across the entire genome have been identified; however, how the rate of evolution might be promoted in individual genes is unclear. Most genes in bacteria are encoded on the leading strand of replication(1-4). This presumably avoids the potentially detrimental head-on collisions that occur between the replication and transcription machineries when genes are encoded on the lagging strand(1-4). Here we identify the ubiquitous (core) genes in Bacillus subtilis and determine that 17% of them are on the lagging strand. We find a higher rate of point mutations in the core genes on the lagging strand compared with those on the leading strand, with this difference being primarily in the amino-acid-changing (nonsynonymous) mutations. We determine that, overall, the genes under strong negative selection against amino-acid-changing mutations tend to be on the leading strand, co-oriented with replication. In contrast, on the basis of the rate of convergent mutations, genes under positive selection for amino-acid-changing mutations are more commonly found on the lagging strand, indicating faster adaptive evolution in many genes in the head-on orientation. Increased gene length and gene expression amounts are positively correlated with the rate of accumulation of nonsynonymous mutations in the head-on genes, suggesting that the conflict between replication and transcription could be a driving force behind these mutations. Indeed, using reversion assays, we show that the difference in the rate of mutagenesis of genes in the two orientations is transcription dependent. Altogether, our findings indicate that head-on replication-transcription conflicts are more mutagenic than co-directional conflicts and that these encounters can significantly increase adaptive structural variation in the coded proteins. We propose that bacteria, and potentially other organisms, promote faster evolution of specific genes through orientation-dependent encounters between DNA replication and transcription.
C1 [Paul, Sandip; Million-Weaver, Samuel; Chattopadhyay, Sujay; Sokurenko, Evgeni; Merrikh, Houra] Univ Washington, Dept Microbiol, Seattle, WA 98195 USA.
C3 University of Washington; University of Washington Seattle
RP Sokurenko, E (corresponding author), Univ Washington, Dept Microbiol, Hlth Sci Bldg J Wing, Seattle, WA 98195 USA.
EM evs@u.washington.edu; merrikh@uw.edu
FU Department of Microbiology at the University of Washington; University of Washington Biophysics Training Grant; National Institutes of Health (NIH) [RC4 AI092828, R01 GM084318]; National Institute of General Medical Sciences [T32GM008268] Funding Source: NIH RePORTER
NR 30
TC 118
Z9 143
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 MAR 28
PY 2013
VL 495
IS 7442
BP 512
EP +
DI 10.1038/nature11989
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 113QN
UT WOS:000316682800046
PM 23538833
DA 2026-03-09
ER

PT J
AU Efeyan, A
   Zoncu, R
   Chang, S
   Gumper, I
   Snitkin, H
   Wolfson, RL
   Kirak, O
   Sabatini, DD
   Sabatini, DM
AF Efeyan, Alejo
   Zoncu, Roberto
   Chang, Steven
   Gumper, Iwona
   Snitkin, Harriet
   Wolfson, Rachel L.
   Kirak, Oktay
   Sabatini, David D.
   Sabatini, David M.
TI Regulation of mTORC1 by the Rag GTPases is necessary for neonatal autophagy and survival
SO NATURE
LA English
DT Article
ID induction; mechanism; lysosome; reveals; kinase; senses
AB The mechanistic target of rapamycin complex 1 (mTORC1) pathway regulates organismal growth in response to many environmental cues, including nutrients and growth factors(1). Cell-based studies showed that mTORC1 senses amino acids through the RagA-D family of GTPases(2,3) (also known as RRAGA, B, C and D), but their importance in mammalian physiology is unknown. Here we generate knock-in mice that express a constitutively active form of RagA (RagA(GTP)) from its endogenous promoter. RagA(GTP/GTP) mice develop normally, but fail to survive postnatal day 1. When delivered by Caesarean section, fasted RagA(GTP/GTP) neonates die almost twice as rapidly as wild-type littermates. Within an hour of birth, wild-type neonates strongly inhibit mTORC1, which coincides with profound hypoglycaemia and a decrease in plasma amino-acid concentrations. In contrast, mTORC1 inhibition does not occur in RagA(GTP/GTP) neonates, despite identical reductions in blood nutrient amounts. With prolonged fasting, wild-type neonates recover their plasma glucose concentrations, but RagA(GTP/GTP) mice remain hypoglycaemic until death, despite using glycogen at a faster rate. The glucose homeostasis defect correlates with the inability of fasted RagA(GTP/GTP) neonates to trigger autophagy and produce amino acids for de novo glucose production. Because profound hypoglycaemia does not inhibit mTORC1 inRagA(GTP/GTP) neonates, we considered the possibility that the Rag pathway signals glucose as well as amino-acid sufficiency to mTORC1. Indeed, mTORC1 is resistant to glucose deprivation in RagA(GTP/GTP) fibroblasts, and glucose, like amino acids, controls its recruitment to the lysosomal surface, the site of mTORC1 activation. Thus, the Rag GTPases signal glucose and amino-acid concentrations to mTORC1, and have an unexpectedly key role in neonates in autophagy induction and thus nutrient homeostasis and viability.
C1 [Efeyan, Alejo; Zoncu, Roberto; Chang, Steven; Wolfson, Rachel L.; Kirak, Oktay; Sabatini, David M.] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA.
   [Efeyan, Alejo; Zoncu, Roberto; Chang, Steven; Wolfson, Rachel L.; Sabatini, David M.] Broad Inst Harvard & Massachusetts Inst Technol, Seven Cambridge Ctr, Cambridge, MA 02142 USA.
   [Efeyan, Alejo; Zoncu, Roberto; Chang, Steven; Wolfson, Rachel L.; Sabatini, David M.] MIT, Dept Biol, Cambridge, MA 02139 USA.
   [Efeyan, Alejo; Zoncu, Roberto; Chang, Steven; Wolfson, Rachel L.; Sabatini, David M.] MIT, David H Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA.
   [Efeyan, Alejo; Zoncu, Roberto; Chang, Steven; Wolfson, Rachel L.; Sabatini, David M.] MIT, Howard Hughes Med Inst, Cambridge, MA 02139 USA.
   [Gumper, Iwona; Snitkin, Harriet; Sabatini, David D.] NYU, Sch Med, Dept Cell Biol, New York, NY 10016 USA.
C3 Massachusetts Institute of Technology (MIT); Whitehead Institute; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); Howard Hughes Medical Institute; Massachusetts Institute of Technology (MIT); New York University
RP Sabatini, DM (corresponding author), Whitehead Inst Biomed Res, 9 Cambridge Ctr, Cambridge, MA 02142 USA.
EM sabatini@wi.mit.edu
FU National Institutes of Health [R01 CA129105, R01 CA103866, R37 AI047389]; American Federation for Aging; Starr Foundation; Koch Institute Frontier Research Program; Ellison Medical Foundation; Human Frontiers Science Program; Jane Coffin Childs Memorial Fund for Medical Research; LAM Foundation; National Cancer Institute [R01CA129105, R01CA103866] Funding Source: NIH RePORTER; National Institute of Allergy and Infectious Diseases [R01AI047389] Funding Source: NIH RePORTER; National Institute of General Medical Sciences [T32GM007753] Funding Source: NIH RePORTER
NR 23
TC 374
Z9 448
U1 0
U2 63
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 31
PY 2013
VL 493
IS 7434
BP 679
EP +
DI 10.1038/nature11745
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 080CU
UT WOS:000314219600058
PM 23263183
DA 2026-03-09
ER

PT J
AU Firstenberg, O
   Peyronel, T
   Liang, QY
   Gorshkov, AV
   Lukin, MD
   Vuletic, V
AF Firstenberg, Ofer
   Peyronel, Thibault
   Liang, Qi-Yu
   Gorshkov, Alexey V.
   Lukin, Mikhail D.
   Vuletic, Vladan
TI Attractive photons in a quantum nonlinear medium
SO NATURE
LA English
DT Article
ID electromagnetically induced transparency; strongly interacting photons; phase-shifts; optics; cavity; atoms; gate
AB The fundamental properties of light derive from its constituent particles-massless quanta (photons) that do not interact with one another(1). However, it has long been known that the realization of coherent interactions between individual photons, akin to those associated with conventional massive particles, could enable a wide variety of novel scientific and engineering applications(2,3). Here we demonstrate a quantum nonlinear medium inside which individual photons travel as massive particles with strong mutual attraction, such that the propagation of photon pairs is dominated by a two-photon bound state(4-7). We achieve this through dispersive coupling of light to strongly interacting atoms in highly excited Rydberg states. We measure the dynamical evolution of the two-photon wave-function using time-resolved quantum state tomography, and demonstrate a conditional phase shift(8) exceeding one radian, resulting in polarization-entangled photon pairs. Particular applications of this technique include all-optical switching, deterministic photonic quantum logic and the generation of strongly correlated states of light(9).
C1 [Firstenberg, Ofer; Lukin, Mikhail D.] Harvard Univ, Dept Phys, Cambridge, MA 02138 USA.
   [Peyronel, Thibault; Liang, Qi-Yu; Vuletic, Vladan] MIT, Dept Phys, Cambridge, MA 02139 USA.
   [Peyronel, Thibault; Liang, Qi-Yu; Vuletic, Vladan] MIT, Elect Res Lab, Cambridge, MA 02139 USA.
   [Gorshkov, Alexey V.] CALTECH, Inst Quantum Informat & Matter, Pasadena, CA 91125 USA.
C3 Harvard University; Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); California Institute of Technology
RP Lukin, MD (corresponding author), Harvard Univ, Dept Phys, Cambridge, MA 02138 USA.
EM lukin@fas.harvard.edu; vuletic@mit.edu
FU NSF; CUA; DARPA; AFOSR Quantum Memories MURI Foundation; Packard Foundation; HQOC; Lee A. DuBridge Foundation; IQIM, an NSF Physics Frontiers Center; Gordon and Betty Moore Foundation; Direct For Mathematical & Physical Scien; Division Of Physics [1205554] Funding Source: National Science Foundation; Direct For Mathematical & Physical Scien; Division Of Physics [1125846] Funding Source: National Science Foundation
NR 31
TC 354
Z9 404
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 OCT 3
PY 2013
VL 502
IS 7469
BP 71
EP +
DI 10.1038/nature12512
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 227IM
UT WOS:000325106000032
PM 24067613
DA 2026-03-09
ER

PT J
AU Cirtain, JW
   Golub, L
   Winebarger, AR
   De Pontieu, B
   Kobayashi, K
   Moore, RL
   Walsh, RW
   Korreck, KE
   Weber, M
   McCauley, P
   Title, A
   Kuzin, S
   DeForest, CE
AF Cirtain, J. W.
   Golub, L.
   Winebarger, A. R.
   De Pontieu, B.
   Kobayashi, K.
   Moore, R. L.
   Walsh, R. W.
   Korreck, K. E.
   Weber, M.
   McCauley, P.
   Title, A.
   Kuzin, S.
   DeForest, C. E.
TI Energy release in the solar corona from spatially resolved magnetic braids
SO NATURE
LA English
DT Article
ID evolving fields; alfvenic waves; neutral sheets; power
AB It is now apparent that there are at least two heating mechanisms in the Sun's outer atmosphere, or corona(1-5). Wave heating may be the prevalent mechanism in quiet solar periods and may contribute to heating the corona to 1,500,000K (refs 1-3). The active corona needs additional heating to reach 2,000,000-4,000,000 K; this heat has been theoretically proposed(6-12) to come from the reconnection and unravelling of magnetic 'braids'. Evidence favouring that process has been inferred(13,14), but has not been generally accepted because observations are sparse and, in general, the braided magnetic strands that are thought(1-3,15-17) to have an angular width of about 0.2 arc seconds have not been resolved(10,18-20). Fine-scale braiding has been seen(21,22) in the chromosphere but not, until now, in the corona. Here we report observations, at a resolution of 0.2 arc seconds, of magnetic braids in a coronal active region that are reconnecting, relaxing and dissipating sufficient energy to heat the structures to about 4,000,000K. Although our 5-minute observations cannot unambiguously identify the field reconnection and subsequent relaxation as the dominant heating mechanism throughout active regions, the energy available from the observed field relaxation in our example is ample for the observed heating.
C1 [Golub, L.; Korreck, K. E.; Weber, M.; McCauley, P.] Harvard Smithsonian Ctr Astrophys, Cambridge, MA 02138 USA.
   [De Pontieu, B.; Title, A.] Lockheed Martin Solar & Astrophys Lab, Palo Alto, CA 94304 USA.
   [Kobayashi, K.] Univ Alabama Huntsville, Ctr Space & Aeronaut Res, Huntsville, AL 35812 USA.
   [Walsh, R. W.] Univ Cent Lancashire, Preston PR1 2HE, Lancs, England.
   [Kuzin, S.] PN Lebedev Phys Inst, Moscow 119991, Russia.
   [DeForest, C. E.] SW Res Inst, Instrumentat & Space Res Div, Boulder, CO 80302 USA.
C3 Smithsonian Astrophysical Observatory; Smithsonian Institution; Harvard University; Lockheed Martin; University of Alabama System; University of Alabama Huntsville; University of Lancashire; Russian Academy of Sciences; Russian Academy of Science Lebedev Physical Institute
EM jonathan.w.cirtain@nasa.gov
FU Russian Foundation for Basic Research [11-02-01079-a]; Presidium of the Russian Academy of Sciences [22]
NR 24
TC 245
Z9 262
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 JAN 24
PY 2013
VL 493
IS 7433
BP 501
EP 503
DI 10.1038/nature11772
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 075GF
UT WOS:000313871400031
PM 23344359
DA 2026-03-09
ER

PT J
AU Lee, SM
   Donaldson, GP
   Mikulski, Z
   Boyajian, S
   Ley, K
   Mazmanian, SK
AF Lee, S. Melanie
   Donaldson, Gregory P.
   Mikulski, Zbigniew
   Boyajian, Silva
   Ley, Klaus
   Mazmanian, Sarkis K.
TI Bacterial colonization factors control specificity and stability of the gut microbiota
SO NATURE
LA English
DT Article
ID commensal; diversity; model
AB Mammals harbour a complex gut microbiome, comprising bacteria that confer immunological, metabolic and neurological benefits(1). Despite advances in sequence-based microbial profiling and myriad studies defining microbiome composition during health and disease, little is known about the molecular processes used by symbiotic bacteria to stably colonize the gastrointestinal tract. We sought to define how mammals assemble and maintain the Bacteroides, one of the most numerically prominent genera of the human microbiome. Here we find that, whereas the gut normally contains hundreds of bacterial species(2,3), germ-free mice mono-associated with a single Bacteroides species are resistant to colonization by the same, but not different, species. To identify bacterial mechanisms for species-specific saturable colonization, we devised an in vivo genetic screen and discovered a unique class of polysaccharide utilization loci that is conserved among intestinal Bacteroides. We named this genetic locus the commensal colonization factors (ccf). Deletion of the ccf genes in the model symbiont, Bacteroides fragilis, results in colonization defects in mice and reduced horizontal transmission. The ccf genes of B. fragilis are upregulated during gut colonization, preferentially at the colonic surface. When we visualize microbial biogeography within the colon, B. fragilis penetrates the colonic mucus and resides deep within crypt channels, whereas ccf mutants are defective in crypt association. Notably, the CCF system is required for B. fragilis colonization following microbiome disruption with Citrobacter rodentium infection or antibiotic treatment, suggesting that the niche within colonic crypts represents a reservoir for bacteria to maintain long-term colonization. These findings reveal that intestinal Bacteroides have evolved species-specific physical interactions with the host that mediate stable and resilient gut colonization, and the CCF system represents a novel molecular mechanism for symbiosis.
C1 [Lee, S. Melanie; Donaldson, Gregory P.; Boyajian, Silva; Mazmanian, Sarkis K.] CALTECH, Div Biol & Biol Engn, Pasadena, CA 91125 USA.
   [Mikulski, Zbigniew; Ley, Klaus] La Jolla Inst Allergy & Immunol, Div Inflammat Biol, La Jolla, CA 92037 USA.
C3 California Institute of Technology; La Jolla Institute for Immunology
RP Mazmanian, SK (corresponding author), CALTECH, Div Biol & Biol Engn, Pasadena, CA 91125 USA.
EM sarkis@caltech.edu
FU National Institutes of Health [GM099535, DK078938]; Crohn's and Colitis Foundation of America;  [GM007616]
NR 27
TC 486
Z9 622
U1 8
U2 353
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 19
PY 2013
VL 501
IS 7467
BP 426
EP +
DI 10.1038/nature12447
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 219XT
UT WOS:000324545700047
PM 23955152
DA 2026-03-09
ER

PT J
AU Ko, H
   Cossell, L
   Baragli, C
   Antolik, J
   Clopath, C
   Hofer, SB
   Mrsic-Flogel, TD
AF Ko, Ho
   Cossell, Lee
   Baragli, Chiara
   Antolik, Jan
   Clopath, Claudia
   Hofer, Sonja B.
   Mrsic-Flogel, Thomas D.
TI The emergence of functional microcircuits in visual cortex
SO NATURE
LA English
DT Article
ID bidirectional synaptic plasticity; receptive-fields; cortical-neurons; orientation selectivity; horizontal connections; pyramidal neurons; striate cortex; in-vivo; networks; model
AB Sensory processing occurs in neocortical microcircuits in which synaptic connectivity is highly structured(1-4) and excitatory neurons form subnetworks that process related sensory information(5,6). However, the developmental mechanisms underlying the formation of functionally organized connectivity in cortical microcircuits remain unknown. Here we directly relate patterns of excitatory synaptic connectivity to visual response properties of neighbouring layer 2/3 pyramidal neurons in mouse visual cortex at different postnatal ages, using two-photon calcium imaging in vivo and multiple whole-cell recordings in vitro. Although neural responses were already highly selective for visual stimuli at eye opening, neurons responding to similar visual features were not yet preferentially connected, indicating that the emergence of feature selectivity does not depend on the precise arrangement of local synaptic connections. After eye opening, local connectivity reorganized extensively: more connections formed selectively between neurons with similar visual responses and connections were eliminated between visually unresponsive neurons, but the overall connectivity rate did not change. We propose a sequential model of cortical microcircuit development based on activity-dependent mechanisms of plasticity whereby neurons first acquire feature preference by selecting feedforward inputs before the onset of sensory experience-a process that may be facilitated by early electrical coupling between neuronal subsets(7-9)-and then patterned input drives the formation of functional subnetworks through a redistribution of recurrent synaptic connections.
C1 [Ko, Ho; Cossell, Lee; Baragli, Chiara; Antolik, Jan; Hofer, Sonja B.; Mrsic-Flogel, Thomas D.] UCL, Dept Neurosci Physiol & Pharmacol, London WC1E 6DE, England.
   [Clopath, Claudia] Columbia Univ, Ctr Theoret Neurosci, New York, NY 10032 USA.
C3 University of London; University College London; Columbia University
RP Hofer, SB (corresponding author), UCL, Dept Neurosci Physiol & Pharmacol, 21 Univ St, London WC1E 6DE, England.
EM s.hofer@ucl.ac.uk; t.mrsic-flogel@ucl.ac.uk
FU Wellcome Trust; Medical Research Council; European Research Council; 7th Framework of European Commission 'EuroV1sion' grant; Swiss National Science Foundation [PA00P3_139703]; Swiss National Science Foundation (SNF) [PA00P3_139703] Funding Source: Swiss National Science Foundation (SNF)
NR 47
TC 309
Z9 373
U1 1
U2 108
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 4
PY 2013
VL 496
IS 7443
BP 96
EP +
DI 10.1038/nature12015
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 117ZZ
UT WOS:000316993400032
PM 23552948
DA 2026-03-09
ER

PT J
AU Erkens, GB
   Hänelt, I
   Goudsmits, JMH
   Slotboom, DJ
   van Oijen, AM
AF Erkens, Guus B.
   Hanelt, Inga
   Goudsmits, Joris M. H.
   Slotboom, Dirk Jan
   van Oijen, Antoine M.
TI Unsynchronised subunit motion in single trimeric sodium-coupled aspartate transporters
SO NATURE
LA English
DT Article
ID pyrococcus-horikoshii; individual subunits; image registration; homolog; dynamics; conductance; translation; substrate; glt(ph)
AB Excitatory amino acid transporters (EAATs) are secondary transport proteins that mediate the uptake of glutamate and other amino acids(1). EAATs fulfil an important role in neuronal signal transmission by clearing the excitatory neurotransmitters from the synaptic cleft after depolarization of the postsynaptic neuron. An intensively studied model system for understanding the transport mechanism of EAATs is the archaeal aspartate transporter Glt(Ph)(2-6). Each subunit in the homotrimeric Glt(Ph) supports the coupled translocation of one aspartate molecule and three Na+ ions(2) as well as an uncoupled flux of Cl- ions(7). Recent crystal structures of Glt(Ph)(3,5,6,8) revealed three possible conformations for the subunits, but it is unclear whether the motions of individual subunits are coordinated to support transport. Here, we report the direct observation of conformational dynamics in individual Glt(Ph) trimers embedded in the membrane by applying single-molecule fluorescence resonance energy transfer (FRET). By analysing the transporters in a lipid bilayer instead of commonly used detergent micelles, we achieve conditions that approximate the physiologically relevant ones. From the kinetics of FRET level transitions we conclude that the three Glt(Ph) subunits undergo conformational changes stochastically and independently of each other.
C1 [Erkens, Guus B.; Hanelt, Inga; Goudsmits, Joris M. H.; Slotboom, Dirk Jan; van Oijen, Antoine M.] Univ Groningen, Zernike Inst Adv Mat, NL-9747 AG Groningen, Netherlands.
   [Hanelt, Inga; Slotboom, Dirk Jan; van Oijen, Antoine M.] Univ Groningen, Groningen Biomol Sci & Biotechnol Inst, NL-9747 AG Groningen, Netherlands.
   [Slotboom, Dirk Jan; van Oijen, Antoine M.] Univ Groningen, Ctr Synthet Biol, NL-9747 AG Groningen, Netherlands.
C3 University of Groningen; University of Groningen; University of Groningen
RP van Oijen, AM (corresponding author), Univ Groningen, Zernike Inst Adv Mat, Nijenborgh 4, NL-9747 AG Groningen, Netherlands.
EM d.j.slotboom@rug.nl; a.m.van.oijen@rug.nl
FU Netherlands Organization for Scientific Research (NWO) [Vici 680-47-607, Vidi 700.54.423, Vici 865.11.001]; European Research Council (ERC Starting) [281098]; European Research Council (ERC) [282083]; Deutsche Forschungsgemeinschaft [HA 6322/1-1]; European Research Council (ERC) [281098] Funding Source: European Research Council (ERC)
NR 28
TC 106
Z9 114
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 OCT 3
PY 2013
VL 502
IS 7469
BP 119
EP +
DI 10.1038/nature12538
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 227IM
UT WOS:000325106000043
PM 24091978
DA 2026-03-09
ER

PT J
AU Förster, S
   Meinel, K
   Hammer, R
   Trautmann, M
   Widdra, W
AF Foerster, Stefan
   Meinel, Klaus
   Hammer, Rene
   Trautmann, Martin
   Widdra, Wolf
TI Quasicrystalline structure formation in a classical crystalline thin-film system
SO NATURE
LA English
DT Article
ID translational symmetry; batio3 films; pt(111); order
AB The discovery of quasicrystals(1)-crystalline structures that show order while lacking periodicity-forced a paradigm shift in crystallography. Initially limited to intermetallic systems(1-4), the observation of quasicrystalline structures has recently expanded to include 'soft' quasicrystals in the fields of colloidal and supermolecular chemistry(5-9). Here we report an aperiodic oxide that grows as a two-dimensional quasicrystal on a periodic single-element substrate. On a Pt(111) substrate with 3-fold symmetry, the perovskite barium titanate BaTiO3 forms a high-temperature interface-driven structure with 12-fold symmetry. The building blocks of this dodecagonal structure assemble with the theoretically predicted Stampfli-Gahler tiling(10,11) having a fundamental length-scale of 0.69 nm. This example of interface-driven formation of ultrathin quasicrystals from a typical periodic perovskite oxide potentially extends the quasicrystal concept to a broader range of materials. In addition, it demonstrates that frustration at the interface between two periodic materials can drive a thin film into an aperiodic quasicrystalline phase, as proposed previously(12). Such structures might also find use as ultrathin buffer layers for the accommodation of large lattice mismatches in conventional epitaxy(13).
C1 [Foerster, Stefan; Meinel, Klaus; Hammer, Rene; Trautmann, Martin; Widdra, Wolf] Univ Halle Wittenberg, Inst Phys, D-06120 Halle, Germany.
   [Widdra, Wolf] Max Planck Inst Mikrostrukturphys, D-06120 Halle, Germany.
C3 Martin Luther University Halle Wittenberg; Max Planck Society
RP Widdra, W (corresponding author), Univ Halle Wittenberg, Inst Phys, D-06120 Halle, Germany.
EM wolf.widdra@physik.uni-halle.de
FU Deutsche Forschungsgemeinschaft [Sonderforschungsbereich 762]
NR 20
TC 168
Z9 183
U1 8
U2 304
PU NATURE PUBLISHING 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 10
PY 2013
VL 502
IS 7470
BP 215
EP +
DI 10.1038/nature12514
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 231RU
UT WOS:000325436100046
PM 24108053
DA 2026-03-09
ER

PT J
AU Eyink, G
   Vishniac, E
   Lalescu, C
   Aluie, H
   Kanov, K
   Bürger, K
   Burns, R
   Meneveau, C
   Szalay, A
AF Eyink, Gregory
   Vishniac, Ethan
   Lalescu, Cristian
   Aluie, Hussein
   Kanov, Kalin
   Buerger, Kai
   Burns, Randal
   Meneveau, Charles
   Szalay, Alexander
TI Flux-freezing breakdown in high-conductivity magnetohydrodynamic turbulence
SO NATURE
LA English
DT Article
ID magnetic reconnection; diffusion; lines
AB The idea of 'frozen-in' magnetic field lines for ideal plasmas(1) is useful to explain diverse astrophysical phenomena(2), for example the shedding of excess angular momentum from protostars by twisting of field lines frozen into the interstellar medium. Frozen-in field lines, however, preclude the rapid changes in magnetic topology observed at high conductivities, as in solar flares(2,3). Microphysical plasma processes are a proposed explanation of the observed high rates(4-6), but it is an open question whether such processes can rapidly reconnect astrophysical flux structures much greater in extent than several thousand ion gyroradii. An alternative explanation(7,8) is that turbulent Richardson advection(9) brings field lines implosively together from distances far apart to separations of the order of gyroradii. Here we report an analysis of a simulation of magnetohydrodynamic turbulence at high conductivity that exhibits Richardson dispersion. This effect of advection in rough velocity fields, which appear non-differentiable in space, leads to line motions that are completely indeterministic or 'spontaneously stochastic', as predicted in analytical studies(10-13). The turbulent breakdown of standard flux freezing at scales greater than the ion gyroradius can explain fast reconnection of very large-scale flux structures, both observed (solar flares and coronal mass ejections) and predicted (the inner heliosheath, accretion disks, gamma-ray bursts and so on). For laminar plasma flows with smooth velocity fields or for low turbulence intensity, stochastic flux freezing reduces to the usual frozen-in condition. [GRAPHICS] .
C1 [Eyink, Gregory; Lalescu, Cristian; Aluie, Hussein] Johns Hopkins Univ, Dept Appl Math & Stat, Baltimore, MD 21218 USA.
   [Eyink, Gregory; Szalay, Alexander] Johns Hopkins Univ, Dept Phys & Astron, Baltimore, MD 21218 USA.
   [Eyink, Gregory; Meneveau, Charles] Johns Hopkins Univ, Dept Mech Engn, Baltimore, MD 21218 USA.
   [Eyink, Gregory; Burns, Randal; Meneveau, Charles; Szalay, Alexander] Johns Hopkins Univ, Inst Data Intens Engn & Sci, Baltimore, MD 21218 USA.
   [Vishniac, Ethan] Univ Saskatchewan, Dept Phys & Engn Phys, Saskatoon, SK S7N 5E2, Canada.
   [Aluie, Hussein] Los Alamos Natl Lab, T Div, Los Alamos, NM 87545 USA.
   [Aluie, Hussein] Los Alamos Natl Lab, Ctr Nonlinear Studies, Los Alamos, NM 87545 USA.
   [Kanov, Kalin; Burns, Randal] Johns Hopkins Univ, Dept Comp Sci, Baltimore, MD 21218 USA.
   [Buerger, Kai] Tech Univ Munich, Fak Informat, D-85748 Garching, Germany.
C3 Johns Hopkins University; Johns Hopkins University; Johns Hopkins University; Johns Hopkins University; University of Saskatchewan; United States Department of Energy (DOE); Los Alamos National Laboratory; United States Department of Energy (DOE); Los Alamos National Laboratory; Johns Hopkins University; Technical University of Munich
RP Eyink, G (corresponding author), Johns Hopkins Univ, Dept Appl Math & Stat, 3400 North Charles St, Baltimore, MD 21218 USA.
EM eyink@jhu.edu
FU US NSF [CDI-II: CMMI0941530, OCI-108849]; JHU's Institute for Data Intensive Engineering Science; National Science and Engineering Research Council of Canada; Direct For Computer & Info Scie & Enginr; Office of Advanced Cyberinfrastructure (OAC) [1040114, 0963185, 1137045] Funding Source: National Science Foundation; Directorate For Engineering; Div Of Civil, Mechanical, & Manufact Inn [0941530] Funding Source: National Science Foundation; Office of Advanced Cyberinfrastructure (OAC); Direct For Computer & Info Scie & Enginr [1136941] Funding Source: National Science Foundation
NR 30
TC 161
Z9 175
U1 0
U2 47
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 23
PY 2013
VL 497
IS 7450
BP 466
EP 469
DI 10.1038/nature12128
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 148OG
UT WOS:000319254000042
PM 23698445
DA 2026-03-09
ER

PT J
AU Moore, JD
   Deschênes, M
   Furuta, T
   Huber, D
   Smear, MC
   Demers, M
   Kleinfeld, D
AF Moore, Jeffrey D.
   Deschenes, Martin
   Furuta, Takahiro
   Huber, Daniel
   Smear, Matthew C.
   Demers, Maxime
   Kleinfeld, David
TI Hierarchy of orofacial rhythms revealed through whisking and breathing
SO NATURE
LA English
DT Article
ID vibrissa movement; motor cortex; motoneurons; neurons; rat; modulation; ingestion; patterns; medulla; nucleus
AB Whisking and sniffing are predominant aspects of exploratory behaviour in rodents. Yet the neural mechanisms that generate and coordinate these and other orofacial motor patterns remain largely uncharacterized. Here we use anatomical, behavioural, electrophysiological and pharmacological tools to show that whisking and sniffing are coordinated by respiratory centres in the ventral medulla. We delineate a distinct region in the ventral medulla that provides rhythmic input to the facial motor neurons that drive protraction of the vibrissae. Neuronal output from this region is reset at each inspiration by direct input from the pre-Botzinger complex, such that high-frequency sniffing has a one-to-one relationship with whisking, whereas basal respiration is accompanied by intervening whisks that occur between breaths. We conjecture that the respiratory nuclei, which project to other premotor regions for oral and facial control, function as a master clock for behaviours that coordinate with breathing.
C1 [Moore, Jeffrey D.; Kleinfeld, David] Univ Calif San Diego, Dept Phys, La Jolla, CA 92093 USA.
   [Deschenes, Martin; Demers, Maxime] Ctr Rech Univ Laval Robert Giffard, Dept Psychiat & Neurosci, Quebec City, PQ G1J 2G3, Canada.
   [Furuta, Takahiro] Kyoto Univ, Grad Sch Med, Dept Morphol Brain Sci, Sakyo Ku, Kyoto 6068501, Japan.
   [Huber, Daniel; Smear, Matthew C.] Howard Hughes Med Inst, Ashburn, VA 20147 USA.
   [Kleinfeld, David] Univ Calif San Diego, Neurobiol Sect, La Jolla, CA 92093 USA.
C3 University of California System; University of California San Diego; Laval University; Kyoto University; Howard Hughes Medical Institute; University of California System; University of California San Diego
RP Deschênes, M (corresponding author), Ctr Rech Univ Laval Robert Giffard, Dept Psychiat & Neurosci, 2601 Canardiere, Quebec City, PQ G1J 2G3, Canada.
EM martin.deschenes@crulrg.ulaval.ca; dk@physics.ucsd.edu
FU Canadian Institutes of Health Research [MT-5877]; Howard Hughes Medical Institute; Japan Society for the Promotion of Science (KAKENHI) [23135519, 24500409]; National Institutes of Health [NS058668, NS066664, NS047101]; US-Israeli Binational Science Foundation [2003222]; Grants-in-Aid for Scientific Research [23135519, 24500409] Funding Source: KAKEN; National Institute of Neurological Disorders and Stroke [P30NS047101] Funding Source: NIH RePORTER
NR 57
TC 237
Z9 288
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 MAY 9
PY 2013
VL 497
IS 7448
BP 205
EP +
DI 10.1038/nature12076
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 139CD
UT WOS:000318558200029
PM 23624373
DA 2026-03-09
ER

PT J
AU Joo, S
   Kim, T
   Shin, SH
   Lim, JY
   Hong, J
   Song, JD
   Chang, J
   Lee, HW
   Rhie, K
   Han, SH
   Shin, KH
   Johnson, M
AF Joo, Sungjung
   Kim, Taeyueb
   Shin, Sang Hoon
   Lim, Ju Young
   Hong, Jinki
   Song, Jin Dong
   Chang, Joonyeon
   Lee, Hyun-Woo
   Rhie, Kungwon
   Han, Suk Hee
   Shin, Kyung-Ho
   Johnson, Mark
TI Magnetic-field-controlled reconfigurable semiconductor logic
SO NATURE
LA English
DT Article
ID magnetoconcentration
AB Logic devices based on magnetism show promise for increasing computational efficiency while decreasing consumed power. They offer zero quiescent power and yet combine novel functions such as programmable logic operation and non-volatile built-in memory(1-5). However, practical efforts to adapt a magnetic device to logic suffer from a low signal-to-noise ratio and other performance attributes that are not adequate for logic gates. Rather than exploiting magnetoresistive effects that result from spin-dependent transport of carriers, we have approached the development of a magnetic logic device in a different way: we use the phenomenon of large magnetoresistance found in non-magnetic semiconductors in high electric fields(6,7). Here we report a device showing a strong diode characteristic that is highly sensitive to both the sign and the magnitude of an external magnetic field, offering a reversible change between two different characteristic states by the application of a magnetic field. This feature results from magnetic control of carrier generation(8) and recombination in an InSb p-n bilayer channel(9). Simple circuits combining such elementary devices are fabricated and tested, and Boolean logic functions including AND, OR, NAND and NOR are performed. They are programmed dynamically by external electric or magnetic signals, demonstrating magnetic-field-controlled semiconductor reconfigurable logic at room temperature. This magnetic technology permits a new kind of spintronic device, characterized as a current switch rather than a voltage switch, and provides a simple and compact platform for non-volatile reconfigurable logic devices.
C1 [Joo, Sungjung; Kim, Taeyueb; Chang, Joonyeon; Han, Suk Hee; Shin, Kyung-Ho] KIST, Spin Convergence Res Ctr, Seoul 130650, South Korea.
   [Joo, Sungjung; Kim, Taeyueb; Hong, Jinki; Rhie, Kungwon] Korea Univ, Dept Display & Semicond Phys, Sejong 339700, South Korea.
   [Shin, Sang Hoon; Lim, Ju Young; Song, Jin Dong] KIST, Nano Photon Res Ctr, Seoul 130650, South Korea.
   [Lee, Hyun-Woo] Pohang Univ Sci & Technol, Dept Phys, Pohang 790784, South Korea.
   [Johnson, Mark] USN, Res Lab, Washington, DC 20375 USA.
C3 Korea Institute of Science & Technology (KIST); Korea University; Korea Institute of Science & Technology (KIST); Pohang University of Science & Technology (POSTECH); United States Department of Defense; United States Navy; United States Naval Research Laboratory; NRL Chesapeake
RP Hong, J (corresponding author), Korea Univ, Dept Display & Semicond Phys, Sejong 339700, South Korea.
EM jkhongjkhong@korea.ac.kr; jdsong@kist.re.kr
FU KIST; NRF; MEST [2010-0000506, 2011-0012386, 2012-0005631, 2012K001280]; industrial strategic technology development programme; MKE [KI002182]; GRL; Office of Naval Research
NR 21
TC 100
Z9 107
U1 2
U2 197
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 7
PY 2013
VL 494
IS 7435
BP 72
EP 76
DI 10.1038/nature11817
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 087DJ
UT WOS:000314741200036
PM 23364687
DA 2026-03-09
ER

PT J
AU Akyuz, N
   Altman, RB
   Blanchard, SC
   Boudker, O
AF Akyuz, Nurunisa
   Altman, Roger B.
   Blanchard, Scott C.
   Boudker, Olga
TI Transport dynamics in a glutamate transporter homologue
SO NATURE
LA English
DT Article
ID translocation; substrate; ribosome; kinetics; binding
AB Glutamate transporters are integral membrane proteins that catalyse neurotransmitter uptake from the synaptic cleft into the cytoplasm of glial cells and neurons(1). Their mechanism of action involves transitions between extracellular (outward)-facing and intracellular (inward)-facing conformations, whereby substrate binding sites become accessible to either side of the membrane(2). This process has been proposed to entail transmembrane movements of three discrete transport domains within a trimeric scaffold(3). Using single-molecule fluorescence resonance energy transfer (smFRET) imaging(4), we have directly observed large-scale transport domain movements in a bacterial homologue of glutamate transporters. We find that individual transport domains alternate between periods of quiescence and periods of rapid transitions, reminiscent of bursting patterns first recorded in single ion channels using patch-clamp methods(5,6). We propose that the switch to the dynamic mode in glutamate transporters is due to separation of the transport domain from the trimeric scaffold, which precedes domain movements across the bilayer. This spontaneous dislodging of the substrate-loaded transport domain is approximately 100-fold slower than subsequent transmembrane movements and may be rate determining in the transport cycle.
C1 [Akyuz, Nurunisa; Altman, Roger B.; Blanchard, Scott C.; Boudker, Olga] Weill Cornell Med Coll, Dept Physiol & Biophys, New York, NY 10064 USA.
C3 Cornell University; Weill Cornell Medicine
RP Blanchard, SC (corresponding author), Weill Cornell Med Coll, Dept Physiol & Biophys, 1300 York Ave, New York, NY 10064 USA.
EM scb2005@med.cornell.edu; olb2003@med.cornell.edu
FU National Institute of Health [5U54GM087519, R01NS064357]
NR 35
TC 141
Z9 159
U1 0
U2 106
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 3
PY 2013
VL 502
IS 7469
BP 114
EP +
DI 10.1038/nature12265
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 227IM
UT WOS:000325106000042
PM 23792560
DA 2026-03-09
ER

PT J
AU Dörr, JR
   Yu, Y
   Milanovic, M
   Beuster, G
   Zasada, C
   Däbritz, JHM
   Lisec, J
   Lenze, D
   Gerhardt, A
   Schleicher, K
   Kratzat, S
   Purfürst, B
   Walenta, S
   Mueller-Klieser, W
   Gräler, M
   Hummel, M
   Keller, U
   Buck, AK
   Dörken, B
   Willmitzer, L
   Reimann, M
   Kempa, S
   Lee, S
   Schmitt, CA
AF Doerr, Jan R.
   Yu, Yong
   Milanovic, Maja
   Beuster, Gregor
   Zasada, Christin
   Daebritz, J. Henry M.
   Lisec, Jan
   Lenze, Dido
   Gerhardt, Anne
   Schleicher, Katharina
   Kratzat, Susanne
   Purfuerst, Bettina
   Walenta, Stefan
   Mueller-Klieser, Wolfgang
   Graeler, Markus
   Hummel, Michael
   Keller, Ulrich
   Buck, Andreas K.
   Doerken, Bernd
   Willmitzer, Lothar
   Reimann, Maurice
   Kempa, Stefan
   Lee, Soyoung
   Schmitt, Clemens A.
TI Synthetic lethal metabolic targeting of cellular senescence in cancer therapy
SO NATURE
LA English
DT Article
ID oncogene-induced senescence; p53 tumor-suppressor; nf-kappa-b; in-vivo; endoplasmic-reticulum; mass-spectrometry; human-cells; autophagy; heterochromatin; lymphomagenesis
AB Activated oncogenes and anticancer chemotherapy induce cellular senescence, a terminal growth arrest of viable cells characterized by S-phase entry-blocking histone 3 lysine 9 trimethylation (H3K9me3)(1,2). Although therapy-induced senescence (TIS) improves long-term outcomes(3), potentially harmful properties of senescent tumour cells make their quantitative elimination a therapeutic priority. Here we use the Em-myc transgenic mouse lymphoma model in which TIS depends on the H3K9 histone methyltransferase Suv39h1 to show the mechanism and therapeutic exploitation of senescence-related metabolic reprogramming in vitro and in vivo. After senescence-inducing chemotherapy, TIS-competent lymphomas but not TIS-incompetent Suv39h1(-) lymphomas show increased glucose utilization and much higher ATP production. We demonstrate that this is linked to massive proteotoxic stress, which is a consequence of the senescence-associated secretory phenotype (SASP) described previously(4-6). SASP-producing TIS cells exhibited endoplasmic reticulum stress, an unfolded protein response (UPR), and increased ubiquitination, thereby targeting toxic proteins for autophagy in an acutely energy-consuming fashion. Accordingly, TIS lymphomas, unlike senescence models that lack a strong SASP response, were more sensitive to blocking glucose utilization or autophagy, which led to their selective elimination through caspase-12-and caspase-3-mediated endoplasmic-reticulum-related apoptosis. Consequently, pharmacological targeting of these metabolic demands on TIS induction in vivo prompted tumour regression and improved treatment outcomes further. These findings unveil the hypercatabolic nature of TIS that is therapeutically exploitable by synthetic lethal metabolic targeting.
C1 [Doerr, Jan R.; Milanovic, Maja; Daebritz, J. Henry M.; Lisec, Jan; Gerhardt, Anne; Schleicher, Katharina; Doerken, Bernd; Reimann, Maurice; Lee, Soyoung; Schmitt, Clemens A.] Charite, Mol Krebsforschungszentrum MKFZ, D-13353 Berlin, Germany.
   [Yu, Yong; Beuster, Gregor; Purfuerst, Bettina; Doerken, Bernd; Lee, Soyoung; Schmitt, Clemens A.] Max Delbruck Ctr Mol Med MDC, D-13125 Berlin, Germany.
   [Zasada, Christin; Kempa, Stefan] Max Delbruck Ctr Mol Med, Berlin Inst Med Syst Biol, D-13125 Berlin, Germany.
   [Lisec, Jan] Deutsch Krebsforschungzentrum DKFZ, German Canc Consortium, D-69120 Heidelberg, Germany.
   [Lenze, Dido; Hummel, Michael] Charite, Dept Pathol, D-10117 Berlin, Germany.
   [Kratzat, Susanne; Keller, Ulrich] Tech Univ Munich, Dept Med 3, D-81675 Munich, Germany.
   [Walenta, Stefan; Mueller-Klieser, Wolfgang] Johannes Gutenberg Univ Mainz, Univ Med, Inst Physiol & Pathophysiol, D-55128 Mainz, Germany.
   [Graeler, Markus] Univ Klinikum Jena, Dept Anesthesiol & Intens Care Med, D-07747 Jena, Germany.
   [Graeler, Markus] Univ Klinikum Jena, Ctr Sepsis Control & Care CSCC, D-07747 Jena, Germany.
   [Buck, Andreas K.] Univ Klinikum Wurzburg, Dept Nucl Med, D-97080 Wurzburg, Germany.
   [Willmitzer, Lothar] Max Planck Inst Mol Plant Physiol, D-14476 Potsdam, Germany.
C3 Free University of Berlin; Humboldt University of Berlin; Charite Universitatsmedizin Berlin; Helmholtz Association; Max Delbruck Center for Molecular Medicine; Helmholtz Association; Max Delbruck Center for Molecular Medicine; Helmholtz Association; German Cancer Research Center (DKFZ); Free University of Berlin; Humboldt University of Berlin; Charite Universitatsmedizin Berlin; Technical University of Munich; Johannes Gutenberg University of Mainz; Friedrich Schiller University of Jena; Friedrich Schiller University of Jena; University of Wurzburg; Max Planck Society
RP Schmitt, CA (corresponding author), Charite, Mol Krebsforschungszentrum MKFZ, Augustenburger Pl 1, D-13353 Berlin, Germany.
EM clemens.schmitt@charite.de
FU Boehringer Ingelheim Foundation; Deutsche Forschungsgemeinschaft [MK576/15-1, SFB 824, SFB/TRR 54]; Helmholtz Association (Helmholtz Alliance 'Preclinical Comprehensive Cancer Center') [HA-305]; Deutsche Krebshilfe [108789]; Excellence Initiative; German Cancer Consortium (GCC); Academy of Finland (AKA) [108789] Funding Source: Academy of Finland (AKA)
NR 46
TC 447
Z9 511
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 SEP 19
PY 2013
VL 501
IS 7467
BP 421
EP +
DI 10.1038/nature12437
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 219XT
UT WOS:000324545700046
PM 23945590
DA 2026-03-09
ER

PT J
AU Holland, G
   Lollar, BS
   Li, L
   Lacrampe-Couloume, G
   Slater, GF
   Ballentine, CJ
AF Holland, G.
   Lollar, B. Sherwood
   Li, L.
   Lacrampe-Couloume, G.
   Slater, G. F.
   Ballentine, C. J.
TI Deep fracture fluids isolated in the crust since the Precambrian era
SO NATURE
LA English
DT Article
ID great artesian basin; noble-gases; witwatersrand basin; hydrocarbon gases; continental-crust; groundwater-flow; u-pb; xenon; origin; stratigraphy
AB Fluids trapped as inclusions within minerals can be billions of years old and preserve a record of the fluid chemistry and environment at the time of mineralization(1-3). Aqueous fluids that have had a similar residence time at mineral interfaces and in fractures (fracture fluids) have not been previously identified. Expulsion of fracture fluids from basement systems with low connectivity occurs through deformation and fracturing of the brittle crust(4). The fractal nature of this process must, at some scale, preserve pockets of interconnected fluid from the earliest crustal history. In one such system, 2.8 kilometres below the surface in a South African gold mine, extant chemoautotrophic microbes have been identified in fluids isolated from the photosphere on timescales of tens of millions of years(5). Deep fracture fluids with similar chemistry have been found in a mine in the Timmins, Ontario, area of the Canadian Precambrian Shield. Here we show that excesses of Xe-124, Xe-126 and Xe-128 in the Timmins mine fluids can be linked to xenon isotope changes in the ancient atmosphere(2) and used to calculate a minimum mean residence time for this fluid of about 1.5 billion years. Further evidence of an ancient fluid system is found in Xe-129 excesses that, owing to the absence of any identifiable mantle input, are probably sourced in sediments and extracted by fluid migration processes operating during or shortly after mineralization at around 2.64 billion years ago. We also provide closed-system radiogenic noble-gas (He-4, Ne-21, Ar-40, Xe-136) residence times. Together, the different noble gases show that ancient pockets of water can survive the crustal fracturing process and remain in the crust for billions of years.
C1 [Holland, G.; Ballentine, C. J.] Univ Manchester, Sch Earth Atmospher & Environm Sci, Manchester M13 9PL, Lancs, England.
   [Holland, G.] Univ Lancaster, Lancaster Environm Ctr, Lancaster LA1 4YQ, England.
   [Li, L.; Lacrampe-Couloume, G.] Univ Toronto, Dept Earth Sci, Toronto, ON M5S 3B1, Canada.
   [Slater, G. F.] McMaster Univ, Sch Geog & Geol, Hamilton, ON L8S 4K1, Canada.
C3 University of Manchester; Lancaster University; University of Toronto; McMaster University
RP Ballentine, CJ (corresponding author), Univ Manchester, Sch Earth Atmospher & Environm Sci, Manchester M13 9PL, Lancs, England.
EM chris.ballentine@manchester.ac.uk
FU NSERC; UK-NERC; Deep Carbon Observatory; Natural Environment Research Council [NE/F002823/1] Funding Source: researchfish; NERC [NE/F002823/1] Funding Source: UKRI
NR 54
TC 163
Z9 190
U1 2
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 MAY 16
PY 2013
VL 497
IS 7449
BP 357
EP +
DI 10.1038/nature12127
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 144PN
UT WOS:000318952000035
PM 23676753
DA 2026-03-09
ER

PT J
AU Gatsogiannis, C
   Lang, AE
   Meusch, D
   Pfaumann, V
   Hofnagel, O
   Benz, R
   Aktories, K
   Raunser, S
AF Gatsogiannis, Christos
   Lang, Alexander E.
   Meusch, Dominic
   Pfaumann, Vanda
   Hofnagel, Oliver
   Benz, Roland
   Aktories, Klaus
   Raunser, Stefan
TI A syringe-like injection mechanism in Photorhabdus luminescens toxins
SO NATURE
LA English
DT Article
ID pore formation; insecticidal toxins; protein toxins; anthrax toxin; complex; bacterium
AB Photorhabdus luminescens is an insect pathogenic bacterium that is symbiotic with entomopathogenic nematodes(1). On invasion of insect larvae, P. luminescens is released from the nematodes and kills the insect through the action of a variety of virulence factors including large tripartite ABC-type toxin complexes(2) (Tcs). Tcs are typically composed of TcA, TcB and TcC proteins and are biologically active only when complete(3-5). Functioning as ADP-ribosyltransferases, TcC proteins were identified as the actual functional components that induce actin-clustering, defects in phagocytosis and cell death(5-7). However, little is known about the translocation of TcC into the cell by the TcA and TcB components. Here we show that TcA in P. luminescens (TcdA1) forms a transmembrane pore and report its structure in the prepore and pore state determined by cryoelectron microscopy. We find that the TcdA1 prepore assembles as a pentamer forming an alpha-helical, vuvuzela-shaped channel less than 1.5 nanometres in diameter surrounded by a large outer shell. Membrane insertion is triggered not only at low pH as expected, but also at high pH, explaining Tc action directly through the midgut of insects(8). Comparisons with structures of the TcdA1 pore inserted into a membrane and in complex with TcdB2 and TccC3 reveal large conformational changes during membrane insertion, suggesting a novel syringe-like mechanism of protein translocation. Our results demonstrate how ABC-type toxin complexes bridge a membrane to insert their lethal components into the cytoplasm of the host cell. We believe that the proposed mechanism is characteristic of the whole ABC-type toxin family. This explanation of toxin translocation is a step towards understanding the host-pathogen interaction and the complex life cycle of P. luminescens and other pathogens, including human pathogenic bacteria, and serves as a strong foundation for the development of biopesticides.
C1 [Gatsogiannis, Christos; Meusch, Dominic; Hofnagel, Oliver; Raunser, Stefan] Max Planck Inst Mol Physiol, Dept Phys Biochem, D-44227 Dortmund, Germany.
   [Lang, Alexander E.; Pfaumann, Vanda; Aktories, Klaus] Univ Freiburg, Inst Expt & Klin Pharmakol & Toxik, D-79104 Freiburg, Germany.
   [Benz, Roland] Jacobs Univ Bremen, Sch Engn & Sci, D-28759 Bremen, Germany.
C3 Max Planck Society; University of Freiburg; Constructor University
RP Raunser, S (corresponding author), Max Planck Inst Mol Physiol, Dept Phys Biochem, D-44227 Dortmund, Germany.
EM stefan.raunser@mpi-dortmund.mpg.de
FU Deutsche Forschungsgemeinschaft [RA 1781/1-1, AK 6/22-1]; Max Planck Society
NR 25
TC 116
Z9 130
U1 0
U2 82
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 28
PY 2013
VL 495
IS 7442
BP 520
EP 523
DI 10.1038/nature11987
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 113QN
UT WOS:000316682800048
PM 23515159
DA 2026-03-09
ER

PT J
AU Dölen, G
   Darvishzadeh, A
   Huang, KW
   Malenka, RC
AF Doelen, Guel
   Darvishzadeh, Ayeh
   Huang, Kee Wui
   Malenka, Robert C.
TI Social reward requires coordinated activity of nucleus accumbens oxytocin and serotonin
SO NATURE
LA English
DT Article
ID hypothalamo-neurohypophyseal system; medium spiny neurons; concurrent activation; affiliative behavior; forebrain circuit; indirect pathways; gene-expression; evolution; dopamine; innervation
AB Social behaviours in species as diverse as honey bees and humans promote group survival but often come at some cost to the individual. Although reinforcement of adaptive social interactions is ostensibly required for the evolutionary persistence of these behaviours, the neural mechanisms by which social reward is encoded by the brain are largely unknown. Here we demonstrate that in mice oxytocin acts as a social reinforcement signal within the nucleus accumbens core, where it elicits a presynaptically expressed long-term depression of excitatory synaptic transmission in medium spiny neurons. Although the nucleus accumbens receives oxytocin-receptor-containing inputs from several brain regions, genetic deletion of these receptors specifically from dorsal raphe nucleus, which provides serotonergic (5-hydroxytryptamine; 5-HT) innervation to the nucleus accumbens, abolishes the reinforcing properties of social interaction. Furthermore, oxytocin-induced synaptic plasticity requires activation of nucleus accumbens 5-HT1B receptors, the blockade of which prevents social reward. These results demonstrate that the rewarding properties of social interaction in mice require the coordinated activity of oxytocin and 5-HT in the nucleus accumbens, a mechanistic insight with implications for understanding the pathogenesis of social dysfunction in neuropsychiatric disorders such as autism.
C1 [Doelen, Guel; Darvishzadeh, Ayeh; Huang, Kee Wui; 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 National Institutes of Health [NIH NS069375]; Simons Foundation Autism Research Initiative; Berry Foundation
NR 47
TC 889
Z9 1051
U1 3
U2 272
PU NATURE PUBLISHING 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 12
PY 2013
VL 501
IS 7466
BP 179
EP +
DI 10.1038/nature12518
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 215XR
UT WOS:000324244900032
PM 24025838
DA 2026-03-09
ER

PT J
AU Kandoth, C
   McLellan, MD
   Vandin, F
   Ye, K
   Niu, BF
   Lu, C
   Xie, MC
   Zhang, QY
   McMichael, JF
   Wyczalkowski, MA
   Leiserson, MDM
   Miller, CA
   Welch, JS
   Walter, MJ
   Wendl, MC
   Ley, TJ
   Wilson, RK
   Raphael, BJ
   Ding, L
AF Kandoth, Cyriac
   McLellan, Michael D.
   Vandin, Fabio
   Ye, Kai
   Niu, Beifang
   Lu, Charles
   Xie, Mingchao
   Zhang, Qunyuan
   McMichael, Joshua F.
   Wyczalkowski, Matthew A.
   Leiserson, Mark D. M.
   Miller, Christopher A.
   Welch, John S.
   Walter, Matthew J.
   Wendl, Michael C.
   Ley, Timothy J.
   Wilson, Richard K.
   Raphael, Benjamin J.
   Ding, Li
TI Mutational landscape and significance across 12 major cancer types
SO NATURE
LA English
DT Article
ID somatic point mutations; brca2 mutations; human breast; survival; pathways; association; discovery; evolution; pbrm1
AB The Cancer Genome Atlas (TCGA) has used the latest sequencing and analysis methods to identify somatic variants across thousands of tumours. Here we present data and analytical results for point mutations and small insertions/deletions from 3,281 tumours across 12 tumour types as part of the TCGA Pan-Cancer effort. We illustrate the distributions of mutation frequencies, types and contexts across tumour types, and establish their links to tissues of origin, environmental/carcinogen influences, and DNA repair defects. Using the integrated data sets, we identified 127 significantly mutated genes from well-known(for example, mitogen-activated protein kinase, phosphatidylinositol-3-OH kinase, Wnt/beta-catenin and receptor tyrosine kinase signalling pathways, and cell cycle control) and emerging (for example, histone, histone modification, splicing, metabolism and proteolysis) cellular processes in cancer. The average number of mutations in these significantly mutated genes varies across tumour types; most tumours have two to six, indicating that the number of driver mutations required during oncogenesis is relatively small. Mutations in transcriptional factors/regulators show tissue specificity, whereas histone modifiers are often mutated across several cancer types. Clinical association analysis identifies genes having a significant effect on survival, and investigations of mutations with respect to clonal/subclonal architecture delineate their temporal orders during tumorigenesis. Taken together, these results lay the groundwork for developing new diagnostics and individualizing cancer treatment.
C1 [Kandoth, Cyriac; McLellan, Michael D.; Ye, Kai; Niu, Beifang; Lu, Charles; Xie, Mingchao; Zhang, Qunyuan; McMichael, Joshua F.; Wyczalkowski, Matthew A.; Miller, Christopher A.; Wendl, Michael C.; Ley, Timothy J.; Wilson, Richard K.; Ding, Li] Washington Univ, Genome Inst, St Louis, MO 63108 USA.
   [Vandin, Fabio; Leiserson, Mark D. M.; Raphael, Benjamin J.] Brown Univ, Dept Comp Sci, Providence, RI 02912 USA.
   [Ye, Kai; Zhang, Qunyuan; Wendl, Michael C.; Ley, Timothy J.; Wilson, Richard K.; Ding, Li] Washington Univ, Dept Genet, St Louis, MO 63108 USA.
   [Welch, John S.; Walter, Matthew J.; Ley, Timothy J.; Ding, Li] Washington Univ, Dept Med, St Louis, MO 63108 USA.
   [Welch, John S.; Walter, Matthew J.; Ley, Timothy J.; Wilson, Richard K.; Ding, Li] Washington Univ, Siteman Canc Ctr, St Louis, MO 63108 USA.
   [Wendl, Michael C.] Washington Univ, Dept Math, St Louis, MO 63108 USA.
C3 Washington University (WUSTL); Brown University; Washington University (WUSTL); Washington University (WUSTL); Siteman Cancer Center; Washington University (WUSTL); Washington University (WUSTL)
RP Ding, L (corresponding author), Washington Univ, Genome Inst, St Louis, MO 63108 USA.
EM lding@genome.wustl.edu
FU National Cancer Institute [R01CA180006, PO1CA101937]; National Human Genome Research Institute [R01HG005690, U54HG003079, U01HG006517]; National Science Foundation [IIS-1016648]; National Cancer Institute [P01CA101937] Funding Source: NIH RePORTER; Direct For Computer & Info Scie & Enginr; Div Of Information & Intelligent Systems [1016648] Funding Source: National Science Foundation
NR 37
TC 3525
Z9 4239
U1 7
U2 431
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 17
PY 2013
VL 502
IS 7471
BP 333
EP +
DI 10.1038/nature12634
PG 20
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 235GY
UT WOS:000325706300045
PM 24132290
DA 2026-03-09
ER

PT J
AU Klose, CSN
   Kiss, EA
   Schwierzeck, V
   Ebert, K
   Hoyler, T
   d'Hargues, Y
   Göppert, N
   Croxford, AL
   Waisman, A
   Tanriver, Y
   Diefenbach, A
AF Klose, Christoph S. N.
   Kiss, Elina A.
   Schwierzeck, Vera
   Ebert, Karolina
   Hoyler, Thomas
   d'Hargues, Yannick
   Goeppert, Nathalie
   Croxford, Andrew L.
   Waisman, Ari
   Tanriver, Yakup
   Diefenbach, Andreas
TI A T-bet gradient controls the fate and function of CCR6-RORγt+ innate lymphoid cells
SO NATURE
LA English
DT Article
ID ror-gamma-t; nkp46(+) cells; ifn-gamma; expression; differentiation; defense; host
AB At mucosal surfaces, the immune system should not initiate inflammatory immune responses to the plethora of antigens constantly present in the environment, but should remain poised to unleash a potent assault on intestinal pathogens.. The transcriptional programs and regulatory factors required for immune cells to switch from homeostatic (often tissue-protective) function(1) to potent antimicrobial immunity are poorly defined. Mucosal retinoic-acidreceptor-related orphan receptor-gamma t-positive (ROR gamma t(+)) innate lymphoid cells (ILCs) are emerging as an important innate lymphocyte population required for immunity to intestinal infections(2). Various subsets of ROR gamma t(+) ILCs have been described(3-8) but the transcriptional programs controlling their specification and fate remain largely unknown. Here we provide evidence that the transcription factor T-bet determines the fate of a distinct lineage of CCR6(-)ROR gamma t(+) ILCs. Postnatally emerging CCR6(-)ROR gamma t(+) ILCs upregulated T-bet and this was controlled by cues from the commensal microbiota and interleukin-23 (IL-23). In contrast, CCR6(+)ROR gamma t(+) ILCs, which arise earlier during ontogeny, did not express T-bet. T-bet instructed the expression of T-bet target genes such as interferon-gamma (IFN-gamma) and of the natural cytotoxicity receptor NKp46. Mice genetically lacking T-bet showed normal development of CCR6(-)ROR gamma t(+) ILCs, but they could not differentiate into NKp46-expressing ROR gamma t(+) ILCs (that is, IL-22-producing natural killer (NK-22) cells)(3,9) and failed to produce IFN-gamma. The production of IFN-gamma by T-bet-expressing CCR6(-)ROR gamma t(+) ILCs was essential for the release of mucus-forming glycoproteins required to protect the epithelial barrier during Salmonella enterica infection(10,11). Salmonella infection also causes severe enterocolitis that is at least partly driven by IFN-gamma(12). Mice deficient for T-bet or depleted of ILCs developed only mild enterocolitis. Thus, graded expression of T-bet in CCR6(-)ROR gamma t(+) MCs facilitates the differentiation of IFN-gamma-producing CCR6(-)ROR gamma t(+) ILCs required to protect the epithelial barrier against Salmonella infections. Co-expression of T-bet and ROR gamma t, which is also found in subsets of IL-17-producing T-helper (T(H)17) cells(13), may be an evolutionarily conserved transcriptional program that originally developed as part of the innate defence against infections but that also confers an increased risk of immune-mediated pathology.
C1 [Klose, Christoph S. N.; Kiss, Elina A.; Schwierzeck, Vera; Ebert, Karolina; Hoyler, Thomas; d'Hargues, Yannick; Goeppert, Nathalie; Tanriver, Yakup; Diefenbach, Andreas] Univ Freiburg, IMMH, D-79104 Freiburg, Germany.
   [Schwierzeck, Vera; Tanriver, Yakup; Diefenbach, Andreas] Univ Med Ctr Freiburg, CCI, D-79106 Freiburg, Germany.
   [Schwierzeck, Vera; Tanriver, Yakup; Diefenbach, Andreas] Univ Freiburg, D-79106 Freiburg, Germany.
   [Ebert, Karolina; d'Hargues, Yannick; Tanriver, Yakup] Univ Freiburg, Med Ctr, Div Renal, D-79106 Freiburg, Germany.
   [Croxford, Andrew L.; Waisman, Ari] Johannes Gutenberg Univ Mainz, Inst Mol Med, D-55131 Mainz, Germany.
   [Croxford, Andrew L.] Univ Zurich, Inst Expt Immunol, CH-8006 Zurich, Switzerland.
   [Diefenbach, Andreas] Univ Freiburg, Ctr Biol Signalling Studies BIOSS, D-79104 Freiburg, Germany.
C3 University of Freiburg; University of Freiburg; University of Freiburg; University of Freiburg; Johannes Gutenberg University of Mainz; University of Zurich; University of Freiburg
RP Diefenbach, A (corresponding author), Univ Freiburg, IMMH, Hermann Herder Str 11, D-79104 Freiburg, Germany.
EM andreas.diefenbach@uniklinik-freiburg.de
FU Deutsche Forschungsgemeinschaft [SFB620/A14, TA436/2-1]; German Federal Ministry of Education and Research [BMBF 01 EO 0803]; EFSD/Lilly grant; European Research Council; CCI Walter-Hitzig-Fellowship; EMBO Long Term Fellowship [ALTF 508-2011]; FP6 Marie Curie Research Train in Network [MRTN-CT-2004-005632]
NR 31
TC 607
Z9 697
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 FEB 14
PY 2013
VL 494
IS 7436
BP 261
EP 265
DI 10.1038/nature11813
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 092QS
UT WOS:000315137700045
PM 23334414
DA 2026-03-09
ER

PT J
AU Penmatsa, A
   Wang, KH
   Gouaux, E
AF Penmatsa, Aravind
   Wang, Kevin H.
   Gouaux, Eric
TI X-ray structure of dopamine transporter elucidates antidepressant mechanism
SO NATURE
LA English
DT Article
ID aminobutyric-acid transporter; high-level expression; serotonin transporter; binding-site; neurotransmitter transporters; structure refinement; bacterial homolog; n-glycosylation; chloride; sodium
AB Antidepressants targeting Na+/Cl--coupled neurotransmitter uptake define a key therapeutic strategy to treat clinical depression and neuropathic pain. However, identifying the molecular interactions that underlie the pharmacological activity of these transport inhibitors, and thus the mechanism by which the inhibitors lead to increased synaptic neurotransmitter levels, has proven elusive. Here we present the crystal structure of the Drosophila melanogaster dopamine transporter at 3.0 angstrom resolution bound to the tricyclic antidepressant nortriptyline. The transporter is locked in an outward-open conformation with nortriptyline wedged between transmembrane helices 1, 3,6 and 8, blocking the transporter from binding substrate and from isomerizing to an inward-facing conformation. Although the overall structure of the dopamine transporter is similar to that of its prokaryotic relative LeuT, there are multiple distinctions, including a kink in transmembrane helix 12 halfway across the membrane bilayer, a latch-like carboxy-terminal helix that caps the cytoplasmic gate, and a cholesterol molecule wedged within a groove formed by transmembrane helices 1a, 5 and 7. Taken together, the dopamine transporter structure reveals the molecular basis for antidepressant action on sodium-coupled neurotransmitter symporters and elucidates critical elements of eukaryotic transporter structure and modulation by lipids, thus expanding our understanding of the mechanism and regulation of neurotransmitter uptake at chemical synapses.
C1 [Penmatsa, Aravind; Wang, Kevin H.; 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; Howard Hughes Medical Institute; Oregon Health & Science University
RP Gouaux, E (corresponding author), Oregon Hlth & Sci Univ, Vollum Inst, 3181 South West Sam Jackson Pk Rd, Portland, OR 97239 USA.
EM gouauxe@ohsu.edu
FU American Heart Association; National Institute of Mental Health; National Institutes of Health
NR 61
TC 521
Z9 591
U1 2
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 NOV 7
PY 2013
VL 503
IS 7474
BP 85
EP +
DI 10.1038/nature12533
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 247AS
UT WOS:000326585600036
PM 24037379
DA 2026-03-09
ER

PT J
AU Pepe, F
   Cameron, AC
   Latham, DW
   Molinari, E
   Udry, S
   Bonomo, AS
   Buchhave, LA
   Charbonneau, D
   Cosentino, R
   Dressing, CD
   Dumusque, X
   Figueira, P
   Fiorenzano, AFM
   Gettel, S
   Harutyunyan, A
   Haywood, RD
   Horne, K
   Lopez-Morales, M
   Lovis, C
   Malavolta, L
   Mayor, M
   Micela, G
   Motalebi, F
   Nascimbeni, V
   Phillips, D
   Piotto, G
   Pollacco, D
   Queloz, D
   Rice, K
   Sasselov, D
   Ségransan, D
   Sozzetti, A
   Szentgyorgyi, A
   Watson, CA
AF Pepe, Francesco
   Cameron, Andrew Collier
   Latham, David W.
   Molinari, Emilio
   Udry, Stephane
   Bonomo, Aldo S.
   Buchhave, Lars A.
   Charbonneau, David
   Cosentino, Rosario
   Dressing, Courtney D.
   Dumusque, Xavier
   Figueira, Pedro
   Fiorenzano, Aldo F. M.
   Gettel, Sara
   Harutyunyan, Avet
   Haywood, Raphaelle D.
   Horne, Keith
   Lopez-Morales, Mercedes
   Lovis, Christophe
   Malavolta, Luca
   Mayor, Michel
   Micela, Giusi
   Motalebi, Fatemeh
   Nascimbeni, Valerio
   Phillips, David
   Piotto, Giampaolo
   Pollacco, Don
   Queloz, Didier
   Rice, Ken
   Sasselov, Dimitar
   Segransan, Damien
   Sozzetti, Alessandro
   Szentgyorgyi, Andrew
   Watson, Christopher A.
TI An Earth-sized planet with an Earth-like density
SO NATURE
LA English
DT Article
ID kepler
AB Recent analyses(1-4) of data from the NASA Kepler spacecraft(5) have established that planets with radii within 25 per cent of the Earth's (R-circle plus) are commonplace throughout the Galaxy, orbiting at least 16.5 per cent of Sun-like stars(1). Because these studies were sensitive to the sizes of the planets but not their masses, the question remains whether these Earth-sized planets are indeed similar to the Earth in bulk composition. The smallest planets for which masses have been accurately determined(6,7) are Kepler-10b (1.42R(circle plus)) and Kepler-36b (1.49R(circle plus)), which are both significantly larger than the Earth. Recently, the planet Kepler-78b was discovered(8) and found to have a radius of only 1.16R(circle plus). Here we report that the mass of this planet is 1.86 Earth masses. The resulting mean density of the planet is 5.57 g cm(-3), which is similar to that of the Earth and implies a composition of iron and rock.
C1 [Pepe, Francesco; Udry, Stephane; Lovis, Christophe; Mayor, Michel; Motalebi, Fatemeh; Queloz, Didier; Segransan, Damien] Univ Geneva, Astron Observ, CH-1290 Versoix, Switzerland.
   [Cameron, Andrew Collier; Haywood, Raphaelle D.; Horne, Keith] Univ St Andrews, Sch Phys & Astron, Scottish Univ Phys Alliance, St Andrews KY16 9SS, Fife, Scotland.
   [Latham, David W.; Buchhave, Lars A.; Charbonneau, David; Dressing, Courtney D.; Dumusque, Xavier; Gettel, Sara; Lopez-Morales, Mercedes; Phillips, David; Sasselov, Dimitar; Szentgyorgyi, Andrew] Harvard Smithsonian Ctr Astrophys, Cambridge, MA 02138 USA.
   [Molinari, Emilio; Cosentino, Rosario; Fiorenzano, Aldo F. M.; Harutyunyan, Avet] INAF Fdn Galileo Galilei, Brena Baja 38712, Spain.
   [Molinari, Emilio] INAF IASF Milano, I-20133 Milan, Italy.
   [Bonomo, Aldo S.; Sozzetti, Alessandro] INAF Osservatorio Astron Torino, I-10025 Pino Torinese, Italy.
   [Buchhave, Lars A.] Univ Copenhagen, Nat Hist Museum Denmark, Ctr Star & Planet Format, DK-1350 Copenhagen, Denmark.
   [Cosentino, Rosario] INAF Osservatorio Astrofis Catania, I-95125 Catania, Italy.
   [Figueira, Pedro] Univ Porto, Ctr Astrofis, P-4150762 Oporto, Portugal.
   [Malavolta, Luca; Piotto, Giampaolo] Univ Padua, Dipartimento Fis & Astron Galileo Galilei, I-35122 Padua, Italy.
   [Malavolta, Luca; Nascimbeni, Valerio; Piotto, Giampaolo] INAF Osservatorio Astron Padova, I-35122 Padua, Italy.
   [Micela, Giusi] INAF Osservatorio Astron Palermo, I-90124 Palermo, Italy.
   [Pollacco, Don] Univ Warwick, Dept Phys, Coventry CV4 7AL, W Midlands, England.
   [Queloz, Didier] Univ Cambridge, Cavendish Lab, Cambridge CB3 0HE, England.
   [Rice, Ken] Univ Edinburgh, Royal Observ, Inst Astron, Scottish Univ Phys Alliance, Edinburgh EH9 3HJ, Midlothian, Scotland.
   [Watson, Christopher A.] Queens Univ Belfast, Sch Math & Phys, Astrophys Res Ctr, Belfast BT7 1NN, Antrim, North Ireland.
C3 University of Geneva; University of St Andrews; Smithsonian Institution; Harvard University; Smithsonian Astrophysical Observatory; Istituto Nazionale Astrofisica (INAF); Istituto Nazionale Astrofisica (INAF); Istituto Nazionale Astrofisica (INAF); University of Copenhagen; Istituto Nazionale Astrofisica (INAF); Universidade do Porto; University of Padua; Istituto Nazionale Astrofisica (INAF); Istituto Nazionale Astrofisica (INAF); University of Warwick; University of Cambridge; University of Edinburgh; Queens University Belfast
RP Pepe, F (corresponding author), Univ Geneva, Astron Observ, 51 Chemin Maillettes, CH-1290 Versoix, Switzerland.
EM francesco.pepe@unige.ch
FU Prodex Program of the Swiss Space Office; Harvard University Origins of Life Initiative; Scottish Universities Physics Alliance; University of Geneva; Smithsonian Astrophysical Observatory; Italian National Astrophysical Institute; University of St Andrews; Queen's University Belfast; University of Edinburgh; European Research Council/European Community through the European Union [239953]; Fundacao para a Ciencia e a Tecnologia [PTDC/CTE-AST/098528/2008, PTDC/CTE-AST/098604/2008]; European Union [313014]; Science and Technology Facilities Council [ST/J500744/1, ST/J00152X/1, ST/I001123/1, PP/F000065/1, ST/K001620/1, 1105238, ST/G001987/1, ST/J004626/1, ST/K006126/1, ST/J001651/1, ST/I001719/1] Funding Source: researchfish; STFC [ST/J00152X/1, ST/K006126/1, ST/I001719/1, ST/K001620/1, ST/G001987/1, ST/I001123/1, ST/J004626/1, ST/J001651/1, ST/J500744/1, PP/F000065/1] Funding Source: UKRI
NR 28
TC 159
Z9 189
U1 0
U2 172
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 21
PY 2013
VL 503
IS 7476
BP 377
EP +
DI 10.1038/nature12768
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 254KG
UT WOS:000327163200036
PM 24172902
DA 2026-03-09
ER

PT J
AU Li, J
   D'Angiolella, V
   Seeley, ES
   Kim, S
   Kobayashi, T
   Fu, WX
   Campos, EI
   Pagano, M
   Dynlacht, BD
AF Li, Ji
   D'Angiolella, Vincenzo
   Seeley, E. Scott
   Kim, Sehyun
   Kobayashi, Tetsuo
   Fu, Wenxiang
   Campos, Eric I.
   Pagano, Michele
   Dynlacht, Brian David
TI USP33 regulates centrosome biogenesis via deubiquitination of the centriolar protein CP110
SO NATURE
LA English
DT Article
ID lindau tumor-suppressor; chromosomal instability; drug targets; cells; abnormality; degradation; carcinoma
AB Centrosome duplication is critical for cell division, and genome instability can result if duplication is not restricted to a single round per cell cycle. Centrosome duplication is controlled in part by CP110, a centriolar protein that positively regulates centriole duplication while restricting centriole elongation and ciliogenesis. Maintenance of normal CP110 levels is essential, as excessive CP110 drives centrosome over-duplication and suppresses ciliogenesis, whereas its depletion inhibits centriole amplification and leads to highly elongated centrioles and aberrant assembly of cilia in growing cells(1,2). CP110 levels are tightly controlled, partly through ubiquitination by the ubiquitin ligase complex SCFcyclin (F) during G2 and M phases of the cell cycle(3). Here, using human cells, we report a new mechanism for the regulation of centrosome duplication that requires USP33, a deubiquitinating enzyme that is able to regulate CP110 levels. USP33 interacts with CP110 and localizes to centrioles primarily in S and G2/M phases, the periods during which centrioles duplicate and elongate. USP33 potently and specifically deubiquitinates CP110, but not other cyclin-F substrates. USP33 activity antagonizes SCFcyclin F-mediated ubiquitination and promotes the generation of supernumerary centriolar foci, whereas ablation of USP33 destabilizes CP110 and thereby inhibits centrosome amplification and mitotic defects. To our knowledge, we have identified the first centriolar deubiquitinatimg enzyme whose expression regulates centrosome homeostasis by countering cyclin-F-mediated destruction of a key substrate. Our results point towards potential therapeutic strategies for inhibiting tumorigenesis associated with centrosome amplification.
C1 [Li, Ji; D'Angiolella, Vincenzo; Kim, Sehyun; Kobayashi, Tetsuo; Fu, Wenxiang; Pagano, Michele; Dynlacht, Brian David] NYU, Sch Med, Smilow Res Ctr, Dept Pathol, New York, NY 10016 USA.
   [Li, Ji; D'Angiolella, Vincenzo; Kim, Sehyun; Kobayashi, Tetsuo; Fu, Wenxiang; Pagano, Michele; Dynlacht, Brian David] NYU, Sch Med, Smilow Res Ctr, Inst Canc, New York, NY 10016 USA.
   [Seeley, E. Scott] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94143 USA.
   [Campos, Eric I.] NYU, Sch Med, Smilow Res Ctr, Dept Biochem, New York, NY 10016 USA.
   [Pagano, Michele] NYU, Sch Med, Smilow Res Ctr, Dept Pathol,Howard Hughes Med Inst, New York, NY 10016 USA.
C3 New York University; New York University; University of California System; University of California San Francisco; New York University; Howard Hughes Medical Institute; New York University
RP Dynlacht, BD (corresponding author), NYU, Sch Med, Smilow Res Ctr, Dept Pathol, 522 1st Ave, New York, NY 10016 USA.
EM Brian.Dynlacht@nyumc.org
FU National Institutes of Health [5R01HD069647-02]; March of Dimes [FY11-432]
NR 20
TC 110
Z9 134
U1 0
U2 26
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 14
PY 2013
VL 495
IS 7440
BP 255
EP 259
DI 10.1038/nature11941
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 113FP
UT WOS:000316652300055
PM 23486064
DA 2026-03-09
ER

PT J
AU Wolfe, SA
   Pisano, DJ
   Lockman, FJ
   McGaugh, SS
   Shaya, EJ
AF Wolfe, Spencer A.
   Pisano, D. J.
   Lockman, Felix J.
   McGaugh, Stacy S.
   Shaya, Edward J.
TI Discrete clouds of neutral gas between the galaxies M31 and M33
SO NATURE
LA English
DT Article
ID tully-fisher relation; high-velocity clouds; intergalactic medium; andromeda galaxy; hi clouds; baryons; halos; field; mass
AB Spiral galaxies must acquire gas to maintain their observed level of star formation beyond the next few billion years(1). A source of this material may be the gas that resides between galaxies, but our understanding of the state and distribution of this gas is incomplete(2). Radio observations(3) of the Local Group of galaxies have revealed hydrogen gas extending from the disk of the galaxy M31 at least halfway to M33. This feature has been interpreted to be the neutral component of a condensing intergalactic filament(4), which would be able to fuel star formation in M31 and M33, but simulations suggest that such a feature could also result from an interaction between both galaxies within the past few billion years (ref. 5). Here we report radio observations showing that about 50 per cent of this gas is composed of clouds, with the rest distributed in an extended, diffuse component. The clouds have velocities comparable to those of M31 and M33, and have properties suggesting that they are unrelated to other Local Group objects. We conclude that the clouds are likely to be transient condensations of gas embedded in an intergalactic filament and are therefore a potential source of fuel for future star formation in M31 and M33.
C1 [Wolfe, Spencer A.; Pisano, D. J.] W Virginia Univ, Dept Phys, Morgantown, WV 26506 USA.
   [Lockman, Felix J.] Natl Radio Astron Observ, Green Bank, WV 24944 USA.
   [McGaugh, Stacy S.] Case Western Reserve Univ, Dept Astron, Cleveland, OH 44106 USA.
   [Shaya, Edward J.] Univ Maryland, Dept Astron, College Pk, MD 20742 USA.
C3 West Virginia University; National Radio Astronomy Observatory (NRAO); University System of Ohio; Case Western Reserve University; University System of Maryland; University of Maryland College Park
RP Wolfe, SA (corresponding author), W Virginia Univ, Dept Phys, POB 6315, Morgantown, WV 26506 USA.
EM swolfe4@mix.wvu.edu
FU NSF [AST-1149491, AST-0908370]; Direct For Mathematical & Physical Scien [1149491] Funding Source: National Science Foundation; Division Of Astronomical Sciences [1149491] Funding Source: National Science Foundation; Division Of Astronomical Sciences; Direct For Mathematical & Physical Scien [0908370] Funding Source: National Science Foundation
NR 26
TC 63
Z9 68
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 MAY 9
PY 2013
VL 497
IS 7448
BP 224
EP 226
DI 10.1038/nature12082
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 139CD
UT WOS:000318558200032
PM 23657349
DA 2026-03-09
ER

PT J
AU Galej, WP
   Oubridge, C
   Newman, AJ
   Nagai, K
AF Galej, Wojciech P.
   Oubridge, Chris
   Newman, Andrew J.
   Nagai, Kiyoshi
TI Crystal structure of Prp8 reveals active site cavity of the spliceosome
SO NATURE
LA English
DT Article
ID splicing factor prp8; small nuclear rnas; messenger-rna; u5 snrnp; secondary-structure; u6 snrna; cross-linking; protein; domain; mechanism
AB The active centre of the spliceosome consists of an intricate network formed by U5, U2 and U6 small nuclear RNAs, and a pre-messenger-RNA substrate. Prp8, a component of the U5 small nuclear ribonucleoprotein particle, crosslinks extensively with this RNA catalytic core. Here we present the crystal structure of yeast Prp8 (residues 885-2413) in complex with Aar2, a U5 small nuclear ribonucleoprotein particle assembly factor. The structure reveals tightly associated domains of Prp8 resembling a bacterial group II intron reverse transcriptase and a type II restriction endonuclease. Suppressors of splice-site mutations, and an intron branch-point crosslink, map to a large cavity formed by the reverse transcriptase thumb, and the endonuclease-like and RNaseH-like domains. This cavity is large enough to accommodate the catalytic core of group II intron RNA. The structure provides crucial insights into the architecture of the spliceosome active site, and reinforces the notion that nuclear pre-mRNA splicing and group II intron splicing have a common origin.
C1 [Galej, Wojciech P.; Oubridge, Chris; Newman, Andrew J.; Nagai, Kiyoshi] MRC Lab Mol Biol, Cambridge CB2 0QH, England.
C3 MRC Laboratory Molecular Biology
RP Nagai, K (corresponding author), MRC Lab Mol Biol, Francis Crick Ave, Cambridge CB2 0QH, England.
EM newman@mrc-lmb.cam.ac.uk; kn@mrc-lmb.cam.ac.uk
FU Cambridge European Trust; Downing College; UK Medical Research Council; MRC [MC_U105184330] Funding Source: UKRI; Medical Research Council [MC_U105184330] Funding Source: researchfish
NR 70
TC 161
Z9 162
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 31
PY 2013
VL 493
IS 7434
BP 638
EP +
DI 10.1038/nature11843
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 080CU
UT WOS:000314219600049
DA 2026-03-09
ER

PT J
AU Ni, LN
   Bronk, P
   Chang, EC
   Lowell, AM
   Flam, JO
   Panzano, VC
   Theobald, DL
   Griffith, LC
   Garrity, PA
AF Ni, Lina
   Bronk, Peter
   Chang, Elaine C.
   Lowell, April M.
   Flam, Juliette O.
   Panzano, Vincent C.
   Theobald, Douglas L.
   Griffith, Leslie C.
   Garrity, Paul A.
TI A gustatory receptor paralogue controls rapid warmth avoidance in Drosophila
SO NATURE
LA English
DT Article
ID neural circuits; heat-sensor; temperature; channel; trpa1; neurons; melanogaster; expression; taste; architecture
AB Behavioural responses to temperature are critical for survival, and animals from insects to humans show strong preferences for specific temperatures(1,2). Preferred temperature selection promotes avoidance of adverse thermal environments in the short term and maintenance of optimal body temperatures over the long term(1,2), but its molecular and cellular basis is largely unknown. Recent studies have generated conflicting views of thermal preference in Drosophila, attributing importance to either internal(3) or peripheral(4) warmth sensors. Here we reconcile these views by showing that thermal preference is not a singular response, but involves multiple systems relevant in different contexts. We found previously that the transient receptor potential channel TRPA1 acts internally to control the slowly developing preference response of flies exposed to a shallow thermal gradient(3). We now find that the rapid response of flies exposed to a steep warmth gradient does not require TRPA1; rather, the gustatory receptor GR28B(D) drives this behaviour through peripheral thermosensors. Gustatory receptors are a large gene family, widely studied in insect gustation and olfaction, and are implicated in host-seeking by insect disease vectors(5-7), but have not previously been implicated in thermosensation. At the molecular level, GR28B(D) misexpression confers thermosensitivity upon diverse cell types, suggesting that it is a warmth sensor. These data reveal a new type of thermosensory molecule and uncover a functional distinction between peripheral and internal warmth sensors in this tiny ectotherm reminiscent of thermoregulatory systems in larger, endothermic animals(2). The use of multiple, distinct molecules to respond to a given temperature, as observed here, may facilitate independent tuning of an animal's distinct thermosensory responses.
C1 [Ni, Lina; Bronk, Peter; Chang, Elaine C.; Lowell, April M.; Flam, Juliette O.; Panzano, Vincent C.; Griffith, Leslie C.; Garrity, Paul A.] Brandeis Univ, Natl Ctr Behav Genom, Waltham, MA 02454 USA.
   [Ni, Lina; Bronk, Peter; Chang, Elaine C.; Lowell, April M.; Flam, Juliette O.; Panzano, Vincent C.; Griffith, Leslie C.; Garrity, Paul A.] Brandeis Univ, Dept Biol, Volen Ctr Complex Syst, Waltham, MA 02454 USA.
   [Theobald, Douglas L.] Brandeis Univ, Dept Biochem, Waltham, MA 02454 USA.
C3 Brandeis University; Brandeis University; Brandeis University
RP Garrity, PA (corresponding author), Brandeis Univ, Natl Ctr Behav Genom, Waltham, MA 02454 USA.
EM pgarrity@brandeis.edu
FU National Institute of Mental Health (NIMH) [EUREKA R01 MH094721]; National Institute of Neurological Disorders and Stroke (NINDS) [PO1 NS044232]; National Science Foundation [IOS-1025307]; National Institute of General Medical Sciences (NIGMS) [R01 GM054408]; NIMH [R01 MH067284]; NIGMS [R01 GM094468]; NINDS National Research Service Award; Division Of Integrative Organismal Systems; Direct For Biological Sciences [1025307] Funding Source: National Science Foundation; National Institute of Mental Health [R01MH067284] Funding Source: NIH RePORTER
NR 31
TC 179
Z9 226
U1 5
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 AUG 29
PY 2013
VL 500
IS 7464
BP 580
EP +
DI 10.1038/nature12390
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 207TD
UT WOS:000323625900035
PM 23925112
DA 2026-03-09
ER

PT J
AU Kumar, R
   DiMenna, L
   Schrode, N
   Liu, TC
   Franck, P
   Muñoz-Descalzo, S
   Hadjantonakis, AK
   Zarrin, AA
   Chaudhuri, J
   Elemento, O
   Evans, T
AF Kumar, Ritu
   DiMenna, Lauren
   Schrode, Nadine
   Liu, Ting-Chun
   Franck, Philipp
   Munoz-Descalzo, Silvia
   Hadjantonakis, Anna-Katerina
   Zarrin, Ali A.
   Chaudhuri, Jayanta
   Elemento, Olivier
   Evans, Todd
TI AID stabilizes stem-cell phenotype by removing epigenetic memory of pluripotency genes
SO NATURE
LA English
DT Article
ID induced cytidine deaminase; dna methylation; expression
AB The activation-induced cytidine deaminase (AID; also known as AICDA) enzyme is required for somatic hypermutation and class switch recombination at the immunoglobulin locus(1). In germinal-centre B cells, AID is highly expressed, and has an inherent mutator activity that helps generate antibody diversity(2). However, AID may also regulate gene expression epigenetically by directly deaminating 5-methylcytosine in concert with base-excision repair to exchange cytosine(3). This pathway promotes gene demethylation, thereby removing epigenetic memory. For example, AID promotes active demethylation of the genome in primordial germ cells(4). However, different studies have suggested either a requirement(5) or a lack of function(6) for AID in promoting pluripotency in somatic nuclei after fusion with embryonic stem cells. Here we tested directly whether AID regulates epigenetic memory by comparing the relative ability of cells lacking AID to reprogram from a differentiated murine cell type to an induced pluripotent stem cell. We show that Aid-null cells are transiently hyper-responsive to the reprogramming process. Although they initiate expression of pluripotency genes, they fail to stabilize in the pluripotent state. The genome of Aid-null cells remains hypermethylated in reprogramming cells, and hypermethylated genes associated with pluripotency fail to be stably upregulated, including many MYC target genes. Recent studies identified a late step of reprogramming associated with methylation status(7), and implicated a secondary set of pluripotency network components(8). AID regulates this late step, removing epigenetic memory to stabilize the pluripotent state.
C1 [Kumar, Ritu; Liu, Ting-Chun; Franck, Philipp; Evans, Todd] Weill Cornell Med Coll, Dept Surg, New York, NY 10065 USA.
   [DiMenna, Lauren; Chaudhuri, Jayanta] Mem Sloan Kettering Canc Ctr, Sloan Kettering Inst, Immunol Program, New York, NY 10065 USA.
   [Schrode, Nadine; Munoz-Descalzo, Silvia; Hadjantonakis, Anna-Katerina] Mem Sloan Kettering Canc Ctr, Sloan Kettering Inst, Dev Biol Program, New York, NY 10065 USA.
   [Zarrin, Ali A.] Genentech Inc, San Francisco, CA 94080 USA.
   [Elemento, Olivier] Weill Cornell Med Coll, Inst Computat Biomed, New York, NY 10065 USA.
C3 Cornell University; Weill Cornell Medicine; Memorial Sloan Kettering Cancer Center; Memorial Sloan Kettering Cancer Center; Roche Holding; Genentech; Roche Holding USA; Cornell University; Weill Cornell Medicine
RP Evans, T (corresponding author), Weill Cornell Med Coll, Dept Surg, New York, NY 10065 USA.
EM tre2003@med.cornell.edu
FU National Institutes of Health [HL056182, AI072194]; National Science Foundation CAREER [1054964]; National Cancer Institute [P30CA008748] Funding Source: NIH RePORTER; National Institute of Allergy and Infectious Diseases [R01AI072194] Funding Source: NIH RePORTER; Div Of Biological Infrastructure; Direct For Biological Sciences [1054964] Funding Source: National Science Foundation
NR 28
TC 78
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 AUG 1
PY 2013
VL 500
IS 7460
BP 89
EP U114
DI 10.1038/nature12299
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 192VK
UT WOS:000322514800034
PM 23803762
DA 2026-03-09
ER

PT J
AU Kettleborough, RNW
   Busch-Nentwich, EM
   Harvey, SA
   Dooley, CM
   de Bruijn, E
   van Eeden, F
   Sealy, I
   White, RJ
   Herd, C
   Nijman, IJ
   Fényes, F
   Mehroke, S
   Scahill, C
   Gibbons, R
   Wali, N
   Carruthers, S
   Hall, A
   Yen, J
   Cuppen, E
   Stemple, DL
AF Kettleborough, Ross N. W.
   Busch-Nentwich, Elisabeth M.
   Harvey, Steven A.
   Dooley, Christopher M.
   de Bruijn, Ewart
   van Eeden, Freek
   Sealy, Ian
   White, Richard J.
   Herd, Colin
   Nijman, Isaac J.
   Fenyes, Fruzsina
   Mehroke, Selina
   Scahill, Catherine
   Gibbons, Richard
   Wali, Neha
   Carruthers, Samantha
   Hall, Amanda
   Yen, Jennifer
   Cuppen, Edwin
   Stemple, Derek L.
TI A systematic genome-wide analysis of zebrafish protein-coding gene function
SO NATURE
LA English
DT Article
ID embryonic stem-cells; identification; inactivation; mutagenesis; disruption; reporter; screen
AB Since the publication of the human reference genome, the identities of specific genes associated with human diseases are being discovered at a rapid rate. A central problem is that the biological activity of these genes is often unclear. Detailed investigations in model vertebrate organisms, typically mice, have been essential for understanding the activities of many orthologues of these disease-associated genes. Although gene-targeting approaches(1-3) and phenotype analysis have led to a detailed understanding of nearly 6,000 protein-coding genes(3,4), this number falls considerably short of the more than 22,000 mouse protein-coding genes(5). Similarly, in zebrafish genetics, one-by-one gene studies using positional cloning(6), insertional mutagenesis(7-9), antisense morpholino oligonucleotides(10), targeted re-sequencing(11-13), and zinc finger and TAL endonucleases(14-17) have made substantial contributions to our understanding of the biological activity of vertebrate genes, but again the number of genes studied falls well short of the more than 26,000 zebrafish protein-coding genes(18). Importantly, for both mice and zebrafish, none of these strategies are particularly suited to the rapid generation of knockouts in thousands of genes and the assessment of their biological activity. Here we describe an active project that aims to identify and phenotype the disruptive mutations in every zebrafish protein-coding gene, using a well-annotated zebrafish reference genome sequence(18,19), high-throughput sequencing and efficient chemical mutagenesis. So far we have identified potentially disruptive mutations in more than 38% of all known zebrafish protein-coding genes. We have developed a multi-allelic phenotyping scheme to efficiently assess the effects of each allele during embryogenesis and have analysed the phenotypic consequences of over 1,000 alleles. All mutant alleles and data are available to the community and our phenotyping scheme is adaptable to phenotypic analysis beyond embryogenesis.
C1 [Kettleborough, Ross N. W.; Busch-Nentwich, Elisabeth M.; Harvey, Steven A.; Dooley, Christopher M.; Sealy, Ian; White, Richard J.; Herd, Colin; Fenyes, Fruzsina; Mehroke, Selina; Scahill, Catherine; Gibbons, Richard; Wali, Neha; Carruthers, Samantha; Hall, Amanda; Yen, Jennifer; Stemple, Derek L.] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England.
   [de Bruijn, Ewart; Nijman, Isaac J.; Cuppen, Edwin] KNAW, Hubrecht Inst, NL-3584 CT Utrecht, Netherlands.
   [de Bruijn, Ewart; Nijman, Isaac J.; Cuppen, Edwin] Univ Med Ctr Utrecht, NL-3584 CT Utrecht, Netherlands.
   [van Eeden, Freek] Univ Sheffield, Dept Biomed Sci, MRC CDBG, Sheffield S10 2TN, S Yorkshire, England.
C3 Wellcome Trust Sanger Institute; Royal Netherlands Academy of Arts & Sciences; Hubrecht Institute (KNAW); Utrecht University; Utrecht University Medical Center; University of Sheffield
RP Stemple, DL (corresponding author), Wellcome Trust Sanger Inst, Wellcome Trust Genome Campus, Cambridge CB10 1SA, England.
EM e.cuppen@hubrecht.eu; ds4@sanger.ac.uk
FU Wellcome Trust [098051]; US National Institutes of Health [5R01HG004819]; EU Sixth Framework Programme (ZF-MODELS) [LSHG-CT-2003-503496]; EU Seventh Framework Programme (ZF-HEALTH); UK Medical Research Council [G0777791]; SmartMix program from the Dutch government [SSM06010]
NR 30
TC 479
Z9 573
U1 2
U2 134
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 25
PY 2013
VL 496
IS 7446
BP 494
EP +
DI 10.1038/nature11992
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 131HU
UT WOS:000317984400039
PM 23594742
DA 2026-03-09
ER

PT J
AU Noda, H
   Lapusta, N
AF Noda, Hiroyuki
   Lapusta, Nadia
TI Stable creeping fault segments can become destructive as a result of dynamic weakening
SO NATURE
LA English
DT Article
ID tohoku-oki earthquake; state-dependent friction; chelungpu fault; fluid pressure; pore-fluid; chi-chi; slip; rupture; taiwan; megathrust
AB Faults in Earth's crust accommodate slow relative motion between tectonic plates through either similarly slow slip or fast, seismic-wave-producing rupture events perceived as earthquakes(1-3). These types of behaviour are often assumed to be separated in space and to occur on two different types of fault segment: one with stable, rate-strengthening friction and the other with rate-weakening friction that leads to stick-slip(2-5). The 2011 Tohoku-Oki earthquake with moment magnitude M-w = 9.0 challenged such assumptions by accumulating its largest seismic slip in the area that had been assumed to be creeping(6-10). Here we propose a model in which stable, rate-strengthening behaviour at low slip rates(11,12) is combined with coseismic weakening due to rapid shear heating of pore fluids(13-16), allowing unstable slip to occur in segments that can creep between events. The model parameters are based on laboratory measurements on samples from the fault of the M-w 7.6 1999 Chi-Chi earthquake(17). The long-term slip behaviour of the model, which we examine using a unique numerical approach that includes all wave effects(16,18), reproduces and explains a number of both long-term and coseismic observations-some of them seemingly contradictory-about the faults at which the Tohoku-Oki and Chi-Chi earthquakes occurred, including there being more high-frequency radiation from areas of lower slip(8,19-21), the largest seismic slip in the Tohoku-Oki earthquake having occurred in a potentially creeping segment(6,7), the overall pattern of previous events in the area(8) and the complexity of the Tohoku-Oki rupture(9). The implication that earthquake rupture may break through large portions of creeping segments, which are at present considered to be barriers, requires a re-evaluation of seismic hazard in many areas.
C1 [Noda, Hiroyuki] Japan Agcy Marine Earth Sci & Technol, Inst Res Earth Evolut, Yokohama, Kanagawa 2360001, Japan.
   [Lapusta, Nadia] CALTECH, Div Geol & Planetary Sci, Pasadena, CA 91125 USA.
   [Lapusta, Nadia] CALTECH, Div Engn & Appl Sci, Pasadena, CA 91125 USA.
C3 Japan Agency for Marine-Earth Science & Technology (JAMSTEC); California Institute of Technology; California Institute of Technology
RP Noda, H (corresponding author), Japan Agcy Marine Earth Sci & Technol, Inst Res Earth Evolut, Yokohama, Kanagawa 2360001, Japan.
EM hnoda@jamstec.go.jp
FU US National Science Foundation (NSF) [EAR 0548277]; Southern California Earthquake Center (SCEC); Gordon and Betty Moore Foundation; NSF [EAR-0106924]; USGS [02HQAG0008]; Division Of Earth Sciences; Directorate For Geosciences [1142183] Funding Source: National Science Foundation
NR 36
TC 435
Z9 502
U1 5
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 JAN 24
PY 2013
VL 493
IS 7433
BP 518
EP +
DI 10.1038/nature11703
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 075GF
UT WOS:000313871400035
PM 23302798
DA 2026-03-09
ER

PT J
AU Baradaran, R
   Berrisford, JM
   Minhas, GS
   Sazanov, LA
AF Baradaran, Rozbeh
   Berrisford, John M.
   Minhas, Gurdeep S.
   Sazanov, Leonid A.
TI Crystal structure of the entire respiratory complex I
SO NATURE
LA English
DT Article
ID nadh-quinone oxidoreductase; electron-transport chain; thermus-thermophilus; hydrophilic domain; escherichia-coli; mitochondria; subunits; ubiquinone; stoichiometry; mechanism
AB Complex I is the first and largest enzyme of the respiratory chain and has a central role in cellular energy production through the coupling of NADH:ubiquinone electron transfer to proton translocation. It is also implicated in many common human neurodegenerative diseases. Here, we report the first crystal structure of the entire, intact complex I (from Thermus thermophilus) at 3.3 angstrom resolution. The structure of the 536-kDa complex comprises 16 different subunits, with a total of 64 transmembrane helices and 9 iron-sulphur clusters. The core fold of subunit Nqo8 (ND1 in humans) is, unexpectedly, similar to a half-channel of the antiporter-like subunits. Small subunits nearby form a linked second half-channel, which completes the fourth proton-translocation pathway (present in addition to the channels in three antiporter-like subunits). The quinone-binding site is unusually long, narrow and enclosed. The quinone headgroup binds at the deep end of this chamber, near iron-sulphur cluster N2. Notably, the chamber is linked to the fourth channel by a 'funnel' of charged residues. The link continues over the entire membrane domain as a flexible central axis of charged and polar residues, and probably has a leading role in the propagation of conformational changes, aided by coupling elements. The structure suggests that a unique, out-of-the-membrane quinone-reaction chamber enables the redox energy to drive concerted long-range conformational changes in the four antiporter-like domains, resulting in translocation of four protons per cycle.
C1 [Baradaran, Rozbeh; Berrisford, John M.; Minhas, Gurdeep S.; Sazanov, Leonid A.] Wellcome Trust Res Labs, MRC, Mitochondrial Biol Unit, Cambridge CB2 0XY, England.
C3 Wellcome Trust Sanger Institute
RP Sazanov, LA (corresponding author), Wellcome Trust Res Labs, MRC, Mitochondrial Biol Unit, MRC Bldg,Hills Rd, Cambridge CB2 0XY, England.
EM sazanov@mrc-mbu.cam.ac.uk
FU Medical Research Council; Medical Research Council [MC_U105674180] Funding Source: researchfish; MRC [MC_U105674180] Funding Source: UKRI
NR 45
TC 664
Z9 757
U1 3
U2 300
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 28
PY 2013
VL 494
IS 7438
BP 443
EP 448
DI 10.1038/nature11871
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 099YI
UT WOS:000315661500030
PM 23417064
DA 2026-03-09
ER

PT J
AU Tata, PR
   Mou, HM
   Pardo-Saganta, A
   Zhao, R
   Prabhu, M
   Law, BM
   Vinarsky, V
   Cho, JL
   Breton, S
   Sahay, A
   Medoff, BD
   Rajagopal, J
AF Tata, Purushothama Rao
   Mou, Hongmei
   Pardo-Saganta, Ana
   Zhao, Rui
   Prabhu, Mythili
   Law, Brandon M.
   Vinarsky, Vladimir
   Cho, Josalyn L.
   Breton, Sylvie
   Sahay, Amar
   Medoff, Benjamin D.
   Rajagopal, Jayaraj
TI Dedifferentiation of committed epithelial cells into stem cells in vivo
SO NATURE
LA English
DT Article
ID progenitor cells; lung development; regeneration; origin; airway; expression; transdifferentiation; maintenance; revert; repair
AB Cellular plasticity contributes to the regenerative capacity of plants, invertebrates, teleost fishes and amphibians. In vertebrates, differentiated cells are known to revert into replicating progenitors, but these cells do not persist as stable stem cells. Here we present evidence that differentiated airway epithelial cells can revert into stable and functional stem cells in vivo. After the ablation of airway stem cells, we observed a surprising increase in the proliferation of committed secretory cells. Subsequent lineage tracing demonstrated that the luminal secretory cells had dedifferentiated into basal stem cells. Dedifferentiated cells were morphologically indistinguishable from stem cells and they functioned as well as their endogenous counterparts in repairing epithelial injury. Single secretory cells clonally dedifferentiated into multipotent stem cells when they were cultured ex vivo without basal stem cells. By contrast, direct contact with a single basal stem cell was sufficient to prevent secretory cell dedifferentiation. In analogy to classical descriptions of amphibian nuclear reprogramming, the propensity of committed cells to dedifferentiate is inversely correlated to their state of maturity. This capacity of committed cells to dedifferentiate into stem cells may have a more general role in the regeneration of many tissues and in multiple disease states, notably cancer.
C1 [Tata, Purushothama Rao; Mou, Hongmei; Pardo-Saganta, Ana; Zhao, Rui; Prabhu, Mythili; Law, Brandon M.; Vinarsky, Vladimir; Sahay, Amar; Rajagopal, Jayaraj] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA.
   [Tata, Purushothama Rao; Mou, Hongmei; Pardo-Saganta, Ana; Zhao, Rui; Prabhu, Mythili; Law, Brandon M.; Vinarsky, Vladimir; Rajagopal, Jayaraj] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA.
   [Tata, Purushothama Rao; Mou, Hongmei; Pardo-Saganta, Ana; Zhao, Rui; Prabhu, Mythili; Law, Brandon M.; Vinarsky, Vladimir; Cho, Josalyn L.; Medoff, Benjamin D.; Rajagopal, Jayaraj] Massachusetts Gen Hosp, Dept Internal Med, Pulm & Crit Care Unit, Boston, MA 02114 USA.
   [Tata, Purushothama Rao; Mou, Hongmei; Pardo-Saganta, Ana; Zhao, Rui; Prabhu, Mythili; Law, Brandon M.; Vinarsky, Vladimir; Sahay, Amar; Rajagopal, Jayaraj] Harvard Stem Cell Inst, Cambridge, MA 02138 USA.
   [Cho, Josalyn L.; Medoff, Benjamin D.] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Charlestown, MA 02129 USA.
   [Breton, Sylvie] Massachusetts Gen Hosp, Ctr Syst Biol, Program Membrane Biol, Boston, MA 02214 USA.
   [Breton, Sylvie] Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02214 USA.
   [Breton, Sylvie] Harvard Univ, Sch Med, Boston, MA 02214 USA.
   [Sahay, Amar] Harvard Univ, Dept Psychiat, Sch Med, Boston, MA 02215 USA.
C3 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 University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard Medical School; Harvard University; Harvard Medical School
RP Rajagopal, J (corresponding author), Massachusetts Gen Hosp, Ctr Regenerat Med, 185 Cambridge St, Boston, MA 02114 USA.
EM jrajagopal@partners.org
FU Harvard Stem Cell Institute Seed Grant; National Institutes of Health-National Heart, Lung, and Blood Institute Early Career Research New Faculty [5P30HL101287-02]; Harvard Stem Cell Institute (HSCI) Junior Investigator Grant; National Heart Lung and Blood Institute [R01HL118185] Funding Source: NIH RePORTER; National Institute of Diabetes and Digestive and Kidney Diseases [P30DK043351] Funding Source: NIH RePORTER
NR 35
TC 545
Z9 652
U1 0
U2 143
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 14
PY 2013
VL 503
IS 7475
BP 218
EP +
DI 10.1038/nature12777
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 250YX
UT WOS:000326894200042
PM 24196716
DA 2026-03-09
ER

PT J
AU Burrell, RA
   McClelland, SE
   Endesfelder, D
   Groth, P
   Weller, MC
   Shaikh, N
   Domingo, E
   Kanu, N
   Dewhurst, SM
   Gronroos, E
   Chew, SK
   Rowan, AJ
   Schenk, A
   Sheffer, M
   Howell, M
   Kschischo, M
   Behrens, A
   Helleday, T
   Bartek, J
   Tomlinson, IR
   Swanton, C
AF Burrell, Rebecca A.
   McClelland, Sarah E.
   Endesfelder, David
   Groth, Petra
   Weller, Marie-Christine
   Shaikh, Nadeem
   Domingo, Enric
   Kanu, Nnennaya
   Dewhurst, Sally M.
   Gronroos, Eva
   Chew, Su Kit
   Rowan, Andrew J.
   Schenk, Arne
   Sheffer, Michal
   Howell, Michael
   Kschischo, Maik
   Behrens, Axel
   Helleday, Thomas
   Bartek, Jiri
   Tomlinson, Ian R.
   Swanton, Charles
TI Replication stress links structural and numerical cancer chromosomal instability
SO NATURE
LA English
DT Article
ID dna-damage response; segregation errors; evolution; origins
AB Cancer chromosomal instability (CIN) results in an increased rate of change of chromosome number and structure and generates intratumour heterogeneity(1,2). CIN is observed in most solid tumours and is associated with both poor prognosis and drug resistance(3,4). Understanding a mechanistic basis for CIN is therefore paramount. Here we find evidence for impaired replication fork progression and increased DNA replication stress in CIN+ colorectal cancer (CRC) cells relative to CIN- CRC cells, with structural chromosome abnormalities precipitating chromosome missegregation in mitosis. We identify three new CIN-suppressor genes (PIGN (also known as MCD4), MEX3C (RKHD2) and ZNF516 (KIAA0222)) encoded on chromosome 18q that are subject to frequent copy number loss in CIN+ CRC. Chromosome 18q loss was temporally associated with aneuploidy onset at the adenoma-carcinoma transition. CIN-suppressor gene silencing leads to DNA replication stress, structural chromosome abnormalities and chromosome missegregation. Supplementing cells with nucleosides, to alleviate replication-associated damage(5), reduces the frequency of chromosome segregation errors after CIN-suppressor gene silencing, and attenuates segregation errors and DNA damage in CIN+ cells. These data implicate a central role for replication stress in the generation of structural and numerical CIN, which may inform new therapeutic approaches to limit intratumour heterogeneity.
C1 [Burrell, Rebecca A.; McClelland, Sarah E.; Endesfelder, David; Shaikh, Nadeem; Kanu, Nnennaya; Dewhurst, Sally M.; Gronroos, Eva; Chew, Su Kit; Rowan, Andrew J.; Howell, Michael; Behrens, Axel; Swanton, Charles] Canc Res UK London Res Inst, London WC2A 3LY, England.
   [Endesfelder, David; Schenk, Arne; Kschischo, Maik] Univ Appl Sci Koblenz, Dept Math & Technol, D-53424 Remagen, Germany.
   [Groth, Petra; Weller, Marie-Christine; Helleday, Thomas] Karolinska lnstitutet, Sci Life Lab, Div Translat Med & Chem Biol, Dept Med Biochem & Biophys, S-17121 Stockholm, Sweden.
   [Domingo, Enric; Tomlinson, Ian R.] Wellcome Trust Ctr Human Genet, Mol & Populat Genet & NIHR Biomed Res Ctr, Oxford OX3 7BN, England.
   [Chew, Su Kit; Swanton, Charles] UCL Canc Inst, London WC1E 6BT, England.
   [Sheffer, Michal] Weizmann Inst Sci, Dept Phys Complex Syst, IL-76100 Rehovot, Israel.
   [Bartek, Jiri] Danish Canc Soc, Res Ctr, DK-2100 Copenhagen, Denmark.
   [Bartek, Jiri] Palacky Univ Olomouc, Inst Mol & Translat Med, CZ-77515 Olomouc, Czech Republic.
C3 Cancer Research UK; Karolinska Institutet; University of Oxford; Wellcome Centre for Human Genetics; University of London; University College London; Weizmann Institute of Science; Danish Cancer Society; Palacky University Olomouc
RP Swanton, C (corresponding author), Canc Res UK London Res Inst, 44 Lincolns Inn Fields, London WC2A 3LY, England.
EM charles.swanton@cancer.org.uk
FU Cancer Research UK; Medical Research Council; EU; Prostate Cancer Foundation; Breast Cancer Research Foundation; Oxford Biomedical Research Centre; Danish Cancer Society; Lundbeck Foundation; European Commission; Swedish Cancer Society; Swedish Research Council; Torsten and Ragnar Soderberg Foundation; Cancer Research UK [15679, 16459] Funding Source: researchfish
NR 27
TC 686
Z9 780
U1 0
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 FEB 28
PY 2013
VL 494
IS 7438
BP 492
EP 496
DI 10.1038/nature11935
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 099YI
UT WOS:000315661500042
PM 23446422
DA 2026-03-09
ER

PT J
AU Okada-Iwabu, M
   Yamauchi, T
   Iwabu, M
   Honma, T
   Hamagami, K
   Matsuda, K
   Yamaguchi, M
   Tanabe, H
   Kimura-Someya, T
   Shirouzu, M
   Ogata, H
   Tokuyama, K
   Ueki, K
   Nagano, T
   Tanaka, A
   Yokoyama, S
   Kadowaki, T
AF Okada-Iwabu, Miki
   Yamauchi, Toshimasa
   Iwabu, Masato
   Honma, Teruki
   Hamagami, Ken-ichi
   Matsuda, Koichi
   Yamaguchi, Mamiko
   Tanabe, Hiroaki
   Kimura-Someya, Tomomi
   Shirouzu, Mikako
   Ogata, Hitomi
   Tokuyama, Kumpei
   Ueki, Kohjiro
   Nagano, Tetsuo
   Tanaka, Akiko
   Yokoyama, Shigeyuki
   Kadowaki, Takashi
TI A small-molecule AdipoR agonist for type 2 diabetes and short life in obesity
SO NATURE
LA English
DT Article
ID activated protein-kinase; fatty-acid oxidation; insulin-resistance; adiponectin levels; skeletal-muscle; crucial role; disease; inflammation; mechanisms; expression
AB Adiponectin secreted from adipocytes binds to adiponectin receptors AdipoR1 and AdipoR2, and exerts antidiabetic effects via activation of AMPK and PPAR-alpha pathways, respectively. Levels of adiponectin in plasma are reduced in obesity, which causes insulin resistance and type 2 diabetes. Thus, orally active small molecules that bind to and activate AdipoR1 and AdipoR2 could ameliorate obesity-related diseases such as type 2 diabetes. Here we report the identification of orally active synthetic small-molecule AdipoR agonists. One of these compounds, AdipoR agonist (AdipoRon), bound to both AdipoR1 and AdipoR2 in vitro. AdipoRon showed very similar effects to adiponectin in muscle and liver, such as activation of AMPK and PPAR-alpha pathways, and ameliorated insulin resistance and glucose intolerance in mice fed a high-fat diet, which was completely obliterated in AdipoR1 and AdipoR2 double-knockout mice. Moreover, AdipoRon ameliorated diabetes of genetically obese rodent model db/db mice, and prolonged the shortened lifespan of db/db mice on a high-fat diet. Thus, orally active AdipoR agonists such as AdipoRon are a promising therapeutic approach for the treatment of obesity-related diseases such as type 2 diabetes.
C1 [Okada-Iwabu, Miki; Yamauchi, Toshimasa; Iwabu, Masato; Hamagami, Ken-ichi; Matsuda, Koichi; Yamaguchi, Mamiko; Ueki, Kohjiro; Kadowaki, Takashi] Univ Tokyo, Grad Sch Med, Dept Diabet & Metab Dis, Tokyo 1130033, Japan.
   [Okada-Iwabu, Miki; Yamauchi, Toshimasa; Iwabu, Masato; Kadowaki, Takashi] Univ Tokyo, Dept Integrated Mol Sci Metab Dis, 22nd Century Med & Res Ctr, Tokyo 1130033, Japan.
   [Okada-Iwabu, Miki; Yamauchi, Toshimasa; Kadowaki, Takashi] Univ Tokyo, Dept Mol Med Sci Metab Regulat, 22nd Century Med & Res Ctr, Tokyo 1130033, Japan.
   [Honma, Teruki; Tanabe, Hiroaki; Kimura-Someya, Tomomi; Shirouzu, Mikako; Tanaka, Akiko; Yokoyama, Shigeyuki] RIKEN Syst & Struct Biol Ctr, Yokohama, Kanagawa 2300045, Japan.
   [Ogata, Hitomi; Tokuyama, Kumpei] Univ Tsukuba, Grad Sch Comprehens Human Sci, Tsukuba, Ibaraki 3058577, Japan.
   [Nagano, Tetsuo; Tanaka, Akiko] Univ Tokyo, Open Innovat Ctr Drug Discovery, Bunkyo Ku, Tokyo 1130033, Japan.
   [Yokoyama, Shigeyuki] Univ Tokyo, Grad Sch Sci, Bunkyo Ku, Tokyo 1130033, Japan.
C3 University of Tokyo; University of Tokyo; University of Tokyo; RIKEN; University of Tsukuba; University of Tokyo; University of Tokyo
RP Kadowaki, T (corresponding author), Univ Tokyo, Grad Sch Med, Dept Diabet & Metab Dis, Tokyo 1130033, Japan.
EM tyamau-tky@umin.net; kadowaki-3im@h.u-tokyo.ac.jp
FU Ministry of Education, Culture, Sports, Science and Technology of Japan [20229008, 25221307, 23689048]; Translational Systems Biology and Medicine Initiative from the Ministry of Education, Culture, Sports, Science and Technology of Japan; Translational Research Network Program from the Ministry of Education, Culture, Sports, Science and Technology of Japan; Cabinet Office, Government of Japan; Grants-in-Aid for Scientific Research [24700694, 24790908, 20229008, 23689048] Funding Source: KAKEN
NR 42
TC 612
Z9 697
U1 7
U2 237
PU NATURE PUBLISHING 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 28
PY 2013
VL 503
IS 7477
BP 493
EP +
DI 10.1038/nature12656
PG 20
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 258MU
UT WOS:000327464200036
PM 24172895
DA 2026-03-09
ER

PT J
AU Casassus, S
   van der Plas, G
   Perez, MS
   Dent, WRF
   Fomalont, E
   Hagelberg, J
   Hales, A
   Jordán, A
   Mawet, D
   Ménard, F
   Wootten, A
   Wilner, D
   Hughes, AM
   Schreiber, MR
   Girard, JH
   Ercolano, B
   Canovas, H
   Román, PE
   Salinas, V
AF Casassus, Simon
   van der Plas, Gerrit
   Sebastian Perez, M.
   Dent, William R. F.
   Fomalont, Ed
   Hagelberg, Janis
   Hales, Antonio
   Jordan, Andres
   Mawet, Dimitri
   Menard, Francois
   Wootten, Al
   Wilner, David
   Hughes, A. Meredith
   Schreiber, Matthias R.
   Girard, Julien H.
   Ercolano, Barbara
   Canovas, Hector
   Roman, Pablo E.
   Salinas, Vachail
TI Flows of gas through a protoplanetary gap
SO NATURE
LA English
DT Article
ID disk surrounding hd-142527; co fundamental emission; herbig ae/be stars; t-tauri; transitional disks; planet formation; molecular gas; ae stars; spectroscopy; accretion
AB The formation of gaseous giant planets is thought to occur in the first few million years after stellar birth. Models(1) predict that the process produces a deep gap in the dust component (shallower in the gas(2-4)). Infrared observations of the disk around the young star HD 142527 (at a distance of about 140 parsecs from Earth) found an inner disk about 10 astronomical units (AU) in radius(5) (1 AU is the Earth-Sun distance), surrounded by a particularly large gap(6) and a disrupted(7) outer disk beyond 140 AU. This disruption is indicative of a perturbing planetary-mass body at about 90 AU. Radio observations(8,9) indicate that the bulk mass is molecular and lies in the outer disk, whose continuum emission has a horseshoe morphology(8). The high stellar accretion rate(10) would deplete the inner disk(11) in less than one year, and to sustain the observed accretion matter must therefore flow from the outer disk and cross the gap. In dynamical models, the putative protoplanets channel outer-disk material into gap-crossing bridges that feed stellar accretion through the inner disk(12). Here we report observations of diffuse CO gas inside the gap, with denser HCO+ gas along gap-crossing filaments. The estimated flow rate of the gas is in the range of 7 x 10(-9) to 2 x 10(-7) solar masses per year, which is sufficient to maintain accretion onto the star at the present rate.
C1 [Casassus, Simon; van der Plas, Gerrit; Sebastian Perez, M.; Menard, Francois; Salinas, Vachail] Univ Chile, Dept Astron, Santiago, Chile.
   [Dent, William R. F.; Hales, Antonio] Joint ALMA Observ, Santiago 7630355, Chile.
   [Dent, William R. F.; Mawet, Dimitri; Girard, Julien H.] European So Observ, Santiago 19, Chile.
   [Fomalont, Ed; Hales, Antonio; Wootten, Al] Natl Radio Astron Observ, Charlottesville, VA 22903 USA.
   [Hagelberg, Janis] Univ Geneva, Observ Geneve, CH-1290 Versoix, Switzerland.
   [Jordan, Andres] Pontificia Univ Catolica Chile, Dept Astron & Astrofis, Santiago, Chile.
   [Menard, Francois] CNRS INSU France UMI 3386, UMI FCA, Grenoble, France.
   [Menard, Francois] UJF Grenoble 1, CNRS, UMR 5274, IPAG, F-48041 Grenoble 9, France.
   [Wilner, David] Harvard Smithsonian Ctr Astrophys, Cambridge, MA 02138 USA.
   [Hughes, A. Meredith] Univ Calif Berkeley, Dept Astron, Berkeley, CA 94720 USA.
   [Schreiber, Matthias R.; Canovas, Hector] Univ Valparaiso, Dept Fis & Astron, Valparaiso, Chile.
   [Ercolano, Barbara] Univ Munich, Univ Observ, D-81679 Munich, Germany.
   [Roman, Pablo E.] Univ Chile, Ctr Math Modeling, Santiago, Chile.
C3 Universidad de Chile; European Southern Observatory; National Radio Astronomy Observatory (NRAO); University of Geneva; Pontificia Universidad Catolica de Chile; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Earth Sciences & Astronomy (INSU); Centre National de la Recherche Scientifique (CNRS); Communaute Universite Grenoble Alpes; Universite Grenoble Alpes (UGA); Harvard University; Smithsonian Astrophysical Observatory; Smithsonian Institution; University of California System; University of California Berkeley; Universidad de Valparaiso; University of Munich; Universidad de Chile
RP Casassus, S (corresponding author), Univ Chile, Dept Astron, Casilla 36-D, Santiago, Chile.
EM scasassus@u.uchile.cl
FU Millennium Nucleus [P10-022-F]; European Union [FONDECYT 1100221, 284405]
NR 30
TC 320
Z9 337
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 JAN 10
PY 2013
VL 493
IS 7431
BP 191
EP 194
DI 10.1038/nature11769
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 066YY
UT WOS:000313259600033
PM 23283173
DA 2026-03-09
ER

PT J
AU Liao, MF
   Cao, EH
   Julius, D
   Cheng, YF
AF Liao, Maofu
   Cao, Erhu
   Julius, David
   Cheng, Yifan
TI Structure of the TRPV1 ion channel determined by electron cryo-microscopy
SO NATURE
LA English
DT Article
ID high-level expression; crystal-structure; voltage; pore; receptor; visualization; selectivity; mutations; reveals; system
AB Transient receptor potential (TRP) channels are sensors for a wide range of cellular and environmental signals, but elucidating how these channels respond to physical and chemical stimuli has been hampered by a lack of detailed structural information. Here we exploit advances in electron cryo-microscopy to determine the structure of a mammalian TRP channel, TRPV1, at 3.4 angstrom resolution, breaking the side-chain resolution barrier for membrane proteins without crystallization. Like voltage-gated channels, TRPV1 exhibits four-fold symmetry around a central ion pathway formed by transmembrane segments 5-6 (S5-S6) and the intervening pore loop, which is flanked by S1-S4 voltage-sensor-like domains. TRPV1 has a wide extracellular 'mouth' with a short selectivity filter. The conserved 'TRP domain' interacts with the S4-S5 linker, consistent with its contribution to allosteric modulation. Subunit organization is facilitated by interactions among cytoplasmic domains, including amino-terminal ankyrin repeats. These observations provide a structural blueprint for understanding unique aspects of TRP channel function.
C1 [Liao, Maofu; Cheng, Yifan] Univ Calif San Francisco, Dept Biochem & Biophys, Keck Adv Microscopy Lab, San Francisco, CA 94158 USA.
   [Cao, Erhu; Julius, David] Univ Calif San Francisco, Dept Physiol, San Francisco, CA 94158 USA.
C3 University of California System; University of California San Francisco; University of California System; University of California San Francisco
RP Julius, D (corresponding author), Univ Calif San Francisco, Dept Physiol, San Francisco, CA 94158 USA.
EM david.julius@ucsf.edu; ycheng@ucsf.edu
FU National Institutes of Health [R01GM098672, S10RR026814, R01NS065071, R01NS047723]; National Science Foundation [DBI-0960271]; University of California, San Francisco Program for Breakthrough Biomedical Research
NR 55
TC 1339
Z9 1632
U1 12
U2 713
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 5
PY 2013
VL 504
IS 7478
BP 107
EP +
DI 10.1038/nature12822
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 264BK
UT WOS:000327851700040
PM 24305160
DA 2026-03-09
ER

PT J
AU Lee, CH
   Orloff, ND
   Birol, T
   Zhu, Y
   Goian, V
   Rocas, E
   Haislmaier, R
   Vlahos, E
   Mundy, JA
   Kourkoutis, LF
   Nie, YF
   Biegalski, MD
   Zhang, JS
   Bernhagen, M
   Benedek, NA
   Kim, Y
   Brock, JD
   Uecker, R
   Xi, XX
   Gopalan, V
   Nuzhnyy, D
   Kamba, S
   Muller, DA
   Takeuchi, I
   Booth, JC
   Fennie, CJ
   Schlom, DG
AF Lee, Che-Hui
   Orloff, Nathan D.
   Birol, Turan
   Zhu, Ye
   Goian, Veronica
   Rocas, Eduard
   Haislmaier, Ryan
   Vlahos, Eftihia
   Mundy, Julia A.
   Kourkoutis, Lena F.
   Nie, Yuefeng
   Biegalski, Michael D.
   Zhang, Jingshu
   Bernhagen, Margitta
   Benedek, Nicole A.
   Kim, Yongsam
   Brock, Joel D.
   Uecker, Reinhard
   Xi, X. X.
   Gopalan, Venkatraman
   Nuzhnyy, Dmitry
   Kamba, Stanislav
   Muller, David A.
   Takeuchi, Ichiro
   Booth, James C.
   Fennie, Craig J.
   Schlom, Darrell G.
TI Exploiting dimensionality and defect mitigation to create tunable microwave dielectrics
SO NATURE
LA English
DT Article
ID thin-films; dependence; ferroelectricity; dispersion; oxides
AB The miniaturization and integration of frequency-agile microwave circuits-relevant to electronically tunable filters, antennas, resonators and phase shifters-with microelectronics offers tantalizing device possibilities, yet requires thin films whose dielectric constant at gigahertz frequencies can be tuned by applying a quasi-static electric field(1). Appropriate systems such as BaxSr1-xTiO3 have a paraelectric-ferroelectric transition just below ambient temperature, providing high tunability(1-3). Unfortunately, such films suffer significant losses arising from defects. Recognizing that progress is stymied by dielectric loss, we start with a system with exceptionally low loss-Srn+1TinO3n+1 phases(4,5)-in which (SrO)(2) crystallographic shear(6,7) planes provide an alternative to the formation of point defects for accommodating non-stoichiometry(8,9). Here we report the experimental realization of a highly tunable ground state arising from the emergence of a local ferroelectric instability(10) in biaxially strained Srn+1TinO3n+1 phases with n >= 3 at frequencies up to 125 GHz. In contrast to traditional methods of modifying ferroelectrics-doping(1-3,11,12) or strain(13-16)-in this unique system an increase in the separation between the (SrO)(2) planes, which can be achieved by changing n, bolsters the local ferroelectric instability. This new control parameter, n, can be exploited to achieve a figure of merit at room temperature that rivals all known tunable microwave dielectrics(3).
C1 [Lee, Che-Hui; Nie, Yuefeng; Zhang, Jingshu; Schlom, Darrell G.] Cornell Univ, Dept Mat Sci & Engn, Ithaca, NY 14853 USA.
   [Lee, Che-Hui; Haislmaier, Ryan; Vlahos, Eftihia; Gopalan, Venkatraman] Penn State Univ, Dept Mat Sci & Engn, University Pk, PA 16802 USA.
   [Orloff, Nathan D.; Booth, James C.] NIST, Boulder, CO 80305 USA.
   [Orloff, Nathan D.] Univ Maryland, Dept Phys, College Pk, MD 20742 USA.
   [Birol, Turan; Zhu, Ye; Mundy, Julia A.; Kourkoutis, Lena F.; Kim, Yongsam; Brock, Joel D.; Muller, David A.; Fennie, Craig J.] Cornell Univ, Sch Appl & Engn Phys, Ithaca, NY 14853 USA.
   [Goian, Veronica; Nuzhnyy, Dmitry; Kamba, Stanislav] Inst Phys ASCR, Prague 18221 8, Czech Republic.
   [Rocas, Eduard] Univ Politecn Cataluna, Dept Signal Theory & Commun, ES-08034 Barcelona, Spain.
   [Kourkoutis, Lena F.; Muller, David A.; Schlom, Darrell G.] Kavli Inst Cornell Nanoscale Sci, Ithaca, NY 14853 USA.
   [Biegalski, Michael D.] Oak Ridge Natl Lab, Ctr Nanophase Mat Sci, Oak Ridge, TN 37831 USA.
   [Bernhagen, Margitta; Uecker, Reinhard] Leibniz Inst Crystal Growth, D-12489 Berlin, Germany.
   [Benedek, Nicole A.] Univ Texas Austin, Mat Sci & Engn Program, Austin, TX 78712 USA.
   [Xi, X. X.] Temple Univ, Dept Phys, Philadelphia, PA 19122 USA.
   [Takeuchi, Ichiro] Univ Maryland, Dept Mat Sci & Engn, College Pk, MD 20742 USA.
C3 Cornell University; Pennsylvania Commonwealth System of Higher Education (PCSHE); Pennsylvania State University; Pennsylvania State University - University Park; National Institute of Standards & Technology (NIST) - USA; University System of Maryland; University of Maryland College Park; Cornell University; Czech Academy of Sciences; Institute of Physics of the Czech Academy of Sciences; Universitat Politecnica de Catalunya; United States Department of Energy (DOE); Oak Ridge National Laboratory; Center for Nanophase Materials Sciences; Leibniz Association; Leibniz Institut fur Kristallzuchtung (IKZ); University of Texas System; University of Texas Austin; Pennsylvania Commonwealth System of Higher Education (PCSHE); Temple University; University System of Maryland; University of Maryland College Park
RP Schlom, DG (corresponding author), Cornell Univ, Dept Mat Sci & Engn, Ithaca, NY 14853 USA.
EM schlom@cornell.edu
FU Army Research Office (ARO) [W911NF-09-1-0415, W911NF-12-1-0437, W911NF-10-1-0345]; National Science Foundation (NSF) through Materials Research Science and Engineering Centers (MRSEC) [DMR-0820404, DMR-1120296]; Czech Science Foundation [P204/12/1163]; Czech Ministry of Education, Youth and Sports [LD12026]; Spanish Government; European Union [EUI-ENIAC-2011-4349, EUI-ENIAC 2010-04252]; NSF [DMR-0820404]; National Defense Science & Engineering Graduate Fellowship; Oak Ridge National Laboratory by the Scientific User Facilities Division, Office of Basic Energy Sciences, US Department of Energy; National Science Foundation [ECCS-0335765]; NSF MRSEC programme [DMR 1120296, NSF IMR-0417392]
NR 47
TC 231
Z9 270
U1 7
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 OCT 24
PY 2013
VL 502
IS 7472
BP 532
EP +
DI 10.1038/nature12582
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 238YN
UT WOS:000325988400050
PM 24132232
DA 2026-03-09
ER

PT J
AU Zimmermann, G
   Papke, B
   Ismail, S
   Vartak, N
   Chandra, A
   Hoffmann, M
   Hahn, SA
   Triola, G
   Wittinghofer, A
   Bastiaens, PIH
   Waldmann, H
AF Zimmermann, Gunther
   Papke, Bjoern
   Ismail, Shehab
   Vartak, Nachiket
   Chandra, Anchal
   Hoffmann, Maike
   Hahn, Stephan A.
   Triola, Gemma
   Wittinghofer, Alfred
   Bastiaens, Philippe I. H.
   Waldmann, Herbert
TI Small molecule inhibition of the KRAS-PDEδ interaction impairs oncogenic KRAS signalling
SO NATURE
LA English
DT Article
ID k-ras; protein prenylation; cancer-therapy; activation; discovery; membrane; ligands; bind; flim; erk
AB The KRAS oncogene product is considered a major target in anticancer drug discovery(1-3). However, direct interference with KRAS signalling has not yet led to clinically useful drugs(3-8). Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDE delta, which sustains the spatial organization of KRAS by facilitating its diffusion in the cytoplasm(9-11). Here we report that interfering with binding of mammalian PDEd to KRAS by means of small molecules provides a novel opportunity to suppress oncogenic RAS signalling by altering its localization to endomembranes. Biochemical screening and subsequent structure-based hit optimization yielded inhibitors of the KRAS-PDE delta interaction that selectively bind to the prenyl-binding pocket of PDE delta with nanomolar affinity, inhibit oncogenic RAS signalling and suppress in vitro and in vivo proliferation of human pancreatic ductal adenocarcinoma cells that are dependent on oncogenic KRAS. Our findings may inspire novel drug discovery efforts aimed at the development of drugs targeting oncogenic RAS.
C1 [Zimmermann, Gunther; Triola, Gemma; Waldmann, Herbert] Max Planck Inst Mol Physiol, Dept Chem Biol, D-44227 Dortmund, Germany.
   [Papke, Bjoern; Vartak, Nachiket; Chandra, Anchal; Bastiaens, Philippe I. H.] Max Planck Inst Mol Physiol, Dept Syst Cell Biol, D-44227 Dortmund, Germany.
   [Ismail, Shehab; Wittinghofer, Alfred] Max Planck Inst Mol Physiol, Struct Biol Grp, D-44227 Dortmund, Germany.
   [Hoffmann, Maike; Hahn, Stephan A.] Ruhr Univ Bochum, Dept Mol Gastrointestinal Oncol, D-44801 Bochum, Germany.
   [Bastiaens, Philippe I. H.; Waldmann, Herbert] TU Dortmund, Fac Chem, D-44227 Dortmund, Germany.
C3 Max Planck Society; Max Planck Society; Max Planck Society; Ruhr University Bochum; Dortmund University of Technology
RP Waldmann, H (corresponding author), Max Planck Inst Mol Physiol, Dept Chem Biol, D-44227 Dortmund, Germany.
EM alfred.wittinghofer@mpi-dortmund.mpg.de; philippe.bastiaens@mpi-dortmund.mpg.de; herbert.waldmann@mpi-dortmund.mpg.de
FU European Research Council under the European Union [268309, 268782]; Fonds der Chemischen Industrie; European Research Council (ERC) [268782] Funding Source: European Research Council (ERC)
NR 26
TC 508
Z9 629
U1 1
U2 238
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 30
PY 2013
VL 497
IS 7451
BP 638
EP 642
DI 10.1038/nature12205
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 152UF
UT WOS:000319556100048
PM 23698361
DA 2026-03-09
ER

PT J
AU Lyra, W
   Kuchner, M
AF Lyra, W.
   Kuchner, M.
TI Formation of sharp eccentric rings in debris disks with gas but without planets
SO NATURE
LA English
DT Article
ID beta-pictoris; fomalhaut b; dust; turbulence; origin; system
AB 'Debris disks' around young stars (analogues of the Kuiper Belt in our Solar System) show a variety of non-trivial structures attributed to planetary perturbations and used to constrain the properties of those planets(1-3). However, these analyses have largely ignored the fact that some debris disks are found to contain small quantities of gas(4-9), a component that all such disks should contain at some level(10,11). Several debris disks have been measured with a dust-to-gas ratio of about unity(4-9), at which the effect of hydrodynamics on the structure of the disk cannot be ignored(12,13). Here we report linear and nonlinear modelling that shows that dust-gas interactions can produce some of the key patterns attributed to planets. We find a robust clumping instability that organizes the dust into narrow, eccentric rings, similar to the Fomalhaut debris disk(14). The conclusion that such disks might contain planets is not necessarily required to explain these systems.
C1 [Lyra, W.] CALTECH, Jet Prop Lab, Pasadena, CA 91109 USA.
   [Lyra, W.] CALTECH, Div Geol & Planetary Sci, Pasadena, CA 91125 USA.
   [Lyra, W.] Amer Museum Nat Hist, Dept Astrophys, New York, NY 10024 USA.
   [Kuchner, M.] NASA, Goddard Space Flight Ctr, Exoplanets & Stellar Astrophys Lab, Greenbelt, MD 21230 USA.
C3 National Aeronautics & Space Administration (NASA); NASA Jet Propulsion Laboratory (JPL); California Institute of Technology; California Institute of Technology; American Museum of Natural History (AMNH); National Aeronautics & Space Administration (NASA); NASA Goddard Space Flight Center
RP Lyra, W (corresponding author), CALTECH, Jet Prop Lab, 4800 Oak Grove Dr, Pasadena, CA 91109 USA.
EM wlyra@caltech.edu; marc.j.kuchner@nasa.gov
FU National Science Foundation [AST10-09802]; National Aeronautics and Space Administration; National Science Foundation; NASA Astrobiology Institute through the Goddard Center for Astrobiology; Direct For Mathematical & Physical Scien; Division Of Astronomical Sciences [1009802] Funding Source: National Science Foundation
NR 30
TC 93
Z9 104
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 JUL 11
PY 2013
VL 499
IS 7457
BP 184
EP 187
DI 10.1038/nature12281
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 179YA
UT WOS:000321557600056
PM 23846656
DA 2026-03-09
ER

PT J
AU Mousavi, SAR
   Chauvin, A
   Pascaud, F
   Kellenberger, S
   Farmer, EE
AF Mousavi, Seyed A. R.
   Chauvin, Adeline
   Pascaud, Francois
   Kellenberger, Stephan
   Farmer, Edward E.
TI GLUTAMATE RECEPTOR-LIKE genes mediate leaf-to-leaf wound signalling
SO NATURE
LA English
DT Article
ID jasmonic acid; atpase activity; arabidopsis; defense; plants; accumulation; potentials; expression; induction; responses
AB Wounded leaves communicate their damage status to one another through a poorly understood process of long-distance signalling. This stimulates the distal production of jasmonates, potent regulators of defence responses. Using non-invasive electrodes we mapped surface potential changes in Arabidopsis thaliana after wounding leaf eight and found that membrane depolarizations correlated with jasmonate signalling domains in undamaged leaves. Furthermore, current injection elicited jasmonoyl-isoleucine accumulation, resulting in a transcriptome enriched in RNAs encoding key jasmonate signalling regulators. From among 34 screened membrane protein mutant lines, mutations in several clade 3 GLUTAMATE RECEPTOR-LIKE genes (GLRs 3.2, 3.3 and 3.6) attenuated wound-induced surface potential changes. Jasmonate-response gene expression in leaves distal to wounds was reduced in a glr3.3 glr3.6 double mutant. This work provides a genetic basis for investigating mechanisms of long-distance wound signalling in plants and indicates that plant genes related to those important for synaptic activity in animals function in organ-to-organ wound signalling.
C1 [Mousavi, Seyed A. R.; Farmer, Edward E.] Univ Lausanne, Dept Plant Mol Biol, CH-1015 Lausanne, Switzerland.
   [Chauvin, Adeline] Univ Geneva, Sch Pharmaceut Sci, CH-1211 Geneva 4, Switzerland.
   [Pascaud, Francois; Kellenberger, Stephan] Univ Lausanne, Dept Pharmacol & Toxicol, CH-1005 Lausanne, Switzerland.
C3 University of Lausanne; University of Geneva; University of Lausanne
RP Farmer, EE (corresponding author), Univ Lausanne, Dept Plant Mol Biol, CH-1015 Lausanne, Switzerland.
EM edward.farmer@unil.ch
FU Faculty of Biology and Medicine Interdisciplinary grant; Swiss NSF [3100A0-122441, 31003A-138235]
NR 54
TC 626
Z9 705
U1 12
U2 443
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 22
PY 2013
VL 500
IS 7463
BP 422
EP +
DI 10.1038/nature12478
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 203TJ
UT WOS:000323316100027
PM 23969459
DA 2026-03-09
ER

PT J
AU Kane, M
   Yadav, SS
   Bitzegeio, J
   Kutluay, SB
   Zang, T
   Wilson, SJ
   Schoggins, JW
   Rice, CM
   Yamashita, M
   Hatziioannou, T
   Bieniasz, PD
AF Kane, Melissa
   Yadav, Shalini S.
   Bitzegeio, Julia
   Kutluay, Sebla B.
   Zang, Trinity
   Wilson, Sam J.
   Schoggins, John W.
   Rice, Charles M.
   Yamashita, Masahiro
   Hatziioannou, Theodora
   Bieniasz, Paul D.
TI MX2 is an interferon-induced inhibitor of HIV-1 infection
SO NATURE
LA English
DT Article
ID immunodeficiency-virus; nuclear import; nondividing cells; lentiviral vector; gene; replication; determinants; restriction; macrophages; protein
AB HIV-1 replication can be inhibited by type I interferon (IFN), and the expression of a number of gene products with anti-HIV-1 activity is induced by type I IFN1,2. However, none of the known antiretroviral proteins can account for the ability of type I IFN to inhibit early, preintegration phases of the HIV-1 replication cycle in human cells(3,4). Here, by comparing gene expression profiles in cell lines that differ in their ability to support the inhibitory action of IFN-alpha at early steps of the HIV-1 replication cycle, we identify myxovirus resistance 2 (MX2) as an interferon-induced inhibitor of HIV-1 infection. Expression of MX2 reduces permissiveness to a variety of lentiviruses, whereas depletion of MX2 using RNA interference reduces the anti-HIV-1 potency of IFN-alpha. HIV-1 reverse transcription proceeds normally in MX2-expressing cells, but 2-long terminal repeat circular forms of HIV-1 DNA are less abundant, suggesting that MX2 inhibits HIV-1 nuclear import, or destabilizes nuclear HIV-1 DNA. Consistent with this notion, mutations in the HIV-1 capsid protein that are known, or suspected, to alter the nuclear import pathways used by HIV-1 confer resistance to MX2, whereas preventing cell division increases MX2 potency. Overall, these findings indicate that MX2 is an effector of the anti-HIV-1 activity of type-I IFN, and suggest that MX2 inhibits HIV-1 infection by inhibiting capsid-dependent nuclear import of subviral complexes.
C1 [Kane, Melissa; Yadav, Shalini S.; Bitzegeio, Julia; Kutluay, Sebla B.; Zang, Trinity; Wilson, Sam J.; Yamashita, Masahiro; Hatziioannou, Theodora; Bieniasz, Paul D.] Aaron Diamond AIDS Res Ctr, New York, NY 10016 USA.
   [Kane, Melissa; Yadav, Shalini S.; Bitzegeio, Julia; Kutluay, Sebla B.; Zang, Trinity; Wilson, Sam J.; Bieniasz, Paul D.] Rockefeller Univ, Lab Retrovirol, New York, NY 10065 USA.
   [Yadav, Shalini S.; Zang, Trinity; Wilson, Sam J.; Bieniasz, Paul D.] Howard Hughes Med Inst, New York, NY 10016 USA.
   [Schoggins, John W.; Rice, Charles M.] Rockefeller Univ, Ctr Study Hepatitis C, New York, NY 10065 USA.
C3 Rockefeller University; Howard Hughes Medical Institute; Rockefeller University
RP Bieniasz, PD (corresponding author), Aaron Diamond AIDS Res Ctr, New York, NY 10016 USA.
EM pbienias@adarc.org
FU National Institutes of Health [R37AI64003, R01AI078788, R01AI100720, AI091707, AI057158, DK095031]; Greenberg Medical Research Institute; Starr Foundation; Howard Hughes Medical Institute; MRC [G0801822, MR/K024752/1] Funding Source: UKRI; National Institute of Allergy and Infectious Diseases [R01AI078788, R01AI100720] Funding Source: NIH RePORTER; Medical Research Council [MR/K024752/1, G0801822] Funding Source: researchfish
NR 30
TC 416
Z9 509
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 OCT 24
PY 2013
VL 502
IS 7472
BP 563
EP +
DI 10.1038/nature12653
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 238YN
UT WOS:000325988400057
PM 24121441
DA 2026-03-09
ER

PT J
AU Kawatani, Y
   Hamilton, K
AF Kawatani, Yoshio
   Hamilton, Kevin
TI Weakened stratospheric quasibiennial oscillation driven by increased tropical mean upwelling
SO NATURE
LA English
DT Article
ID brewer-dobson circulation; changing climate; qbo; period; model; modulation; air; age
AB The zonal wind in the tropical stratosphere switches between prevailing easterlies and westerlies with a period of about 28 months(1). In the lowermost stratosphere, the vertical structure of this quasibiennial oscillation (QBO) is linked to the mean upwelling(2-4), which itself is a key factor in determining stratospheric composition. Evidence for changes in the QBO have until now been equivocal, raising questions as to the extent of stratospheric circulation changes in a global warming context. Here we report an analysis of near-equatorial radiosonde observations for 1953-2012, and reveal a long-term trend of weakening amplitude in the zonal wind QBO in the tropical lower stratosphere. The trend is particularly notable at the 70-hectopascal pressure level (an altitude of about 19 kilometres), where the QBO amplitudes dropped by roughly one-third over the period. This trend is also apparent in the global warming simulations of the four models in the Coupled Model Intercomparison Project Phase 5 (CMIP5) that realistically simulate the QBO. The weakening is most reasonably explained as resulting from a trend of increased mean tropical upwelling in the lower stratosphere. Almost all comprehensive climate models have projected an intensifying tropical upwelling in global warming scenarios(5-7), but attempts to estimate changes in the upwelling by using observational data have yielded ambiguous, inconclusive or contradictory results(8-10). Our discovery of a weakening trend in the lower-stratosphere QBO amplitude provides strong support for the existence of a long-term trend of enhanced upwelling near the tropical tropopause.
C1 [Kawatani, Yoshio] Japan Agcy Marine Earth Sci & Technol, Res Inst Global Change, Kanazawa Ku, Yokohama, Kanagawa 2360001, Japan.
   [Hamilton, Kevin] Univ Hawaii Manoa, SOEST, Int Pacific Res Ctr, Honolulu, HI 96822 USA.
C3 Japan Agency for Marine-Earth Science & Technology (JAMSTEC); University of Hawaii System; University of Hawaii Manoa
RP Kawatani, Y (corresponding author), Japan Agcy Marine Earth Sci & Technol, Res Inst Global Change, Kanazawa Ku, 3173-25 Showamachi, Yokohama, Kanagawa 2360001, Japan.
EM yoskawatani@jamstec.go.jp
FU Japan Agency for Marine-Earth Science and Technology through International Pacific Research Center; Ministry of the Environment, Japan [A-1201]; JSPS KAKENHI [23740363, 24340113]; NASA [NNX07AG53G]; NOAA [NA11NMF4320128]; International Pacific Research Center; Data Integration and Analysis System (DIAS) Fund for National Key Technology from MEXT; Grants-in-Aid for Scientific Research [23740363] Funding Source: KAKEN
NR 29
TC 105
Z9 107
U1 0
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 MAY 23
PY 2013
VL 497
IS 7450
BP 478
EP +
DI 10.1038/nature12140
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 148OG
UT WOS:000319254000045
PM 23698448
DA 2026-03-09
ER

PT J
AU Shukla, AK
   Manglik, A
   Kruse, AC
   Xiao, KH
   Reis, RI
   Tseng, WC
   Staus, DP
   Hilger, D
   Uysal, S
   Huang, LY
   Paduch, M
   Tripathi-Shukla, P
   Koide, A
   Koide, S
   Weis, WI
   Kossiakoff, AA
   Kobilka, BK
   Lefkowitz, RJ
AF Shukla, Arun K.
   Manglik, Aashish
   Kruse, Andrew C.
   Xiao, Kunhong
   Reis, Rosana I.
   Tseng, Wei-Chou
   Staus, Dean P.
   Hilger, Daniel
   Uysal, Serdar
   Huang, Li-Yin
   Paduch, Marcin
   Tripathi-Shukla, Prachi
   Koide, Akiko
   Koide, Shohei
   Weis, William I.
   Kossiakoff, Anthony A.
   Kobilka, Brian K.
   Lefkowitz, Robert J.
TI Structure of active β-arrestin-1 bound to a G-protein-coupled receptor phosphopeptide
SO NATURE
LA English
DT Article
ID crystal-structure; beta-arrestin; ternary complex; ligand-binding; conformation; state; endocytosis; mechanism; domain
AB The functions of G-protein-coupled receptors (GPCRs) are primarily mediated and modulated by three families of proteins: the heterotrimeric G proteins, the G-protein-coupled receptor kinases (GRKs) and the arrestins(1). G proteins mediate activation of second-messenger-generating enzymes and other effectors, GRKs phosphorylate activated receptors(2), and arrestins subsequently bind phosphorylated receptors and cause receptor desensitization(3). Arrestins activated by interaction with phosphorylated receptors can also mediate G-protein-independent signalling by serving as adaptors to link receptors to numerous signalling pathways(4). Despite their central role in regulation and signalling of GPCRs, a structural understanding of beta-arrestin activation and interaction with GPCRs is still lacking. Here we report the crystal structure of beta-arrestin-1 (also called arrestin-2) in complex with a fully phosphorylated 29-amino-acid carboxy-terminal peptide derived from the human V2 vasopressin receptor (V2Rpp). This peptide has previously been shown to functionally and conformationally activate beta-arrestin-1 (ref. 5). To capture this active conformation, we used a conformationally selective synthetic antibody fragment (Fab30) that recognizes the phosphopeptide-activated state of beta-arrestin-1. The structure of the beta-arrestin-1-V2Rpp-Fab30 complex shows marked conformational differences in beta-arrestin-1 compared to its inactive conformation. These include rotation of the amino- and carboxy-terminal domains relative to each other, and a major reorientation of the 'lariat loop' implicated in maintaining the inactive state of beta-arrestin-1. These results reveal, at high resolution, a receptor-interacting interface on beta-arrestin, and they indicate a potentially general molecular mechanism for activation of these multifunctional signalling and regulatory proteins.
C1 [Shukla, Arun K.; Xiao, Kunhong; Reis, Rosana I.; Tseng, Wei-Chou; Staus, Dean P.; Huang, Li-Yin; Tripathi-Shukla, Prachi; Lefkowitz, Robert J.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA.
   [Manglik, Aashish; Kruse, Andrew C.; Hilger, Daniel; Weis, William I.; Kobilka, Brian K.] Stanford Univ, Sch Med, Stanford, CA 94305 USA.
   [Uysal, Serdar; Paduch, Marcin; Koide, Akiko; Koide, Shohei; Kossiakoff, Anthony A.] Univ Chicago, Dept Biochem & Mol Biol, Chicago, IL 60637 USA.
   [Weis, William I.] Stanford Univ, Sch Med, Dept Biol Struct, Stanford, CA 94305 USA.
   [Lefkowitz, Robert J.] Duke Univ, Med Ctr, Howard Hughes Med Inst, Durham, NC 27710 USA.
   [Lefkowitz, Robert J.] Duke Univ, Med Ctr, Dept Biochem, Durham, NC 27706 USA.
C3 Duke University; Stanford University; University of Chicago; Stanford University; Howard Hughes Medical Institute; Duke University; Duke University
RP Kobilka, BK (corresponding author), Stanford Univ, Sch Med, Stanford, CA 94305 USA.
EM kobilka@stanford.edu; lefko001@receptor-biol.duke.edu
FU Stanford Medical Scientist Training Program; American Heart Association; National Science Foundation; National Institutes of Health [NS028471, HL16037, HL70631, GM072688, GM087519, HL 075443]; Mathers Foundation; Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior-CAPES; National Heart Lung and Blood Institute [R01HL016037] Funding Source: NIH RePORTER; National Institute of Neurological Disorders and Stroke [R01NS028471] Funding Source: NIH RePORTER
NR 38
TC 361
Z9 426
U1 1
U2 114
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 2
PY 2013
VL 497
IS 7447
BP 137
EP +
DI 10.1038/nature12120
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 134OK
UT WOS:000318221500049
PM 23604254
DA 2026-03-09
ER

PT J
AU Dougan, SK
   Ashour, J
   Karssemeijer, RA
   Popp, MW
   Avalos, AM
   Barisa, M
   Altenburg, AF
   Ingram, JR
   Cragnolini, JJ
   Guo, CG
   Alt, FW
   Jaenisch, R
   Ploegh, HL
AF Dougan, Stephanie K.
   Ashour, Joseph
   Karssemeijer, Roos A.
   Popp, Maximilian W.
   Avalos, Ana M.
   Barisa, Marta
   Altenburg, Arwen F.
   Ingram, Jessica R.
   Cragnolini, Juan Jose
   Guo, Chunguang
   Alt, Frederick W.
   Jaenisch, Rudolf
   Ploegh, Hidde L.
TI Antigen-specific B-cell receptor sensitizes B cells to infection by influenza virus
SO NATURE
LA English
DT Article
ID transnuclear mice; t-cells; in-vivo; memory; lung; strains; entry
AB Influenza A virus-specific B lymphocytes and the antibodies they produce protect against infection(1). However, the outcome of interactions between an influenza haemagglutinin-specific B cell via its receptor (BCR) and virus is unclear. Through somatic cell nuclear transfer we generated mice that harbour B cells with a BCR specific for the haemagglutinin of influenza A/WSN/33 virus (FluBI mice). Their B cells secrete an immunoglobulin gamma 2b that neutralizes infectious virus. Whereas B cells from FluBI and control mice bind equivalent amounts of virus through interaction of haemagglutinin with surface-disposed sialic acids, the A/WSN/33 virus infects only the haemagglutinin-specific B cells. Mere binding of virus is not sufficient for infection of B cells: this requires interactions of the BCR with haemagglutinin, causing both disruption of antibody secretion and FluBI B-cell death within 18 h. In mice infected with A/WSN/33, lung-resident FluBI B cells are infected by the virus, thus delaying the onset of protective antibody release into the lungs, whereas FluBI cells in the draining lymph node are not infected and proliferate. We propose that influenza targets and kills influenza-specific B cells in the lung, thus allowing the virus to gain purchase before the initiation of an effective adaptive response.
C1 [Dougan, Stephanie K.; Ashour, Joseph; Karssemeijer, Roos A.; Popp, Maximilian W.; Avalos, Ana M.; Barisa, Marta; Altenburg, Arwen F.; Ingram, Jessica R.; Cragnolini, Juan Jose; Jaenisch, Rudolf; Ploegh, Hidde L.] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA.
   [Popp, Maximilian W.; Ploegh, Hidde L.] MIT, Dept Biol, Cambridge, MA 02139 USA.
   [Guo, Chunguang; Alt, Frederick W.] Boston Childrens Hosp, Boston, MA 02115 USA.
C3 Massachusetts Institute of Technology (MIT); Whitehead Institute; Massachusetts Institute of Technology (MIT); Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital
RP Ploegh, HL (corresponding author), Whitehead Inst Biomed Res, 9 Cambridge Ctr, Cambridge, MA 02142 USA.
EM ploegh@wi.mit.edu
FU Cancer Research Institute; Human Frontiers Science Program; National Institutes of Health; American Association for Cancer Research-Pancreatic Cancer Action Network
NR 30
TC 57
Z9 68
U1 1
U2 38
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 21
PY 2013
VL 503
IS 7476
BP 406
EP +
DI 10.1038/nature12637
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 254KG
UT WOS:000327163200043
PM 24141948
DA 2026-03-09
ER

PT J
AU Diehl, GE
   Longman, RS
   Zhang, JX
   Breart, B
   Galan, C
   Cuesta, A
   Schwab, SR
   Littman, DR
AF Diehl, Gretchen E.
   Longman, Randy S.
   Zhang, Jing-Xin
   Breart, Beatrice
   Galan, Carolina
   Cuesta, Adolfo
   Schwab, Susan R.
   Littman, Dan R.
TI Microbiota restricts trafficking of bacteria to mesenteric lymph nodes by CX3CR1hi cells
SO NATURE
LA English
DT Article
ID dendritic cells; host; salmonella; inflammation; tolerance; responses; tissue
AB The intestinal microbiota has a critical role in immune system and metabolic homeostasis, but it must be tolerated by the host to avoid inflammatory responses that can damage the epithelial barrier separating the host from the luminal contents(1-6). Breakdown of this regulation and the resulting inappropriate immune response to commensals are thought to lead to the development of inflammatory bowel diseases such as Crohn's disease and ulcerative colitis(7). We proposed that the intestinal immune system is instructed by the microbiota to limit responses to luminal antigens. Here we demonstrate in mice that, at steady state, the microbiota inhibits the transport of both commensal and pathogenic bacteria from the lumen to a key immune inductive site, the mesenteric lymph nodes (MLNs). However, in the absence of Myd88 or under conditions of antibiotic-induced dysbiosis, non-invasive bacteria were trafficked to the MLNs in a CCR7-dependent manner, and induced both T-cell responses and IgA production. Trafficking was carried out by CX(3)CR1(hi) mononuclear phagocytes, an intestinal-cell population previously reported to be non-migratory(8). These findings define a central role for commensals in regulating the migration to the MLNs of CX(3)CR1(hi) mononuclear phagocytes endowed with the ability to capture luminal bacteria, thereby compartmentalizing the intestinal immune response to avoid inflammation.
C1 [Diehl, Gretchen E.; Longman, Randy S.; Zhang, Jing-Xin; Breart, Beatrice; Galan, Carolina; Cuesta, Adolfo; Schwab, Susan R.; Littman, Dan R.] NYU, Sch Med, Kimmel Ctr Biol & Med, Mol Pathogenesis Program,Skirball Inst, New York, NY 10016 USA.
   [Longman, Randy S.] Columbia Univ, Dept Med, Div Digest & Liver Dis, New York, NY 10032 USA.
   [Cuesta, Adolfo; Littman, Dan R.] NYU, Sch Med, Howard Hughes Med Inst, New York, NY 10016 USA.
C3 New York University; Columbia University; Howard Hughes Medical Institute; New York University
RP Diehl, GE (corresponding author), NYU, Sch Med, Kimmel Ctr Biol & Med, Mol Pathogenesis Program,Skirball Inst, New York, NY 10016 USA.
EM Gretchen.Diehl@med.nyu.edu
FU National Cancer Institute [5P30CA016087-32]; American Cancer Society; National Institutes of Health (NIH) [T32 CA009161, T32 DK083256-02, R01AI085166]; Human Frontier Science Program Long-Term Fellowship; Howard Hughes Medical Institute; National Cancer Institute [P30CA016087] Funding Source: NIH RePORTER; National Institute of Allergy and Infectious Diseases [R01AI085166] Funding Source: NIH RePORTER; National Institute of Diabetes and Digestive and Kidney Diseases [T32DK083256] Funding Source: NIH RePORTER
NR 30
TC 392
Z9 490
U1 0
U2 99
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 7
PY 2013
VL 494
IS 7435
BP 116
EP 120
DI 10.1038/nature11809
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 087DJ
UT WOS:000314741200045
PM 23334413
DA 2026-03-09
ER

PT J
AU Song, YM
   Xie, YZ
   Malyarchuk, V
   Xiao, JL
   Jung, I
   Choi, KJ
   Liu, ZJ
   Park, H
   Lu, CF
   Kim, RH
   Li, R
   Crozier, KB
   Huang, YG
   Rogers, JA
AF Song, Young Min
   Xie, Yizhu
   Malyarchuk, Viktor
   Xiao, Jianliang
   Jung, Inhwa
   Choi, Ki-Joong
   Liu, Zhuangjian
   Park, Hyunsung
   Lu, Chaofeng
   Kim, Rak-Hwan
   Li, Rui
   Crozier, Kenneth B.
   Huang, Yonggang
   Rogers, John A.
TI Digital cameras with designs inspired by the arthropod eye
SO NATURE
LA English
DT Article
ID superposition eye; optics
AB In arthropods, evolution has created a remarkably sophisticated class of imaging systems, with a wide-angle field of view, low aberrations, high acuity to motion and an infinite depth of field(1-3). A challenge in building digital cameras with the hemispherical, compound apposition layouts of arthropod eyes is that essential design requirements cannot be met with existing planar sensor technologies or conventional optics. Here we present materials, mechanics and integration schemes that afford scalable pathways to working, arthropod-inspired cameras with nearly full hemispherical shapes (about 160 degrees). Their surfaces are densely populated by imaging elements (artificial ommatidia), which are comparable in number (180) to those of the eyes of fire ants (Solenopsis fugax) and bark beetles(4,5) (Hylastes nigrinus). The devices combine elastomeric compound optical elements with deformable arrays of thin silicon photodetectors into integrated sheets that can be elastically transformed from the planar geometries in which they are fabricated to hemispherical shapes for integration into apposition cameras. Our imaging results and quantitative ray-tracing-based simulations illustrate key features of operation. These general strategies seem to be applicable to other compound eye devices, such as those inspired by moths and lacewings(6,7) (refracting superposition eyes), lobster and shrimp(8) (reflecting superposition eyes), and houseflies(9) (neural superposition eyes).
C1 [Song, Young Min; Xie, Yizhu; Malyarchuk, Viktor; Kim, Rak-Hwan; Rogers, John A.] Univ Illinois, Dept Mat Sci & Engn, Beckman Inst Adv Sci & Technol, 1304 W Green St, Urbana, IL 61801 USA.
   [Song, Young Min; Xie, Yizhu; Malyarchuk, Viktor; Kim, Rak-Hwan; Rogers, John A.] Univ Illinois, Frederick Seitz Mat Res Lab, Urbana, IL 61801 USA.
   [Xiao, Jianliang] Univ Colorado, Dept Mech Engn, Boulder, CO 80309 USA.
   [Jung, Inhwa] Kyung Hee Univ, Dept Mech Engn, Yongin 446701, Gyeonggi Do, South Korea.
   [Choi, Ki-Joong; Rogers, John A.] Univ Illinois, Dept Chem, Urbana, IL 61801 USA.
   [Liu, Zhuangjian] ASTAR, Inst High Performance Comp, Singapore 138632, Singapore.
   [Park, Hyunsung; Crozier, Kenneth B.] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA.
   [Lu, Chaofeng] Zhejiang Univ, Dept Civil Engn, Hangzhou 310058, Zhejiang, Peoples R China.
   [Lu, Chaofeng] Zhejiang Univ, Soft Matter Res Ctr, Hangzhou 310058, Zhejiang, Peoples R China.
   [Lu, Chaofeng; Li, Rui; Huang, Yonggang] Northwestern Univ, Dept Civil & Environm Engn, Dept Mech Engn, Evanston, IL 60208 USA.
   [Li, Rui] Dalian Univ Technol, Dept Engn Mech, State Key Lab Struct Anal Ind Equipment, Dalian 116024, Peoples R China.
C3 University of Illinois System; University of Illinois Urbana-Champaign; University of Illinois System; University of Illinois Urbana-Champaign; University of Colorado System; University of Colorado Boulder; Kyung Hee University; University of Illinois System; University of Illinois Urbana-Champaign; Agency for Science Technology & Research (A*STAR); A*STAR - Institute of High Performance Computing (IHPC); Harvard University; Zhejiang University; Zhejiang University; Northwestern University; Dalian University of Technology
RP Rogers, JA (corresponding author), Univ Illinois, Dept Mat Sci & Engn, Beckman Inst Adv Sci & Technol, 1304 W Green St, Urbana, IL 61801 USA.
EM jrogers@illinois.edu
FU Defense Advanced Research Projects Agency (DARPA) Nanoelectromechanical /Microelectromechanical Science AMP; Technology (N/MEMS SAMP;T) Fundamentals programme by the Space and Naval Warfare Systems Center Pacific (SPAWAR) [N66001-10-1-4008]; National Science Foundation through an Emerging Frontiers in Research and Innovation (EFRI) programme; Directorate For Engineering; Emerging Frontiers & Multidisciplinary Activities [0937847] Funding Source: National Science Foundation; Div Of Electrical, Commun & Cyber Sys; Directorate For Engineering [1307561] Funding Source: National Science Foundation
NR 30
TC 1011
Z9 1156
U1 21
U2 1072
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 2
PY 2013
VL 497
IS 7447
BP 95
EP 99
DI 10.1038/nature12083
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 134OK
UT WOS:000318221500040
PM 23636401
DA 2026-03-09
ER

PT J
AU Flot, JF
   Hespeels, B
   Li, X
   Noel, B
   Arkhipova, I
   Danchin, EGJ
   Hejnol, A
   Henrissat, B
   Koszul, R
   Aury, JM
   Barbe, V
   Barthelemy, RM
   Bast, J
   Bazykin, GA
   Chabrol, O
   Couloux, A
   Da Rocha, M
   Da Silva, C
   Gladyshev, E
   Gouret, P
   Hallatschek, O
   Hecox-Lea, B
   Labadie, K
   Lejeune, B
   Piskurek, O
   Poulain, J
   Rodriguez, F
   Ryan, JF
   Vakhrusheva, OA
   Wajnberg, E
   Wirth, B
   Yushenova, I
   Kellis, M
   Kondrashov, AS
   Welch, DBM
   Pontarotti, P
   Weissenbach, J
   Wincker, P
   Jaillon, O
   Van Doninck, K
AF Flot, Jean-Francois
   Hespeels, Boris
   Li, Xiang
   Noel, Benjamin
   Arkhipova, Irina
   Danchin, Etienne G. J.
   Hejnol, Andreas
   Henrissat, Bernard
   Koszul, Romain
   Aury, Jean-Marc
   Barbe, Valerie
   Barthelemy, Roxane-Marie
   Bast, Jens
   Bazykin, Georgii A.
   Chabrol, Olivier
   Couloux, Arnaud
   Da Rocha, Martine
   Da Silva, Corinne
   Gladyshev, Eugene
   Gouret, Philippe
   Hallatschek, Oskar
   Hecox-Lea, Bette
   Labadie, Karine
   Lejeune, Benjamin
   Piskurek, Oliver
   Poulain, Julie
   Rodriguez, Fernando
   Ryan, Joseph F.
   Vakhrusheva, Olga A.
   Wajnberg, Eric
   Wirth, Benedicte
   Yushenova, Irina
   Kellis, Manolis
   Kondrashov, Alexey S.
   Welch, David B. Mark
   Pontarotti, Pierre
   Weissenbach, Jean
   Wincker, Patrick
   Jaillon, Olivier
   Van Doninck, Karine
TI Genomic evidence for ameiotic evolution in the bdelloid rotifer Adineta vaga
SO NATURE
LA English
DT Article
ID gene conversion
AB Loss of sexual reproduction is considered an evolutionary dead end for metazoans, but bdelloid rotifers challenge this view as they appear to have persisted asexually for millions of years(1). Neither male sex organs nor meiosis have ever been observed in these microscopic animals: oocytes are formed through mitotic divisions, with no reduction of chromosome number and no indication of chromosome pairing(2). However, current evidence does not exclude that they may engage in sex on rare, cryptic occasions. Here we report the genome of a bdelloid rotifer, Adineta vaga (Davis, 1873)(3), and show that its structure is incompatible with conventional meiosis. At gene scale, the genome of A. vaga is tetraploid and comprises both anciently duplicated segments and less divergent allelic regions. However, in contrast to sexual species, the allelic regions are rearranged and sometimes even found on the same chromosome. Such structure does not allow meiotic pairing; instead, we find abundant evidence of gene conversion, which may limit the accumulation of deleterious mutations in the absence of meiosis. Gene families involved in resistance to oxidation, carbohydrate metabolism and defence against transposons are significantly expanded, which may explain why transposable elements cover only 3% of the assembled sequence. Furthermore, 8% of the genes are likely to be of non-metazoan origin and were probably acquired horizontally. This apparent convergence between bdelloids and prokaryotes sheds new light on the evolutionary significance of sex.
C1 [Flot, Jean-Francois; Hespeels, Boris; Li, Xiang; Lejeune, Benjamin; Van Doninck, Karine] Univ Namur, Dept Biol, URBE, Lab Evolutionary Genet & Ecol, B-5000 Namur, Belgium.
   [Flot, Jean-Francois; Hespeels, Boris; Li, Xiang; Lejeune, Benjamin; Van Doninck, Karine] Namur Res Inst Life Sci NARILIS, B-5000 Namur, Belgium.
   [Flot, Jean-Francois; Noel, Benjamin; Aury, Jean-Marc; Barbe, Valerie; Couloux, Arnaud; Da Silva, Corinne; Labadie, Karine; Poulain, Julie; Weissenbach, Jean; Wincker, Patrick; Jaillon, Olivier] Ctr Natl Sequencage, GENOSCOPE, CEA Inst Genom, F-91057 Evry, France.
   [Flot, Jean-Francois; Weissenbach, Jean; Wincker, Patrick; Jaillon, Olivier] Univ Evry, UMR8030, F-91057 Evry, France.
   [Flot, Jean-Francois; Weissenbach, Jean; Wincker, Patrick; Jaillon, Olivier] CNRS, UMR 8030, F-91057 Evry, France.
   [Flot, Jean-Francois; Hallatschek, Oskar] Max Planck Inst Dynam & Self Org, D-37073 Gottingen, Germany.
   [Arkhipova, Irina; Gladyshev, Eugene; Hecox-Lea, Bette; Rodriguez, Fernando; Yushenova, Irina; Welch, David B. Mark] Marine Biol Lab, Josephine Bay Paul Ctr Comparat Mol Biol & Evolut, Woods Hole, MA 02543 USA.
   [Danchin, Etienne G. J.; Da Rocha, Martine; Wajnberg, Eric] INRA, UMR ISA 1355, Inst Sophia Agrobiotech, F-06903 Sophia Antipolis, France.
   [Danchin, Etienne G. J.; Da Rocha, Martine; Wajnberg, Eric] CNRS, UMR ISA 7254, Inst Sophia Agrobiotech, F-06903 Sophia Antipolis, France.
   [Danchin, Etienne G. J.; Da Rocha, Martine; Wajnberg, Eric] Univ Nice Sophia Antipolis, UMR ISA, Inst Sophia Agrobiotech, F-06903 Sophia Antipolis, France.
   [Hejnol, Andreas; Ryan, Joseph F.] Univ Bergen, Sars Int Ctr Marine Mol Biol, N-5008 Bergen, Norway.
   [Henrissat, Bernard] Aix Marseille Univ, CNRS, UMR Architecture & Fonct Macromol Biol 7257, F-13288 Marseille, France.
   [Koszul, Romain] Inst Pasteur, CNRS, UMR 3525, Grp Spatial Regulat Genomes,Dept Genomes & Genet, F-75724 Paris, France.
   [Barthelemy, Roxane-Marie; Chabrol, Olivier; Gouret, Philippe; Wirth, Benedicte; Pontarotti, Pierre] Aix Marseille Univ, LATP UMR CNRS 7353, F-13331 Marseille 3, France.
   [Bast, Jens] Univ Gottingen, JF Blumenbach Inst Zool & Anthropol, D-37073 Gottingen, Germany.
   [Bazykin, Georgii A.; Vakhrusheva, Olga A.; Kondrashov, Alexey S.] Moscow MV Lomonosov State Univ, Dept Bioengn & Bioinformat, Moscow 119991, Russia.
   [Bazykin, Georgii A.; Vakhrusheva, Olga A.] Russian Acad Sci, Kharkevich Inst, Inst Informat Transmiss Problems, Moscow 127994, Russia.
   [Hallatschek, Oskar] Univ Calif Berkeley, Dept Phys, Berkeley, CA 94720 USA.
   [Hecox-Lea, Bette] Northeastern Univ, Dept Biol, Boston, MA 02115 USA.
   [Piskurek, Oliver] Univ Gottingen, Courant Res Ctr Geobiol, D-37077 Gottingen, Germany.
   [Kellis, Manolis; Jaillon, Olivier] Broad Inst MIT & Harvard, MIT Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA.
   [Kondrashov, Alexey S.] Univ Michigan, Inst Life Sci, Ann Arbor, MI 48109 USA.
   [Kondrashov, Alexey S.] Univ Michigan, Dept Ecol & Evolutionary Biol, Ann Arbor, MI 48109 USA.
C3 University of Namur; Universite Paris Saclay; 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); Max Planck Society; Marine Biological Laboratory - Woods Hole; INRAE; Universite Cote d'Azur; Centre National de la Recherche Scientifique (CNRS); Universite Cote d'Azur; Universite Cote d'Azur; University of Bergen; Centre National de la Recherche Scientifique (CNRS); Aix-Marseille Universite; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB); Pasteur Network; Universite Paris Cite; Institut Pasteur Paris; Aix-Marseille Universite; University of Gottingen; Lomonosov Moscow State University; Russian Academy of Sciences; Kharkevich Institute for Information Transmission Problems of the RAS; University of California System; University of California Berkeley; Northeastern University; University of Gottingen; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; University of Michigan System; University of Michigan; University of Michigan System; University of Michigan
RP Jaillon, O (corresponding author), Ctr Natl Sequencage, GENOSCOPE, CEA Inst Genom, 2 Rue Gaston Cremieux,CP5706, F-91057 Evry, France.
EM jean-francois.flot@ds.mpg.de; ojaillon@genoscope.cns.fr; karine.vandoninck@fundp.ac.be
FU Genoscope-CES; US National Science Foundation [MCB-0821956, MCB-1121334, MCB-0923676]; German Research Foundation [HA 5163/2-1]; Ministry of Education and Science of the Russian Federation [11.G34.31.0008]; NSF CAREER [0644282]; FRFC from the Belgian Fonds National de la Recherche Scientifique (FNRS) [2.4.655.09.F]; University of Namur; Direct For Biological Sciences; Div Of Biological Infrastructure [0644282] Funding Source: National Science Foundation; Direct For Biological Sciences; Div Of Molecular and Cellular Bioscience [1121334, 0821956] Funding Source: National Science Foundation; Div Of Biological Infrastructure; Direct For Biological Sciences [1039946] Funding Source: National Science Foundation; National Health and Medical Research Council (NHMRC) [1121334, 1039946] Funding Source: National Health and Medical Research Council (NHMRC)
NR 30
TC 285
Z9 315
U1 1
U2 187
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 22
PY 2013
VL 500
IS 7463
BP 453
EP 457
DI 10.1038/nature12326
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 203TJ
UT WOS:000323316100034
PM 23873043
DA 2026-03-09
ER

PT J
AU Balewski, JB
   Krupp, AT
   Gaj, A
   Peter, D
   Büchler, HP
   Löw, R
   Hofferberth, S
   Pfau, T
AF Balewski, Jonathan B.
   Krupp, Alexander T.
   Gaj, Anita
   Peter, David
   Buechler, Hans Peter
   Loew, Robert
   Hofferberth, Sebastian
   Pfau, Tilman
TI Coupling a single electron to a Bose-Einstein condensate
SO NATURE
LA English
DT Article
ID creation; ion
AB The coupling of electrons to matter lies at the heart of our understanding of material properties such as electrical conductivity. Electron-phonon coupling can lead to the formation of a Cooper pair out of two repelling electrons, which forms the basis for Bardeen-Cooper-Schrieffer superconductivity(1). Here we study the interaction of a single localized electron with a Bose-Einstein condensate and show that the electron can excite phonons and eventually trigger a collective oscillation of the whole condensate. We find that the coupling is surprisingly strong compared to that of ionic impurities, owing to the more favourable mass ratio. The electron is held in place by a single charged ionic core, forming a Rydberg bound state. This Rydberg electron is described by a wavefunction extending to a size of up to eight micrometres, comparable to the dimensions of the condensate. In such a state, corresponding to a principal quantum number of n = 202, the Rydberg electron is interacting with several tens of thousands of condensed atoms contained within its orbit. We observe surprisingly long lifetimes and finite size effects caused by the electron exploring the outer regions of the condensate. We anticipate future experiments on electron orbital imaging, the investigation of phonon-mediated coupling of single electrons, and applications in quantum optics.
C1 [Balewski, Jonathan B.; Krupp, Alexander T.; Gaj, Anita; Loew, Robert; Hofferberth, Sebastian; Pfau, Tilman] Univ Stuttgart, Phys Inst 5, D-70569 Stuttgart, Germany.
   [Peter, David; Buechler, Hans Peter] Univ Stuttgart, Inst Theoret Phys 3, D-70569 Stuttgart, Germany.
C3 University of Stuttgart; University of Stuttgart
RP Pfau, T (corresponding author), Univ Stuttgart, Phys Inst 5, Pfaffenwaldring 57, D-70569 Stuttgart, Germany.
EM t.pfau@physik.uni-stuttgart.de
FU Deutsche Forschungsgemeinschaft (DFG) [SFB/TRR21, PF 381/4-2]; ERC [267100]; EU Marie Curie programme ITN-Coherence [265031]; DFG [HO 4787/1-1]
NR 25
TC 128
Z9 136
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 OCT 31
PY 2013
VL 502
IS 7473
BP 664
EP 667
DI 10.1038/nature12592
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 243CC
UT WOS:000326293200043
PM 24172977
DA 2026-03-09
ER

PT J
AU Sarraf, SA
   Raman, M
   Guarani-Pereira, V
   Sowa, ME
   Huttlin, EL
   Gygi, SP
   Harper, JW
AF Sarraf, Shireen A.
   Raman, Malavika
   Guarani-Pereira, Virginia
   Sowa, Mathew E.
   Huttlin, Edward L.
   Gygi, Steven P.
   Harper, J. Wade
TI Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization
SO NATURE
LA English
DT Article
ID phosphorylation analysis; protein-phosphorylation; pink1; degradation; mitophagy; activation; proteasome; promotes; vdac1
AB The PARKIN ubiquitin ligase (also known as PARK2) and its regulatory kinase PINK1 (also known as PARK6), often mutated in familial early-onset Parkinson's disease, have central roles in mitochondrial homeostasis and mitophagy(1-3). Whereas PARKIN is recruited to the mitochondrial outer membrane (MOM) upon depolarization via PINK1 action and can ubiquitylate porin, mitofusin and Miro proteins on the MOM1,4-11, the full repertoire of PARKIN substrates-the PARKIN-dependent ubiquitylome-remains poorly defined. Here we use quantitative diGly capture proteomics (diGly)(12,13) to elucidate the ubiquitylation site specificity and topology of PARKIN-dependent target modification in response to mitochondrial depolarization. Hundreds of dynamically regulated ubiquitylation sites in dozens of proteins were identified, with strong enrichment for MOM proteins, indicating that PARKIN dramatically alters the ubiquitylation status of the mitochondrial proteome. Using complementary interaction proteomics, we found depolarization-dependent PARKIN association with numerous MOM targets, autophagy receptors, and the proteasome. Mutation of the PARKIN active site residue C431, which has been found mutated in Parkinson's disease patients, largely disrupts these associations. Structural and topological analysis revealed extensive conservation of PARKIN-dependent ubiquitylation sites on cytoplasmic domains in vertebrate and Drosophila melanogaster MOM proteins. These studies provide a resource for understanding how the PINK1-PARKIN pathway re-sculpts the proteome to support mitochondrial homeostasis.
C1 [Sarraf, Shireen A.; Raman, Malavika; Guarani-Pereira, Virginia; Sowa, Mathew E.; Huttlin, Edward L.; Gygi, Steven P.; Harper, J. Wade] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA.
C3 Harvard University; Harvard Medical School
RP Harper, JW (corresponding author), Harvard Univ, Sch Med, Dept Cell Biol, 240 Longwood Ave, Boston, MA 02115 USA.
EM wade_harper@hms.harvard.edu
FU NIH [GM070565, GM095567, GM067945, CA139885]; Michael J. Fox Foundation for Parkinson's Research; National Institute of General Medical Sciences [R01GM067945] Funding Source: NIH RePORTER
NR 33
TC 863
Z9 988
U1 1
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 APR 18
PY 2013
VL 496
IS 7445
BP 372
EP +
DI 10.1038/nature12043
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 126FV
UT WOS:000317599200040
PM 23503661
DA 2026-03-09
ER

PT J
AU Liao, HX
   Lynch, R
   Zhou, TQ
   Gao, F
   Alam, SM
   Boyd, SD
   Fire, AZ
   Roskin, KM
   Schramm, CA
   Zhang, ZH
   Zhu, J
   Shapiro, L
   Mullikin, JC
   Gnanakaran, S
   Hraber, P
   Wiehe, K
   Kelsoe, G
   Yang, G
   Xia, SM
   Montefiori, DC
   Parks, R
   Lloyd, KE
   Scearce, RM
   Soderberg, KA
   Cohen, M
   Kamanga, G
   Louder, MK
   Tran, LM
   Chen, Y
   Cai, FP
   Chen, SR
   Moquin, S
   Du, XL
   Joyce, MG
   Srivatsan, S
   Zhang, BS
   Zheng, AQ
   Shaw, GM
   Hahn, BH
   Kepler, TB
   Korber, BTM
   Kwong, PD
   Mascola, JR
   Haynes, BF
AF Liao, Hua-Xin
   Lynch, Rebecca
   Zhou, Tongqing
   Gao, Feng
   Alam, S. Munir
   Boyd, Scott D.
   Fire, Andrew Z.
   Roskin, Krishna M.
   Schramm, Chaim A.
   Zhang, Zhenhai
   Zhu, Jiang
   Shapiro, Lawrence
   Mullikin, James C.
   Gnanakaran, S.
   Hraber, Peter
   Wiehe, Kevin
   Kelsoe, Garnett
   Yang, Guang
   Xia, Shi-Mao
   Montefiori, David C.
   Parks, Robert
   Lloyd, Krissey E.
   Scearce, Richard M.
   Soderberg, Kelly A.
   Cohen, Myron
   Kamanga, Gift
   Louder, Mark K.
   Tran, Lillian M.
   Chen, Yue
   Cai, Fangping
   Chen, Sheri
   Moquin, Stephanie
   Du, Xiulian
   Joyce, M. Gordon
   Srivatsan, Sanjay
   Zhang, Baoshan
   Zheng, Anqi
   Shaw, George M.
   Hahn, Beatrice H.
   Kepler, Thomas B.
   Korber, Bette T. M.
   Kwong, Peter D.
   Mascola, John R.
   Haynes, Barton F.
TI Co-evolution of a broadly neutralizing HIV-1 antibody and founder virus
SO NATURE
LA English
DT Article
ID b-cell responses; human monoclonal-antibody; in-situ proteolysis; cd4 binding-site; conformational epitope; potent neutralization; envelope glycoprotein; subtype-b; crystallization; evolution
AB Current human immunodeficiency virus-1 (HIV-1) vaccines elicit strain-specific neutralizing antibodies. However, cross-reactive neutralizing antibodies arise in approximately 20% of HIV-1-infected individuals, and details of their generation could provide a blueprint for effective vaccination. Here we report the isolation, evolution and structure of a broadly neutralizing antibody from an African donor followed from the time of infection. The mature antibody, CH103, neutralized approximately 55% of HIV-1 isolates, and its co-crystal structure with the HIV-1 envelope protein gp120 revealed a new loop-based mechanism of CD4-binding-site recognition. Virus and antibody gene sequencing revealed concomitant virus evolution and antibody maturation. Notably, the unmutated common ancestor of the CH103 lineage avidly bound the transmitted/founder HIV-1 envelope glycoprotein, and evolution of antibody neutralization breadth was preceded by extensive viral diversification in and near the CH103 epitope. These data determine the viral and antibody evolution leading to induction of a lineage of HIV-1 broadly neutralizing antibodies, and provide insights into strategies to elicit similar antibodies by vaccination.
C1 [Liao, Hua-Xin; Gao, Feng; Alam, S. Munir; Wiehe, Kevin; Kelsoe, Garnett; Yang, Guang; Xia, Shi-Mao; Montefiori, David C.; Parks, Robert; Lloyd, Krissey E.; Scearce, Richard M.; Soderberg, Kelly A.; Chen, Yue; Cai, Fangping; Chen, Sheri; Haynes, Barton F.] Duke Univ, Sch Med, Dept Med, Human Vaccine Inst, Durham, NC 27710 USA.
   [Liao, Hua-Xin; Gao, Feng; Alam, S. Munir; Wiehe, Kevin; Kelsoe, Garnett; Yang, Guang; Xia, Shi-Mao; Montefiori, David C.; Parks, Robert; Lloyd, Krissey E.; Scearce, Richard M.; Soderberg, Kelly A.; Chen, Yue; Cai, Fangping; Chen, Sheri; Haynes, Barton F.] Duke Univ, Sch Med, Dept Immunol, Human Vaccine Inst, Durham, NC 27710 USA.
   [Liao, Hua-Xin; Gao, Feng; Alam, S. Munir; Wiehe, Kevin; Kelsoe, Garnett; Yang, Guang; Xia, Shi-Mao; Montefiori, David C.; Parks, Robert; Lloyd, Krissey E.; Scearce, Richard M.; Soderberg, Kelly A.; Chen, Yue; Cai, Fangping; Chen, Sheri; Haynes, Barton F.] Duke Ctr HIV AIDS Vaccine Immunol & Immunogen Dis, Durham, NC 27710 USA.
   [Lynch, Rebecca; Zhou, Tongqing; Zhu, Jiang; Shapiro, Lawrence; Louder, Mark K.; Tran, Lillian M.; Moquin, Stephanie; Du, Xiulian; Joyce, M. Gordon; Srivatsan, Sanjay; Zhang, Baoshan; Zheng, Anqi; Kwong, Peter D.; Mascola, John R.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
   [Boyd, Scott D.; Fire, Andrew Z.; Roskin, Krishna M.] Stanford Univ, Dept Pathol, Palo Alto, CA 94305 USA.
   [Schramm, Chaim A.; Zhang, Zhenhai; Shapiro, Lawrence] Columbia Univ, Dept Biochem & Mol Biophys, New York, NY 10032 USA.
   [Mullikin, James C.] NIH, NISC Comparat Sequencing Program, Bethesda, MD 20892 USA.
   [Mullikin, James C.] NHGRI, NIH Intramural Sequencing Ctr, NIH, Bethesda, MD 20892 USA.
   [Gnanakaran, S.; Hraber, Peter; Korber, Bette T. M.] Los Alamos Natl Lab, Div Theoret, Los Alamos, NM 87544 USA.
   [Cohen, Myron] Univ N Carolina, Dept Med, Chapel Hill, NC 27599 USA.
   [Cohen, Myron] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27599 USA.
   [Cohen, Myron] Univ N Carolina, Dept Microbiol & Immunol, Chapel Hill, NC 27599 USA.
   [Kamanga, Gift] Univ North Carolina Project, Kamuzu Cent Hosp, Lilongwe, Malawi.
   [Shaw, George M.; Hahn, Beatrice H.] Univ Penn, Perelman Sch Med, Dept Med, Philadelphia, PA 19104 USA.
   [Shaw, George M.; Hahn, Beatrice H.] Univ Penn, Perelman Sch Med, Dept Microbiol, Philadelphia, PA 19104 USA.
   [Kepler, Thomas B.] Boston Univ, Dept Microbiol, Boston, MA 02215 USA.
C3 Duke University; Duke University; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID); Stanford University; Columbia University; National Institutes of Health (NIH) - USA; National Institutes of Health (NIH) - USA; NIH National Human Genome Research Institute (NHGRI); United States Department of Energy (DOE); Los Alamos National Laboratory; 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 Pennsylvania; University of Pennsylvania; Boston University
RP Liao, HX (corresponding author), Duke Univ, Sch Med, Dept Med, Human Vaccine Inst, Durham, NC 27710 USA.
EM hliao@duke.edu; barton.haynes@duke.edu
FU National Institutes of Allergy and Infectious Diseases (NIAID); intramural National Institutes of Health (NIH); NIH, NIAID [AI067854, AI100645]; US Department of Energy, Basic Energy Sciences, Office of Science [W-31-109-Eng-38]; National Human Genome Research Institute [ZIAHG200330, ZIBHG000196] Funding Source: NIH RePORTER; National Institute of Allergy and Infectious Diseases [ZIAAI005022] Funding Source: NIH RePORTER; National Institute of Allergy and Infectious Diseases; National Institute of Diabetes and Digestive and Kidney Diseases; Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Institute on Aging; National Institute on Minority Health and Health Disparities; National Cancer Institute; National Institute of Dental and Craniofacial Research; National Heart Lung and Blood Institute; National Institute of Nursing Research; National Institute on Drug Abuse [P30AI050410] Funding Source: NIH RePORTER
NR 71
TC 828
Z9 1020
U1 0
U2 244
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 25
PY 2013
VL 496
IS 7446
BP 469
EP +
DI 10.1038/nature12053
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 131HU
UT WOS:000317984400034
PM 23552890
DA 2026-03-09
ER

PT J
AU Read, BA
   Kegel, J
   Klute, MJ
   Kuo, A
   Lefebvre, SC
   Maumus, F
   Mayer, C
   Miller, J
   Monier, A
   Salamov, A
   Young, J
   Aguilar, M
   Claverie, JM
   Frickenhaus, S
   Gonzalez, K
   Herman, EK
   Lin, YC
   Napier, J
   Ogata, H
   Sarno, AF
   Shmutz, J
   Schroeder, D
   de Vargas, C
   Verret, F
   von Dassow, P
   Valentin, K
   Van de Peer, Y
   Wheeler, G
   Dacks, JB
   Delwiche, CF
   Dyhrman, ST
   Glöckner, G
   John, U
   Richards, T
   Worden, AZ
   Zhang, XY
   Grigoriev, IV
   Allen, AE
   Bidle, K
   Borodovsky, M
   Bowler, C
   Brownlee, C
   Cock, JM
   Elias, M
   Gladyshev, VN
   Groth, M
   Guda, C
   Hadaegh, A
   Iglesias-Rodriguez, MD
   Jenkins, J
   Jones, BM
   Lawson, T
   Leese, F
   Lindquist, E
   Lobanov, A
   Lomsadze, A
   Malik, SB
   Marsh, ME
   Mackinder, L
   Mock, T
   Mueller-Roeber, B
   Pagarete, A
   Parker, M
   Probert, I
   Quesneville, H
   Raines, C
   Rensing, SA
   Riaño-Pachón, DM
   Richier, S
   Rokitta, S
   Shiraiwa, Y
   Soanes, DM
   van der Giezen, M
   Wahlund, TM
   Williams, B
   Wilson, W
   Wolfe, G
   Wurch, LL
AF Read, Betsy A.
   Kegel, Jessica
   Klute, Mary J.
   Kuo, Alan
   Lefebvre, Stephane C.
   Maumus, Florian
   Mayer, Christoph
   Miller, John
   Monier, Adam
   Salamov, Asaf
   Young, Jeremy
   Aguilar, Maria
   Claverie, Jean-Michel
   Frickenhaus, Stephan
   Gonzalez, Karina
   Herman, Emily K.
   Lin, Yao-Cheng
   Napier, Johnathan
   Ogata, Hiroyuki
   Sarno, Analissa F.
   Shmutz, Jeremy
   Schroeder, Declan
   de Vargas, Colomban
   Verret, Frederic
   von Dassow, Peter
   Valentin, Klaus
   Van de Peer, Yves
   Wheeler, Glen
   Dacks, Joel B.
   Delwiche, Charles F.
   Dyhrman, Sonya T.
   Gloeckner, Gernot
   John, Uwe
   Richards, Thomas
   Worden, Alexandra Z.
   Zhang, Xiaoyu
   Grigoriev, Igor V.
   Allen, Andrew E.
   Bidle, Kay
   Borodovsky, M.
   Bowler, C.
   Brownlee, Colin
   Cock, J. Mark
   Elias, Marek
   Gladyshev, Vadim N.
   Groth, Marco
   Guda, Chittibabu
   Hadaegh, Ahmad
   Iglesias-Rodriguez, Maria Debora
   Jenkins, J.
   Jones, Bethan M.
   Lawson, Tracy
   Leese, Florian
   Lindquist, Erika
   Lobanov, Alexei
   Lomsadze, Alexandre
   Malik, Shehre-Banoo
   Marsh, Mary E.
   Mackinder, Luke
   Mock, Thomas
   Mueller-Roeber, Bernd
   Pagarete, Antonio
   Parker, Micaela
   Probert, Ian
   Quesneville, Hadi
   Raines, Christine
   Rensing, Stefan A.
   Riano-Pachon, Diego Mauricio
   Richier, Sophie
   Rokitta, Sebastian
   Shiraiwa, Yoshihiro
   Soanes, Darren M.
   van der Giezen, Mark
   Wahlund, Thomas M.
   Williams, Bryony
   Wilson, Willie
   Wolfe, Gordon
   Wurch, Louie L.
TI Pan genome of the phytoplankton Emiliania underpins its global distribution
SO NATURE
LA English
DT Article
ID huxleyi prymnesiophyceae; high light; indicators; growth
AB Coccolithophores have influenced the global climate for over 200 million years(1). These marine phytoplankton can account for 20 per cent of total carbon fixation in some systems(2). They form blooms that can occupy hundreds of thousands of square kilometres and are distinguished by their elegantly sculpted calcium carbonate exoskeletons (coccoliths), rendering them visible from space(3). Although coccolithophores export carbon in the form of organic matter and calcite to the sea floor, they also release CO2 in the calcification process. Hence, they have a complex influence on the carbon cycle, driving either CO2 production or uptake, sequestration and export to the deep ocean(4). Here we report the first haptophyte reference genome, from the coccolithophore Emiliania huxleyi strain CCMP1516, and sequences from 13 additional isolates. Our analyses reveal a pan genome (core genes plus genes distributed variably between strains) probably supported by an atypical complement of repetitive sequence in the genome. Comparisons across strains demonstrate that E. huxleyi, which has long been considered a single species, harbours extensive genome variability reflected in different metabolic repertoires. Genome variability within this species complex seems to underpin its capacity both to thrive in habitats ranging from the equator to the subarctic and to form large-scale episodic blooms under a wide variety of environmental conditions.
C1 [Read, Betsy A.; Sarno, Analissa F.; Wahlund, Thomas M.] Calif State Univ San Marcos, Dept Biol Sci, San Marcos, CA 92096 USA.
   [Kegel, Jessica; Frickenhaus, Stephan; Valentin, Klaus; John, Uwe; Rokitta, Sebastian] Helmholtz Ctr Polar & Marine Res AWI, Alfred Wegener Inst, D-27570 Bremerhaven, Germany.
   [Klute, Mary J.; Aguilar, Maria; Herman, Emily K.; Dacks, Joel B.] Univ Alberta, Dept Cell Biol, Edmonton, AB T6G 2H7, Canada.
   [Kuo, Alan; Salamov, Asaf; Shmutz, Jeremy; Grigoriev, Igor V.; Lindquist, Erika] US DOE, Joint Genome Inst, Walnut Creek, CA 94598 USA.
   [Lefebvre, Stephane C.; Allen, Andrew E.] J Craig Venter Inst, San Diego, CA 92121 USA.
   [Maumus, Florian; Quesneville, Hadi] INRA, Unite Rech Genom Info, F-78026 Versailles, France.
   [Mayer, Christoph] Forsch Museum, D-53113 Bonn, Germany.
   [Mayer, Christoph; Leese, Florian] Ruhr Univ Bochum, Dept Anim Ecol Evolut & Biodivers, D-44801 Bochum, Germany.
   [Miller, John; Delwiche, Charles F.] Univ Maryland, College Pk, MD 20742 USA.
   [Miller, John; Delwiche, Charles F.] Univ Maryland, Maryland Agr Expt Stn, College Pk, MD 20742 USA.
   [Monier, Adam; Worden, Alexandra Z.] Monterey Bay Aquarium Res Inst, Moss Landing, CA 95039 USA.
   [Young, Jeremy] UCL, Dept Earth Sci, London WC1E 6BT, England.
   [Claverie, Jean-Michel; Ogata, Hiroyuki] Aix Marseille Univ, Mediterranean Inst Microbiol, CNRS, Struct & Genom Informat Lab, FR-3479 Marseille, France.
   [Frickenhaus, Stephan] Hsch Bremerhaven, D-27568 Bremerhaven, Germany.
   [Gonzalez, Karina] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA.
   [Lin, Yao-Cheng; Van de Peer, Yves] Univ Ghent VIB, Dept Plant Syst Biol, B-9052 Ghent, Belgium.
   [Napier, Johnathan] Rothamsted Res, Dept Biol Chem, Harpenden AL5 2JQ, Herts, England.
   [Shmutz, Jeremy; Jenkins, J.] HudsonAlpha Genome Sequencing Ctr, Huntsville, AL 35806 USA.
   [Schroeder, Declan; Wheeler, Glen; Brownlee, Colin; Mackinder, Luke] Marine Biol Assoc United Kingdom Lab, Plymouth PL1 2PB, Devon, England.
   [de Vargas, Colomban; Probert, Ian] CNRS, UMR 7144, F-29682 Roscoff, France.
   [de Vargas, Colomban; Probert, Ian] Univ Paris 06, EPEP Team, Stn Biol Roscoff, F-29682 Roscoff, France.
   [Verret, Frederic] Univ Essex, Sch Biol Sci, Colchester CO4 3SQ, Essex, England.
   [von Dassow, Peter] Pontificia Univ Catolica Chile, Fac Ciencias Biol, Dept Ecol, Santiago, Chile.
   [Wheeler, Glen] Plymouth Marine Lab, Plymouth PL1 3DH, Devon, England.
   [Dyhrman, Sonya T.; Wurch, Louie L.] Woods Hole Oceanog Inst, Dept Biol, Woods Hole, MA 02543 USA.
   [Dyhrman, Sonya T.] Columbia Univ, Dept Earth & Environm Sci, Palisades, NY 10964 USA.
   [Dyhrman, Sonya T.] Columbia Univ, Lamont Doherty Earth Observ, Palisades, NY 10964 USA.
   [Gloeckner, Gernot] Univ Cologne, Fac Med, Inst Biochem 1, D-50931 Cologne, Germany.
   [Gloeckner, Gernot] Leibniz Inst Freshwater Ecol & Inland Fisheries, D-12587 Berlin, Germany.
   [Richards, Thomas] Nat Hist Museum, Dept Zool, London SW7 5BD, England.
   [Zhang, Xiaoyu; Hadaegh, Ahmad] Calif State Univ San Marcos, Dept Comp Sci & Informat Syst, San Marcos, CA 92096 USA.
   [Bidle, Kay] Rutgers State Univ, Inst Marine & Coastal Sci, Environm Biophys & Mol Ecol Grp, New Brunswick, NJ 08901 USA.
   [Borodovsky, M.; Lomsadze, Alexandre] Georgia Tech, Joint Georgia Tech & Emory Dept Biomed Engn, Sch Computat Sci & Engn, Atlanta, GA 30322 USA.
   [Borodovsky, M.] Moscow Inst Phys & Technol, Dept Bioinformat, Moscow 117303, Russia.
   [Bowler, C.] Inst Natl Sante & Rech Med U1024, Environm & Evolutionary Genom Sect, Inst Biol lEcole Normale Super, Ctr Natl Rech Sci,UMR8197, F-75230 Paris, France.
   [Cock, J. Mark] CNRS, UMR 7139, Lab Int Associe Dispersal & Adaptat Marin Species, Stn Biol Roscoff, F-29682 Roscoff, France.
   [Cock, J. Mark] UPMC Univ Paris 06, Marine Plants & Biomol Lab, UMR 7139, Stn Biol Roscoff, F-29682 Roscoff, France.
   [Elias, Marek] Univ Ostrava, Fac Sci, Dept Biol & Ecol, Life Sci Res Ctr, Ostrava 71000, Czech Republic.
   [Gladyshev, Vadim N.; Lobanov, Alexei] Brigham & Womens Hosp, Harvard Med Sch, Dept Med, Div Genet, Boston, MA 02115 USA.
   [Groth, Marco] Leibniz Inst Age Res, Fritz Lipmann Inst, D-07745 Jena, Germany.
   [Guda, Chittibabu] Univ Nebraska Med Ctr, Dept Genet, Cell Biol & Anat, Omaha, NE 68198 USA.
   [Iglesias-Rodriguez, Maria Debora] Univ California Santa Barbara, Dept Ecol Evolut & Marine Biol, Santa Barbara, CA 93106 USA.
   [Iglesias-Rodriguez, Maria Debora; Jones, Bethan M.; Richier, Sophie] Univ Southampton, Ocean & Earth Sci Natl Oceanog Ctr Southampton, Southampton SO17 1BJ, Hants, England.
   [Jones, Bethan M.] Oregon State Univ, Dept Microbiol, Corvallis, OR 97331 USA.
   [Lawson, Tracy; Raines, Christine] Univ Essex, Sch Biol Sci, Colchester CO4 3SQ, Essex, England.
   [Malik, Shehre-Banoo] Dalhousie Univ, Canadian Inst Adv Res, Integrated Microbial Biodivers Program, Halifax, NS B3H 4R2, Canada.
   [Marsh, Mary E.] Univ Texas Houston Med Sch, Houston, TX 77030 USA.
   [Mock, Thomas] Univ E Anglia, Sch Environm Sci, Norwich NR4 7TJ, Norfolk, England.
   [Mueller-Roeber, Bernd] Univ Potsdam, Inst Biochem & Biol, D-14476 Potsdam, Germany.
   [Pagarete, Antonio] Univ Bergen, Dept Biol, N-5006 Bergen, Norway.
   [Parker, Micaela] Univ Washington, Ctr Environm Genom, PNW Ctr Human Hlth & Ocean Studies, Seattle, WA 98195 USA.
   [Rensing, Stefan A.] Univ Freiburg, Fac Biol, BIOSS Ctr Biol Signalling Studies, D-79098 Freiburg, Germany.
   [Rensing, Stefan A.] Univ Marburg, Fac Biol, D-35043 Marburg, Germany.
   [Riano-Pachon, Diego Mauricio] Univ Los Andes, Dept Ciencias Biol, Bogota 111711, DC, Colombia.
   [Richier, Sophie] CNRS, INSU, UMR 7093, Lab Oceanog Villefranche, F-06230 Villefranche Sur Mer, France.
   [Richier, Sophie] Univ Paris 06, Observ Oceanol Villefranche, F-06230 Villefranche Sur Mer, France.
   [Shiraiwa, Yoshihiro] Univ Tsukuba, Fac Life & Environm Sci, Tsukuba, Ibaraki 3058572, Japan.
   [Soanes, Darren M.; van der Giezen, Mark; Williams, Bryony] Univ Exeter, Coll Life & Environm Sci, Exeter EX4 4QD, Devon, England.
   [Wilson, Willie] Bigelow Lab Ocean Sci, Provasoli Guillard Natl Ctr, E Boothbay, ME 04544 USA.
   [Wolfe, Gordon] California State Univ, Dept Biol Sci, Chico, CA 95929 USA.
   [Wurch, Louie L.] Oak Ridge Natl Lab, Oak Ridge, TN 37831 USA.
C3 California State University System; California State University San Marcos; Helmholtz Association; Alfred Wegener Institute, Helmholtz Centre for Polar & Marine Research; University of Alberta; United States Department of Energy (DOE); Joint BioEnergy Institute - JBEI; Joint Genome Institute - JGI; J. Craig Venter Institute; INRAE; Universite Paris Saclay; Ruhr University Bochum; University System of Maryland; University of Maryland College Park; University System of Maryland; University of Maryland College Park; Monterey Bay Aquarium Research Institute; University of London; University College London; Centre National de la Recherche Scientifique (CNRS); Aix-Marseille Universite; Harvard University; Harvard Medical School; Ghent University; Flanders Institute for Biotechnology (VIB); UK Research & Innovation (UKRI); Biotechnology and Biological Sciences Research Council (BBSRC); Rothamsted Research; HudsonAlpha Institute for Biotechnology; Marine Biological Association United Kingdom; Centre National de la Recherche Scientifique (CNRS); CNRS - Institute of Ecology & Environment (INEE); Sorbonne Universite; Sorbonne Universite; University of Essex; Pontificia Universidad Catolica de Chile; Plymouth Marine Laboratory; Woods Hole Oceanographic Institution; Columbia University; Columbia University; University of Cologne; Leibniz Association; Leibniz Institut fur Gewasserokologie und Binnenfischerei (IGB); Natural History Museum London; California State University System; California State University San Marcos; Rutgers University System; Rutgers University New Brunswick; University System of Georgia; Georgia Institute of Technology; Moscow Institute of Physics & Technology; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB); Institut National de la Sante et de la Recherche Medicale (Inserm); Centre National de la Recherche Scientifique (CNRS); Sorbonne Universite; Sorbonne Universite; University of Ostrava; Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Brigham & Women's Hospital; Leibniz Association; Leibniz Institut fur Alternsforschung - Fritz-Lipmann-Institut (FLI); University of Nebraska System; University of Nebraska Medical Center; University of California System; University of California Santa Barbara; University of Southampton; Oregon State University; University of Essex; Dalhousie University; Canadian Institute for Advanced Research (CIFAR); University of Texas System; University of Texas Health Science Center Houston; University of East Anglia; University of Potsdam; University of Bergen; University of Washington; University of Washington Seattle; University of Freiburg; Philipps University Marburg; Universidad de los Andes (Colombia); Sorbonne Universite; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Earth Sciences & Astronomy (INSU); Sorbonne Universite; University of Tsukuba; University of Exeter; Bigelow Laboratory for Ocean Sciences; California State University System; California State University East Bay; California State University Chico; United States Department of Energy (DOE); Oak Ridge National Laboratory
RP Read, BA (corresponding author), Calif State Univ San Marcos, Dept Biol Sci, San Marcos, CA 92096 USA.
EM bread@csusm.edu
FU Office of Science of the US Department of Energy (DOE) [7DE-AC02-05CH11231]; National Health and Medical Research Council (NHMRC) [1061883] Funding Source: National Health and Medical Research Council (NHMRC); Directorate For Engineering; Emerging Frontiers & Multidisciplinary Activities [0938157] Funding Source: National Science Foundation; Division Of Ocean Sciences; Directorate For Geosciences [1061883] Funding Source: National Science Foundation; Biotechnology and Biological Sciences Research Council [BBS/E/C/00005207] Funding Source: researchfish; Natural Environment Research Council [pml010004, NBAF010005, NE/E018319/1] Funding Source: researchfish; BBSRC [BBS/E/C/00005207] Funding Source: UKRI; NERC [pml010004, NE/E018319/1, NBAF010005] Funding Source: UKRI
NR 28
TC 401
Z9 455
U1 7
U2 321
PU NATURE PUBLISHING 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 11
PY 2013
VL 499
IS 7457
BP 209
EP 213
DI 10.1038/nature12221
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 179YA
UT WOS:000321557600062
PM 23760476
DA 2026-03-09
ER

PT J
AU Takeo, M
   Chou, WC
   Sun, Q
   Lee, W
   Rabbani, P
   Loomis, C
   Taketo, MM
   Ito, M
AF Takeo, Makoto
   Chou, Wei Chin
   Sun, Qi
   Lee, Wendy
   Rabbani, Piul
   Loomis, Cynthia
   Taketo, M. Mark
   Ito, Mayumi
TI Wnt activation in nail epithelium couples nail growth to digit regeneration
SO NATURE
LA English
DT Article
ID hair follicle; mouse; cells; mice; amputation; mutation; tip
AB The tips of mammalian digits can regenerate after amputation(1,2), like those of amphibians. It is unknown why this capacity is limited to the area associated with the nail(2-4). Here we show that nail stem cells (NSCs) reside in the proximal nail matrix and that the mechanisms governing NSC differentiation are coupled directly with their ability to orchestrate digit regeneration. Early nail progenitors undergo Wnt-dependent differentiation into the nail. After amputation, this Wnt activation is required for nail regeneration and also for attracting nerves that promote mesenchymal blastema growth, leading to the regeneration of the digit. Amputations proximal to the Wnt-active nail progenitors result in failure to regenerate the nail or digit. Nevertheless, beta-catenin stabilization in the NSC region induced their regeneration. These results establish a link between NSC differentiation and digit regeneration, and suggest that NSCs may have the potential to contribute to the development of novel treatments for amputees.
C1 [Takeo, Makoto; Chou, Wei Chin; Sun, Qi; Lee, Wendy; Rabbani, Piul; Loomis, Cynthia; Ito, Mayumi] NYU, Sch Med, Ronald O Perelman Dept Dermatol, New York, NY 10016 USA.
   [Takeo, Makoto; Chou, Wei Chin; Sun, Qi; Lee, Wendy; Rabbani, Piul; Loomis, Cynthia; Ito, Mayumi] NYU, Sch Med, Dept Cell Biol, New York, NY 10016 USA.
   [Taketo, M. Mark] Kyoto Univ, Grad Sch Med, Dept Pharmacol, Kyoto 6068501, Japan.
C3 New York University; New York University; Kyoto University
RP Ito, M (corresponding author), NYU, Sch Med, Ronald O Perelman Dept Dermatol, New York, NY 10016 USA.
EM Mayumi.Ito@nyumc.org
FU Genome Technology Center at NYU (National Institutes of Health (NIH)) [5P30CA0016087-32, P30 CA016087-30]; NYU Kimmel Stem Cell Center; NYSTEM [C026880]; NIH National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) [1R01AR059768-01A1]; Ellison Medical Foundation; Department of Dermatology and Cell Biology; Helen and Martin Kimmel Center for Stem Cell Biology, at NYU; National Cancer Institute [P30CA016087] Funding Source: NIH RePORTER; National Institute of Arthritis and Musculoskeletal and Skin Diseases [R01AR059768] Funding Source: NIH RePORTER
NR 38
TC 189
Z9 233
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 11
PY 2013
VL 499
IS 7457
BP 228
EP +
DI 10.1038/nature12214
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 179YA
UT WOS:000321557600066
PM 23760480
DA 2026-03-09
ER

PT J
AU Jiang, C
   Srinivasan, SG
AF Jiang, Chao
   Srinivasan, Srivilliputhur G.
TI Unexpected strain-stiffening in crystalline solids
SO NATURE
LA English
DT Article
ID instability; plasticity; strength; aluminum; science; carbon
AB Strain-stiffening-an increase in material stiffness at large strains-is a vital mechanism by which many soft biological materials thwart excessive deformation to protect tissue integrity(1-3). Understanding the fundamental science of strain-stiffening and incorporating this concept into the design of metals and ceramics for advanced applications is an attractive prospect. Using cementite (Fe3C) and aluminium borocarbide (Al3BC3) as prototypes, here we show via quantum-mechanical calculations that strain-stiffening also occurs, surprisingly, in simple inorganic crystalline solids and confers exceptionally high strengths to these two solids, which have anomalously low resistance to deformation near equilibrium. For Fe3C and Al3BC3, their ideal shear strength to shear modulus ratios attain remarkably high values of 1.14 and 1.34 along the (010)[ 001] and (0001) [01 (1) over bar0] slip systems, respectively. These values are more than seven times larger than the original Frenkel value of 1/2 pi (refs 4, 5) and are the highest yet reported for crystalline solids. The extraordinary stiffening of Fe3C arises from the strain-induced reversible 'cross-linking' between weakly coupled edge- and corner-sharing Fe6C slabs. This new bond formation creates a strong, three-dimensional covalent bond network that resists large shear deformation. Unlike Fe3C, no new bond forms in Al3BC3 but stiffening still occurs because strong repulsion between Al and B in a compressed Al-B bond unsettles the existing covalent bond network. These discoveries challenge the conventional wisdom that large shear modulus is a reliable predictor of hardness and strength of materials(4-7), and provide new lessons for materials selection and design.
C1 [Jiang, Chao] Los Alamos Natl Lab, Struct Property Relat Grp MST 8, Los Alamos, NM 87545 USA.
   [Srinivasan, Srivilliputhur G.] Univ N Texas, Dept Mat Sci & Engn, Denton, TX 76203 USA.
C3 United States Department of Energy (DOE); Los Alamos National Laboratory; University of North Texas System; University of North Texas Denton
RP Jiang, C (corresponding author), Univ Wisconsin, Dept Mat Sci & Engn, 1509 Univ Ave, Madison, WI 53706 USA.
EM chaopsu@gmail.com; srinivasan.srivilliputhur@unt.edu
FU Los Alamos National Laboratory (LANL); National Science Foundation [0846444]; Div Of Civil, Mechanical, & Manufact Inn; Directorate For Engineering [0846444] Funding Source: National Science Foundation
NR 30
TC 66
Z9 70
U1 2
U2 209
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 18
PY 2013
VL 496
IS 7445
BP 339
EP 342
DI 10.1038/nature12008
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 126FV
UT WOS:000317599200032
PM 23575634
DA 2026-03-09
ER

PT J
AU Egholm, DL
   Knudsen, MF
   Sandiford, M
AF Egholm, David L.
   Knudsen, Mads F.
   Sandiford, Mike
TI Lifespan of mountain ranges scaled by feedbacks between landsliding and erosion by rivers
SO NATURE
LA English
DT Article
ID sediment-flux; landscape evolution; bedrock incision; rock-uplift; bed-load; model; rates; topography; hillslopes; himalayas
AB An important challenge in geomorphology is the reconciliation of the high fluvial incision rates observed in tectonically active mountain ranges with the long-term preservation of significant mountain-range relief in ancient, tectonically inactive orogenic belts(1-3). River bedrock erosion and sediment transport are widely recognized to be the principal controls on the lifespan of mountain ranges. But the factors controlling the rate of erosion(4-8) and the reasons why they seem to vary significantly as a function of tectonic activity remain controversial. Here we use computational simulations to show that the key to understanding variations in the rate of erosion between tectonically active and inactive mountain ranges may relate to a bidirectional coupling between bedrock river incision and landslides. Whereas fluvial incision steepens surrounding hillslopes and increases landslide frequency(9), landsliding affects fluvial erosion rates in two fundamentally distinct ways. On the one hand, large landslides overwhelm the river transport capacity and cause upstream build up of sediment that protects the river bed from further erosion(9-11). On the other hand, in delivering abrasive agents to the streams(4-6), landslides help accelerate fluvial erosion. Our models illustrate how this coupling has fundamentally different implications for rates of fluvial incision in active and inactive mountain ranges. The coupling there-fore provides a plausible physical explanation for the preservation of significant mountain-range relief in old orogenic belts, up to several hundred million years after tectonic activity has effectively ceased.
C1 [Egholm, David L.; Knudsen, Mads F.] Aarhus Univ, Dept Geosci, DK-8000 Aarhus C, Denmark.
   [Sandiford, Mike] Univ Melbourne, Sch Earth Sci, Melbourne, Vic 3010, Australia.
C3 Aarhus University; University of Melbourne
RP Egholm, DL (corresponding author), Aarhus Univ, Dept Geosci, Hoegh Guldbergs Gade 2, DK-8000 Aarhus C, Denmark.
EM david@geo.au.dk
FU Danish Council for Independent Research under the Sapere Aude programme; Carlsberg Foundation; Villum Foundation; ARC [DP110104098]; AISRF; Villum Fonden [00007263] Funding Source: researchfish
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NR 43
TC 135
Z9 162
U1 2
U2 162
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 27
PY 2013
VL 498
IS 7455
BP 475
EP +
DI 10.1038/nature12218
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 171LH
UT WOS:000320929400050
PM 23803847
DA 2026-03-09
ER

PT J
AU Austin, C
   Smith, TM
   Bradman, A
   Hinde, K
   Joannes-Boyau, R
   Bishop, D
   Hare, DJ
   Doble, P
   Eskenazi, B
   Arora, M
AF Austin, Christine
   Smith, Tanya M.
   Bradman, Asa
   Hinde, Katie
   Joannes-Boyau, Renaud
   Bishop, David
   Hare, Dominic J.
   Doble, Philip
   Eskenazi, Brenda
   Arora, Manish
TI Barium distributions in teeth reveal early-life dietary transitions in primates
SO NATURE
LA English
DT Article
ID trace-elements; enamel; neanderthal; diagenesis; chemistry; spectrometry; behavior; history; growth
AB Early-life dietary transitions reflect fundamental aspects of primate evolution and are important determinants of health in contemporary human populations(1,2). Weaning is critical to developmental and reproductive rates; early weaning can have detrimental health effects but enables shorter inter-birth intervals, which influences population growth(3). Uncovering early-life dietary history in fossils is hampered by the absence of prospectively validated biomarkers that are not modified during fossilization(4). Here we show that large dietary shifts in early life manifest as compositional variations in dental tissues. Teeth from human children and captive macaques, with prospectively recorded diet histories, demonstrate that barium (Ba) distributions accurately reflect dietary transitions from the introduction of mother's milk through the weaning process. We also document dietary transitions in a Middle Palaeolithic juvenile Neanderthal, which shows a pattern of exclusive breastfeeding for seven months, followed by seven months of supplementation. After this point, Ba levels in enamel returned to baseline prenatal levels, indicating an abrupt cessation of breastfeeding at 1.2 years of age. Integration of Ba spatial distributions and histological mapping of tooth formation enables novel studies of the evolution of human life history, dietary ontogeny in wild primates, and human health investigations through accurate reconstructions of breastfeeding history.
C1 [Austin, Christine; Arora, Manish] Icahn Sch Med Mt Sinai, Dept Prevent Med, New York, NY 10029 USA.
   [Austin, Christine; Arora, Manish] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
   [Austin, Christine; Arora, Manish] Westmead Hosp, Westmead Millennium Inst, Inst Dent Res, Sydney, NSW 2145, Australia.
   [Austin, Christine; Arora, Manish] Univ Sydney, Fac Dent, Sydney, NSW 2145, Australia.
   [Smith, Tanya M.; Hinde, Katie] Harvard Univ, Dept Human Evolutionary Biol, Cambridge, MA 02138 USA.
   [Bradman, Asa; Eskenazi, Brenda] Univ Calif Berkeley, Sch Publ Hlth, Ctr Environm Res & Childrens Hlth, Berkeley, CA 94720 USA.
   [Hinde, Katie] Calif Natl Primate Res Ctr, Davis, CA 95616 USA.
   [Joannes-Boyau, Renaud] So Cross Univ, Lismore, NSW 2480, Australia.
   [Bishop, David; Hare, Dominic J.; Doble, Philip] Univ Technol Sydney, Elemental Bioimaging Facil, Sydney, NSW 2007, Australia.
   [Hare, Dominic J.] Univ Melbourne, Florey Inst Neurosci & Mental Hlth, Parkville, Vic 3010, Australia.
C3 Icahn School of Medicine at Mount Sinai; Harvard University; Harvard T.H. Chan School of Public Health; University of Sydney; Westmead Institute for Medical Research; NSW Health; Westmead Hospital; University of Sydney; Harvard University; University of California System; University of California Berkeley; Southern Cross University; University of Technology Sydney; Florey Institute of Neuroscience & Mental Health; University of Melbourne
RP Arora, M (corresponding author), Icahn Sch Med Mt Sinai, Dept Prevent Med, New York, NY 10029 USA.
EM marora@hsph.harvard.edu
FU US Environmental Protection Agency [RD 83171001, RD 82670901]; US National Institutes of Environmental Health Sciences [PO1 ES009605]; NSF [BCS-0921978]; Max Planck Institute for Evolutionary Anthropology; Australian Research Council [DP120101752, LP100200254]; SCU postdoctoral Fellowship grant; National Institute of Environmental Health Sciences [4R00ES019597-03]; NHMRC [APP1028372]; Agilent Technologies; Kennelec Scientific; Australian Research Council [LP100200254] Funding Source: Australian Research Council
NR 34
TC 189
Z9 221
U1 0
U2 162
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 13
PY 2013
VL 498
IS 7453
BP 216
EP +
DI 10.1038/nature12169
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 162RR
UT WOS:000320283400045
PM 23698370
DA 2026-03-09
ER

PT J
AU Roach, NT
   Venkadesan, M
   Rainbow, MJ
   Lieberman, DE
AF Roach, Neil T.
   Venkadesan, Madhusudhan
   Rainbow, Michael J.
   Lieberman, Daniel E.
TI Elastic energy storage in the shoulder and the evolution of high-speed throwing in Homo
SO NATURE
LA English
DT Article
ID humeral torsion; baseball; biomechanics; retroversion
AB Some primates, including chimpanzees, throw objects occasionally(1,2), but only humans regularly throw projectiles with high speed and accuracy. Darwin noted that the unique throwing abilities of humans, which were made possible when bipedalism emancipated the arms, enabled foragers to hunt effectively using projectiles(3). However, there has been little consideration of the evolution of throwing in the years since Darwin made his observations, in part because of a lack of evidence of when, how and why hominins evolved the ability to generate high-speed throws(4-8). Here we use experimental studies of humans throwing projectiles to show that our throwing capabilities largely result from several derived anatomical features that enable elastic energy storage and release at the shoulder. These features first appear together approximately 2 million years ago in the species Homo erectus. Taking into consideration archaeological evidence suggesting that hunting activity intensified around this time(9), we conclude that selection for throwing as a means to hunt probably had an important role in the evolution of the genus Homo.
C1 [Roach, Neil T.; Lieberman, Daniel E.] Harvard Univ, Dept Human Evolutionary Biol, Cambridge, MA 02138 USA.
   [Roach, Neil T.] George Washington Univ, Dept Anthropol, Ctr Adv Study Hominid Paleobiol, Washington, DC 20052 USA.
   [Venkadesan, Madhusudhan] Tata Inst Fundamental Res, Natl Ctr Biol Sci, Bangalore 560065, Karnataka, India.
   [Rainbow, Michael J.] Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Spaulding Natl Running Ctr, Cambridge, MA 02138 USA.
C3 Harvard University; George Washington University; Tata Institute of Fundamental Research (TIFR); National Centre for Biological Sciences (NCBS); Harvard University
RP Roach, NT (corresponding author), Harvard Univ, Dept Human Evolutionary Biol, Cambridge, MA 02138 USA.
EM ntroach@email.gwu.edu
FU National Science Foundation [BCS-0961943]; American School for Prehistoric Research; Wellcome Trust/DBT India Alliance [500158/Z/09/Z]
NR 33
TC 221
Z9 257
U1 1
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 JUN 27
PY 2013
VL 498
IS 7455
BP 483
EP +
DI 10.1038/nature12267
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 171LH
UT WOS:000320929400052
PM 23803849
DA 2026-03-09
ER

PT J
AU Ring, AM
   Manglik, A
   Kruse, AC
   Enos, MD
   Weis, WI
   Garcia, KC
   Kobilka, BK
AF Ring, Aaron M.
   Manglik, Aashish
   Kruse, Andrew C.
   Enos, Michael D.
   Weis, William I.
   Garcia, K. Christopher
   Kobilka, Brian K.
TI Adrenaline-activated structure of β2-adrenoceptor stabilized by an engineered nanobody
SO NATURE
LA English
DT Article
ID protein-coupled receptor; adrenergic-receptor; ligand-binding; agonist; adrenoceptor; rhodopsin; complex; display; serine; state
AB G-protein-coupled receptors (GPCRs) are integral membrane proteins that have an essential role in human physiology, yet the molecular processes through which they bind to their endogenous agonists and activate effector proteins remain poorly understood. So far, it has not been possible to capture an active-state GPCR bound to its native neurotransmitter. Crystal structures of agonist-bound GPCRs have relied on the use of either exceptionally high-affinity agonists(1,2) or receptor stabilization by mutagenesis(3-5). Many natural agonists such as adrenaline, which activates the beta(2)-adrenoceptor (beta(2)AR), bind with relatively low affinity, and they are often chemically unstable. Using directed evolution, we engineered a high-affinity camelid antibody fragment that stabilizes the active state of the beta(2)AR, and used this to obtain crystal structures of the activated receptor bound to multiple ligands. Here we present structures of the active-state human beta(2)AR bound to three chemically distinct agonists: the ultrahigh-affinity agonist BI167107, the high-affinity catecholamine agonist hydroxybenzyl isoproterenol, and the low-affinity endogenous agonist adrenaline. The crystal structures reveal a highly conserved overall ligand recognition and activation mode despite diverse ligand chemical structures and affinities that range from 100 nM to similar to 80 pM. Overall, the adrenaline-bound receptor structure is similar to the others, but it has substantial rearrangements in extracellular loop three and the extracellular tip of transmembrane helix 6. These structures also reveal a water-mediated hydrogen bond between two conserved tyrosines, which appears to stabilize the active state of the beta(2)AR and related GPCRs.
C1 [Ring, Aaron M.; Manglik, Aashish; Kruse, Andrew C.; Enos, Michael D.; Weis, William I.; Garcia, K. Christopher; Kobilka, Brian K.] Stanford Univ, Dept Mol & Cellular Physiol, Stanford, CA 94305 USA.
   [Ring, Aaron M.; Enos, Michael D.; Weis, William I.; Garcia, K. Christopher] Stanford Univ, Dept Biol Struct, Stanford, CA 94305 USA.
   [Garcia, K. Christopher] Stanford Univ, Sch Med, Howard Hughes Med Inst, Stanford, CA 94305 USA.
C3 Stanford University; Stanford University; Howard Hughes Medical Institute; Stanford University
RP Garcia, KC (corresponding author), Stanford Univ, Dept Mol & Cellular Physiol, Stanford, CA 94305 USA.
EM kcgarcia@stanford.edu; kobilka@stanford.edu
FU Stanford Medical Scientist Training Program; American Heart Association; National Science Foundation; Ruth L. Kirschstein National Research Service Award; National Institutes of Health [NS02847123, GM08311806]; Mathers Foundation; Howard Hughes Medical Institute; National Institute of General Medical Sciences [R01GM083118] Funding Source: NIH RePORTER; National Institute of Neurological Disorders and Stroke [R01NS028471] Funding Source: NIH RePORTER
NR 27
TC 429
Z9 488
U1 2
U2 191
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 24
PY 2013
VL 502
IS 7472
BP 575
EP +
DI 10.1038/nature12572
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 238YN
UT WOS:000325988400060
PM 24056936
DA 2026-03-09
ER

PT J
AU You, CH
   Okano, H
   Hui, S
   Zhang, ZG
   Kim, M
   Gunderson, CW
   Wang, YP
   Lenz, P
   Yan, DL
   Hwa, T
AF You, Conghui
   Okano, Hiroyuki
   Hui, Sheng
   Zhang, Zhongge
   Kim, Minsu
   Gunderson, Carl W.
   Wang, Yi-Ping
   Lenz, Peter
   Yan, Dalai
   Hwa, Terence
TI Coordination of bacterial proteome with metabolism by cyclic AMP signalling
SO NATURE
LA English
DT Article
ID lac operon expression; escherichia-coli; catabolite repression; adenylate-cyclase; phosphotransferase system; transient repression; beta-galactosidase; gene-expression; growth; glucose
AB The cyclic AMP (cAMP)-dependent catabolite repression effect in Escherichia coli is among the most intensely studied regulatory processes in biology. However, the physiological function(s) of cAMP signalling and its molecular triggers remain elusive. Here we use a quantitative physiological approach to show that cAMP signalling tightly coordinates the expression of catabolic proteins with biosynthetic and ribosomal proteins, in accordance with the cellular metabolic needs during exponential growth. The expression of carbon catabolic genes increased linearly with decreasing growth rates upon limitation of carbon influx, but decreased linearly with decreasing growth rate upon limitation of nitrogen or sulphur influx. In contrast, the expression of biosynthetic genes showed the opposite linear growth-rate dependence as the catabolic genes. A coarse-grained mathematical model provides a quantitative framework for understanding and predicting gene expression responses to catabolic and anabolic limitations. A scheme of integral feedback control featuring the inhibition of cAMP signalling by metabolic precursors is proposed and validated. These results reveal a key physiological role of cAMP-dependent catabolite repression: to ensure that proteomic resources are spent on distinct metabolic sectors as needed in different nutrient environments. Our findings underscore the power of quantitative physiology in unravelling the underlying functions of complex molecular signalling networks.
C1 [You, Conghui; Okano, Hiroyuki; Hui, Sheng; Kim, Minsu; Hwa, Terence] Univ Calif San Diego, Dept Phys, La Jolla, CA 92093 USA.
   [You, Conghui; Okano, Hiroyuki; Zhang, Zhongge; Gunderson, Carl W.; Hwa, Terence] Univ Calif San Diego, Div Biol Sci, Sect Mol Biol, La Jolla, CA 92093 USA.
   [Hui, Sheng; Hwa, Terence] Univ Calif San Diego, Ctr Theoret Biol Phys, La Jolla, CA 92093 USA.
   [Wang, Yi-Ping] Peking Univ, Coll Life Sci, State Key Lab Prot & Plant Gene Res, Beijing 100871, Peoples R China.
   [Lenz, Peter] Univ Marburg, Dept Phys, D-35032 Marburg, Germany.
   [Lenz, Peter] Univ Marburg, Ctr Synthet Microbiol, D-35032 Marburg, Germany.
   [Yan, Dalai] Indiana Univ Sch Med, Dept Microbiol & Immunol, Indianapolis, IN 46202 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; Peking University; Philipps University Marburg; Philipps University Marburg; Indiana University System; Indiana University Bloomington
RP Hwa, T (corresponding author), Univ Calif San Diego, Dept Phys, La Jolla, CA 92093 USA.
EM hwa@ucsd.edu
FU Human Frontiers in Science Program [RGP0022]; NSF [PHY1058793]; NSF through the Center for Theoretical Biological Physics [PHY0822283]; Division Of Physics; Direct For Mathematical & Physical Scien [1058793] Funding Source: National Science Foundation; Division Of Physics; Direct For Mathematical & Physical Scien [1308264] Funding Source: National Science Foundation; National Institute of General Medical Sciences [R01GM095903] Funding Source: NIH RePORTER
NR 48
TC 314
Z9 375
U1 2
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 AUG 15
PY 2013
VL 500
IS 7462
BP 301
EP 306
DI 10.1038/nature12446
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 201AF
UT WOS:000323112400025
PM 23925119
DA 2026-03-09
ER

PT J
AU Xiong, XL
   Martin, SR
   Haire, LF
   Wharton, SA
   Daniels, RS
   Bennett, MS
   McCauley, JW
   Collins, PJ
   Walker, PA
   Skehel, JJ
   Gamblin, SJ
AF Xiong, Xiaoli
   Martin, Stephen R.
   Haire, Lesley F.
   Wharton, Stephen A.
   Daniels, Rodney S.
   Bennett, Michael S.
   McCauley, John W.
   Collins, Patrick J.
   Walker, Philip A.
   Skehel, John J.
   Gamblin, Steven J.
TI Receptor binding by an H7N9 influenza virus from humans
SO NATURE
LA English
DT Article
ID human infection; a virus; hemagglutinin; transmission; fusion; h9n2; pathogenicity; cell
AB Of the 132 people known to have been infected with H7N9 influenza viruses in China, 37 died, and many were severely ill(1). Infection seems to have involved contact with infected poultry(2,3). We have examined the receptor-binding properties of this H7N9 virus and compared them with those of an avian H7N3 virus. We find that the human H7 virus has significantly higher affinity for alpha-2, 6-linked sialic acid analogues ('human receptor') than avian H7 while retaining the strong binding to alpha-2,3-linked sialic acid analogues ('avian receptor') characteristic of avian viruses. The human H7 virus does not, therefore, have the preference for human versus avian receptors characteristic of pandemic viruses. X-ray crystallography of the receptor-binding protein, haemagglutinin (HA), in complex with receptor analogues indicates that both human and avian receptors adopt different conformations when bound to human H7 HA than they do when bound to avian H7 HA. Human receptor bound to human H7 HA exits the binding site in a different direction to that seen in complexes formed by HAs from pandemic viruses(4,5) and from an aerosol-transmissible H5 mutant(6). The human-receptor-binding properties of human H7 probably arise from the introduction of two bulky hydrophobic residues by the substitutions Gln226Leu and Gly186Val. The former is shared with the 1957 H2 and 1968 H3 pandemic viruses and with the aerosol-transmissible H5 mutant. We conclude that the human H7 virus has acquired some of the receptor-binding characteristics that are typical of pandemic viruses, but its retained preference for avian receptor may restrict its further evolution towards a virus that could transmit efficiently between humans, perhaps by binding to avian-receptor-rich mucins in the human respiratory tract(7) rather than to cellular receptors.
C1 [Xiong, Xiaoli; Martin, Stephen R.; Haire, Lesley F.; Collins, Patrick J.; Walker, Philip A.; Skehel, John J.; Gamblin, Steven J.] Ridgeway, Natl Inst Med Res, MRC, Mill Hill, London NW7 1AA, England.
   [Wharton, Stephen A.; Daniels, Rodney S.; Bennett, Michael S.; McCauley, John W.] Ridgeway, Natl Inst Med Res, MRC, WHO Collaborating Ctr Reference & Res Influenza, London NW7 1AA, England.
C3 MRC National Institute for Medical Research; MRC National Institute for Medical Research
RP Gamblin, SJ (corresponding author), Ridgeway, Natl Inst Med Res, MRC, Mill Hill, London NW7 1AA, England.
EM skeheljj@nimr.mrc.ac.uk; sgambli@nimr.mrc.ac.uk
FU Medical Research Council [U117584222, U117570592, U117585868, U117512723]; MRC [MC_U117584222, MC_U117585868] Funding Source: UKRI; Medical Research Council [MC_U117584222, MC_U117585868] Funding Source: researchfish
NR 29
TC 271
Z9 303
U1 3
U2 114
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 25
PY 2013
VL 499
IS 7459
BP 496
EP +
DI 10.1038/nature12372
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 187YP
UT WOS:000322157900044
PM 23787694
DA 2026-03-09
ER

PT J
AU Vicoso, B
   Bachtrog, D
AF Vicoso, Beatriz
   Bachtrog, Doris
TI Reversal of an ancient sex chromosome to an autosome in Drosophila
SO NATURE
LA English
DT Article
ID determining mechanisms; x-chromosome; y-chromosm; genes; melanogaster; evolution; alignment; diptera; reptiles; insects
AB Although transitions of sex-determination mechanisms are frequent in species with homomorphic sex chromosomes(1-3), heteromorphic sex chromosomes are thought to represent a terminal evolutionary stage owing to chromosome-specific adaptations such as dosage compensation or an accumulation of sex-specific mutations(1,4). Here we show that an autosome of Drosophila, the dot chromosome, was ancestrally a differentiated X chromosome. We analyse the whole genome of true fruitflies (Tephritidae), flesh flies (Sarcophagidae) and soldier flies (Stratiomyidae) to show that genes located on the dot chromosome of Drosophila are X-linked in outgroup species, whereas Drosophila X-linked genes are autosomal. We date this chromosomal transition to early drosophilid evolution by sequencing the genome of other Drosophilidae. Our results reveal several puzzling aspects of Drosophila dot chromosome biology to be possible remnants of its former life as a sex chromosome, such as its minor feminizing role in sex determination(5) or its targeting by a chromosome-specific regulatory mechanism(6). We also show that patterns of biased gene expression of the dot chromosome during early embryogenesis, oogenesis and spermatogenesis resemble that of the current X chromosome. Thus, although sex chromosomes are not necessarily evolutionary end points and can revert back to an autosomal inheritance, the highly specialized genome architecture of this former X chromosome suggests that severe fitness costs must be overcome for such a turnover to occur.
C1 [Vicoso, Beatriz; Bachtrog, Doris] Univ Calif Berkeley, Dept Integrat Biol, Ctr Theoret Evolutionary Genom, Berkeley, CA 94720 USA.
C3 University of California System; University of California Berkeley
RP Bachtrog, D (corresponding author), Univ Calif Berkeley, Dept Integrat Biol, Ctr Theoret Evolutionary Genom, Berkeley, CA 94720 USA.
EM dbachtrog@berkeley.edu
FU National Institutes of Health [R01GM076007, R01GM093182]; Packard Fellowship
NR 38
TC 165
Z9 185
U1 1
U2 105
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 18
PY 2013
VL 499
IS 7458
BP 332
EP +
DI 10.1038/nature12235
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 184RJ
UT WOS:000321910700035
PM 23792562
DA 2026-03-09
ER

PT J
AU Karlsson, FH
   Tremaroli, V
   Nookaew, I
   Bergström, G
   Behre, CJ
   Fagerberg, B
   Nielsen, J
   Bäckhed, F
AF Karlsson, Fredrik H.
   Tremaroli, Valentina
   Nookaew, Intawat
   Bergstrom, Goran
   Behre, Carl Johan
   Fagerberg, Bjorn
   Nielsen, Jens
   Backhed, Fredrik
TI Gut metagenome in European women with normal, impaired and diabetic glucose control
SO NATURE
LA English
DT Article
ID intestinal microbiota; insulin sensitivity; risk; classification; discovery; program; obesity; gender; age
AB Type 2 diabetes (T2D) is a result of complex gene-environment interactions, and several risk factors have been identified, including age, family history, diet, sedentary lifestyle and obesity. Statistical models that combine known risk factors for T2D can partly identify individuals at high risk of developing the disease. However, these studies have so far indicated that human genetics contributes little to the models, whereas socio-demographic and environmental factors have greater influence(1). Recent evidence suggests the importance of the gut microbiota as an environmental factor, and an altered gut microbiota has been linked to metabolic diseases including obesity(2,3), diabetes(4) and cardiovascular disease(5). Here we use shotgun sequencing to characterize the faecal metagenome of 145 European women with normal, impaired or diabetic glucose control. We observe compositional and functional alterations in the metagenomes of women with T2D, and develop a mathematical model based on metagenomic profiles that identified T2D with high accuracy. We applied this model to women with impaired glucose tolerance, and show that it can identify women who have a diabetes-like metabolism. Furthermore, glucose control and medication were unlikely to have major confounding effects. We also applied our model to a recently described Chinese cohort(4) and show that the discriminant metagenomicmarkers for T2D differ between the European and Chinese cohorts. Therefore, metagenomic predictive tools for T2D should be specific for the age and geographical location of the populations studied.
C1 [Karlsson, Fredrik H.; Nookaew, Intawat; Nielsen, Jens] Chalmers Univ Technol, Dept Chem & Biol Engn, SE-41296 Gothenburg, Sweden.
   [Tremaroli, Valentina; Bergstrom, Goran; Behre, Carl Johan; Fagerberg, Bjorn; Backhed, Fredrik] Univ Gothenburg, Inst Med, Dept Mol & Clin Med, Wallenberg Lab, SE-41345 Gothenburg, Sweden.
   [Tremaroli, Valentina; Bergstrom, Goran; Behre, Carl Johan; Fagerberg, Bjorn; Backhed, Fredrik] Univ Gothenburg, Inst Med, Dept Mol & Clin Med, Sahlgrenska Ctr Cardiovasc & Metab Res, SE-41345 Gothenburg, Sweden.
   [Backhed, Fredrik] Univ Copenhagen, Fac Hlth Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Sect Metab Receptol & Enteroendocrinol, DK-2200 Copenhagen, Denmark.
C3 Chalmers University of Technology; University of Gothenburg; University of Gothenburg; Novo Nordisk Foundation; University of Copenhagen
RP Nielsen, J (corresponding author), Chalmers Univ Technol, Dept Chem & Biol Engn, SE-41296 Gothenburg, Sweden.
EM nielsenj@chalmers.se; fredrik.backhed@wlab.gu.se
FU Swedish Research Council; NovoNordisk foundation; Torsten Soderberg's foundation; Ragnar Soderberg's foundation; Swedish Diabetes foundation; Swedish Heart Lung Foundation; IngaBritt och Arne Lundbergs foundation; Chalmers foundation; Bioinformatics Infrastructure for Life Sciences (BILS); Knut and Alice Wallenberg foundation; Swedish Foundation for Strategic Research; AstraZeneca R&D Molndal, Sweden; Region Vastra Gotaland; Sahlgrenska University Hospital
NR 37
TC 2393
Z9 2794
U1 10
U2 604
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 6
PY 2013
VL 498
IS 7452
BP 99
EP +
DI 10.1038/nature12198
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 158DC
UT WOS:000319947800041
PM 23719380
DA 2026-03-09
ER

PT J
AU Senyuk, B
   Liu, QK
   He, SL
   Kamien, RD
   Kusner, RB
   Lubensky, TC
   Smalyukh, II
AF Senyuk, Bohdan
   Liu, Qingkun
   He, Sailing
   Kamien, Randall D.
   Kusner, Robert B.
   Lubensky, Tom C.
   Smalyukh, Ivan I.
TI Topological colloids
SO NATURE
LA English
DT Article
ID nematic liquid-crystals; point-defects; frustration; shape; dna
AB Smoke, fog, jelly, paints, milk and shaving cream are common everyday examples of colloids(1), a type of soft matter consisting of tiny particles dispersed in chemically distinct host media. Being abundant in nature, colloids also find increasingly important applications in science and technology, ranging from direct probing of kinetics in crystals and glasses(2) to fabrication of third-generation quantum-dot solar cells(3). Because naturally occurring colloids have a shape that is typically determined by minimization of interfacial tension (for example, during phase separation) or faceted crystal growth(1), their surfaces tend to have minimum-area spherical or topologically equivalent shapes such as prisms and irregular grains (all continuously deformable-homeomorphic-to spheres). Although toroidal DNA condensates and vesicles with different numbers of handles can exist(4-7) and soft matter defects can be shaped as rings(8) and knots(9), the role of particle topology in colloidal systems remains unexplored. Here we fabricate and study colloidal particles with different numbers of handles and genus g ranging from 1 to 5. When introduced into a nematic liquid crystal-a fluid made of rod-like molecules that spontaneously align along the so-called 'director'(10)-these particles induce three-dimensional director fields and topological defects dictated by colloidal topology. Whereas electric fields, photothermal melting and laser tweezing cause transformations between configurations of particle-induced structures, three-dimensional nonlinear optical imaging reveals that topological charge is conserved and that the total charge of particle-induced defects always obeys predictions of the Gauss-Bonnet and Poincare-Hopf index theorems(11-13). This allows us to establish and experimentally test the procedure for assignment and summation of topological charges in three-dimensional director fields. Our findings lay the groundwork for new applications of colloids and liquid crystals that range from topological memory devices(14), through new types of self-assembly(15-23), to the experimental study of low-dimensional topology(6,7,11-13).
C1 [Senyuk, Bohdan; Liu, Qingkun; Smalyukh, Ivan I.] Univ Colorado, Dept Phys, Boulder, CO 80309 USA.
   [Senyuk, Bohdan; Smalyukh, Ivan I.] Univ Colorado, Mat Sci & Engn Program, Dept Elect Comp & Energy Engn, Boulder, CO 80309 USA.
   [Senyuk, Bohdan; Smalyukh, Ivan I.] Univ Colorado, Crystal Mat Res Ctr, Boulder, CO 80309 USA.
   [Liu, Qingkun; He, Sailing] Zhejiang Univ, Ctr Opt & Elect Res, Hangzhou 310058, Zhejiang, Peoples R China.
   [Kamien, Randall D.; Lubensky, Tom C.] Univ Penn, Dept Phys & Astron, Philadelphia, PA 19104 USA.
   [Kusner, Robert B.] Univ Massachusetts, Dept Math & Stat, Amherst, MA 01003 USA.
   [Smalyukh, Ivan I.] Natl Renewable Energy Lab, Renewable & Sustainable Energy Inst, Boulder, CO 80309 USA.
   [Smalyukh, Ivan I.] Univ Colorado, 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; Zhejiang University; University of Pennsylvania; University of Massachusetts System; University of Massachusetts Amherst; University of Colorado System; University of Colorado Boulder
RP Smalyukh, II (corresponding author), Univ Colorado, Dept Phys, Boulder, CO 80309 USA.
EM ivan.smalyukh@colorado.edu
FU International Institute for Complex Adaptive Matter; National Science Foundation [DMR-0844115, DMR-0820579, DMR-0847782, PHY11-25915, DMR-1120901]; Direct For Mathematical & Physical Scien; Division Of Materials Research [1120901, 0847782] Funding Source: National Science Foundation
NR 33
TC 290
Z9 323
U1 5
U2 827
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 10
PY 2013
VL 493
IS 7431
BP 200
EP 205
DI 10.1038/nature11710
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 066YY
UT WOS:000313259600035
PM 23263182
DA 2026-03-09
ER

PT J
AU Smetacek, V
   Zingone, A
AF Smetacek, Victor
   Zingone, Adriana
TI Green and golden seaweed tides on the rise
SO NATURE
LA English
DT Article
ID largest macroalgal bloom; harmful algal blooms; yellow sea; ulva-prolifera; waters; enteromorpha; sargassum; responses; growth; region
AB Sudden beaching of huge seaweed masses smother the coastline and form rotting piles on the shore. The number of reports of these events in previously unaffected areas has increased worldwide in recent years. These 'seaweed tides' can harm tourism-based economies, smother aquaculture operations or disrupt traditional artisanal fisheries. Coastal eutrophication is the obvious, ultimate explanation for the increase in seaweed biomass, but the proximate processes that are responsible for individual beaching events are complex and require dedicated study to develop effective mitigation strategies. Harvesting the macroalgae, a valuable raw material, before they beach could well be developed into an effective solution.
C1 [Smetacek, Victor] Helmholtz Ctr Polar & Marine Res, Alfred Wegener Inst, D-27570 Bremerhaven, Germany.
   [Zingone, Adriana] Ecol & Evolut Plankton, Stn Zool Anton Dohrn, I-80121 Naples, Italy.
C3 Helmholtz Association; Alfred Wegener Institute, Helmholtz Centre for Polar & Marine Research; Stazione Zoologica Anton Dohrn
RP Smetacek, V (corresponding author), Helmholtz Ctr Polar & Marine Res, Alfred Wegener Inst, Handelshafen 12, D-27570 Bremerhaven, Germany.
EM victor.smetacek@awi.de; zingone@szn.it
NR 48
TC 751
Z9 854
U1 34
U2 557
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 5
PY 2013
VL 504
IS 7478
BP 84
EP 88
DI 10.1038/nature12860
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 264BK
UT WOS:000327851700029
PM 24305152
DA 2026-03-09
ER

PT J
AU Retallack, GJ
AF Retallack, Gregory J.
TI Ediacaran life on land
SO NATURE
LA English
DT Article
ID compaction; paleosols; moraines; fossils; growth; soils
AB Ediacaran (635-542 million years ago) fossils have been regarded as early animal ancestors of the Cambrian evolutionary explosion of marine invertebrate phyla(1), as giant marine protists(2) and as lichenized fungi(3). Recent documentation of palaeosols in the Ediacara Member of the Rawnsley Quartzite of South Australia(4) confirms past interpretations of lagoonal-aeolian deposition based on synsedimentary ferruginization and loessic texture(5,6). Further evidence for palaeosols comes from non-marine facies, dilation cracks, soil nodules, sand crystals, stable isotopic data and mass balance geochemistry(4). Here I show that the uppermost surfaces of the palaeosols have a variety of fossils in growth position, including Charniodiscus, Dickinsonia, Hallidaya, Parvancorina, Phyllozoon, Praecambridium, Rugoconites, Tribrachidium and 'old-elephant skin' (ichnogenus Rivularites(7)). These fossils were preserved as ferruginous impressions, like plant fossils(8), and biological soil crusts(9,10) of Phanerozoic eon sandy palaeosols. Sand crystals after gypsum(11) and nodules of carbonate(12) are shallow within the palaeosols(4), even after correcting for burial compaction(13). Periglacial involutions and modest geochemical differentiation of the palaeosols are evidence of a dry, cold temperate Ediacaran palaeoclimate in South Australia(4). This new interpretation of some Ediacaran fossils as large sessile organisms of cool, dry soils, is compatible with observations that Ediacaran fossils were similar in appearance and preservation to lichens and other microbial colonies of biological soil crusts(3), rather than marine animals(1), or protists(2).
C1 Univ Oregon, Dept Geol Sci, Eugene, OR 97403 USA.
C3 University of Oregon
RP Retallack, GJ (corresponding author), Univ Oregon, Dept Geol Sci, Eugene, OR 97403 USA.
EM gregr@uoregon.edu
FU PRF fund of the American Chemical Society
NR 30
TC 122
Z9 143
U1 0
U2 182
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 3
PY 2013
VL 493
IS 7430
BP 89
EP 92
DI 10.1038/nature11777
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 062QC
UT WOS:000312933800036
PM 23235827
DA 2026-03-09
ER

PT J
AU Reichardt, BW
   Unger, F
   Vazirani, U
AF Reichardt, Ben W.
   Unger, Falk
   Vazirani, Umesh
TI Classical command of quantum systems
SO NATURE
LA English
DT Article
ID key distribution; bells-inequality; computation; security; states; proof
AB Quantum computation and cryptography both involve scenarios in which a user interacts with an imperfectly modelled or 'untrusted' system. It is therefore of fundamental and practical interest to devise tests that reveal whether the system is behaving as instructed. In 1969, Clauser, Horne, Shimony and Holt proposed an experimental test that can be passed by a quantum-mechanical system but not by a system restricted to classical physics. Here we extend this test to enable the characterization of a large quantum system. We describe a scheme that can be used to determine the initial state and to classically command the system to evolve according to desired dynamics. The bipartite system is treated as two black boxes, with no assumptions about their inner workings except that they obey quantum physics. The scheme works even if the system is explicitly designed to undermine it; any misbehaviour is detected. Among its applications, our scheme makes it possible to test whether a claimed quantum computer is truly quantum. It also advances towards a goal of quantum cryptography: namely, the use of 'untrusted' devices to establish a shared random key, with security based on the validity of quantum physics.
C1 [Reichardt, Ben W.] Univ So Calif, Dept Elect Engn, Los Angeles, CA 90089 USA.
   [Unger, Falk] Knight Capital Grp Inc, Santa Clara, CA 95054 USA.
   [Vazirani, Umesh] Univ Calif Berkeley, Div Comp Sci, Berkeley, CA 94720 USA.
C3 University of Southern California; University of California System; University of California Berkeley
RP Reichardt, BW (corresponding author), Univ So Calif, Dept Elect Engn, Los Angeles, CA 90089 USA.
EM ben.reichardt@usc.edu
FU NSERC; ARO-DTO; Mitacs; US NSF [CCF-0905626]; Templeton grant [21674]; Direct For Computer & Info Scie & Enginr [0905626] Funding Source: National Science Foundation; Direct For Computer & Info Scie & Enginr; Division of Computing and Communication Foundations [1254119] Funding Source: National Science Foundation; Division of Computing and Communication Foundations [0905626] Funding Source: National Science Foundation
NR 40
TC 280
Z9 310
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 APR 25
PY 2013
VL 496
IS 7446
BP 456
EP 460
DI 10.1038/nature12035
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 131HU
UT WOS:000317984400032
PM 23619692
DA 2026-03-09
ER

PT J
AU Wallace, DJ
   Greenberg, DS
   Sawinski, J
   Rulla, S
   Notaro, G
   Kerr, JND
AF Wallace, Damian J.
   Greenberg, David S.
   Sawinski, Juergen
   Rulla, Stefanie
   Notaro, Giuseppe
   Kerr, Jason N. D.
TI Rats maintain an overhead binocular field at the expense of constant fusion
SO NATURE
LA English
DT Article
ID head movements; eye; experience; reflex; see
AB Fusing left and right eye images into a single view is dependent on precise ocular alignment, which relies on coordinated eye movements. During movements of the head this alignment is maintained by numerous reflexes. Although rodents share with other mammals the key components of eye movement control, the coordination of eye movements in freely moving rodents is unknown. Here we show that movements of the two eyes in freely moving rats differ fundamentally from the precisely controlled eye movements used by other mammals to maintain continuous binocular fusion. The observed eye movements serve to keep the visual fields of the two eyes continuously overlapping above the animal during free movement, but not continuously aligned. Overhead visual stimuli presented to rats freely exploring an open arena evoke an immediate shelter-seeking behaviour, but are ineffective when presented beside the arena. We suggest that continuously overlapping visual fields overhead would be of evolutionary benefit for predator detection by minimizing blind spots.
C1 [Wallace, Damian J.; Greenberg, David S.; Sawinski, Juergen; Rulla, Stefanie; Notaro, Giuseppe; Kerr, Jason N. D.] Max Planck Inst Biol Cybernet, Network Imaging Grp, D-72076 Tubingen, Germany.
   [Notaro, Giuseppe; Kerr, Jason N. D.] Bernstein Ctr Computat Neurosci Tubingen, D-72076 Tubingen, Germany.
C3 Max Planck Society
RP Kerr, JND (corresponding author), Max Planck Inst Biol Cybernet, Network Imaging Grp, Spemannstr 41, D-72076 Tubingen, Germany.
EM jason@tuebingen.mpg.de
FU German Federal Ministry of Education and Research (BMBF) [FKZ: 01GQ1002]; Max Planck Society
NR 27
TC 215
Z9 252
U1 0
U2 57
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 6
PY 2013
VL 498
IS 7452
BP 65
EP 69
DI 10.1038/nature12153
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 158DC
UT WOS:000319947800033
PM 23708965
DA 2026-03-09
ER

PT J
AU Seed, KD
   Lazinski, DW
   Calderwood, SB
   Camilli, A
AF Seed, Kimberley D.
   Lazinski, David W.
   Calderwood, Stephen B.
   Camilli, Andrew
TI A bacteriophage encodes its own CRISPR/Cas adaptive response to evade host innate immunity
SO NATURE
LA English
DT Article
ID cas systems; phage; interference; archaea; defense; rna; dna; resistance; evolution; pathogen
AB Bacteriophages (or phages) are the most abundant biological entities on earth, and are estimated to outnumber their bacterial prey by tenfold(1). The constant threat of phage predation has led to the evolution of a broad range of bacterial immunity mechanisms that in turn result in the evolution of diverse phage immune evasion strategies, leading to a dynamic co-evolutionary arms race(2,3). Although bacterial innate immune mechanisms against phage abound, the only documented bacterial adaptive immune system is the CRISPR/Cas (clustered regularly interspaced short palindromic repeats/CRISPR-associated proteins) system, which provides sequence-specific protection from invading nudeic acids, including phage(4-11). Here we show a remarkable turn of events, in which a phage-encoded CRISPR/Cas system is used to counteract a phage inhibitory chromosomal island of the bacterial host. A successful lytic infection by the phage is dependent on sequence identity between CRISPR spacers and the target chromosomal island. In the absence of such targeting, the phage-encoded CRISPR/Cas system can acquire new spacers to evolve rapidly and ensure effective targeting of the chromosomal island to restore phage replication.
C1 [Seed, Kimberley D.; Lazinski, David W.; Camilli, Andrew] Tufts Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02111 USA.
   [Seed, Kimberley D.; Lazinski, David W.; Camilli, Andrew] Tufts Univ, Dept Mol Biol & Microbiol, Boston, MA 02111 USA.
   [Calderwood, Stephen B.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA.
   [Calderwood, Stephen B.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
C3 Howard Hughes Medical Institute; Tufts University; Tufts University; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard Medical School
RP Camilli, A (corresponding author), Tufts Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02111 USA.
EM andrew.camilli@tufts.edu
FU US National Institutes of Health [AI055058, AI045746, AI058935]
NR 30
TC 293
Z9 389
U1 4
U2 236
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 28
PY 2013
VL 494
IS 7438
BP 489
EP 491
DI 10.1038/nature11927
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 099YI
UT WOS:000315661500041
PM 23446421
DA 2026-03-09
ER

PT J
AU Wesemann, DR
   Portuguese, AJ
   Meyers, RM
   Gallagher, MP
   Cluff-Jones, K
   Magee, JM
   Panchakshari, RA
   Rodig, SJ
   Kepler, TB
   Alt, FW
AF Wesemann, Duane R.
   Portuguese, Andrew J.
   Meyers, Robin M.
   Gallagher, Michael P.
   Cluff-Jones, Kendra
   Magee, Jennifer M.
   Panchakshari, Rohit A.
   Rodig, Scott J.
   Kepler, Thomas B.
   Alt, Frederick W.
TI Microbial colonization influences early B-lineage development in the gut lamina propria
SO NATURE
LA English
DT Article
ID antibody repertoire development; cell development; rag expression; recombination; immunization; tolerance; genes; mouse; fetal; mice
AB The RAG1/RAG2 endonuclease (RAG) initiates the V(D)J recombination reaction that assembles immunoglobulin heavy (IgH) and light (IgL) chain variable region exons from germline gene segments to generate primary antibody repertoires(1). IgH V(D)J assembly occurs in progenitor (pro-) B cells followed by that of IgL in precursor (pre-) B cells. Expression of IgH mu and IgL (Ig kappa or Ig lambda) chains generates IgM, which is expressed on immature B cells as the B-cell antigen-binding receptor (BCR). Rag expression can continue in immature B cells(2), allowing continued Ig kappa V(D)J recombination that replaces the initial V kappa J kappa exon with one that generates a new specificity(3-5). This 'receptor editing' process, which can also lead to Ig lambda V(D)J recombination and expression(3,6,7), provides a mechanism whereby antigen encounter at the Rag-expressing immature B-cell stage helps shape pre-immune BCR repertoires. As the major site of postnatal B-cell development, the bone marrow is the principal location of primary immunoglobulin repertoire diversification in mice. Here we report that early B-cell development also occurs within the mouse intestinal lamina propria (LP), where the associated V(D)J recombination/receptor editing processes modulate primary LP immunoglobulin repertoires. At weanling age in normally housed mice, the LP contains a population of Rag-expressing B-lineage cells that harbour intermediates indicative of ongoing V(D)J recombination and which contain cells with pro-B, pre-B and editing phenotypes. Consistent with LP-specific receptor editing, Rag-expressing LP B-lineage cells have similar V-H repertoires, but significantly different V kappa repertoires, compared to those of Rag2-expressing bone marrow counterparts. Moreover, colonization of germ-free mice leads to an increased ratio of Ig lambda-expressing versus Ig kappa-expressing B cells specifically in the LP. We conclude that B-cell development occurs in the intestinal mucosa, where it is regulated by extracellular signals from commensal microbes that influence gut immunoglobulin repertoires.
C1 [Wesemann, Duane R.; Portuguese, Andrew J.; Meyers, Robin M.; Gallagher, Michael P.; Cluff-Jones, Kendra; Magee, Jennifer M.; Panchakshari, Rohit A.; Alt, Frederick W.] Childrens Hosp Boston, Program Cellular & Mol Med, Boston, MA 02115 USA.
   [Wesemann, Duane R.; Portuguese, Andrew J.; Meyers, Robin M.; Gallagher, Michael P.; Cluff-Jones, Kendra; Magee, Jennifer M.; Panchakshari, Rohit A.; Alt, Frederick W.] Childrens Hosp Boston, Dept Med, Boston, MA 02115 USA.
   [Wesemann, Duane R.; Portuguese, Andrew J.; Meyers, Robin M.; Gallagher, Michael P.; Cluff-Jones, Kendra; Magee, Jennifer M.; Panchakshari, Rohit A.; Alt, Frederick W.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
   [Wesemann, Duane R.; Portuguese, Andrew J.; Meyers, Robin M.; Gallagher, Michael P.; Cluff-Jones, Kendra; Magee, Jennifer M.; Panchakshari, Rohit A.; Alt, Frederick W.] Howard Hughes Med Inst, Boston, MA 02115 USA.
   [Wesemann, Duane R.] Brigham & Womens Hosp, Dept Med, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA.
   [Rodig, Scott J.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
   [Kepler, Thomas B.] Boston Univ, Sch Med, Dept Microbiol, Boston, MA 02215 USA.
C3 Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Program in Cellular & Molecular Medicine (PCMM); Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Harvard University; Harvard Medical School; Howard Hughes Medical Institute; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Boston University
RP Alt, FW (corresponding author), Childrens Hosp Boston, Program Cellular & Mol Med, Boston, MA 02115 USA.
EM dwesemann@research.bwh.harvard.edu; alt@enders.tch.harvard.edu
FU National Institutes of Health [AI020047, AI89972, HHSN272201000053C]; Lymphoma and Leukemia SCOR [7009-12]; American Academy of Allergy Asthma and Immunology; CSL-Behring; Career Award for Medical Scientists from the Burroughs Wellcome Fund; National Institute of Allergy and Infectious Diseases [R01AI020047] Funding Source: NIH RePORTER
NR 30
TC 217
Z9 290
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 SEP 5
PY 2013
VL 501
IS 7465
BP 
EP 
DI 10.1038/nature12496
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AL8YC
UT WOS:000339424700001
PM 23965619
DA 2026-03-09
ER

PT J
AU Ofek, EO
   Sullivan, M
   Cenko, SB
   Kasliwal, MM
   Gal-Yam, A
   Kulkarni, SR
   Arcavi, I
   Bildsten, L
   Bloom, JS
   Horesh, A
   Howell, DA
   Filippenko, AV
   Laher, R
   Murray, D
   Nakar, E
   Nugent, PE
   Silverman, JM
   Shaviv, NJ
   Surace, J
   Yaron, O
AF Ofek, E. O.
   Sullivan, M.
   Cenko, S. B.
   Kasliwal, M. M.
   Gal-Yam, A.
   Kulkarni, S. R.
   Arcavi, I.
   Bildsten, L.
   Bloom, J. S.
   Horesh, A.
   Howell, D. A.
   Filippenko, A. V.
   Laher, R.
   Murray, D.
   Nakar, E.
   Nugent, P. E.
   Silverman, J. M.
   Shaviv, N. J.
   Surace, J.
   Yaron, O.
TI An outburst from a massive star 40 days before a supernova explosion
SO NATURE
LA English
DT Article
ID luminous supernova; envelope; discovery; sn-2006gy
AB Some observations suggest that very massive stars experience extreme mass-loss episodes shortly before they explode as supernovae(1-4), as do several models(5-7). Establishing a causal connection between these mass-loss episodes and the final explosion would provide a novel way to study pre-supernova massive-star evolution. Here we report. observations of a mass-loss event detected 40 days before the explosion of the type IIn supernova SN 2010mc (also known as PTF 10tel). Our photometric and spectroscopic data suggest that this event is a result of an energetic outburst, radiating at least 6 x 10(47) erg of energy and releasing about 10(-2) solar masses of material at typical velocities of 2,000 km s(-1). The temporal proximity of the mass-loss outburst and the supernova explosion implies a causal connection between them. Moreover, we find that the outburst luminosity and velocity are consistent with the predictions of the wave-driven pulsation model(6), and disfavour alternative suggestions(7).
C1 [Ofek, E. O.; Gal-Yam, A.; Arcavi, I.; Yaron, O.] Weizmann Inst Sci, Benoziyo Ctr Astrophys, IL-76100 Rehovot, Israel.
   [Sullivan, M.] Univ Southampton, Sch Phys & Astron, Southampton SO17 1BJ, Hants, England.
   [Sullivan, M.] Univ Oxford, Dept Phys Astrophys, Oxford OX1 3RH, England.
   [Cenko, S. B.; Bloom, J. S.; Filippenko, A. V.; Nugent, P. E.; Silverman, J. M.] Univ Calif Berkeley, Dept Astron, Berkeley, CA 94720 USA.
   [Kasliwal, M. M.] Observ Carnegie Inst Sci, Pasadena, CA 91101 USA.
   [Kulkarni, S. R.; Horesh, A.] CALTECH, Div Phys Math & Astron, Pasadena, CA 91125 USA.
   [Bildsten, L.] Univ Calif Santa Barbara, Kavli Inst Theoret Phys, Santa Barbara, CA 93106 USA.
   [Bildsten, L.; Howell, D. A.] Univ Calif Santa Barbara, Dept Phys, Santa Barbara, CA 93106 USA.
   [Bloom, J. S.] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Berkeley, CA 94720 USA.
   [Howell, D. A.] Las Cumbres Observ Global Telescope Network, Goleta, CA 93117 USA.
   [Laher, R.; Surace, J.] CALTECH, Spitzer Sci Ctr, Pasadena, CA 91125 USA.
   [Murray, D.] Univ Wisconsin, Dept Phys, Milwaukee, WI 53211 USA.
   [Nakar, E.] Tel Aviv Univ, Sch Phys & Astron, IL-69978 Tel Aviv, Israel.
   [Silverman, J. M.] Univ Texas Austin, Dept Astron, Austin, TX 78712 USA.
   [Shaviv, N. J.] Hebrew Univ Jerusalem, Racah Inst Phys, IL-91904 Jerusalem, Israel.
C3 Weizmann Institute of Science; University of Southampton; University of Oxford; University of California System; University of California Berkeley; Carnegie Institution for Science; California Institute of Technology; University of California System; University of California Santa Barbara; University of California System; University of California Santa Barbara; United States Department of Energy (DOE); Lawrence Berkeley National Laboratory; University of California System; University of California Berkeley; California Institute of Technology; University of Wisconsin System; University of Wisconsin Milwaukee; Tel Aviv University; University of Texas System; University of Texas Austin; Hebrew University of Jerusalem
RP Ofek, EO (corresponding author), Weizmann Inst Sci, Benoziyo Ctr Astrophys, IL-76100 Rehovot, Israel.
EM eran@astro.caltech.edu
FU Arye Dissentshik career development chair; Helen Kimmel Center for Planetary Science; Israeli Ministry of Science; Royal Society; NSF; Israeli Science Foundation; German-Israeli Foundation; ERC; US Department of Energy; Gary and Cynthia Bengier, the Richard and Rhoda Goldman Fund; Christopher R. Redlich Fund; TABASGO Foundation; Direct For Mathematical & Physical Scien; Division Of Astronomical Sciences [1009987, 1109174] Funding Source: National Science Foundation; Division Of Astronomical Sciences; Direct For Mathematical & Physical Scien [1211916] Funding Source: National Science Foundation
NR 29
TC 197
Z9 215
U1 0
U2 17
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 7
PY 2013
VL 494
IS 7435
BP 65
EP 67
DI 10.1038/nature11877
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 087DJ
UT WOS:000314741200034
PM 23389540
DA 2026-03-09
ER

PT J
AU Rais, Y
   Zviran, A
   Geula, S
   Gafni, O
   Chomsky, E
   Viukov, S
   Mansour, AA
   Caspi, I
   Krupalnik, V
   Zerbib, M
   Maza, I
   Mor, N
   Baran, D
   Weinberger, L
   Jaitin, DA
   Lara-Astiaso, D
   Blecher-Gonen, R
   Shipony, Z
   Mukamel, Z
   Hagai, T
   Gilad, S
   Amann-Zalcenstein, D
   Tanay, A
   Amit, I
   Novershtern, N
   Hanna, JH
AF Rais, Yoach
   Zviran, Asaf
   Geula, Shay
   Gafni, Ohad
   Chomsky, Elad
   Viukov, Sergey
   Mansour, Abed AlFatah
   Caspi, Inbal
   Krupalnik, Vladislav
   Zerbib, Mirie
   Maza, Itay
   Mor, Nofar
   Baran, Dror
   Weinberger, Leehee
   Jaitin, Diego A.
   Lara-Astiaso, David
   Blecher-Gonen, Ronnie
   Shipony, Zohar
   Mukamel, Zohar
   Hagai, Tzachi
   Gilad, Shlomit
   Amann-Zalcenstein, Daniela
   Tanay, Amos
   Amit, Ido
   Novershtern, Noa
   Hanna, Jacob H.
TI Deterministic direct reprogramming of somatic cells to pluripotency
SO NATURE
LA English
DT Article
ID dna methylation; nurd; component; network; complex; nanog; mbd3
AB Somatic cells can be inefficiently and stochastically reprogrammed into induced pluripotent stem(iPS) cells by exogenous expression of Oct4 (also called Pou5f1), Sox2, Klf4 and Myc (hereafter referred to as OSKM). The nature of the predominant rate-limiting barrier(s) preventing the majority of cells to successfully and synchronously reprogram remains to be defined. Here we show that depleting Mbd3, a core member of the Mbd3/NuRD (nucleosome remodelling and deacetylation) repressor complex, together with OSKM transduction and reprogramming in naive pluripotency promoting conditions, result in deterministic and synchronized iPS cell reprogramming (near 100% efficiency within seven days from mouse and human cells). Our findings uncover a dichotomous molecular function for the reprogramming factors, serving to reactivate endogenous pluripotency networks while simultaneously directly recruiting the Mbd3/NuRD repressor complex that potently restrains the reactivation of OSKM downstream target genes. Subsequently, the latter interactions, which are largely depleted during early pre-implantation development in vivo, lead to a stochastic and protracted reprogramming trajectory towards pluripotency in vitro. The deterministic reprogramming approach devised here offers a novel platform for the dissection of molecular dynamics leading to establishing pluripotency at unprecedented flexibility and resolution.
C1 [Rais, Yoach; Zviran, Asaf; Geula, Shay; Gafni, Ohad; Chomsky, Elad; Viukov, Sergey; Mansour, Abed AlFatah; Caspi, Inbal; Krupalnik, Vladislav; Zerbib, Mirie; Maza, Itay; Mor, Nofar; Baran, Dror; Weinberger, Leehee; Novershtern, Noa; Hanna, Jacob H.] Weizmann Inst Sci, Dept Mol Genet, IL-76100 Rehovot, Israel.
   [Jaitin, Diego A.; Lara-Astiaso, David; Blecher-Gonen, Ronnie; Amit, Ido] Weizmann Inst Sci, Dept Immunol, IL-76100 Rehovot, Israel.
   [Shipony, Zohar; Mukamel, Zohar; Tanay, Amos] Weizmann Inst Sci, Dept Regulat Biol, IL-76100 Rehovot, Israel.
   [Shipony, Zohar; Mukamel, Zohar; Tanay, Amos] Weizmann Inst Sci, Dept Comp Sci, IL-76100 Rehovot, Israel.
   [Hagai, Tzachi] Weizmann Inst Sci, Dept Biol Struct, IL-76100 Rehovot, Israel.
   [Gilad, Shlomit; Amann-Zalcenstein, Daniela] Weizmann Inst Sci, Israel Natl Ctr Personalized Med, 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; 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 Leona M. and Harry B. Helmsley Charitable Trust; ERC [StG-281906, StG-309788]; BIRAX initiative; Israel Science Foundation; ICRF; Fritz Thyssen Stiftung; The Benoziyo Endowment fund; Alon Scholar Program; HFSP Career Development Award, an ISF-Bikura; Weizmann Dean fellowship; Weizmann Institute management
NR 40
TC 427
Z9 541
U1 1
U2 244
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 3
PY 2013
VL 502
IS 7469
BP 65
EP +
DI 10.1038/nature12587
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 227IM
UT WOS:000325106000031
PM 24048479
DA 2026-03-09
ER

PT J
AU Bretschneider, T
   Heim, JB
   Heine, D
   Winkler, R
   Busch, B
   Kusebauch, B
   Stehle, T
   Zocher, G
   Hertweck, C
AF Bretschneider, Tom
   Heim, Joel B.
   Heine, Daniel
   Winkler, Robert
   Busch, Benjamin
   Kusebauch, Bjoern
   Stehle, Thilo
   Zocher, Georg
   Hertweck, Christian
TI Vinylogous chain branching catalysed by a dedicated polyketide synthase module
SO NATURE
LA English
DT Article
ID combinatorial biosynthesis; bacterial endosymbiont; crystal-structure; enzymology; evolution; logic
AB Bacteria use modular polyketide synthases (PKSs) to assemble complex polyketides, many of which are leads for the development of clinical drugs, in particular anti-infectives and anti-tumoral agents(1). Because these multifarious compounds are notoriously difficult to synthesize, they are usually produced by microbial fermentation. During the past two decades, an impressive body of knowledge on modular PKSs(2,3) has been gathered that not only provides detailed insight into the biosynthetic pathways but also allows the rational engineering of enzymatic processing lines to yield structural analogues(4,5). Notably, a hallmark of all PKS modules studied so far is the head-to-tail fusion of acyl and malonyl building blocks, which leads to linear backbones. Yet, structural diversity is limited by this uniform assembly mode. Here we demonstrate a new type of PKS module from the endofungal bacterium Burkholderia rhizoxinica that catalyses a Michael-type acetyl addition to generate a branch in the carbon chain. In vitro reconstitution of the entire PKS module, X-ray structures of a ketosynthase-branching didomain and mutagenesis experiments revealed a crucial role of the ketosynthase domain in branching the carbon chain. We present a trapped intermediary state in which acyl carrier protein and ketosynthase are covalently linked by the branched polyketide and suggest a new mechanism for chain alkylation, which is functionally distinct from terpenoid-like beta-branching. For the rice seedling blight toxin rhizoxin, one of the strongest known anti-mitotic agents, the non-canonical polyketide modification is indispensable for phytotoxic and anti-tumoral activities. We propose that the formation of related pharmacophoric groups follows the same general scheme and infer a unifying vinylogous branching reaction for PKS modules with a ketosynthase-branching-acyl-carrier-protein architecture. This study unveils the structure and function of a new PKS module that broadens the biosynthetic scope of polyketide biosynthesis and sets the stage for rationally creating structural diversity.
C1 [Bretschneider, Tom; Heine, Daniel; Winkler, Robert; Busch, Benjamin; Kusebauch, Bjoern; Hertweck, Christian] Leibniz Inst Nat Prod Res & Infect Biol HKI, Dept Biomol Chem, D-07745 Jena, Germany.
   [Heim, Joel B.; Stehle, Thilo; Zocher, Georg] Univ Tubingen, Interfac Inst Biochem, D-72076 Tubingen, Germany.
   [Stehle, Thilo] Vanderbilt Univ, Sch Med, Dept Pediat, Nashville, TN 37232 USA.
   [Hertweck, Christian] Univ Jena, Chair Nat Prod Chem, D-07737 Jena, Germany.
C3 Leibniz Association; Hans Knoll Institute (HKI); Eberhard Karls University of Tubingen; Vanderbilt University; Friedrich Schiller University of Jena
RP Hertweck, C (corresponding author), Leibniz Inst Nat Prod Res & Infect Biol HKI, Dept Biomol Chem, D-07745 Jena, Germany.
EM georg.zocher@uni-tuebingen.de; christian.hertweck@hki-jena.de
FU DFG [SFB 766]; Studienstiftung des Deutschen Volkes
NR 43
TC 97
Z9 111
U1 2
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 OCT 3
PY 2013
VL 502
IS 7469
BP 124
EP +
DI 10.1038/nature12588
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 227IM
UT WOS:000325106000044
PM 24048471
DA 2026-03-09
ER

PT J
AU Archibald, RF
   Kaspi, VM
   Ng, CY
   Gourgouliatos, KN
   Tsang, D
   Scholz, P
   Beardmore, AP
   Gehrels, N
   Kennea, JA
AF Archibald, R. F.
   Kaspi, V. M.
   Ng, C. -Y.
   Gourgouliatos, K. N.
   Tsang, D.
   Scholz, P.
   Beardmore, A. P.
   Gehrels, N.
   Kennea, J. A.
TI An anti-glitch in a magnetar
SO NATURE
LA English
DT Article
ID x-ray pulsar; variable spin-down; neutron-stars; 1e 2259+586; sgr 1900+14; rotation; magnetospheres; superfluidity; bursts
AB Magnetars are neutron stars with X-ray and soft gamma-ray outbursts thought to be powered by intense internal magnetic fields(1). Like conventional neutron stars in the form of radio pulsars, magnetars exhibit 'glitches' during which angular momentum is believed to be transferred between the solid outer crust and the superfluid component of the inner crust(2-4). The several hundred observed glitches in radio pulsars(5,6) and magnetars(7) have involved a sudden spin-up (increase in the angular velocity) of the star, presumably because the interior superfluid was rotating faster than the crust. Here we report X-ray timing observations of the magnetar 1E 2259+586 (ref. 8), which exhibited a clear 'anti-glitch'-a sudden spin-down. We show that this event, like some previous magnetar spin-up glitches(9), was accompanied by multiple X-ray radiative changes and a significant spin-down rate change. Such behaviour is not predicted by models of neutron star spin-down and, if of internal origin, is suggestive of differential rotation in the magnetar, supporting the need for a rethinking of glitch theory for all neutron stars(10,11).
C1 [Archibald, R. F.; Kaspi, V. M.; Ng, C. -Y.; Gourgouliatos, K. N.; Tsang, D.; Scholz, P.] McGill Univ, Dept Phys, Montreal, PQ H3A 2T8, Canada.
   [Ng, C. -Y.] Univ Hong Kong, Dept Phys, Hong Kong, Hong Kong, Peoples R China.
   [Beardmore, A. P.] Univ Leicester, Dept Phys & Astron, Leicester LE1 7RH, Leics, England.
   [Gehrels, N.] NASA, Astrophys Sci Div, Goddard Space Flight Ctr, Greenbelt, MD 20771 USA.
   [Kennea, J. A.] Penn State Univ, Dept Astron & Astrophys, Davey Lab 525, University Pk, PA 16802 USA.
C3 McGill University; University of Hong Kong; University of Leicester; National Aeronautics & Space Administration (NASA); NASA Goddard Space Flight Center; Pennsylvania Commonwealth System of Higher Education (PCSHE); Pennsylvania State University; Pennsylvania State University - University Park
RP Kaspi, VM (corresponding author), McGill Univ, Dept Phys, 3600 Univ St, Montreal, PQ H3A 2T8, Canada.
EM vkaspi@physics.mcgill.ca
FU Natural Sciences and Engineering Research Council of Canada; Canadian Institute for Advanced Research; Fonds de Recherche Nature et Technologies Quebec; Canada Research Chairs Program; Lorne Trottier Chair in Astrophysics and Cosmology; Centre de Recherche en Astrophysique du Quebec; UK Space Agency [ST/J000841/1] Funding Source: researchfish
NR 26
TC 116
Z9 135
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 MAY 30
PY 2013
VL 497
IS 7451
BP 591
EP 593
DI 10.1038/nature12159
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 152UF
UT WOS:000319556100037
PM 23719460
DA 2026-03-09
ER

PT J
AU Heneka, MT
   Kummer, MP
   Stutz, A
   Delekate, A
   Schwartz, S
   Vieira-Saecker, A
   Griep, A
   Axt, D
   Remus, A
   Tzeng, TC
   Gelpi, E
   Halle, A
   Korte, M
   Latz, E
   Golenbock, DT
AF Heneka, Michael T.
   Kummer, Markus P.
   Stutz, Andrea
   Delekate, Andrea
   Schwartz, Stephanie
   Vieira-Saecker, Ana
   Griep, Angelika
   Axt, Daisy
   Remus, Anita
   Tzeng, Te-Chen
   Gelpi, Ellen
   Halle, Annett
   Korte, Martin
   Latz, Eicke
   Golenbock, Douglas T.
TI NLRP3 is activated in Alzheimer's disease and contributes to pathology in APP/PS1 mice
SO NATURE
LA English
DT Article
ID long-term potentiation; amyloid clearance; beta; microglia; cns; interleukin-1-beta; expression; il-1-beta; enzyme; memory
AB Alzheimer's disease is the world's most common dementing illness. Deposition of amyloid-beta peptide drives cerebral neuroinflammation by activating microglia(1,2). Indeed, amyloid-beta activation of the NLRP3 inflammasome in microglia is fundamental for interleukin-1 beta maturation and subsequent inflammatory events(3). However, it remains unknown whether NLRP3 activation contributes to Alzheimer's disease in vivo. Here we demonstrate strongly enhanced active caspase-1 expression in human mild cognitive impairment and brains with Alzheimer's disease, suggesting a role for the inflammasome in this neurodegenerative disease. Nlrp3(-/-) or Casp1(-/-) mice carrying mutations associated with familial Alzheimer's disease were largely protected from loss of spatial memory and other sequelae associated with Alzheimer's disease, and demonstrated reduced brain caspase-1 and interleukin-1 beta activation as well as enhanced amyloid-beta clearance. Furthermore, NLRP3 inflammasome deficiency skewed microglial cells to an M2 phenotype and resulted in the decreased deposition of amyloid-beta in the APP/PS1 model of Alzheimer's disease. These results show an important role for the NLRP3/caspase-1 axis in the pathogenesis of Alzheimer's disease, and suggest that NLRP3 inflammasome inhibition represents a new therapeutic intervention for the disease.
C1 [Heneka, Michael T.; Kummer, Markus P.; Schwartz, Stephanie; Vieira-Saecker, Ana; Griep, Angelika; Axt, Daisy] Univ Bonn, Dept Neurol, Clin Neurosci Unit, D-53127 Bonn, Germany.
   [Heneka, Michael T.; Latz, Eicke] DZNE, D-53175 Bonn, Germany.
   [Stutz, Andrea; Latz, Eicke] Univ Bonn, Inst Innate Immun, D-53127 Bonn, Germany.
   [Delekate, Andrea; Remus, Anita; Korte, Martin] Tech Univ Carolo Wilhelmina Braunschweig, Inst Zool, Div Cellular Neurobiol, D-38106 Braunschweig, Germany.
   [Tzeng, Te-Chen; Latz, Eicke; Golenbock, Douglas T.] Univ Massachusetts, Sch Med, Dept Med, Worcester, MA 01605 USA.
   [Tzeng, Te-Chen; Latz, Eicke; Golenbock, Douglas T.] Univ Massachusetts, Sch Med, Div Infect Dis & Immunol, Worcester, MA 01605 USA.
   [Gelpi, Ellen] Univ Barcelona, Hosp Clin, IDIBAPS, Neurol Tissue Bank, E-08036 Barcelona, Spain.
   [Halle, Annett] Ctr Adv European Studies & Res CAESAR, D-53175 Bonn, Germany.
   [Korte, Martin] AG NIND, HZI, Helmholtz Ctr Infect Res, D-38124 Braunschweig, Germany.
C3 University of Bonn; Helmholtz Association; German Center for Neurodegenerative Diseases (DZNE); University of Bonn; Braunschweig University of Technology; University of Massachusetts System; University of Massachusetts Worcester; University of Massachusetts System; University of Massachusetts Worcester; University of Barcelona; Hospital Clinic de Barcelona; IDIBAPS; Center of Advanced European Studies & Research (CAESAR); Helmholtz Association; Helmholtz-Center for Infection Research
RP Latz, E (corresponding author), DZNE, D-53175 Bonn, Germany.
EM michael.Heneka@ukb.uni-bonn.de; eicke.latz@uni-bonn.de; douglas.golenbock@umassmed.edu
FU Dana Foundation; National Institutes of Health; Deutsche Forschungsgemeinschaft
NR 30
TC 2297
Z9 2687
U1 12
U2 628
PU NATURE PUBLISHING 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 31
PY 2013
VL 493
IS 7434
BP 674
EP +
DI 10.1038/nature11729
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 080CU
UT WOS:000314219600057
PM 23254930
DA 2026-03-09
ER

PT J
AU Commisso, C
   Davidson, SM
   Soydaner-Azeloglu, RG
   Parker, SJ
   Kamphorst, JJ
   Hackett, S
   Grabocka, E
   Nofal, M
   Drebin, JA
   Thompson, CB
   Rabinowitz, JD
   Metallo, CM
   Vander Heiden, MG
   Bar-Sagi, D
AF Commisso, Cosimo
   Davidson, Shawn M.
   Soydaner-Azeloglu, Rengin G.
   Parker, Seth J.
   Kamphorst, Jurre J.
   Hackett, Sean
   Grabocka, Elda
   Nofal, Michel
   Drebin, Jeffrey A.
   Thompson, Craig B.
   Rabinowitz, Joshua D.
   Metallo, Christian M.
   Vander Heiden, Matthew G.
   Bar-Sagi, Dafna
TI Macropinocytosis of protein is an amino acid supply route in Ras-transformed cells
SO NATURE
LA English
DT Article
ID mass isotopomer distributions; k-ras; glutamine-metabolism; h-ras; cancer; src; fibroblasts; carcinoma; pathways; growth
AB Macropinocytosis is a highly conserved endocytic process by which extracellular fluid and its contents are internalized into cells through large, heterogeneous vesicles known as macropinosomes. Oncogenic Ras proteins have been shown to stimulate macropinocytosis but the functional contribution of this uptake mechanism to the transformed phenotype remains unknown(1-3). Here we show that Ras-transformed cells use macropinocytosis to transport extracellular protein into the cell. The internalized protein undergoes proteolytic degradation, yielding amino acids including glutamine that can enter central carbon metabolism. Accordingly, the dependence of Ras-transformed cells on free extracellular glutamine for growth can be suppressed by the macropinocytic uptake of protein. Consistent with macropinocytosis representing an important route of nutrient uptake in tumours, its pharmacological inhibition compromises the growth of Ras-transformed pancreatic tumour xenografts. These results identify macropinocytosis as a mechanism by which cancer cells support their unique metabolic needs and point to the possible exploitation of this process in the design of anticancer therapies.
C1 [Commisso, Cosimo; Soydaner-Azeloglu, Rengin G.; Grabocka, Elda; Bar-Sagi, Dafna] NYU, Sch Med, Dept Biochem & Mol Pharmacol, New York, NY 10016 USA.
   [Davidson, Shawn M.; Vander Heiden, Matthew G.] MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA.
   [Davidson, Shawn M.; Vander Heiden, Matthew G.] MIT, Dept Biol, Cambridge, MA 02139 USA.
   [Parker, Seth J.; Metallo, Christian M.] Univ Calif San Diego, Dept Bioengn, La Jolla, CA 92093 USA.
   [Kamphorst, Jurre J.; Hackett, Sean; Nofal, Michel; Rabinowitz, Joshua D.] Princeton Univ, Carl Icahn Lab, Lewis Sigler Inst Integrat Genom, Princeton, NJ 08544 USA.
   [Drebin, Jeffrey A.] Hosp Univ Penn, Dept Surg, Philadelphia, PA 19104 USA.
   [Thompson, Craig B.] Mem Sloan Kettering Canc Ctr, Canc Biol & Genet Program, New York, NY 10065 USA.
   [Vander Heiden, Matthew G.] Dana Farber Canc Inst, Boston, MA 02115 USA.
C3 New York University; Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); University of California System; University of California San Diego; Princeton University; University of Pennsylvania; Memorial Sloan Kettering Cancer Center; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute
RP Bar-Sagi, D (corresponding author), NYU, Sch Med, Dept Biochem & Mol Pharmacol, New York, NY 10016 USA.
EM dafna.bar-sagi@nyumc.org
FU National Institutes of Health (NIH) [R01CA055360, 5 P30CA016087-32]; Canadian Institutes of Health Research; AACR provided by the Pancreatic Cancer Action Network; Burroughs Wellcome Fund; Damon Runyon Cancer Research Foundation; Smith Family; Stern family; Broad Institute; National Cancer Institute [P01-CA117969, P30-CA14051-39]; Hope Funds for Cancer Research Fellowship [HFCR-11-03-01]; Stand Up To Cancer (SU2C) Pancreatic Cancer Dream Team Award; NICHD; National Cancer Institute [R01CA163591, P30CA016087, P30CA014051, P01CA117969] Funding Source: NIH RePORTER
NR 31
TC 1361
Z9 1616
U1 6
U2 250
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 30
PY 2013
VL 497
IS 7451
BP 633
EP +
DI 10.1038/nature12138
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 152UF
UT WOS:000319556100047
PM 23665962
DA 2026-03-09
ER

PT J
AU Oka, Y
   Butnaru, M
   von Buchholtz, L
   Ryba, NJP
   Zuker, CS
AF Oka, Yuki
   Butnaru, Matthew
   von Buchholtz, Lars
   Ryba, Nicholas J. P.
   Zuker, Charles S.
TI High salt recruits aversive taste pathways
SO NATURE
LA English
DT Article
ID carbonic-anhydrase; in-vivo; amiloride; cells; receptors; bitter; discrimination; transduction; specificity; suppression
AB In the tongue, distinct classes of taste receptor cells detect the five basic tastes; sweet, sour, bitter, sodium salt and umami(1,2). Among these qualities, bitter and sour stimuli are innately aversive, whereas sweet and umami are appetitive and generally attractive to animals. By contrast, salty taste is unique in that increasing salt concentration fundamentally transforms an innately appetitive stimulus into a powerfully aversive one(3-7). This appetitive-aversive balance helps to maintain appropriate salt consumption(3,4,6,8), and represents an important part of fluid and electrolyte homeostasis. We have shown previously that the appetitive responses to NaCl are mediated by taste receptor cells expressing the epithelial sodium channel, ENaCs8, but the cellular substrate for salt aversion was unknown. Here we examine the cellular and molecular basis for the rejection of high concentrations of salts. We show that high salt recruits the two primary aversive taste pathways by activating the sour- and bitter-taste-sensing cells. We also demonstrate that genetic silencing of these pathways abolishes behavioural aversion to concentrated salt, without impairing salt attraction. Notably, mice devoid of salt-aversion pathways show unimpeded, continuous attraction even to very high concentrations of NaCl. We propose that the 'co-opting' of sour and bitter neural pathways evolved as a means to ensure that high levels of salt reliably trigger robust behavioural rejection, thus preventing its potentially detrimental effects on health.
C1 [Oka, Yuki; Butnaru, Matthew; Zuker, Charles S.] Columbia Univ, Howard Hughes Med Inst, New York, NY 10032 USA.
   [Oka, Yuki; Butnaru, Matthew; Zuker, Charles S.] Columbia Univ, Dept Biochem & Mol Biophys, New York, NY 10032 USA.
   [Oka, Yuki; Butnaru, Matthew; Zuker, Charles S.] Columbia Univ, Dept Neurosci, Columbia Coll Phys & Surg, New York, NY 10032 USA.
   [von Buchholtz, Lars; Ryba, Nicholas J. P.] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA.
C3 Columbia University; Howard Hughes Medical Institute; Columbia University; Columbia University; National Institutes of Health (NIH) - USA; NIH National Institute of Dental & Craniofacial Research (NIDCR)
RP Zuker, CS (corresponding author), Columbia Univ, Howard Hughes Med Inst, New York, NY 10032 USA.
EM nick.ryba@nih.gov; cz2195@columbia.edu
FU Japan Society for Promotion of Science; National Institutes of Health and National Institute of Dental and Craniofacial Research; National Institute of Dental and Craniofacial Research [ZIADE000561] Funding Source: NIH RePORTER
NR 30
TC 290
Z9 368
U1 1
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 FEB 28
PY 2013
VL 494
IS 7438
BP 472
EP 475
DI 10.1038/nature11905
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 099YI
UT WOS:000315661500037
PM 23407495
DA 2026-03-09
ER

PT J
AU Creighton, CJ
   Morgan, M
   Gunaratne, PH
   Wheeler, DA
   Gibbs, RA
   Robertson, AG
   Chu, A
   Beroukhim, R
   Cibulskis, K
   Signoretti, S
   Vandin, F
   Wu, HT
   Raphael, BJ
   Verhaak, RGW
   Tamboli, P
   Torres-Garcia, W
   Akbani, R
   Weinstein, JN
   Reuter, V
   Hsieh, JJ
   Brannon, AR
   Hakimi, AA
   Jacobsen, A
   Ciriello, G
   Reva, B
   Ricketts, CJ
   Linehan, WM
   Stuart, JM
   Rathmell, WK
   Shen, H
   Laird, PW
   Muzny, D
   Davis, C
   Morgan, M
   Xi, L
   Chang, K
   Kakkar, N
   Treviño, LR
   Benton, S
   Reid, JG
   Morton, D
   Doddapaneni, H
   Han, Y
   Lewis, L
   Dinh, H
   Kovar, C
   Zhu, YM
   Santibanez, J
   Wang, M
   Hale, W
   Kalra, D
   Creighton, CJ
   Wheeler, DA
   Gibbs, RA
   Getz, G
   Cibulskis, K
   Lawrence, MS
   Sougnez, C
   Carter, SL
   Sivachenko, A
   Lichtenstein, L
   Stewart, C
   Voet, D
   Fisher, S
   Gabriel, SB
   Lander, E
   Beroukhim, R
   Schumacher, SE
   Tabak, B
   Saksena, G
   Onofrio, RC
   Carter, SL
   Cherniack, AD
   Gentry, J
   Ardlie, K
   Sougnez, C
   Getz, G
   Gabriel, SB
   Meyerson, M
   Robertson, AG
   Chu, AD
   Chun, HJE
   Mungall, AJ
   Sipahimalani, P
   Stoll, D
   Ally, A
   Balasundaram, M
   Butterfield, YSN
   Carlsen, R
   Carter, C
   Chuah, E
   Coope, RJN
   Dhalla, N
   Gorski, S
   Guin, R
   Hirst, C
   Hirst, M
   Holt, RA
   Lebovitz, C
   Lee, D
   Li, HYI
   Mayo, M
   Moore, RA
   Pleasance, E
   Plettner, P
   Schein, JE
   Shafiei, A
   Slobodan, JR
   Tam, A
   Thiessen, N
   Varhol, RJ
   Wye, N
   Zhao, YJ
   Birol, I
   Jones, SJM
   Marra, MA
   Auman, JT
   Tan, DH
   Jones, CD
   Hoadley, KA
   Mieczkowski, PA
   Mose, LE
   Jefferys, SR
   Topal, M
   Liquori, C
   Turman, YJ
   Shi, Y
   Waring, S
   Buda, E
   Walsh, J
   Wu, JY
   Bodenheimer, T
   Hoyle, AP
   Simons, JV
   Soloway, M
   Balu, S
   Parker, JS
   Hayes, DN
   Perou, CM
   Kucherlapati, R
   Park, P
   Shen, H
   Triche, T
   Weisenberger, DJ
   Lai, PH
   Bootwalla, MS
   Maglinte, DT
   Mahurkar, S
   Berman, BP
   Van den Berg, DJ
   Cope, L
   Baylin, SB
   Laird, PW
   Creighton, CJ
   Wheeler, DA
   Getz, G
   Noble, MS
   DiCara, D
   Zhang, HL
   Cho, J
   Heiman, DI
   Gehlenborg, N
   Voet, D
   Mallard, W
   Lin, P
   Frazer, S
   Stojanov, P
   Liu, YC
   Zhou, LH
   Kim, J
   Lawrence, MS
   Chin, L
   Vandin, F
   Wu, HT
   Raphael, BJ
   Benz, C
   Yau, C
   Reynolds, SM
   Shmulevich, I
   Verhaak, RGW
   Torres-Garcia, W
   Vegesna, R
   Kim, H
   Zhang, W
   Cogdell, D
   Jonasch, E
   Ding, ZY
   Lu, YL
   Akbani, R
   Zhang, NX
   Unruh, AK
   Casasent, TD
   Wakefield, C
   Tsavachidou, D
   Chin, L
   Mills, GB
   Weinstein, JN
   Jacobsen, A
   Brannon, AR
   Ciriello, G
   Schultz, N
   Hakimi, AA
   Reva, B
   Antipin, Y
   Gao, JJ
   Cerami, E
   Gross, B
   Aksoy, BA
   Sinha, R
   Weinhold, N
   Sumer, SO
   Taylor, BS
   Shen, RL
   Ostrovnaya, I
   Hsieh, JJ
   Berger, MF
   Ladanyi, M
   Sander, C
   Fei, SS
   Stout, A
   Spellman, PT
   Rubin, DL
   Liu, TT
   Stuart, JM
   Ng, S
   Paull, EO
   Carlin, D
   Goldstein, T
   Waltman, P
   Ellrott, K
   Zhu, J
   Haussler, D
   Gunaratne, PH
   Xiao, WM
   Shelton, C
   Gardner, J
   Penny, R
   Sherman, M
   Mallery, D
   Morris, S
   Paulauskis, J
   Burnett, K
   Shelton, T
   Signoretti, S
   Kaelin, WG
   Choueiri, T
   Atkins, MB
   Penny, R
   Burnett, K
   Mallery, D
   Curley, E
   Tickoo, S
   Reuter, V
   Rathmell, WK
   Thorne, L
   Boice, L
   Huang, M
   Fisher, JC
   Linehan, WM
   Vocke, CD
   Peterson, J
   Worrell, R
   Merino, MJ
   Schmidt, LS
   Tamboli, P
   Czerniak, BA
   Aldape, KD
   Wood, CG
   Boyd, J
   Weaver, J
   Iacocca, MV
   Petrelli, N
   Witkin, G
   Brown, J
   Czerwinski, C
   Huelsenbeck-Dill, L
   Rabeno, B
   Myers, J
   Morrison, C
   Bergsten, J
   Eckman, J
   Harr, J
   Smith, C
   Tucker, K
   Zach, LA
   Bshara, W
   Gaudioso, C
   Morrison, C
   Dhir, R
   Maranchie, J
   Nelson, J
   Parwani, A
   Potapova, O
   Fedosenko, K
   Cheville, JC
   Thompson, RH
   Signoretti, S
   Kaelin, WG
   Atkins, MB
   Tickoo, S
   Reuter, V
   Linehan, WM
   Vocke, CD
   Peterson, J
   Merino, MJ
   Schmidt, LS
   Tamboli, P
   Mosquera, JM
   Rubin, MA
   Blute, ML
   Rathmell, WK
   Pihl, T
   Jensen, M
   Sfeir, R
   Kahn, A
   Chu, A
   Kothiyal, P
   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
   Davidsen, T
   Wang, ZN
   Yang, LM
   Tarnuzzer, RW
   Zhang, JS
   Eley, G
   Ferguson, ML
   Shaw, KRM
   Guyer, MS
   Ozenberger, BA
   Sofia, HJ
AF Creighton, Chad J.
   Morgan, Margaret
   Gunaratne, Preethi H.
   Wheeler, David A.
   Gibbs, Richard A.
   Robertson, A. Gordon
   Chu, Andy
   Beroukhim, Rameen
   Cibulskis, Kristian
   Signoretti, Sabina
   Vandin, Fabio
   Wu, Hsin-Ta
   Raphael, Benjamin J.
   Verhaak, Roel G. W.
   Tamboli, Pheroze
   Torres-Garcia, Wandaliz
   Akbani, Rehan
   Weinstein, John N.
   Reuter, Victor
   Hsieh, James J.
   Brannon, A. Rose
   Hakimi, A. Ari
   Jacobsen, Anders
   Ciriello, Giovanni
   Reva, Boris
   Ricketts, Christopher J.
   Linehan, W. Marston
   Stuart, Joshua M.
   Rathmell, W. Kimryn
   Shen, Hui
   Laird, Peter W.
   Muzny, Donna
   Davis, Caleb
   Morgan, Margaret
   Xi, Liu
   Chang, Kyle
   Kakkar, Nipun
   Trevino, Lisa R.
   Benton, Susan
   Reid, Jeffrey G.
   Morton, Donna
   Doddapaneni, Harsha
   Han, Yi
   Lewis, Lora
   Dinh, Huyen
   Kovar, Christie
   Zhu, Yiming
   Santibanez, Jireh
   Wang, Min
   Hale, Walker
   Kalra, Divya
   Creighton, Chad J.
   Wheeler, David A.
   Gibbs, Richard A.
   Getz, Gad
   Cibulskis, Kristian
   Lawrence, Michael S.
   Sougnez, Carrie
   Carter, Scott L.
   Sivachenko, Andrey
   Lichtenstein, Lee
   Stewart, Chip
   Voet, Doug
   Fisher, Sheila
   Gabriel, Stacey B.
   Lander, Eric
   Beroukhim, Rameen
   Schumacher, Steve E.
   Tabak, Barbara
   Saksena, Gordon
   Onofrio, Robert C.
   Carter, Scott L.
   Cherniack, Andrew D.
   Gentry, Jeff
   Ardlie, Kristin
   Sougnez, Carrie
   Getz, Gad
   Gabriel, Stacey B.
   Meyerson, Matthew
   Robertson, A. Gordon
   Chu, Andy
   Chun, Hye-Jung E.
   Mungall, Andrew J.
   Sipahimalani, Payal
   Stoll, Dominik
   Ally, Adrian
   Balasundaram, Miruna
   Butterfield, Yaron S. N.
   Carlsen, Rebecca
   Carter, Candace
   Chuah, Eric
   Coope, Robin J. N.
   Dhalla, Noreen
   Gorski, Sharon
   Guin, Ranabir
   Hirst, Carrie
   Hirst, Martin
   Holt, Robert A.
   Lebovitz, Chandra
   Lee, Darlene
   Li, Haiyan I.
   Mayo, Michael
   Moore, Richard A.
   Pleasance, Erin
   Plettner, Patrick
   Schein, Jacqueline E.
   Shafiei, Arash
   Slobodan, Jared R.
   Tam, Angela
   Thiessen, Nina
   Varhol, Richard J.
   Wye, Natasja
   Zhao, Yongjun
   Birol, Inanc
   Jones, Steven J. M.
   Marra, Marco A.
   Auman, J. Todd
   Tan, Donghui
   Jones, Corbin D.
   Hoadley, Katherine A.
   Mieczkowski, Piotr A.
   Mose, Lisle E.
   Jefferys, Stuart R.
   Topal, MichaelD.
   Liquori, Christina
   Turman, Yidi J.
   Shi, Yan
   Waring, Scot
   Buda, Elizabeth
   Walsh, Jesse
   Wu, Junyuan
   Bodenheimer, Tom
   Hoyle, Alan P.
   Simons, Janae V.
   Soloway, MathewG.
   Balu, Saianand
   Parker, Joel S.
   Hayes, D. Neil
   Perou, Charles M.
   Kucherlapati, Raju
   Park, Peter
   Shen, Hui
   Triche, Timothy, Jr.
   Weisenberger, Daniel J.
   Lai, Phillip H.
   Bootwalla, Moiz S.
   Maglinte, Dennis T.
   Mahurkar, Swapna
   Berman, Benjamin P.
   Van den Berg, David J.
   Cope, Leslie
   Baylin, Stephen B.
   Laird, Peter W.
   Creighton, Chad J.
   Wheeler, David A.
   Getz, Gad
   Noble, Michael S.
   DiCara, Daniel
   Zhang, Hailei
   Cho, Juok
   Heiman, David I.
   Gehlenborg, Nils
   Voet, Doug
   Mallard, William
   Lin, Pei
   Frazer, Scott
   Stojanov, Petar
   Liu, Yingchun
   Zhou, Lihua
   Kim, Jaegil
   Lawrence, Michael S.
   Chin, Lynda
   Vandin, Fabio
   Wu, Hsin-Ta
   Raphael, Benjamin J.
   Benz, Christopher
   Yau, Christina
   Reynolds, Sheila M.
   Shmulevich, Ilya
   Verhaak, Roel G. W.
   Torres-Garcia, Wandaliz
   Vegesna, Rahul
   Kim, Hoon
   Zhang, Wei
   Cogdell, David
   Jonasch, Eric
   Ding, Zhiyong
   Lu, Yiling
   Akbani, Rehan
   Zhang, Nianxiang
   Unruh, Anna K.
   Casasent, Tod D.
   Wakefield, Chris
   Tsavachidou, Dimitra
   Chin, Lynda
   Mills, Gordon B.
   Weinstein, John N.
   Jacobsen, Anders
   Brannon, A. Rose
   Ciriello, Giovanni
   Schultz, Nikolaus
   Hakimi, A. Ari
   Reva, Boris
   Antipin, Yevgeniy
   Gao, Jianjiong
   Cerami, Ethan
   Gross, Benjamin
   Aksoy, B. Arman
   Sinha, Rileen
   Weinhold, Nils
   Sumer, S. Onur
   Taylor, Barry S.
   Shen, Ronglai
   Ostrovnaya, Irina
   Hsieh, James J.
   Berger, Michael F.
   Ladanyi, Marc
   Sander, Chris
   Fei, Suzanne S.
   Stout, Andrew
   Spellman, Paul T.
   Rubin, Daniel L.
   Liu, Tiffany T.
   Stuart, Joshua M.
   Sam Ng
   Paull, Evan O.
   Carlin, Daniel
   Goldstein, Theodore
   Waltman, Peter
   Ellrott, Kyle
   Zhu, Jing
   Haussler, David
   Gunaratne, Preethi H.
   Xiao, Weimin
   Shelton, Candace
   Gardner, Johanna
   Penny, Robert
   Sherman, Mark
   Mallery, David
   Morris, Scott
   Paulauskis, Joseph
   Burnett, Ken
   Shelton, Troy
   Signoretti, Sabina
   Kaelin, William G.
   Choueiri, Toni
   Atkins, Michael B.
   Penny, Robert
   Burnett, Ken
   Mallery, David
   Curley, Erin
   Tickoo, Satish
   Reuter, Victor
   Rathmell, W. Kimryn
   Thorne, Leigh
   Boice, Lori
   Huang, Mei
   Fisher, Jennifer C.
   Linehan, W. Marston
   Vocke, Cathy D.
   Peterson, James
   Worrell, Robert
   Merino, Maria J.
   Schmidt, Laura S.
   Tamboli, Pheroze
   Czerniak, Bogdan A.
   Aldape, Kenneth D.
   Wood, Christopher G.
   Boyd, Jeff
   Weaver, JoEllen
   Iacocca, Mary V.
   Petrelli, Nicholas
   Witkin, Gary
   Brown, Jennifer
   Czerwinski, Christine
   Huelsenbeck-Dill, Lori
   Rabeno, Brenda
   Myers, Jerome
   Morrison, Carl
   Bergsten, Julie
   Eckman, John
   Harr, Jodi
   Smith, Christine
   Tucker, Kelinda
   Zach, Leigh Anne
   Bshara, Wiam
   Gaudioso, Carmelo
   Morrison, Carl
   Dhir, Rajiv
   Maranchie, Jodi
   Nelson, Joel
   Parwani, Anil
   Potapova, Olga
   Fedosenko, Konstantin
   Cheville, John C.
   Thompson, R. Houston
   Signoretti, Sabina
   Kaelin, William G.
   Atkins, Michael B.
   Tickoo, Satish
   Reuter, Victor
   Linehan, W. Marston
   Vocke, Cathy D.
   Peterson, James
   Merino, Maria J.
   Schmidt, Laura S.
   Tamboli, Pheroze
   Mosquera, Juan M.
   Rubin, Mark A.
   Blute, Michael L.
   Rathmell, W. Kimryn
   Pihl, Todd
   Jensen, Mark
   Sfeir, Robert
   Kahn, Ari
   Chu, Anna
   Kothiyal, Prachi
   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.
   Davidsen, Tanja
   Wang, Zhining
   Yang, Liming
   Tarnuzzer, Roy W.
   Zhang, Jiashan
   Eley, Greg
   Ferguson, Martin L.
   Shaw, Kenna R. Mills
   Guyer, Mark S.
   Ozenberger, Bradley A.
   Sofia, Heidi J.
TI Comprehensivemolecular characterization of clear cell renal cell carcinoma
SO NATURE
LA English
DT Article
ID kidney cancer; tumor-suppressor; genetic-basis; methylation; protein; arm
AB Genetic changes underlying clear cell renal cell carcinoma(ccRCC) include alterations in genes controlling cellular oxygen sensing (for example, VHL) and the maintenance of chromatin states (for example, PBRM1). We surveyed more than 400 tumours using different genomic platforms and identified 19 significantly mutated genes. The PI(3) K/AKT pathway was recurrently mutated, suggesting this pathway as a potential therapeutic target. Widespread DNA hypomethylation was associated with mutation of the H3K36 methyltransferase SETD2, and integrative analysis suggested that mutations involving the SWI/SNF chromatin remodelling complex (PBRM1, ARID1A, SMARCA4) could have far-reaching effects on other pathways. Aggressive cancers demonstrated evidence of a metabolic shift, involving downregulation of genes involved in the TCA cycle, decreased AMPK and PTEN protein levels, upregulation of the pentose phosphate pathway and the glutamine transporter genes, increased acetyl-CoA carboxylase protein, and altered promoter methylation of miR-21 (also known as MIR21) and GRB10. Remodelling cellular metabolism thus constitutes a recurrent pattern in ccRCC that correlates with tumour stage and severity and offers new views on the opportunities for disease treatment.
C1 [Creighton, Chad J.; Morgan, Margaret; Gunaratne, Preethi H.; Wheeler, David A.; Gibbs, Richard A.; Muzny, Donna; Davis, Caleb; Xi, Liu; Chang, Kyle; Kakkar, Nipun; Trevino, Lisa R.; Benton, Susan; Reid, Jeffrey G.; Morton, Donna; Doddapaneni, Harsha; Han, Yi; Lewis, Lora; Dinh, Huyen; Kovar, Christie; Zhu, Yiming; Santibanez, Jireh; Wang, Min; Hale, Walker; Kalra, Divya] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA.
   Baylor Coll Med, Dan L Duncan Canc Ctr, Houston, TX 77030 USA.
   [Xiao, Weimin] Univ Houston, Dept Biol & Biochem, Houston, TX 77204 USA.
   [Robertson, A. Gordon; Chu, Andy; Chun, Hye-Jung E.; Mungall, Andrew J.; Sipahimalani, Payal; Stoll, Dominik; Ally, Adrian; Balasundaram, Miruna; Butterfield, Yaron S. N.; Carlsen, Rebecca; Carter, Candace; Chuah, Eric; Coope, Robin J. N.; Dhalla, Noreen; Gorski, Sharon; Guin, Ranabir; Hirst, Carrie; Hirst, Martin; Holt, Robert A.; Lebovitz, Chandra; Lee, Darlene; Li, Haiyan I.; Mayo, Michael; Moore, Richard A.; Pleasance, Erin; Plettner, Patrick; Schein, Jacqueline E.; Shafiei, Arash; Slobodan, Jared R.; Tam, Angela; Thiessen, Nina; Varhol, Richard J.; Wye, Natasja; Zhao, Yongjun; Birol, Inanc; Jones, Steven J. M.; Marra, Marco A.] BC Canc Agcy, Canadas Michael Smith Genome Sci Ctr, Vancouver, BC V5Z, Canada.
   [Beroukhim, Rameen; Beroukhim, Rameen; Carter, Scott L.] Harvard Univ, Dept Med, Sch Med, Boston, MA 02215 USA.
   [Beroukhim, Rameen; Cibulskis, Kristian; Getz, Gad; Lawrence, Michael S.; Sougnez, Carrie; Carter, Scott L.; Sivachenko, Andrey; Lichtenstein, Lee; Stewart, Chip; Voet, Doug; Fisher, Sheila; Gabriel, Stacey B.; Lander, Eric; Beroukhim, Rameen; Schumacher, Steve E.; Tabak, Barbara; Saksena, Gordon; Onofrio, Robert C.; Cherniack, Andrew D.; Gentry, Jeff; Ardlie, Kristin; Meyerson, Matthew; Noble, Michael S.; DiCara, Daniel; Zhang, Hailei; Cho, Juok; Heiman, David I.; Gehlenborg, Nils; Mallard, William; Lin, Pei; Frazer, Scott; Stojanov, Petar; Liu, Yingchun; Zhou, Lihua; Kim, Jaegil; Chin, Lynda] Eli & Edythe L Broad Inst Massachusetts Inst Tech, Cambridge, MA 02142 USA.
   [Beroukhim, Rameen; Carter, Scott L.; Sivachenko, Andrey; Lichtenstein, Lee; Stewart, Chip; Fisher, Sheila; Lander, Eric; Beroukhim, Rameen; Schumacher, Steve E.; Tabak, Barbara; Saksena, Gordon; Onofrio, Robert C.; Cherniack, Andrew D.; Gentry, Jeff; Ardlie, Kristin; Meyerson, Matthew; Noble, Michael S.; DiCara, Daniel; Zhang, Hailei; Cho, Juok; Heiman, David I.; Gehlenborg, Nils; Mallard, William; Lin, Pei; Frazer, Scott; Stojanov, Petar; Liu, Yingchun; Zhou, Lihua; Kim, Jaegil] Harvard Univ, Cambridge, MA 02142 USA.
   [Signoretti, Sabina; Meyerson, Matthew] Harvard Univ, Dept Pathol, Sch Med, Boston, MA 02215 USA.
   [Vandin, Fabio; Wu, Hsin-Ta; Raphael, Benjamin J.] Brown Univ, Dept Comp Sci, Providence, RI 02912 USA.
   [Verhaak, Roel G. W.; Torres-Garcia, Wandaliz; Akbani, Rehan; Weinstein, John N.; Vegesna, Rahul; Kim, Hoon; Jonasch, Eric; Ding, Zhiyong; Zhang, Nianxiang; Unruh, Anna K.; Casasent, Tod D.; Wakefield, Chris] Univ Texas MD Anderson Canc Ctr, Dept Bioinformat & Computat Biol, Houston, TX 77030 USA.
   [Tamboli, Pheroze; Zhang, Wei; Cogdell, David; Czerniak, Bogdan A.; Aldape, Kenneth D.] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA.
   [Reuter, Victor; Brannon, A. Rose; Berger, Michael F.; Tickoo, Satish] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10065 USA.
   [Hsieh, James J.; Hakimi, A. Ari; Ladanyi, Marc] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10065 USA.
   [Jacobsen, Anders; Ciriello, Giovanni; Reva, Boris; Schultz, Nikolaus; Antipin, Yevgeniy; Gao, Jianjiong; Cerami, Ethan; Gross, Benjamin; Aksoy, B. Arman; Sinha, Rileen; Weinhold, Nils; Sumer, S. Onur; Taylor, Barry S.; Shen, Ronglai; Sander, Chris] Mem Sloan Kettering Canc Ctr, Computat Biol Ctr, New York, NY 10065 USA.
   [Ricketts, Christopher J.; Linehan, W. Marston; Vocke, Cathy D.; Peterson, James; Worrell, Robert; Merino, Maria J.; Schmidt, Laura S.] NCI, Urol Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
   [Stuart, Joshua M.; Sam Ng; Paull, Evan O.; Carlin, Daniel; Goldstein, Theodore; Waltman, Peter; Ellrott, Kyle; Zhu, Jing; Haussler, David] Univ Calif Santa Cruz, Dept Biomol Engn, Santa Cruz, CA 95064 USA.
   [Sam Ng; Paull, Evan O.; Carlin, Daniel; Goldstein, Theodore; Waltman, Peter; Ellrott, Kyle; Zhu, Jing; Haussler, David] Univ Calif Santa Cruz, Ctr Biomol Sci & Engn, Santa Cruz, CA 95064 USA.
   [Rathmell, W. Kimryn; Hoadley, Katherine A.; Liquori, Christina; Turman, Yidi J.; Shi, Yan; Waring, Scot; Buda, Elizabeth; Walsh, Jesse; Wu, Junyuan; Bodenheimer, Tom; Hoyle, Alan P.; Simons, Janae V.; Soloway, MathewG.; Balu, Saianand; Parker, Joel S.; Hayes, D. Neil; Perou, Charles M.; Thorne, Leigh; Boice, Lori; Huang, Mei; Fisher, Jennifer C.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA.
   [Shen, Hui; Laird, Peter W.; Triche, Timothy, Jr.; Weisenberger, Daniel J.; Lai, Phillip H.; Bootwalla, Moiz S.; Maglinte, Dennis T.; Mahurkar, Swapna; Berman, Benjamin P.; Van den Berg, David J.] Univ So Calif, USC Epigenome Ctr, Los Angeles, CA 90033 USA.
   [Auman, J. Todd] Univ N Carolina, Eshelman Sch Pharm, Chapel Hill, NC 27599 USA.
   [Tan, Donghui] Univ N Carolina, Carolina Ctr Genome Sci, Chapel Hill, NC 27599 USA.
   [Jones, Corbin D.] Univ N Carolina, Dept Biol, Chapel Hill, NC 27599 USA.
   [Hoadley, Katherine A.; Mose, Lisle E.; Topal, MichaelD.; Perou, Charles M.] Univ N Carolina, Dept Pathol & Lab Med, Chapel Hill, NC 27599 USA.
   [Hoadley, Katherine A.; Mieczkowski, Piotr A.; Jefferys, Stuart R.; Topal, MichaelD.; Perou, Charles M.] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA.
   [Hayes, D. Neil] Univ N Carolina, Dept Internal Med, Div Med Oncol, Chapel Hill, NC 27599 USA.
   [Kucherlapati, Raju] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02215 USA.
   [Kucherlapati, Raju; Park, Peter] Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA.
   [Park, Peter; Gehlenborg, Nils] Harvard Univ, Ctr Biomed Informat, Sch Med, Boston, MA 02115 USA.
   [Park, Peter] Childrens Hosp, Informat Program, Boston, MA 02115 USA.
   [Cope, Leslie; Baylin, Stephen B.] Johns Hopkins Univ, Canc Biol Div, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21231 USA.
   [Reynolds, Sheila M.; Shmulevich, Ilya] Inst Syst Biol, Seattle, WA 98109 USA.
   [Lu, Yiling; Tsavachidou, Dimitra; Mills, Gordon B.] Univ Texas MD Anderson Canc Ctr, Dept Syst Biol, Houston, TX 77030 USA.
   Univ Texas MD Anderson Canc Ctr, Dept Genom Med, Houston, TX 77054 USA.
   [Ostrovnaya, Irina] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10065 USA.
   [Fei, Suzanne S.; Stout, Andrew; Spellman, Paul T.] Oregon Hlth & Sci Univ, Dept Mol & Med Genet, Portand, OR 97239 USA.
   [Rubin, Daniel L.; Liu, Tiffany T.] Stanford Univ, Dept Radiol, Med Ctr, Stanford, CA 94305 USA.
   [Haussler, David] Univ Calif Santa Cruz, Howard Hughes Med Inst, Santa Cruz, CA 95064 USA.
   [Shelton, Candace; Gardner, Johanna; Penny, Robert; Sherman, Mark; Mallery, David; Morris, Scott; Paulauskis, Joseph; Burnett, Ken; Shelton, Troy; Curley, Erin] Int Genom Consortium, Phoenix, AZ 85004 USA.
   [Atkins, Michael B.] Georgetown Univ, Georgetown Lombardi Comprehens Canc Ctr, Washington, DC 20057 USA.
   SAIC Frederick Inc, Basic Sci Program, Frederick Natl Lab, Frederick, MD 21702 USA.
   [Wood, Christopher G.] Univ Texas MD Anderson Canc Ctr, Dept Urol, Houston, TX 77030 USA.
   [Boyd, Jeff; Weaver, JoEllen] Fox Chase Canc Ctr, Canc Biol Program, Philadelphia, PA 19111 USA.
   [Iacocca, Mary V.; Petrelli, Nicholas; Witkin, Gary; Brown, Jennifer; Czerwinski, Christine; Huelsenbeck-Dill, Lori; Rabeno, Brenda] Christiana Care, Helen F Graham Canc Ctr, Newark, DC 19713 USA.
   [Myers, Jerome; Morrison, Carl; Bergsten, Julie; Eckman, John; Harr, Jodi; Smith, Christine; Tucker, Kelinda; Zach, Leigh Anne] Penrose St Francis Hlth Serv, Colorado Springs, CO 80907 USA.
   [Bshara, Wiam; Gaudioso, Carmelo; Morrison, Carl] Roswell Pk Canc Inst, Dept Pathol, Buffalo, NY 14263 USA.
   [Dhir, Rajiv; Maranchie, Jodi; Nelson, Joel; Parwani, Anil] Univ Pittsburgh, Dept Pathol, Pittsburgh, PA 15213 USA.
   [Potapova, Olga] Cureline Inc, San Francisco, CA 94080 USA.
   [Fedosenko, Konstantin] St Petersburg City Clin Oncol Dispensary, St Petersburg 198255, Russia.
   [Mosquera, Juan M.; Rubin, Mark A.] Weill Cornell Coll Med, Dept Pathol & Lab Med, New York, NY 10065 USA.
   [Blute, Michael L.] Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA.
   [Pihl, Todd; Jensen, Mark; Sfeir, Robert; Kahn, Ari; Chu, Anna; Kothiyal, Prachi; 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.; Davidsen, Tanja; Wang, Zhining; Yang, Liming; Tarnuzzer, Roy W.; Zhang, Jiashan; Shaw, Kenna R. Mills] NCI, Canc Genome Atlas Program Off, Ctr Canc Genom, Bethesda, MD 20892 USA.
   [Eley, Greg] TCGA Consultant Scimentis LLC, Atlanta, GA 30666 USA.
   [Ferguson, Martin L.] MLF Consulting, Arlington, MA 02474 USA.
   [Guyer, Mark S.; Ozenberger, Bradley A.; Sofia, Heidi J.] NHGRI, NIH, Bethesda, MD 20892 USA.
   [Beroukhim, Rameen; Meyerson, Matthew; Stojanov, Petar; Kaelin, William G.; Choueiri, Toni] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA.
   [Benz, Christopher; Yau, Christina] Buck Inst Res Aging, Novato, CA 94945 USA.
   [Beroukhim, Rameen; Schumacher, Steve E.; Tabak, Barbara] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA.
   Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
   Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
   [Cheville, John C.; Thompson, R. Houston] Mayo Clin, Rochester, MN 55905 USA.
   Brigham & Womens Hosp, Dept Pathol, Boston, MA 02215 USA.
   Howard Hughes Med Inst, Chevy Chase, MD 20815 USA.
C3 Baylor College of Medicine; Baylor College of Medicine; University of Houston System; University of Houston; British Columbia Cancer Agency; Harvard University; Harvard Medical School; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Harvard University; Harvard University; Harvard Medical School; Brown University; University of Texas System; UTMD Anderson Cancer Center; University of Texas System; UTMD Anderson Cancer Center; Memorial Sloan Kettering Cancer Center; Memorial Sloan Kettering Cancer Center; Memorial Sloan Kettering Cancer Center; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); University of California System; University of California Santa Cruz; University of California System; University of California Santa Cruz; University of North Carolina; University of North Carolina Chapel Hill; University of Southern California; 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; Harvard University; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard University; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Johns Hopkins University; Johns Hopkins Medicine; Institute for Systems Biology (ISB); University of Texas System; UTMD Anderson Cancer Center; University of Texas System; UTMD Anderson Cancer Center; Memorial Sloan Kettering Cancer Center; Stanford University; Howard Hughes Medical Institute; University of California System; University of California Santa Cruz; International Genomics Consortium; Georgetown University; Science Applications International Corporation (SAIC); SAIC-Frederick; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); Frederick National Laboratory for Cancer Research; University of Texas System; UTMD Anderson Cancer Center; Fox Chase Cancer Center; Christiana Care Health System; Helen F. Graham Cancer Center & Research Institute; Roswell Park Comprehensive Cancer Center; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh; Cornell University; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; SRA International; 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 Human Genome Research Institute (NHGRI); Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Buck Institute for Research on Aging; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Mayo Clinic; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Howard Hughes Medical Institute
RP Gibbs, RA (corresponding author), Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA.
EM agibbs@bcm.edu; linehanm@mail.nih.gov
FU National Cancer Institute [T32CA082088, T32CA071341, P30CA016672, ZICBC011044] Funding Source: NIH RePORTER; NCATS NIH HHS [UL1 TR000005] Funding Source: Medline; NCI NIH HHS [U24 CA144025, U24 CA143883, P30 CA016672, U24 CA143866, T32 CA071341, U24 CA143843, R01 CA068490, U24 CA143867, T32 CA082088, U24 CA143845, U24 CA143858, U24 CA143848, U24 CA143799, U24 CA143882, U24 CA143835, K24 CA172355, P30 CA008748, U24 CA143840] Funding Source: Medline; NHGRI NIH HHS [R01 HG005690, U54 HG003067, U54 HG003079, U54 HG003273] Funding Source: Medline; Direct For Biological Sciences [0845783] Funding Source: National Science Foundation; Div Of Biological Infrastructure [0845783] Funding Source: National Science Foundation
NR 33
TC 2560
Z9 2846
U1 8
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 JUL 4
PY 2013
VL 499
IS 7456
BP 43
EP +
DI 10.1038/nature12222
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 176ED
UT WOS:000321285600029
PM 23792563
DA 2026-03-09
ER

PT J
AU Zheng, HJ
   Wisedchaisri, G
   Gonen, T
AF Zheng, Hongjin
   Wisedchaisri, Goragot
   Gonen, Tamir
TI Crystal structure of a nitrate/nitrite exchanger
SO NATURE
LA English
DT Article
ID major facilitator superfamily; escherichia-coli; nitrate uptake; nitrite transport; mechanism; nark; denitrification; channel; protein; system
AB Mineral nitrogen in nature is often found in the form of nitrate (NO3-). Numerous microorganisms evolved to assimilate nitrate and use it as a major source of mineral nitrogen uptake(1). Nitrate, which is central in nitrogen metabolism, is first reduced to nitrite (NO2-) through a two-electron reduction reaction(2,3). The accumulation of cellular nitrite can be harmful because nitrite can be reduced to the cytotoxic nitric oxide. Instead, nitrite is rapidly removed from the cell by channels and transporters, or reduced to ammonium or dinitrogen through the action of assimilatory enzymes(3). Despite decades of effort no structure is currently available for any nitrate transport protein and the mechanism by which nitrate is transported remains largely unknown. Here we report the structure of a bacterial nitrate/nitrite transport protein, NarK, from Escherichia coli, with and without substrate. The structures reveal a positively charged substrate-translocation pathway lacking protonatable residues, suggesting that NarK functions as a nitrate/nitrite exchanger and that protons are unlikely to be co-transported. Conserved arginine residues comprise the substrate-binding pocket, which is formed by association of helices from the two halves of NarK. Key residues that are important for substrate recognition and transport are identified and related to extensive mutagenesis and functional studies. We propose that NarK exchanges nitrate for nitrite by a rocker switch mechanism facilitated by inter-domain hydrogen bond networks.
C1 [Zheng, Hongjin; Wisedchaisri, Goragot; Gonen, Tamir] Howard Hughes Med Inst, Ashburn, VA 20147 USA.
C3 Howard Hughes Medical Institute
RP Gonen, T (corresponding author), Howard Hughes Med Inst, Janelia Farm Res Campus,19700 Helix Dr, Ashburn, VA 20147 USA.
EM gonent@janelia.hhmi.org
FU Office of Science, Office of Basic Energy Sciences, of the US Department of Energy [DE-AC02-05CH11231]; Howard Hughes Medical Institute
NR 34
TC 88
Z9 97
U1 1
U2 158
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 30
PY 2013
VL 497
IS 7451
BP 647
EP +
DI 10.1038/nature12139
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 152UF
UT WOS:000319556100050
PM 23665960
DA 2026-03-09
ER

PT J
AU Dang, I
   Gorelik, R
   Sousa-Blin, C
   Derivery, E
   Guérin, C
   Linkner, J
   Nemethova, M
   Dumortier, JG
   Giger, FA
   Chipysheva, TA
   Ermilova, VD
   Vacher, S
   Campanacci, V
   Herrada, I
   Planson, AG
   Fetics, S
   Henriot, V
   David, V
   Oguievetskaia, K
   Lakisic, G
   Pierre, F
   Steffen, A
   Boyreau, A
   Peyriéras, N
   Rottner, K
   Zinn-Justin, S
   Cherfils, J
   Bièche, I
   Alexandrova, AY
   David, NB
   Small, JV
   Faix, J
   Blanchoin, L
   Gautreau, A
AF Dang, Irene
   Gorelik, Roman
   Sousa-Blin, Carla
   Derivery, Emmanuel
   Guerin, Christophe
   Linkner, Joern
   Nemethova, Maria
   Dumortier, Julien G.
   Giger, Florence A.
   Chipysheva, Tamara A.
   Ermilova, Valeria D.
   Vacher, Sophie
   Campanacci, Valerie
   Herrada, Isaline
   Planson, Anne-Gaelle
   Fetics, Susan
   Henriot, Veronique
   David, Violaine
   Oguievetskaia, Ksenia
   Lakisic, Goran
   Pierre, Fabienne
   Steffen, Anika
   Boyreau, Adeline
   Peyrieras, Nadine
   Rottner, Klemens
   Zinn-Justin, Sophie
   Cherfils, Jacqueline
   Bieche, Ivan
   Alexandrova, Antonina Y.
   David, Nicolas B.
   Small, J. Victor
   Faix, Jan
   Blanchoin, Laurent
   Gautreau, Alexis
TI Inhibitory signalling to the Arp2/3 complex steers cell migration
SO NATURE
LA English
DT Article
ID actin polymerization; motility; networks; dynamics; protein; lamellipodia; nucleation; prediction; vertebrate; alignment
AB Cell migration requires the generation of branched actin networks that power the protrusion of the plasma membrane inlamellipodia(1,2). The actin-related proteins 2 and 3 (Arp2/3) complex is the molecular machine that nucleates these branched actin networks(3). This machine is activated at the leading edge of migrating cells by Wiskott-Aldrich syndrome protein (WASP)-family verprolin-homologous protein (WAVE, also known as SCAR). The WAVE complex is itself directly activated by the small GTPase Rac, which induces lamellipodia(4-6). However, how cells regulate the directionality of migration is poorly understood. Here we identify a new protein, Arpin, that inhibits the Arp2/3 complex in vitro, and show that Rac signalling recruits and activates Arpin at the lamellipodial tip, like WAVE. Consistently, after depletion of the inhibitory Arpin, lamellipodia protrude faster and cells migrate faster. A major role of this inhibitory circuit, however, is to control directional persistence of migration. Indeed, Arpin depletion in both mammalian cells and Dictyostelium discoideum amoeba resulted in straighter trajectories, whereas Arpin microinjection in fish keratocytes, one of the most persistent systems of cell migration, induced these cells to turn. The coexistence of the Rac-Arpin-Arp2/3 inhibitory circuit with the Rac-WAVE-Arp2/3 activatory circuit can account for this conserved role of Arpin in steering cell migration.
C1 [Dang, Irene; Gorelik, Roman; Sousa-Blin, Carla; Derivery, Emmanuel; Henriot, Veronique; David, Violaine; Oguievetskaia, Ksenia; Lakisic, Goran; Pierre, Fabienne; Gautreau, Alexis] CNRS, Grp Cytoskeleton Cell Morphogenesis, Lab Enzymol & Biochim Struct, UPR3082, F-91190 Gif Sur Yvette, France.
   [Guerin, Christophe; Blanchoin, Laurent] CNRS CEA INRA UJF, Lab Physiol Cellulaire & Vegetale, Inst Rech Technol & Sci Vivant IRTSV, F-38054 Grenoble, France.
   [Linkner, Joern; Faix, Jan] Hannover Med Sch, Inst Biophys Chem, D-30625 Hannover, Germany.
   [Nemethova, Maria; Small, J. Victor] Inst Mol Biotechnol, A-1030 Vienna, Austria.
   [Dumortier, Julien G.; Giger, Florence A.; David, Nicolas B.] Inst Biol ENS, ENS, CNRS UMR8197, INSERM U1024, F-75005 Paris, France.
   [Chipysheva, Tamara A.; Ermilova, Valeria D.; Alexandrova, Antonina Y.] Russian Acad Med Sci, NN Blokhin Canc Res Ctr, Inst Carcinogenesis, Moscow 115478, Russia.
   [Vacher, Sophie; Bieche, Ivan] Hop Rene Huguenin, Inst Curie, Oncogenet Lab, F-92210 St Cloud, France.
   [Campanacci, Valerie; Planson, Anne-Gaelle; Fetics, Susan; Cherfils, Jacqueline] CNRS, Grp Small Prot G, Lab Enzymol & Biochim Struct, UPR3082, F-91190 Gif Sur Yvette, France.
   [Herrada, Isaline; Zinn-Justin, Sophie] CEA Saclay, CNRS URA2096, Lab Biol Struct & Radiobiol IBiTec S, F-91190 Gif Sur Yvette, France.
   [Steffen, Anika; Rottner, Klemens] Univ Bonn, Inst Genet, D-53115 Bonn, Germany.
   [Boyreau, Adeline; Peyrieras, Nadine] CNRS, Inst Neurobiol Alfred Fessard, Inst Syst Complexes & NeD, UPR3294, F-91190 Gif Sur Yvette, France.
   [Rottner, Klemens] Helmholtz Ctr Infect Res, D-38124 Braunschweig, Germany.
C3 Centre National de la Recherche Scientifique (CNRS); Universite Paris Saclay; Communaute Universite Grenoble Alpes; Universite Grenoble Alpes (UGA); CEA; Centre National de la Recherche Scientifique (CNRS); INRAE; Hannover Medical School; Vienna Biocenter (VBC); Institute of Molecular Biotechnology (IMBA); Universite PSL; Ecole Normale Superieure (ENS); Institut National de la Sante et de la Recherche Medicale (Inserm); Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB); Russian Academy of Medical Sciences; N.N. Blokhin Russian Cancer Research Center; Rene Huguenin Hospital; UNICANCER; Universite PSL; Institut Curie; Universite Paris Saclay; Centre National de la Recherche Scientifique (CNRS); Universite Paris Saclay; CEA; University of Bonn; Centre National de la Recherche Scientifique (CNRS); Universite Paris Saclay; Helmholtz Association; Helmholtz-Center for Infection Research
RP Gautreau, A (corresponding author), CNRS, Grp Cytoskeleton Cell Morphogenesis, Lab Enzymol & Biochim Struct, UPR3082, F-91190 Gif Sur Yvette, France.
EM alexis.gautreau@lebs.cnrs-gif.fr
FU Agence Nationale pour la Recherche [ANR-08-BLAN-0012-CSD 8, ANR-08-PCVI-0010-03, ANR-11-BSV8-0010-02]; Association pour la Recherche sur le Cancer [SFI20101201512, PDF20111204331, SFI20111203770]; Bio-Emergences IBISA facility; Fundacao para a Ciencia e a Tecnologia [SFRH/BPD/46451/2008]; Austrian Science Fund [FWF P21292-B09]; Deutsche Forschungsgemeinschaft [FA 330/5-1]; Russian Ministry of Education and Science [8066, 2012-1.1-12-000-1002-064]; Austrian Science Fund (FWF) [I 516] Funding Source: researchfish; Fundação para a Ciência e a Tecnologia [SFRH/BPD/46451/2008] Funding Source: FCT; Agence Nationale de la Recherche (ANR) [ANR-08-PCVI-0010, ANR-11-BSV8-0010] Funding Source: Agence Nationale de la Recherche (ANR)
NR 46
TC 191
Z9 223
U1 1
U2 71
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 14
PY 2013
VL 503
IS 7475
BP 281
EP +
DI 10.1038/nature12611
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 250YX
UT WOS:000326894200055
PM 24132237
DA 2026-03-09
ER

PT J
AU Shulaker, MM
   Hills, G
   Patil, N
   Wei, H
   Chen, HY
   PhilipWong, HS
   Mitra, S
AF Shulaker, Max M.
   Hills, Gage
   Patil, Nishant
   Wei, Hai
   Chen, Hong-Yu
   PhilipWong, H. -S.
   Mitra, Subhasish
TI Carbon nanotube computer
SO NATURE
LA English
DT Article
ID circuits; single
AB The miniaturization of electronic devices has been the principal driving force behind the semiconductor industry, and has brought about major improvements in computational power and energy efficiency. Although advances with silicon-based electronics continue to be made, alternative technologies are being explored. Digital circuits based on transistors fabricated from carbon nanotubes (CNTs) have the potential to outperform silicon by improving the energy-delay product, a metric of energy efficiency, by more than an order of magnitude. Hence, CNTs are an exciting complement to existing semiconductor technologies(1,2). Owing to substantial fundamental imperfections inherent in CNTs, however, only very basic circuit blocks have been demonstrated. Here we show how these imperfections can be overcome, and demonstrate the first computer built entirely using CNT-based transistors. The CNT computer runs an operating system that is capable of multitasking: as a demonstration, we perform counting and integer-sorting simultaneously. In addition, we implement 20 different instructions from the commercial MIPS instruction set to demonstrate the generality of our CNT computer. This experimental demonstration is the most complex carbon-based electronic system yet realized. It is a considerable advance because CNTs are prominent among a variety of emerging technologies that are being considered for the next generation of highly energy-efficient electronic systems(3,4).
C1 [Shulaker, Max M.; Hills, Gage; Wei, Hai; Chen, Hong-Yu; PhilipWong, H. -S.; Mitra, Subhasish] Stanford Univ, Stanford, CA 94305 USA.
   [Patil, Nishant] SK Hynix Memory Solut, San Jose, CA 95134 USA.
C3 Stanford University
RP Shulaker, MM (corresponding author), Stanford Univ, Gates Bldg,Room 331,353 Serra Mall, Stanford, CA 94305 USA.
EM maxms@stanford.edu
FU NSF (CISE) [CNS-1059020, CCF-0726791, CCF-0702343, CCF-0643319]; FCRP [C2S2]; FCRP FENA; STARNet SONIC; Stanford Graduate Fellowship; Hertz Foundation Fellowship; Division Of Computer and Network Systems; Direct For Computer & Info Scie & Enginr [1059020] Funding Source: National Science Foundation
NR 30
TC 841
Z9 1000
U1 12
U2 631
PU NATURE PUBLISHING 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 26
PY 2013
VL 501
IS 7468
BP 526
EP +
DI 10.1038/nature12502
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 223RP
UT WOS:000324826300053
PM 24067711
DA 2026-03-09
ER

PT J
AU Collins, JJ
   Wang, B
   Lambrus, BG
   Tharp, ME
   Iyer, H
   Newmark, PA
AF Collins, James J., III
   Wang, Bo
   Lambrus, Bramwell G.
   Tharp, Marla E.
   Iyer, Harini
   Newmark, Phillip A.
TI Adult somatic stem cells in the human parasite Schistosoma mansoni
SO NATURE
LA English
DT Article
ID dna-synthesis; planarian; regeneration; growth; pluripotency; regulators; genome; model; sex
AB Schistosomiasis is among the most prevalent human parasitic diseases, affecting more than 200 million people worldwide(1). The aetiological agents of this disease are trematode flatworms (Schistosoma) that live and lay eggs within the vasculature of the host. These eggs lodge in host tissues, causing inflammatory responses that are the primary cause of morbidity. Because these parasites can live and reproduce within human hosts for decades', elucidating the mechanisms that promote their longevity is of fundamental importance. Although adult pluripotent stem cells, called neoblasts, drive long-term homeostatic tissue maintenance in long-lived free-living flatworms(3,4) (for example, planarians), and neoblast-like cells have been described in some parasitic tapeworms', little is known about whether similar cell types exist in any trematode species. Here we describe a population of neoblast-like cells in the trematode Schistosoma mansoni. These cells resemble planarian neoblasts morphologically and share their ability to proliferate and differentiate into derivatives of multiple germ layers. Capitalizing on available genomic resources(6,7) and RNA-seq-based gene expression profiling, we find that these schistosome neoblast-like cells express a fibroblast growth factor receptor orthologue. Using RNA interference we demonstrate that this gene is required for the maintenance of these neoblast-like cells. Our observations indicate that adaptation of developmental strategies shared by free-living ancestors to modern-day schistosomes probably contributed to the success of these animals as long-lived obligate parasites. We expect that future studies deciphering the function of these neoblast-like cells will have important implications for understanding the biology of these devastating parasites.
C1 [Collins, James J., III; Wang, Bo; Lambrus, Bramwell G.; Tharp, Marla E.; Iyer, Harini; Newmark, Phillip A.] Univ Illinois, Howard Hughes Med Inst, Urbana, IL 61801 USA.
   [Collins, James J., III; Wang, Bo; Lambrus, Bramwell G.; Tharp, Marla E.; Iyer, Harini; Newmark, Phillip A.] Univ Illinois, Dept Cell & Dev Biol, Urbana, IL 61801 USA.
   [Collins, James J., III; Newmark, Phillip A.] Univ Illinois, Neurosci Program, Urbana, IL 61801 USA.
   [Wang, Bo] Univ Illinois, Inst Genom Biol, Urbana, IL 61801 USA.
C3 University of Illinois System; University of Illinois Urbana-Champaign; Howard Hughes Medical Institute; University of Illinois System; University of Illinois Urbana-Champaign; University of Illinois System; University of Illinois Urbana-Champaign; University of Illinois System; University of Illinois Urbana-Champaign
RP Newmark, PA (corresponding author), Univ Illinois, Howard Hughes Med Inst, Urbana, IL 61801 USA.
EM pnewmark@life.illinois.edu
FU NIAID [HHSN272201000005I]; NIH [F32 HD062124, R21 AI099642]
NR 30
TC 192
Z9 211
U1 0
U2 94
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 28
PY 2013
VL 494
IS 7438
BP 476
EP 479
DI 10.1038/nature11924
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 099YI
UT WOS:000315661500038
PM 23426263
DA 2026-03-09
ER

PT J
AU Kafri, R
   Levy, J
   Ginzberg, MB
   Oh, S
   Lahav, G
   Kirschner, MW
AF Kafri, Ran
   Levy, Jason
   Ginzberg, Miriam B.
   Oh, Seungeun
   Lahav, Galit
   Kirschner, Marc W.
TI Dynamics extracted from fixed cells reveal feedback linking cell growth to cell cycle
SO NATURE
LA English
DT Article
ID mass
AB Biologists have long been concerned about what constrains variation in cell size, but progress in this field has been slow and stymied by experimental limitations'. Here we describe a new method, ergodic rate analysis (ERA), that uses single-cell measurements of fixed steady-state populations to accurately infer the rates of molecular events, including rates of cell growth. ERA exploits the fact that the number of cells in a particular state is related to the average transit time through that state(2). With this method, it is possible to calculate full time trajectories of any feature that can be labelled in fixed cells, for example levels of phosphoproteins or total cellular mass. Using ERA we find evidence for a size-discriminatory process at the G1/S transition that acts to decrease cell-to-cell size variation.
C1 [Kafri, Ran; Ginzberg, Miriam B.; Oh, Seungeun; Lahav, Galit; Kirschner, Marc W.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA.
   [Levy, Jason] Univ Ottawa, Dept Math & Stat, Ottawa, ON K1N 6N5, Canada.
C3 Harvard University; Harvard Medical School; University of Ottawa
RP Kirschner, MW (corresponding author), Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA.
EM marc@hms.harvard.edu
FU National Institute of General Medical Sciences [GM26875]
NR 11
TC 172
Z9 209
U1 1
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 FEB 28
PY 2013
VL 494
IS 7438
BP 480
EP 483
DI 10.1038/nature11897
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 099YI
UT WOS:000315661500039
PM 23446419
DA 2026-03-09
ER

PT J
AU Wu, C
   Yosef, N
   Thalhamer, T
   Zhu, C
   Xiao, S
   Kishi, Y
   Regev, A
   Kuchroo, VK
AF Wu, Chuan
   Yosef, Nir
   Thalhamer, Theresa
   Zhu, Chen
   Xiao, Sheng
   Kishi, Yasuhiro
   Regev, Aviv
   Kuchroo, Vijay K.
TI Induction of pathogenic TH17 cells by inducible salt-sensing kinase SGK1
SO NATURE
LA English
DT Article
ID protein-kinase; serum; activation; differentiation; transcription; system
AB T(H)17 cells (interleukin-17 (IL-17)-producing helper T cells) are highly proinflammatory cells that are critical for clearing extracellular pathogens and for inducing multiple autoimmune diseases(1). IL-23 has a critical role in stabilizing and reinforcing the T(H)17 phenotype by increasing expression of IL-23 receptor (IL-23R) and endowing T(H)17 cells with pathogenic effector functions(2,3). However, the precise molecular mechanism by which IL-23 sustains the T(H)17 response and induces pathogenic effector functions has not been elucidated. Here we used transcriptional profiling of developing T(H)17 cells to construct a model of their signalling network and nominate major nodes that regulate T(H)17 development. We identified serum glucocorticoid kinase 1 (SGK1), a serine/threonine kinase(4), as an essential node downstream of IL-23 signalling. SGK1 is critical for regulating IL-23R expression and stabilizing the T(H)17 cell phenotype by deactivation of mouse Foxo1, a direct repressor of IL-23R expression. SGK1 has been shown to govern Na+ transport and salt (NaCl) homeostasis in other cells(5-8). We show here that a modest increase in salt concentration induces SGK1 expression, promotes IL-23R expression and enhances T(H)17 cell differentiation in vitro and in vivo, accelerating the development of autoimmunity. Loss of SGK1 abrogated Na+-mediated T(H)17 differentiation in an IL-23-dependent manner. These data demonstrate that SGK1 has a critical role in the induction of pathogenic T(H)17 cells and provide a molecular insight into a mechanism by which an environmental factor such as a high salt diet triggers T(H)17 development and promotes tissue inflammation.
C1 [Wu, Chuan; Yosef, Nir; Thalhamer, Theresa; Zhu, Chen; Xiao, Sheng; Kishi, Yasuhiro; Kuchroo, Vijay K.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Neurol Dis, Boston, MA 02115 USA.
   [Yosef, Nir; Regev, Aviv; Kuchroo, Vijay K.] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.
   [Regev, Aviv] MIT, Dept Biol, Howard Hughes Med Inst, Cambridge, MA 02140 USA.
C3 Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard Medical School; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Howard Hughes Medical Institute; Massachusetts Institute of Technology (MIT)
RP Regev, A (corresponding author), Broad Inst MIT & Harvard, 7 Cambridge Ctr, Cambridge, MA 02142 USA.
EM aregev@broad.mit.edu; vkuchroo@rics.bwh.harvard.edu
FU US National Institutes of Health [NS030843, NS045937, AI073748, AI045757, 1P01HG005062-01, 1P50HG006193-01, DP1-OD003958-01, K01DK090105]; National MS Society [RG2571]; Howard Hughes Medical Institute; Klarman Cell Observatory; Guthy Jackson Foundation; Austrian Science Fund (FWF) [J 3091-B12]
NR 23
TC 856
Z9 967
U1 0
U2 120
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 25
PY 2013
VL 496
IS 7446
BP 513
EP 517
DI 10.1038/nature11984
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 131HU
UT WOS:000317984400043
PM 23467085
DA 2026-03-09
ER

PT J
AU Galagan, JE
   Minch, K
   Peterson, M
   Lyubetskaya, A
   Azizi, E
   Sweet, L
   Gomes, A
   Rustad, T
   Dolganov, G
   Glotova, I
   Abeel, T
   Mahwinney, C
   Kennedy, AD
   Allard, R
   Brabant, W
   Krueger, A
   Jaini, S
   Honda, B
   Yu, WH
   Hickey, MJ
   Zucker, J
   Garay, C
   Weiner, B
   Sisk, P
   Stolte, C
   Winkler, JK
   Van de Peer, Y
   Iazzetti, P
   Camacho, D
   Dreyfuss, J
   Liu, Y
   Dorhoi, A
   Mollenkopf, HJ
   Drogaris, P
   Lamontagne, J
   Zhou, YY
   Piquenot, J
   Park, ST
   Raman, S
   Kaufmann, SHE
   Mohney, RP
   Chelsky, D
   Moody, DB
   Sherman, DR
   Schoolnik, GK
AF Galagan, James E.
   Minch, Kyle
   Peterson, Matthew
   Lyubetskaya, Anna
   Azizi, Elham
   Sweet, Linsday
   Gomes, Antonio
   Rustad, Tige
   Dolganov, Gregory
   Glotova, Irina
   Abeel, Thomas
   Mahwinney, Chris
   Kennedy, Adam D.
   Allard, Rene
   Brabant, William
   Krueger, Andrew
   Jaini, Suma
   Honda, Brent
   Yu, Wen-Han
   Hickey, Mark J.
   Zucker, Jeremy
   Garay, Christopher
   Weiner, Brian
   Sisk, Peter
   Stolte, Christian
   Winkler, Jessica K.
   Van de Peer, Yves
   Iazzetti, Paul
   Camacho, Diogo
   Dreyfuss, Jonathan
   Liu, Yang
   Dorhoi, Anca
   Mollenkopf, Hans-Joachim
   Drogaris, Paul
   Lamontagne, Julie
   Zhou, Yiyong
   Piquenot, Julie
   Park, Sang Tae
   Raman, Sahadevan
   Kaufmann, Stefan H. E.
   Mohney, Robert P.
   Chelsky, Daniel
   Moody, D. Branch
   Sherman, David R.
   Schoolnik, Gary K.
TI The Mycobacterium tuberculosis regulatory network and hypoxia
SO NATURE
LA English
DT Article
ID controlling gene-expression; free mycolic acids; devr dosr regulon; virulence; cholesterol; insights; protein; phop; biosynthesis; macrophages
AB We have taken the first steps towards a complete reconstruction of the Mycobacterium tuberculosis regulatory network based on ChIP-Seq and combined this reconstruction with system-wide profiling of messenger RNAs, proteins, metabolites and lipids during hypoxia and re-aeration. Adaptations to hypoxia are thought to have a prominent role in M. tuberculosis pathogenesis. Using ChIP-Seq combined with expression data from the induction of the same factors, we have reconstructed a draft regulatory network based on 50 transcription factors. This network model revealed a direct interconnection between the hypoxic response, lipid catabolism, lipid anabolism and the production of cell wall lipids. As a validation of this model, in response to oxygen availability we observe substantial alterations in lipid content and changes in gene expression and metabolites in corresponding metabolic pathways. The regulatory network reveals transcription factors underlying these changes, allows us to computationally predict expression changes, and indicates that Rv0081 is a regulatory hub.
C1 [Galagan, James E.; Peterson, Matthew; Mahwinney, Chris; Krueger, Andrew; Jaini, Suma; Honda, Brent; Yu, Wen-Han; Garay, Christopher; Iazzetti, Paul; Camacho, Diogo; Dreyfuss, Jonathan] Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA.
   [Galagan, James E.; Park, Sang Tae; Raman, Sahadevan] Boston Univ, Dept Microbiol, Boston, MA 02215 USA.
   [Galagan, James E.; Lyubetskaya, Anna; Azizi, Elham; Gomes, Antonio; Glotova, Irina] Boston Univ, Bioinformat Program, Boston, MA 02215 USA.
   [Galagan, James E.; Abeel, Thomas; Zucker, Jeremy; Weiner, Brian; Sisk, Peter; Stolte, Christian] Eli & Edythe L Broad Inst Harvard & MIT, Cambridge, MA 02142 USA.
   [Minch, Kyle; Rustad, Tige; Brabant, William; Hickey, Mark J.; Winkler, Jessica K.; Sherman, David R.] Seattle Biomed Res Inst, Seattle, WA 98109 USA.
   [Sweet, Linsday; Moody, D. Branch] Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA.
   [Sweet, Linsday; Moody, D. Branch] Harvard Univ, Sch Med, Boston, MA 02115 USA.
   [Dolganov, Gregory; Liu, Yang; Schoolnik, Gary K.] Stanford Med Sch, Dept Med, Stanford, CA 94305 USA.
   [Dolganov, Gregory; Liu, Yang; Schoolnik, Gary K.] Stanford Med Sch, Dept Microbiol & Immunol, Stanford, CA 94305 USA.
   [Abeel, Thomas; Van de Peer, Yves] Univ Ghent, Dept Plant Biotechnol & Bioinformat, B-9052 Ghent, Belgium.
   [Kennedy, Adam D.; Mohney, Robert P.] Metabolon Inc, Durham, NC 27713 USA.
   [Allard, Rene; Drogaris, Paul; Lamontagne, Julie; Zhou, Yiyong; Piquenot, Julie; Chelsky, Daniel] Capr Prote Inc, Montreal, PQ H4S 2C8, Canada.
   [Dorhoi, Anca; Kaufmann, Stefan H. E.] Max Planck Inst Infect Biol, Dept Immunol, D-10117 Berlin, Germany.
   [Mollenkopf, Hans-Joachim] Max Planck Inst Infect Biol, Microarray Core Facil, D-10117 Berlin, Germany.
   [Sherman, David R.] Univ Washington, Dept Global Hlth, Interdisciplinary Program Pathobiol, Seattle, WA 98195 USA.
   [Schoolnik, Gary K.] Stanford Med Sch, Dept Med, Div Infect Dis & Geog Med, Stanford, CA 94305 USA.
C3 Boston University; Boston University; Boston University; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Center for Infectious Disease Research; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard University; Harvard Medical School; Stanford University; Stanford University; Ghent University; Metabolon; Max Planck Society; Max Planck Society; University of Washington; University of Washington Seattle; Stanford University
RP Galagan, JE (corresponding author), Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA.
EM jgalag@bu.edu
FU National Institute of Allergy and Infectious Diseases National Institute of Health, Department of Health and Human Services [HHSN272200800059C, U19 AI 076217, R01 AI 071155]; Paul G. Allen Family Foundation; National Science Foundation Pre-doctoral Fellowship Program; Burroughs Wellcome Fund Award for Translational Research; National Institute of Allergy and Infectious Diseases [T32AI007509] Funding Source: NIH RePORTER
NR 46
TC 352
Z9 426
U1 1
U2 149
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 11
PY 2013
VL 499
IS 7457
BP 178
EP 183
DI 10.1038/nature12337
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 179YA
UT WOS:000321557600055
PM 23823726
DA 2026-03-09
ER

PT J
AU Ammannito, E
   De Sanctis, MC
   Palomba, E
   Longobardo, A
   Mittlefehldt, DW
   McSween, HY
   Marchi, S
   Capria, MT
   Capaccioni, F
   Frigeri, A
   Pieters, CM
   Ruesch, O
   Tosi, F
   Zambon, F
   Carraro, F
   Fonte, S
   Hiesinger, H
   Magni, G
   McFadden, LA
   Raymond, CA
   Russell, CT
   Sunshine, JM
AF Ammannito, E.
   De Sanctis, M. C.
   Palomba, E.
   Longobardo, A.
   Mittlefehldt, D. W.
   McSween, H. Y.
   Marchi, S.
   Capria, M. T.
   Capaccioni, F.
   Frigeri, A.
   Pieters, C. M.
   Ruesch, O.
   Tosi, F.
   Zambon, F.
   Carraro, F.
   Fonte, S.
   Hiesinger, H.
   Magni, G.
   McFadden, L. A.
   Raymond, C. A.
   Russell, C. T.
   Sunshine, J. M.
TI Olivine in an unexpected location on Vesta's surface
SO NATURE
LA English
DT Article
ID asteroid 4 vesta; reflectance; geochemistry; diogenites; pyroxenes; mixtures; core; size
AB Olivine is a major component of the mantle of differentiated bodies, including Earth. Howardite, eucrite and diogenite (HED) meteorites represent regolith, basaltic-crust, lower-crust and possibly ultramafic-mantle samples of asteroid Vesta, which is the lone surviving, large, differentiated, basaltic rocky protoplanet in the Solar System(1). Only a few of these meteorites, the orthopyroxene-rich diogenites, contain olivine, typically with a concentration of less than 25 per cent by volume(2). Olivine was tentatively identified on Vesta(3,4), on the basis of spectral and colour data, but other observations did not confirm its presence(5). Here we report that olivine is indeed present locally on Vesta's surface but that, unexpectedly, it has not been found within the deep, south-pole basins, which are thought to be excavated mantle rocks(6-8). Instead, it occurs as near-surface materials in the northern hemisphere. Unlike the meteorites, the olivine-rich (more than 50 per cent by volume) material is not associated with diogenite but seems to be mixed with howardite, the most common(7,9) surface material. Olivine is exposed in crater walls and in ejecta scattered diffusely over a broad area. The size of the olivine exposures and the absence of associated diogenite favour a mantle source, but the exposures are located far from the deep impact basins. The amount and distribution of observed olivine-rich material suggest a complex evolutionary history for Vesta.
C1 [Ammannito, E.; De Sanctis, M. C.; Palomba, E.; Longobardo, A.; Marchi, S.; Capria, M. T.; Capaccioni, F.; Frigeri, A.; Tosi, F.; Zambon, F.; Carraro, F.; Fonte, S.; Magni, G.] INAF, Ist Astrofis & Planetol Spaziali, I-00133 Rome, Italy.
   [Mittlefehldt, D. W.] NASA, Lyndon B Johnson Space Ctr, Houston, TX 77058 USA.
   [McSween, H. Y.] Univ Tennessee, Dept Earth & Planetary Sci, Knoxville, TN 37996 USA.
   [Marchi, S.] NASA, Lunar Sci Inst, Boulder, CO 80302 USA.
   [Pieters, C. M.] Brown Univ, Dept Geol Sci, Providence, RI 02912 USA.
   [Ruesch, O.; Hiesinger, H.] Univ Munster, Inst Planetol, D-48149 Munster, Germany.
   [McFadden, L. A.] NASA, Goddard Space Flight Ctr, Greenbelt, MD 20771 USA.
   [Raymond, C. A.] CALTECH, Jet Prop Lab, Pasadena, CA 91109 USA.
   [Russell, C. T.] Univ Calif Los Angeles, Los Angeles, CA 90095 USA.
   [Sunshine, J. M.] Univ Maryland, Dept Astron, College Pk, MD 20742 USA.
C3 Istituto Nazionale Astrofisica (INAF); National Aeronautics & Space Administration (NASA); NASA Johnson Space Center; University of Tennessee System; University of Tennessee Knoxville; National Aeronautics & Space Administration (NASA); Brown University; University of Munster; National Aeronautics & Space Administration (NASA); NASA Goddard Space Flight Center; California Institute of Technology; National Aeronautics & Space Administration (NASA); NASA Jet Propulsion Laboratory (JPL); University of California System; University of California Los Angeles; University System of Maryland; University of Maryland College Park
RP De Sanctis, MC (corresponding author), INAF, Ist Astrofis & Planetol Spaziali, I-00133 Rome, Italy.
EM eleonora.ammannito@iaps.inaf.it; mariacristina.desanctis@iaps.inaf.it
FU Dawn Instrument, Operations and Science teams; Dawn Framing Camera team; Italian Space Agency [I/004/12/0]; NASA through the Dawn mission; Dawn at Vesta Participating Scientists Program
NR 30
TC 79
Z9 81
U1 1
U2 32
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 5
PY 2013
VL 504
IS 7478
BP 122
EP +
DI 10.1038/nature12665
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 264BK
UT WOS:000327851700043
PM 24196707
DA 2026-03-09
ER

PT J
AU Pelechano, V
   Wei, W
   Steinmetz, LM
AF Pelechano, Vicent
   Wei, Wu
   Steinmetz, Lars M.
TI Extensive transcriptional heterogeneity revealed by isoform profiling
SO NATURE
LA English
DT Article
ID genome-wide analysis; saccharomyces-cerevisiae; yeast; polyadenylation; organization; translation; switch
AB Transcript function is determined by sequence elements arranged on an individual RNA molecule. Variation in transcripts can affect messenger RNA stability, localization and translation(1), or produce truncated proteins that differ in localization(2) or function(3). Given the existence of overlapping, variable transcript isoforms, determining the functional impact of the transcriptome requires identification of full-length transcripts, rather than just the genomic regions that are transcribed(4,5). Here, by jointly determining both transcript ends for millions of RNA molecules, we reveal an extensive layer of isoform diversity previously hidden among overlapping RNA molecules. Variation in transcript boundaries seems to be the rule rather than the exception, even within a single population of yeast cells. Over 26 major transcript isoforms per protein-coding gene were expressed in yeast. Hundreds of short coding RNAs and truncated versions of proteins are concomitantly encoded by alternative transcript isoforms, increasing protein diversity. In addition, approximately 70% of genes express alternative isoforms that vary in post-transcriptional regulatory elements, and tandem genes frequently produce overlapping or even bicistronic transcripts. This extensive transcript diversity is generated by a relatively simple eukaryotic genome with limited splicing, and within a genetically homogeneous population of cells. Our findings have implications for genome compaction, evolution and phenotypic diversity between single cells. These data also indicate that isoform diversity as well as RNA abundance should be considered when assessing the functional repertoire of genomes.
C1 [Pelechano, Vicent; Wei, Wu; Steinmetz, Lars M.] European Mol Biol Lab EMBL, Genome Biol Unit, D-69117 Heidelberg, Germany.
   [Wei, Wu; Steinmetz, Lars M.] Stanford Univ, Stanford Genome Technol Ctr, Palo Alto, CA 94304 USA.
C3 European Molecular Biology Laboratory (EMBL); Stanford University
RP Steinmetz, LM (corresponding author), European Mol Biol Lab EMBL, Genome Biol Unit, Meyerhofstr 1, D-69117 Heidelberg, Germany.
EM larsms@embl.de
FU National Institutes of Health; EMBO fellowship
NR 27
TC 331
Z9 399
U1 2
U2 77
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 2
PY 2013
VL 497
IS 7447
BP 127
EP +
DI 10.1038/nature12121
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 134OK
UT WOS:000318221500047
PM 23615609
DA 2026-03-09
ER

PT J
AU Bergin, EA
   Cleeves, LI
   Gorti, U
   Zhang, K
   Blake, GA
   Green, JD
   Andrews, SM
   Evans, NJ
   Henning, T
   Öberg, K
   Pontoppidan, K
   Qi, CH
   Salyk, C
   van Dishoeck, EF
AF Bergin, Edwin A.
   Cleeves, L. Ilsedore
   Gorti, Uma
   Zhang, Ke
   Blake, Geoffrey A.
   Green, Joel D.
   Andrews, Sean M.
   Evans, Neal J., II
   Henning, Thomas
   Oeberg, Karin
   Pontoppidan, Klaus
   Qi, Chunhua
   Salyk, Colette
   van Dishoeck, Ewine F.
TI An old disk still capable of forming a planetary system
SO NATURE
LA English
DT Article
ID tw hya; gas; emission; search; pacs; line; hd
AB From the masses of the planets orbiting the Sun, and the abundance of elements relative to hydrogen, it is estimated that when the Solar System formed, the circumstellar disk must have had a minimum mass of around 0.01 solar masses within about 100 astronomical units of the star(1-4). (One astronomical unit is the EarthSun distance.) The main constituent of the disk, gaseous molecular hydrogen, does not efficiently emit radiation from the disk mass reservoir(5), and so the most common measure of the disk mass is dust thermal emission and lines of gaseous carbon monoxide(6). Carbon monoxide emission generally indicates properties of the disk surface, and the conversion from dust emission to gas mass requires knowledge of the grain properties and the gas-to-dust mass ratio, which probably differ from their interstellar values(7,8). As a result, mass estimates vary by orders of magnitude, as exemplified by the relatively old (3-10 million years) star TW Hydrae(9,10), for which the range is 0.0005-0.06 solar masses(11-14). Here we report the detection of the fundamental rotational transition of hydrogen deuteride from the direction of TW Hydrae. Hydrogen deuteride is a good tracer of disk gas because it follows the distribution of molecular hydrogen and its emission is sensitive to the total mass. The detection of hydrogen deuteride, combined with existing observations and detailed models, implies a disk mass of more than 0.05 solar masses, which is enough to form a planetary system like our own.
C1 [Bergin, Edwin A.; Cleeves, L. Ilsedore] Univ Michigan, Dept Astron, Ann Arbor, MI 48109 USA.
   [Gorti, Uma] SETI Inst, Mountain View, CA 94043 USA.
   [Gorti, Uma] NASA, Ames Res Ctr, Moffett Field, CA 94035 USA.
   [Zhang, Ke] CALTECH, Div Phys Math & Astron, Pasadena, CA 91125 USA.
   [Blake, Geoffrey A.] CALTECH, Div Geol & Planetary Sci, Pasadena, CA 91125 USA.
   [Green, Joel D.; Evans, Neal J., II] Univ Texas Austin, Dept Astron, Austin, TX 78712 USA.
   [Andrews, Sean M.; Oeberg, Karin; Qi, Chunhua] Harvard Smithsonian Ctr Astrophys, Cambridge, MA 02138 USA.
   [Henning, Thomas] Max Planck Inst Astron, D-69117 Heidelberg, Germany.
   [Pontoppidan, Klaus] Space Telescope Sci Inst, Baltimore, MD 21218 USA.
   [Salyk, Colette] Natl Opt Astron Observ, Tucson, AZ 85719 USA.
   [van Dishoeck, Ewine F.] Max Planck Inst Extraterr Phys, D-85748 Garching, Germany.
   [van Dishoeck, Ewine F.] Leiden Univ, Leiden Observ, NL-2300 RA Leiden, Netherlands.
C3 University of Michigan System; University of Michigan; SETI Institute; National Aeronautics & Space Administration (NASA); NASA Ames Research Center; California Institute of Technology; California Institute of Technology; University of Texas System; University of Texas Austin; Smithsonian Astrophysical Observatory; Smithsonian Institution; Harvard University; Max Planck Society; Space Telescope Science Institute; National Optical Astronomy Observatory; Max Planck Society; Leiden University; Leiden University - Excl LUMC
RP Bergin, EA (corresponding author), Univ Michigan, Dept Astron, 500 Church St, Ann Arbor, MI 48109 USA.
EM ebergin@umich.edu
FU NASA through JPL/Caltech; US National Science Foundation [1008800]; Direct For Mathematical & Physical Scien; Division Of Astronomical Sciences [1008800] Funding Source: National Science Foundation; Division Of Astronomical Sciences; Direct For Mathematical & Physical Scien [1109857] Funding Source: National Science Foundation
NR 30
TC 290
Z9 316
U1 0
U2 25
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 31
PY 2013
VL 493
IS 7434
BP 644
EP 646
DI 10.1038/nature11805
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 080CU
UT WOS:000314219600050
PM 23364742
DA 2026-03-09
ER

PT J
AU Sun, XJ
   Wang, ZX
   Wang, L
   Jiang, YW
   Kost, N
   Soong, TD
   Chen, WY
   Tang, ZY
   Nakadai, T
   Elemento, O
   Fischle, W
   Melnick, A
   Patel, DJ
   Nimer, SD
   Roeder, RG
AF Sun, Xiao-Jian
   Wang, Zhanxin
   Wang, Lan
   Jiang, Yanwen
   Kost, Nils
   Soong, T. David
   Chen, Wei-Yi
   Tang, Zhanyun
   Nakadai, Tomoyoshi
   Elemento, Olivier
   Fischle, Wolfgang
   Melnick, Ari
   Patel, Dinshaw J.
   Nimer, Stephen D.
   Roeder, Robert G.
TI A stable transcription factor complex nucleated by oligomeric AML1-ETO controls leukaemogenesis
SO NATURE
LA English
DT Article
ID acute myeloid-leukemia; fusion partner; eto; proteins; t(8/21); binding; differentiation; domain; seq; translocation
AB Transcription factors are frequently altered in leukaemia through chromosomal translocation, mutation or aberrant expression(1). AML1-ETO, a fusion protein generated by the t(8;21) translocation in acute myeloid leukaemia, is a transcription factor implicated in both gene repression and activation(2). AML1-ETO oligomerization, mediated by the NHR2 domain, is critical for leukaemogenesis(3-6), making it important to identify co-regulatory factors that 'read' the NHR2 oligomerization and contribute to leukaemogenesis(4). Here we show that, in human leukaemic cells, AML1-ETO resides in and functions through a stable AML1-ETO-containing transcription factor complex (AETFC) that contains several haematopoietic transcription (co)factors. These AETFC components stabilize the complex through multivalent interactions, provide multiple DNA-binding domains for diverse target genes, co-localize genome wide, cooperatively regulate gene expression, and contribute to leukaemogenesis. Within the AETFC complex, AML1-ETO oligomerization is required for a specific interaction between the oligomerized NHR2 domain and a novel NHR2-binding (N2B) motif in E proteins. Crystallographic analysis of the NHR2-N2B complex reveals a unique interaction pattern in which an N2B peptide makes direct contact with side chains of two NHR2 domains as a dimer, providing a novel model of how dimeric/oligomeric transcription factors create a new protein-binding interface through dimerization/oligomerization. Intriguingly, disruption of this interaction by point mutations abrogates AML1-ETO-induced haematopoietic stem/progenitor cell self-renewal and leukaemogenesis. These results reveal new mechanisms of action of AML1-ETO, and provide a potential therapeutic target in t(8;21)-positive acute myeloid leukaemia.
C1 [Sun, Xiao-Jian; Chen, Wei-Yi; Tang, Zhanyun; Nakadai, Tomoyoshi; Roeder, Robert G.] Rockefeller Univ, Lab Biochem & Mol Biol, New York, NY 10065 USA.
   [Wang, Zhanxin; Patel, Dinshaw J.] Mem Sloan Kettering Canc Ctr, Sloan Kettering Inst, Struct Biol Program, New York, NY 10065 USA.
   [Wang, Lan; Nimer, Stephen D.] Mem Sloan Kettering Canc Ctr, Sloan Kettering Inst, Mol Pharmacol & Chem Program, New York, NY 10065 USA.
   [Wang, Lan; Nimer, Stephen D.] Univ Miami, Miller Sch Med, Sylvester Comprehens Canc Ctr, Miami, FL 33136 USA.
   [Jiang, Yanwen; Melnick, Ari] Weill Cornell Med Coll, Dept Med, Div Hematol & Med Oncol, New York, NY 10065 USA.
   [Kost, Nils; Fischle, Wolfgang] Max Planck Inst Biophys Chem, Lab Chromatin Biochem, D-37077 Gottingen, Germany.
   [Soong, T. David; Elemento, Olivier] Weill Cornell Med Coll, Inst Computat Biomed, New York, NY 10065 USA.
C3 Rockefeller University; Memorial Sloan Kettering Cancer Center; Memorial Sloan Kettering Cancer Center; University of Miami; Cornell University; Weill Cornell Medicine; Max Planck Society; Cornell University; Weill Cornell Medicine
RP Roeder, RG (corresponding author), Rockefeller Univ, Lab Biochem & Mol Biol, New York, NY 10065 USA.
EM roeder@rockefeller.edu
FU National Institutes of Health (NIH) [CA163086, CA129325, CA113872, CA166835]; Starr Cancer Consortium [I5-A554]; Leukemia and Lymphoma Society (LLS) SCOR [7013-02, 7132-08]; Rockefeller University Center for Clinical and Translational Science from NIH [UL1RR024143]; Abby Rockefeller Mauze Trust; Maloris Foundation; National Cancer Institute [R01CA163086, P30CA008748, R01CA166835] Funding Source: NIH RePORTER
NR 37
TC 123
Z9 146
U1 0
U2 45
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 1
PY 2013
VL 500
IS 7460
BP 93
EP U120
DI 10.1038/nature12287
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 192VK
UT WOS:000322514800035
PM 23812588
DA 2026-03-09
ER

PT J
AU Wong, SD
   Srnec, M
   Matthews, ML
   Liu, LV
   Kwak, Y
   Park, K
   Bell, CB
   Alp, EE
   Zhao, JY
   Yoda, Y
   Kitao, S
   Seto, M
   Krebs, C
   Bollinger, JM
   Solomon, EI
AF Wong, Shaun D.
   Srnec, Martin
   Matthews, Megan L.
   Liu, Lei V.
   Kwak, Yeonju
   Park, Kiyoung
   Bell, Caleb B., III
   Alp, E. Ercan
   Zhao, Jiyong
   Yoda, Yoshitaka
   Kitao, Shinji
   Seto, Makoto
   Krebs, Carsten
   Bollinger, J. Martin, Jr.
   Solomon, Edward I.
TI Elucidation of the Fe(IV)=O intermediate in the catalytic cycle of the halogenase SyrB2
SO NATURE
LA English
DT Article
ID resonance vibrational spectroscopy; auxiliary basis-sets; gaussian-basis sets; correlation-energy; molecular calculations; aliphatic halogenase; electronic-structure; scattering beamline; row atoms; iron
AB Mononuclear non-haem iron (NHFe) enzymes catalyse a broad range of oxidative reactions, including halogenation, hydroxylation, ring closure, desaturation and aromatic ring cleavage reactions. They are involved in a number of biological processes, including phenylalanine metabolism, the production of neuro-transmitters, the hypoxic response and the biosynthesis of secondary metabolites(1-3). The reactive intermediate in the catalytic cycles of these enzymes is a high-spin S = 2 Fe(IV)=O species, which has been trapped for a number of NHFe enzymes(4-8), including the halogenase SyrB2 (syringomycin biosynthesis enzyme 2). Computational studies aimed at understanding the reactivity of this Fe(IV)=O intermediate(9-13) are limited in applicability owing to the paucity of experimental knowledge about its geometric and electronic structure. Synchrotron-based nuclear resonance vibrational spectroscopy (NRVS) is a sensitive and effective method that defines the dependence of the vibrational modes involving Fe on the nature of the Fe(IV)=O active site(14-16). Here we present NRVS structural characterization of the reactive Fe(IV)=O intermediate of a NHFe enzyme, namely the halogenase SyrB2 from the bacterium Pseudomonas syringae pv. syringae. This intermediate reacts via an initial hydrogen-atom abstraction step, performing subsequent halogenation of the native substrate or hydroxylation of non-native substrates(17). Acorrelation of the experimental NRVS data to electronic structure calculations indicates that the substrate directs the orientation of the Fe(IV)=O intermediate, presenting specific frontier molecular orbitals that can activate either selective halogenation or hydroxylation.
C1 [Wong, Shaun D.; Srnec, Martin; Liu, Lei V.; Kwak, Yeonju; Park, Kiyoung; Bell, Caleb B., III; Solomon, Edward I.] Stanford Univ, Dept Chem, Stanford, CA 94305 USA.
   [Matthews, Megan L.; Krebs, Carsten; Bollinger, J. Martin, Jr.] Penn State Univ, Dept Chem, University Pk, PA 16802 USA.
   [Alp, E. Ercan; Zhao, Jiyong] Argonne Natl Lab, APS XFD, Argonne, IL 60439 USA.
   [Yoda, Yoshitaka] JASRI, SPring 8, Hyogo 6795198, Japan.
   [Kitao, Shinji; Seto, Makoto] Kyoto Univ, Inst Res Reactor, Osaka 5900494, Japan.
   [Krebs, Carsten; Bollinger, J. Martin, Jr.] Penn State Univ, Dept Biochem & Mol Biol, University Pk, PA 16802 USA.
   [Solomon, Edward I.] SLAC Natl Accelerator Lab, Menlo Pk, CA 94025 USA.
C3 Stanford University; Pennsylvania Commonwealth System of Higher Education (PCSHE); Pennsylvania State University; Pennsylvania State University - University Park; United States Department of Energy (DOE); Argonne National Laboratory; Kyoto University; Pennsylvania Commonwealth System of Higher Education (PCSHE); Pennsylvania State University; Pennsylvania State University - University Park; Stanford University; United States Department of Energy (DOE); SLAC National Accelerator Laboratory
RP Krebs, C (corresponding author), Penn State Univ, Dept Chem, University Pk, PA 16802 USA.
EM ckrebs@psu.edu; edward.solomon@stanford.edu
FU National Institutes of Health [GM-40392, GM-69657]; National Science Foundation [MCB-0919027, MCB-642058, CHE-724084]; Department of Energy, Office of Science [DE-AC-02-06CH11357]; National Institute of General Medical Sciences [R01GM040392] Funding Source: NIH RePORTER
NR 55
TC 203
Z9 252
U1 4
U2 215
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 18
PY 2013
VL 499
IS 7458
BP 320
EP +
DI 10.1038/nature12304
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 184RJ
UT WOS:000321910700032
PM 23868262
DA 2026-03-09
ER

PT J
AU Owen, SF
   Tuncdemir, SN
   Bader, PL
   Tirko, NN
   Fishell, G
   Tsien, RW
AF Owen, Scott F.
   Tuncdemir, Sebnem N.
   Bader, Patrick L.
   Tirko, Natasha N.
   Fishell, Gord
   Tsien, Richard W.
TI Oxytocin enhances hippocampal spike transmission by modulating fast-spiking interneurons
SO NATURE
LA English
DT Article
ID rat hippocampus; feedforward inhibition; pyramidal neurons; synaptic depression; autism; norepinephrine; motherhood; activation; excitation; frequency
AB Neuromodulatory control by oxytocin is essential to a wide range of social(1,2), parental(3) and stress-related behaviours(4). Autism spectrum disorders (ASD) are associated with deficiencies in oxytocin levels(5) and with genetic alterations of the oxytocin receptor (OXTR)(6). Thirty years ago, Muhlethaler et al.(7) found that oxytocin increases the firing of inhibitory hippocampal neurons, but it remains unclear how elevated inhibition could account for the ability of oxytocin to improve information processing in the brain. Here we describe in mammalian hippocampus a simple yet powerful mechanism by which oxytocin enhances cortical information transfer while simultaneously lowering background activity, thus greatly improving the signal-to-noise ratio. Increased fast-spiking interneuron activity not only suppresses spontaneous pyramidal cell firing, but also enhances the fidelity of spike transmission and sharpens spike timing. Use-dependent depression at the fast-spiking interneuron-pyramidal cell synapse is both necessary and sufficient for the enhanced spike throughput. We show the generality of this novel circuit mechanism by activation of fast-spiking interneurons with cholecystokinin or channelrhodopsin-2. This provides insight into how a diffusely delivered neuromodulator can improve the performance of neural circuitry that requires synapse specificity and millisecond precision.
C1 [Owen, Scott F.; Bader, Patrick L.; Tsien, Richard W.] Stanford Univ, Sch Med, Dept Mol & Cellular Physiol, Stanford, CA 94305 USA.
   [Tuncdemir, Sebnem N.; Bader, Patrick L.; Tirko, Natasha N.; Fishell, Gord; Tsien, Richard W.] NYU, Inst Neurosci, New York, NY 10016 USA.
C3 Stanford University; New York University
RP Tsien, RW (corresponding author), Stanford Univ, Sch Med, Dept Mol & Cellular Physiol, 279 Campus Dr, Stanford, CA 94305 USA.
EM richard.tsien@nyumc.org
FU Burnett Family Fund; Mosbacher Fund; Mathers Foundation; National Institute of Mental Health [MH064070, MH071739]; National Institute of Neurological Disorders and Stroke [NS024067]; Simons Foundation [95395]; NDSEG fellowship; NIMH-NRSA fellowship [F31MH084430]; SNSF; SFGBM fellowship [PASMP3_140063/1]; National Institute of Mental Health [R01MH071739] Funding Source: NIH RePORTER; Swiss National Science Foundation (SNF) [PASMP3_140063] Funding Source: Swiss National Science Foundation (SNF)
NR 36
TC 268
Z9 326
U1 0
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 AUG 22
PY 2013
VL 500
IS 7463
BP 458
EP +
DI 10.1038/nature12330
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 203TJ
UT WOS:000323316100035
PM 23913275
DA 2026-03-09
ER

PT J
AU Aubert, J
   Finlay, CC
   Fournier, A
AF Aubert, Julien
   Finlay, Christopher C.
   Fournier, Alexandre
TI Bottom-up control of geomagnetic secular variation by the Earth's inner core
SO NATURE
LA English
DT Article
ID magnetic-field; rotation; surface; models; stratification; evolution; steady; growth; flow
AB Temporal changes in the Earth's magnetic field, known as geomagnetic secular variation, occur most prominently at low latitudes in the Atlantic hemisphere(1,2) (that is, from 290 degrees east to 90 degrees east), whereas in the Pacific hemisphere there is comparatively little activity. This is a consequence of the geographical localization of intense, westward drifting, equatorial magnetic flux patches at the core surface(3). Despite successes in explaining the morphology of the geomagnetic field(4), numerical models of the geodynamo have so far failed to account systematically for this striking pattern of geomagnetic secular variation. Here we show that it can be reproduced provided that two mechanisms relying on the inner core are jointly considered. First, gravitational coupling(5) aligns the inner core with the mantle, forcing the flow of liquid metal in the outer core into a giant, westward drifting, sheet-like gyre(6). The resulting shear concentrates azimuthal magnetic flux at low latitudes close to the core-mantle boundary, where it is expelled by core convection and subsequently transported westward. Second, differential inner-core growth(7,8), fastest below Indonesia(6,9), causes an asymmetric buoyancy release in the outer core which in turn distorts the gyre, forcing it to become eccentric, in agreement with recent core flow inversions(6,10,11). This bottom-up heterogeneous driving of core convection dominates top-down driving from mantle thermal heterogeneities, and localizes magnetic variations in a longitudinal sector centred beneath the Atlantic, where the eccentric gyre reaches the core surface. To match the observed pattern of geomagnetic secular variation, the solid material forming the inner core must now be in a state of differential growth rather than one of growth and melting induced by convective translation(7,8).
C1 [Aubert, Julien; Fournier, Alexandre] Univ Paris Diderot, Inst Phys Globe Paris, Sorbonne Paris Cite, UMR 7154,CNRS, F-75005 Paris, France.
   [Finlay, Christopher C.] Tech Univ Denmark, Natl Space Inst, Div Geomagnetism, DK-2800 Lyngby, Denmark.
C3 Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Earth Sciences & Astronomy (INSU); Universite Paris Cite; Technical University of Denmark
RP Aubert, J (corresponding author), Univ Paris Diderot, Inst Phys Globe Paris, Sorbonne Paris Cite, UMR 7154,CNRS, F-75005 Paris, France.
EM aubert@ipgp.fr
FU French Agence Nationale de la Recherche [ANR-2011-BS56-011]; GENCI-IDRIS [2012-042122, 2013-042122]
NR 35
TC 172
Z9 177
U1 0
U2 65
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 10
PY 2013
VL 502
IS 7470
BP 219
EP +
DI 10.1038/nature12574
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 231RU
UT WOS:000325436100047
PM 24108054
DA 2026-03-09
ER

PT J
AU Barve, A
   Wagner, A
AF Barve, Aditya
   Wagner, Andreas
TI A latent capacity for evolutionary innovation through exaptation in metabolic systems
SO NATURE
LA English
DT Article
ID escherichia-coli; genotype networks; evolvability; recruitment; robustness; database; ligand; genes; kegg; rna
AB Some evolutionary innovations may originate non-adaptively as exaptations, or pre-adaptations, which are by-products of other adaptive traits(1-5). Examples include feathers, which originated before they were used in flight(2), and lens crystallins, which are light-refracting proteins that originated as enzymes(6). The question of how often adaptive traits have non-adaptive origins has profound implications for evolutionary biology, but is difficult to address systematically. Here we consider this issue in metabolism, one of the most ancient biological systems that is central to all life. We analyse a metabolic trait of great adaptive importance: the ability of a metabolic reaction network to synthesize all biomass from a single source of carbon and energy. We use novel computational methods to sample randomly many metabolic networks that can sustain life on any given carbon source but contain an otherwise random set of known biochemical reactions. We show that when we require such networks to be viable on one particular carbon source, they are typically also viable on multiple other carbon sources that were not targets of selection. For example, viability on glucose may entail viability on up to 44 other sole carbon sources. Any one adaptation in these metabolic systems typically entails multiple potential exaptations. Metabolic systems thus contain a latent potential for evolutionary innovations with non-adaptive origins. Our observations suggest that many more metabolic traits may have non-adaptive origins than is appreciated at present. They also challenge our ability to distinguish adaptive from non-adaptive traits.
C1 [Barve, Aditya; Wagner, Andreas] Univ Zurich, Inst Evolutionary Biol & Environm Sci, CH-8057 Zurich, Switzerland.
   [Barve, Aditya; Wagner, Andreas] Swiss Inst Bioinformat, CH-1015 Lausanne, Switzerland.
   [Wagner, Andreas] Santa Fe Inst, Santa Fe, NM 87501 USA.
C3 University of Zurich; Swiss Institute of Bioinformatics; The Santa Fe Institute
RP Wagner, A (corresponding author), Univ Zurich, Inst Evolutionary Biol & Environm Sci, Bldg Y27,Winterthurerstr 190, CH-8057 Zurich, Switzerland.
EM andreas.wagner@ieu.uzh.ch
FU Swiss National Science Foundation [315230-129708]
NR 40
TC 112
Z9 127
U1 1
U2 76
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 8
PY 2013
VL 500
IS 7461
BP 203
EP +
DI 10.1038/nature12301
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 197CH
UT WOS:000322825500034
PM 23851393
DA 2026-03-09
ER

PT J
AU Ristè, D
   Dukalski, M
   Watson, CA
   de Lange, G
   Tiggelman, MJ
   Blanter, YM
   Lehnert, KW
   Schouten, RN
   DiCarlo, L
AF Riste, D.
   Dukalski, M.
   Watson, C. A.
   de Lange, G.
   Tiggelman, M. J.
   Blanter, Ya. M.
   Lehnert, K. W.
   Schouten, R. N.
   DiCarlo, L.
TI Deterministic entanglement of superconducting qubits by parity measurement and feedback
SO NATURE
LA English
DT Article
ID quantum teleportation
AB The stochastic evolution of quantum systems during measurement is arguably the most enigmatic feature of quantum mechanics. Measuring a quantum system typically steers it towards a classical state, destroying the coherence of an initial quantum superposition and the entanglement with other quantum systems. Remarkably, the measurement of a shared property between non-interacting quantum systems can generate entanglement, starting from an uncorrelated state. Of special interest in quantum computing is the parity measurement(1), which projects the state of multiple qubits (quantum bits) to a state with an even or odd number of excited qubits. A parity meter must discern the two qubit-excitation parities with high fidelity while preserving coherence between same-parity states. Despite numerous proposals for atomic(2), semiconducting(1,3-7) and superconducting qubits(8,9), realizing a parity meter that creates entanglement for both even and odd measurement results has remained an outstanding challenge. Here we perform a time-resolved, continuous parity measurement of two superconducting qubits using the cavity in a three-dimensional circuit quantum electrodynamics(10,11) architecture and phase-sensitive parametric amplification(12). Using postselection, we produce entanglement by parity measurement reaching 88 per cent fidelity to the closest Bell state. Incorporating the parity meter in a feedback-control loop, we transform the entanglement generation from probabilistic to fully deterministic, achieving 66 per cent fidelity to a target Bell state on demand. These realizations of a parity meter and a feedback-enabled deterministic measurement protocol provide key ingredients for active quantum error correction in the solid state(13-15).
C1 [Riste, D.; Dukalski, M.; Watson, C. A.; de Lange, G.; Tiggelman, M. J.; Blanter, Ya. M.; Schouten, R. N.; DiCarlo, L.] Delft Univ Technol, Kavli Inst Nanosci, NL-2600 GA Delft, Netherlands.
   [Lehnert, K. W.] Univ Colorado, JILA, NIST, Boulder, CO 80309 USA.
   [Lehnert, K. W.] Univ Colorado, Dept Phys, Boulder, CO 80309 USA.
C3 Delft University of Technology; University of Colorado System; University of Colorado Boulder; National Institute of Standards & Technology (NIST) - USA; University of Colorado System; University of Colorado Boulder
RP DiCarlo, L (corresponding author), Delft Univ Technol, Kavli Inst Nanosci, POB 5046, NL-2600 GA Delft, Netherlands.
EM l.dicarlo@tudelft.nl
FU Dutch Organization for Fundamental Research on Matter (FOM); Netherlands Organization for Scientific Research (NWO); EU; DARPA QuEST programme
NR 36
TC 282
Z9 324
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 OCT 17
PY 2013
VL 502
IS 7471
BP 350
EP +
DI 10.1038/nature12513
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 235GY
UT WOS:000325706300048
PM 24132292
DA 2026-03-09
ER

PT J
AU Dahl-Jensen, D
   Albert, MR
   Aldahan, A
   Azuma, N
   Balslev-Clausen, D
   Baumgartner, M
   Berggren, AM
   Bigler, M
   Binder, T
   Blunier, T
   Bourgeois, JC
   Brook, EJ
   Buchardt, SL
   Buizert, C
   Capron, E
   Chappellaz, J
   Chung, J
   Clausen, HB
   Cvijanovic, I
   Davies, SM
   Ditlevsen, P
   Eicher, O
   Fischer, H
   Fisher, DA
   Fleet, LG
   Gfeller, G
   Gkinis, V
   Gogineni, S
   Goto-Azuma, K
   Grinsted, A
   Gudlaugsdottir, H
   Guillevic, M
   Hansen, SB
   Hansson, M
   Hirabayashi, M
   Hong, S
   Hur, SD
   Huybrechts, P
   Hvidberg, CS
   Iizuka, Y
   Jenk, T
   Johnsen, SJ
   Jones, TR
   Jouzel, J
   Karlsson, NB
   Kawamura, K
   Keegan, K
   Kettner, E
   Kipfstuhl, S
   Kjær, HA
   Koutnik, M
   Kuramoto, T
   Köhler, P
   Laepple, T
   Landais, A
   Langen, PL
   Larsen, LB
   Leuenberger, D
   Leuenberger, M
   Leuschen, C
   Li, J
   Lipenkov, V
   Martinerie, P
   Maselli, OJ
   Masson-Delmotte, V
   McConnell, JR
   Miller, H
   Mini, O
   Miyamoto, A
   Montagnat-Rentier, M
   Mulvaney, R
   Muscheler, R
   Orsi, AJ
   Paden, J
   Panton, C
   Pattyn, F
   Petit, JR
   Pol, K
   Popp, T
   Possnert, G
   Prié, F
   Prokopiou, M
   Quiquet, A
   Rasmussen, SO
   Raynaud, D
   Ren, J
   Reutenauer, C
   Ritz, C
   Röckmann, T
   Rosen, JL
   Rubino, M
   Rybak, O
   Samyn, D
   Sapart, CJ
   Schilt, A
   Schmidt, AMZ
   Schwander, J
   Schüpbach, S
   Seierstad, I
   Severinghaus, JP
   Sheldon, S
   Simonsen, SB
   Sjolte, J
   Solgaard, AM
   Sowers, T
   Sperlich, P
   Steen-Larsen, HC
   Steffen, K
   Steffensen, JP
   Steinhage, D
   Stocker, TF
   Stowasser, C
   Sturevik, AS
   Sturges, WT
   Sveinbjörnsdottir, A
   Svensson, A
   Tison, JL
   Uetake, J
   Vallelonga, P
   van de Wal, RSW
   van der Wel, G
   Vaughn, BH
   Vinther, B
   Waddington, E
   Wegner, A
   Weikusat, I
   White, JWC
   Wilhelms, F
   Winstrup, M
   Witrant, E
   Wolff, EW
   Xiao, C
   Zheng, J
AF Dahl-Jensen, D.
   Albert, M. R.
   Aldahan, A.
   Azuma, N.
   Balslev-Clausen, D.
   Baumgartner, M.
   Berggren, A. -M.
   Bigler, M.
   Binder, T.
   Blunier, T.
   Bourgeois, J. C.
   Brook, E. J.
   Buchardt, S. L.
   Buizert, C.
   Capron, E.
   Chappellaz, J.
   Chung, J.
   Clausen, H. B.
   Cvijanovic, I.
   Davies, S. M.
   Ditlevsen, P.
   Eicher, O.
   Fischer, H.
   Fisher, D. A.
   Fleet, L. G.
   Gfeller, G.
   Gkinis, V.
   Gogineni, S.
   Goto-Azuma, K.
   Grinsted, A.
   Gudlaugsdottir, H.
   Guillevic, M.
   Hansen, S. B.
   Hansson, M.
   Hirabayashi, M.
   Hong, S.
   Hur, S. D.
   Huybrechts, P.
   Hvidberg, C. S.
   Iizuka, Y.
   Jenk, T.
   Johnsen, S. J.
   Jones, T. R.
   Jouzel, J.
   Karlsson, N. B.
   Kawamura, K.
   Keegan, K.
   Kettner, E.
   Kipfstuhl, S.
   Kjaer, H. A.
   Koutnik, M.
   Kuramoto, T.
   Koehler, P.
   Laepple, T.
   Landais, A.
   Langen, P. L.
   Larsen, L. B.
   Leuenberger, D.
   Leuenberger, M.
   Leuschen, C.
   Li, J.
   Lipenkov, V.
   Martinerie, P.
   Maselli, O. J.
   Masson-Delmotte, V.
   McConnell, J. R.
   Miller, H.
   Mini, O.
   Miyamoto, A.
   Montagnat-Rentier, M.
   Mulvaney, R.
   Muscheler, R.
   Orsi, A. J.
   Paden, J.
   Panton, C.
   Pattyn, F.
   Petit, J. -R.
   Pol, K.
   Popp, T.
   Possnert, G.
   Prie, F.
   Prokopiou, M.
   Quiquet, A.
   Rasmussen, S. O.
   Raynaud, D.
   Ren, J.
   Reutenauer, C.
   Ritz, C.
   Rockmann, T.
   Rosen, J. L.
   Rubino, M.
   Rybak, O.
   Samyn, D.
   Sapart, C. J.
   Schilt, A.
   Schmidt, A. M. Z.
   Schwander, J.
   Schuepbach, S.
   Seierstad, I.
   Severinghaus, J. P.
   Sheldon, S.
   Simonsen, S. B.
   Sjolte, J.
   Solgaard, A. M.
   Sowers, T.
   Sperlich, P.
   Steen-Larsen, H. C.
   Steffen, K.
   Steffensen, J. P.
   Steinhage, D.
   Stocker, T. F.
   Stowasser, C.
   Sturevik, A. S.
   Sturges, W. T.
   Sveinbjornsdottir, A.
   Svensson, A.
   Tison, J. -L.
   Uetake, J.
   Vallelonga, P.
   van de Wal, R. S. W.
   van der Wel, G.
   Vaughn, B. H.
   Vinther, B.
   Waddington, E.
   Wegner, A.
   Weikusat, I.
   White, J. W. C.
   Wilhelms, F.
   Winstrup, M.
   Witrant, E.
   Wolff, E. W.
   Xiao, C.
   Zheng, J.
TI Eemian interglacial reconstructed from a Greenland folded ice core
SO NATURE
LA English
DT Article
ID antarctic ice; air content; sea-level; climate; record; temperature; sheet; grip; variability; delta-o-18
AB Efforts to extract a Greenland ice core with a complete record of the Eemian interglacial (130,000 to 115,000 years ago) have until now been unsuccessful. The response of the Greenland ice sheet to the warmer-than-present climate of the Eemian has thus remained unclear. Here we present the new North Greenland Eemian Ice Drilling ('NEEM') ice core and show only a modest ice-sheet response to the strong warming in the early Eemian. We reconstructed the Eemian record from folded ice using globally homogeneous parameters known from dated Greenland and Antarctic ice-core records. On the basis of water stable isotopes, NEEM surface temperatures after the onset of the Eemian (126,000 years ago) peaked at 8 +/- 4 degrees Celsius above the mean of the past millennium, followed by a gradual cooling that was probably driven by the decreasing summer insolation. Between 128,000 and 122,000 years ago, the thickness of the northwest Greenland ice sheet decreased by 400 +/- 250 metres, reaching surface elevations 122,000 years ago of 130 +/- 300 metres lower than the present. Extensive surface melt occurred at the NEEM site during the Eemian, a phenomenon witnessed when melt layers formed again at NEEM during the exceptional heat of July 2012. With additional warming, surface melt might become more common in the future.
C1 [Dahl-Jensen, D.; Balslev-Clausen, D.; Blunier, T.; Buchardt, S. L.; Buizert, C.; Clausen, H. B.; Cvijanovic, I.; Ditlevsen, P.; Gkinis, V.; Grinsted, A.; Guillevic, M.; Hansen, S. B.; Hvidberg, C. S.; Jenk, T.; Johnsen, S. J.; Karlsson, N. B.; Kettner, E.; Kjaer, H. A.; Langen, P. L.; Larsen, L. B.; Panton, C.; Popp, T.; Rasmussen, S. O.; Reutenauer, C.; Rubino, M.; Schmidt, A. M. Z.; Seierstad, I.; Sheldon, S.; Simonsen, S. B.; Sjolte, J.; Solgaard, A. M.; Sperlich, P.; Steffensen, J. P.; Stowasser, C.; Svensson, A.; Vallelonga, P.; Vinther, B.; Winstrup, M.] Univ Copenhagen, Niels Bohr Inst, Ctr Ice & Climate, DK-2100 Copenhagen K, Denmark.
   [Albert, M. R.; Keegan, K.] Dartmouth Coll, Thayer Sch Engn, Hanover, NH 03755 USA.
   [Aldahan, A.; Berggren, A. -M.; Samyn, D.; Sturevik, A. S.] Uppsala Univ, Dept Earth Sci, S-75236 Uppsala, Sweden.
   [Azuma, N.; Samyn, D.] Nagaoka Univ Technol, Dept Mech Engn, Nagaoka, Niigata 9402188, Japan.
   [Baumgartner, M.; Bigler, M.; Eicher, O.; Fischer, H.; Gfeller, G.; Leuenberger, D.; Leuenberger, M.; Mini, O.; Schilt, A.; Schwander, J.; Schuepbach, S.; Stocker, T. F.; van der Wel, G.] Univ Bern, Inst Phys, CH-3012 Bern, Switzerland.
   [Baumgartner, M.; Bigler, M.; Eicher, O.; Fischer, H.; Gfeller, G.; Leuenberger, D.; Leuenberger, M.; Mini, O.; Schilt, A.; Schwander, J.; Schuepbach, S.; Stocker, T. F.; van der Wel, G.] Univ Bern, Oeschger Ctr Climate Change Res, CH-3012 Bern, Switzerland.
   [Binder, T.] Heidelberg Univ, IWR, D-69115 Heidelberg, Germany.
   [Bourgeois, J. C.; Fisher, D. A.; Zheng, J.] Geol Survey Canada, Nat Resources Canada, Ottawa, ON K1A 0E8, Canada.
   [Brook, E. J.; Buizert, C.; Rosen, J. L.; Schilt, A.] Oregon State Univ, Coll Earth Ocean & Atmospher Sci, Corvallis, OR 97331 USA.
   [Capron, E.; Guillevic, M.; Jouzel, J.; Landais, A.; Masson-Delmotte, V.; Pol, K.; Prie, F.] CEA CNRS UVSQ, CEA Saclay, Lab Sci Climat & Environm, IPSL, F-91191 Gif Sur Yvette, France.
   [Capron, E.; Fleet, L. G.; Mulvaney, R.; Pol, K.; Wolff, E. W.] British Antarctic Survey, Cambridge CB3 0ET, England.
   [Chappellaz, J.; Martinerie, P.; Montagnat-Rentier, M.; Petit, J. -R.; Quiquet, A.; Raynaud, D.; Ritz, C.] UJF Grenoble 1, CNRS, LGGE, F-38402 St Martin Dheres, France.
   [Chung, J.; Hur, S. D.] Korea Polar Res Inst, Inchon 406840, South Korea.
   [Davies, S. M.] Swansea Univ, Coll Sci, Dept Geog, Swansea SA2 8PP, W Glam, Wales.
   [Gkinis, V.; Jones, T. R.; Vaughn, B. H.; White, J. W. C.] Univ Colorado, INSTAAR, Boulder, CO 80309 USA.
   [Gogineni, S.; Leuschen, C.; Li, J.; Paden, J.] Univ Kansas, CReSIS, Lawrence, KS 66045 USA.
   [Goto-Azuma, K.; Hirabayashi, M.; Kawamura, K.; Kuramoto, T.; Uetake, J.] Natl Inst Polar Res, Tachikawa, Tokyo 1908518, Japan.
   [Gudlaugsdottir, H.; Sveinbjornsdottir, A.] Univ Iceland, Inst Earth & Sci, IS-107 Reykjavik, Iceland.
   [Hansson, M.; Iizuka, Y.] Stockholm Univ, Dept Phys Geog & Quaternary Geol, S-10691 Stockholm, Sweden.
   [Hong, S.; Steen-Larsen, H. C.] Inha Univ, Dept Ocean Sci, Inchon 402751, South Korea.
   [Huybrechts, P.; Rybak, O.] Vrije Univ Brussel, Dept Geog, B-1050 Brussels, Belgium.
   [Kuramoto, T.] Shinshu Univ, Inst Mt Sci, Matsumoto, Nagano 3908621, Japan.
   [Kipfstuhl, S.; Koehler, P.; Laepple, T.; Miller, H.; Steinhage, D.; Wegner, A.; Weikusat, I.; Wilhelms, F.] Alfred Wegener Inst Polar & Marine Res, D-27515 Bremerhaven, Germany.
   [Koutnik, M.; Waddington, E.] Univ Washington, Dept Earth & Space Sci, Seattle, WA 98195 USA.
   [Lipenkov, V.] Arctic & Antarctic Res Inst, St Petersburg 199397, Russia.
   [Maselli, O. J.; McConnell, J. R.] Nevada Syst Higher Educ, Desert Res Inst, Reno, NV 89512 USA.
   [Iizuka, Y.; Miyamoto, A.] Hokkaido Univ, Inst Low Temp Sci, Sapporo, Hokkaido 0600819, Japan.
   [Muscheler, R.; Sjolte, J.] Lund Univ, Dept Geol, SE-22362 Lund, Sweden.
   [Orsi, A. J.; Severinghaus, J. P.] Univ Calif San Diego, Scripps Inst Oceanog, La Jolla, CA 92093 USA.
   [Pattyn, F.; Tison, J. -L.] Univ Libre Bruxelles, Lab Glaciol, B-1050 Brussels, Belgium.
   [Possnert, G.] Uppsala Univ, Tandem Lab, S-75120 Uppsala, Sweden.
   [Prokopiou, M.; Rockmann, T.; Sapart, C. J.; van de Wal, R. S. W.] Univ Utrecht, Inst Marine & Atmospher Res Utrecht IMAU, NL-3584 CC Utrecht, Netherlands.
   [Ren, J.; Xiao, C.] Chinese Acad Sci, Cold & Arid Reg Environm & Engn Res Inst, State Key Lab Cryospher Sci, Lanzhou 730000, Peoples R China.
   [Rubino, M.] CSIRO Marine & Atmospher Res, Ctr Australian Weather & Climate Res, Aspendale, Vic 3195, Australia.
   [Sowers, T.] Penn State Univ, Earth & Environm Syst Inst, University Pk, PA 16802 USA.
   [Steffen, K.] Univ Colorado, CIRES, Boulder, CO 80309 USA.
   [Sturges, W. T.] Univ E Anglia, Norwich NR4 7TJ, Norfolk, England.
   [Witrant, E.] UJF Grenoble 1, Grenoble Image Parole Signal Automat GIPSA Lab, CNRS, UMR 5216, F-38402 St Martin Dheres, France.
   [Xiao, C.] Chinese Acad Meteorol Sci, China Inst Climate Syst, Beijing 100081, Peoples R China.
C3 University of Copenhagen; Niels Bohr Institute; Dartmouth College; Uppsala University; Nagaoka University of Technology; University of Bern; University of Bern; Ruprecht Karls University Heidelberg; Natural Resources Canada; Lands & Minerals Sector - Natural Resources Canada; Geological Survey of Canada; Oregon State University; CEA; Universite Paris Saclay; Universite Paris Cite; UK Research & Innovation (UKRI); Natural Environment Research Council (NERC); NERC British Antarctic Survey; Centre National de la Recherche Scientifique (CNRS); Communaute Universite Grenoble Alpes; Universite Grenoble Alpes (UGA); Korea Polar Research Institute (KOPRI); Korea Institute of Ocean Science & Technology (KIOST); Swansea University; University of Colorado System; University of Colorado Boulder; University of Kansas; Research Organization of Information & Systems (ROIS); National Institute of Polar Research (NIPR) - Japan; University of Iceland; Stockholm University; Inha University; Vrije Universiteit Brussel; Shinshu University; Helmholtz Association; Alfred Wegener Institute, Helmholtz Centre for Polar & Marine Research; University of Washington; University of Washington Seattle; Arctic & Antarctic Research Institute; Nevada System of Higher Education (NSHE); Desert Research Institute NSHE; Hokkaido University; Lund University; University of California System; University of California San Diego; Scripps Institution of Oceanography; Universite Libre de Bruxelles; Uppsala University; Utrecht University; Chinese Academy of Sciences; Cold & Arid Regions Environmental & Engineering Research Institute, CAS; Commonwealth Scientific & Industrial Research Organisation (CSIRO); Pennsylvania Commonwealth System of Higher Education (PCSHE); Pennsylvania State University; Pennsylvania State University - University Park; University of Colorado System; University of Colorado Boulder; University of East Anglia; 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); China Meteorological Administration; Chinese Academy of Meteorological Sciences (CAMS)
RP Dahl-Jensen, D (corresponding author), Univ Copenhagen, Niels Bohr Inst, Ctr Ice & Climate, Juliane Maries Vej 30, DK-2100 Copenhagen K, Denmark.
EM ddj@gfy.ku.dk
FU 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); South Korea (KOPRI); The Netherlands (NWO/ALW); Sweden (VR); Switzerland (SNF); United Kingdom (NERC); USA (US NSF, Office of Polar Programs); EU; Office of Polar Programs (OPP); Directorate For Geosciences [0806377, 0806407, 0806414] Funding Source: National Science Foundation; Office of Polar Programs (OPP); Directorate For Geosciences [0909541, 0806387] Funding Source: National Science Foundation; Office Of The Director; Office Of Internatl Science &Engineering [0968391] Funding Source: National Science Foundation; NERC [bas0100024, NE/F020600/1, NE/F021194/1] Funding Source: UKRI; Grants-in-Aid for Scientific Research [22540426, 21671001, 23681001, 22221002, 21221002] Funding Source: KAKEN; Natural Environment Research Council [NE/F020600/1, bas0100024, NE/F021194/1] Funding Source: researchfish
NR 50
TC 545
Z9 593
U1 4
U2 615
PU NATURE PUBLISHING 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 24
PY 2013
VL 493
IS 7433
BP 489
EP 494
DI 10.1038/nature11789
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 075GF
UT WOS:000313871400029
PM 23344358
DA 2026-03-09
ER

PT J
AU Kvitsiani, D
   Ranade, S
   Hangya, B
   Taniguchi, H
   Huang, JZ
   Kepecs, A
AF Kvitsiani, D.
   Ranade, S.
   Hangya, B.
   Taniguchi, H.
   Huang, J. Z.
   Kepecs, A.
TI Distinct behavioural and network correlates of two interneuron types in prefrontal cortex
SO NATURE
LA English
DT Article
ID gabaergic neurons; pyramidal cells; cerebral-cortex; in-vivo; inhibition; information; computation; responses; features; subtypes
AB Neurons in the prefrontal cortex exhibit diverse behavioural correlates(1-4), an observation that has been attributed to cell-type diversity. To link identified neuron types with network and behavioural functions, we recorded from the two largest genetically defined inhibitory interneuron classes, the perisomatically targeting parvalbumin (PV) and the dendritically targeting somatostatin (SOM) neurons(5-8) in anterior cingulate cortex of mice performing a reward foraging task. Here we show that PV and a subtype of SOM neurons form functionally homogeneous populations showing a double dissociation between both their inhibitory effects and behavioural correlates. Out of several events pertaining to behaviour, a subtype of SOM neurons selectively responded at reward approach, whereas PV neurons responded at reward leaving and encoded preceding stay duration. These behavioural correlates of PV and SOM neurons defined a behavioural epoch and a decision variable important for foraging (whether to stay or to leave), a crucial function attributed to the anterior cingulate cortex(9-11). Furthermore, PV neurons could fire in millisecond synchrony, exerting fast and powerful inhibition on principal cell firing, whereas the inhibitory effect of SOM neurons on firing output was weak and more variable, consistent with the idea that they respectively control the outputs of, and inputs to, principal neurons(12-16). These results suggest a connection between the circuit-level function of different interneuron types in regulating the flow of information and the behavioural functions served by the cortical circuits. Moreover, these observations bolster the hope that functional response diversity during behaviour can in part be explained by cell-type diversity.
C1 [Kvitsiani, D.; Ranade, S.; Hangya, B.; Taniguchi, H.; Huang, J. Z.; Kepecs, A.] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA.
C3 Cold Spring Harbor Laboratory
RP Kepecs, A (corresponding author), Cold Spring Harbor Lab, 1 Bungtown Rd, Cold Spring Harbor, NY 11724 USA.
EM kepecs@cshl.edu
FU Klingenstein Foundation; John Merck Foundation; Sloan Foundation; Whitehall Foundation; National Institute of Neurological Disorders and Stroke (National Institutes of Health) [R01NS075531]; Swartz Foundation; The Robert Lee and Clara Guthrie Patterson Trust Postdoctoral Fellowship; Human Frontier Science Program; Marie Curie International Outgoing Fellowship within the EU Seventh Framework Programme for Research and Technological Development; National Institute of Neurological Disorders and Stroke [R01NS075531] Funding Source: NIH RePORTER
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NR 44
TC 381
Z9 477
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 JUN 20
PY 2013
VL 498
IS 7454
BP 363
EP +
DI 10.1038/nature12176
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 166XI
UT WOS:000320592900040
PM 23708967
DA 2026-03-09
ER

PT J
AU Picotti, P
   Clément-Ziza, M
   Lam, H
   Campbell, DS
   Schmidt, A
   Deutsch, EW
   Röst, H
   Sun, Z
   Rinner, O
   Reiter, L
   Shen, Q
   Michaelson, JJ
   Frei, A
   Alberti, S
   Kusebauch, U
   Wollscheid, B
   Moritz, RL
   Beyer, A
   Aebersold, R
AF Picotti, Paola
   Clement-Ziza, Mathieu
   Lam, Henry
   Campbell, David S.
   Schmidt, Alexander
   Deutsch, Eric W.
   Roest, Hannes
   Sun, Zhi
   Rinner, Oliver
   Reiter, Lukas
   Shen, Qin
   Michaelson, Jacob J.
   Frei, Andreas
   Alberti, Simon
   Kusebauch, Ulrike
   Wollscheid, Bernd
   Moritz, Robert L.
   Beyer, Andreas
   Aebersold, Ruedi
TI A complete mass-spectrometric map of the yeast proteome applied to quantitative trait analysis
SO NATURE
LA English
DT Article
ID saccharomyces-cerevisiae; peptide identification; budding yeast; expression; prediction; library; proteins; sequence; tandem; assays
AB Experience from different fields of life sciences suggests that accessible, complete reference maps of the components of the system under study are highly beneficial research tools. Examples of such maps include libraries of the spectroscopic properties of molecules, or databases of drug structures in analytical or forensic chemistry. Such maps, and methods to navigate them, constitute reliable assays to probe any sample for the presence and amount of molecules contained in the map. So far, attempts to generate such maps for any proteome have failed to reach complete proteome coverage(1-3). Here we use a strategy based on high-throughput peptide synthesis and mass spectrometry to generate an almost complete reference map (97% of the genome-predicted proteins) of the Saccharomyces cerevisiae proteome. We generated two versions of this mass-spectrometric map, one supporting discovery-driven (shotgun)(3,4) and the other supporting hypothesis-driven (targeted)(5,6) proteomic measurements. Together, the two versions of the map constitute a complete set of proteomic assays to support most studies performed with contemporary proteomic technologies. To show the utility of the maps, we applied them to a protein quantitative trait locus (QTL) analysis(7), which requires precise measurement of the same set of peptides over a large number of samples. Protein measurements over 78 S. cerevisiae strains revealed a complex relationship between independent genetic loci, influencing the levels of related proteins. Our results suggest that selective pressure favours the acquisition of sets of polymorphisms that adapt protein levels but also maintain the stoichiometry of functionally related pathway members.
C1 [Picotti, Paola; Roest, Hannes; Rinner, Oliver; Reiter, Lukas; Shen, Qin; Frei, Andreas; Wollscheid, Bernd; Aebersold, Ruedi] ETH, Inst Mol Syst Biol, Dept Biol, CH-8093 Zurich, Switzerland.
   [Picotti, Paola] ETH, Inst Biochem, Dept Biol, CH-8093 Zurich, Switzerland.
   [Clement-Ziza, Mathieu; Michaelson, Jacob J.; Beyer, Andreas] Tech Univ Dresden, Ctr Biotechnol, D-01069 Dresden, Germany.
   [Lam, Henry] Hong Kong Univ Sci & Technol, Dept Chem & Biomol Engn, Hong Kong, Hong Kong, Peoples R China.
   [Lam, Henry] Hong Kong Univ Sci & Technol, Div Biomed Engn, Hong Kong, Hong Kong, Peoples R China.
   [Campbell, David S.; Deutsch, Eric W.; Sun, Zhi; Kusebauch, Ulrike; Moritz, Robert L.] Inst Syst Biol, Seattle, WA 98103 USA.
   [Schmidt, Alexander] Univ Basel, Prote Core Facil Biozentrum, CH-4056 Basel, Switzerland.
   [Rinner, Oliver; Reiter, Lukas] Biognosys AG, CH-8093 Zurich, Switzerland.
   [Shen, Qin] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutr Sci, Shanghai 200031, Peoples R China.
   [Alberti, Simon] Max Planck Inst Mol Cell Biol & Genet, D-01307 Dresden, Germany.
   [Aebersold, Ruedi] Competence Ctr Syst Physiol & Metab Dis, CH-8093 Zurich, Switzerland.
   [Aebersold, Ruedi] Univ Zurich, Fac Sci, CH-8057 Zurich, Switzerland.
C3 Swiss Federal Institutes of Technology Domain; ETH Zurich; Swiss Federal Institutes of Technology Domain; ETH Zurich; Technische Universitat Dresden; Hong Kong University of Science & Technology; Hong Kong University of Science & Technology; Institute for Systems Biology (ISB); University of Basel; Chinese Academy of Sciences; Max Planck Society; University of Zurich
RP Aebersold, R (corresponding author), ETH, Inst Mol Syst Biol, Dept Biol, CH-8093 Zurich, Switzerland.
EM paola.picotti@bc.biol.ethz.ch; andreas.beyer@biotec.tu-dresden.de; aebersold@imsb.biol.ethz.ch
FU ETH Zurich; Swiss National Science Foundation [3100A0-107679]; National Heart, Lung and Blood Institute, National Institutes of Health [N01-HV-28179]; National Science Foundation MRI [0923536]; Luxembourg Centre for Systems Biomedicine; University of Luxembourg; SystemsX.ch; Swiss initiative for systems biology; Foerderungsprofessur grant from the Swiss National Science Foundation [PP00P3_133670]; European Union Seventh Framework Program Reintegration grant [FP7-PEOPLE-2010-RG-277147]; Promedica Stiftung [2-70669-11]; University Grant Council of the Hong Kong Special Administrative Region Government, China [HKUST DAG08/09.EG02]; Klaus Tschira Foundation; European Union FP7 HEALTH grant [HEALTH-F4-2008-223539]; European Research Council [ERC-2008-AdG 233226]; SystemsX.ch, the Swiss Initiative for Systems Biolod; Swiss National Science Foundation (SNF) [PP00P3_133670] Funding Source: Swiss National Science Foundation (SNF); Direct For Biological Sciences; Div Of Biological Infrastructure [0923536] Funding Source: National Science Foundation
NR 30
TC 233
Z9 274
U1 0
U2 195
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 14
PY 2013
VL 494
IS 7436
BP 266
EP 270
DI 10.1038/nature11835
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 092QS
UT WOS:000315137700046
PM 23334424
DA 2026-03-09
ER

PT J
AU Herzberg, C
   Asimow, PD
   Ionov, DA
   Vidito, C
   Jackson, MG
   Geist, D
AF Herzberg, Claude
   Asimow, Paul D.
   Ionov, Dmitri A.
   Vidito, Chris
   Jackson, Matthew G.
   Geist, Dennis
TI Nickel and helium evidence for melt above the core-mantle boundary
SO NATURE
LA English
DT Article
ID partition-coefficients; barberton komatiites; oxidation-state; magma ocean; peridotite; olivine; systematics; garnet; heterogeneity; evolution
AB High He-3/He-4 ratios in some basalts have generally been interpreted as originating in an incompletely degassed lower-mantle source(1-9). This helium source may have been isolated at the core-mantle boundary region since Earth's accretion(4-6). Alternatively, it may have taken part in whole-mantle convection and crust production over the age of the Earth(7-9); if so, it is now either a primitive refugium at the core-mantle boundary(8) or is distributed throughout the lower mantle(7,9). Here we constrain the problem using lavas from Baffin Island, West Greenland, the Ontong Java Plateau, Isla Gorgona and Fernandina (Galapagos). Olivine phenocryst compositions show that these lavas originated from a peridotite source that was about 20 per cent higher in nickel content than in the modern mid-ocean-ridge basalt source. Where data are available, these lavas also have high He-3/He-4. We propose that a less-degassed nickel-rich source formed by core-mantle interaction during the crystallization of a melt-rich layer or basal magma ocean(5,6), and that this source continues to be sampled by mantle plumes. The spatial distribution of this source may be constrained by nickel partitioning experiments at the pressures of the core-mantle boundary.
C1 [Herzberg, Claude; Vidito, Chris] Rutgers State Univ, Dept Earth & Planetary Sci, Piscataway, NJ 08854 USA.
   [Asimow, Paul D.] CALTECH, Pasadena, CA 91125 USA.
   [Ionov, Dmitri A.] Univ St Etienne, Dept Geol, F-42023 St Etienne 2, France.
   [Ionov, Dmitri A.] CNRS, UMR 6524, Lab Magmas & Volcans, F-42023 St Etienne, France.
   [Jackson, Matthew G.] Boston Univ, Dept Earth & Environm, Boston, MA 02215 USA.
   [Geist, Dennis] Univ Idaho, Dept Geol Sci, Moscow, ID 83844 USA.
C3 Rutgers University System; Rutgers University New Brunswick; California Institute of Technology; Universite Jean Monnet; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Earth Sciences & Astronomy (INSU); Universite Clermont Auvergne (UCA); Boston University; University of Idaho
RP Herzberg, C (corresponding author), Rutgers State Univ, Dept Earth & Planetary Sci, 610 Taylor Rd, Piscataway, NJ 08854 USA.
EM herzberg@rci.rutgers.edu
FU French INSU-CNRS; NSF [EAR-1119522, EAR1145271]; Division Of Earth Sciences; Directorate For Geosciences [1119522] Funding Source: National Science Foundation
NR 45
TC 84
Z9 97
U1 5
U2 140
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 17
PY 2013
VL 493
IS 7432
BP 393
EP U134
DI 10.1038/nature11771
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 071TA
UT WOS:000313615900049
PM 23302797
DA 2026-03-09
ER

PT J
AU Wang, XM
   Abraham, S
   McKenzie, JAG
   Jeffs, N
   Swire, M
   Tripathi, VB
   Luhmann, UFO
   Lange, CAK
   Zhai, ZH
   Arthur, HM
   Bainbridge, JWB
   Moss, SE
   Greenwood, J
AF Wang, Xiaomeng
   Abraham, Sabu
   McKenzie, Jenny A. G.
   Jeffs, Natasha
   Swire, Matthew
   Tripathi, Vineeta B.
   Luhmann, Ulrich F. O.
   Lange, Clemens A. K.
   Zhai, Zhenhua
   Arthur, Helen M.
   Bainbridge, James W. B.
   Moss, Stephen E.
   Greenwood, John
TI LRG1 promotes angiogenesis by modulating endothelial TGF-β signalling
SO NATURE
LA English
DT Article
ID oxygen-induced retinopathy; retinal vein occlusion; growth-factor-beta; choroidal neovascularization; pathological angiogenesis; vascular development; basement-membrane; gene-expression; mouse; endoglin
AB Aberrant neovascularization contributes to diseases such as cancer, blindness and atherosclerosis, and is the consequence of inappropriate angiogenic signalling. Although many regulators of pathogenic angiogenesis have been identified, our understanding of this process is incomplete. Here we explore the transcriptome of retinal microvessels isolated from mouse models of retinal disease that exhibit vascular pathology, and uncover an upregulated gene, leucine-rich alpha-2-glycoprotein 1 (Lrg1), of previously unknown function. We show that in the presence of transforming growth factor-beta 1 (TGF-beta 1), LRG1 is mitogenic to endothelial cells and promotes angiogenesis. Mice lacking Lrg1 develop a mild retinal vascular phenotype but exhibit a significant reduction in pathological ocular angiogenesis. LRG1 binds directly to the TGF-beta accessory receptor endoglin, which, in the presence of TGF-beta 1, results in promotion of the pro-angiogenic Smad1/5/8 signalling pathway. LRG1 antibody blockade inhibits this switch and attenuates angiogenesis. These studies reveal a new regulator of angiogenesis that mediates its effect by modulating TGF-beta signalling.
C1 [Wang, Xiaomeng; Abraham, Sabu; McKenzie, Jenny A. G.; Jeffs, Natasha; Swire, Matthew; Tripathi, Vineeta B.; Moss, Stephen E.; Greenwood, John] UCL Inst Ophthalmol, Dept Cell Biol, London EC1V 9EL, England.
   [Luhmann, Ulrich F. O.; Lange, Clemens A. K.; Bainbridge, James W. B.] UCL Inst Ophthalmol, Dept Genet, London EC1V 9EL, England.
   [Lange, Clemens A. K.; Bainbridge, James W. B.] Moorfields Eye Hosp, NIHR Biomed Res Ctr Ophthalmol, London EC1V 2PD, England.
   [Lange, Clemens A. K.] Univ Eye Hosp Freiburg, D-79106 Freiburg, Germany.
   [Zhai, Zhenhua; Arthur, Helen M.] Newcastle Univ, Inst Med Genet, Newcastle Upon Tyne NE1 3BZ, Tyne & Wear, England.
C3 University of London; University College London; University of London; University College London; University of London; University College London; Moorfields Eye Hospital NHS Foundation Trust; University of Freiburg; Newcastle University - UK
RP Greenwood, J (corresponding author), UCL Inst Ophthalmol, Dept Cell Biol, London EC1V 9EL, England.
EM s.moss@ucl.ac.uk; j.greenwood@ucl.ac.uk
FU Lowy Medical Research Foundation; Medical Research Council; Wellcome Trust; UCL Business (Proof of Concept Grant); Rosetrees Trust; NIHR Research Professorship; British Heart Foundation Senior Fellowship; MRC [G1000466, G0902206] Funding Source: UKRI; British Heart Foundation [RG/12/2/29416] Funding Source: researchfish; Medical Research Council [G1000466, G0902206] Funding Source: researchfish; National Institute for Health Research [NIHR-RP-011-003] Funding Source: researchfish
NR 46
TC 441
Z9 499
U1 0
U2 149
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 18
PY 2013
VL 499
IS 7458
BP 306
EP +
DI 10.1038/nature12345
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 184RJ
UT WOS:000321910700029
PM 23868260
DA 2026-03-09
ER

PT J
AU Lloyd, KG
   Schreiber, L
   Petersen, DG
   Kjeldsen, KU
   Lever, MA
   Steen, AD
   Stepanauskas, R
   Richter, M
   Kleindienst, S
   Lenk, S
   Schramm, A
   Jorgensen, BB
AF Lloyd, Karen G.
   Schreiber, Lars
   Petersen, Dorthe G.
   Kjeldsen, Kasper U.
   Lever, Mark A.
   Steen, Andrew D.
   Stepanauskas, Ramunas
   Richter, Michael
   Kleindienst, Sara
   Lenk, Sabine
   Schramm, Andreas
   Jorgensen, Bo Barker
TI Predominant archaea in marine sediments degrade detrital proteins
SO NATURE
LA English
DT Article
ID aarhus bay; rna genes; one-cell; bacteria; genome; quantification; clostripain; metagenome; indicators; phylogeny
AB Half of the microbial cells in the Earth's oceans are found in sediments(1). Many of these cells are members of the Archaea(2), single-celled prokaryotes in a domain of life separate from Bacteria and Eukaryota. However, most of these archaea lack cultured representatives, leaving their physiologies and placement on the tree of life uncertain. Here we show that the uncultured miscellaneous crenar-chaeotal group (MCG) and marine benthic group-D (MBG-D) are among the most numerous archaea in the marine sub-sea floor. Single-cell genomic sequencing of one cell of MCG and three cells of MBG-D indicated that they form new branches basal to the archaeal phyla Thaumarchaeota(3) and Aigarchaeota(4), for MCG, and the order Thermoplasmatales, for MBG-D. All four cells encoded extracellular protein-degrading enzymes such as gingipain and clostripain that are known to be effective in environments chemically similar to marine sediments. Furthermore, we found these two types of peptidase to be abundant and active in marine sediments, indicating that uncultured archaea may have a previously undiscovered role in protein remineralization in anoxic marine sediments.
C1 [Lloyd, Karen G.; Schreiber, Lars; Petersen, Dorthe G.; Kjeldsen, Kasper U.; Lever, Mark A.; Schramm, Andreas; Jorgensen, Bo Barker] Aarhus Univ, Dept Biosci, Ctr Geomicrobiol, DK-8000 Aarhus, Denmark.
   [Lloyd, Karen G.; Steen, Andrew D.] Univ Tennessee, Knoxville, TN 37996 USA.
   [Stepanauskas, Ramunas] Bigelow Lab Ocean Sci, East Boothbay, ME 04544 USA.
   [Richter, Michael] Ribocon GmbH, D-28359 Bremen, Germany.
   [Kleindienst, Sara; Lenk, Sabine] Max Planck Inst Marine Microbiol, D-28359 Bremen, Germany.
C3 Aarhus University; University of Tennessee System; University of Tennessee Knoxville; Bigelow Laboratory for Ocean Sciences; Max Planck Society
RP Lloyd, KG (corresponding author), Aarhus Univ, Dept Biosci, Ctr Geomicrobiol, DK-8000 Aarhus, Denmark.
EM klloyd@utk.edu
FU Danish National Research Foundation; German Max Planck Society; NSF Center for Dark Energy Biosphere Investigations [NSF-157595]; Danish Council for Independent Research-Natural Sciences; Villum Kann Rasmussen Foundation; EU Marie Curie fellowship; German Research Foundation; USA National Science Foundation [EF-826924, OCE-821374, OCE-1019242]; Directorate For Geosciences; Division Of Ocean Sciences [1232982] Funding Source: National Science Foundation; Div Of Biological Infrastructure; Direct For Biological Sciences [1226726] Funding Source: National Science Foundation
NR 60
TC 432
Z9 490
U1 4
U2 291
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 11
PY 2013
VL 496
IS 7444
BP 215
EP +
DI 10.1038/nature12033
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 122VM
UT WOS:000317346300040
PM 23535597
DA 2026-03-09
ER

PT J
AU Rhinn, H
   Fujita, R
   Qiang, L
   Cheng, R
   Lee, JH
   Abeliovich, A
AF Rhinn, Herve
   Fujita, Ryousuke
   Qiang, Liang
   Cheng, Rong
   Lee, Joseph H.
   Abeliovich, Asa
TI RETRACTED: Integrative genomics identifies APOE ε4 effectors in Alzheimer's disease (Retracted article. See vol. 523, 2015)
SO NATURE
LA English
DT Article; Retracted Publication
ID amyloid precursor protein; apolipoprotein-e; wide association; common variants; beta-secretase; expression; onset; risk; receptor-2; metabolism
AB Late-onset Alzheimer's disease (LOAD) risk is strongly influenced by genetic factors such as the presence of the apolipoprotein E epsilon 4 allele (referred to here as APOE4), as well as non-genetic determinants including ageing. To pursue mechanisms by which these affect human brain physiology and modify LOAD risk, we initially analysed whole-transcriptome cerebral cortex gene expression data in unaffected APOE4 carriers and LOAD patients. APOE4 carrier status was associated with a consistent transcriptomic shift that broadly resembled the LOAD profile. Differential co-expression correlation network analysis of the APOE4 and LOAD transcriptomic changes identified a set of candidate core regulatory mediators. Several of these-including APBA2, FYN, RNF219 and SV2A-encode known or novel modulators of LOAD associated amyloid beta A4 precursor protein (APP) endocytosis and metabolism. Furthermore, a genetic variant within RNF219 was found to affect amyloid deposition in human brain and LOAD age-of-onset. These data implicate an APOE4 associated molecular pathway that promotes LOAD.
C1 [Rhinn, Herve; Fujita, Ryousuke; Qiang, Liang; Abeliovich, Asa] Columbia Univ, Dept Pathol, New York, NY 10032 USA.
   [Rhinn, Herve; Fujita, Ryousuke; Qiang, Liang; Abeliovich, Asa] Columbia Univ, Dept Cell Biol, New York, NY 10032 USA.
   [Rhinn, Herve; Fujita, Ryousuke; Qiang, Liang; Abeliovich, Asa] Columbia Univ, Dept Neurol, New York, NY 10032 USA.
   [Rhinn, Herve; Fujita, Ryousuke; Qiang, Liang; Cheng, Rong; Lee, Joseph H.; Abeliovich, Asa] Columbia Univ, Taub Inst Alzheimers Dis & Aging Brain, New York, NY 10032 USA.
   [Lee, Joseph H.] Columbia Univ, Gertrude H Sergievsky Ctr, New York, NY 10032 USA.
   [Lee, Joseph H.] Columbia Univ, Dept Epidemiol, New York, NY 10032 USA.
C3 Columbia University; Columbia University; Columbia University; Columbia University; Columbia University; Columbia University
RP Abeliovich, A (corresponding author), Columbia Univ, Dept Pathol, 650 W 168th St, New York, NY 10032 USA.
EM aa900@columbia.edu
FU National Institutes of Health (NIH) [R01AG042317, R01NS064433]; Alzheimer's Disease Neuroimaging Initiative (ADNI) (NIH) [U01 AG024904]; National Institute on Aging; National Institute of Biomedical Imaging and Bioengineering; Canadian Institutes of Health Research; NIH [P30 AG010129, K01 AG030514];  [R37 AG015473];  [R01 MH084995]
NR 57
TC 116
Z9 141
U1 3
U2 117
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 1
PY 2013
VL 500
IS 7460
BP 45
EP U62
DI 10.1038/nature12415
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 192VK
UT WOS:000322514800024
PM 23883936
DA 2026-03-09
ER

PT J
AU Jiang, HC
   Block, MS
   Mishmash, RV
   Garrison, JR
   Sheng, DN
   Motrunich, OI
   Fisher, MPA
AF Jiang, Hong-Chen
   Block, Matthew S.
   Mishmash, Ryan V.
   Garrison, James R.
   Sheng, D. N.
   Motrunich, Olexei I.
   Fisher, Matthew P. A.
TI Non-Fermi-liquid d-wave metal phase of strongly interacting electrons
SO NATURE
LA English
DT Article
ID valence-bond state; quantum renormalization-groups; superconductivity; physics; transport; diagram; system; model
AB Developing a theoretical framework for conducting electronic fluids qualitatively distinct from those described by Landau's Fermi-liquid theory is of central importance to many outstanding problems in condensed matter physics. One such problem is that, above the transition temperature and near optimal doping, high-transition-temperature copper-oxide superconductors exhibit 'strange metal' behaviour that is inconsistent with being a traditional Landau Fermi liquid. Indeed, a microscopic theory of a strange-metal quantum phase could shed new light on the interesting low-temperature behaviour in the pseudogap regime and on the d-wave superconductor itself. Here we present a theory for a specific example of a strange metal-the 'd-wave metal'. Using variational wavefunctions, gauge theoretic arguments, and ultimately large-scale density matrix renormalization group calculations, we show that this remarkable quantum phase is the ground state of a reasonable microscopic Hamiltonian-the usual t-J model with electron kinetic energy t and two-spin exchange J supplemented with a frustrated electron 'ring-exchange' term, which we here examine extensively on the square lattice two-leg ladder. These findings constitute an explicit theoretical example of a genuine non-Fermi-liquid metal existing as the ground state of a realistic model.
C1 [Mishmash, Ryan V.; Garrison, James R.; Fisher, Matthew P. A.] Univ Calif Santa Barbara, Dept Phys, Santa Barbara, CA 93106 USA.
   [Jiang, Hong-Chen] Univ Calif Santa Barbara, Kavli Inst Theoret Phys, Santa Barbara, CA 93106 USA.
   [Block, Matthew S.] Univ Kentucky, Dept Phys & Astron, Lexington, KY 40506 USA.
   [Sheng, D. N.] Calif State Univ Northridge, Dept Phys & Astron, Northridge, CA 91330 USA.
   [Motrunich, Olexei I.] CALTECH, Dept Phys, Pasadena, CA 91125 USA.
C3 University of California System; University of California Santa Barbara; University of California System; University of California Santa Barbara; University of Kentucky; California State University System; California State University Northridge; California Institute of Technology
RP Mishmash, RV (corresponding author), Univ Calif Santa Barbara, Dept Phys, Santa Barbara, CA 93106 USA.
EM mishmash@physics.ucsb.edu
FU NSF under the KITP [PHY05-51164]; MRSEC [DMR-1121053]; NSF [DMR-1101912, DMR-1056536, DMR-0906816, DMR-1205734, DMR-0907145, CNS-0960316]; Caltech Institute of Quantum Information and Matter, an NSF Physics Frontiers Center; Gordon and Betty Moore Foundation; Center for Scientific Computing from the CNSI, MRL: an NSF MRSEC [DMR-1121053]; Direct For Computer & Info Scie & Enginr; Division Of Computer and Network Systems [0960316] Funding Source: National Science Foundation; Direct For Mathematical & Physical Scien [1101912] Funding Source: National Science Foundation; Direct For Mathematical & Physical Scien; Division Of Materials Research [0906816] Funding Source: National Science Foundation; Direct For Mathematical & Physical Scien; Division Of Physics [1125565] Funding Source: National Science Foundation; Division Of Materials Research [1101912] Funding Source: National Science Foundation; Division Of Materials Research; Direct For Mathematical & Physical Scien [1205734] Funding Source: National Science Foundation
NR 50
TC 65
Z9 72
U1 2
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 JAN 3
PY 2013
VL 493
IS 7430
BP 39
EP 44
DI 10.1038/nature11732
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 062QC
UT WOS:000312933800026
PM 23254935
DA 2026-03-09
ER

PT J
AU Mante, V
   Sussillo, D
   Shenoy, KV
   Newsome, WT
AF Mante, Valerio
   Sussillo, David
   Shenoy, Krishna V.
   Newsome, William T.
TI Context-dependent computation by recurrent dynamics in prefrontal cortex
SO NATURE
LA English
DT Article
ID perceptual decision; parietal cortex; area mt; attention; memory; selection; model
AB Prefrontal cortex is thought to have a fundamental role in flexible, context-dependent behaviour, but the exact nature of the computations underlying this role remains largely unknown. In particular, individual prefrontal neurons often generate remarkably complex responses that defy deep understanding of their contribution to behaviour. Here we study prefrontal cortex activity in macaque monkeys trained to flexibly select and integrate noisy sensory inputs towards a choice. We find that the observed complexity and functional roles of single neurons are readily understood in the framework of a dynamical process unfolding at the level of the population. The population dynamics can be reproduced by a trained recurrent neural network, which suggests a previously unknown mechanism for selection and integration of task-relevant inputs. This mechanism indicates that selection and integration are two aspects of a single dynamical process unfolding within the same prefrontal circuits, and potentially provides a novel, general framework for understanding context-dependent computations.
C1 [Mante, Valerio; Newsome, William T.] Stanford Univ, Howard Hughes Med Inst, Stanford, CA 94305 USA.
   [Mante, Valerio; Shenoy, Krishna V.; Newsome, William T.] Stanford Univ, Dept Neurobiol, Stanford, CA 94305 USA.
   [Sussillo, David; Shenoy, Krishna V.] Stanford Univ, Dept Elect Engn, Stanford, CA 94305 USA.
   [Sussillo, David; Shenoy, Krishna V.] Stanford Univ, Neurosci Program, Stanford, CA 94305 USA.
   [Shenoy, Krishna V.] Stanford Univ, Dept Bioengn, Stanford, CA 94305 USA.
C3 Howard Hughes Medical Institute; Stanford University; Stanford University; Stanford University; Stanford University; Stanford University
RP Mante, V (corresponding author), Univ Zurich, ETH Zurich, Inst Neuroinformat, CH-8057 Zurich, Switzerland.
EM valerio@ini.phys.ethz.ch; sussillo@stanford.edu
FU HHMI; Air Force Research Laboratory [FA9550-07-1-0537]; NIH Director's Pioneer Award [1DP1OD006409]; DARPA REPAIR [N66001-10-C-2010]
NR 50
TC 1164
Z9 1429
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 NOV 7
PY 2013
VL 503
IS 7474
BP 78
EP +
DI 10.1038/nature12742
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 247AS
UT WOS:000326585600035
PM 24201281
DA 2026-03-09
ER

PT J
AU Chandra, V
   Huang, PX
   Potluri, N
   Wu, DL
   Kim, YC
   Rastinejad, F
AF Chandra, Vikas
   Huang, Pengxiang
   Potluri, Nalini
   Wu, Dalei
   Kim, Youngchang
   Rastinejad, Fraydoon
TI Multidomain integration in the structure of the HNF-4α nuclear receptor complex
SO NATURE
LA English
DT Article
ID ligand-binding domain; ppar-gamma-rxr; transcription factors; dna-binding; hyperinsulinemic hypoglycemia; phosphorylation; identification; mutations; elements; hnf4a
AB The hepatocyte nuclear factor 4 alpha (HNF-4 alpha; also known as NR2A1) is a member of the nuclear receptor (NR) family of transcription factors, which have conserved DNA-binding domains and ligand-binding domains(1,2). HNF-4 alpha is the most abundant DNA-binding protein in the liver, where some 40% of the actively transcribed genes have a HNF-4 alpha response element(1,3,4). These regulated genes are largely involved in the hepatic gluconeogenic program and lipid metabolism(3,5,6). In the pancreas HNF-4 alpha is also a master regulator, controlling an estimated 11% of islet genes(7). HNF-4 alpha protein mutations are linked to maturity-onset diabetes of the young, type 1 (MODY1) and hyperinsulinaemic hypoglycaemia(8-11). Previous structural analyses of NRs, although productive in elucidating the structure of individual domains, have lagged behind in revealing the connectivity patterns of NR domains. Here we describe the 2.9 angstrom crystal structure of the multidomain human HNF-4 alpha homodimer bound to its DNA response element and coactivatorderived peptides. A convergence zone connects multiple receptor domains in an asymmetric fashion, joining distinct elements from each monomer. An arginine target of PRMT1 methylation protrudes directly into this convergence zone and sustains its integrity. A serine target of protein kinase C is also responsible for maintaining domain-domain interactions. These post-translational modifications lead to changes in DNA binding by communicating through the tightly connected surfaces of the quaternary fold. We find that some MODY1 mutations, positioned on the ligand-binding domain and hinge regions of the receptor, compromise DNA binding at a distance by communicating through the interjunctional surfaces of the complex. The overall domain representation of the HNF-4 alpha homodimer is different from that of the PPAR-gamma-RXR-alpha heterodimer, even when both NR complexes are assembled on the same DNA element. Our findings suggest that unique quaternary folds and interdomain connections in NRs could be exploited by small-molecule allosteric modulators that affect distal functions in these polypeptides.
C1 [Chandra, Vikas; Huang, Pengxiang; Potluri, Nalini; Wu, Dalei; Rastinejad, Fraydoon] Sanford Burnham Med Res Inst, Metab Signaling & Dis Program, Orlando, FL 32827 USA.
   [Kim, Youngchang] Argonne Natl Lab, Struct Biol Ctr, Biosci Div, Argonne, IL 60439 USA.
C3 Sanford Burnham Prebys Medical Discovery Institute; United States Department of Energy (DOE); Argonne National Laboratory
RP Rastinejad, F (corresponding author), Sanford Burnham Med Res Inst, Metab Signaling & Dis Program, Orlando, FL 32827 USA.
EM frastinejad@sanfordburnham.org
FU National Institutes of Health [R01 DK094147, R01 DK097475]
NR 28
TC 176
Z9 207
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 MAR 21
PY 2013
VL 495
IS 7441
BP 394
EP 398
DI 10.1038/nature11966
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 113EY
UT WOS:000316650500048
PM 23485969
DA 2026-03-09
ER

PT J
AU Canzio, D
   Liao, MF
   Naber, N
   Pate, E
   Larson, A
   Wu, SP
   Marina, DB
   Garcia, JF
   Madhani, HD
   Cooke, R
   Schuck, P
   Cheng, YF
   Narlikar, GJ
AF Canzio, Daniele
   Liao, Maofu
   Naber, Nariman
   Pate, Edward
   Larson, Adam
   Wu, Shenping
   Marina, Diana B.
   Garcia, Jennifer F.
   Madhani, Hiten D.
   Cooke, Roger
   Schuck, Peter
   Cheng, Yifan
   Narlikar, Geeta J.
TI A conformational switch in HP1 releases auto-inhibition to drive heterochromatin assembly
SO NATURE
LA English
DT Article
ID histone h3; shadow domain; self-association; family proteins; lysine 9; chromodomain; methylation; particle; binding; visualization
AB A hallmark of histone H3 lysine 9 (H3K9)-methylated heterochromatin, conserved from the fission yeast Schizosaccharomyces pombe to humans, is its ability to spread to adjacent genomic regions(1-6). Central to heterochromatin spread is heterochromatin protein 1 (HP1), which recognizes H3K9-methylated chromatin, oligomerizes and forms a versatile platform that participates in diverse nuclear functions, ranging from gene silencing to chromosome segregation(1-6). How HP1 proteins assemble on methylated nucleosomal templates and how the HP1-nucleosome complex achieves functional versatility remain poorly understood. Here we show that binding of the key S. pombe HP1 protein, Swi6, to methylated nucleosomes drives a switch from an auto-inhibited state to a spreading-competent state. In the auto-inhibited state, a histonemimic sequence in one Swi6 monomer blocks methyl-mark recognition by the chromodomain of another monomer. Auto-inhibition is relieved by recognition of two template features, the H3K9 methyl mark and nucleosomal DNA. Cryo-electron-microscopy-based reconstruction of the Swi6-nucleosome complex provides the overall architecture of the spreading-competent state in which two unbound chromodomain sticky ends appear exposed. Disruption of the switch between the auto-inhibited and spreading-competent states disrupts heterochromatin assembly and gene silencing in vivo. These findings are reminiscent of other conditionally activated polymerization processes, such as actin nucleation, and open up a new class of regulatory mechanisms that operate on chromatin in vivo.
C1 [Canzio, Daniele; Liao, Maofu; Naber, Nariman; Larson, Adam; Wu, Shenping; Marina, Diana B.; Garcia, Jennifer F.; Madhani, Hiten D.; Cooke, Roger; Cheng, Yifan; Narlikar, Geeta J.] Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94158 USA.
   [Canzio, Daniele] Univ Calif San Francisco, Chem & Chem Biol Grad Program, San Francisco, CA 94158 USA.
   [Pate, Edward] Washington State Univ, Voiland Sch Chem Engn & Bioengn, Pullman, WA 99164 USA.
   [Larson, Adam; Marina, Diana B.; Garcia, Jennifer F.] Univ Calif San Francisco, Tetrad Grad Program, San Francisco, CA 94158 USA.
   [Schuck, Peter] Nat Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD 20892 USA.
C3 University of California System; University of California San Francisco; University of California System; University of California San Francisco; Washington State University; University of California System; University of California San Francisco; National Institutes of Health (NIH) - USA; NIH National Institute of Biomedical Imaging & Bioengineering (NIBIB)
RP Narlikar, GJ (corresponding author), Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94158 USA.
EM geeta.narlikar@ucsf.edu
FU Hillblom foundation; American Cancer Society; Leukemia and Lymphoma Society; National Institutes of Health (NIH) [R01GM071801, AR053720]; UCSF Program for Breakthrough Biomedical Research; NIBIB, NIH; National Institute of General Medical Sciences [R01GM071801] Funding Source: NIH RePORTER
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NR 40
TC 124
Z9 154
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 APR 18
PY 2013
VL 496
IS 7445
BP 377
EP +
DI 10.1038/nature12032
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 126FV
UT WOS:000317599200041
PM 23485968
DA 2026-03-09
ER

PT J
AU Xing, WM
   Busino, L
   Hinds, TR
   Marionni, ST
   Saifee, NH
   Bush, MF
   Pagano, M
   Zheng, N
AF Xing, Weiman
   Busino, Luca
   Hinds, Thomas R.
   Marionni, Samuel T.
   Saifee, Nabiha H.
   Bush, Matthew F.
   Pagano, Michele
   Zheng, Ning
TI SCFFBXL3 ubiquitin ligase targets cryptochromes at their cofactor pocket
SO NATURE
LA English
DT Article
ID circadian clock; crystal-structure; mammalian cry1; photolyase; mechanism; phosphorylation; identification; coordination; degradation; oscillation
AB The cryptochrome (CRY) flavoproteins act as blue-light receptors in plants and insects, but perform light-independent functions at the core of the mammalian circadian clock. To drive clock oscillations, mammalian CRYs associate with the Period proteins (PERs) and together inhibit the transcription of their own genes. The SCFFBXL3 ubiquitin ligase complex controls this negative feedback loop by promoting CRY ubiquitination and degradation. However, the molecular mechanisms of their interactions and the functional role of flavin adenine dinucleotide (FAD) binding in CRYs remain poorly understood. Here we report crystal structures of mammalian CRY2 in its apo, FAD-bound and FBXL3-SKP1-complexed forms. Distinct from other cryptochromes of known structures, mammalian CRY2 binds FAD dynamically with an open cofactor pocket. Notably, the F-box protein FBXL3 captures CRY2 by simultaneously occupying its FAD-binding pocket with a conserved carboxy-terminal tail and burying its PER-binding interface. This novel F-box-protein-substrate bipartite interaction is susceptible to disruption by both FAD and PERs, suggesting a new avenue for pharmacological targeting of the complex and a multifaceted regulatory mechanism of CRY ubiquitination.
C1 [Xing, Weiman; Hinds, Thomas R.; Saifee, Nabiha H.; Zheng, Ning] Univ Washington, Dept Pharmacol, Seattle, WA 98195 USA.
   [Xing, Weiman; Zheng, Ning] Univ Washington, Howard Hughes Med Inst, Seattle, WA 98195 USA.
   [Busino, Luca; Pagano, Michele] NYU, Sch Med, Dept Pathol, NYU Canc Inst, New York, NY 10016 USA.
   [Marionni, Samuel T.; Bush, Matthew F.] Univ Washington, Dept Chem, Seattle, WA 98195 USA.
   [Pagano, Michele] NYU, Sch Med, Howard Hughes Med Inst, New York, NY 10016 USA.
C3 University of Washington; University of Washington Seattle; University of Washington; University of Washington Seattle; Howard Hughes Medical Institute; New York University; University of Washington; University of Washington Seattle; Howard Hughes Medical Institute; New York University
RP Zheng, N (corresponding author), Univ Washington, Dept Pharmacol, Box 357280, Seattle, WA 98195 USA.
EM nzheng@u.washington.edu
FU Howard Hughes Medical Institute; National Institutes of Health [R01-CA107134, 5T32-HL007151, R01-GM057587, R37-CA-076584, R21-CA161108]; University of Washington
NR 42
TC 192
Z9 238
U1 0
U2 89
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 4
PY 2013
VL 496
IS 7443
BP 64
EP +
DI 10.1038/nature11964
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 117ZZ
UT WOS:000316993400025
PM 23503662
DA 2026-03-09
ER

PT J
AU Tedeschi, A
   Wutz, G
   Huet, S
   Jaritz, M
   Wuensche, A
   Schirghuber, E
   Davidson, IF
   Tang, W
   Cisneros, DA
   Bhaskara, V
   Nishiyama, T
   Vaziri, A
   Wutz, A
   Ellenberg, J
   Peters, JM
AF Tedeschi, Antonio
   Wutz, Gordana
   Huet, Sebastien
   Jaritz, Markus
   Wuensche, Annelie
   Schirghuber, Erika
   Davidson, Iain Finley
   Tang, Wen
   Cisneros, David A.
   Bhaskara, Venugopal
   Nishiyama, Tomoko
   Vaziri, Alipasha
   Wutz, Anton
   Ellenberg, Jan
   Peters, Jan-Michael
TI Wapl is an essential regulator of chromatin structure and chromosome segregation
SO NATURE
LA English
DT Article
ID cohesin; protein; expression; separase; anaphase; binding; mice; organization; centromeres; interphase
AB Mammalian genomes contain several billion base pairs of DNA that are packaged in chromatin fibres. At selected gene loci, cohesin complexes have been proposed to arrange these fibres into higher-order structures(1-7), but how important this function is for determining overall chromosome architecture and how the process is regulated are not well understood. Using conditional mutagenesis in the mouse, here we show that depletion of the cohesin-associated protein Wapl(8,9) stably locks cohesin on DNA, leads to clustering of cohesin in axial structures, and causes chromatin condensation in interphase chromosomes. These findings reveal that the stability of cohesin-DNA interactions is an important determinant of chromatin structure, and indicate that cohesin has an architectural role in interphase chromosome territories. Furthermore, we show that regulation of cohesin-DNA interactions by Wapl is important for embryonic development, expression of genes such as c-myc (also known as Myc), and cell cycle progression. In mitosis, Wapl-mediated release of cohesin from DNA is essential for proper chromosome segregation and protects cohesin from cleavage by the protease separase, thus enabling mitotic exit in the presence of functional cohesin complexes.
C1 [Tedeschi, Antonio; Wutz, Gordana; Jaritz, Markus; Schirghuber, Erika; Davidson, Iain Finley; Tang, Wen; Cisneros, David A.; Bhaskara, Venugopal; Nishiyama, Tomoko; Vaziri, Alipasha; Wutz, Anton; Peters, Jan-Michael] Res Inst Mol Pathol IMP, A-1030 Vienna, Austria.
   [Huet, Sebastien; Wuensche, Annelie; Ellenberg, Jan] European Mol Biol Lab, Cell Biol & Biophys Unit, D-69117 Heidelberg, Germany.
   [Huet, Sebastien] Inst Genet & Dev Rennes, CNRS, UMR 6290, F-35043 Rennes, France.
   [Huet, Sebastien] Univ Europeenne Bretagne, Univ Rennes 1, Struct Federat Rech Biosit, Fac Med, F-35043 Rennes, France.
   [Cisneros, David A.; Vaziri, Alipasha] Univ Vienna, Max F Perutz Labs, A-1030 Vienna, Austria.
   [Cisneros, David A.; Vaziri, Alipasha] Univ Vienna, Res Platform Quantum Phenomena& Nanoscale Biol Sy, A-1030 Vienna, Austria.
C3 Vienna Biocenter (VBC); Research Institute of Molecular Pathology (IMP); European Molecular Biology Laboratory (EMBL); Universite de Rennes; 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 Bretagne Occidentale; Universite de Rennes; Institut National de la Sante et de la Recherche Medicale (Inserm); Vienna Biocenter (VBC); Max F. Perutz Laboratories (MFPL); University of Vienna; University of Vienna
RP Peters, JM (corresponding author), Res Inst Mol Pathol IMP, Dr Bohr Gasse 7, A-1030 Vienna, Austria.
EM jan-michael.peters@imp.ac.at
FU European Molecular Biology Organization (EMBO); Japanese Society for the Promotion of Science (JSPS); Agence National de la Recherche [JCJC-SVSE2-2011]; European Union [FP7-PEOPLE-2011-CIG]; MFPL VIPS Program (BMWF); MFPL VIPS Program (City of Vienna); Vienna Science and Technology Fund (WWTF) [VRG10-11]; Research Platform Quantum Phenomena and Nanoscale Biological Systems (QuNaBioS); Boehringer Ingelheim; Austrian Science Fund (FWF) [SFB F34, Z196-B20]; Austrian Research Promotion Agency (FFG, Laura Bassi Center for Optimized Structural Studies); Vienna Science and Technology Fund [WWTF LS09-13]; European Community [241548 (MitoSys)]; Grants-in-Aid for Scientific Research [25711002] Funding Source: KAKEN
NR 45
TC 266
Z9 319
U1 2
U2 56
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 26
PY 2013
VL 501
IS 7468
BP 564
EP +
DI 10.1038/nature12471
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 223RP
UT WOS:000324826300062
PM 23975099
DA 2026-03-09
ER

PT J
AU Wilson, AM
   Lowe, JC
   Roskilly, K
   Hudson, PE
   Golabek, KA
   McNutt, JW
AF Wilson, A. M.
   Lowe, J. C.
   Roskilly, K.
   Hudson, P. E.
   Golabek, K. A.
   McNutt, J. W.
TI Locomotion dynamics of hunting in wild cheetahs
SO NATURE
LA English
DT Article
ID acinonyx-jubatus; functional-anatomy; running speed; limitations; ecology; gps
AB Although the cheetah is recognised as the fastest land animal, little is known about other aspects of its notable athleticism, particularly when hunting in the wild. Here we describe and use a new tracking collar of our own design, containing a combination of Global Positioning System (GPS) and inertial measurement units, to capture the locomotor dynamics and outcome of 367 predominantly hunting runs of five wild cheetahs in Botswana. A remarkable top speed of 25.9 ms(-1) (58 m.p.h. or 93 km h(-1)) was recorded, but most cheetah hunts involved only moderate speeds. We recorded some of the highest measured values for lateral and forward acceleration, deceleration and body-mass-specific power for any terrestrial mammal. To our knowledge, this is the first detailed locomotor information on the hunting dynamics of a large cursorial predator in its natural habitat.
C1 [Wilson, A. M.; Lowe, J. C.; Roskilly, K.; Hudson, P. E.] Univ London, Royal Vet Coll, Struct & Mot Lab, Hatfield AL9 7TA, Herts, England.
   [Golabek, K. A.; McNutt, J. W.] Botswana Predator Conservat Trust, Maun, Botswana.
C3 University of London; University of London Royal Veterinary College
RP Wilson, AM (corresponding author), Univ London, Royal Vet Coll, Struct & Mot Lab, Hatfield AL9 7TA, Herts, England.
EM awilson@rvc.ac.uk
FU EPSRC [EP/H013016/1]; BBSRC [BB/J018007/1]; DARPA M3 Program [W91CRB-11-C-0048]; Boston Dynamics; BBSRC [BB/J018007/1] Funding Source: UKRI; EPSRC [EP/H013016/1] Funding Source: UKRI; Biotechnology and Biological Sciences Research Council [BB/J018007/1] Funding Source: researchfish; Engineering and Physical Sciences Research Council [EP/H013016/1] Funding Source: researchfish
NR 32
TC 296
Z9 343
U1 7
U2 384
PU NATURE PUBLISHING 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 13
PY 2013
VL 498
IS 7453
BP 185
EP +
DI 10.1038/nature12295
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 162RR
UT WOS:000320283400038
PM 23765495
DA 2026-03-09
ER

PT J
AU Oisi, Y
   Ota, KG
   Kuraku, S
   Fujimoto, S
   Kuratani, S
AF Oisi, Yasuhiro
   Ota, Kinya G.
   Kuraku, Shigehiro
   Fujimoto, Satoko
   Kuratani, Shigeru
TI Craniofacial development of hagfishes and the evolution of vertebrates
SO NATURE
LA English
DT Article
ID lethenteron-japonicum; bdellostoma stouti; lampetra-japonica; trigeminal nerve; neural crest; genes; expression; lampreys; adenohypophysis; organization
AB Cyclostomes, the living jawless vertebrates including hagfishes and lampreys, represent the most basal lineage of vertebrates. Although the monophyly of cyclostomes has been supported by recent molecular analyses, the phenotypic traits of hagfishes, especially the lack of some vertebrate-defining features and the reported endodermal origin of the adenohypophysis, have been interpreted as hagfishes exhibiting a more ancestral state than those of all other vertebrates. Furthermore, the adult anatomy of hagfishes cannot be compared easily with that of lampreys. Here we describe the craniofacial development of a series of staged hagfish embryos, which shows that their adenohypophysis arises ectodermally, consistent with the molecular phylogenetic data. This finding also allowed us to identify a pan-cyclostome pattern, one not shared by jawed vertebrates. Comparative analyses indicated that many of the hagfish-specific traits can be explained by changes secondarily introduced into the hagfish lineage. We also propose a possibility that the pan-cyclostome pattern may reflect the ancestral programme for the craniofacial development of all living vertebrates.
C1 [Oisi, Yasuhiro] Kobe Univ, Grad Sch Sci, Dept Biol, Kobe, Hyogo 6578501, Japan.
   [Oisi, Yasuhiro; Fujimoto, Satoko; Kuratani, Shigeru] RIKEN Ctr Dev Biol, Lab Evolutionary Morphol, Kobe, Hyogo 6500047, Japan.
   [Ota, Kinya G.] Acad Sinica, Inst Cellular & Organism Biol, Marine Res Stn, Yilan 26242, Taiwan.
   [Kuraku, Shigehiro] RIKEN Ctr Dev Biol, Genome Resource & Anal Unit, Kobe, Hyogo 6500047, Japan.
C3 Kobe University; RIKEN; Academia Sinica - Taiwan; RIKEN
RP Kuratani, S (corresponding author), RIKEN Ctr Dev Biol, Lab Evolutionary Morphol, Kobe, Hyogo 6500047, Japan.
EM saizo@cdb.riken.jp
FU Grants-in-Aid for Scientific Research [22128003] Funding Source: KAKEN
NR 50
TC 110
Z9 120
U1 1
U2 130
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 10
PY 2013
VL 493
IS 7431
BP 175
EP 180
DI 10.1038/nature11794
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 066YY
UT WOS:000313259600030
PM 23254938
DA 2026-03-09
ER

PT J
AU Craig, OE
   Saul, H
   Lucquin, A
   Nishida, Y
   Taché, K
   Clarke, L
   Thompson, A
   Altoft, DT
   Uchiyama, J
   Ajimoto, M
   Gibbs, K
   Isaksson, S
   Heron, CP
   Jordan, P
AF Craig, O. E.
   Saul, H.
   Lucquin, A.
   Nishida, Y.
   Tache, K.
   Clarke, L.
   Thompson, A.
   Altoft, D. T.
   Uchiyama, J.
   Ajimoto, M.
   Gibbs, K.
   Isaksson, S.
   Heron, C. P.
   Jordan, P.
TI Earliest evidence for the use of pottery
SO NATURE
LA English
DT Article
ID archaeological ceramic vessels; japanese islands; east-asia; products; europe; technology; residues; lipids; acids
AB Pottery was a hunter-gatherer innovation that first emerged in East Asia between 20,000 and 12,000 calibrated years before present(1,2) (cal BP), towards the end of the Late Pleistocene epoch, a period of time when humans were adjusting to changing climates and new environments. Ceramic container technologies were one of a range of late glacial adaptations that were pivotal to structuring subsequent cultural trajectories in different regions of the world, but the reasons for their emergence and widespread uptake are poorly understood. The first ceramic containers must have provided prehistoric hunter-gatherers with attractive new strategies for processing and consuming foodstuffs, but virtually nothing is known of how early pots were used. Here we report the chemical analysis of food residues associated with Late Pleistocene pottery, focusing on one of the best-studied prehistoric ceramic sequences in the world, the Japanese Jomon. We demonstrate that lipids can be recovered reliably from charred surface deposits adhering to pottery dating from about 15,000 to 11,800 cal BP (the Incipient Jomon period), the oldest pottery so far investigated, and that in most cases these organic compounds are unequivocally derived from processing freshwater and marine organisms. Stable isotope data support the lipid evidence and suggest that most of the 101 charred deposits analysed, from across the major islands of Japan, were derived from high-trophic-level aquatic food. Productive aquatic ecotones were heavily exploited by late glacial foragers(3), perhaps providing an initial impetus for investment in ceramic container technology, and paving the way for further intensification of pottery use by hunter-gatherers in the early Holocene epoch. Now that we have shown that it is possible to analyse organic residues from some of the world's earliest ceramic vessels, the subsequent development of this critical technology can be clarified through further widespread testing of hunter-gatherer pottery from later periods.
C1 [Craig, O. E.; Saul, H.; Lucquin, A.; Tache, K.; Altoft, D. T.] Univ York, Dept Archaeol, BioArCh, York YO10 5DD, N Yorkshire, England.
   [Saul, H.; Nishida, Y.] Niigata Prefectural Museum Hist, Nagaoka, Niigata 9402035, Japan.
   [Clarke, L.; Heron, C. P.] Univ Bradford, Bradford BD7 1DP, W Yorkshire, England.
   [Clarke, L.] Manchester Metropolitan Univ, Sch Sci & Environm Sci, Div Chem & Environm Sci, Manchester M1 5GD, Lancs, England.
   [Thompson, A.] Univ Liverpool, Sch Environm Sci, Liverpool L69 3GP, Merseyside, England.
   [Uchiyama, J.] Res Inst Humanity & Nat, Kita Ku, Kyoto 6038047, Japan.
   [Ajimoto, M.] Wakasa Hist & Folklore Museum, Obama, Fukui 9170241, Japan.
   [Gibbs, K.] Univ Aberdeen, Dept Archaeol, Aberdeen AB24 3UF, Scotland.
   [Isaksson, S.] Stockholm Univ, Ctr Study Cultural Evolut, SE-10691 Stockholm, Sweden.
   [Isaksson, S.] Stockholm Univ, Dept Archaeol & Class Studies, Archaeol Res Lab, SE-10691 Stockholm, Sweden.
   [Jordan, P.] Univ Groningen, Arctic Ctr, NL-9700 AS Groningen, Netherlands.
C3 University of York - UK; University of Bradford; Manchester Metropolitan University; University of Liverpool; Research Institute for Humanity & Nature (RIHN); University of Aberdeen; Stockholm University; Stockholm University; University of Groningen
RP Craig, OE (corresponding author), Univ York, Dept Archaeol, BioArCh, York YO10 5DD, N Yorkshire, England.
EM oliver.craig@york.ac.uk
FU Leverhulme trust [F/00 152/AM]; Japanese Society for the Promotion of Science [PE 11560]
NR 30
TC 253
Z9 293
U1 4
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 APR 18
PY 2013
VL 496
IS 7445
BP 351
EP 354
DI 10.1038/nature12109
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 126FV
UT WOS:000317599200035
PM 23575637
DA 2026-03-09
ER

PT J
AU DuBois, RM
   Vaney, MC
   Tortorici, MA
   Al Kurdi, R
   Barba-Spaeth, G
   Krey, T
   Rey, FA
AF DuBois, Rebecca M.
   Vaney, Marie-Christine
   Tortorici, M. Alejandra
   Al Kurdi, Rana
   Barba-Spaeth, Giovanna
   Krey, Thomas
   Rey, Felix A.
TI Functional and evolutionary insight from the crystal structure of rubella virus protein E1
SO NATURE
LA English
DT Article
ID borne encephalitis-virus; envelope protein; fusion protein; glycoprotein; receptor; responses; surface; domain; entry; form
AB Little is known about the three-dimensional organization of rubella virus, which causes a relatively mild measles-like disease in children but leads to serious congenital health problems when contracted in utero(1). Although rubella virus belongs to the same family as the mosquito-borne alphaviruses, in many respects it is more similar to other aerosol-transmitted human viruses such as the agents of measles and mumps. Although the use of the triple MMR (measles, mumps and rubella) live vaccine has limited its incidence in western countries, congenital rubella syndrome remains an important health problem in the developing world. Here we report the 1.8 angstrom resolution crystal structure of envelope glycoprotein E1, the main antigen and sole target of neutralizing antibodies against rubella virus. E1 is the main player during entry into target cells owing to its receptor-binding and membrane-fusion functions. The structure reveals the epitope and the neutralization mechanism of an important category of protecting antibodies against rubella infection. It also shows that rubella virus E1 is a class II fusion protein, which had hitherto only been structurally characterized for the arthropod-borne alphaviruses and flaviviruses. In addition, rubella virus E1 has an extensive membrane-fusion surface that includes a metal site, reminiscent of the T-cell immunoglobulin and mucin family of cellular proteins that bind phosphatidylserine lipids at the plasma membrane of cells undergoing apoptosis. Such features have not been seen in any fusion protein crystallized so far. Structural comparisons show that the class II fusion proteins from alphaviruses and flaviviruses, despite belonging to different virus families, are closer to each other than they are to rubella virus E1. This suggests that the constraints on arboviruses imposed by alternating cycles between vertebrates and arthropods resulted in more conservative evolution. By contrast, in the absence of this constraint, the strictly human rubella virus seems to have drifted considerably into a unique niche as sole member of the Rubivirus genus.
C1 [DuBois, Rebecca M.; Vaney, Marie-Christine; Tortorici, M. Alejandra; Al Kurdi, Rana; Barba-Spaeth, Giovanna; Krey, Thomas; Rey, Felix A.] Inst Pasteur, Dept Virol, Unite Virol Struct, F-75724 Paris 15, France.
   [DuBois, Rebecca M.; Vaney, Marie-Christine; Tortorici, M. Alejandra; Al Kurdi, Rana; Barba-Spaeth, Giovanna; Krey, Thomas; Rey, Felix A.] CNRS, URA 3015, F-75724 Paris 15, France.
C3 Pasteur Network; Universite Paris Cite; Institut Pasteur Paris; Centre National de la Recherche Scientifique (CNRS)
RP Rey, FA (corresponding author), Inst Pasteur, Dept Virol, Unite Virol Struct, F-75724 Paris 15, France.
EM rey@pasteur.fr
FU 'Pasteur-Howard' fellowship; Merck-Serono from the French Government [ANR-10-LABX-62-IBEID];  [ANR-05-MIIM-012-02-Dentry]
NR 41
TC 80
Z9 96
U1 2
U2 70
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 24
PY 2013
VL 493
IS 7433
BP 552
EP +
DI 10.1038/nature11741
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 075GF
UT WOS:000313871400042
PM 23292515
DA 2026-03-09
ER

PT J
AU Bennartz, R
   Shupe, MD
   Turner, DD
   Walden, VP
   Steffen, K
   Cox, CJ
   Kulie, MS
   Miller, NB
   Pettersen, C
AF Bennartz, R.
   Shupe, M. D.
   Turner, D. D.
   Walden, V. P.
   Steffen, K.
   Cox, C. J.
   Kulie, M. S.
   Miller, N. B.
   Pettersen, C.
TI July 2012 Greenland melt extent enhanced by low-level liquid clouds
SO NATURE
LA English
DT Article
ID ice-sheet; arctic surface; snow
AB Melting of the world's major ice sheets can affect human and environmental conditions by contributing to sea-level rise. In July 2012, an historically rare period of extended surface melting was observed across almost the entire Greenland ice sheet(1,2), raising questions about the frequency and spatial extent of such events. Here we show that low-level clouds consisting of liquid water droplets ('liquid clouds'), via their radiative effects, played a key part in this melt event by increasing near-surface temperatures. We used a suite of surface-based observations(3), remote sensing data, and a surface energy-balance model. At the critical surface melt time, the clouds were optically thick enough and low enough to enhance the down-welling infrared flux at the surface. At the same time they were optically thin enough to allow sufficient solar radiation to penetrate through them and raise surface temperatures above the melting point. Outside this narrow range in cloud optical thickness, the radiative contribution to the surface energy budget would have been diminished, and the spatial extent of this melting event would have been smaller. We further show that these thin, low-level liquid clouds occur frequently, both over Greenland and across the Arctic, being present around 30-50 per cent of the time(3-6). Our results may help to explain the difficulties that global climate models have in simulating the Arctic surface energy budget(7-9), particularly as models tend to under-predict the formation of optically thin liquid clouds at supercooled temperatures(6)-a process potentially necessary to account fully for temperature feedbacks in a warming Arctic climate.
C1 [Bennartz, R.] Univ Wisconsin, Madison, WI 53706 USA.
   [Shupe, M. D.; Steffen, K.] Univ Colorado, CIRES, Boulder, CO 80305 USA.
   [Shupe, M. D.; Steffen, K.] NOAA, ESRL, Boulder, CO 80305 USA.
   [Turner, D. D.] NOAA, Natl Severe Storms Lab, Norman, OK 73072 USA.
   [Walden, V. P.; Cox, C. J.] Univ Idaho, Dept Geog, Moscow, ID 83844 USA.
   [Steffen, K.] Swiss Fed Res Inst WSL, CH-8903 Birmensdorf, Switzerland.
   [Kulie, M. S.; Miller, N. B.; Pettersen, C.] Univ Wisconsin, Space Sci & Engn Ctr, Madison, WI 53706 USA.
C3 University of Wisconsin System; University of Wisconsin Madison; University of Colorado System; University of Colorado Boulder; National Oceanic Atmospheric Admin (NOAA) - USA; National Oceanic Atmospheric Admin (NOAA) - USA; University of Idaho; Swiss Federal Institutes of Technology Domain; Swiss Federal Institute for Forest, Snow & Landscape Research; University of Wisconsin System; University of Wisconsin Madison
RP Bennartz, R (corresponding author), Univ Wisconsin, Madison, WI 53706 USA.
EM bennartz@aos.wisc.edu
FU US National Science Foundation, Arctic Observing Network (AON) programme [ARC-0904152, 0856773, 0856559]; Directorate For Geosciences; Division Of Polar Programs [0856559] Funding Source: National Science Foundation; Directorate For Geosciences; Office of Polar Programs (OPP) [0904152, 0856773] Funding Source: National Science Foundation; Office of Polar Programs (OPP); Directorate For Geosciences [1303879, 1414314, 1314156, 1304692] Funding Source: National Science Foundation
NR 26
TC 279
Z9 318
U1 0
U2 128
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 4
PY 2013
VL 496
IS 7443
BP 83
EP 86
DI 10.1038/nature12002
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 117ZZ
UT WOS:000316993400029
PM 23552947
DA 2026-03-09
ER

PT J
AU Dean, CR
   Wang, L
   Maher, P
   Forsythe, C
   Ghahari, F
   Gao, Y
   Katoch, J
   Ishigami, M
   Moon, P
   Koshino, M
   Taniguchi, T
   Watanabe, K
   Shepard, KL
   Hone, J
   Kim, P
AF Dean, C. R.
   Wang, L.
   Maher, P.
   Forsythe, C.
   Ghahari, F.
   Gao, Y.
   Katoch, J.
   Ishigami, M.
   Moon, P.
   Koshino, M.
   Taniguchi, T.
   Watanabe, K.
   Shepard, K. L.
   Hone, J.
   Kim, P.
TI Hofstadter's butterfly and the fractal quantum Hall effect in moire superlattices
SO NATURE
LA English
DT Article
ID scanning-tunneling-microscopy; hexagonal boron-nitride; magnetoresistance oscillations; energy-spectrum; magnetic-fields; bloch electrons; graphene; conductance
AB Electrons moving through a spatially periodic lattice potential develop a quantized energy spectrum consisting of discrete Bloch bands. In two dimensions, electrons moving through a magnetic field also develop a quantized energy spectrum, consisting of highly degenerate Landau energy levels. When subject to both a magnetic field and a periodic electrostatic potential, two-dimensional systems of electrons exhibit a self-similar recursive energy spectrum(1). Known as Hofstadter's butterfly, this complex spectrum results from an interplay between the characteristic lengths associated with the two quantizing fields(1-10), and is one of the first quantum fractals discovered in physics. In the decades since its prediction, experimental attempts to study this effect have been limited by difficulties in reconciling the two length scales. Typical atomic lattices (with periodicities of less than one nanometre) require unfeasibly large magnetic fields to reach the commensurability condition, and in artificially engineered structures (with periodicities greater than about 100 nanometres) the corresponding fields are too small to overcome disorder completely(11-17). Here we demonstrate that moire superlattices arising in bilayer graphene coupled to hexagonal boron nitride provide a periodic modulation with ideal length scales of the order of ten nanometres, enabling unprecedented experimental access to the fractal spectrum. We confirm that quantum Hall features associated with the fractal gaps are described by two integer topological quantum numbers, and report evidence of their recursive structure. Observation of a Hofstadter spectrum in bilayer graphene means that it is possible to investigate emergent behaviour within a fractal energy landscape in a system with tunable internal degrees of freedom.
C1 [Dean, C. R.] CUNY, Dept Phys, New York, NY 10031 USA.
   [Wang, L.; Gao, Y.; Hone, J.] Columbia Univ, Dept Mech Engn, New York, NY 10027 USA.
   [Maher, P.; Forsythe, C.; Ghahari, F.; Kim, P.] Columbia Univ, Dept Phys, New York, NY 10027 USA.
   [Katoch, J.; Ishigami, M.] Univ Cent Florida, Dept Phys, Orlando, FL 32816 USA.
   [Katoch, J.; Ishigami, M.] Univ Cent Florida, Nanosci Technol Ctr, Orlando, FL 32816 USA.
   [Moon, P.; Koshino, M.] Tohoku Univ, Dept Phys, Sendai, Miyagi 9808578, Japan.
   [Taniguchi, T.; Watanabe, K.] Natl Inst Mat Sci, Tsukuba, Ibaraki 3050044, Japan.
   [Shepard, K. L.] Columbia Univ, Dept Elect Engn, New York, NY 10027 USA.
C3 City University of New York (CUNY) System; Columbia University; Columbia University; State University System of Florida; University of Central Florida; State University System of Florida; University of Central Florida; Tohoku University; National Institute for Materials Science; Columbia University
RP Kim, P (corresponding author), Columbia Univ, Dept Phys, 538 W 120th St, New York, NY 10027 USA.
EM pk2015@columbia.edu
FU US National Science Foundation [DMR-0654118, 0955625]; State of Florida; US Department of Energy [DE-FG02-05ER46215]; AFOSR MURI; DARPA under Office of Naval Research [N00014-1210814]; U.S. Department of Energy (DOE) [DE-FG02-05ER46215] Funding Source: U.S. Department of Energy (DOE); Grants-in-Aid for Scientific Research [23246116, 25107005, 25107004, 23310096, 24740193] Funding Source: KAKEN; Division Of Materials Research; Direct For Mathematical & Physical Scien [0955625] Funding Source: National Science Foundation
NR 30
TC 1469
Z9 1741
U1 5
U2 779
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 30
PY 2013
VL 497
IS 7451
BP 598
EP 602
DI 10.1038/nature12186
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 152UF
UT WOS:000319556100039
PM 23676673
DA 2026-03-09
ER

PT J
AU Giustina, M
   Mech, A
   Ramelow, S
   Wittmann, B
   Kofler, J
   Beyer, J
   Lita, A
   Calkins, B
   Gerrits, T
   Nam, S
   Ursin, R
   Zeilinger, A
AF Giustina, Marissa
   Mech, Alexandra
   Ramelow, Sven
   Wittmann, Bernhard
   Kofler, Johannes
   Beyer, Joern
   Lita, Adriana
   Calkins, Brice
   Gerrits, Thomas
   Nam, SaeWoo
   Ursin, Rupert
   Zeilinger, Anton
TI Bell violation using entangled photons without the fair-sampling assumption
SO NATURE
LA English
DT Article
ID inequality
AB The violation of a Bell inequality is an experimental observation that forces the abandonment of a local realistic viewpoint-namely, one in which physical properties are (probabilistically) defined before and independently of measurement, and in which no physical influence can propagate faster than the speed of light(1,2). All such experimental violations require additional assumptions depending on their specific construction, making them vulnerable to so-called loopholes. Here we use entangled photons to violate a Bell inequality while closing the fair-sampling loophole, that is, without assuming that the sample of measured photons accurately represents the entire ensemble(3). To do this, we use the Eberhard form of Bell's inequality, which is not vulnerable to the fair-sampling assumption and which allows a lower collection efficiency than other forms(4). Technical improvements of the photon source(5,6) and high-efficiency transition-edge sensors(7) were crucial for achieving a sufficiently high collection efficiency. Our experiment makes the photon the first physical system for which each of the main loopholes has been closed, albeit in different experiments.
C1 [Giustina, Marissa; Mech, Alexandra; Ramelow, Sven; Wittmann, Bernhard; Kofler, Johannes; Ursin, Rupert; Zeilinger, Anton] Austrian Acad Sci, IQOQI, A-1090 Vienna, Austria.
   [Giustina, Marissa; Mech, Alexandra; Ramelow, Sven; Wittmann, Bernhard; Zeilinger, Anton] Univ Vienna, Fac Phys, A-1090 Vienna, Austria.
   [Kofler, Johannes] Max Planck Inst Quantum Opt MPQ, D-85748 Garching, Germany.
   [Beyer, Joern] Phys Tech Bundesanstalt, D-10587 Berlin, Germany.
   [Lita, Adriana; Calkins, Brice; Gerrits, Thomas; Nam, SaeWoo] NIST, Boulder, CO 80305 USA.
C3 Austrian Academy of Sciences; University of Vienna; Max Planck Society; Physikalisch-Technische Bundesanstalt (PTB); National Institute of Standards & Technology (NIST) - USA
RP Giustina, M (corresponding author), Austrian Acad Sci, IQOQI, Boltzmanngasse 3, A-1090 Vienna, Austria.
EM marissa.giustina@univie.ac.at; anton.zeilinger@univie.ac.at
FU ERC [QIT4QAD 227844]; Austrian Science Fund (FWF) [SFB F4008, CoQuS]; Q-ESSENCE [248095]; QAP [15848]; Marie Curie Research Training Network EMALI [MRTN-CT-2006-035369]; John Templeton Foundation; NIST Quantum Information Science Initiative (QISI), an agency of the US Government; Austrian Science Fund (FWF) [W1210] Funding Source: Austrian Science Fund (FWF)
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NR 29
TC 358
Z9 391
U1 1
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 MAY 9
PY 2013
VL 497
IS 7448
BP 227
EP 230
DI 10.1038/nature12012
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 139CD
UT WOS:000318558200033
PM 23584590
DA 2026-03-09
ER

PT J
AU Vieira, JD
   Marrone, DP
   Chapman, SC
   De Breuck, C
   Hezaveh, YD
   Weiss, A
   Aguirre, JE
   Aird, KA
   Aravena, M
   Ashby, MLN
   Bayliss, M
   Benson, BA
   Biggs, AD
   Bleem, LE
   Bock, JJ
   Bothwell, M
   Bradford, CM
   Brodwin, M
   Carlstrom, JE
   Chang, CL
   Crawford, TM
   Crites, AT
   de Haan, T
   Dobbs, MA
   Fomalont, EB
   Fassnacht, CD
   George, EM
   Gladders, MD
   Gonzalez, AH
   Greve, TR
   Gullberg, B
   Halverson, NW
   High, FW
   Holder, GP
   Holzapfel, WL
   Hoover, S
   Hrubes, JD
   Hunter, TR
   Keisler, R
   Lee, AT
   Leitch, EM
   Lueker, M
   Luong-Van, D
   Malkan, M
   McIntyre, V
   McMahon, JJ
   Mehl, J
   Menten, KM
   Meyer, SS
   Mocanu, LM
   Murphy, EJ
   Natoli, T
   Padin, S
   Plagge, T
   Reichardt, CL
   Rest, A
   Ruel, J
   Ruhl, JE
   Sharon, K
   Schaffer, KK
   Shaw, L
   Shirokoff, E
   Spilker, JS
   Stalder, B
   Staniszewski, Z
   Stark, AA
   Story, K
   Vanderlinde, K
   Welikala, N
   Williamson, R
AF Vieira, J. D.
   Marrone, D. P.
   Chapman, S. C.
   De Breuck, C.
   Hezaveh, Y. D.
   Weiss, A.
   Aguirre, J. E.
   Aird, K. A.
   Aravena, M.
   Ashby, M. L. N.
   Bayliss, M.
   Benson, B. A.
   Biggs, A. D.
   Bleem, L. E.
   Bock, J. J.
   Bothwell, M.
   Bradford, C. M.
   Brodwin, M.
   Carlstrom, J. E.
   Chang, C. L.
   Crawford, T. M.
   Crites, A. T.
   de Haan, T.
   Dobbs, M. A.
   Fomalont, E. B.
   Fassnacht, C. D.
   George, E. M.
   Gladders, M. D.
   Gonzalez, A. H.
   Greve, T. R.
   Gullberg, B.
   Halverson, N. W.
   High, F. W.
   Holder, G. P.
   Holzapfel, W. L.
   Hoover, S.
   Hrubes, J. D.
   Hunter, T. R.
   Keisler, R.
   Lee, A. T.
   Leitch, E. M.
   Lueker, M.
   Luong-Van, D.
   Malkan, M.
   McIntyre, V.
   McMahon, J. J.
   Mehl, J.
   Menten, K. M.
   Meyer, S. S.
   Mocanu, L. M.
   Murphy, E. J.
   Natoli, T.
   Padin, S.
   Plagge, T.
   Reichardt, C. L.
   Rest, A.
   Ruel, J.
   Ruhl, J. E.
   Sharon, K.
   Schaffer, K. K.
   Shaw, L.
   Shirokoff, E.
   Spilker, J. S.
   Stalder, B.
   Staniszewski, Z.
   Stark, A. A.
   Story, K.
   Vanderlinde, K.
   Welikala, N.
   Williamson, R.
TI Dusty starburst galaxies in the early Universe as revealed by gravitational lensing
SO NATURE
LA English
DT Article
ID south-pole telescope; submillimeter galaxy; molecular gas; deep-field; redshift; counts; model
AB In the past decade, our understanding of galaxy evolution has been revolutionized by the discovery that luminous, dusty starburst galaxies were 1,000 times more abundant in the early Universe than at present(1,2). It has, however, been difficult to measure the complete redshift distribution of these objects, especially at the highest redshifts (z>4). Here we report a redshift survey at a wavelength of three millimetres, targeting carbon monoxide line emission from the star-forming molecular gas in the direction of extraordinarily bright millimetre-wave-selected sources. High-resolution imaging demonstrates that these sources are strongly gravitationally lensed by foreground galaxies. We detect spectral lines in 23 out of 26 sources and multiple lines in 12 of those 23 sources, from which we obtain robust, unambiguous redshifts. At least 10 of the sources are found to lie at z > 4, indicating that the fraction of dusty starburst galaxies at high redshifts is greater than previously thought. Models of lens geometries in the sample indicate that the background objects are ultra-luminous infrared galaxies, powered by extreme bursts of star formation.
C1 [Vieira, J. D.; Bock, J. J.; Lueker, M.; Padin, S.; Shirokoff, E.; Staniszewski, Z.] CALTECH, Pasadena, CA 91125 USA.
   [Marrone, D. P.; Bothwell, M.; Spilker, J. S.] Univ Arizona, Steward Observ, Tucson, AZ 85721 USA.
   [Chapman, S. C.] Dalhousie Univ, Dept Phys & Atmospher Sci, Halifax, NS B3H 3J5, Canada.
   [Chapman, S. C.] Univ Cambridge, Inst Astron, Cambridge CB3 0HA, England.
   [De Breuck, C.; Aravena, M.; Biggs, A. D.; Gullberg, B.] European So Observ, D-85748 Garching, Germany.
   [Hezaveh, Y. D.; de Haan, T.; Dobbs, M. A.; Holder, G. P.; Shaw, L.; Vanderlinde, K.] McGill Univ, Dept Phys, Montreal, PQ H3A 2T8, Canada.
   [Weiss, A.; Menten, K. M.] Max Planck Inst Radioastron, D-53121 Bonn, Germany.
   [Aguirre, J. E.] Univ Penn, Philadelphia, PA 19104 USA.
   [Aird, K. A.; Hrubes, J. D.; Luong-Van, D.] Univ Chicago, Chicago, IL 60637 USA.
   [Ashby, M. L. N.; Stalder, B.; Stark, A. A.] Harvard Smithsonian Ctr Astrophys, Cambridge, MA 02138 USA.
   [Bayliss, M.; Ruel, J.] Harvard Univ, Dept Phys, Cambridge, MA 02138 USA.
   [Benson, B. A.; Bleem, L. E.; Carlstrom, J. E.; Chang, C. L.; Crawford, T. M.; Crites, A. T.; Gladders, M. D.; High, F. W.; Hoover, S.; Keisler, R.; Leitch, E. M.; McMahon, J. J.; Mehl, J.; Meyer, S. S.; Mocanu, L. M.; Natoli, T.; Padin, S.; Plagge, T.; Sharon, K.; Schaffer, K. K.; Story, K.; Williamson, R.] Univ Chicago, Kavli Inst Cosmol Phys, Chicago, IL 60637 USA.
   [Benson, B. A.; Carlstrom, J. E.; Chang, C. L.; Hoover, S.; McMahon, J. J.; Meyer, S. S.] Univ Chicago, Enrico Fermi Inst, Chicago, IL 60637 USA.
   [Bleem, L. E.; Carlstrom, J. E.; Keisler, R.; Meyer, S. S.; Natoli, T.; Story, K.] Univ Chicago, Dept Phys, Chicago, IL 60637 USA.
   [Bock, J. J.; Bradford, C. M.] CALTECH, Jet Prop Lab, Pasadena, CA 91109 USA.
   [Brodwin, M.] Univ Missouri, Dept Phys & Astron, Kansas City, MO 64110 USA.
   [Carlstrom, J. E.; Crawford, T. M.; Crites, A. T.; Gladders, M. D.; High, F. W.; Leitch, E. M.; Mehl, J.; Meyer, S. S.; Mocanu, L. M.; Padin, S.; Plagge, T.; Sharon, K.; Williamson, R.] Univ Chicago, Dept Astron & Astrophys, Chicago, IL 60637 USA.
   [Carlstrom, J. E.; Chang, C. L.] Argonne Natl Lab, Argonne, IL 60439 USA.
   [Fomalont, E. B.; Hunter, T. R.] Natl Radio Astron Observ, Charlottesville, VA 22903 USA.
   [Fassnacht, C. D.] Univ Calif Davis, Dept Phys, Davis, CA 95616 USA.
   [George, E. M.; Holzapfel, W. L.; Lee, A. T.; Reichardt, C. L.] Univ Calif Berkeley, Dept Phys, Berkeley, CA 94720 USA.
   [Gonzalez, A. H.] Univ Florida, Dept Astron, Gainesville, FL 32611 USA.
   [Greve, T. R.] UCL, Dept Phys & Astron, London WC1E 6BT, England.
   [Halverson, N. W.] Univ Colorado, Dept Astrophys & Planetary Sci, Boulder, CO 80309 USA.
   [Halverson, N. W.] Univ Colorado, Dept Phys, Boulder, CO 80309 USA.
   [Lee, A. T.] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Dept Phys, Berkeley, CA 94720 USA.
   [Malkan, M.] Univ Calif Los Angeles, Dept Phys & Astron, Los Angeles, CA 90095 USA.
   [McIntyre, V.] CSIRO, Australia Telescope Natl Facil, Epping, NSW 1710, Australia.
   [McMahon, J. J.] Univ Michigan, Dept Phys, Ann Arbor, MI 48109 USA.
   [Murphy, E. J.] Observ Carnegie Inst Sci, Pasadena, CA 91101 USA.
   [Rest, A.] Space Telescope Sci Inst, Baltimore, MD 21218 USA.
   [Ruhl, J. E.; Staniszewski, Z.] Case Western Reserve Univ, Dept Phys, Ctr Educ & Res Cosmol & Astrophys, Cleveland, OH 44106 USA.
   [Sharon, K.] Univ Michigan, Dept Astron, Ann Arbor, MI 48109 USA.
   [Schaffer, K. K.] Sch Art Inst Chicago, Liberal Arts Dept, Chicago, IL 60603 USA.
   [Shaw, L.] Yale Univ, Dept Phys, New Haven, CT 06520 USA.
   [Welikala, N.] Univ Paris 11, Inst Astrophys Spatiale, F-91405 Orsay, France.
   [Welikala, N.] CNRS, F-91405 Orsay, France.
C3 California Institute of Technology; University of Arizona; Dalhousie University; University of Cambridge; European Southern Observatory; McGill University; Max Planck Society; University of Pennsylvania; University of Chicago; Smithsonian Astrophysical Observatory; Smithsonian Institution; Harvard University; Harvard University; University of Chicago; University of Chicago; University of Chicago; National Aeronautics & Space Administration (NASA); NASA Jet Propulsion Laboratory (JPL); California Institute of Technology; University of Missouri System; University of Missouri Kansas City; University of Chicago; United States Department of Energy (DOE); Argonne National Laboratory; National Radio Astronomy Observatory (NRAO); University of California System; University of California Davis; University of California System; University of California Berkeley; State University System of Florida; University of Florida; University of London; University College London; University of Colorado System; University of Colorado Boulder; University of Colorado System; University of Colorado Boulder; 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 Los Angeles; Commonwealth Scientific & Industrial Research Organisation (CSIRO); Australia Telescope National Facility; University of Michigan System; University of Michigan; Carnegie Institution for Science; Space Telescope Science Institute; University System of Ohio; Case Western Reserve University; University of Michigan System; University of Michigan; School of the Art Institute of Chicago; Yale University; Universite Paris Saclay; Sorbonne Universite; Centre National de la Recherche Scientifique (CNRS)
RP Vieira, JD (corresponding author), CALTECH, 1200 East Calif Blvd, Pasadena, CA 91125 USA.
EM vieira@caltech.edu
FU National Science Foundation; Kavli Foundation; Gordon and Betty Moore Foundation; NASA from the Space Telescope Science Institute; NSERC; CRC; ClfAR; Direct For Mathematical & Physical Scien; Division Of Physics [1125897] Funding Source: National Science Foundation; Division Of Astronomical Sciences; Direct For Mathematical & Physical Scien [1009012] Funding Source: National Science Foundation; STFC [ST/I005544/1, ST/J000647/1] Funding Source: UKRI; Science and Technology Facilities Council [ST/I005544/1, ST/J000647/1, ST/H00243X/1] Funding Source: researchfish
NR 27
TC 278
Z9 298
U1 0
U2 19
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 21
PY 2013
VL 495
IS 7441
BP 344
EP 347
DI 10.1038/nature12001
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 113EY
UT WOS:000316650500037
PM 23485967
DA 2026-03-09
ER

PT J
AU Tian, YJ
   Xu, B
   Yu, DL
   Ma, YM
   Wang, YB
   Jiang, YB
   Hu, WT
   Tang, CC
   Gao, YF
   Luo, K
   Zhao, ZS
   Wang, LM
   Wen, B
   He, JL
   Liu, ZY
AF Tian, Yongjun
   Xu, Bo
   Yu, Dongli
   Ma, Yanming
   Wang, Yanbin
   Jiang, Yingbing
   Hu, Wentao
   Tang, Chengchun
   Gao, Yufei
   Luo, Kun
   Zhao, Zhisheng
   Wang, Li-Min
   Wen, Bin
   He, Julong
   Liu, Zhongyuan
TI Ultrahard nanotwinned cubic boron nitride
SO NATURE
LA English
DT Article
ID mechanical-property; high-pressure; maximum strength; high-temperature; hardness; diamond; nucleation; metals; copper; tools
AB Cubic boron nitride (cBN) is a well known superhard material that has a wide range of industrial applications. Nanostructuring of cBN is an effective way to improve its hardness by virtue of the Hall-Petch effect-the tendency for hardness to increase with decreasing grain size(1,2). Polycrystalline cBN materials are often synthesized by using the martensitic transformation of a graphite-like BN precursor, in which high pressures and temperatures lead to puckering of the BN layers(3). Such approaches have led to synthetic polycrystalline cBN having grain sizes as small as similar to 14 nm (refs 1, 2, 4, 5). Here we report the formation of cBN with a nanostructure dominated by fine twin domains of average thickness similar to 3.8 nm. This nanotwinned cBN was synthesized from specially prepared BN precursor nanoparticles possessing onion-like nested structures with intrinsically puckered BN layers and numerous stacking faults. The resulting nanotwinned cBN bulk samples are optically transparent with a striking combination of physical properties: an extremely high Vickers hardness (exceeding 100 GPa, the optimal hardness of synthetic diamond), a high oxidization temperature (similar to 1,294 degrees C) and a large fracture toughness (>12 MPa m(1/2), well beyond the toughness of commercial cemented tungsten carbide, similar to 10 MPa m(1/2)). We show that hardening of cBN is continuous with decreasing twin thickness down to the smallest sizes investigated, contrasting with the expected reverse Hall-Petch effect below a critical grain size or the twin thickness of similar to 10-15 nm found in metals and alloys.
C1 [Tian, Yongjun; Xu, Bo; Yu, Dongli; Hu, Wentao; Gao, Yufei; Luo, Kun; Zhao, Zhisheng; Wang, Li-Min; Wen, Bin; He, Julong; Liu, Zhongyuan] Yanshan Univ, State Key Lab Metastable Mat Sci & Technol, Qinhuangdao 066004, Peoples R China.
   [Ma, Yanming] Jilin Univ, State Key Lab Superhard Mat, Changchun 130012, Peoples R China.
   [Wang, Yanbin] Univ Chicago, Ctr Adv Radiat Sources, Chicago, IL 60439 USA.
   [Jiang, Yingbing] Univ New Mexico, TEM Lab, Albuquerque, NM 87131 USA.
   [Tang, Chengchun] Hebei Univ Technol, Sch Mat Sci & Engn, Tianjin 300130, Peoples R China.
C3 Yanshan University; Jilin University; University of Chicago; University of New Mexico; Hebei University of Technology
RP Tian, YJ (corresponding author), Yanshan Univ, State Key Lab Metastable Mat Sci & Technol, Qinhuangdao 066004, Peoples R China.
EM fhcl@ysu.edu.cn
FU Ministry of Science and Technology of China [2011CB808205, 2010CB731605]; National Natural Science Foundation of China [51121061, 51172197, 11025418, 91022029]; US National Science Foundation [EAR-0968456]; Directorate For Geosciences; Division Of Earth Sciences [0968823] Funding Source: National Science Foundation; Division Of Earth Sciences; Directorate For Geosciences [0968456, 0968858] Funding Source: National Science Foundation
NR 30
TC 730
Z9 807
U1 17
U2 1477
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 17
PY 2013
VL 493
IS 7432
BP 385
EP 388
DI 10.1038/nature11728
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 071TA
UT WOS:000313615900047
PM 23325219
DA 2026-03-09
ER

PT J
AU Jones, W
   Klin, A
AF Jones, Warren
   Klin, Ami
TI Attention to eyes is present but in decline in 2-6-month-old infants later diagnosed with autism
SO NATURE
LA English
DT Article
ID spectrum disorders; children
AB Deficits in eye contact have been a hallmark of autism(1,2) since the condition's initial description(3). They are cited widely as a diagnostic feature(4) and figure prominently in clinical instruments(5); however, the early onset of these deficits has not been known. Here we show in a prospective longitudinal study that infants later diagnosed with autism spectrum disorders (ASDs) exhibit mean decline in eye fixation from 2 to 6 months of age, a pattern not observed in infants who do not develop ASD. These observations mark the earliest known indicators of social disability in infancy, but also falsify a prior hypothesis: in the first months of life, this basic mechanism of social adaptive action-eye looking-is not immediately diminished in infants later diagnosed with ASD; instead, eye looking appears to begin at normative levels prior to decline. The timing of decline highlights a narrow developmental window and reveals the early derailment of processes that would otherwise have a key role in canalizing typical social development. Finally, the observation of this decline in eye fixation-rather than outright absence-offers a promising opportunity for early intervention that could build on the apparent preservation of mechanisms subserving reflexive initial orientation towards the eyes.
C1 [Jones, Warren; Klin, Ami] Childrens Healthcare Atlanta, Marcus Autism Ctr, Atlanta, GA 30329 USA.
   [Jones, Warren; Klin, Ami] Emory Univ, Sch Med, Dept Pediat, Div Autism & Related Disabil, Atlanta, GA 30022 USA.
   [Jones, Warren; Klin, Ami] Emory Univ, Ctr Translat Social Neurosci, Atlanta, GA 30022 USA.
C3 Children's Healthcare of Atlanta (CHOA); Emory University; Emory University
RP Jones, W (corresponding author), Childrens Healthcare Atlanta, Marcus Autism Ctr, Atlanta, GA 30329 USA.
EM warren.jones@emory.edu; ami.klin@emory.edu
FU Simons Foundation; National Institute of Mental Health [R01 MH083727]; Marcus Foundation; Whitehead Foundation; Georgia Research Alliance; National Institute of Mental Health [P50MH100029] Funding Source: NIH RePORTER
NR 37
TC 883
Z9 1096
U1 9
U2 265
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 19
PY 2013
VL 504
IS 7480
BP 427
EP +
DI 10.1038/nature12715
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 273ZR
UT WOS:000328575300050
PM 24196715
DA 2026-03-09
ER

PT J
AU Fudge, TJ
   Steig, EJ
   Markle, BR
   Schoenemann, SW
   Ding, QH
   Taylor, KC
   McConnell, JR
   Brook, EJ
   Sowers, T
   White, JWC
   Alley, RB
   Cheng, H
   Clow, GD
   Cole-Dai, J
   Conway, H
   Cuffey, KM
   Edwards, JS
   Edwards, RL
   Edwards, R
   Fegyveresi, JM
   Ferris, D
   Fitzpatrick, JJ
   Johnson, J
   Hargreaves, G
   Lee, JE
   Maselli, OJ
   Mason, W
   McGwire, KC
   Mitchell, LE
   Mortensen, N
   Neff, P
   Orsi, AJ
   Popp, TJ
   Schauer, AJ
   Severinghaus, JP
   Sigl, M
   Spencer, MK
   Vaughn, BH
   Voigt, DE
   Waddington, ED
   Wang, XF
   Wong, GJ
AF Fudge, T. J.
   Steig, Eric J.
   Markle, Bradley R.
   Schoenemann, Spruce W.
   Ding, Qinghua
   Taylor, Kendrick C.
   McConnell, Joseph R.
   Brook, Edward J.
   Sowers, Todd
   White, James W. C.
   Alley, Richard B.
   Cheng, Hai
   Clow, Gary D.
   Cole-Dai, Jihong
   Conway, Howard
   Cuffey, Kurt M.
   Edwards, Jon S.
   Edwards, R. Lawrence
   Edwards, Ross
   Fegyveresi, John M.
   Ferris, David
   Fitzpatrick, Joan J.
   Johnson, Jay
   Hargreaves, Geoffrey
   Lee, James E.
   Maselli, Olivia J.
   Mason, William
   McGwire, Kenneth C.
   Mitchell, Logan E.
   Mortensen, Nicolai
   Neff, Peter
   Orsi, Anais J.
   Popp, Trevor J.
   Schauer, Andrew J.
   Severinghaus, Jeffrey P.
   Sigl, Michael
   Spencer, Matthew K.
   Vaughn, Bruce H.
   Voigt, Donald E.
   Waddington, Edwin D.
   Wang, Xianfeng
   Wong, Gifford J.
TI Onset of deglacial warming in West Antarctica driven by local orbital forcing
SO NATURE
LA English
DT Article
ID abrupt climate-change; ice-core; atmospheric co2; high-resolution; carbon-dioxide; greenland; circulation; temperature; timescales; chronology
AB The cause of warming in the Southern Hemisphere during the most recent deglaciation remains a matter of debate(1,2). Hypotheses for a Northern Hemisphere trigger, through oceanic redistributions of heat, are based in part on the abrupt onset of warming seen in East Antarctic ice cores and dated to 18,000 years ago, which is several thousand years after high-latitude Northern Hemisphere summer insolation intensity began increasing from its minimum, approximately 24,000 years ago(3,4). An alternative explanation is that local solar insolation changes cause the Southern Hemisphere to warm independently(2,5). Here we present results from a new, annually resolved ice-core record from West Antarctica that reconciles these two views. The records show that 18,000 years ago snow accumulation in West Antarctica began increasing, coincident with increasing carbon dioxide concentrations, warming in East Antarctica and cooling in the Northern Hemisphere(6) associated with an abrupt decrease in Atlantic meridional overturning circulation(7). However, significant warming in West Antarctica began at least 2,000 years earlier. Circum-Antarctic sea-ice decline, driven by increasing local insolation, is the likely cause of this warming. The marine-influenced West Antarctic records suggest a more active role for the Southern Ocean in the onset of deglaciation than is inferred from ice cores in the East Antarctic interior, which are largely isolated from sea-ice changes.
C1 [Fudge, T. J.; Steig, Eric J.; Markle, Bradley R.; Schoenemann, Spruce W.; Ding, Qinghua; Conway, Howard; Neff, Peter; Schauer, Andrew J.; Waddington, Edwin D.] Univ Washington, Dept Earth & Space Sci, Seattle, WA 98195 USA.
   [Steig, Eric J.; Ding, Qinghua] Univ Washington, Quaternary Res Ctr, Seattle, WA 98195 USA.
   [Taylor, Kendrick C.; McConnell, Joseph R.; Maselli, Olivia J.; McGwire, Kenneth C.; Sigl, Michael] Nevada Syst Higher Educ, Desert Res Inst, Reno, NV 89512 USA.
   [Brook, Edward J.; Edwards, Jon S.; Lee, James E.; Mitchell, Logan E.] Oregon State Univ, Coll Earth Ocean & Atmospher Sci, Corvallis, OR 97331 USA.
   [Sowers, Todd; Alley, Richard B.; Fegyveresi, John M.; Voigt, Donald E.] Penn State Univ, Earth & Environm Syst Inst, University Pk, PA 16802 USA.
   [White, James W. C.] Univ Colorado, Dept Geol Sci, Boulder, CO 80309 USA.
   [White, James W. C.] Dept Environm Studies, Boulder, CO 80309 USA.
   [White, James W. C.; Vaughn, Bruce H.] Univ Colorado, INSTAAR, Boulder, CO 80309 USA.
   [Alley, Richard B.; Fegyveresi, John M.; Voigt, Donald E.] Penn State Univ, Dept Geosci, University Pk, PA 16802 USA.
   [Cheng, Hai] Xi An Jiao Tong Univ, Inst Global Environm Change, Xian 710049, Peoples R China.
   [Cheng, Hai; Edwards, R. Lawrence] Univ Minnesota, Dept Earth Sci, Minneapolis, MN 55455 USA.
   [Clow, Gary D.] US Geol Survey, Geosci & Environm Change Sci Ctr, Lakewood, CO 80225 USA.
   [Cole-Dai, Jihong; Ferris, David] S Dakota State Univ, Dept Chem & Biochem, Brookings, SD 57007 USA.
   [Cuffey, Kurt M.] Univ Calif Berkeley, Dept Geog, Berkeley, CA 94720 USA.
   [Edwards, Ross] Curtin Univ Technol, Dept Imaging & Appl Phys, Perth, WA 6102, Australia.
   [Fitzpatrick, Joan J.] US Geol Survey, Denver, CO 80225 USA.
   [Johnson, Jay; Mortensen, Nicolai] Univ Wisconsin, Space Sci Engn Ctr, Madison, WI 53706 USA.
   [Hargreaves, Geoffrey] US Geol Survey, Natl Ice Core Lab, Denver, CO 80225 USA.
   [Mason, William] EMECH Designs, Brooklyn, WI 53521 USA.
   [Neff, Peter] Victoria Univ Wellington, Antarctic Res Ctr, Wellington 6012, New Zealand.
   [Orsi, Anais J.; Severinghaus, Jeffrey P.] Univ Calif San Diego, Scripps Inst Oceanog, La Jolla, CA 92037 USA.
   [Popp, Trevor J.] Univ Copenhagen, Niels Bohr Inst, Ctr Ice & Climate, DK-2100 Copenhagen, Denmark.
   [Spencer, Matthew K.] Lake Super State Univ, Dept Geol & Phys, Sault Ste Marie, MI 49783 USA.
   [Wang, Xianfeng] Nanyang Technol Univ, Earth Observ Singapore, Singapore 639798, Singapore.
   [Wong, Gifford J.] Dartmouth Coll, Dept Earth Sci, Hanover, NH 03755 USA.
C3 University of Washington; University of Washington Seattle; University of Washington; University of Washington Seattle; Nevada System of Higher Education (NSHE); Desert Research Institute NSHE; Oregon State University; Pennsylvania Commonwealth System of Higher Education (PCSHE); Pennsylvania State University; Pennsylvania State University - University Park; University of Colorado System; University of Colorado Boulder; University of Colorado System; University of Colorado Boulder; Pennsylvania Commonwealth System of Higher Education (PCSHE); Pennsylvania State University; Pennsylvania State University - University Park; Xi'an Jiaotong University; University of Minnesota System; University of Minnesota Twin Cities; United States Department of the Interior; United States Geological Survey; South Dakota State University; University of California System; University of California Berkeley; Curtin University; United States Department of the Interior; United States Geological Survey; University of Wisconsin System; University of Wisconsin Madison; United States Department of the Interior; United States Geological Survey; Victoria University Wellington; University of California System; University of California San Diego; Scripps Institution of Oceanography; University of Copenhagen; Niels Bohr Institute; Lake Superior State University; Nanyang Technological University; Dartmouth College
RP Fudge, TJ (corresponding author), Univ Washington, Dept Earth & Space Sci, Seattle, WA 98195 USA.
EM tjfudge@uw.edu
FU US National Science Foundation (NSF); NSF [0944197, 1043092, 0537930, 0944348, 0944191, 0440817, 0440819, 0230396, 0538427, 0839093, 1043518, 1043500, 05379853, 1043167, 1043528, 0539578, 0539232, 1103403, 0739780, 0637211, 0538553, 0839066, 0538657, 1043421, 1043313, 0801490]; NASA NESSF; USGS Climate and Land Use Change Program; National Natural Science Foundation of China [41230524]; Singapore National Research Foundation [NRFF2011-08]; Directorate For Geosciences [0539232] Funding Source: National Science Foundation; Directorate For Geosciences; Division Of Polar Programs [0739780] Funding Source: National Science Foundation; Directorate For Geosciences; Division Of Polar Programs [0440819, 0944191] Funding Source: National Science Foundation; Directorate For Geosciences; Office of Polar Programs (OPP) [0839066, 0537930, 1043092, 1043500, 0539578, 0839093, 0538553, 1043518] Funding Source: National Science Foundation; Div Atmospheric & Geospace Sciences; Directorate For Geosciences [1103403] Funding Source: National Science Foundation; Office Of Internatl Science &Engineering; Office Of The Director [0968391] Funding Source: National Science Foundation; Office of Polar Programs (OPP) [0539232] Funding Source: National Science Foundation; Office of Polar Programs (OPP); Directorate For Geosciences [0538657, 0944348, 0637211, 1043528, 0944197, 1043313, 0538427, 1043167, 1043421] Funding Source: National Science Foundation
NR 55
TC 271
Z9 313
U1 3
U2 223
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 22
PY 2013
VL 500
IS 7463
BP 440
EP +
DI 10.1038/nature12376
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 203TJ
UT WOS:000323316100031
PM 23945585
DA 2026-03-09
ER

PT J
AU Watanabe, S
   Rost, BR
   Camacho-Pérez, M
   Davis, MW
   Söhl-Kielczynski, B
   Rosenmund, C
   Jorgensen, EM
AF Watanabe, Shigeki
   Rost, Benjamin R.
   Camacho-Perez, Marcial
   Davis, M. Wayne
   Soehl-Kielczynski, Berit
   Rosenmund, Christian
   Jorgensen, Erik M.
TI Ultrafast endocytosis at mouse hippocampal synapses
SO NATURE
LA English
DT Article
ID clathrin-mediated endocytosis; synaptic vesicle endocytosis; transmitter release; autaptic cultures; fusion; membrane; exocytosis; transmission; retrieval; mechanism
AB To sustain neurotransmission, synaptic vesicles and their associated proteins must be recycled locally at synapses. Synaptic vesicles are thought to be regenerated approximately 20 s after fusion by the assembly of clathrin scaffolds or in approximately 1 s by the reversal of fusion pores via 'kiss-and-run' endocytosis. Here we use optogenetics to stimulate cultured hippocampal neurons with a single stimulus, rapidly freeze them after fixed intervals and examine the ultrastructure using electron microscopy-'flash-and-freeze' electron microscopy. Docked vesicles fuse and collapse into the membrane within 30 ms of the stimulus. Compensatory endocytosis occurs within 50 to 100 ms at sites flanking the active zone. Invagination is blocked by inhibition of actin polymerization, and scission is blocked by inhibiting dynamin. Because intact synaptic vesicles are not recovered, this form of recycling is not compatible with kiss-and-run endocytosis; moreover, it is 200-fold faster than clathrin-mediated endocytosis. It is likely that 'ultrafast endocytosis' is specialized to restore the surface area of the membrane rapidly.
C1 [Watanabe, Shigeki; Davis, M. Wayne; Jorgensen, Erik M.] Univ Utah, Dept Biol, Salt Lake City, UT 84112 USA.
   [Watanabe, Shigeki; Davis, M. Wayne; Jorgensen, Erik M.] Univ Utah, Howard Hughes Med Inst, Salt Lake City, UT 84112 USA.
   [Rost, Benjamin R.; Camacho-Perez, Marcial; Soehl-Kielczynski, Berit; Rosenmund, Christian] Charite, Neurosci Res Ctr, D-10117 Berlin, Germany.
C3 Utah System of Higher Education; University of Utah; Howard Hughes Medical Institute; Utah System of Higher Education; University of Utah; Free University of Berlin; Humboldt University of Berlin; Charite Universitatsmedizin Berlin
RP Jorgensen, EM (corresponding author), Univ Utah, Dept Biol, Salt Lake City, UT 84112 USA.
EM christian.rosenmund@charite.de; jorgensen@biology.utah.edu
FU EMBO; US National Institutes of Health [NS034307]; European Research Council [249939 SYNVGLUT]; German Research Council [EXC 257, SFB 665, SFB958]; National Institute of Neurological Disorders and Stroke [R01NS034307] Funding Source: NIH RePORTER
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   TORRITARELLI F, 1985, J CELL BIOL, V101, P1386, DOI 10.1083/jcb.101.4.1386
   Varoqueaux F, 2002, P NATL ACAD SCI USA, V99, P9037, DOI 10.1073/pnas.122623799
   Verstreken P, 2002, CELL, V109, P101, DOI 10.1016/S0092-8674(02)00688-8
   VONGERSDORFF H, 1994, NATURE, V367, P735, DOI 10.1038/367735a0
   Watanabe S, 2013, ELIFE, V2, P0, DOI 10.7554/eLife.00723
   Wienisch M, 2006, NAT NEUROSCI, V9, P1019, DOI 10.1038/nn1739
   Yamada H, 2009, BIOCHEM BIOPH RES CO, V390, P1142, DOI 10.1016/j.bbrc.2009.10.105
   Zhang Q, 2007, P NATL ACAD SCI USA, V104, P17843, DOI 10.1073/pnas.0706906104
NR 54
TC 428
Z9 510
U1 6
U2 106
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 12
PY 2013
VL 504
IS 7479
BP 242
EP +
DI 10.1038/nature12809
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 267TQ
UT WOS:000328121500029
PM 24305055
DA 2026-03-09
ER

PT J
AU Bondy-Denomy, J
   Pawluk, A
   Maxwell, KL
   Davidson, AR
AF Bondy-Denomy, Joe
   Pawluk, April
   Maxwell, Karen L.
   Davidson, Alan R.
TI Bacteriophage genes that inactivate the CRISPR/Cas bacterial immune system
SO NATURE
LA English
DT Article
ID genome sequence; pseudomonas; rna; resistance; phage; interference; defense; dna
AB A widespread system used by bacteria for protection against potentially dangerous foreign DNA molecules consists of the clustered regularly interspaced short palindromic repeats (CRISPR) coupled with cas (CRISPR-associated) genes(1). Similar to RNA interference in eukaryotes(2), these CRISPR/Cas systems use small RNAs for sequence-specific detection and neutralization of invading genomes(3). Here we describe the first examples of genes that mediate the inhibition of a CRISPR/Cas system. Five distinct 'anti-CRISPR' genes were found in the genomes of bacteriophages infecting Pseudomonas aeruginosa. Mutation of the anti-CRISPR gene of a phage rendered it unable to infect bacteria with a functional CRISPR/Cas system, and the addition of the same gene to the genome of a CRISPR/Cas-targeted phage allowed it to evade the CRISPR/Cas system. Phage-encoded anti-CRISPR genes may represent a widespread mechanism for phages to overcome the highly prevalent CRISPR/Cas systems. The existence of anti-CRISPR genes presents new avenues for the elucidation of CRISPR/Cas functional mechanisms and provides new insight into the co-evolution of phages and bacteria.
C1 [Bondy-Denomy, Joe; Davidson, Alan R.] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A8, Canada.
   [Pawluk, April; Davidson, Alan R.] Univ Toronto, Dept Biochem, Toronto, ON M5S 1A8, Canada.
   [Maxwell, Karen L.] Univ Toronto, Donnelly Ctr Cellular & Biomol Res, Toronto, ON M5S 3E1, Canada.
C3 University of Toronto; University of Toronto; University of Toronto
RP Davidson, AR (corresponding author), Univ Toronto, Dept Mol Genet, 100 Coll St, Toronto, ON M5S 1A8, Canada.
EM alan.davidson@utoronto.ca
FU Canadian Institutes for Health Research [MOP- 6279, XNE86943]; CIHR Canada Graduate Scholarship Doctoral Award
NR 31
TC 650
Z9 815
U1 5
U2 527
PU NATURE PUBLISHING 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 17
PY 2013
VL 493
IS 7432
BP 429
EP U181
DI 10.1038/nature11723
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 071TA
UT WOS:000313615900057
PM 23242138
DA 2026-03-09
ER

PT J
AU Stevens, NJ
   Seiffert, ER
   O'Connor, PM
   Roberts, EM
   Schmitz, MD
   Krause, C
   Gorscak, E
   Ngasala, S
   Hieronymus, TL
   Temu, J
AF Stevens, Nancy J.
   Seiffert, Erik R.
   O'Connor, Patrick M.
   Roberts, Eric M.
   Schmitz, Mark D.
   Krause, Cornelia
   Gorscak, Eric
   Ngasala, Sifa
   Hieronymus, Tobin L.
   Temu, Joseph
TI Palaeontological evidence for an Oligocene divergence between Old World monkeys and apes
SO NATURE
LA English
DT Article
ID rukwa rift basin; primate evolution; early miocene; victoriapithecus; paleogene; genus
AB Apes and Old World monkeys are prominent components of modern African and Asian ecosystems, yet the earliest phases of their evolutionary history have remained largely undocumented(1). The absence of crown catarrhine fossils older than similar to 20 million years (Myr) has stood in stark contrast to molecular divergence estimates of similar to 25-30 Myr for the split between Cercopithecoidea (Old World monkeys) and Hominoidea (apes), implying long ghost lineages for both clades(2-4). Here we describe the oldest known fossil 'ape', represented by a partial mandible preserving dental features that place it with 'nyanzapithecine' stem hominoids. Additionally, we report the oldest stem member of the Old World monkey clade, represented by a lower third molar. Both specimens were recovered from a precisely dated 25.2-Myr-old stratum in the Rukwa Rift, a segment of the western branch of the East African Rift in Tanzania. These finds extend the fossil record of apes and Old World monkey swell into the Oligocene epoch of Africa, suggesting a possible link between diversification of crown catarrhines and changes in the African landscape brought about by previously unrecognized tectonic activity(5) in the East African rift system.
C1 [Stevens, Nancy J.; O'Connor, Patrick M.; Krause, Cornelia] Ohio Univ, Dept Biomed Sci, Heritage Coll Osteopath Med, Athens, OH 45701 USA.
   [Stevens, Nancy J.; O'Connor, Patrick M.; Krause, Cornelia] Ohio Univ, Ctr Ecol & Evolutionary Studies, Athens, OH 45701 USA.
   [Seiffert, Erik R.] SUNY Stony Brook, Dept Anat Sci, Stony Brook, NY 11794 USA.
   [Roberts, Eric M.] James Cook Univ, Sch Earth & Environm Sci, Townsville, Qld 4811, Australia.
   [Schmitz, Mark D.] Boise State Univ, Sch Geosci, Boise, ID 83725 USA.
   [Gorscak, Eric] Ohio Univ, Dept Biol Sci, Athens, OH 45701 USA.
   [Ngasala, Sifa] Michigan State Univ, Dept Geol Sci, E Lansing, MI 48824 USA.
   [Hieronymus, Tobin L.] Northeast Ohio Med Univ, Dept Anat & Neurobiol, Rootstown, OH 44272 USA.
   [Temu, Joseph] Tanzania Antiqu Unit, Dar Es Salaam, Tanzania.
C3 University System of Ohio; Ohio University; University System of Ohio; Ohio University; State University of New York (SUNY) System; Stony Brook University; James Cook University; Boise State University; University System of Ohio; Ohio University; Michigan State University; University System of Ohio; Northeast Ohio Medical University (NEOMED)
RP Stevens, NJ (corresponding author), Ohio Univ, Dept Biomed Sci, Heritage Coll Osteopath Med, Athens, OH 45701 USA.
EM stevensn@ohio.edu
FU Tanzania Commission for Science and Technology; US National Science Foundation [EAR-0617561, EAR/IF-0933619, BCS-1127164]; National Geographic Society (CRE); Louis B. Leakey Foundation; Ohio University Heritage College of Osteopathic Medicine; Ohio University Office of Research and Sponsored Programs; Directorate For Geosciences; Division Of Earth Sciences [0933619] Funding Source: National Science Foundation; Division Of Behavioral and Cognitive Sci; Direct For Social, Behav & Economic Scie [1127164] Funding Source: National Science Foundation
NR 30
TC 148
Z9 182
U1 0
U2 76
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 30
PY 2013
VL 497
IS 7451
BP 611
EP 614
DI 10.1038/nature12161
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 152UF
UT WOS:000319556100042
PM 23676680
DA 2026-03-09
ER

PT J
AU Miles, BWJ
   Stokes, CR
   Vieli, A
   Cox, NJ
AF Miles, B. W. J.
   Stokes, C. R.
   Vieli, A.
   Cox, N. J.
TI Rapid, climate-driven changes in outlet glaciers on the Pacific coast of East Antarctica
SO NATURE
LA English
DT Article
ID ice-sheet; sea-ice; annular mode; mass-loss; greenland; variability; peninsula; margins; shelves; adelie
AB Observations of ocean-terminating outlet glaciers in Greenland and West Antarctica(1-6) indicate that their contribution to sea level is accelerating as a result of increased velocity, thinning and retreat(7-11). Thinning has also been reported along the margin of the much larger East Antarctic ice sheet(1), but whether glaciers are advancing or retreating there is largely unknown, and there has been no attempt to place such changes in the context of localized mass loss(7,9) or climatic or oceanic forcing. Here we present multidecadal trends in the terminus position of 175 ocean-terminating outlet glaciers along 5,400 kilometres of the margin of the East Antarctic ice sheet, and reveal widespread and synchronous changes. Despite large fluctuations between glaciers-linked to their size-three epochal patterns emerged: 63 per cent of glaciers retreated from 1974 to 1990, 72 per cent advanced from 1990 to 2000, and 58 per cent advanced from 2000 to 2010. These trends were most pronounced along the warmer western South Pacific coast, whereas glaciers along the cooler Ross Sea coast experienced no significant changes. We find that glacier change along the Pacific coast is consistent with a rapid and coherent response to air temperature and sea-ice trends, linked through the dominant mode of atmospheric variability (the Southern Annular Mode). We conclude that parts of the world's largest ice sheet may be more vulnerable to external forcing than recognized previously.
C1 [Miles, B. W. J.; Stokes, C. R.; Vieli, A.; Cox, N. J.] Univ Durham, Dept Geog, Durham DH1 3LE, England.
C3 Durham University
RP Stokes, CR (corresponding author), Univ Durham, Dept Geog, Sci Site,South Rd, Durham DH1 3LE, England.
EM c.r.stokes@durham.ac.uk
NR 34
TC 88
Z9 98
U1 0
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 AUG 29
PY 2013
VL 500
IS 7464
BP 563
EP +
DI 10.1038/nature12382
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 207TD
UT WOS:000323625900031
PM 23985874
DA 2026-03-09
ER

PT J
AU Takahashi, Y
   Inui, Y
   Chihara, M
   Asano, T
   Terawaki, R
   Noda, S
AF Takahashi, Yasushi
   Inui, Yoshitaka
   Chihara, Masahiro
   Asano, Takashi
   Terawaki, Ryo
   Noda, Susumu
TI A micrometre-scale Raman silicon laser with a microwatt threshold
SO NATURE
LA English
DT Article
ID photonic crystal nanocavity; wave-guides; heterostructure nanocavity; on-insulator; amplification; absorption; scattering; emission; design; cavity
AB The application of novel technologies to silicon electronics has been intensively studied with a view to overcoming the physical limitations of Moore's law, that is, the observation that the number of components on integrated chips tends to double every two years. For example, silicon devices have enormous potential for photonic integrated circuits on chips compatible with complementary metal-oxide-semiconductor devices, with various key elements having been demonstrated in the past decade(1-6). In particular, a focus on the exploitation of the Raman effect has added active optical functionality to pure silicon(7-10), culminating in the realization of a continuous-wave all-silicon laser(11). This achievement is an important step towards silicon photonics, but the desired miniaturization to micrometre dimensions and the reduction of the threshold for laser action to microwatt powers have yet to be achieved: such lasers remain limited to centimetre-sized cavities with thresholds higher than 20 milliwatts(12), even with the assistance of reverse-biased p-i-n diodes. Here we demonstrate a continuous-wave Raman silicon laser using a photonic-crystal, high-quality-factor nanocavity without any p-i-n diodes, yielding a device with a cavity size of less than 10 micrometres and an unprecedentedly low lasing threshold of 1 microwatt. Our nanocavity design exploits the principle that the strength of light-matter interactions is proportional to the ratio of quality factor to the cavity volume and allows drastic enhancement of the Raman gain beyond that predicted theoretically(13,14). Such a device may make it possible to construct practical silicon lasers and amplifiers for large-scale integration in photonic circuits.
C1 [Takahashi, Yasushi; Chihara, Masahiro; Terawaki, Ryo] Osaka Prefecture Univ, Res Org 21st Century, Nanosci & Nanotechnol Res Ctr, Sakai, Osaka 5998570, Japan.
   [Takahashi, Yasushi] Japan Sci & Technol Agcy, PRESTO, Kawaguchi, Saitama 3320012, Japan.
   [Inui, Yoshitaka; Asano, Takashi; Noda, Susumu] Kyoto Univ, Dept Elect Sci & Engn, Kyoto 6158510, Japan.
   [Noda, Susumu] Kyoto Univ, Photon & Elect Sci & Engn Ctr, Kyoto 6158510, Japan.
C3 Osaka Metropolitan University; Japan Science & Technology Agency (JST); Kyoto University; Kyoto University
RP Takahashi, Y (corresponding author), Osaka Prefecture Univ, Res Org 21st Century, Nanosci & Nanotechnol Res Ctr, Sakai, Osaka 5998570, Japan.
EM y-takahashi@21c.osakafu-u.ac.jp; snoda@kuee.kyoto-u.ac.jp
FU NanoSquare programme; Funds for the Development of Human Resources in Science and Technology; JST, PRESTO; MEXT KAKENHI [23104721, 21104512]; JSPS KAKENHI [23686015, 20226002]; Asahi Grass Foundation; Ministry of Economy, Trade and Industry (METI) through its 'Future Pioneering Projects'; CPHoST programme; Grants-in-Aid for Scientific Research [20226002, 21104512, 23686015] Funding Source: KAKEN
NR 30
TC 209
Z9 239
U1 2
U2 199
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 27
PY 2013
VL 498
IS 7455
BP 470
EP 474
DI 10.1038/nature12237
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 171LH
UT WOS:000320929400049
PM 23803846
DA 2026-03-09
ER

PT J
AU Kaidi, A
   Jackson, SP
AF Kaidi, Abderrahmane
   Jackson, Stephen P.
TI RETRACTED: KAT5 tyrosine phosphorylation couples chromatin sensing to ATM signalling (Retracted Article)
SO NATURE
LA English
DT Article; Retracted Publication
ID dna-damage response; histone h3 methylation; double-strand breaks; c-abl; activates atm; kinase; protein; autophosphorylation; acetylation; inhibition
AB KAT5 tyrosine phosphorylation, mediated by the tyrosine kinase c-Abl, increases after DNA damage, promoting KAT5 binding to histone H3K9me3, which triggers KAT5-mediated acetylation of the ATM kinase; this promotes the activation of the DNA damage checkpoint and cell survival. The detection of DNA lesions within chromatin represents a critical step in cellular responses to DNA damage. However, the regulatory mechanisms that couple chromatin sensing to DNA-damage signalling in mammalian cells are not well understood. Here we show that tyrosine phosphorylation of the protein acetyltransferase KAT5 (also known as TIP60) increases after DNA damage in a manner that promotes KAT5 binding to the histone mark H3K9me3. This triggers KAT5-mediated acetylation of the ATM kinase, promoting DNA-damage-checkpoint activation and cell survival. We also establish that chromatin alterations can themselves enhance KAT5 tyrosine phosphorylation and ATM-dependent signalling, and identify the proto-oncogene c-Abl as a mediator of this modification. These findings define KAT5 tyrosine phosphorylation as a key event in the sensing of genomic and chromatin perturbations, and highlight a key role for c-Abl in such processes. Sensing genomic and chromatin perturbations When DNA experiences a double-strand break, the enzyme ATM (ataxia telangiectasia mutated) kinase is activated. Binding of the acetyltransferase KAT5 to the modified histone mark H3K9me3 facilitates ATM activation by acetylating the kinase. In this article, Abderrahmane Kaidi and Stephen Jackson show that the c-Abl kinase phosphorylates KAT5 on tyrosine 44 after DNA damage, enhancing its interaction with H3K9me3 and allowing ATM-mediated signalling to initiate the DNA damage checkpoint. These findings may help explain the mechanism of action of the lysine deacetylase inhibitors that are being developed as therapeutic agents, and could therefore inform on how such drugs might be best used against cancer and neurodegenerative diseases.
C1 [Kaidi, Abderrahmane; Jackson, Stephen P.] Univ Cambridge, Gurdon Inst, Tennis Court Rd, Cambridge CB2 1QN, England.
   [Kaidi, Abderrahmane; Jackson, Stephen P.] Univ Cambridge, Dept Biochem, Cambridge CB2 1QN, England.
   [Jackson, Stephen P.] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England.
C3 University of Cambridge; University of Cambridge; Wellcome Trust Sanger Institute
RP Jackson, SP (corresponding author), Univ Cambridge, Gurdon Inst, Tennis Court Rd, Cambridge CB2 1QN, England.
EM s.jackson@gurdon.cam.ac.uk
FU Cancer Research UK [C6/A11224]; European Research Council; European Community Seventh Framework Programme [HEALTH-F2-2010-259893]; CRUK [C6946/A14492]; Wellcome Trust [WT092096]; Herchel Smith Fellowship from the University of Cambridge
NR 35
TC 133
Z9 155
U1 1
U2 20
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 15
PY 2013
VL 498
IS 7452
BP 
EP 
DI 10.1038/nature12201
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA VI6RP
UT WOS:000507637600001
PM 23708966
DA 2026-03-09
ER

PT J
AU Haibe-Kains, B
   El-Hachem, N
   Birkbak, NJ
   Jin, AC
   Beck, AH
   Aerts, HJWL
   Quackenbush, J
AF Haibe-Kains, Benjamin
   El-Hachem, Nehme
   Birkbak, Nicolai Juul
   Jin, Andrew C.
   Beck, Andrew H.
   Aerts, Hugo J. W. L.
   Quackenbush, John
TI Inconsistency in large pharmacogenomic studies
SO NATURE
LA English
DT Article
ID drug; set
AB Two large-scale pharmacogenomic studies were published recently in this journal. Genomic data are well correlated between studies; however, the measured drug response data are highly discordant. Although the source of inconsistencies remains uncertain, it has potential implications for using these outcome measures to assess gene-drug associations or select potential anticancer drugs on the basis of their reported results.
C1 [Haibe-Kains, Benjamin; El-Hachem, Nehme] Univ Montreal, Inst Rech Clin Montreal, Montreal, PQ, Canada.
   [Haibe-Kains, Benjamin] Univ Hlth Network, Princess Margaret Canc Ctr, Ontario Canc Inst, Toronto, ON M5G 2M9, Canada.
   [Birkbak, Nicolai Juul] Tech Univ Denmark, Dept Syst Biol, Ctr Biol Sequence Anal, DK-2800 Lyngby, Denmark.
   [Jin, Andrew C.; Beck, Andrew H.] Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA.
   [Jin, Andrew C.; Beck, Andrew H.] Harvard Univ, Sch Med, Boston, MA 02215 USA.
   [Aerts, Hugo J. W. L.; Quackenbush, John] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA.
   [Aerts, Hugo J. W. L.; Quackenbush, John] Dana Farber Canc Inst, Ctr Canc Computat Biol, Boston, MA 02215 USA.
   [Aerts, Hugo J. W. L.] Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol & Radiol,Med Sch, Boston, MA 02215 USA.
   [Aerts, Hugo J. W. L.] Maastricht Univ, Dept Radiat Oncol, NL-6200 MD Maastricht, Netherlands.
   [Quackenbush, John] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA.
C3 Institut de Recherche Clinique de Montreal (IRCM); Universite de Montreal; University of Toronto; University Health Network Toronto; Princess Margaret Cancer Centre; Technical University of Denmark; Harvard University; Harvard University Medical Affiliates; Beth Israel Deaconess Medical Center; Harvard University; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Brigham & Women's Hospital; Maastricht University; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute
RP Haibe-Kains, B (corresponding author), Univ Montreal, Inst Rech Clin Montreal, Montreal, PQ, Canada.
EM bhaibeka@uhnresearch.ca
FU IRCM; Klarman Family Foundation; NIH [CA087969]; Villum Kann Rasmussen Foundation; Dr Miriam and Sheldon G. Adelson Medical Research Foundation; NCI GAME-ON Cancer Post-GWAS initiative [U19 CA148065-01]
NR 18
TC 391
Z9 466
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 DEC 19
PY 2013
VL 504
IS 7480
BP 389
EP +
DI 10.1038/nature12831
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 273ZR
UT WOS:000328575300042
PM 24284626
DA 2026-03-09
ER

PT J
AU Hanada, T
   Weitzer, S
   Mair, B
   Bernreuther, C
   Wainger, BJ
   Ichida, J
   Hanada, R
   Orthofer, M
   Cronin, SJ
   Komnenovic, V
   Minis, A
   Sato, F
   Mimata, H
   Yoshimura, A
   Tamir, I
   Rainer, J
   Kofler, R
   Yaron, A
   Eggan, KC
   Woolf, CJ
   Glatzel, M
   Herbst, R
   Martinez, J
   Penninger, JM
AF Hanada, Toshikatsu
   Weitzer, Stefan
   Mair, Barbara
   Bernreuther, Christian
   Wainger, Brian J.
   Ichida, Justin
   Hanada, Reiko
   Orthofer, Michael
   Cronin, Shane J.
   Komnenovic, Vukoslav
   Minis, Adi
   Sato, Fuminori
   Mimata, Hiromitsu
   Yoshimura, Akihiko
   Tamir, Ido
   Rainer, Johannes
   Kofler, Reinhard
   Yaron, Avraham
   Eggan, Kevin C.
   Woolf, Clifford J.
   Glatzel, Markus
   Herbst, Ruth
   Martinez, Javier
   Penninger, Josef M.
TI CLP1 links tRNA metabolism to progressive motor-neuron loss
SO NATURE
LA English
DT Article
ID 3-end formation; phosphorylation; endonuclease; stress; enzyme; mouse; hclp1; site; ia
AB CLP1 was the first mammalian RNA kinase to be identified. However, determining its in vivo function has been elusive. Here we generated kinase-dead Clp1 (Clp1(K/K)) mice that show a progressive loss of spinal motor neurons associated with axonal degeneration in the peripheral nerves and denervation of neuromuscular junctions, resulting in impaired motor function, muscle weakness, paralysis and fatal respiratory failure. Transgenic rescue experiments show that CLP1 functions in motor neurons. Mechanistically, loss of CLP1 activity results in accumulation of a novel set of small RNA fragments, derived from aberrant processing of tyrosine pre-transfer RNA. These tRNA fragments sensitize cells to oxidative-stress-induced p53 (also known as TRP53) activation and p53-dependent cell death. Genetic inactivation of p53 rescues Clp1(K/K) mice from the motor neuron loss, muscle denervation and respiratory failure. Our experiments uncover a mechanistic link between tRNA processing, formation of a new RNA species and progressive loss of lower motor neurons regulated by p53.
C1 [Hanada, Toshikatsu; Weitzer, Stefan; Mair, Barbara; Hanada, Reiko; Orthofer, Michael; Komnenovic, Vukoslav; Martinez, Javier; Penninger, Josef M.] Austrian Acad Sci, IMBA, Inst Mol Biotechnol, A-1030 Vienna, Austria.
   [Bernreuther, Christian; Glatzel, Markus] Univ Med Ctr Hamburg Eppendorf, Inst Neuropathol, D-20246 Hamburg, Germany.
   [Wainger, Brian J.; Cronin, Shane J.; Woolf, Clifford J.] Boston Childrens Hosp, Program Neurobiol, Boston, MA 02115 USA.
   [Wainger, Brian J.; Cronin, Shane J.; Woolf, Clifford J.] Boston Childrens Hosp, FM Kirby Neurobiol Ctr, Boston, MA 02115 USA.
   [Wainger, Brian J.] Massachusetts Gen Hosp, Department Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA.
   [Ichida, Justin; Eggan, Kevin C.] Harvard Stem Cell Inst, Dept Stem Cell & Regenerat Biol, Howard Hughes Med Inst, Boston, MA 02115 USA.
   [Minis, Adi; Yaron, Avraham] Weizmann Inst Sci, Dept Biol Chem, IL-76100 Rehovot, Israel.
   [Sato, Fuminori; Mimata, Hiromitsu] Oita Univ, Dept Urol, Fac Med, Oita 8795593, Japan.
   [Yoshimura, Akihiko] Keio Univ, Dept Microbiol & Immunol, Sch Med, Shinjuku Ku, Tokyo 1608582, Japan.
   [Tamir, Ido] Campus Sci Support Facil GmbH, A-1030 Vienna, Austria.
   [Rainer, Johannes; Kofler, Reinhard] Med Univ Innsbruck, Div Mol Pathophysiol, Bioctr, A-6020 Innsbruck, Austria.
   [Woolf, Clifford J.] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA.
   [Herbst, Ruth] Med Univ Vienna, Ctr Brain Res, A-1090 Vienna, Austria.
C3 Austrian Academy of Sciences; Vienna Biocenter (VBC); Institute of Molecular Biotechnology (IMBA); University of Hamburg; University Medical Center Hamburg-Eppendorf; 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; Massachusetts General Hospital; Howard Hughes Medical Institute; Harvard University; Weizmann Institute of Science; Oita University; Keio University; Medical University of Innsbruck; Harvard University; Harvard Medical School; Medical University of Vienna
RP Martinez, J (corresponding author), Austrian Acad Sci, IMBA, Inst Mol Biotechnol, A-1030 Vienna, Austria.
EM javier.martinez@imba.oeaw.ac.at; josef.penninger@imba.oeaw.ac.at
FU Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA); Austrian Ministry of Sciences; Austrian Academy of Sciences; AustroMouse network of Genome Research in Austria (GEN-AU); Apoptosis systems biology applied to cancer and AIDS (ApoSys); European Research Council Advanced Grant from the European Union; IMBA; GEN-AU (AustroMouse); Japan Society for the Promotion of Science; Astellas Foundation; National Institutes of Health (NIH) [K99NS077435-01A1]; German Research Foundation (DFG) [FG885, GRK 1459]; Landesexzellenzinitiative Hamburg (Neurodapt); Austrian Science Fund [P19223, P21667]; NIH [NS038253]; Austrian Science Fund (FWF) [P19223, P21667] Funding Source: Austrian Science Fund (FWF)
NR 27
TC 205
Z9 244
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 MAR 28
PY 2013
VL 495
IS 7442
BP 474
EP 480
DI 10.1038/nature11923
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 113QN
UT WOS:000316682800038
PM 23474986
DA 2026-03-09
ER

PT J
AU Jia, JZ
   Zhao, SC
   Kong, XY
   Li, YR
   Zhao, GY
   He, WM
   Appels, R
   Pfeifer, M
   Tao, Y
   Zhang, XY
   Jing, RL
   Zhang, C
   Ma, YZ
   Gao, LF
   Gao, C
   Spannagl, M
   Mayer, KFX
   Li, D
   Pan, SK
   Zheng, FY
   Hu, Q
   Xia, XC
   Li, JW
   Liang, QS
   Chen, J
   Wicker, T
   Gou, CY
   Kuang, HH
   He, GY
   Luo, YD
   Keller, B
   Xia, QJ
   Lu, P
   Wang, JY
   Zou, HF
   Zhang, RZ
   Xu, JY
   Gao, JL
   Middleton, C
   Quan, ZW
   Liu, GM
   Wang, J
   Yang, HM
   Liu, X
   He, ZH
   Mao, L
   Wang, J
AF Jia, Jizeng
   Zhao, Shancen
   Kong, Xiuying
   Li, Yingrui
   Zhao, Guangyao
   He, Weiming
   Appels, Rudi
   Pfeifer, Matthias
   Tao, Yong
   Zhang, Xueyong
   Jing, Ruilian
   Zhang, Chi
   Ma, Youzhi
   Gao, Lifeng
   Gao, Chuan
   Spannagl, Manuel
   Mayer, Klaus F. X.
   Li, Dong
   Pan, Shengkai
   Zheng, Fengya
   Hu, Qun
   Xia, Xianchun
   Li, Jianwen
   Liang, Qinsi
   Chen, Jie
   Wicker, Thomas
   Gou, Caiyun
   Kuang, Hanhui
   He, Genyun
   Luo, Yadan
   Keller, Beat
   Xia, Qiuju
   Lu, Peng
   Wang, Junyi
   Zou, Hongfeng
   Zhang, Rongzhi
   Xu, Junyang
   Gao, Jinlong
   Middleton, Christopher
   Quan, Zhiwu
   Liu, Guangming
   Wang, Jian
   Yang, Huanming
   Liu, Xu
   He, Zhonghu
   Mao, Long
   Wang, Jun
TI Aegilops tauschii draft genome sequence reveals a gene repertoire for wheat adaptation
SO NATURE
LA English
DT Article
ID nucleotide-binding site; polyploid wheat; hexaploid wheat; molecular-basis; dna; domestication; hardness; program; protein; origin
AB About 8,000 years ago in the Fertile Crescent, a spontaneous hybridization of the wild diploid grass Aegilops tauschii (2n = 14; DD) with the cultivated tetraploid wheat Triticum turgidum (2n = 4x = 28; AABB) resulted in hexaploid wheat (T. aestivum; 2n = 6x = 42; AABBDD)(1,2). Wheat has since become a primary staple crop worldwide as a result of its enhanced adaptability to a wide range of climates and improved grain quality for the production of baker's flour(2). Here we describe sequencing the Ae. tauschii genome and obtaining a roughly 90-fold depth of short reads from libraries with various insert sizes, to gain a better understanding of this genetically complex plant. The assembled scaffolds represented 83.4% of the genome, of which 65.9% comprised transposable elements. We generated comprehensive RNA-Seq data and used it to identify 43,150 protein-coding genes, of which 30,697 (71.1%) were uniquely anchored to chromosomes with an integrated high-density genetic map. Whole-genome analysis revealed gene family expansion in Ae. tauschii of agronomically relevant gene families that were associated with disease resistance, abiotic stress tolerance and grain quality. This draft genome sequence provides insight into the environmental adaptation of bread wheat and can aid in defining the large and complicated genomes of wheat species.
C1 [Jia, Jizeng; Kong, Xiuying; Zhao, Guangyao; Zhang, Xueyong; Jing, Ruilian; Ma, Youzhi; Gao, Lifeng; Xia, Xianchun; Zhang, Rongzhi; Liu, Xu; He, Zhonghu; Mao, Long] Chinese Acad Agr Sci, Inst Crop Sci, Natl Key Facil Crop Gene Resources & Genet Improv, Beijing 100081, Peoples R China.
   [Zhao, Shancen; Li, Yingrui; He, Weiming; Tao, Yong; Zhang, Chi; Gao, Chuan; Li, Dong; Pan, Shengkai; Zheng, Fengya; Li, Jianwen; Liang, Qinsi; Chen, Jie; Gou, Caiyun; He, Genyun; Luo, Yadan; Xia, Qiuju; Lu, Peng; Wang, Junyi; Zou, Hongfeng; Xu, Junyang; Gao, Jinlong; Quan, Zhiwu; Wang, Jian; Yang, Huanming; Wang, Jun] BGI Shenzhen, Shenzhen 518083, Peoples R China.
   [Zhao, Shancen; Zheng, Fengya] Chinese Univ Hong Kong, State Key Lab Agrobiotechnol, Shatin, Hong Kong, Peoples R China.
   [Zhao, Shancen; Zheng, Fengya] Chinese Univ Hong Kong, Sch Life Sci, Shatin, Hong Kong, Peoples R China.
   [Appels, Rudi] Murdoch Univ, Ctr Comparat Genom, Perth, WA 6150, Australia.
   [Pfeifer, Matthias; Spannagl, Manuel; Mayer, Klaus F. X.] Helmholtz Ctr Munich, MIPS Inst Bioinformat & Syst Biol, D-85764 Neuherberg, Germany.
   [Hu, Qun; Kuang, Hanhui] Huazhong Agr Univ, Coll Hort & Forestry, Dept Vegetable Crops, Wuhan 430070, Peoples R China.
   [Wicker, Thomas; Keller, Beat; Middleton, Christopher] Univ Zurich, Inst Plant Biol, CH-8008 Zurich, Switzerland.
   [Liu, Guangming] Natl Supercomp Ctr Tianjin, Tianjin 300457, Peoples R China.
   [He, Zhonghu] Int Maize & Wheat Improvement Ctr CIMMYT, Texcoco 56130, Mexico.
   [Wang, Jun] Univ Copenhagen, Dept Biol, DK-2200 Copenhagen, Denmark.
   [Wang, Jun] King Abdulaziz Univ, Jeddah 21589, Saudi Arabia.
C3 Chinese Academy of Agricultural Sciences; Institute of Crop Sciences, CAAS; Beijing Genomics Institute (BGI); Chinese University of Hong Kong; Chinese University of Hong Kong; Murdoch University; Helmholtz Association; Helmholtz-Center Munich - German Research Center for Environmental Health; Huazhong Agricultural University; University of Zurich; CGIAR; International Maize & Wheat Improvement Center (CIMMYT); University of Copenhagen; King Abdulaziz University
RP Wang, J (corresponding author), BGI Shenzhen, Shenzhen 518083, Peoples R China.
EM jzjia@mail.caas.net.cn; liuxu01@caas.cn; zhhe@public3.bta.net.cn; maolong@caas.net.cn; wangj@genomics.cn
FU National 863 Project [2012AA10A308, 2011AA100104]; International S&T Cooperation Program of China [2008DFB30080]; National Natural Science Foundation of China [31171548, 31071415]; National Basic Research Program of China [2010CB125900]; Core Research Budget of the Non-profit Governmental Research [201013]; National Program on R&D of Transgenic Plants [2011ZX08009-001, 2011ZX08002-002]
NR 30
TC 624
Z9 852
U1 5
U2 423
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 4
PY 2013
VL 496
IS 7443
BP 91
EP 95
DI 10.1038/nature12028
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 117ZZ
UT WOS:000316993400031
PM 23535592
DA 2026-03-09
ER

PT J
AU Russell, AB
   LeRoux, M
   Hathazi, K
   Agnello, DM
   Ishikawa, T
   Wiggins, PA
   Wai, SN
   Mougous, JD
AF Russell, Alistair B.
   LeRoux, Michele
   Hathazi, Krisztina
   Agnello, Danielle M.
   Ishikawa, Takahiko
   Wiggins, Paul A.
   Wai, Sun Nyunt
   Mougous, Joseph D.
TI Diverse type VI secretion phospholipases are functionally plastic antibacterial effectors
SO NATURE
LA English
DT Article
ID complete genome sequence; pseudomonas-aeruginosa; membrane-lipids; virulence; expression; protein; system; identification; prediction; survival
AB Membranes allow the compartmentalization of biochemical processes and are therefore fundamental to life. The conservation of the cellular membrane, combined with its accessibility to secreted proteins, has made it a common target of factors mediating antagonistic interactions between diverse organisms. Here we report the discovery of a diverse superfamily of bacterial phospholipase enzymes. Within this superfamily, we defined enzymes with phospholipase A(1) and A(2) activity, which are common in host-cell-targeting bacterial toxins and the venoms of certain insects and reptiles(1,2). However, we find that the fundamental role of the superfamily is to mediate antagonistic bacterial interactions as effectors of the type VI secretion system (T6SS) translocation apparatus; accordingly, we name these proteins type VI lipase effectors. Our analyses indicate that PldA of Pseudomonas aeruginosa, a eukaryotic-like phospholipase D-3, is a member of the type VI lipase effector superfamily and the founding substrate of the haemolysin co-regulated protein secretion island II T6SS (H2-T6SS). Although previous studies have specifically implicated PldA and the H2-T6SS in pathogenesis(3-5), we uncovered a specific role for the effector and its secretory machinery in intra-and interspecies bacterial interactions. Furthermore, we find that this effector achieves its antibacterial activity by degrading phosphatidylethanolamine, the major component of bacterial membranes. The surprising finding that virulence-associated phospholipases can serve as specific antibacterial effectors suggests that interbacterial interactions are a relevant factor driving the continuing evolution of pathogenesis.
C1 [Russell, Alistair B.; LeRoux, Michele; Agnello, Danielle M.; Mougous, Joseph D.] Univ Washington, Dept Microbiol, Seattle, WA 98195 USA.
   [LeRoux, Michele; Mougous, Joseph D.] Univ Washington, Mol & Cellular Biol Program, Seattle, WA 98195 USA.
   [Hathazi, Krisztina; Ishikawa, Takahiko; Wai, Sun Nyunt] Umea Univ, Dept Mol Biol, SE-90187 Umea, Sweden.
   [Hathazi, Krisztina; Ishikawa, Takahiko; Wai, Sun Nyunt] Umea Univ, Lab Mol Infect Med Sweden MIMS, SE-90187 Umea, Sweden.
   [Wiggins, Paul A.] Univ Washington, Dept Phys, Seattle, WA 98195 USA.
   [Wiggins, Paul A.] Univ Washington, Dept Bioengn, Seattle, WA 98195 USA.
C3 University of Washington; University of Washington Seattle; University of Washington; University of Washington Seattle; Umea University; Umea University; University of Washington; University of Washington Seattle; University of Washington; University of Washington Seattle
RP Mougous, JD (corresponding author), Univ Washington, Dept Microbiol, Seattle, WA 98195 USA.
EM mougous@u.washington.edu
FU National Institutes of Health (NIH) [AI080609, AI057141, AI105268, GM07270]; Cystic Fibrosis Foundation [CFR565-CR07]; National Science Foundation [PHY-084845, MCB-1151043, DGE-0718124]; Swedish Research Council [2010-3073, 2007-8673 UCMR Linnaeus, 2006-7431 MIMS]; Faculty of Medicine, Umea University; University of Washington Royalty Research Fund; Sloan Foundation; Burroughs Wellcome Fund; National Institute of Allergy and Infectious Diseases [R01AI080609] Funding Source: NIH RePORTER
NR 48
TC 321
Z9 378
U1 4
U2 176
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 25
PY 2013
VL 496
IS 7446
BP 508
EP +
DI 10.1038/nature12074
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 131HU
UT WOS:000317984400042
PM 23552891
DA 2026-03-09
ER

PT J
AU Allen, AS
   Berkovic, SF
   Cossette, P
   Delanty, N
   Dlugos, D
   Eichler, EE
   Epstein, MP
   Glauser, T
   Goldstein, DB
   Han, YJ
   Heinzen, EL
   Hitomi, Y
   Howell, KB
   Johnson, MR
   Kuzniecky, R
   Lowenstein, DH
   Lu, YF
   Madou, MRZ
   Marson, AG
   Mefford, HC
   Nieh, SE
   O'Brien, TJ
   Ottman, R
   Petrovski, S
   Poduri, A
   Ruzzo, EK
   Scheffer, IE
   Sherr, EH
   Yuskaitis, CJ
   Abou-Khalil, B
   Alldredge, BK
   Bautista, JF
   Berkovic, SF
   Boro, A
   Cascino, GD
   Consalvo, D
   Crumrine, P
   Devinsky, O
   Dlugos, D
   Epstein, MP
   Fiol, M
   Fountain, NB
   French, J
   Friedman, D
   Geller, EB
   Glauser, T
   Glynn, S
   Haut, SR
   Hayward, J
   Helmers, SL
   Joshi, S
   Kanner, A
   Kirsch, HE
   Knowlton, RC
   Kossoff, E
   Kuperman, R
   Kuzniecky, R
   Lowenstein, DH
   McGuire, SM
   Motika, PV
   Novotny, EJ
   Ottman, R
   Paolicchi, JM
   Parent, JM
   Park, K
   Poduri, A
   Scheffer, IE
   Shellhaas, RA
   Sherr, EH
   Shih, JJ
   Singh, R
   Sirven, J
   Smith, MC
   Sullivan, J
   Thio, LL
   Venkat, A
   Vining, EPG
   Von Allmen, GK
   Weisenberg, JL
   Widdess-Walsh, P
   Winawer, MR
AF Allen, Andrew S.
   Berkovic, Samuel F.
   Cossette, Patrick
   Delanty, Norman
   Dlugos, Dennis
   Eichler, Evan E.
   Epstein, Michael P.
   Glauser, Tracy
   Goldstein, David B.
   Han, Yujun
   Heinzen, Erin L.
   Hitomi, Yuki
   Howell, Katherine B.
   Johnson, Michael R.
   Kuzniecky, Ruben
   Lowenstein, Daniel H.
   Lu, Yi-Fan
   Madou, Maura R. Z.
   Marson, Anthony G.
   Mefford, Heather C.
   Nieh, Sahar Esmaeeli
   O'Brien, Terence J.
   Ottman, Ruth
   Petrovski, Slave
   Poduri, Annapurna
   Ruzzo, Elizabeth K.
   Scheffer, Ingrid E.
   Sherr, Elliott H.
   Yuskaitis, Christopher J.
   Abou-Khalil, Bassel
   Alldredge, Brian K.
   Bautista, Jocelyn F.
   Berkovic, Samuel F.
   Boro, Alex
   Cascino, Gregory D.
   Consalvo, Damian
   Crumrine, Patricia
   Devinsky, Orrin
   Dlugos, Dennis
   Epstein, Michael P.
   Fiol, Miguel
   Fountain, Nathan B.
   French, Jacqueline
   Friedman, Daniel
   Geller, Eric B.
   Glauser, Tracy
   Glynn, Simon
   Haut, Sheryl R.
   Hayward, Jean
   Helmers, Sandra L.
   Joshi, Sucheta
   Kanner, Andres
   Kirsch, Heidi E.
   Knowlton, Robert C.
   Kossoff, Erich
   Kuperman, Rachel
   Kuzniecky, Ruben
   Lowenstein, Daniel H.
   McGuire, Shannon M.
   Motika, Paul V.
   Novotny, Edward J.
   Ottman, Ruth
   Paolicchi, Juliann M.
   Parent, Jack M.
   Park, Kristen
   Poduri, Annapurna
   Scheffer, Ingrid E.
   Shellhaas, Renee A.
   Sherr, Elliott H.
   Shih, Jerry J.
   Singh, Rani
   Sirven, Joseph
   Smith, Michael C.
   Sullivan, Joseph
   Thio, Liu Lin
   Venkat, Anu
   Vining, Eileen P. G.
   Von Allmen, Gretchen K.
   Weisenberg, Judith L.
   Widdess-Walsh, Peter
   Winawer, Melodie R.
TI De novo mutations in epileptic encephalopathies
SO NATURE
LA English
DT Article
ID epilepsy; disease
AB Epileptic encephalopathies are a devastating group of severe childhood epilepsy disorders for which the cause is often unknown(1). Here we report a screen for de novo mutations in patients with two classical epileptic encephalopathies: infantile spasms (n = 149) and Lennox-Gastaut syndrome (n = 115). We sequenced the exomes of 264 probands, and their parents, and confirmed 329 de novo mutations. A likelihood analysis showed a significant excess of de novo mutations in the similar to 4,000 genes that are the most intolerant to functional genetic variation in the human population (P = 2.9 x 10(-3)). Among these are GABRB3, with de novo mutations in four patients, and ALG13, with the same de novo mutation in two patients; both genes show clear statistical evidence of association with epileptic encephalopathy. Given the relevant site-specific mutation rates, the probabilities of these outcomes occurring by chance are P = 4.1 x 10(-10) and P = 7.8 x 10(-12), respectively. Other genes with de novo mutations in this cohort include CACNA1A, CHD2, FLNA, GABRA1, GRIN1, GRIN2B, HNRNPU, IQSEC2, MTOR and NEDD4L. Finally, we show that the de novo mutations observed are enriched in specific gene sets including genes regulated by the fragile X protein (P < 10(-8)), as has been reported previously for autism spectrum disorders(2).
C1 [Allen, Andrew S.] Duke Univ, Med Ctr, Dept Biostat & Bioinformat, Duke Clin Res Inst, Durham, NC 27710 USA.
   [Allen, Andrew S.] Duke Univ, Med Ctr, Ctr Human Genome Variat, Durham, NC 27710 USA.
   [Berkovic, Samuel F.; Petrovski, Slave] Univ Melbourne Austin Hlth, Dept Med, Epilepsy Res Ctr, Heidelberg, Vic 3084, Australia.
   [Cossette, Patrick] Univ Montreal, CHUM Hop Notre Dame Montre, Montreal, PQ H2L 4M1, Canada.
   [Cossette, Patrick] CHUM Res Ctr, Montreal, PQ H2L 4M1, Canada.
   [Delanty, Norman] Royal Coll Surg, Dublin 9, Ireland.
   [Delanty, Norman] Beaumont Hosp, Dept Neurol, Dublin 9, Ireland.
   [Dlugos, Dennis; Venkat, Anu] Univ Penn, Perelman Sch Med, Childrens Hosp Philadelphia, Dept Neurol & Pediat, Philadelphia, PA 19104 USA.
   [Eichler, Evan E.] Univ Washington, Sch Med, Dept Gen Sci, Seattle, WA 98195 USA.
   [Eichler, Evan E.] Univ Washington, Howard Hughes Med Inst, Seattle, WA 98195 USA.
   [Epstein, Michael P.] Emory Univ, Sch Med, Dept Human Genet, Atlanta, GA 30322 USA.
   [Glauser, Tracy] Cincinnati Childrens Hosp Med Ctr, Div Neurol, Cincinnati, OH 45229 USA.
   [Goldstein, David B.; Han, Yujun; Heinzen, Erin L.; Hitomi, Yuki; Lu, Yi-Fan; Petrovski, Slave; Ruzzo, Elizabeth K.] Duke Univ, Sch Med, Ctr Human Genome Variat, Durham, NC 27708 USA.
   [Howell, Katherine B.] Royal Childrens Hosp Melbourne, Dept Neurol, Parkville, Vic 3052, Australia.
   [Johnson, Michael R.] Ctr Clin Translat Div Brain Sci, London SW7 2AZ, England.
   [Kuzniecky, Ruben; French, Jacqueline; Friedman, Daniel] NYU, Sch Med, Dept Neurol, Comprehens Epilepsy Ctr, New York, NY 10016 USA.
   [Lowenstein, Daniel H.; Madou, Maura R. Z.; Kirsch, Heidi E.; Sullivan, Joseph] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA.
   [Marson, Anthony G.] Univ Liverpool, Ctr Clin Sci, Dept Mol & Clin Pharmacol, Liverpool L9 7LJ, Merseyside, England.
   [Mefford, Heather C.] Univ Washington, Div Med Genet, Dept Pediat, Seattle, WA 98115 USA.
   [Nieh, Sahar Esmaeeli] Univ Calif San Francisco, San Francisco, CA 94143 USA.
   [O'Brien, Terence J.; Petrovski, Slave] Royal Melbourne Hosp, Dept Med, Parkville, Vic 3146, Australia.
   [O'Brien, Terence J.; Petrovski, Slave] Royal Melbourne Hosp, Dept Neurol, Parkville, Vic 3146, Australia.
   [Ottman, Ruth] Columbia Univ, Dept Epidemiol, New York, NY 10027 USA.
   [Ottman, Ruth] Columbia Univ, Dept Neurol, New York, NY 10027 USA.
   [Ottman, Ruth] Columbia Univ, GH Sergievsky Ctr, New York, NY 10027 USA.
   [Ottman, Ruth] New York State Psychiat Inst & Hosp, Div Epidemiol, New York, NY 10032 USA.
   [Poduri, Annapurna] Boston Childrens Hosp, Dept Neurol, Div Epilepsy & Clin Neurophysiol, Boston, MA 02115 USA.
   [Scheffer, Ingrid E.] Univ Melbourne Austin Hlth, Dept Med, Epilepsy Res Ctr, Heidelberg, Vic 3084, Australia.
   [Scheffer, Ingrid E.] Univ Melbourne, Florey Inst, Parkville, Vic 3052, Australia.
   [Scheffer, Ingrid E.] Univ Melbourne, Dept Pediat, Royal Childrens Hosp, Parkville, Vic 3052, Australia.
   [Sherr, Elliott H.] Univ Calif San Francisco, Pediat & Inst Human Genet, Dept Neurol, San Francisco, CA 94158 USA.
   [Yuskaitis, Christopher J.] Harvard Univ, Sch Med, Boston Childrens Hosp, Dept Neurol, Boston, MA 02115 USA.
   [Abou-Khalil, Bassel; Paolicchi, Juliann M.] Vanderbilt Univ, Med Ctr, Dept Neurol, Nashville, TN 37232 USA.
   [Alldredge, Brian K.] Univ Calif San Francisco, Sch Med, UCSF Sch Pharm, Dept Clin Pharm,Dept Neurol, San Francisco, CA 94143 USA.
   [Bautista, Jocelyn F.] Cleveland Clin Neurol Inst, Cleveland Clin Lerner Coll Med & Epilepsy Ctr, Dept Neurol, Cleveland, OH 44195 USA.
   [Boro, Alex] Albert Einstein Coll Med, Montefiore Med Ctr, Dept Neurol, Bronx, NY 10467 USA.
   [Cascino, Gregory D.] Mayo Clin, Div Epilepsy, Rochester, MN 55905 USA.
   [Consalvo, Damian] Ramos Meji Hosp, Div Neurol, Epilepsy Ctr, RA-1221 Buenos Aires, DF, Argentina.
   [Crumrine, Patricia] Univ Pittsburgh, UPMC, Med Epilepsy Program & EEG & Child Neurol, Childrens Hosp Pittsburgh,Sch Med, Pittsburgh, PA 15224 USA.
   [Devinsky, Orrin] NYU, Sch Med, St Barnabas Epilepsy Ctr, New York, NY 10016 USA.
   [Fiol, Miguel] Univ Minnesota, Sch Med, Epilepsy Care Ctr, Dept Neurol, Minneapolis, MN 55414 USA.
   [Fountain, Nathan B.] Univ Virginia, FE Dreifuss Comprehens Epilepsy Program, Charlottesville, VA 22908 USA.
   [Geller, Eric B.; Widdess-Walsh, Peter] St Barnabas Hosp, Div Neurol, Livingston, NJ 07039 USA.
   [Glynn, Simon] Univ Michigan Hlth Syst, Dept Neurol, Comprehens Epilepsy Program, Ann Arbor, MI 48109 USA.
   [Haut, Sheryl R.] Montefiore Med Ctr, Comprehens Epilepsy Ctr, Bronx, NY 10467 USA.
   [Hayward, Jean] Kaiser Permanente Grp, Oakland, CA 94618 USA.
   [Helmers, Sandra L.] Emory Univ, Sch Med, Atlanta, GA 30322 USA.
   [Joshi, Sucheta] Univ Michigan, Ann Arbor, MI 48109 USA.
   [Kanner, Andres; Smith, Michael C.] Rush Univ, Med Ctr, Rush Epilepsy Ctr, Dept Neurol Sci, Chicago, IL 60612 USA.
   [Kirsch, Heidi E.] Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94143 USA.
   [Knowlton, Robert C.] Univ Texas Houston, Sch Med, Houston, TX 77030 USA.
   [Kossoff, Erich] Johns Hopkins Univ Hosp, Child Neurol Pediat Neurol Residency Program, Baltimore, MD 21287 USA.
   [Kuperman, Rachel] Childrens Hosp, Epilepsy Program, Oakland, CA 94609 USA.
   [Kuperman, Rachel] Res Ctr Oakland, Oakland, CA 94609 USA.
   [McGuire, Shannon M.] Childrens Hosp Epilepsy Ctr New Orleans, New Orleans, LA 70118 USA.
   [Motika, Paul V.] Oregon Hlth & Sci Univ, Comprehens Epilepsy Ctr, Portland, OR 97239 USA.
   [Novotny, Edward J.] Univ Washington, Sch Med, Seattle Childrens Hosp, Dept Neurol, Seattle, WA 98105 USA.
   [Novotny, Edward J.] Univ Washington, Sch Med, Seattle Childrens Hosp, Dept Pediat, Seattle, WA 98105 USA.
   [Paolicchi, Juliann M.] Weill Cornell Med Ctr, New York, NY 10065 USA.
   [Parent, Jack M.] Univ Michigan, Med Ctr, Dept Neurol & Neurosci, Grad Program, Ann Arbor, MI 49108 USA.
   [Parent, Jack M.] Ann Arbor Vet Adm Healthcare Syst, Ann Arbor, MI 48105 USA.
   [Park, Kristen] Univ Colorado, Childrens Hosp Colorado, Sch Med, Dept Neurol, Denver, CO 80045 USA.
   Univ Colorado, Childrens Hosp Colorado, Sch Med, Dept Pediat, Denver, CO 80045 USA.
   [Shellhaas, Renee A.] Univ Michigan, Ann Arbor, MI USA.
   [Shih, Jerry J.] Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA.
   [Singh, Rani] Univ Michigan Hlth Syst, Div Pediat Neurol, Ann Arbor, MI 48109 USA.
   [Sirven, Joseph] Mayo Clin, Dept Neurol, Scottsdale, AZ 85259 USA.
   [Thio, Liu Lin] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA.
   [Vining, Eileen P. G.] Dept Neurol, Baltimore, MD 21287 USA.
   [Von Allmen, Gretchen K.] Univ Texas Houston, Sch Med, Div Child & Adolescent Neurol, Dept Pediat, Houston, TX 77030 USA.
   [Weisenberg, Judith L.] Washington Univ, Sch Med, Div Pediat Neurol, Dept Neurol, St Louis, MO 63110 USA.
   [Winawer, Melodie R.] Columbia Univ, Dept Neurol, New York, NY 10032 USA.
   [Winawer, Melodie R.] Columbia Univ, GH Sergievsky Ctr, New York, NY 10032 USA.
C3 Duke University; Duke University; University of Melbourne; Universite de Montreal; Universite de Montreal; Royal College of Surgeons in Ireland - RCSI; Beaumont Hospital Dublin; University of Pennsylvania; Pennsylvania Medicine; Childrens Hospital of Philadelphia; University of Washington; University of Washington Seattle; University of Washington; University of Washington Seattle; Howard Hughes Medical Institute; Emory University; Cincinnati Children's Hospital Medical Center; Duke University; Royal Children's Hospital Melbourne; New York University; University of California System; University of California San Francisco; University of Liverpool; University of Washington; University of Washington Seattle; University of California System; University of California San Francisco; Melbourne Health; Royal Melbourne Hospital; Melbourne Health; Royal Melbourne Hospital; Columbia University; Columbia University; Columbia University; New York State Psychiatry Institute; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; University of Melbourne; University of Melbourne; Florey Institute of Neuroscience & Mental Health; Royal Children's Hospital Melbourne; University of Melbourne; University of California System; University of California San Francisco; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Harvard Medical School; Vanderbilt University; University of California System; University of California San Francisco; Cleveland Clinic Foundation; University System of Ohio; Case Western Reserve University; Montefiore Medical Center; Albert Einstein College of Medicine; Yeshiva University; Mayo Clinic; Hospital Ramos Mejia; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh; New York University; University of Minnesota System; University of Minnesota Twin Cities; University of Virginia; University of Michigan System; University of Michigan; Montefiore Medical Center; Albert Einstein College of Medicine; Kaiser Permanente; Emory University; University of Michigan System; University of Michigan; Rush University; University of California System; University of California San Francisco; University of Texas System; University of Texas Health Science Center Houston; Johns Hopkins University; Johns Hopkins Medicine; Children's Hospital Los Angeles; Children's Hospital Oakland Research Institute; Children's Hospital of New Orleans; Oregon Health & Science University; Seattle Children's Hospital; University of Washington; University of Washington Seattle; Seattle Children's Hospital; University of Washington; University of Washington Seattle; Cornell University; Weill Cornell Medicine; Weill Cornell Medical Center; University of Michigan System; University of Michigan; University of Colorado System; University of Colorado Anschutz Medical Campus; University of Colorado Denver; Children's Hospital Colorado; Children's Hospital Colorado; University of Colorado System; University of Colorado Denver; University of Colorado Anschutz Medical Campus; University of Michigan System; University of Michigan; Mayo Clinic; University of Michigan System; University of Michigan; Mayo Clinic; Mayo Clinic Phoenix; Washington University (WUSTL); University of Texas System; University of Texas Health Science Center Houston; Washington University (WUSTL); Columbia University; Columbia University
RP Allen, AS (corresponding author), Duke Univ, Med Ctr, Dept Biostat & Bioinformat, Duke Clin Res Inst, Durham, NC 27710 USA.
FU National Institute of Neurological Disorders and Stroke [NS053998, NS077364, NS077274, NS077303, NS077276]; Richard Thalheimer Philanthropic Fund; ARRA [1RC2NS070342]; NIAID [R56AI098588]; Ellison Medical Foundation New Scholar award [AG-NS-0441-08]; SAID-Frederick, Inc. [M11-074]; Center for HIV/AIDS Vaccine Immunology ("CHAVI") from the National Institute of Allergy and Infectious Diseases, National Institutes of Health [UO1AIO67854]
NR 31
TC 1240
Z9 1415
U1 4
U2 185
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 12
PY 2013
VL 501
IS 7466
BP 217
EP +
DI 10.1038/nature12439
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 215XR
UT WOS:000324244900040
PM 23934111
DA 2026-03-09
ER

PT J
AU Elmegreen, BG
   Rubio, M
   Hunter, DA
   Verdugo, C
   Brinks, E
   Schruba, A
AF Elmegreen, Bruce G.
   Rubio, Monica
   Hunter, Deidre A.
   Verdugo, Celia
   Brinks, Elias
   Schruba, Andreas
TI Carbon monoxide in clouds at low metallicity in the dwarf irregular galaxy WLM
SO NATURE
LA English
DT Article
ID star-formation; dust property; gas; co; emission; mass; abundances; dynamics; excess; disk
AB Carbon monoxide (CO) is the primary tracer for interstellar clouds where stars form, but it has never been detected in galaxies in which the oxygen abundance relative to hydrogen is less than 20 per cent of that of the Sun, even though such 'low-metallicity' galaxies often form stars. This raises the question of whether stars can form in dense gas without molecules, cooling to the required near-zero temperatures by atomic transitions and dust radiation rather than by molecular line emission(1); and it highlights uncertainties about star formation in the early Universe, when the metallicity was generally low. Here we report the detection of CO in two regions of a local dwarf irregular galaxy, WLM, where the metallicity is 13 per cent of the solar value(2,3). We use new submillimetre observations and archival far-infrared observations to estimate the cloud masses, which are both slightly greater than 100,000 solar masses. The clouds have produced stars at a rate per molecule equal to 10 per cent of that in the local Orion nebula cloud. The CO fraction of the molecular gas is also low, about 3 per cent of the Milky Way value. These results suggest that in small galaxies both star-forming cores and CO molecules become increasingly rare in molecular hydrogen clouds as the metallicity decreases.
C1 [Elmegreen, Bruce G.] TJ Watson Res Ctr, IBM Res Div, Yorktown Hts, NY 10598 USA.
   [Rubio, Monica; Verdugo, Celia] Univ Chile, Dept Astron, Santiago, Chile.
   [Hunter, Deidre A.] Lowell Observ, Flagstaff, AZ 86001 USA.
   [Brinks, Elias] Univ Hertfordshire, Ctr Astrophys Res, Hatfield AL10 9AB, Herts, England.
   [Schruba, Andreas] CALTECH, Cahill Ctr Astron & Astrophys, Pasadena, CA 91125 USA.
C3 International Business Machines (IBM); IBM USA; Universidad de Chile; University of Hertfordshire; California Institute of Technology
RP Elmegreen, BG (corresponding author), TJ Watson Res Ctr, IBM Res Div, 1101 Kitchawan Rd, Yorktown Hts, NY 10598 USA.
EM bge@us.ibm.com
FU US National Science Foundation [AST-0707563, AST-0707426]; CONICYT (FONDECYT) [1080335]; Chilean Center for Astrophysics FONDAP [15010003]; Deutsche Forschungsgemeinschaft [1177]; STFC [ST/J001333/1] Funding Source: UKRI; Science and Technology Facilities Council [ST/J001333/1] Funding Source: researchfish
NR 30
TC 50
Z9 52
U1 0
U2 12
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 28
PY 2013
VL 495
IS 7442
BP 487
EP 489
DI 10.1038/nature11933
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 113QN
UT WOS:000316682800040
PM 23538829
DA 2026-03-09
ER

PT J
AU Zhang, G
   Li, JX
   Purkayastha, S
   Tang, YZ
   Zhang, H
   Yin, Y
   Li, B
   Liu, G
   Cai, DS
AF Zhang, Guo
   Li, Juxue
   Purkayastha, Sudarshana
   Tang, Yizhe
   Zhang, Hai
   Yin, Ye
   Li, Bo
   Liu, Gang
   Cai, Dongsheng
TI Hypothalamic programming of systemic ageing involving IKK-β, NF-κB and GnRH
SO NATURE
LA English
DT Article
ID tumor-necrosis-factor; extends life-span; mouse model; neurons; microglia; longevity; obesity; mice; inflammation; neurogenesis
AB Ageing is a result of gradual and overall functional deteriorations across the body; however, it is unknown whether an individual tissue primarily works to mediate the ageing progress and control lifespan. Here we show that the hypothalamus is important for the development of whole-body ageing in mice, and that the underlying basis involves hypothalamic immunity mediated by I kappa B kinase-beta (IKK-beta), nuclear factor kappa B (NF-kappa B) and related microglianeuron immune crosstalk. Several interventional models were developed showing that ageing retardation and lifespan extension are achieved in mice by preventing ageing-related hypothalamic or brain IKK-beta and NF-kappa B activation. Mechanistic studies further revealed that IKK-beta and NF-kappa B inhibit gonadotropin-releasing hormone (GnRH) to mediate ageing-related hypothalamic GnRH decline, and GnRH treatment amends ageing-impaired neurogenesis and decelerates ageing. In conclusion, the hypothalamus has a programmatic role in ageing development via immune-neuroendocrine integration, and immune inhibition or GnRH restoration in the hypothalamus/brain represent two potential strategies for optimizing lifespan and combating ageing-related health problems.
C1 [Zhang, Guo; Li, Juxue; Purkayastha, Sudarshana; Tang, Yizhe; Zhang, Hai; Yin, Ye; Li, Bo; Liu, Gang; Cai, Dongsheng] Albert Einstein Coll Med, Dept Mol Pharmacol, Bronx, NY 10461 USA.
   [Zhang, Guo; Li, Juxue; Purkayastha, Sudarshana; Tang, Yizhe; Zhang, Hai; Yin, Ye; Li, Bo; Liu, Gang; Cai, Dongsheng] Albert Einstein Coll Med, Diabet Res Ctr, Bronx, NY 10461 USA.
   [Zhang, Guo; Li, Juxue; Purkayastha, Sudarshana; Tang, Yizhe; Zhang, Hai; Yin, Ye; Li, Bo; Liu, Gang; Cai, Dongsheng] Albert Einstein Coll Med, Inst Aging, Bronx, NY 10461 USA.
C3 Montefiore Medical Center; Albert Einstein College of Medicine; Yeshiva University; Yeshiva University; Montefiore Medical Center; Albert Einstein College of Medicine; Yeshiva University; Montefiore Medical Center; Albert Einstein College of Medicine
RP Cai, DS (corresponding author), Albert Einstein Coll Med, Dept Mol Pharmacol, Bronx, NY 10461 USA.
EM dongsheng.cai@einstein.yu.edu
FU National Institutes of Health (NIH) [R01 AG031774, R01 DK078750]; American Diabetes Association [1-12-BS-20]; Irma T. Hirschl Scholarship; National Institute on Aging [R01AG031774] Funding Source: NIH RePORTER
NR 44
TC 709
Z9 820
U1 2
U2 217
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 9
PY 2013
VL 497
IS 7448
BP 211
EP +
DI 10.1038/nature12143
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 139CD
UT WOS:000318558200030
PM 23636330
DA 2026-03-09
ER

PT J
AU Kaltenbrunner, M
   Sekitani, T
   Reeder, J
   Yokota, T
   Kuribara, K
   Tokuhara, T
   Drack, M
   Schwödiauer, R
   Graz, I
   Bauer-Gogonea, S
   Bauer, S
   Someya, T
AF Kaltenbrunner, Martin
   Sekitani, Tsuyoshi
   Reeder, Jonathan
   Yokota, Tomoyuki
   Kuribara, Kazunori
   Tokuhara, Takeyoshi
   Drack, Michael
   Schwoediauer, Reinhard
   Graz, Ingrid
   Bauer-Gogonea, Simona
   Bauer, Siegfried
   Someya, Takao
TI An ultra-lightweight design for imperceptible plastic electronics
SO NATURE
LA English
DT Article
ID field-effect transistors; organic transistors; thin-film; n-channel; silicon; performance; circuits; semiconductors; mechanics; pressure
AB Electronic devices have advanced from their heavy, bulky origins to become smart, mobile appliances. Nevertheless, they remain rigid, which precludes their intimate integration into everyday life. Flexible, textile and stretchable electronics are emerging research areas and may yield mainstream technologies(1-3). Rollable and unbreakable backplanes with amorphous silicon field-effect transistors on steel substrates only 3 mu m thick have been demonstrated(4). On polymer substrates, bending radii of 0.1 mm have been achieved inflexible electronic devices(5-7). Concurrently, the need for compliant electronics that can not only be flexed but also conform to three-dimensional shapes has emerged(3). Approaches include the transfer of ultrathin polyimide layers encapsulating silicon CMOS circuits onto pre-stretched elastomers(8), the use of conductive elastomers integrated with organic field-effect transistors (OFETs) on polyimide islands(9), and fabrication of OFETs and gold interconnects on elastic substrates(10) to realize pressure, temperature and optical sensors(11-14). Here we present a platform that makes electronics both virtually unbreakable(4) and imperceptible. Fabricated directly on ultrathin (1 mu m) polymer foils, our electronic circuits are light (3 g m(-2)) and ultraflexible and conform to their ambient, dynamic environment. Organic transistors with an ultra-dense oxide gate dielectric a few nanometres thick formed at room temperature enable sophisticated large-area electronic foils with unprecedented mechanical and environmental stability: they withstand repeated bending to radii of 5 mu m and less, can be crumpled like paper, accommodate stretching up to 230% on prestrained elastomers, and can be operated at high temperatures and in aqueous environments. Because manufacturing costs of organic electronics are potentially low, imperceptible electronic foils may be as common in the future as plastic wrap is today. Applications include matrix-addressed tactile sensor foils for health care and monitoring, thin-film heaters, temperature and infrared sensors, displays(15), and organic solar cells(16).
C1 [Kaltenbrunner, Martin; Sekitani, Tsuyoshi; Reeder, Jonathan; Yokota, Tomoyuki; Kuribara, Kazunori; Tokuhara, Takeyoshi; Someya, Takao] Univ Tokyo, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1138656, Japan.
   [Kaltenbrunner, Martin; Sekitani, Tsuyoshi; Someya, Takao] Japan Sci & Technol Agcy JST, Exploratory Res Adv Technol ERATO, Bunkyo Ku, Tokyo 1130032, Japan.
   [Kaltenbrunner, Martin; Drack, Michael; Schwoediauer, Reinhard; Graz, Ingrid; Bauer-Gogonea, Simona; Bauer, Siegfried] Johannes Kepler Univ Linz, A-4040 Linz, Austria.
C3 University of Tokyo; Japan Science & Technology Agency (JST); Johannes Kepler University Linz
RP Someya, T (corresponding author), Univ Tokyo, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1138656, Japan.
EM martin@ntech.t.u-tokyo.ac.jp; someya@ee.t.u-tokyo.ac.jp
FU JST Someya Bio-Harmonized ERATO; ERC; Wilhelm Macke Foundation; mobility programme of the Johannes Kepler University Linz (KIP)
NR 40
TC 2227
Z9 2514
U1 36
U2 3005
PU NATURE PUBLISHING 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 25
PY 2013
VL 499
IS 7459
BP 458
EP +
DI 10.1038/nature12314
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 187YP
UT WOS:000322157900036
PM 23887430
DA 2026-03-09
ER

PT J
AU Rinke, C
   Schwientek, P
   Sczyrba, A
   Ivanova, NN
   Anderson, IJ
   Cheng, JF
   Darling, A
   Malfatti, S
   Swan, BK
   Gies, EA
   Dodsworth, JA
   Hedlund, BP
   Tsiamis, G
   Sievert, SM
   Liu, WT
   Eisen, JA
   Hallam, SJ
   Kyrpides, NC
   Stepanauskas, R
   Rubin, EM
   Hugenholtz, P
   Woyke, T
AF Rinke, Christian
   Schwientek, Patrick
   Sczyrba, Alexander
   Ivanova, Natalia N.
   Anderson, Iain J.
   Cheng, Jan-Fang
   Darling, Aaron
   Malfatti, Stephanie
   Swan, Brandon K.
   Gies, Esther A.
   Dodsworth, Jeremy A.
   Hedlund, Brian P.
   Tsiamis, George
   Sievert, Stefan M.
   Liu, Wen-Tso
   Eisen, Jonathan A.
   Hallam, Steven J.
   Kyrpides, Nikos C.
   Stepanauskas, Ramunas
   Rubin, Edward M.
   Hugenholtz, Philip
   Woyke, Tanja
TI Insights into the phylogeny and coding potential of microbial dark matter
SO NATURE
LA English
DT Article
ID lateral gene-transfer; hydrothermal vent; sp-nov.; diversity; bacteria; division; verrucomicrobia; metagenomics; superphylum; chlamydiae
AB Genome sequencing enhances our understanding of the biological world by providing blueprints for the evolutionary and functional diversity that shapes the biosphere. However, microbial genomes that are currently available are of limited phylogenetic breadth, owing to our historical inability to cultivate most microorganisms in the laboratory. We apply single-cell genomics to target and sequence 201 uncultivated archaeal and bacterial cells from nine diverse habitats belonging to 29 major mostly uncharted branches of the tree of life, so-called 'microbial dark matter'. With this additional genomic information, we are able to resolve many intra-and inter-phylum-level relationships and to propose two new superphyla. We uncover unexpected metabolic features that extend our understanding of biology and challenge established boundaries between the three domains of life. These include a novel amino acid use for the opal stop codon, an archaeal-type purine synthesis in Bacteria and complete sigma factors in Archaea similar to those in Bacteria. The single-cell genomes also served to phylogenetically anchor up to 20% of metagenomic reads in some habitats, facilitating organism-level interpretation of ecosystem function. This study greatly expands the genomic representation of the tree of life and provides a systematic step towards a better understanding of biological evolution on our planet.
C1 [Rinke, Christian; Schwientek, Patrick; Sczyrba, Alexander; Ivanova, Natalia N.; Anderson, Iain J.; Cheng, Jan-Fang; Malfatti, Stephanie; Kyrpides, Nikos C.; Rubin, Edward M.; Woyke, Tanja] DOE Joint Genome Inst, Walnut Creek, CA 94598 USA.
   [Sczyrba, Alexander] Univ Bielefeld, Ctr Biotechnol, D-33602 Bielefeld, Germany.
   [Darling, Aaron; Eisen, Jonathan A.] Univ Calif Davis, Dept Evolut & Ecol, Davis, CA 95616 USA.
   [Darling, Aaron] Univ Technol Sydney, Inst I3, Ultimo, NSW 2007, Australia.
   [Swan, Brandon K.; Stepanauskas, Ramunas] Bigelow Lab Ocean Sci, East Boothbay, ME 04544 USA.
   [Gies, Esther A.; Hallam, Steven J.] Univ British Columbia, Dept Microbiol & Immunol, Vancouver, BC V6T 1Z3, Canada.
   [Gies, Esther A.; Hallam, Steven J.] Univ British Columbia, Grad Program Bioinformat, Vancouver, BC V6T 1Z3, Canada.
   [Dodsworth, Jeremy A.; Hedlund, Brian P.] Univ Nevada, Sch Life Sci, Las Vegas, NV 89154 USA.
   [Tsiamis, George] Univ Patras, Dept Environm & Nat Resources Management, Agrinion 30100, TK, Greece.
   [Sievert, Stefan M.] Woods Hole Oceanog Inst, Dept Biol, Woods Hole, MA 02543 USA.
   [Liu, Wen-Tso] Univ Illinois, Dept Civil & Environm Engn, Urbana, IL 61802 USA.
   [Hugenholtz, Philip] Univ Queensland, Sch Chem & Mol Biosci, Australian Ctr Ecogenom, St Lucia, Qld 4072, Australia.
   [Hugenholtz, Philip] Univ Queensland, Inst Mol Biosci, St Lucia, Qld 4072, Australia.
C3 United States Department of Energy (DOE); University of Bielefeld; University of California System; University of California Davis; University of Technology Sydney; Bigelow Laboratory for Ocean Sciences; University of British Columbia; University of British Columbia; Nevada System of Higher Education (NSHE); University of Nevada Las Vegas; University of Patras; Woods Hole Oceanographic Institution; University of Illinois System; University of Illinois Urbana-Champaign; University of Queensland; University of Queensland
RP Hugenholtz, P (corresponding author), Univ Queensland, Sch Chem & Mol Biosci, Australian Ctr Ecogenom, St Lucia, Qld 4072, Australia.
EM p.hugenholtz@uq.edu.au; twoyke@lbl.gov
FU Office of Science of the US Department of Energy [DE-AC02-05CH11231]; BMBF [031A190]; NASA [EXO-NNX11AR78G]; NSF [OISE 096842, OCE-0452333, OCE-1136727, DEB-841933, EF-826924, OCE-1232982, OCE-821374, OCE-1136488]; WHOI's Andrew W. Mellon Fund for Innovative Research; Canadian Foundation for Innovation; British Columbia Knowledge Development Fund; National Sciences and Engineering Research Council (NSERC) of Canada; TULA foundation; Alfred P. Sloan Foundation; Australian Research Council [DP120103498]; Directorate For Geosciences; Division Of Ocean Sciences [1232982, 1136488] Funding Source: National Science Foundation; Division Of Ocean Sciences; Directorate For Geosciences [1136727] Funding Source: National Science Foundation; Div Of Biological Infrastructure; Direct For Biological Sciences [1226726] Funding Source: National Science Foundation; Office Of Internatl Science &Engineering; Office Of The Director [0968421] Funding Source: National Science Foundation
NR 50
TC 1708
Z9 2044
U1 14
U2 794
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 25
PY 2013
VL 499
IS 7459
BP 431
EP 437
DI 10.1038/nature12352
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 187YP
UT WOS:000322157900031
PM 23851394
DA 2026-03-09
ER

PT J
AU Delling, M
   DeCaen, PG
   Doerner, JF
   Febvay, S
   Clapham, DE
AF Delling, Markus
   DeCaen, Paul G.
   Doerner, Julia F.
   Febvay, Sebastien
   Clapham, David E.
TI Primary cilia are specialized calcium signalling organelles
SO NATURE
LA English
DT Article
ID hedgehog; links
AB Primary cilia are solitary, non-motile extensions of the centriole found on nearly all nucleated eukaryotic cells between cell divisions. Only similar to 200-300 nm in diameter and a few micrometres long, they are separated from the cytoplasm by the ciliary neck and basal body. Often called sensory cilia, they are thought to receive chemical and mechanical stimuli and initiate specific cellular signal transduction pathways. When activated by a ligand, hedgehog pathway proteins, such as GLI2 and smoothened (SMO), translocate from the cell into the cilium(1,2). Mutations in primary ciliary proteins are associated with severe developmental defects(3). The ionic conditions, permeability of the primary cilia membrane, and effectiveness of the diffusion barriers between the cilia and cell body are unknown. Here we show that cilia are a unique calcium compartment regulated by a heteromeric TRP channel, PKD1L1-PKD2L1, in mice and humans. In contrast to the hypothesis that polycystin (PKD) channels initiate changes in ciliary calcium that are conducted into the cytoplasm(4), we show that changes in ciliary calcium concentration occur without substantially altering global cytoplasmic calcium. PKD1L1-PKD2L1 acts as a ciliary calcium channel controlling ciliary calcium concentration and thereby modifying SMO-activated GLI2 translocation and GLI1 expression.
C1 [Delling, Markus; DeCaen, Paul G.; Doerner, Julia F.; Febvay, Sebastien; Clapham, David E.] Boston Childrens Hosp, Howard Hughes Med Inst, Dept Cardiol, Boston, MA 02115 USA.
   [Clapham, David E.] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA.
C3 Howard Hughes Medical Institute; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Harvard University; Harvard Medical School
RP Clapham, DE (corresponding author), Boston Childrens Hosp, Howard Hughes Med Inst, Dept Cardiol, 320 Longwood Ave, Boston, MA 02115 USA.
EM dclapham@enders.tch.harvard.edu
FU NIH [T32-HL007572]; National Heart Lung and Blood Institute [T32HL007572] Funding Source: NIH RePORTER
NR 24
TC 394
Z9 453
U1 3
U2 65
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 12
PY 2013
VL 504
IS 7479
BP 311
EP +
DI 10.1038/nature12833
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 267TQ
UT WOS:000328121500043
PM 24336288
DA 2026-03-09
ER

PT J
AU Beronja, S
   Janki, P
   Heller, E
   Lien, WH
   Keyes, BE
   Oshimori, N
   Fuchs, E
AF Beronja, Slobodan
   Janki, Peter
   Heller, Evan
   Lien, Wen-Hui
   Keyes, Brice E.
   Oshimori, Naoki
   Fuchs, Elaine
TI RNAi screens in mice identify physiological regulators of oncogenic growth
SO NATURE
LA English
DT Article
ID hair follicle morphogenesis; beta-catenin; stem-cells; tgf-beta; differentiation; homeostasis; carcinomas; expression; leukemia; reveals
AB Tissue growth is the multifaceted outcome of a cell's intrinsic capabilities and its interactions with the surrounding environment. Decoding these complexities is essential for understanding human development and tumorigenesis. Here we tackle this problem by carrying out the first genome-wide RNA-interference-mediated screens in mice. Focusing on skin development and oncogenic (Hras(G12V)-induced) hyperplasia, our screens uncover previously unknown as well as anticipated regulators of embryonic epidermal growth. Among the top oncogenic screen hits are Mllt6 and the Wnt effector beta-catenin, which maintain Hras(G12V)-dependent hyperproliferation. We also expose beta-catenin as an unanticipated antagonist of normal epidermal growth, functioning through Wnt-independent intercellular adhesion. Finally, we validate functional significance in mouse and human cancers, thereby establishing the feasibility of in vivo mammalian genome-wide investigations to dissect tissue development and tumorigenesis. By documenting some oncogenic growth regulators, we pave the way for future investigations of other hits and raise promise for unearthing new targets for cancer therapies.
C1 [Beronja, Slobodan; Janki, Peter; Heller, Evan; Lien, Wen-Hui; Keyes, Brice E.; Oshimori, Naoki; Fuchs, Elaine] Rockefeller Univ, Howard Hughes Med Inst, Lab Mammalian Cell Biol & Dev, New York, NY 10065 USA.
C3 Rockefeller University; Howard Hughes Medical Institute
RP Fuchs, E (corresponding author), Rockefeller Univ, Howard Hughes Med Inst, Lab Mammalian Cell Biol & Dev, New York, NY 10065 USA.
EM fuchslb@rockefeller.edu
FU NIH [R37-AR27883, K99-AR061469]; Emerald Foundation; Human Frontiers Science Program Postdoctoral Fellowship; National Institute of Arthritis and Musculoskeletal and Skin Diseases [R37AR027883] Funding Source: NIH RePORTER
NR 44
TC 136
Z9 160
U1 0
U2 65
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 12
PY 2013
VL 501
IS 7466
BP 185
EP +
DI 10.1038/nature12464
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 215XR
UT WOS:000324244900033
PM 23945586
DA 2026-03-09
ER

PT J
AU Costa, Y
   Ding, JJ
   Theunissen, TW
   Faiola, F
   Hore, TA
   Shliaha, PV
   Fidalgo, M
   Saunders, A
   Lawrence, M
   Dietmann, S
   Das, S
   Levasseur, DN
   Li, Z
   Xu, MJ
   Reik, W
   Silva, JCR
   Wang, JL
AF Costa, Yael
   Ding, Junjun
   Theunissen, Thorold W.
   Faiola, Francesco
   Hore, Timothy A.
   Shliaha, Pavel V.
   Fidalgo, Miguel
   Saunders, Arven
   Lawrence, Moyra
   Dietmann, Sabine
   Das, Satyabrata
   Levasseur, Dana N.
   Li, Zhe
   Xu, Mingjiang
   Reik, Wolf
   Silva, Jose C. R.
   Wang, Jianlong
TI NANOG-dependent function of TET1 and TET2 in establishment of pluripotency
SO NATURE
LA English
DT Article
ID cell self-renewal; 5-hydroxymethylcytosine; protein; dna; conversion; network; genes
AB Molecular control of the pluripotent state is thought to reside in a core circuitry of master transcription factors including the homeodomain-containing protein NANOG(1,2), which has an essential role in establishing ground state pluripotency during somatic cell reprogramming(3,4). Whereas the genomic occupancy of NANOG has been extensively investigated, comparatively little is known about NANOG-associated proteins(5) and their contribution to the NANOG-mediated reprogramming process. Using enhanced purification techniques and a stringent computational algorithm, we identify 27 high-confidence protein interaction partners of NANOG in mouse embryonic stem cells. These consist of 19 previously unknown partners of NANOG that have not been reported before, including the ten-eleven translocation (TET) family methylcytosine hydroxylase TET1. We confirm physical association of NANOG with TET1, and demonstrate that TET1, in synergy with NANO G, enhances the efficiency of reprogramming. We also find physical associatinn and reprogramming synergy of TET2 with NANOG, and demonstrate that knockdown of TET2 abolishes the reprogramming synergy of NANOG with a catalytically deficient mutant of TET1. These results indicate that the physical interaction between NANOG and TET1/TET2 proteins facilitates reprogramming in a manner that is dependent on the catalytic activity of TET1/TET2. TET1 and NANOG co-occupy genomic loci of genes associated with both maintenance of pluripotency and lineage commitment in embryonic stem cells, and TET1 binding is reduced upon NANOG depletion. Co-expression of NANOG and TET1 increases 5-hydroxymethylcytosine levels at the top-ranked common target loci Esrrb and Oct4 (also called Pou5f1), resulting in priming of their expression before reprogramming to naive pluripotency. We propose that TET1 is recruited by NANOG to enhance the expression of a subset of key reprogramming target genes. These results provide an insight into the reprogramming mechanism of NANOG and uncover a new role for 5-methykytosine hydroxylases in the establishment of naive pluripotency.
C1 [Costa, Yael; Theunissen, Thorold W.; Lawrence, Moyra; Dietmann, Sabine; Silva, Jose C. R.] Univ Cambridge, Wellcome Trust Med Res Council Cambridge Stem Cel, Cambridge CB2 1QR, England.
   [Ding, Junjun; Faiola, Francesco; Fidalgo, Miguel; Saunders, Arven; Wang, Jianlong] Mt Sinai Sch Med, Black Family Stem Cell Inst, Grad Sch Biol Sci, Dept Dev & Regenerat Biol, New York, NY 10029 USA.
   [Theunissen, Thorold W.; Lawrence, Moyra; Silva, Jose C. R.] Univ Cambridge, Dept Biochem, Cambridge CB2 1QR, England.
   [Hore, Timothy A.; Reik, Wolf] Babraham Inst, Epigenet Programme, Cambridge CB22 3AT, England.
   [Shliaha, Pavel V.] Univ Cambridge, Cambridge Ctr Prote, Cambridge Syst Biol Ctr, Cambridge CB2 1QR, England.
   [Das, Satyabrata; Levasseur, Dana N.] Univ Iowa, Dept Internal Med, Iowa City, IA 52242 USA.
   [Li, Zhe; Xu, Mingjiang] Indiana Univ, Dept Pediat, Indianapolis, IN 46202 USA.
   [Reik, Wolf] Univ Cambridge, Ctr Trophoblast Res, Cambridge CB2 3EG, England.
C3 University of Cambridge; Icahn School of Medicine at Mount Sinai; University of Cambridge; UK Research & Innovation (UKRI); Biotechnology and Biological Sciences Research Council (BBSRC); Babraham Institute; University of Cambridge; University of Iowa; Indiana University System; Indiana University Indianapolis; University of Cambridge
RP Wang, JL (corresponding author), Mt Sinai Sch Med, Black Family Stem Cell Inst, Grad Sch Biol Sci, Dept Dev & Regenerat Biol, New York, NY 10029 USA.
EM jcs64@cam.ac.uk; jianlong.wang@mssm.edu
FU NIH [1R01-GM095942-01A1]; New York state Department of Health (NYSTEM) [C026420]; Black Family Stem Cell Institute; Wellcome Trust [WT086692MA, WT079249]; Isaac Newton Trust [11.19(ad)]; BBSRC; MRC; Wellcome Trust; EU; BBSRC [BB/H008071/1] Funding Source: UKRI; MRC [G0700098] Funding Source: UKRI; Biotechnology and Biological Sciences Research Council [BB/H008071/1] Funding Source: researchfish; Medical Research Council [G0700098] Funding Source: researchfish
NR 26
TC 357
Z9 434
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 MAR 21
PY 2013
VL 495
IS 7441
BP 370
EP 374
DI 10.1038/nature11925
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 113EY
UT WOS:000316650500043
PM 23395962
DA 2026-03-09
ER

PT J
AU Lappalainen, T
   Sammeth, M
   Friedländer, MR
   't Hoen, PAC
   Monlong, J
   Rivas, MA
   Gonzàlez-Porta, M
   Kurbatova, N
   Griebel, T
   Ferreira, PG
   Barann, M
   Wieland, T
   Greger, L
   van Iterson, M
   Almlöf, J
   Ribeca, P
   Pulyakhina, I
   Esser, D
   Giger, T
   Tikhonov, A
   Sultan, M
   Bertier, G
   MacArthur, DG
   Lek, M
   Lizano, E
   Buermans, HPJ
   Padioleau, I
   Schwarzmayr, T
   Karlberg, O
   Ongen, H
   Kilpinen, H
   Beltran, S
   Gut, M
   Kahlem, K
   Amstislavskiy, V
   Stegle, O
   Pirinen, M
   Montgomery, SB
   Donnelly, P
   McCarthy, MI
   Flicek, P
   Strom, TM
   Lehrach, H
   Schreiber, S
   Sudbrak, R
   Carracedo, A
   Antonarakis, SE
   Haesler, R
   Syvaenen, AC
   Van Ommen, GJ
   Brazma, A
   Meitinger, T
   Rosenstiel, P
   Guigó, R
   Gut, IG
   Estivill, X
   Dermitzakis, ET
AF Lappalainen, Tuuli
   Sammeth, Michael
   Friedlaender, Marc R.
   't Hoen, Peter A. C.
   Monlong, Jean
   Rivas, Manuel A.
   Gonzalez-Porta, Mar
   Kurbatova, Natalja
   Griebel, Thasso
   Ferreira, Pedro G.
   Barann, Matthias
   Wieland, Thomas
   Greger, Liliana
   van Iterson, Maarten
   Almloef, Jonas
   Ribeca, Paolo
   Pulyakhina, Irina
   Esser, Daniela
   Giger, Thomas
   Tikhonov, Andrew
   Sultan, Marc
   Bertier, Gabrielle
   MacArthur, Daniel G.
   Lek, Monkol
   Lizano, Esther
   Buermans, Henk P. J.
   Padioleau, Ismael
   Schwarzmayr, Thomas
   Karlberg, Olof
   Ongen, Halit
   Kilpinen, Helena
   Beltran, Sergi
   Gut, Marta
   Kahlem, Katja
   Amstislavskiy, Vyacheslav
   Stegle, Oliver
   Pirinen, Matti
   Montgomery, Stephen B.
   Donnelly, Peter
   McCarthy, Mark I.
   Flicek, Paul
   Strom, Tim M.
   Lehrach, Hans
   Schreiber, Stefan
   Sudbrak, Ralf
   Carracedo, Angel
   Antonarakis, Stylianos E.
   Haesler, Robert
   Syvaenen, Ann-Christine
   Van Ommen, Gert-Jan
   Brazma, Alvis
   Meitinger, Thomas
   Rosenstiel, Philip
   Guigo, Roderic
   Gut, Ivo G.
   Estivill, Xavier
   Dermitzakis, Emmanouil T.
TI Transcriptome and genome sequencing uncovers functional variation in humans
SO NATURE
LA English
DT Article
ID gene-expression; landscape; variants
AB Genome sequencing projects are discovering millions of genetic variants in humans, and interpretation of their functional effects is essential for understanding the genetic basis of variation in human traits. Here we report sequencing and deep analysis of messenger RNA and microRNA from lymphoblastoid cell lines of 462 individuals from the 1000 Genomes Project-the first uniformly processed high-throughput RNA-sequencing data from multiple human populations with high-quality genome sequences. We discover extremely widespread genetic variation affecting the regulation of most genes, with transcript structure and expression level variation being equally common but genetically largely independent. Our characterization of causal regulatory variation sheds light on the cellular mechanisms of regulatory and loss-of-function variation, and allows us to infer putative causal variants for dozens of disease-associated loci. Altogether, this study provides a deep understanding of the cellular mechanisms of transcriptome variation and of the landscape of functional variants in the human genome.
C1 [Lappalainen, Tuuli; Giger, Thomas; Padioleau, Ismael; Ongen, Halit; Kilpinen, Helena; Montgomery, Stephen B.; Antonarakis, Stylianos E.; Dermitzakis, Emmanouil T.] Univ Geneva, Sch Med, Dept Genet Med & Dev, CH-1211 Geneva, Switzerland.
   [Lappalainen, Tuuli; Padioleau, Ismael; Ongen, Halit; Kilpinen, Helena; Antonarakis, Stylianos E.; Dermitzakis, Emmanouil T.] Univ Geneva, iG3, CH-1211 Geneva, Switzerland.
   [Lappalainen, Tuuli; Padioleau, Ismael; Ongen, Halit; Kilpinen, Helena; Dermitzakis, Emmanouil T.] Swiss Inst Bioinformat, CH-1211 Geneva, Switzerland.
   [Sammeth, Michael; Griebel, Thasso; Ribeca, Paolo; Beltran, Sergi; Gut, Marta; Kahlem, Katja; Gut, Ivo G.] Ctr Nacl Anal Genom, Barcelona 08028, Catalonia, Spain.
   [Sammeth, Michael; Friedlaender, Marc R.; Monlong, Jean; Ferreira, Pedro G.; Bertier, Gabrielle; Lizano, Esther; Guigo, Roderic; Estivill, Xavier] CRG, Barcelona 08003, Catalonia, Spain.
   [Sammeth, Michael; Friedlaender, Marc R.; Monlong, Jean; Ferreira, Pedro G.; Bertier, Gabrielle; Lizano, Esther; Guigo, Roderic; Estivill, Xavier] UPF, Barcelona 08003, Catalonia, Spain.
   [Sammeth, Michael; Friedlaender, Marc R.; Monlong, Jean; Ferreira, Pedro G.; Lizano, Esther; Guigo, Roderic; Estivill, Xavier] CRG Hosp del Mar Res Inst, Barcelona 08003, Catalonia, Spain.
   [Friedlaender, Marc R.; Lizano, Esther; Estivill, Xavier] CRG CIBERESP, Barcelona 08003, Catalonia, Spain.
   ['t Hoen, Peter A. C.; van Iterson, Maarten; Pulyakhina, Irina; Buermans, Henk P. J.; Van Ommen, Gert-Jan] Leiden Univ, Med Ctr, Dept Human Genet, NL-2300 RC Leiden, Netherlands.
   [Rivas, Manuel A.; Pirinen, Matti; Donnelly, Peter; McCarthy, Mark I.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.
   [Gonzalez-Porta, Mar; Kurbatova, Natalja; Greger, Liliana; Tikhonov, Andrew; Stegle, Oliver; Flicek, Paul; Brazma, Alvis] EBI, EMBL, Hinxton CB10 1SD, England.
   [Barann, Matthias; Esser, Daniela; Schreiber, Stefan; Haesler, Robert; Rosenstiel, Philip] Univ Kiel, Inst Clin Mol Biol, D-24105 Kiel, Germany.
   [Wieland, Thomas; Schwarzmayr, Thomas; Strom, Tim M.; Meitinger, Thomas] Helmholtz Zentrum Munchen, Inst Human Genet, D-85764 Neuherberg, Germany.
   [Almloef, Jonas; Karlberg, Olof; Syvaenen, Ann-Christine] Uppsala Univ, Dept Med Sci, Mol Med & Sci Life Lab, S-75185 Uppsala, Sweden.
   [Sultan, Marc; Amstislavskiy, Vyacheslav; Lehrach, Hans; Sudbrak, Ralf] Max Planck Inst Mol Genet, D-14195 Berlin, Germany.
   [MacArthur, Daniel G.; Lek, Monkol] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA.
   [MacArthur, Daniel G.; Lek, Monkol] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA 02142 USA.
   [Buermans, Henk P. J.] Leiden Genome Technol Ctr, NL-2300 RC Leiden, Netherlands.
   [McCarthy, Mark I.] Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford OX3 7BN, England.
   [Strom, Tim M.; Meitinger, Thomas] Tech Univ Munich, Inst Human Genet, D-81675 Munich, Germany.
   [Lehrach, Hans; Sudbrak, Ralf] Dahlem Ctr Genome Res & Med Syst Biol, D-14195 Berlin, Germany.
   [Carracedo, Angel] Univ Santiago de Compostela, CIBERER, Genom Med Grp, Fdn Publ Galega Med Xen SERGAS, Santiago De Compostela, Spain.
   [Meitinger, Thomas] Deutsch Forschungszentrum Herz Kreislauferkrankun, Partner Site Munich Heart Alliance, D-81675 Munich, Germany.
C3 University of Geneva; University of Geneva; Swiss Institute of Bioinformatics; Barcelona Institute of Science & Technology; Pompeu Fabra University; Centre de Regulacio Genomica (CRG); Pompeu Fabra University; Hospital del Mar Research Institute; Hospital del Mar; CIBER - Centro de Investigacion Biomedica en Red; CIBERESP; Leiden University; Leiden University Medical Center (LUMC); Leiden University - Excl LUMC; University of Oxford; Wellcome Centre for Human Genetics; European Molecular Biology Laboratory (EMBL); European Bioinformatics Institute; University of Kiel; Helmholtz Association; Helmholtz-Center Munich - German Research Center for Environmental Health; Uppsala University; Max Planck Society; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; University of Oxford; Technical University of Munich; Universidade de Santiago de Compostela; CIBER - Centro de Investigacion Biomedica en Red; CIBERER; Munich Heart Alliance
RP Lappalainen, T (corresponding author), Univ Geneva, Sch Med, Dept Genet Med & Dev, CH-1211 Geneva, Switzerland.
EM tuuli.e.lappalainen@gmail.com; emmanouil.dermitzakis@unige.ch
FU European Commission [261123]; Swiss National Science Foundation [130326, 130342, 127375, 144082]; Louis Jeantet Foundation; ERC [260927, 294653, 249968]; NIH-NIMH [MH090941]; Spanish Plan Nacional (NOVADIS) [SAF2008-00357]; Generalitat de Catalunya AGAUR [2009 SGR-1502]; Instituto de Salud Carlos III (FIS/FEDER) [PI11/00733, PS09/02368]; Spanish Plan Nacional [BIO2011-26205]; ESGI; READNA [2008-201418]; Spanish Ministry of Economy and Competitiveness (MINECO); Generalitat de Catalunya; DFG Cluster of Excellence Inflammation at Interfaces; INTERREG4A project HIT-ID; BMBF IHEC project DEEP [SP 2.3]; German Centre for Cardiovascular Research (DZHK); German Ministry of Education and Research [01GR0802, 01GM0867, 01GR0804, 16EX1020C]; EurocanPlatform [FP7 260791]; ENGAGE [HEALTH-F4-2007-201413]; CAGEKID [241669]; Centre for Medical Systems Biology; Swedish Research Council [C0524801, A028001]; Knut and Alice Wallenberg Foundation [2011.0073]; German Federal Ministry of Education and Research [01GS08201]; Max Planck Society; Wellcome Trust [WT085532, 081917, 090367, 090532, 098381, 076113, 083270]; European Molecular Biology Laboratory; Medical Research Council UK [G0601261]; Wellcome Trust Centre for Human Genetics [090532/Z/09/Z, 075491/Z/04/B]; WTCCC2 project [085475/B/08/Z, 085475/Z/08/Z]; Royal Society Wolfson Merit Award; Wellcome Trust Senior Investigator Award [095552/Z/11/Z]; EMBO long-term fellowship EMBO-ALTF [2010-337]; NIH-NIGMS [R01 GM104371]; Marie Curie; Clarendon Fund of the University of Oxford; Nuffield Department of Medicine; EMBO long-term fellowship [ALTF225-2011]; Emil Aaltonen Foundation; Academy of Finland; Medical Research Council [G0601261] Funding Source: researchfish; Wellcome Trust [095552/Z/11/Z] Funding Source: researchfish; European Research Council (ERC) [294653, 260927, 249968] Funding Source: European Research Council (ERC); MRC [G0601261] Funding Source: UKRI; Wellcome Trust [095552/Z/11/Z] Funding Source: Wellcome Trust
NR 35
TC 1412
Z9 1699
U1 2
U2 192
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 26
PY 2013
VL 501
IS 7468
BP 506
EP 511
DI 10.1038/nature12531
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 223RP
UT WOS:000324826300049
PM 24037378
DA 2026-03-09
ER

PT J
AU Guenther, UP
   Yandek, LE
   Niland, CN
   Campbell, FE
   Anderson, D
   Anderson, VE
   Harris, ME
   Jankowsky, E
AF Guenther, Ulf-Peter
   Yandek, Lindsay E.
   Niland, Courtney N.
   Campbell, Frank E.
   Anderson, David
   Anderson, Vernon E.
   Harris, Michael E.
   Jankowsky, Eckhard
TI Hidden specificity in an apparently nonspecific RNA-binding protein
SO NATURE
LA English
DT Article
ID ribonuclease-p; transcription factors; quantitative-analysis; enzyme specificity; landscapes; holoenzyme; kinetics; sequence; recognition; catalysis
AB Nucleic-acid-binding proteins are generally viewed as either specific or nonspecific, depending on characteristics of their binding sites in DNA or RNA(1,2). Most studies have focused on specific proteins, which identify cognate sites by binding with highest affinities to regions with defined signatures in sequence, structure or both(1-4). Proteins that bind to sites devoid of defined sequence or structure signatures are considered nonspecific(1,2,5). Substrate binding by these proteins is poorly understood, and it is not known to what extent seemingly nonspecific proteins discriminate between different binding sites, aside from those sequestered by nucleic acid structures(6). Here we systematically examine substrate binding by the apparently nonspecific RNA-binding protein C5, and find clear discrimination between different binding site variants. C5 is the protein subunit of the transfer RNA processing ribonucleoprotein enzyme RNase P from Escherichia coli. The protein binds 59 leaders of precursor tRNAs at a site without sequence or structure signatures. We measure functional binding of C5 to all possible sequence variants in its substrate binding site, using a high-throughput sequencing kinetics approach (HITS-KIN) that simultaneously follows processing of thousands of RNA species. C5 binds different substrate variants with affinities varying by orders of magnitude. The distribution of functional affinities of C5 for all substrate variants resembles affinity distributions of highly specific nucleic acid binding proteins. Unlike these specific proteins, C5 does not bind its physiological RNA targets with the highest affinity, but with affinities near the median of the distribution, a region that is not associated with a sequence signature. We delineate defined rules governing substrate recognition by C5, which reveal specificity that is hidden in cellular substrates for RNase P. Our findings suggest that apparently nonspecific and specific RNA-binding modes may not differ fundamentally, but represent distinct parts of common affinity distributions.
C1 [Guenther, Ulf-Peter; Campbell, Frank E.; Jankowsky, Eckhard] Case Western Reserve Univ, Ctr RNA Mol Biol, Cleveland, OH 44106 USA.
   [Guenther, Ulf-Peter; Yandek, Lindsay E.; Niland, Courtney N.; Anderson, Vernon E.; Harris, Michael E.; Jankowsky, Eckhard] Case Western Reserve Univ, Sch Med, Dept Biochem, Cleveland, OH 44106 USA.
   [Anderson, David] CUNY, Baruch Coll, Zicklin Sch Business, Dept Management, New York, NY 10010 USA.
C3 University System of Ohio; Case Western Reserve University; University System of Ohio; Case Western Reserve University; City University of New York (CUNY) System; Baruch College (CUNY)
RP Harris, ME (corresponding author), Case Western Reserve Univ, Sch Med, Dept Biochem, Cleveland, OH 44106 USA.
EM meh2@case.edu; exj13@case.edu
FU US National Institutes of Health (NIH) [GM067700, GM099720, CSTA UL1RR024989, GM056740, GM096000, T32 GM008056]; DFG
NR 38
TC 77
Z9 97
U1 0
U2 63
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 17
PY 2013
VL 502
IS 7471
BP 385
EP +
DI 10.1038/nature12543
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 235GY
UT WOS:000325706300056
PM 24056935
DA 2026-03-09
ER

PT J
AU Hamasaki, M
   Furuta, N
   Matsuda, A
   Nezu, A
   Yamamoto, A
   Fujita, N
   Oomori, H
   Noda, T
   Haraguchi, T
   Hiraoka, Y
   Amano, A
   Yoshimori, T
AF Hamasaki, Maho
   Furuta, Nobumichi
   Matsuda, Atsushi
   Nezu, Akiko
   Yamamoto, Akitsugu
   Fujita, Naonobu
   Oomori, Hiroko
   Noda, Takeshi
   Haraguchi, Tokuko
   Hiraoka, Yasushi
   Amano, Atsuo
   Yoshimori, Tamotsu
TI Autophagosomes form at ER-mitochondria contact sites
SO NATURE
LA English
DT Article
ID endoplasmic-reticulum; membrane; lc3; dissection; proteins; atg14l; cells
AB Autophagy is a tightly regulated intracellular bulk degradation/recycling system that has fundamental roles in cellular homeostasis(1). Autophagy is initiated by isolation membranes, which form and elongate as they engulf portions of the cytoplasm and organelles. Eventually isolation membranes dose to form double membrane-bound autophagosomes and fuse with lysosomes to degrade their contents. The physiological role of autophagy has been determined since its discovery, but the origin of autophagosomal membranes has remained unclear. At present, there is much controversy about the organelle from which the membranes originate-the endoplasmic reticulum (ER), mitochondria and plasma membrane(1,2). Here we show that autophagosomes form at the ER-mitochondria contact site in mammalian cells. Imaging data reveal that the pre-autophagosome/autophagosome marker ATG14 (also known as ATG14L) relocalizes to the ER-mitochondria contact site after starvation, and the autophagosome-formation marker ATG5 also localizes at the site until formation is complete. Subcellular fractionation showed that ATG14 co-fractionates in the mitochondria-associated ER membrane(3-5) fraction under starvation conditions. Disruption of the ER-mitochondria contact site prevents the formation of ATG14 puncta. The ER-resident SNARE protein syntaxin 17 (STX17) binds ATG14 and recruits it to the ER-mitochondria contact site. These results provide new insight into organelle biogenesis by demonstrating that the ER-mitochondria contact site is important in autophagosome formation.
C1 [Hamasaki, Maho; Nezu, Akiko; Fujita, Naonobu; Noda, Takeshi; Yoshimori, Tamotsu] Osaka Univ, Grad Sch Med, Dept Genet, Suita, Osaka 5650871, Japan.
   [Hamasaki, Maho; Nezu, Akiko; Fujita, Naonobu; Noda, Takeshi; Yoshimori, Tamotsu] Osaka Univ, Grad Sch Frontier Biosci, Lab Intracellular Membrane Dynam, Suita, Osaka 5650871, Japan.
   [Furuta, Nobumichi; Amano, Atsuo] Osaka Univ, Grad Sch Dent, Ctr Oral Frontier Sci, Dept Oral Frontier Biol, Suita, Osaka 5650871, Japan.
   [Matsuda, Atsushi; Haraguchi, Tokuko; Hiraoka, Yasushi] Natl Inst Informat & Commun Technol, Nishi Ku, Kobe, Hyogo 6512492, Japan.
   [Matsuda, Atsushi; Haraguchi, Tokuko; Hiraoka, Yasushi] Osaka Univ, Grad Sch Frontier Biosci, Nucl Dynam Grp, Suita, Osaka 5650871, Japan.
   [Yamamoto, Akitsugu] Nagahama Inst Biosci & Technol, Fac Biosci, Dept Cell Biol, Nagahama, Shiga 5260829, Japan.
   [Oomori, Hiroko] Osaka Univ, Res Inst Microbial Dis, Suita, Osaka 5650871, Japan.
   [Amano, Atsuo] Osaka Univ, Grad Sch Dent, Dept Prevent Dent, Suita, Osaka 5650871, Japan.
C3 University of Osaka; University of Osaka; University of Osaka; National Institute of Information & Communications Technology (NICT) - Japan; University of Osaka; Nagahama Institute of Bio-Science & Technology; University of Osaka; University of Osaka
RP Yoshimori, T (corresponding author), Osaka Univ, Grad Sch Med, Dept Genet, 2-2 Yaniadaoka, Suita, Osaka 5650871, Japan.
EM amanoa@dent.osaka-u.ac.jp; tamyoshi@fbs.osaka-u.ac.jp
FU Ministry of Education, Culture, Sports, Science and Technology, Japan; Grants-in-Aid for Scientific Research [24770113, 23390477, 25840075, 24659933, 20114002, 23247034] Funding Source: KAKEN
NR 26
TC 1416
Z9 1641
U1 5
U2 277
PU NATURE PUBLISHING 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 21
PY 2013
VL 495
IS 7441
BP 389
EP 393
DI 10.1038/nature11910
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 113EY
UT WOS:000316650500047
PM 23455425
DA 2026-03-09
ER

PT J
AU Alonzo, F
   Kozhaya, L
   Rawlings, SA
   Reyes-Robles, T
   DuMont, AL
   Myszka, DG
   Landau, NR
   Unutmaz, D
   Torres, VJ
AF Alonzo, Francis, III
   Kozhaya, Lina
   Rawlings, Stephen A.
   Reyes-Robles, Tamara
   DuMont, Ashley L.
   Myszka, David G.
   Landau, Nathaniel R.
   Unutmaz, Derya
   Torres, Victor J.
TI CCR5 is a receptor for Staphylococcus aureus leukotoxin ED
SO NATURE
LA English
DT Article
ID human-immunodeficiency-virus; protein-coupled receptors; chemokine receptors; hiv-1 infection; biosensor technology; small-molecule; coreceptor; resistant; cells; identification
AB Pore-forming toxins are critical virulence factors for many bacterial pathogens and are central to Staphylococcus aureus-mediated killing of host cells. S. aureus encodes pore-forming bi-component leukotoxins that are toxic towards neutrophils, but also specifically target other immune cells. Despite decades since the first description of staphylococcal leukocidal activity, the host factors responsible for the selectivity of leukotoxins towards different immune cells remain unknown. Here we identify the human immunodeficiency virus (HIV) co-receptor CCR5 as a cellular determinant required for cytotoxic targeting of subsets of myeloid cells and T lymphocytes by the S. aureus leukotoxin ED (LukED). We further demonstrate that LukED-dependent cell killing is blocked by CCR5 receptor antagonists, including the HIV drug maraviroc. Remarkably, CCR5-deficient mice are largely resistant to lethal S. aureus infection, highlighting the importance of CCR5 targeting in S. aureus pathogenesis. Thus, depletion of CCR5(+) leukocytes by LukED suggests a new immune evasion mechanism of S. aureus that can be therapeutically targeted.
C1 [Alonzo, Francis, III; Kozhaya, Lina; Rawlings, Stephen A.; Reyes-Robles, Tamara; DuMont, Ashley L.; Landau, Nathaniel R.; Unutmaz, Derya; Torres, Victor J.] NYU, Sch Med, Dept Microbiol, New York, NY 10016 USA.
   [Unutmaz, Derya] NYU, Sch Med, Dept Pathol, New York, NY 10016 USA.
   [Unutmaz, Derya] NYU, Sch Med, Dept Med, New York, NY 10016 USA.
   [Myszka, David G.] Biosensor Tools LLC, Salt Lake City, UT 84103 USA.
C3 New York University; New York University; New York University
RP Torres, VJ (corresponding author), NYU, Sch Med, Dept Microbiol, New York, NY 10016 USA.
EM derya.unutmaz@nyumc.org; victor.torres@nyumc.org
FU New York University School of Medicine Development Funds; American Heart Association Scientist Development Grant [09SDG2060036]; National Institutes of Health (NIH) [R56-AI091856-01A1]; NIH [T32-AI007180, R42-MH084372-02A1, R21-AI087973, R01-AI065303]; National Institute of Allergy and Infectious Diseases [T32AI007180] Funding Source: NIH RePORTER
NR 44
TC 243
Z9 293
U1 0
U2 122
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 3
PY 2013
VL 493
IS 7430
BP 51
EP +
DI 10.1038/nature11724
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 062QC
UT WOS:000312933800028
PM 23235831
DA 2026-03-09
ER

PT J
AU Lai, F
   Orom, UA
   Cesaroni, M
   Beringer, M
   Taatjes, DJ
   Blobel, GA
   Shiekhattar, R
AF Lai, Fan
   Orom, Ulf A.
   Cesaroni, Matteo
   Beringer, Malte
   Taatjes, Dylan J.
   Blobel, Gerd A.
   Shiekhattar, Ramin
TI Activating RNAs associate with Mediator to enhance chromatin architecture and transcription
SO NATURE
LA English
DT Article
ID opitz-kaveggia-syndrome; long noncoding rnas; gene-expression; histone h3; genome; identification; med12; mutation; complex
AB Recent advances in genomic research have revealed the existence of a large number of transcripts devoid of protein-coding potential in multiple organisms(1-8). Although the functional role for long non-coding RNAs (lncRNAs) has been best defined in epigenetic phenomena such as X-chromosome inactivation and imprinting, different classes of lncRNAs may have varied biological functions(8-13). We and others have identified a class of lncRNAs, termed ncRNA-activating (ncRNA-a), that function to activate their neighbouring genes using a cis-mediated mechanism(5,14-16). To define the precise mode by which such enhancer-like RNAs function, we depleted factors with known roles in transcriptional activation and assessed their role in RNA-dependent activation. Here we report that depletion of the components of the co-activator complex, Mediator, specifically and potently diminished the ncRNA-induced activation of transcription in a heterologous reporter assay using human HEK293 cells. In vivo, Mediator is recruited to ncRNA-a target genes and regulates their expression. We show that ncRNA-a interact with Mediator to regulate its chromatin localization and kinase activity towards histone H3 serine 10. The Mediator complex harbouring disease-causing MED12 mutations(17,18) displays diminished ability to associate with activating ncRNAs. Chromosome conformation capture confirmed the presence of DNA looping between the ncRNA-a loci and its targets. Importantly, depletion of Mediator subunits or ncRNA-a reduced the chromatin looping between the two loci. Our results identify the human Mediator complex as the transducer of activating ncRNAs and highlight the importance of Mediator and activating ncRNA association in human disease.
C1 [Lai, Fan; Cesaroni, Matteo; Shiekhattar, Ramin] Wistar Inst Anat & Biol, Philadelphia, PA 19104 USA.
   [Orom, Ulf A.] Max Planck Inst Mol Genet, D-14195 Berlin, Germany.
   [Beringer, Malte] Ctr Regulacio Genom, Barcelona 08003, Spain.
   [Beringer, Malte] UPF, Barcelona 08003, Spain.
   [Taatjes, Dylan J.] Univ Colorado, Dept Chem & Biochem, Boulder, CO 80309 USA.
   [Blobel, Gerd A.] Childrens Hosp Philadelphia, Div Hematol, Philadelphia, PA 19104 USA.
C3 The Wistar Institute; Max Planck Society; Barcelona Institute of Science & Technology; Pompeu Fabra University; Centre de Regulacio Genomica (CRG); Pompeu Fabra University; University of Colorado System; University of Colorado Boulder; University of Pennsylvania; Pennsylvania Medicine; Childrens Hospital of Philadelphia
RP Shiekhattar, R (corresponding author), Wistar Inst Anat & Biol, 3601 Spruce St, Philadelphia, PA 19104 USA.
EM shiekhattar@wistar.org
FU NIH [P30 CA 010815]; NCI [R01 CA127364];  [5R37DK058044]; National Cancer Institute [P30CA010815] Funding Source: NIH RePORTER; National Institute of Diabetes and Digestive and Kidney Diseases [R01DK058044] Funding Source: NIH RePORTER
NR 27
TC 711
Z9 853
U1 1
U2 165
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 28
PY 2013
VL 494
IS 7438
BP 497
EP 501
DI 10.1038/nature11884
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 099YI
UT WOS:000315661500043
PM 23417068
DA 2026-03-09
ER

PT J
AU Eatough, RP
   Falcke, H
   Karuppusamy, R
   Lee, KJ
   Champion, DJ
   Keane, EF
   Desvignes, G
   Schnitzeler, DHFM
   Spitler, LG
   Kramer, M
   Klein, B
   Bassa, C
   Bower, GC
   Brunthaler, A
   Cognard, I
   Deller, AT
   Demorest, PB
   Freire, PCC
   Kraus, A
   Lyne, AG
   Noutsos, A
   Stappers, B
   Wex, N
AF Eatough, R. P.
   Falcke, H.
   Karuppusamy, R.
   Lee, K. J.
   Champion, D. J.
   Keane, E. F.
   Desvignes, G.
   Schnitzeler, D. H. F. M.
   Spitler, L. G.
   Kramer, M.
   Klein, B.
   Bassa, C.
   Bower, G. C.
   Brunthaler, A.
   Cognard, I.
   Deller, A. T.
   Demorest, P. B.
   Freire, P. C. C.
   Kraus, A.
   Lyne, A. G.
   Noutsos, A.
   Stappers, B.
   Wex, N.
TI A strong magnetic field around the supermassive black hole at the centre of the Galaxy
SO NATURE
LA English
DT Article
ID sagittarius-a-asterisk; galactic-center; linear-polarization; faraday-rotation; central parsec; accretion; radio; discovery; emission; disks
AB Earth's nearest candidate supermassive black hole lies at the centre of the Milky Way(1). Its electromagnetic emission is thought to be powered by radiatively inefficient accretion of gas from its environment(2), which is a standard mode of energy supply for most galactic nuclei. X-ray measurements have already resolved a tenuous hot gas component from which the black hole can be fed(3). The magnetization of the gas, however, which is a crucial parameter determining the structure of the accretion flow, remains unknown. Strong magnetic fields can influence the dynamics of accretion, remove angular momentum from the infalling gas(4), expel matter through relativistic jets(5) and lead to synchrotron emission such as that previously observed(6-8). Here we report multi-frequency radio measurements of a newly discovered pulsar close to the Galactic Centre(9-12) and show that the pulsar's unusually large Faraday rotation (the rotation of the plane of polarization of the emission in the presence of an external magnetic field) indicates that there is a dynamically important magnetic field near the black hole. If this field is accreted down to the event horizon it provides enough magnetic flux to explain the observed emission-from radio to X-ray wavelengths-from the black hole.
C1 [Eatough, R. P.; Falcke, H.; Karuppusamy, R.; Lee, K. J.; Champion, D. J.; Desvignes, G.; Schnitzeler, D. H. F. M.; Spitler, L. G.; Kramer, M.; Klein, B.; Brunthaler, A.; Freire, P. C. C.; Kraus, A.; Noutsos, A.; Wex, N.] Max Planck Inst Radioastron, D-53121 Bonn, Germany.
   [Falcke, H.] Radboud Univ Nijmegen, Dept Astrophys, Inst Math Astrophys & Particle Phys, NL-6500 GL Nijmegen, Netherlands.
   [Falcke, H.; Deller, A. T.] ASTRON, NL-7990 AA Dwingeloo, Netherlands.
   [Keane, E. F.; Kramer, M.; Bassa, C.; Lyne, A. G.; Stappers, B.] Univ Manchester, Sch Phys & Astron, Jodrell Bank Ctr Astrophys, Manchester M13 9PL, Lancs, England.
   [Klein, B.] Bonn Rhein Sieg Univ Appl Sci, D-53757 St Augustin, Germany.
   [Bower, G. C.] Univ Calif Berkeley, Dept Astron, Berkeley, CA 94720 USA.
   [Cognard, I.] Univ Orleans, CNRS, LPC2E, F-45071 Orleans, France.
   [Cognard, I.] Nancay Paris Observ, F-18330 Nancay, France.
   [Demorest, P. B.] Natl Radio Astron Observ, Charlottesville, VA 22903 USA.
C3 Max Planck Society; Radboud University Nijmegen; University of Manchester; Jodrell Bank Centre for Astrophysics; Hochschule Bonn Rhein Sieg; University of California System; University of California Berkeley; Centre National de la Recherche Scientifique (CNRS); Universite de Orleans; Universite PSL; Observatoire de Paris; National Radio Astronomy Observatory (NRAO)
RP Eatough, RP (corresponding author), Max Planck Inst Radioastron, Hugel 69, D-53121 Bonn, Germany.
EM reatough@mpifr-bonn.mpg.de
FU European Research Council for the ERC Starting Grant BEACON [279702]; ERC Advanced Grant LEAP [227947]; Advanced Grant of the European Research Council under the European Union's Seventh Framework Programme [227610]; Region Centre in France; STFC [ST/J001562/1] Funding Source: UKRI; Science and Technology Facilities Council [ST/J001562/1] Funding Source: researchfish; Direct For Mathematical & Physical Scien [1009421] Funding Source: National Science Foundation; Division Of Astronomical Sciences [1009421] Funding Source: National Science Foundation
NR 30
TC 387
Z9 420
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 SEP 19
PY 2013
VL 501
IS 7467
BP 391
EP 394
DI 10.1038/nature12499
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 219XT
UT WOS:000324545700039
PM 23945588
DA 2026-03-09
ER

PT J
AU Ng, KM
   Ferreyra, JA
   Higginbottom, SK
   Lynch, JB
   Kashyap, PC
   Gopinath, S
   Naidu, N
   Choudhury, B
   Weimer, BC
   Monack, DM
   Sonnenburg, JL
AF Ng, Katharine M.
   Ferreyra, Jessica A.
   Higginbottom, Steven K.
   Lynch, Jonathan B.
   Kashyap, Purna C.
   Gopinath, Smita
   Naidu, Natasha
   Choudhury, Biswa
   Weimer, Bart C.
   Monack, Denise M.
   Sonnenburg, Justin L.
TI Microbiota-liberated host sugars facilitate post-antibiotic expansion of enteric pathogens
SO NATURE
LA English
DT Article
ID clostridium-difficile; escherichia-coli; carbon nutrition; sialic acids; mouse model; typhimurium; transmission; diversity; disrupts; provides
AB The human intestine, colonized by a dense community of resident microbes, is a frequent target of bacterial pathogens. Undisturbed, this intestinal microbiota provides protection from bacterial infections. Conversely, disruption of the microbiota with oral antibiotics often precedes the emergence of several enteric pathogens(1-4). How pathogens capitalize upon the failure of microbiota-afforded protection is largely unknown. Here we show that two antibiotic-associated pathogens, Salmonella enterica serovar Typhimurium (S. typhimurium) and Clostridium difficile, use a common strategy of catabolizing microbiota-liberated mucosal carbohydrates during their expansion within the gut. S. typhimurium accesses fucose and sialic acid within the lumen of the gut in a microbiota-dependent manner, and genetic ablation of the respective catabolic pathways reduces its competitiveness in vivo. Similarly, C. difficile expansion is aided by microbiota-induced elevation of sialic acid levels in vivo. Colonization of gnotobiotic mice with a sialidase-deficient mutant of Bacteroides thetaiotaomicron, a model gut symbiont, reduces free sialic acid levels resulting in C. difficile downregulating its sialic acid catabolic pathway and exhibiting impaired expansion. These effects are reversed by exogenous dietary administration of free sialic acid. Furthermore, antibiotic treatment of conventional mice induces a spike in free sialic acid and mutants of both Salmonella and C. difficile that are unable to catabolize sialic acid exhibit impaired expansion. These data show that antibiotic-induced disruption of the resident microbiota and subsequent alteration in mucosal carbohydrate availability are exploited by these two distantly related enteric pathogens in a similar manner. This insight suggests new therapeutic approaches for preventing diseases caused by antibiotic-associated pathogens.
C1 [Ng, Katharine M.; Ferreyra, Jessica A.; Higginbottom, Steven K.; Lynch, Jonathan B.; Kashyap, Purna C.; Gopinath, Smita; Monack, Denise M.; Sonnenburg, Justin L.] Stanford Univ, Sch Med, Dept Microbiol & Immunol, Stanford, CA 94305 USA.
   [Naidu, Natasha; Choudhury, Biswa] Univ Calif San Diego, Glycobiol Res & Training Ctr, San Diego, CA 92093 USA.
   [Weimer, Bart C.] Univ Calif Davis, Dept Populat Hlth & Reprod, Davis, CA 95616 USA.
C3 Stanford University; University of California System; University of California San Diego; University of California System; University of California Davis
RP Sonnenburg, JL (corresponding author), Stanford Univ, Sch Med, Dept Microbiol & Immunol, Stanford, CA 94305 USA.
EM jsonnenburg@stanford.edu
FU NSF [R01-DK085025]; Burroughs Wellcome Fund; National Institute of Allergy and Infectious Diseases [T32AI007328] Funding Source: NIH RePORTER; National Institute of Diabetes and Digestive and Kidney Diseases [R01DK085025] Funding Source: NIH RePORTER
NR 39
TC 790
Z9 984
U1 5
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 OCT 3
PY 2013
VL 502
IS 7469
BP 96
EP +
DI 10.1038/nature12503
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 227IM
UT WOS:000325106000038
PM 23995682
DA 2026-03-09
ER

PT J
AU Middleton, MJ
   Miller-Jones, JCA
   Markoff, S
   Fender, R
   Henze, M
   Hurley-Walker, N
   Scaife, AMM
   Roberts, TP
   Walton, D
   Carpenter, J
   Macquart, JP
   Bower, GC
   Gurwell, M
   Pietsch, W
   Haberl, F
   Harris, J
   Daniel, M
   Miah, J
   Done, C
   Morgan, JS
   Dickinson, H
   Charles, P
   Burwitz, V
   Della Valle, M
   Freyberg, M
   Greiner, J
   Hernanz, M
   Hartmann, DH
   Hatzidimitriou, D
   Riffeser, A
   Sala, G
   Seitz, S
   Reig, P
   Rau, A
   Orio, M
   Titterington, D
   Grainge, K
AF Middleton, Matthew J.
   Miller-Jones, James C. A.
   Markoff, Sera
   Fender, Rob
   Henze, Martin
   Hurley-Walker, Natasha
   Scaife, Anna M. M.
   Roberts, Timothy P.
   Walton, Dominic
   Carpenter, John
   Macquart, Jean-Pierre
   Bower, Geoffrey C.
   Gurwell, Mark
   Pietsch, Wolfgang
   Haberl, Frank
   Harris, Jonathan
   Daniel, Michael
   Miah, Junayd
   Done, Chris
   Morgan, John S.
   Dickinson, Hugh
   Charles, Phil
   Burwitz, Vadim
   Della Valle, Massimo
   Freyberg, Michael
   Greiner, Jochen
   Hernanz, Margarita
   Hartmann, Dieter H.
   Hatzidimitriou, Despina
   Riffeser, Arno
   Sala, Gloria
   Seitz, Stella
   Reig, Pablo
   Rau, Arne
   Orio, Marina
   Titterington, David
   Grainge, Keith
TI Bright radio emission from an ultraluminous stellar-mass microquasar in M 31
SO NATURE
LA English
DT Article
ID x-ray source; black-hole binary; superluminal source; grs 1915+105; j1819.3-2525; evolution; systems; chandra; galaxy; model
AB A subset of ultraluminous X-ray sources (those with luminosities of less than 10(40) erg s(-1); ref. 1) are thought to be powered by the accretion of gas onto black holes with masses of similar to 5-20M(circle dot), probably by means of an accretion disk(2,3). The X-ray and radio emission are coupled in such Galactic sources; the radio emission originates in a relativistic jet thought to be launched from the innermost regions near the black hole(4,5), with the most powerful emission occurring when the rate of infalling matter approaches a theoretical maximum (the Eddington limit). Only four such maximal sources are known in the Milky Way(6), and the absorption of soft X-rays in the interstellar medium hinders the determination of the causal sequence of events that leads to the ejection of the jet. Here we report radio and X-ray observations of a bright new X-ray source in the nearby galaxy M 31, whose peak luminosity exceeded 10(39) erg s(-1). The radio luminosity is extremely high and shows variability on a timescale of tens of minutes, arguing that the source is highly compact and powered by accretion close to the Eddington limit onto a black hole of stellar mass. Continued radio and X-ray monitoring of such sources should reveal the causal relationship between the accretion flow and the powerful jet emission.
C1 [Middleton, Matthew J.; Roberts, Timothy P.; Harris, Jonathan; Daniel, Michael; Miah, Junayd; Done, Chris] Univ Durham, Dept Phys, Durham DH1 3LE, England.
   [Middleton, Matthew J.; Markoff, Sera] Astron Inst Anton Pannekoek, NL-1098 XH Amsterdam, Netherlands.
   [Miller-Jones, James C. A.; Hurley-Walker, Natasha; Macquart, Jean-Pierre; Morgan, John S.] Curtin Univ Technol, Int Ctr Radio Astron Res, Perth, WA 6845, Australia.
   [Fender, Rob; Scaife, Anna M. M.; Charles, Phil] Univ Southampton, Sch Phys & Astron, Southampton SO17 1BJ, Hants, England.
   [Henze, Martin; Pietsch, Wolfgang; Haberl, Frank; Burwitz, Vadim; Freyberg, Michael; Greiner, Jochen; Rau, Arne] Max Planck Inst Extraterr Phys, D-85748 Garching, Germany.
   [Walton, Dominic] Univ Cambridge, Inst Astron, Cambridge CB3 0HA, England.
   [Walton, Dominic; Carpenter, John] CALTECH, Dept Astron, Pasadena, CA 91125 USA.
   [Macquart, Jean-Pierre] Curtin Univ Technol, ARC Ctr Excellence All Sky Astrophys CAASTRO, Perth, WA 6845, Australia.
   [Bower, Geoffrey C.] Univ Calif Berkeley, Dept Astron, Berkeley, CA 94720 USA.
   [Gurwell, Mark] Harvard Smithsonian Ctr Astrophys, Cambridge, MA 02138 USA.
   [Dickinson, Hugh] Stockholm Univ, Oskar Klein Ctr, AlbaNova, SE-10691 Stockholm, Sweden.
   [Charles, Phil] Univ Cape Town, Dept Astron, ZA-7701 Rondebosch, South Africa.
   [Della Valle, Massimo] Osserv Astron Capodimonte, INAF, I-80131 Naples, Italy.
   [Della Valle, Massimo] Int Ctr Relativist Astrophys, I-65122 Pescara, Italy.
   [Hernanz, Margarita] Fac Ciencies, Inst Space Sci CSIC IEEC, Barcelona 08193, Spain.
   [Hartmann, Dieter H.] Clemson Univ, Dept Phys & Astron, Kinard Lab 118, Clemson, SC 29631 USA.
   [Hatzidimitriou, Despina] Univ Athens, Fac Phys, Dept Astrophys Astron & Mech, Athens 15784, Greece.
   [Riffeser, Arno; Seitz, Stella] Univ Munich, Univ Observ Munich, D-81679 Munich, Germany.
   [Sala, Gloria] EUETIB UPC IEEC, Dept Phys & Nucl Engn, Barcelona 08036, Spain.
   [Reig, Pablo] Fdn Res & Technol Hellas, Iraklion 71110, Crete, Greece.
   [Orio, Marina] Osserv Astron Padova, I-35122 Padua, Italy.
   [Titterington, David; Grainge, Keith] Univ Cambridge, Cavendish Lab, Astrophys Grp, Cambridge CB3 0HE, England.
C3 Durham University; University of Amsterdam; University of Western Australia; Curtin University; University of Southampton; Max Planck Society; University of Cambridge; California Institute of Technology; Curtin University; University of California System; University of California Berkeley; Harvard University; Smithsonian Astrophysical Observatory; Smithsonian Institution; Oskar Klein Centre; Stockholm University; University of Cape Town; Istituto Nazionale Astrofisica (INAF); Institut d'Estudis Espacials de Catalunya (IEEC); Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Instituto de Ciencias del Espacio (ICE); Clemson University; National & Kapodistrian University of Athens; University of Munich; Universitat Politecnica de Catalunya; Institut d'Estudis Espacials de Catalunya (IEEC); Foundation for Research & Technology - Hellas (FORTH); University of Padua; Istituto Nazionale Astrofisica (INAF); University of Cambridge
RP Middleton, MJ (corresponding author), Univ Durham, Dept Phys, Durham DH1 3LE, England.
EM m.j.middleton@durham.ac.uk
FU Science and Technology Facilities Council (STFC); Netherlands Organization for Scientific Research Vidi Fellowship; European Research Council; Cambridge University; STFC;  [BMWI/DLR];  [FKZ 50 OR 1010]; Science and Technology Facilities Council [ST/F00723X/1, ST/J001600/1, ST/G001588/1] Funding Source: researchfish; Division Of Astronomical Sciences; Direct For Mathematical & Physical Scien [1140063] Funding Source: National Science Foundation; STFC [ST/J001600/1, ST/F00723X/1, ST/G001588/1] Funding Source: UKRI
NR 30
TC 114
Z9 118
U1 0
U2 27
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 10
PY 2013
VL 493
IS 7431
BP 187
EP 190
DI 10.1038/nature11697
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 066YY
UT WOS:000313259600032
PM 23235823
DA 2026-03-09
ER

PT J
AU Paull, D
   Emmanuele, V
   Weiss, KA
   Treff, N
   Stewart, L
   Hua, HQ
   Zimmer, M
   Kahler, DJ
   Goland, RS
   Noggle, SA
   Prosser, R
   Hirano, M
   Sauer, MV
   Egli, D
AF Paull, Daniel
   Emmanuele, Valentina
   Weiss, Keren A.
   Treff, Nathan
   Stewart, Latoya
   Hua, Haiqing
   Zimmer, Matthew
   Kahler, David J.
   Goland, Robin S.
   Noggle, Scott A.
   Prosser, Robert
   Hirano, Michio
   Sauer, Mark V.
   Egli, Dieter
TI Nuclear genome transfer in human oocytes eliminates mitochondrial DNA variants
SO NATURE
LA English
DT Article
ID meiotic spindle; human embryos; cell-lines; stem-cells; mouse; segregation; mtdna; vitrification; microtubules; deficiency
AB Mitochondrial DNA mutations transmitted maternally within the oocyte cytoplasm often cause life-threatening disorders. Here we explore the use of nuclear genome transfer between unfertilized oocytes of two donors to prevent the transmission of mitochondrial mutations. Nuclear genome transfer did not reduce developmental efficiency to the blastocyst stage, and genome integrity was maintained provided that spontaneous oocyte activation was avoided through the transfer of incompletely assembled spindle-chromosome complexes. Mitochondrial DNA transferred with the nuclear genome was initially detected at levels below 1%, decreasing in blastocysts and stem-cell lines to undetectable levels, and remained undetectable after passaging for more than one year, clonal expansion, differentiation into neurons, cardiomyocytes or beta-cells, and after cellular reprogramming. Stem cells and differentiated cells had mitochondrial respiratory chain enzyme activities and oxygen consumption rates indistinguishable from controls. These results demonstrate the potential of nuclear genome transfer to prevent the transmission of mitochondrial disorders in humans.
C1 [Paull, Daniel; Weiss, Keren A.; Stewart, Latoya; Hua, Haiqing; Zimmer, Matthew; Kahler, David J.; Noggle, Scott A.; Egli, Dieter] New York Stem Cell Fdn Lab, New York, NY 10032 USA.
   [Emmanuele, Valentina; Hirano, Michio] Columbia Univ, Dept Neurol, New York, NY 10032 USA.
   [Treff, Nathan] Reprod Med Associates New Jersey, Morristown, NJ 07960 USA.
   [Hua, Haiqing; Goland, Robin S.] Columbia Univ, Coll Phys & Surg, Naomi Berrie Diabet Ctr, New York, NY 10032 USA.
   [Prosser, Robert; Sauer, Mark V.] Columbia Univ, Coll Phys & Surg, Ctr Womens Reprod Care, New York, NY 10019 USA.
   [Sauer, Mark V.] Columbia Univ, Coll Phys & Surg, Dept Obstet & Gynecol, New York, NY 10032 USA.
C3 The New York Stem Cell Foundation; Columbia University; Reproductive Medicine Associates of New Jersey; Columbia University; Columbia University; Columbia University
RP Egli, D (corresponding author), New York Stem Cell Fdn Lab, New York, NY 10032 USA.
EM mvs9@columbia.edu; d.egli@nyscf.org
FU New York Stem Cell Foundation; New York State Stem Cell Science award [C026184]; Bernard and Anne Spitzer Fund
NR 47
TC 202
Z9 233
U1 0
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 JAN 31
PY 2013
VL 493
IS 7434
BP 632
EP +
DI 10.1038/nature11800
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 080CU
UT WOS:000314219600048
PM 23254936
DA 2026-03-09
ER

PT J
AU Schultze, M
   Bothschafter, EM
   Sommer, A
   Holzner, S
   Schweinberger, W
   Fiess, M
   Hofstetter, M
   Kienberger, R
   Apalkov, V
   Yakovlev, VS
   Stockman, MI
   Krausz, F
AF Schultze, Martin
   Bothschafter, Elisabeth M.
   Sommer, Annkatrin
   Holzner, Simon
   Schweinberger, Wolfgang
   Fiess, Markus
   Hofstetter, Michael
   Kienberger, Reinhard
   Apalkov, Vadym
   Yakovlev, Vladislav S.
   Stockman, Mark I.
   Krausz, Ferenc
TI Controlling dielectrics with the electric field of light
SO NATURE
LA English
DT Article
ID superlattices; localization
AB The control of the electric and optical properties of semiconductors with microwave fields forms the basis of modern electronics, information processing and optical communications. The extension of such control to optical frequencies calls for wideband materials such as dielectrics, which require strong electric fields to alter their physical properties(1-5). Few-cycle laser pulses permit damage-free exposure of dielectrics to electric fields of several volts per angstrom(6) and significant modifications in their electronic system(6-13). Fields of such strength and temporal confinement can turn a dielectric from an insulating state to a conducting state within the optical period(14). However, to extend electric signal control and processing to light frequencies depends on the feasibility of reversing these effects approximately as fast as they can be induced. Here we study the underlying electron processes with sub-femtosecond solid-state spectroscopy, which reveals the feasibility of manipulating the electronic structure and electric polarizability of a dielectric reversibly with the electric field of light. We irradiate a dielectric (fused silica) with a waveform-controlled near-infrared few-cycle light field of several volts per angstrom and probe changes in extreme-ultraviolet absorptivity and near-infrared reflectivity on a timescale of approximately a hundred attoseconds to a few femtoseconds. The field-induced changes follow, in a highly nonlinear fashion, the turn-on and turn-off behaviour of the driving field, in agreement with the predictions of a quantum mechanical model. The ultrafast reversibility of the effects implies that the physical properties of a dielectric can be controlled with the electric field of light, offering the potential for petahertz-bandwidth signal manipulation.
C1 [Schultze, Martin; Bothschafter, Elisabeth M.; Sommer, Annkatrin; Holzner, Simon; Schweinberger, Wolfgang; Fiess, Markus; Kienberger, Reinhard; Krausz, Ferenc] Max Planck Inst Quantum Opt, D-85748 Garching, Germany.
   [Schultze, Martin; Hofstetter, Michael; Yakovlev, Vladislav S.; Krausz, Ferenc] Univ Munich, Fak Phys, D-80539 Munich, Germany.
   [Bothschafter, Elisabeth M.; Kienberger, Reinhard] Tech Univ Munich, Phys Dept, D-85748 Garching, Germany.
   [Apalkov, Vadym; Stockman, Mark I.] Georgia State Univ, Dept Phys, Atlanta, GA 30340 USA.
C3 Max Planck Society; University of Munich; Technical University of Munich; University System of Georgia; Georgia State University
RP Schultze, M (corresponding author), Max Planck Inst Quantum Opt, Hans Kopfermann Str 1, D-85748 Garching, Germany.
EM martin.schultze@mpq.mpg.de; mstockman@gsu.edu; krausz@lmu.de
FU Max Planck Society; Deutsche Forschungsgemeinschaft Cluster of Excellence: Munich Centre for Advanced Photonics; Chemical Sciences, Biosciences and Geosciences Division [DEFG02-01ER15213]; Materials Sciences and Engineering Division of the Office of the Basic Energy Sciences, Office of Science, US Department of Energy [DE-FG02-11ER46789]
NR 23
TC 506
Z9 572
U1 0
U2 389
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 3
PY 2013
VL 493
IS 7430
BP 75
EP 78
DI 10.1038/nature11720
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 062QC
UT WOS:000312933800033
PM 23222519
DA 2026-03-09
ER

PT J
AU Granger, AJ
   Shi, Y
   Lu, W
   Cerpas, M
   Nicoll, RA
AF Granger, Adam J.
   Shi, Yun
   Lu, Wei
   Cerpas, Manuel
   Nicoll, Roger A.
TI LTP requires a reserve pool of glutamate receptors independent of subunit type
SO NATURE
LA English
DT Article
ID ampa receptor; synaptic plasticity; long-term; surface expression; glur1 subunit; trafficking; phosphorylation; camkii; synapses; neurons
AB Long-term potentiation (LTP) of synaptic transmission is thought to be an important cellular mechanism underlying memory formation. A widely accepted model posits that LTP requires the cytoplasmic carboxyl tail (C-tail) of the AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptor subunit GluA1. To find the minimum necessary requirement of the GluA1 C-tail for LTP in mouse CA1 hippocampal pyramidal neurons, we used a single-cell molecular replacement strategy to replace all endogenous AMPA receptors with transfected subunits. In contrast to the prevailing model, we found no requirement of the GluA1 C-tail for LTP. In fact, replacement with the GluA2 subunit showed normal LTP, as did an artificially expressed kainate receptor not normally found at these synapses. The only conditions under which LTP was impaired were those with markedly decreased AMPA receptor surface expression, indicating a requirement for a reserve pool of receptors. These results demonstrate the synapse's remarkable flexibility to potentiate with a variety of glutamate receptor subtypes, requiring a fundamental change in our thinking with regard to the core molecular events underlying synaptic plasticity.
C1 [Granger, Adam J.] Univ Calif San Francisco, Grad Program Neurosci, San Francisco, CA 94158 USA.
   [Shi, Yun; Lu, Wei; Cerpas, Manuel; Nicoll, Roger A.] Univ Calif San Francisco, Dept Cellular & Mol Pharmacol, 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 Nicoll, RA (corresponding author), Univ Calif San Francisco, Dept Cellular & Mol Pharmacol, San Francisco, CA 94143 USA.
EM nicoll@cmp.uscf.edu
FU National Science Foundation; National Institute of Health
NR 42
TC 252
Z9 304
U1 0
U2 105
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 24
PY 2013
VL 493
IS 7433
BP 495
EP +
DI 10.1038/nature11775
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 075GF
UT WOS:000313871400030
PM 23235828
DA 2026-03-09
ER

PT J
AU Peng, SS
   Piao, SL
   Ciais, P
   Myneni, RB
   Chen, AP
   Chevallier, F
   Dolman, AJ
   Janssens, IA
   Peñuelas, J
   Zhang, GX
   Vicca, S
   Wan, SQ
   Wang, SP
   Zeng, H
AF Peng, Shushi
   Piao, Shilong
   Ciais, Philippe
   Myneni, Ranga B.
   Chen, Anping
   Chevallier, Frederic
   Dolman, Albertus J.
   Janssens, Ivan A.
   Penuelas, Josep
   Zhang, Gengxin
   Vicca, Sara
   Wan, Shiqiang
   Wang, Shiping
   Zeng, Hui
TI Asymmetric effects of daytime and night-time warming on Northern Hemisphere vegetation
SO NATURE
LA English
DT Article
ID net primary production; carbon-dioxide; ridge regression; leaf respiration; climate-change; satellite; temperature; impact; growth
AB Temperature data over the past five decades show faster warming of the global land surface during the night than during the day(1). This asymmetric warming is expected to affect carbon assimilation and consumption in plants, because photosynthesis in most plants occurs during daytime and is more sensitive to the maximum daily temperature, T-max, whereas plant respiration occurs throughout the day(2) and is therefore influenced by both T-max and the minimum daily temperature, T-min. Most studies of the response of terrestrial ecosystems to climate warming, however, ignore this asymmetric forcing effect on vegetation growth and carbon dioxide (CO2) fluxes(3-6). Here we analyse the interannual covariations of the satellite-derived normalized difference vegetation index (NDVI, an indicator of vegetation greenness) with Tmax and Tmin over the Northern Hemisphere. After removing the correlation between Tmax and Tmin, we find that the partial correlation between Tmax and NDVI is positive in most wet and cool ecosystems over boreal regions, but negative in dry temperate regions. In contrast, the partial correlation between Tmin and NDVI is negative in boreal regions, and exhibits a more complex behaviour in dry temperate regions. We detect similar patterns in terrestrial net CO2 exchange maps obtained from a global atmospheric inversion model. Additional analysis of the long-term atmospheric CO2 concentration record of the station Point Barrow in Alaska suggests that the peak-to-peak amplitude of CO2 increased by 23 +/- 11% for a +1 degrees C anomaly in T-max from May to September over lands north of 51 degrees N, but decreased by 28 +/- 14% for a +1 degrees C anomaly in T-min. These lines of evidence suggest that asymmetric diurnal warming, a process that is currently not taken into account in many global carbon cycle models, leads to a divergent response of Northern Hemisphere vegetation growth and carbon sequestration to rising temperatures.
C1 [Peng, Shushi; Piao, Shilong] Peking Univ, Coll Urban & Environm Sci, Sinofrench Inst Earth Syst Sci, Beijing 100871, Peoples R China.
   [Piao, Shilong; Zhang, Gengxin; Wang, Shiping] Chinese Acad Sci, Inst Tibetan Plateau Res, Beijing 100085, Peoples R China.
   [Ciais, Philippe; Chevallier, Frederic] CEA, CNRS, LSCE, CE, F-91191 Gif Sur Yvette, France.
   [Myneni, Ranga B.] Boston Univ, Dept Earth & Environm, Boston, MA 02215 USA.
   [Chen, Anping] Princeton Univ, Dept Ecol & Evolutionary Biol, Princeton, NJ 08544 USA.
   [Dolman, Albertus J.] Vrije Univ Amsterdam, Dept Earth Sci, NL-1081 HV Amsterdam, Netherlands.
   [Janssens, Ivan A.; Vicca, Sara] Univ Antwerp, Dept Biol, B-2610 Antwerp, Belgium.
   [Penuelas, Josep] CREAF, Barcelona 08193, Catalonia, Spain.
   [Penuelas, Josep] UAB, CSIC, CEAB, Global Ecol Unit,CREAF, Barcelona 08193, Catalonia, Spain.
   [Wan, Shiqiang] Henan Univ, Coll Life Sci, Kaifeng 475001, Peoples R China.
   [Zeng, Hui] Peking Univ, Shenzhen Grad Sch, Shenzhen 518055, Peoples R China.
C3 Peking University; Chinese Academy of Sciences; Institute of Tibetan Plateau Research, CAS; Centre National de la Recherche Scientifique (CNRS); CEA; Universite Paris Saclay; Boston University; Princeton University; Vrije Universiteit Amsterdam; University of Antwerp; Centro de Investigacion Ecologica y Aplicaciones Forestales (CREAF-CERCA); Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Centre d'Estudis Avancats de Blanes (CEAB); University of Barcelona; Autonomous University of Barcelona; Centro de Investigacion Ecologica y Aplicaciones Forestales (CREAF-CERCA); Henan University; Peking University Shenzhen Graduate School (PKU Shenzhen); Peking University
RP Piao, SL (corresponding author), Peking Univ, Coll Urban & Environm Sci, Sinofrench Inst Earth Syst Sci, Beijing 100871, Peoples R China.
EM slpiao@pku.edu.cn; zengh@pkusz.edu.cn
FU National Natural Science Foundation of China [41125004, 31021001]; National Basic Research Program of China [2010CB950601, 2013CB956303]; Foundation for Sino-EU Research Cooperation of the Ministry of Science and Technology of China [1003]; Chinese Ministry of Environmental Protection [201209031]
NR 42
TC 563
Z9 690
U1 31
U2 1013
PU NATURE PUBLISHING 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 5
PY 2013
VL 501
IS 7465
BP 88
EP +
DI 10.1038/nature12434
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 211ER
UT WOS:000323888300037
PM 24005415
DA 2026-03-09
ER

PT J
AU Hirano, M
   Guo, P
   McCurley, N
   Schorpp, M
   Das, S
   Boehm, T
   Cooper, MD
AF Hirano, Masayuki
   Guo, Peng
   McCurley, Nathanael
   Schorpp, Michael
   Das, Sabyasachi
   Boehm, Thomas
   Cooper, Max D.
TI Evolutionary implications of a third lymphocyte lineage in lampreys
SO NATURE
LA English
DT Article
ID gamma-delta; adaptive immunity; t-cells; receptor; antigen
AB Jawed vertebrates (gnathostomes) and jawless vertebrates (cyclostomes) have different adaptive immune systems(1,2). Gnathostomes use T- and B-cell antigen receptors belonging to the immunoglobulin superfamily(3,4). Cyclostomes, the lampreys and hagfish, instead use leucine-rich repeat proteins to construct variable lymphocyte receptors (VLRs), two types of which, VLRA and VLRB, are reciprocally expressed by lymphocytes resembling gnathostome T and B cells(5-7). Here we define another lineage of T-cell-like lymphocytes that express the recently identified VLRC receptors(8,9). Both VLRC+ and VLRA(+) lymphocytes express orthologues of genes that gnathostome gamma delta and alpha beta T cells use for their differentiation, undergo VLRC and VLRA assembly and repertoire diversification in the 'thymoid' gill region, and express their VLRs solely as cell-surface proteins. Our findings suggest that the genetic programmes for two primordial T-cell lineages and a prototypic B-cell lineage were already present in the last common vertebrate ancestor approximately 500 million years ago. We propose that functional specialization of distinct T-cell-like lineages was an ancient feature of a primordial immune system.
C1 [Hirano, Masayuki; Guo, Peng; McCurley, Nathanael; Das, Sabyasachi; Cooper, Max D.] Emory Univ, Emory Vaccine Ctr, Atlanta, GA 30322 USA.
   [Hirano, Masayuki; Guo, Peng; McCurley, Nathanael; Das, Sabyasachi; Cooper, Max D.] Emory Univ, Dept Pathol & Lab Med, Atlanta, GA 30322 USA.
   [Schorpp, Michael; Boehm, Thomas] Max Planck Inst Immunobiol & Epigenet, Dept Dev Immunol, D-79108 Freiburg, Germany.
C3 Emory University; Emory University; Max Planck Society
RP Cooper, MD (corresponding author), Emory Univ, Emory Vaccine Ctr, 1462 Clifton Rd North East, Atlanta, GA 30322 USA.
EM max.cooper@emory.edu
FU National Institutes of Health [R01AI072435, R01GM100151]; Georgia Research Alliance; Max Planck Society; National Institute of Allergy and Infectious Diseases [R01AI072435] Funding Source: NIH RePORTER
NR 21
TC 180
Z9 210
U1 1
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 SEP 19
PY 2013
VL 501
IS 7467
BP 435
EP +
DI 10.1038/nature12467
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 219XT
UT WOS:000324545700049
PM 23934109
DA 2026-03-09
ER

PT J
AU Pedersen, BP
   Kumar, H
   Waight, AB
   Risenmay, AJ
   Roe-Zurz, Z
   Chau, BH
   Schlessinger, A
   Bonomi, M
   Harries, W
   Sali, A
   Johri, AK
   Stroud, RM
AF Pedersen, Bjorn P.
   Kumar, Hemant
   Waight, Andrew B.
   Risenmay, Aaron J.
   Roe-Zurz, Zygy
   Chau, Bryant H.
   Schlessinger, Avner
   Bonomi, Massimiliano
   Harries, William
   Sali, Andrej
   Johri, Atul K.
   Stroud, Robert M.
TI Crystal structure of a eukaryotic phosphate transporter
SO NATURE
LA English
DT Article
ID saccharomyces-cerevisiae; piriformospora-indica; molecular-dynamics; force-field; protein; specificity; prediction; mechanism; sequence; carriers
AB Phosphate is crucial for structural and metabolic needs, including nucleotide and lipid synthesis, signalling and chemical energy storage. Proton-coupled transporters of the major facilitator superfamily (MFS) are essential for phosphate uptake in plants and fungi, and also have a function in sensing external phosphate levels as transceptors(1-5). Here we report the 2.9 angstrom structure of a fungal (Piriformospora indica) high-affinity phosphate transporter, PiPT, in an inward-facing occluded state, with bound phosphate visible in the membrane-buried binding site. The structure indicates both proton and phosphate exit pathways and suggests a modified asymmetrical 'rocker-switch' mechanism of phosphate transport. PiPT is related to several human transporter families, most notably the organic cation and anion transporters of the solute carrier family (SLC22), which are implicated in cancer-drug resistance(6,7). We modelled representative cation and anion SLC22 transporters based on the PiPT structure to surmise the structural basis for substrate binding and charge selectivity in this important family. The PiPT structure demonstrates and expands on principles of substrate transport by the MFS transporters and illuminates principles of phosphate uptake in particular.
C1 [Pedersen, Bjorn P.; Kumar, Hemant; Waight, Andrew B.; Risenmay, Aaron J.; Roe-Zurz, Zygy; Chau, Bryant H.; Harries, William; Stroud, Robert M.] Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94158 USA.
   [Kumar, Hemant; Johri, Atul K.] Jawaharlal Nehru Univ, Sch Life Sci, New Delhi 110067, India.
   [Schlessinger, Avner; Bonomi, Massimiliano; Sali, Andrej] Univ Calif San Francisco, Calif Inst Quantitat Biosci, Dept Pharmaceut Chem, Dept Bioengn & Therapeut Sci, San Francisco, CA 94158 USA.
C3 University of California System; University of California San Francisco; Jawaharlal Nehru University, New Delhi; University of California System; University of California San Francisco
RP Stroud, RM (corresponding author), Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94158 USA.
EM stroud@msg.ucsf.edu
FU Carlsberg Foundation; Danish Cancer Society; Woods Whelan foundation; Council of Scientific and Industrial Research, Government of India; Jawaharlal Nehru University, New Delhi; NIH [F32 GM088991, U01 GM61390, U54 GM094625, GM24485, GM073210]; National Institute of General Medical Sciences [R01GM024485] Funding Source: NIH RePORTER
NR 63
TC 195
Z9 229
U1 1
U2 150
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 25
PY 2013
VL 496
IS 7446
BP 533
EP 536
DI 10.1038/nature12042
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 131HU
UT WOS:000317984400047
PM 23542591
DA 2026-03-09
ER

PT J
AU Key, K
   Constable, S
   Liu, LJ
   Pommier, A
AF Key, Kerry
   Constable, Steven
   Liu, Lijun
   Pommier, Anne
TI Electrical image of passive mantle upwelling beneath the northern East Pacific Rise
SO NATURE
LA English
DT Article
ID midocean ridges; melt experiment; region; heterogeneity; generation; peridotite; asymmetry; dynamics; basalt; models
AB Melt generated by mantle upwelling is fundamental to the production of new oceanic crust at mid-ocean ridges, yet the forces controlling this process are debated(1,2). Passive-flow models predict symmetric upwelling due to viscous drag from the diverging tectonic plates, but have been challenged by geophysical observations of asymmetric upwelling(3-5) that suggest anomalous mantle pressure and temperature gradients(2,6,7), and by observations of concentrated upwelling centres(8) consistent with active models where buoyancy forces give rise to focused convective flow(2). Here we use sea-floor magnetotelluric soundings at the fast-spreading northern East Pacific Rise to image mantle electrical structure to a depth of about 160 kilometres. Our data reveal a symmetric, high-conductivity region at depths of 20-90 kilometres that is consistent with partial melting of passively upwelling mantle(9-11). The triangular region of conductive partial melt matches passive-flow predictions, suggesting that melt focusing to the ridge occurs in the porous melting region rather than along the shallower base of the thermal lithosphere. A deeper conductor observed east of the ridge at a depth of more than 100 kilometres is explained by asymmetric upwelling due to viscous coupling across two nearby transform faults. Significant electrical anisotropy occurs only in the shallowest mantle east of the ridge axis, where high vertical conductivity at depths of 10-20 kilometres indicates localized porous conduits. This suggests that a coincident seismic-velocity anomaly(12) is evidence of shallow magma transport channels(13,14) rather than deeper off-axis upwelling. We interpret the mantle electrical structure as evidence that plate-driven passive upwelling dominates this ridge segment, with dynamic forces being negligible.
C1 [Key, Kerry; Constable, Steven] Univ Calif San Diego, Scripps Inst Oceanog, Inst Geophys & Planetary Phys, La Jolla, CA 92093 USA.
   [Liu, Lijun] Univ Illinois, Dept Geol, Coll Liberal Arts & Sci, Urbana, IL 61801 USA.
   [Pommier, Anne] Arizona State Univ, Sch Earth & Space Explorat, Tempe, AZ 85287 USA.
C3 University of California System; University of California San Diego; Scripps Institution of Oceanography; University of Illinois System; University of Illinois Urbana-Champaign; Arizona State University; Arizona State University-Tempe
RP Key, K (corresponding author), Univ Calif San Diego, Scripps Inst Oceanog, Inst Geophys & Planetary Phys, La Jolla, CA 92093 USA.
EM kkey@ucsd.edu
FU US NSF [OCE-0241597]; Seafloor Electromagnetic Methods Consortium at Scripps Institution of Oceanography
NR 33
TC 139
Z9 162
U1 2
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 MAR 28
PY 2013
VL 495
IS 7442
BP 500
EP +
DI 10.1038/nature11932
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 113QN
UT WOS:000316682800043
PM 23538832
DA 2026-03-09
ER

PT J
AU Ferrier, KL
   Huppert, KL
   Perron, JT
AF Ferrier, Ken L.
   Huppert, Kimberly L.
   Perron, J. Taylor
TI Climatic control of bedrock river incision
SO NATURE
LA English
DT Article
ID erosion rates; landscape response; sierra-nevada; model; kauai; precipitation; variability; tectonics; evolution; volcanism
AB Bedrock river incision drives the development of much of Earth's surface topography(1-3), and thereby shapes the structure of mountain belts(4) and modulates Earth's habitability through its effects on soil erosion(5), nutrient fluxes(6) and global climate(7). Although it has long been expected that river incision rates should depend strongly on precipitation rates, quantifying the effects of precipitation rates on bedrock river incision rates has proved difficult, partly because river incision rates are difficult to measure and partly because non-climatic factors can obscure climatic effects at sites where river incision rates have been measured(8,9). Here we present measurements of river incision rates across one of Earth's steepest rainfall gradients, which show that precipitation rates do indeed influence long-term bedrock river incision rates. We apply a widely used empirical law for bedrock river incision(3,9-11) to a series of rivers on the Hawaiian island of Kaua'i, where mean annual precipitation ranges from 0.5 metres to 9.5 metres (ref. 12)-over 70 per cent of the global range(13)-and river incision rates averaged over millions of years can be inferred from the depth of river canyons and the age of the volcanic bedrock. Both a time-averaged analysis and numerical modelling of transient river incision reveal that the long-term efficiency of bedrock river incision across Kaua'i is positively correlated with upstream-averaged mean annual precipitation rates. We provide theoretical context for this result by demonstrating that our measurements are consistent with a linear dependence of river incision rates on stream power, the rate of energy expenditure by the flow on the riverbed. These observations provide rare empirical evidence for the long-proposed coupling between climate and river incision, suggesting that previously proposed feed-backs among topography, climate and tectonics may occur.
C1 [Ferrier, Ken L.; Huppert, Kimberly L.; Perron, J. Taylor] MIT, Dept Earth Atmospher & Planetary Sci, Cambridge, MA 02139 USA.
C3 Massachusetts Institute of Technology (MIT)
RP Ferrier, KL (corresponding author), Harvard Univ, Dept Earth & Planetary Sci, 20 Oxford St, Cambridge, MA 02138 USA.
EM ferrier@fas.harvard.edu
FU Massachusetts Institute of Technology
NR 39
TC 207
Z9 248
U1 3
U2 156
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 11
PY 2013
VL 496
IS 7444
BP 206
EP +
DI 10.1038/nature11982
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 122VM
UT WOS:000317346300038
PM 23579679
DA 2026-03-09
ER

PT J
AU Mossadegh-Keller, N
   Sarrazin, S
   Kandalla, PK
   Espinosa, L
   Stanley, ER
   Nutt, SL
   Moore, J
   Sieweke, MH
AF Mossadegh-Keller, Noushine
   Sarrazin, Sandrine
   Kandalla, Prashanth K.
   Espinosa, Leon
   Stanley, E. Richard
   Nutt, Stephen L.
   Moore, Jordan
   Sieweke, Michael H.
TI M-CSF instructs myeloid lineage fate in single haematopoietic stem cells
SO NATURE
LA English
DT Article
ID progenitor cells; in-vivo; commitment; macrophage; diversification; infection; hierarchy; cytokines; choice; mice
AB Under stress conditions such as infection or inflammation the body rapidly needs to generate new blood cells that are adapted to the challenge. Haematopoietic cytokines are known to increase output of specific mature cells by affecting survival, expansion and differentiation of lineage-committed progenitors(1,2), but it has been debated whether long-term haematopoietic stem cells (HSCs) are susceptible to direct lineage-specifying effects of cytokines. Although genetic changes in transcription factor balance can sensitize HSCs to cytokine instruction(3), the initiation of HSC commitment is generally thought to be triggered by stochastic fluctuation in cell-intrinsic regulators such as lineage-specific transcription factors(4-7), leaving cytokines to ensure survival and proliferation of the progeny cells(8,9). Here we show that macrophage colony-stimulating factor (M-CSF, also called CSF1), a myeloid cytokine released during infection and inflammation, can directly induce the myeloid master regulator PU.1 and instruct myeloid cell-fate change in mouse HSCs, independently of selective survival or proliferation. Video imaging and single-cell gene expression analysis revealed that stimulation of highly purified HSCs with M-CSF in culture resulted in activation of the PU.1 promoter and an increased number of PU.1(+) cells with myeloid gene signature and differentiation potential. In vivo, high systemic levels of M-CSF directly stimulated M-CSF-receptor-dependent activation of endogenous PU.1 protein in single HSCs and induced a PU.1-dependent myeloid differentiation preference. Our data demonstrate that lineage-specific cytokines can act directly on HSCs in vitro and in vivo to instruct a change of cell identity. This fundamentally changes the current view of how HSCs respond to environmental challenge and implicates stress-induced cytokines as direct instructors of HSC fate.
C1 [Mossadegh-Keller, Noushine; Sarrazin, Sandrine; Kandalla, Prashanth K.; Sieweke, Michael H.] Aix Marseille Univ, Ctr Immunol Marseille Luminy, UM2, F-13288 Marseille 09, France.
   [Mossadegh-Keller, Noushine; Sarrazin, Sandrine; Kandalla, Prashanth K.; Sieweke, Michael H.] INSERM, U1104, F-13288 Marseille 09, France.
   [Mossadegh-Keller, Noushine; Sarrazin, Sandrine; Kandalla, Prashanth K.; Sieweke, Michael H.] CNRS, UMR7280, F-13288 Marseille 09, France.
   [Espinosa, Leon] CNRS, Chim Bacterienne Lab, UMR 7283, F-13009 Marseille, France.
   [Stanley, E. Richard] Albert Einstein Coll Med, Dept Dev & Mol Biol, Bronx, NY 10461 USA.
   [Nutt, Stephen L.] Walter & Eliza Hall Inst Med Res, Parkville, Vic 3052, Australia.
   [Moore, Jordan] Fluidigm Corp, San Francisco, CA 94080 USA.
   [Sieweke, Michael H.] Max Delbruck Ctr Mol Med, D-13125 Berlin, Germany.
C3 Aix-Marseille Universite; Universite de Montpellier; Institut National de la Sante et de la Recherche Medicale (Inserm); Institut National de la Sante et de la Recherche Medicale (Inserm); Centre National de la Recherche Scientifique (CNRS); Aix-Marseille Universite; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB); Montefiore Medical Center; Albert Einstein College of Medicine; Yeshiva University; Walter & Eliza Hall Institute; Standard BioTools Inc.; Helmholtz Association; Max Delbruck Center for Molecular Medicine
RP Sieweke, MH (corresponding author), Aix Marseille Univ, Ctr Immunol Marseille Luminy, UM2, Campus Luminy,Case 906, F-13288 Marseille 09, France.
EM sarrazin@ciml.univ-mrs.fr; sieweke@ciml.univ-mrs.fr
FU Association pour la recherche sur le Cancer [3422]; Agence nationale de la Recherche [BLAN07-1_205752]; NIH [CA 32551]
NR 37
TC 293
Z9 361
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 MAY 9
PY 2013
VL 497
IS 7448
BP 239
EP +
DI 10.1038/nature12026
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 139CD
UT WOS:000318558200036
PM 23575636
DA 2026-03-09
ER

PT J
AU Nicholl, M
   Smartt, SJ
   Jerkstrand, A
   Inserra, C
   McCrum, M
   Kotak, R
   Fraser, M
   Wright, D
   Chen, TW
   Smith, K
   Young, DR
   Sim, SA
   Valenti, S
   Howell, DA
   Bresolin, F
   Kudritzki, RP
   Tonry, JL
   Huber, ME
   Rest, A
   Pastorello, A
   Tomasella, L
   Cappellaro, E
   Benetti, S
   Mattila, S
   Kankare, E
   Kangas, T
   Leloudas, G
   Sollerman, J
   Taddia, F
   Berger, E
   Chornock, R
   Narayan, G
   Stubbs, CW
   Foley, RJ
   Lunnan, R
   Soderberg, A
   Sanders, N
   Milisavljevic, D
   Margutti, R
   Kirshner, RP
   Elias-Rosa, N
   Morales-Garoffolo, A
   Taubenberger, S
   Botticella, MT
   Gezari, S
   Urata, Y
   Rodney, S
   Riess, AG
   Scolnic, D
   Wood-Vasey, WM
   Burgett, WS
   Chambers, K
   Flewelling, HA
   Magnier, EA
   Kaiser, N
   Metcalfe, N
   Morgan, J
   Price, PA
   Sweeney, W
   Waters, C
AF Nicholl, M.
   Smartt, S. J.
   Jerkstrand, A.
   Inserra, C.
   McCrum, M.
   Kotak, R.
   Fraser, M.
   Wright, D.
   Chen, T-W
   Smith, K.
   Young, D. R.
   Sim, S. A.
   Valenti, S.
   Howell, D. A.
   Bresolin, F.
   Kudritzki, R. P.
   Tonry, J. L.
   Huber, M. E.
   Rest, A.
   Pastorello, A.
   Tomasella, L.
   Cappellaro, E.
   Benetti, S.
   Mattila, S.
   Kankare, E.
   Kangas, T.
   Leloudas, G.
   Sollerman, J.
   Taddia, F.
   Berger, E.
   Chornock, R.
   Narayan, G.
   Stubbs, C. W.
   Foley, R. J.
   Lunnan, R.
   Soderberg, A.
   Sanders, N.
   Milisavljevic, D.
   Margutti, R.
   Kirshner, R. P.
   Elias-Rosa, N.
   Morales-Garoffolo, A.
   Taubenberger, S.
   Botticella, M. T.
   Gezari, S.
   Urata, Y.
   Rodney, S.
   Riess, A. G.
   Scolnic, D.
   Wood-Vasey, W. M.
   Burgett, W. S.
   Chambers, K.
   Flewelling, H. A.
   Magnier, E. A.
   Kaiser, N.
   Metcalfe, N.
   Morgan, J.
   Price, P. A.
   Sweeney, W.
   Waters, C.
TI Slowly fading super-luminous supernovae that are not pair-instability explosions
SO NATURE
LA English
DT Article
ID core-collapse supernovae; ultraluminous supernovae; superluminous supernovae; low-metallicity; ic supernovae; light curves; magnetar; 2007bi; ni-56
AB Super-luminous supernovae(1-4) that radiate more than 1044 ergs per second at their peak luminosity have recently been discovered in faint galaxies at redshifts of 0.1-4. Some evolve slowly, resembling models of 'pair-instability' supernovae(5,6). Such models involve stars with original masses 140-260 times that of the Sun that now have carbon-oxygen cores of 65-130 solar masses. In these stars, the photons that prevent gravitational collapse are converted to electron-positron pairs, causing rapid contraction and thermonuclear explosions. Many solar masses of Ni-56 are synthesized; this isotope decays to Fe-56 via Co-56, powering bright light curves(7,8). Such massive progenitors are expected to have formed from metal-poor gas in the early Universe(9). Recently, supernova 2007bi in a galaxy at redshift 0.127 (about 12 billion years after the Big Bang) with a metallicity one-third that of the Sun was observed to look like a fading pair-instability supernova(1,10). Here we report observations of two slow-to-fade super-luminous supernovae that show relatively fast rise times and blue colours, which are incompatible with pair-instability models. Their late-time light-curve and spectral similarities to supernova 2007bi call the nature of that event into question. Our early spectra closely resemble typical fast-declining super-luminous supernovae(2,11,12), which are not powered by radio-activity. Modelling our observations with 10-16 solar masses of magnetar-energized(13,14) ejecta demonstrates the possibility of a common explosion mechanism. The lack of unambiguous nearby pair-instability events suggests that their local rate of occurrence is less than 6 x 10(-6) times that of the core-collapse rate.
C1 [Nicholl, M.; Smartt, S. J.; Jerkstrand, A.; Inserra, C.; McCrum, M.; Kotak, R.; Fraser, M.; Wright, D.; Chen, T-W; Smith, K.; Young, D. R.; Sim, S. A.] Queens Univ Belfast, Sch Math & Phys, Astrophys Res Ctr, Belfast BT7 1NN, Antrim, North Ireland.
   [Valenti, S.; Howell, D. A.] Global Telescope Network, Las Cumbres Observ, Goleta, CA 93117 USA.
   [Valenti, S.; Howell, D. A.] Univ Calif Santa Barbara, Dept Phys, Santa Barbara, CA 93106 USA.
   [Bresolin, F.; Kudritzki, R. P.; Tonry, J. L.; Huber, M. E.; Burgett, W. S.; Chambers, K.; Flewelling, H. A.; Magnier, E. A.; Kaiser, N.; Morgan, J.; Sweeney, W.; Waters, C.] Univ Hawaii, Inst Astron, Honolulu, HI 96822 USA.
   [Rest, A.] Space Telescope Sci Inst, Baltimore, MD 21218 USA.
   [Pastorello, A.; Tomasella, L.; Cappellaro, E.; Benetti, S.] Osserv Astron Padova, INAF, I-35122 Padua, Italy.
   [Mattila, S.; Kankare, E.] Univ Turku, Finnish Ctr Astron ESO FINCA, FI-21500 Piikkio, Finland.
   [Mattila, S.; Kankare, E.; Kangas, T.] Univ Turku, Tuorla Observ, Dept Phys & Astron, FI-21500 Piikkio, Finland.
   [Leloudas, G.] Stockholm Univ, Oskar Klein Ctr, Dept Phys, S-10691 Stockholm, Sweden.
   [Leloudas, G.] Univ Copenhagen, Dark Cosmol Ctr, Niels Bohr Inst, DK-2100 Copenhagen, Denmark.
   [Sollerman, J.; Taddia, F.] Stockholm Univ, Oskar Klein Ctr, Dept Astron, S-10691 Stockholm, Sweden.
   [Berger, E.; Chornock, R.; Narayan, G.; Stubbs, C. W.; Foley, R. J.; Lunnan, R.; Soderberg, A.; Sanders, N.; Milisavljevic, D.; Margutti, R.; Kirshner, R. P.] Harvard Smithsonian Ctr Astrophys, Cambridge, MA 02138 USA.
   [Kirshner, R. P.] Univ Calif Santa Barbara, Kavli Inst Theoret Phys, Santa Barbara, CA 93106 USA.
   [Elias-Rosa, N.; Morales-Garoffolo, A.] Inst Ciencies Espai IEEC CSIC, Fac Ciencies, Bellaterra 08193, Spain.
   [Taubenberger, S.] Max Planck Inst Astrophys, D-85741 Garching, Germany.
   [Botticella, M. T.] Osserv Astron Capodimonte, INAF, I-80131 Naples, Italy.
   [Gezari, S.] Univ Maryland, Dept Astron, College Pk, MD 20742 USA.
   [Urata, Y.] Natl Cent Univ, Inst Astron, Chungli 32054, Taiwan.
   [Rodney, S.; Riess, A. G.; Scolnic, D.] Johns Hopkins Univ, Dept Phys & Astron, Baltimore, MD 21218 USA.
   [Wood-Vasey, W. M.] Univ Pittsburgh, Pittsburgh Particle Phys Astrophys & Cosmol Ctr, Dept Phys & Astron, Pittsburgh, PA 15260 USA.
   [Metcalfe, N.] Univ Durham, Dept Phys, Durham DH1 3LE, England.
   [Price, P. A.] Princeton Univ, Dept Astrophys Sci, Princeton, NJ 08544 USA.
C3 Queens University Belfast; University of California System; University of California Santa Barbara; University of Hawaii System; Space Telescope Science Institute; Istituto Nazionale Astrofisica (INAF); University of Padua; University of Turku; University of Turku; Oskar Klein Centre; Stockholm University; University of Copenhagen; Niels Bohr Institute; Oskar Klein Centre; Stockholm University; Smithsonian Institution; Harvard University; Smithsonian Astrophysical Observatory; University of California System; University of California Santa Barbara; Institut d'Estudis Espacials de Catalunya (IEEC); Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Instituto de Ciencias del Espacio (ICE); Max Planck Society; Istituto Nazionale Astrofisica (INAF); University System of Maryland; University of Maryland College Park; National Central University; Johns Hopkins University; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh; Durham University; Princeton University
RP Nicholl, M (corresponding author), Queens Univ Belfast, Sch Math & Phys, Astrophys Res Ctr, Belfast BT7 1NN, Antrim, North Ireland.
EM mnicholl03@qub.ac.uk
FU NASA through the Planetary Science Division of the NASA Science Mission Directorate [NNX08AR22G]; National Science Foundation [AST-1238877]; University of Maryland; NSF [AST-1009749, AST-121196]; Swedish Research Council [623-2011-7117];  [291222]; STFC [ST/I001123/1] Funding Source: UKRI; Science and Technology Facilities Council [ST/I001123/1] Funding Source: researchfish; Direct For Mathematical & Physical Scien [1009749] Funding Source: National Science Foundation; Direct For Mathematical & Physical Scien; Division Of Astronomical Sciences [1211196] Funding Source: National Science Foundation; Division Of Astronomical Sciences [1009749] Funding Source: National Science Foundation; Division Of Astronomical Sciences; Direct For Mathematical & Physical Scien [1238877] Funding Source: National Science Foundation
NR 31
TC 236
Z9 255
U1 1
U2 28
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 17
PY 2013
VL 502
IS 7471
BP 346
EP +
DI 10.1038/nature12569
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 235GY
UT WOS:000325706300047
PM 24132291
DA 2026-03-09
ER

PT J
AU Jiang, J
   Jing, YC
   Cost, GJ
   Chiang, JC
   Kolpa, HJ
   Cotton, AM
   Carone, DM
   Carone, BR
   Shivak, DA
   Guschin, DY
   Pearl, JR
   Rebar, EJ
   Byron, M
   Gregory, PD
   Brown, CJ
   Urnov, FD
   Hall, LL
   Lawrence, JB
AF Jiang, Jun
   Jing, Yuanchun
   Cost, Gregory J.
   Chiang, Jen-Chieh
   Kolpa, Heather J.
   Cotton, Allison M.
   Carone, Dawn M.
   Carone, Benjamin R.
   Shivak, David A.
   Guschin, Dmitry Y.
   Pearl, Jocelynn R.
   Rebar, Edward J.
   Byron, Meg
   Gregory, Philip D.
   Brown, Carolyn J.
   Urnov, Fyodor D.
   Hall, Lisa L.
   Lawrence, Jeanne B.
TI Translating dosage compensation to trisomy 21
SO NATURE
LA English
DT Article
ID embryonic stem-cells; human xist gene; dna methylation; x-chromosome; inactivation; rna; expression
AB Down's syndrome is a common disorder with enormous medical and social costs, caused by trisomy for chromosome 21. We tested the concept that gene imbalance across an extra chromosome can be de facto corrected by manipulating a single gene, XIST (the X-inactivation gene). Using genome editing with zinc finger nucleases, we inserted a large, inducible XIST transgene into the DYRK1A locus on chromosome 21, in Down's syndrome pluripotent stem cells. The XIST non-coding RNA coats chromosome 21 and triggers stable heterochromatin modifications, chromosome-wide transcriptional silencing and DNA methylation to form a 'chromosome 21 Barr body'. This provides a model to study human chromosome inactivation and creates a system to investigate genomic expression changes and cellular pathologies of trisomy 21, free from genetic and epigenetic noise. Notably, deficits in proliferation and neural rosette formation are rapidly reversed upon silencing one chromosome 21. Successful trisomy silencing in vitro also surmounts the major first step towards potential development of 'chromosome therapy'.
C1 [Jiang, Jun; Jing, Yuanchun; Chiang, Jen-Chieh; Kolpa, Heather J.; Carone, Dawn M.; Carone, Benjamin R.; Byron, Meg; Hall, Lisa L.; Lawrence, Jeanne B.] Univ Massachusetts, Sch Med, Dept Cell & Dev Biol, Worcester, MA 01655 USA.
   [Cost, Gregory J.; Shivak, David A.; Guschin, Dmitry Y.; Pearl, Jocelynn R.; Rebar, Edward J.; Gregory, Philip D.; Urnov, Fyodor D.] Sangamo BioSci, Richmond, CA 94804 USA.
   [Cotton, Allison M.; Brown, Carolyn J.] Univ British Columbia, Dept Med Genet, Vancouver, BC V6T 1Z3, Canada.
C3 University of Massachusetts System; University of Massachusetts Worcester; Sangamo Therapeutics, Inc.; University of British Columbia
RP Lawrence, JB (corresponding author), Univ Massachusetts, Sch Med, Dept Cell & Dev Biol, 55 Lake Ave North, Worcester, MA 01655 USA.
EM furnov@sangamo.com; Jeanne.Lawrence@umassmed.edu
FU CIHR [MOP-13680]; NIH [1F32CA154086, 2T32HD007439];  [GM053234];  [GM085548];  [GM096400 RC4]
NR 35
TC 251
Z9 302
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 AUG 15
PY 2013
VL 500
IS 7462
BP 296
EP +
DI 10.1038/nature12394
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 201AF
UT WOS:000323112400024
PM 23863942
DA 2026-03-09
ER

PT J
AU Jin, FL
   Li, Y
   Dixon, JR
   Selvaraj, S
   Ye, Z
   Lee, AY
   Yen, CA
   Schmitt, AD
   Espinoza, CA
   Ren, B
AF Jin, Fulai
   Li, Yan
   Dixon, Jesse R.
   Selvaraj, Siddarth
   Ye, Zhen
   Lee, Ah Young
   Yen, Chia-An
   Schmitt, Anthony D.
   Espinoza, Celso A.
   Ren, Bing
TI A high-resolution map of the three-dimensional chromatin interactome in human cells
SO NATURE
LA English
DT Article
ID gene-expression; organization; genm; principles; landscape; enhancers; insights
AB A large number of cis-regulatory sequences have been annotated in the human genome(1,2), but defining their target genes remains a challenge(3). One strategy is to identify the long-range looping interactions at these elements with the use of chromosome conformation capture (3C)-based techniques(4). However, previous studies lack either the resolution or coverage to permit a whole-genome, unbiased view of chromatin interactions. Here we report a comprehensive chromatin interaction map generated in human fibroblasts using a genome-wide 3C analysis method (Hi-C)(5). We determined over one million long-range chromatin interactions at 5-10-kb resolution, and uncovered general principles of chromatin organization at different types of genomic features. We also characterized the dynamics of promoter-enhancer contacts after TNF-alpha signalling in these cells. Unexpectedly, we found that TNF-alpha-responsive enhancers are already in contact with their target promoters before signalling. Such pre-existing chromatin looping, which also exists in other cell types with different extracellular signalling, is a strong predictor of gene induction. Our observations suggest that the three-dimensional chromatin landscape, once established in a particular cell type, is relatively stable and could influence the selection or activation of target genes by a ubiquitous transcription activator in a cell-specific manner.
C1 [Jin, Fulai; Li, Yan; Dixon, Jesse R.; Selvaraj, Siddarth; Ye, Zhen; Lee, Ah Young; Yen, Chia-An; Schmitt, Anthony D.; Espinoza, Celso A.; Ren, Bing] Ludwig Inst Canc Res, La Jolla, CA 92093 USA.
   [Dixon, Jesse R.] Univ Calif San Diego, UCSD Med Scientist Training Program, Sch Med, La Jolla, CA 92093 USA.
   [Selvaraj, Siddarth] Univ Calif San Diego, UCSD Bioinformat & Syst Biol Grad Program, La Jolla, CA 92093 USA.
   [Schmitt, Anthony D.] Univ Calif San Diego, UCSD Biomed Sci Grad Program, Sch Med, La Jolla, CA 92093 USA.
   [Ren, Bing] Univ Calif San Diego, Sch Med, Moores Canc Ctr, Dept Cellular & Mol Med,Inst Genome 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; 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 of Regenerative Medicine [RN2-00905]; US National Institutes of Health [P50 GM085764-03, U01 ES017166]; National Institute of General Medical Sciences [T32GM008666, T32GM007198] Funding Source: NIH RePORTER
NR 30
TC 1042
Z9 1274
U1 0
U2 179
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 14
PY 2013
VL 503
IS 7475
BP 290
EP 294
DI 10.1038/nature12644
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 250YX
UT WOS:000326894200057
PM 24141950
DA 2026-03-09
ER

PT J
AU Yamanaka, S
   Mehta, S
   Reyes-Turcu, FE
   Zhuang, FL
   Fuchs, RT
   Rong, YK
   Robb, GB
   Grewal, SIS
AF Yamanaka, Soichiro
   Mehta, Sameet
   Reyes-Turcu, Francisca E.
   Zhuang, Fanglei
   Fuchs, Ryan T.
   Rong, Yikang
   Robb, Gregory B.
   Grewal, Shiv I. S.
TI RNAi triggered by specialized machinery silences developmental genes and retrotransposons
SO NATURE
LA English
DT Article
ID meiotic messenger-rnas; fission yeast; elimination; promotes; complex; transcriptome; surveillance; maintenance; methylation; nucleation
AB RNA interference (RNAi) is a conserved mechanism in which small interfering RNAs (siRNAs) guide the degradation of cognate RNAs, but also promote heterochromatin assembly at repetitive DNA elements such as centromeric repeats(1,2). However, the full extent of RNAi functions and its endogenous targets have not been explored. Here we show that, in the fission yeast Schizosaccharomyces pombe, RNAi and heterochromatin factors cooperate to silence diverse loci, including sexual differentiation genes, genes encoding transmembrane proteins, and retrotransposons that are also targeted by the exosome RNA degradation machinery. In the absence of the exosome, transcripts are processed preferentially by the RNAi machinery, revealing siRNA clusters and a corresponding increase in heterochromatin modifications across large domains containing genes and retrotransposons. We show that the generation of siRNAs and heterochromatin assembly by RNAi is triggered by a mechanism involving the canonical poly(A) polymerase Pla1 and an associated RNA surveillance factor Red1, which also activate the exosome. Notably, siRNA production and heterochromatin modifications at these target loci are regulated by environmental growth conditions, and by developmental signals that induce gene expression during sexual differentiation. Our analyses uncover an interaction between RNAi and the exosome that is conserved in Drosophila, and show that differentiation signals modulate RNAi silencing to regulate developmental genes.
C1 [Yamanaka, Soichiro; Mehta, Sameet; Reyes-Turcu, Francisca E.; Rong, Yikang; Grewal, Shiv I. S.] NCI, Biochem & Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
   [Zhuang, Fanglei; Fuchs, Ryan T.; Robb, Gregory B.] New England Biolabs Inc, Ipswich, MA 01938 USA.
C3 National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); New England Biolabs
RP Grewal, SIS (corresponding author), NCI, Biochem & Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
EM grewals@mail.nih.gov
FU National Institutes of Health, National Cancer Institute; National Cancer Institute [ZIABC010523, ZIABC011208] Funding Source: NIH RePORTER
NR 32
TC 121
Z9 149
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 JAN 24
PY 2013
VL 493
IS 7433
BP 557
EP +
DI 10.1038/nature11716
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 075GF
UT WOS:000313871400043
PM 23151475
DA 2026-03-09
ER

PT J
AU Helmstaedter, M
   Briggman, KL
   Turaga, SC
   Jain, V
   Seung, HS
   Denk, W
AF Helmstaedter, Moritz
   Briggman, Kevin L.
   Turaga, Srinivas C.
   Jain, Viren
   Seung, H. Sebastian
   Denk, Winfried
TI Connectomic reconstruction of the inner plexiform layer in the mouse retina
SO NATURE
LA English
DT Article
ID ganglion-cells; bipolar cells; direction-selectivity; electron-microscopy; amacrine cells; synaptic connections; rabbit retina; microcircuitry; circuit; morphology
AB Comprehensive high-resolution structural maps are central to functional exploration and understanding in biology. For the nervous system, in which high resolution and large spatial extent are both needed, such maps are scarce as they challenge data acquisition and analysis capabilities. Here we present for the mouse inner plexiform layer-the main computational neuropil region in the mammalian retina-the dense reconstruction of 950 neurons and their mutual contacts. This was achieved by applying a combination of crowd-sourced manual annotation and machine-learning-based volume segmentation to serial block-face electron microscopy data. We characterize a new type of retinal bipolar interneuron and show that we can subdivide a known type based on connectivity. Circuit motifs that emerge from our data indicate a functional mechanism for a known cellular response in a ganglion cell that detects localized motion, and predict that another ganglion cell is motion sensitive.
C1 [Helmstaedter, Moritz; Briggman, Kevin L.; Denk, Winfried] Max Planck Inst Med Res, D-69120 Heidelberg, Germany.
   [Turaga, Srinivas C.; Jain, Viren; Seung, H. Sebastian] MIT, Howard Hughes Med Inst, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA.
C3 Max Planck Society; Massachusetts Institute of Technology (MIT); Howard Hughes Medical Institute
RP Helmstaedter, M (corresponding author), Max Planck Inst Neurobiol, D-82152 Martinsried, Germany.
EM mhelmstaedter@neuro.mpg.de
FU Max-Planck Society; DFG; Gatsby Charitable Foundation
NR 51
TC 724
Z9 881
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 AUG 8
PY 2013
VL 500
IS 7461
BP 168
EP +
DI 10.1038/nature12346
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 197CH
UT WOS:000322825500027
PM 23925239
DA 2026-03-09
ER

PT J
AU Silverio, DL
   Torker, S
   Pilyugina, T
   Vieira, EM
   Snapper, ML
   Haeffner, F
   Hoveyda, AH
AF Silverio, Daniel L.
   Torker, Sebastian
   Pilyugina, Tatiana
   Vieira, Erika M.
   Snapper, Marc L.
   Haeffner, Fredrik
   Hoveyda, Amir H.
TI Simple organic molecules as catalysts for enantioselective synthesis of amines and alcohols
SO NATURE
LA English
DT Article
ID asymmetric allylation; hydrazono esters; analogs; allylboration; crotylation; derivatives; efficient; imines
AB The discovery of catalysts that can be used to synthesize complex organic compounds by enantioselective transformations is central to advances in the life sciences(1); for this reason, many chemists aim to discover catalysts that allow for preparation of chiral molecules as predominantly one mirror-image isomer(2). The ideal catalyst should not contain precious elements' and should bring reactions to completion in a few hours through operationally simple procedures. Here we introduce a set of small organic molecules that can catalyse reactions of unsaturated organoboron reagents with imines and carbonyls; the products of the reactions are enantiomerically pure amines and alcohols, which might serve as intermediates in the preparation of biologically active molecules. A distinguishing feature of this catalyst class is the presence of a 'key' proton embedded within their structure. Catalysts are derived from the abundant amino add valine and are prepared in large quantities in four steps with inexpensive reagents. Reactions are scalable, do not demand stringent conditions, and can be performed with as little as 0.25 mole per cent catalyst in less than six hours at room temperature to generate products in more than 85 per cent yield and >= 97:3 enantiomeric ratio. The efficiency, selectivity and operational simplicity of the transformations and the range of boron-based reagents are expected to render this advance important for future progress in syntheses of amines and alcohols, which are useful in chemistry, biology and medicine.
C1 [Silverio, Daniel L.; Torker, Sebastian; Pilyugina, Tatiana; Vieira, Erika M.; Snapper, Marc L.; Haeffner, Fredrik; Hoveyda, Amir H.] Boston Coll, Dept Chem, Merkert Chem Ctr, Chestnut Hill, MA 02467 USA.
C3 Boston College
RP Hoveyda, AH (corresponding author), Boston Coll, Dept Chem, Merkert Chem Ctr, Chestnut Hill, MA 02467 USA.
EM amir.hoveyda@bc.edu
FU US National Institutes of Health, Institute of General Medical Sciences [GM-57212]
NR 30
TC 194
Z9 208
U1 0
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 FEB 14
PY 2013
VL 494
IS 7436
BP 216
EP 221
DI 10.1038/nature11844
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 092QS
UT WOS:000315137700035
PM 23407537
DA 2026-03-09
ER

PT J
AU Li, TQ
   Patz, A
   Mouchliadis, L
   Yan, JQ
   Lograsso, TA
   Perakis, IE
   Wang, JG
AF Li, Tianqi
   Patz, Aaron
   Mouchliadis, Leonidas
   Yan, Jiaqiang
   Lograsso, Thomas A.
   Perakis, Ilias E.
   Wang, Jigang
TI Femtosecond switching of magnetism via strongly correlated spin-charge quantum excitations
SO NATURE
LA English
DT Article
ID transition-metal oxides; phase-separation; density-wave; ultrafast; manganite; pulses; state; order
AB The technological demand to push the gigahertz (10(9) hertz) switching speed limit of today's magnetic memory and logic devices into the terahertz (10(12) hertz) regime underlies the entire field of spin-electronics and integrated multi-functional devices. This challenge is met by all-optical magnetic switching based on coherent spin manipulation(1). By analogy to femtosecond chemistry and photosynthetic dynamics(2)-in which photoproducts of chemical and biochemical reactions can be influenced by creating suitable superpositions of molecular states-femtosecond-laser-excited coherence between electronic states can switch magnetic order by 'suddenly' breaking the delicate balance between competing phases of correlated materials: for example, manganites exhibiting colossal magneto-resistance suitable for applications(3,4). Here we show femtosecond (10(-15) seconds) photo-induced switching from anti-ferromagnetic to ferromagnetic ordering in Pr0.7Ca0.3MnO3, by observing the establishment (within about 120 femtoseconds) of a huge temperature-dependent magnetization with photo-excitation threshold behaviour absent in the optical reflectivity. The development of ferromagnetic correlations during the femtosecond laser pulse reveals an initial quantum coherent regime of magnetism, distinguished from the picosecond (10(-12) seconds) lattice-heating regime characterized by phase separation without threshold behaviour(5,6). Our simulations reproduce the nonlinear femtosecond spin generation and underpin fast quantum spin-flip fluctuations correlated with coherent superpositions of electronic states to initiate local ferromagnetic correlations. These results merge two fields, femtosecond magnetism in metals and band insulators(1,7-9), and non-equilibrium phase transitions of strongly correlated electrons(10-17), in which local interactions exceeding the kinetic energy produce a complex balance of competing orders.
C1 [Li, Tianqi; Patz, Aaron; Wang, Jigang] Iowa State Univ, Dept Phys & Astron, Ames, IA 50011 USA.
   [Li, Tianqi; Patz, Aaron; Yan, Jiaqiang; Lograsso, Thomas A.; Wang, Jigang] US DOE, Ames Lab, Ames, IA 50011 USA.
   [Mouchliadis, Leonidas; Perakis, Ilias E.] Univ Crete, Dept Phys, Iraklion 71003, Crete, Greece.
   [Mouchliadis, Leonidas; Perakis, Ilias E.] Fdn Res & Technol Hellas, Inst Elect Struct & Laser, Iraklion 71110, Crete, Greece.
C3 Iowa State University; United States Department of Energy (DOE); Ames National Laboratory; University of Crete; Foundation for Research & Technology - Hellas (FORTH)
RP Wang, JG (corresponding author), Iowa State Univ, Dept Phys & Astron, Ames, IA 50011 USA.
EM ilias@physics.uoc.gr; jgwang@iastate.edu
FU National Science Foundation [DMR-1055352]; US Department of Energy-Basic Energy Sciences [DE-AC02-7CH11358]; Project BIOSOLENUTI [FP7-REGPOT-2008-1, 229927]; EU Social Fund; National resources through the THALES program NANOPHOS; Division Of Materials Research; Direct For Mathematical & Physical Scien [1055352] Funding Source: National Science Foundation
NR 30
TC 158
Z9 182
U1 1
U2 333
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 4
PY 2013
VL 496
IS 7443
BP 69
EP 73
DI 10.1038/nature11934
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 117ZZ
UT WOS:000316993400026
PM 23552945
DA 2026-03-09
ER

PT J
AU Bayraktar, OA
   Doe, CQ
AF Bayraktar, Omer Ali
   Doe, Chris Q.
TI Combinatorial temporal patterning in progenitors expands neural diversity
SO NATURE
LA English
DT Article
ID amplifying neuroblast lineages; drosophila brain-development; twin-of-eyeless; central complex; stem-cells; transcription factors; factor grainyhead; gene-expression; mushroom body; nervous-system
AB Human outer subventricular zone (OSVZ) neural progenitors and Drosophila type II neuroblasts both generate intermediate neural progenitors (INPs) that populate the adult cerebral cortex or central complex, respectively. It is unknown whether INPs simply expand or also diversify neural cell types. Here we show that Drosophila INPs sequentially generate distinct neural subtypes, that INPs sequentially express Dichaete, Grainy head and Eyeless transcription factors, and that these transcription factors are required for the production of distinct neural subtypes. Moreover, parental type II neuroblasts also sequentially express transcription factors and generate different neuronal/glial progeny over time, providing a second temporal identity axis. We conclude that neuroblast and INP temporal patterning axes act together to generate increased neural diversity within the adult central complex; OSVZ progenitors may use similar mechanisms to increase neural diversity in the human brain.
C1 [Bayraktar, Omer Ali; Doe, Chris Q.] Univ Oregon, Howard Hughes Med Inst, Eugene, OR 97403 USA.
   [Bayraktar, Omer Ali; Doe, Chris Q.] Univ Oregon, Inst Mol Biol, Eugene, OR 97403 USA.
   [Doe, Chris Q.] Univ Oregon, Inst Neurosci, Eugene, OR 97403 USA.
C3 Howard Hughes Medical Institute; University of Oregon; University of Oregon; University of Oregon
RP Doe, CQ (corresponding author), Univ Oregon, Howard Hughes Med Inst, Eugene, OR 97403 USA.
EM cdoe@uoregon.edu
FU National Institutes of Health (NIH) [T32HD216345, T32GM007413]; NIH [R01HD27056]; Howard Hughes Medical Institute; Eunice Kennedy Shriver National Institute of Child Health and Human Development [R37HD027056, R01HD027056] Funding Source: NIH RePORTER; National Institute of General Medical Sciences [T32GM007759, T32GM007413] Funding Source: NIH RePORTER
NR 47
TC 144
Z9 182
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 JUN 27
PY 2013
VL 498
IS 7455
BP 449
EP +
DI 10.1038/nature12266
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 171LH
UT WOS:000320929400045
PM 23783519
DA 2026-03-09
ER

PT J
AU Crowe, SA
   Dossing, LN
   Beukes, NJ
   Bau, M
   Kruger, SJ
   Frei, R
   Canfield, DE
AF Crowe, Sean A.
   Dossing, Lasse N.
   Beukes, Nicolas J.
   Bau, Michael
   Kruger, Stephanus J.
   Frei, Robert
   Canfield, Donald E.
TI Atmospheric oxygenation three billion years ago
SO NATURE
LA English
DT Article
ID hexavalent chromium; pongola supergroup; oxidation; sulfur; ga; isotopes; fractionation; witwatersrand; evolution; kinetics
AB It is widely assumed that atmospheric oxygen concentrations remained persistently low (less than 10(-5) times present levels) for about the first 2 billion years of Earth's history(1). The first long-term oxygenation of the atmosphere is thought to have taken place around 2.3 billion years ago, during the Great Oxidation Event(2,3). Geochemical indications of transient atmospheric oxygenation, however, date back to 2.6-2.7 billion years ago(4-6). Here we examine the distribution of chromium isotopes and redox-sensitive metals in the approximately 3-billion-year-old Nsuze palaeosol and in the near-contemporaneous Ijzermyn iron formation from the Pongola Supergroup, South Africa. We find extensive mobilization of redox-sensitive elements through oxidative weathering. Furthermore, using our data we compute a best minimum estimate for atmospheric oxygen concentrations at that time of 331024 times present levels. Overall, our findings suggest that there were appreciable levels of atmospheric oxygen about 3 billion years ago, more than 600 million years before the Great Oxidation Event and some 300-400 million years earlier than previous indications for Earth surface oxygenation.
C1 [Crowe, Sean A.; Dossing, Lasse N.; Canfield, Donald E.] Univ Southern Denmark, Inst Biol, DK-5230 Odense, Denmark.
   [Crowe, Sean A.; Dossing, Lasse N.; Canfield, Donald E.] Univ Southern Denmark, Nord Ctr Earth Evolut, DK-5230 Odense, Denmark.
   [Dossing, Lasse N.; Frei, Robert] Univ Copenhagen, Dept Geosci & Nat Resource Management, DK-1350 Copenhagen, Denmark.
   [Dossing, Lasse N.; Frei, Robert] Univ Copenhagen, Nord Ctr Earth Evolut, DK-1350 Copenhagen, Denmark.
   [Beukes, Nicolas J.; Kruger, Stephanus J.] Univ Johannesburg, Dept Geol, ZA-2006 Johannesburg, South Africa.
   [Bau, Michael] Jacobs Univ Bremen, Earth & Space Sci Program, D-28759 Bremen, Germany.
C3 University of Southern Denmark; University of Southern Denmark; University of Copenhagen; University of Copenhagen; University of Johannesburg; Constructor University
RP Crowe, SA (corresponding author), Univ British Columbia, Life Sci Ctr, Dept Microbiol & Immunol, 2350 Hlth Sci Mall, Vancouver, BC V6T 1Z3, Canada.
EM sean.crowe@ubc.ca
FU Agouron Institute Geobiology Fellowship; NSERC PDF; Danish National Research Foundation [DNRF53]; Danish Agency for Science, Technology, and Innovation; European Research Council; National Research Foundation in Pretoria
NR 30
TC 507
Z9 585
U1 3
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 SEP 26
PY 2013
VL 501
IS 7468
BP 535
EP +
DI 10.1038/nature12426
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 223RP
UT WOS:000324826300055
PM 24067713
DA 2026-03-09
ER

PT J
AU Raymond, PA
   Hartmann, J
   Lauerwald, R
   Sobek, S
   McDonald, C
   Hoover, M
   Butman, D
   Striegl, R
   Mayorga, E
   Humborg, C
   Kortelainen, P
   Dürr, H
   Meybeck, M
   Ciais, P
   Guth, P
AF Raymond, Peter A.
   Hartmann, Jens
   Lauerwald, Ronny
   Sobek, Sebastian
   McDonald, Cory
   Hoover, Mark
   Butman, David
   Striegl, Robert
   Mayorga, Emilio
   Humborg, Christoph
   Kortelainen, Pirkko
   Duerr, Hans
   Meybeck, Michel
   Ciais, Philippe
   Guth, Peter
TI Global carbon dioxide emissions from inland waters
SO NATURE
LA English
DT Article
ID size distribution; lakes; reservoirs; abundance; streams; fluxes; budget; land; trends; rivers
AB Carbon dioxide (CO2) transfer from inland waters to the atmosphere, known as CO2 evasion, is a component of the global carbon cycle. Global estimates of CO2 evasion have been hampered, however, by the lack of a framework for estimating the inland water surface area and gas transfer velocity and by the absence of a global CO2 database. Here we report regional variations in global inland water surface area, dissolved CO2 and gas transfer velocity. We obtain global CO2 evasion rates of 1.8(-0.25)(+0.25) petagrams of carbon (Pg C) per year from streams and rivers and 0.32(-0.26)(+0.52) Pg C yr(-1) from lakes and reservoirs, where the upper and lower limits are respectively the 5th and 95th confidence interval percentiles. The resulting global evasion rate of 2.1 Pg C yr(-1) is higher than previous estimates owing to a larger stream and river evasion rate. Our analysis predicts global hotspots in stream and river evasion, with about 70 per cent of the flux occurring over just 20 per cent of the land surface. The source of inland water CO2 is still not known with certainty and new studies are needed to research the mechanisms controlling CO2 evasion globally.
C1 [Raymond, Peter A.; Hoover, Mark; Butman, David] Yale Univ, Sch Forestry & Environm Studies, New Haven, CT 06511 USA.
   [Hartmann, Jens; Lauerwald, Ronny] Univ Hamburg, Inst Geol, D-20146 Hamburg, Germany.
   [Lauerwald, Ronny] Univ Libre Bruxelles, Dept Earth & Environm Sci, B-1050 Brussels, Belgium.
   [Sobek, Sebastian] Uppsala Univ, Dept Ecol & Genet, SE-75236 Uppsala, Sweden.
   [McDonald, Cory] Wisconsin Dept Nat Resources, Madison, WI 53716 USA.
   [Butman, David; Striegl, Robert] US Geol Survey, Natl Res Program, Boulder, CO 80303 USA.
   [Mayorga, Emilio] Univ Washington, Appl Phys Lab, Seattle, WA 98105 USA.
   [Humborg, Christoph] Stockholm Univ, Dept Appl Environm Sci, S-10691 Stockholm, Sweden.
   [Kortelainen, Pirkko] Finnish Environm Inst, FI-00251 Helsinki, Finland.
   [Duerr, Hans] Univ Waterloo, Dept Earth & Environm Sci, Waterloo, ON N2L 3G1, Canada.
   [Meybeck, Michel] Univ Paris 06, Unite Mixte Rech CNRS UPMC Sisyphe, F-75252 Paris 05, France.
   [Ciais, Philippe] LSCE IPSL, F-91191 Gif Sur Yvette, France.
   [Guth, Peter] US Naval Acad, Dept Oceanog, Annapolis, MD 21402 USA.
C3 Yale University; University of Hamburg; Universite Libre de Bruxelles; Uppsala University; United States Department of the Interior; United States Geological Survey; University of Washington; University of Washington Seattle; Stockholm University; Finnish Environment Institute; University of Waterloo; Sorbonne Universite; Universite Paris Saclay; United States Department of Defense; United States Navy; United States Naval Academy
RP Raymond, PA (corresponding author), Yale Univ, Sch Forestry & Environm Studies, 195 Prospect St, New Haven, CT 06511 USA.
EM peter.raymond@yale.edu
FU NASA [NNX11AH68G]; L-IPSL labex program; Formas; EU project GeoCarbon [U4603EUU1104]; DFG [EXC 177, DFG HA 4472/6-1]; NASA [145780, NNX11AH68G] Funding Source: Federal RePORTER
NR 50
TC 1939
Z9 2338
U1 50
U2 1504
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 21
PY 2013
VL 503
IS 7476
BP 355
EP 359
DI 10.1038/nature12760
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 254KG
UT WOS:000327163200032
PM 24256802
DA 2026-03-09
ER

PT J
AU Godefroit, P
   Cau, A
   Hu, DY
   Escuillié, F
   Wu, WH
   Dyke, G
AF Godefroit, Pascal
   Cau, Andrea
   Hu Dong-Yu
   Escuillie, Franois
   Wu Wenhao
   Dyke, Gareth
TI A Jurassic avialan dinosaur from China resolves the early phylogenetic history of birds
SO NATURE
LA English
DT Article
ID maniraptoran dinosaur; long feathers; theropod; archaeopteryx; evolution
AB The recent discovery of small paravian theropod dinosaurs with well-preserved feathers in the Middle-Late Jurassic Tiaojishan Formation of Liaoning Province (northeastern China)(1-4) has challenged the pivotal position of Archaeopteryx(3,4), regarded from its discovery to be the most basal bird. Removing Archaeopteryx from the base of Avialae to nest within Deinonychosauria implies that typical bird flight, powered by the forelimbs only, either evolved at least twice, or was subsequently lost or modified in some deinonychosaurians(3,5). Here we describe the complete skeleton of a new paravian from the Tiaojishan Formation of Liaoning Province, China. Including this new taxon in a comprehensive phylogenetic analysis for basal Paraves does the following: (1) it recovers it as the basal-most avialan; (2) it confirms the avialan status of Archaeopteryx; (3) it places Troodontidae as the sister-group to Avialae; (4) it supports a single origin of powered flight within Paraves; and (5) it implies that the early diversification of Paraves and Avialae took place in the Middle-Late Jurassic period.
C1 [Godefroit, Pascal] Royal Belgian Inst Nat Sci, Operat Direct Earth & Hist Life, B-1000 Brussels, Belgium.
   [Cau, Andrea] Museo Geol Giovanni Capellini, I-40127 Bologna, Italy.
   [Hu Dong-Yu] Shenyang Normal Univ, Inst Paleontol, Shenyang 110034, Peoples R China.
   [Hu Dong-Yu] NE Normal Univ, Minist Educ, Key Lab Vegetat Ecol, Changchun 130024, Peoples R China.
   [Escuillie, Franois] Eldonia, F-3800 Gannat, France.
   [Wu Wenhao] Jilin Univ, Res Ctr Paleontol & Stratig, Changchun 130021, Peoples R China.
   [Dyke, Gareth] Univ Southampton, Natl Oceanog Ctr, Southampton SO14 3ZH, Hants, England.
C3 Royal Belgian Institute of Natural Sciences; Shenyang Normal University; Northeast Normal University - China; Jilin University; University of Southampton; NERC National Oceanography Centre
RP Godefroit, P (corresponding author), Royal Belgian Inst Nat Sci, Operat Direct Earth & Hist Life, Rue Vautier 29, B-1000 Brussels, Belgium.
EM Pascal.Godefroit@naturalsciences.be
FU SPP Politique scientifique (Belgium) [BL/36/62]; Key Laboratory of Evolutionary Systematics of Vertebrates [CAS2011LESV011]; National Natural Science Foundation of China [41172026]
NR 28
TC 140
Z9 163
U1 3
U2 256
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 20
PY 2013
VL 498
IS 7454
BP 359
EP 362
DI 10.1038/nature12168
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 166XI
UT WOS:000320592900039
PM 23719374
DA 2026-03-09
ER

PT J
AU Pi, HJ
   Hangya, B
   Kvitsiani, D
   Sanders, JI
   Huang, ZJ
   Kepecs, A
AF Pi, Hyun-Jae
   Hangya, Balazs
   Kvitsiani, Duda
   Sanders, Joshua I.
   Huang, Z. Josh
   Kepecs, Adam
TI Cortical interneurons that specialize in disinhibitory control
SO NATURE
LA English
DT Article
ID gabaergic neurons; immunoreactive interneurons; disynaptic inhibition; molecular composition; transgenic mice; pyramidal cells; visual-cortex; innervation; selectivity; activation
AB In the mammalian cerebral cortex the diversity of interneuronal subtypes underlies a division of labour subserving distinct modes of inhibitory control(1-7). A unique mode of inhibitory control may be provided by inhibitory neurons that specifically suppress the firing of other inhibitory neurons. Such disinhibition could lead to the selective amplification of local processing and serve the important computational functions of gating and gain modulation(8,9). Although several interneuron populations are known to target other interneurons to varying degrees(10-15), little is known about interneurons specializing in disinhibition and their in vivo function. Here we show that a class of interneurons that express vasoactive intestinal polypeptide (VIP) mediates disinhibitory control in multiple areas of neocortex and is recruited by reinforcement signals. By combining optogenetic activation with single-cell recordings, we examined the functional role of VIP interneurons in awake mice, and investigated the underlying circuit mechanisms in vitro in auditory and medial prefrontal cortices. We identified a basic disinhibitory circuit module in which activation of VIP interneurons transiently suppresses primarily somatostatin- and a fraction of parvalbumin-expressing inhibitory interneurons that specialize in the control of the input and output of principal cells, respectively(3,6,16,17). During the performance of an auditory discrimination task, reinforcement signals (reward and punishment) strongly and uniformly activated VIP neurons in auditory cortex, and in turn VIP recruitment increased the gain of a functional subpopulation of principal neurons. These results reveal a specific cell type and microcircuit underlying disinhibitory control in cortex and demonstrate that it is activated under specific behavioural conditions.
C1 [Pi, Hyun-Jae; Hangya, Balazs; Kvitsiani, Duda; Sanders, Joshua I.; Huang, Z. Josh; Kepecs, Adam] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA.
   [Hangya, Balazs] Hungarian Acad Sci, Inst Expt Med, Lab Cerebral Cortex Res, H-1083 Budapest, Hungary.
C3 Cold Spring Harbor Laboratory; Hungarian Academy of Sciences; HUN-REN; HUN-REN Institute of Experimental Medicine
RP Kepecs, A (corresponding author), Cold Spring Harbor Lab, 1 Bungtown Rd, Cold Spring Harbor, NY 11724 USA.
EM kepecs@cshl.edu
FU NIH NINDS [R01NS075531]; Klingenstein Foundation; John Merck Foundation; Sloan Foundation; NIH NIMH [U01MH078844]; Swartz Foundation; EU; Robert Lee and Clara Guthrie Patterson Trust; Human Frontier Science Program; National Institute of Neurological Disorders and Stroke [R01NS075531] Funding Source: NIH RePORTER
NR 37
TC 824
Z9 999
U1 3
U2 134
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 28
PY 2013
VL 503
IS 7477
BP 521
EP +
DI 10.1038/nature12676
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 258MU
UT WOS:000327464200042
PM 24097352
DA 2026-03-09
ER

PT J
AU Ko, M
   An, J
   Bandukwala, HS
   Chavez, L
   Äijö, T
   Pastor, WA
   Segal, MF
   Li, HM
   Koh, KP
   Lähdesmäki, H
   Hogan, PG
   Aravind, L
   Rao, A
AF Ko, Myunggon
   An, Jungeun
   Bandukwala, Hozefa S.
   Chavez, Lukas
   Aijo, Tarmo
   Pastor, William A.
   Segal, Matthew F.
   Li, Huiming
   Koh, Kian Peng
   Lahdesmaki, Harri
   Hogan, Patrick G.
   Aravind, L.
   Rao, Anjana
TI Modulation of TET2 expression and 5-methylcytosine oxidation by the CXXC domain protein IDAX
SO NATURE
LA English
DT Article
ID cpg islands; 5-hydroxymethylcytosine content; dna; binding; differentiation; complex; database; pathway; rinf
AB TET (ten-eleven-translocation) proteins are Fe(II)- and alpha-ketogluta-rate-dependent dioxygenases(1-3) that modify the methylation status of DNA by successively oxidizing 5-methylcytosine to 5-hydroxymethylcytosine, 5-formylcytosine and 5-carboxycytosine(1,3-5), potential intermediates in the active erasure of DNA-methylation marks(5,6). Here we show that IDAX (also known as CXXC4), a reported inhibitor of Wnt signalling(7) that has been implicated in malignant renal cell carcinoma(8) and colonic villous adenoma(9), regulates TET2 protein expression. IDAX was originally encoded within an ancestral TET2 gene that underwent a chromosomal gene inversion during evolution, thus separating the TET2 CXXC domain from the catalytic domain. The IDAX CXXC domain binds DNA sequences containing unmethylated CpG dinucleotides, localizes to promoters and CpG islands in genomic DNA and interacts directly with the catalytic domain of TET2. Unexpectedly, IDAX expression results in caspase activation and TET2 protein downregulation, in a manner that depends on DNA binding through the IDAX CXXC domain, suggesting that IDAX recruits TET2 to DNA before degradation. IDAX depletion prevents TET2 downregulation in differentiating mouse embryonic stem cells, and short hairpin RNA against IDAX increases TET2 protein expression in the human monocytic cell line U937. Notably, we find that the expression and activity of TET3 is also regulated through its CXXC domain. Taken together, these results establish the separate and linked CXXC domains of TET2 and TET3, respectively, as previously unknown regulators of caspase activation and TET enzymatic activity.
C1 [Ko, Myunggon; An, Jungeun; Bandukwala, Hozefa S.; Chavez, Lukas; Aijo, Tarmo; Pastor, William A.; Segal, Matthew F.; Hogan, Patrick G.; Rao, Anjana] La Jolla Inst Allergy & Immunol, Div Signaling & Gene Express, La Jolla, CA 92037 USA.
   [Aijo, Tarmo; Lahdesmaki, Harri] Aalto Univ, Sch Sci, Dept Informat & Comp Sci, FI-00076 Aalto, Finland.
   [Li, Huiming; Koh, Kian Peng; Rao, Anjana] Harvard Univ, Sch Med, Boston, MA 02115 USA.
   [Li, Huiming; Koh, Kian Peng; Rao, Anjana] Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA.
   [Aravind, L.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
   [Rao, Anjana] Sanford Consortium Regenerat Med, La Jolla, CA 92037 USA.
C3 La Jolla Institute for Immunology; Aalto University; Harvard University; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Program in Cellular & Molecular Medicine (PCMM); National Institutes of Health (NIH) - USA; NIH National Library of Medicine (NLM)
RP Rao, A (corresponding author), La Jolla Inst Allergy & Immunol, Div Signaling & Gene Express, La Jolla, CA 92037 USA.
EM arao@liai.org
FU National Institutes of Health (NIH) [HD065812, CA151535]; California Institute of Regenerative Medicine and Translational Research [RM-01729]; Leukemia and Lymphoma Society [TRP 6187-12]; NIH [AI40127]; Leukemia and Lymphoma Society; Lady Tata Memorial Trust; GlaxoSmithKline-Immune Disease Institute Alliance; National Science Foundation; National Institute of Allergy and Infectious Diseases [R01AI040127] Funding Source: NIH RePORTER
NR 40
TC 311
Z9 393
U1 0
U2 93
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 2
PY 2013
VL 497
IS 7447
BP 122
EP +
DI 10.1038/nature12052
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 134OK
UT WOS:000318221500046
PM 23563267
DA 2026-03-09
ER

PT J
AU Kloosterman, B
   Abelenda, JA
   Gomez, MDC
   Oortwijn, M
   de Boer, JM
   Kowitwanich, K
   Horvath, BM
   van Eck, HJ
   Smaczniak, C
   Prat, S
   Visser, RGF
   Bachem, CWB
AF Kloosterman, Bjorn
   Abelenda, Jose A.
   Carretero Gomez, Maria del Mar
   Oortwijn, Marian
   de Boer, Jan M.
   Kowitwanich, Krissana
   Horvath, Beatrix M.
   van Eck, Herman J.
   Smaczniak, Cezary
   Prat, Salome
   Visser, Richard G. F.
   Bachem, Christian W. B.
TI Naturally occurring allele diversity allows potato cultivation in northern latitudes
SO NATURE
LA English
DT Article
ID flowering-time; arabidopsis; constans; tuberization; gene; plants; fkf1
AB Potato (Solanum tuberosum L.) originates from the Andes and evolved short-day-dependent tuber formation as a vegetative propagation strategy. Here we describe the identification of a central regulator underlying a major-effect quantitative trait locus for plant maturity and initiation of tuber development. We show that this gene belongs to the family of DOF (DNA-binding with one finger) transcription factors' and regulates tuberization and plant life cycle length, by acting as a mediator between the circadian clock and the StSP6A mobile tuberization signal(2). We also show that natural allelic variants evade post-translational light regulation, allowing cultivation outside the geographical centre of origin of potato. Potato is a member of the Solanaceae family and is one of the world's most important food crops. This annual plant originates from the Andean regions of South America(3). Potato develops tubers from underground stems called stolons. Its equatorial origin makes potato essentially short-day dependent for tuberization and potato will not make tubers in the long-day conditions of spring and summer in the northern latitudes. When introduced in temperate zones, wild material will form tubers in the course of the autumnal shortening of day-length. Thus, one of the first selected traits in potato leading to a European potato type(4) is likely to have been long-day acclimation for tuberization. Potato breeders can exploit the naturally occurring variation in tuberization onset and life cycle length, allowing varietal breeding for different latitudes, harvest times and markets.
C1 [Kloosterman, Bjorn; Carretero Gomez, Maria del Mar; Oortwijn, Marian; de Boer, Jan M.; Kowitwanich, Krissana; van Eck, Herman J.; Visser, Richard G. F.; Bachem, Christian W. B.] Wageningen UR, Dept Plant Sci, Lab Plant Breeding, NL-6700 AJ Wageningen, Netherlands.
   [Abelenda, Jose A.; Prat, Salome] CSIC, Ctr Nacl Biotecnol, Dept Genet Mol & Plantas, E-28049 Madrid, Spain.
   [Horvath, Beatrix M.] Univ Utrecht, NL-3508 TC Utrecht, Netherlands.
   [van Eck, Herman J.; Visser, Richard G. F.] Ctr BioSyst Genom, NL-6700 AB Wageningen, Netherlands.
   [Smaczniak, Cezary] Wageningen UR, Dept Plant Sci, Mol Biol Lab, NL-6700 AJ Wageningen, Netherlands.
C3 Wageningen University & Research; Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Centro Nacional de Biotecnologia (CNB); Utrecht University; Centre for BioSystems Genomics; Wageningen University & Research
RP Bachem, CWB (corresponding author), Wageningen UR, Dept Plant Sci, Lab Plant Breeding, POB 386, NL-6700 AJ Wageningen, Netherlands.
EM Christian.Bachem@wur.nl
FU Technology Foundation STW [WGC.7795, WPB.5283]; FP6 integrated Project [EU-Sol PL016214]; Almeria University Fund
NR 23
TC 318
Z9 377
U1 5
U2 256
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 14
PY 2013
VL 495
IS 7440
BP 246
EP 250
DI 10.1038/nature11912
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 113FP
UT WOS:000316652300053
PM 23467094
DA 2026-03-09
ER

PT J
AU Venkatraman, A
   He, XC
   Thorvaldsen, JL
   Sugimura, R
   Perry, JM
   Tao, F
   Zhao, M
   Christenson, MK
   Sanchez, R
   Yu, JY
   Peng, L
   Haug, JS
   Paulson, A
   Li, H
   Zhong, XB
   Clemens, TL
   Bartolomei, MS
   Li, LH
AF Venkatraman, Aparna
   He, Xi C.
   Thorvaldsen, Joanne L.
   Sugimura, Ryohichi
   Perry, John M.
   Tao, Fang
   Zhao, Meng
   Christenson, Matthew K.
   Sanchez, Rebeca
   Yu, Jaclyn Y.
   Peng, Lai
   Haug, Jeffrey S.
   Paulson, Ariel
   Li, Hua
   Zhong, Xiao-bo
   Clemens, Thomas L.
   Bartolomei, Marisa S.
   Li, Linheng
TI Maternal imprinting at the H19-Igf2 locus maintains adult haematopoietic stem cell quiescence
SO NATURE
LA English
DT Article
ID probe level data; self-renewal; rna-seq; growth; niche; expression; genes; differentiation; identification; normalization
AB The epigenetic regulation of imprinted genes by monoallelic DNA methylation of either maternal or paternal alleles is critical for embryonic growth and development(1). Imprinted genes were recently shown to be expressed in mammalian adult stem cells to support self-renewal of neural and lung stem cells(2-4); however, a role for imprinting per se in adult stem cells remains elusive. Here we show upregulation of growth-restricting imprinted genes, including in the H19-Igf2 locus(5), in long-term haematopoietic stem cells and their downregulation upon haematopoietic stem cell activation and proliferation. A differentially methylated region upstream of H19 (H19-DMR), serving as the imprinting control region, determines the reciprocal expression of H19 from the maternal allele and Igf2 from the paternal allele(1). In addition, H19 serves as a source of miR-675, which restricts Igf1r expression(6). We demonstrate that conditional deletion of the maternal but not the paternal H19-DMR reduces adult haematopoietic stem cell quiescence, a state required for long-term maintenance of haematopoietic stem cells, and compromises haematopoietic stem cell function. Maternal-specific H19-DMR deletion results in activation of the Igf2-Igfr1 pathway, as shown by the translocation of phosphorylated FoxO3 (an inactive form) from nucleus to cytoplasm and the release of FoxO3-mediated cell cycle arrest, thus leading to increased activation, proliferation and eventual exhaustion of haematopoietic stem cells. Mechanistically, maternal-specific H19-DMR deletion leads to Igf2 upregulation and increased translation of Igf1r, which is normally suppressed by H19-derived miR-675. Similarly, genetic inactivation of Igf1r partly rescues the H19-DMR deletion phenotype. Our work establishes a new role for this unique form of epigenetic control at the H19-Igf2 locus in maintaining adult stem cells.
C1 [Venkatraman, Aparna; He, Xi C.; Sugimura, Ryohichi; Perry, John M.; Tao, Fang; Zhao, Meng; Christenson, Matthew K.; Sanchez, Rebeca; Yu, Jaclyn Y.; Haug, Jeffrey S.; Paulson, Ariel; Li, Hua; Li, Linheng] Stowers Inst Med Res, Kansas City, MO 64110 USA.
   [Venkatraman, Aparna] Christian Med Coll & Hosp, Ctr Stem Cell Res, Vellore 632002, Tamil Nadu, India.
   [Thorvaldsen, Joanne L.; Bartolomei, Marisa S.] Univ Penn, Dept Cell & Dev Biol, Philadelphia, PA 19104 USA.
   [Sanchez, Rebeca] Inst Recerca Vall Dhebron, Cell Therapy & Genet Lab, Barcelona 08035, Spain.
   [Peng, Lai; Zhong, Xiao-bo] Univ Kansas, Med Ctr, Dept Pharmacol Toxicol & Therapeut, Kansas City, KS 66160 USA.
   [Clemens, Thomas L.] Johns Hopkins Med, Ctr Musculoskeletal Res, Baltimore, MD 21287 USA.
   [Li, Linheng] Univ Kansas, Med Ctr, Dept Pathol & Lab Med, Kansas City, KS 66160 USA.
C3 Stowers Institute for Medical Research; Christian Medical College & Hospital (CMCH) Vellore; University of Pennsylvania; Autonomous University of Barcelona; Hospital Universitari Vall d'Hebron; Vall d'Hebron Institut de Recerca (VHIR); University of Kansas; University of Kansas Medical Center; Johns Hopkins University; Johns Hopkins Medicine; University of Kansas; University of Kansas Medical Center
RP Li, LH (corresponding author), Stowers Inst Med Res, Kansas City, MO 64110 USA.
EM lil@stowers.org
FU Stowers Institute for Medical Research; Department of Biotechnology, Ministry of Science and Technology, Government of India; National Institutes of Health [GM51279]; National Institute of General Medical Sciences [R01GM051279] Funding Source: NIH RePORTER
NR 42
TC 228
Z9 259
U1 0
U2 57
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 15
PY 2013
VL 500
IS 7462
BP 345
EP +
DI 10.1038/nature12303
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 201AF
UT WOS:000323112400035
PM 23863936
DA 2026-03-09
ER

PT J
AU Engel, C
   Sainsbury, S
   Cheung, AC
   Kostrewa, D
   Cramer, P
AF Engel, Christoph
   Sainsbury, Sarah
   Cheung, Alan C.
   Kostrewa, Dirk
   Cramer, Patrick
TI RNA polymerase I structure and transcription regulation
SO NATURE
LA English
DT Article
ID cross-linking; dna-binding; architecture; subunits; subcomplex; complex; tfiif; phosphorylation; crystallization; recruitment
AB Transcription of ribosomal RNA by RNA polymerase (Pol) I initiates ribosome biogenesis and regulates eukaryotic cell growth. The crystal structure of Pol I from the yeast Saccharomyces cerevisiae at 2.8 angstrom resolution reveals all 14 subunits of the 590-kilodalton enzyme, and shows differences to Pol II. An 'expander' element occupies the DNA template site and stabilizes an expanded active centre cleft with an unwound bridge helix. A 'connector' element invades the cleft of an adjacent polymerase and stabilizes an inactive polymerase dimer. The connector and expander must detach during Pol I activation to enable transcription initiation and cleft contraction by convergent movement of the polymerase 'core' and 'shelf' modules. Conversion between an inactive expanded and an active contracted polymerase state may generally underlie transcription. Regulatory factors can modulate the core-shelf interface that includes a 'composite' active site for RNA chain initiation, elongation, proofreading and termination.
C1 [Engel, Christoph; Sainsbury, Sarah; Cheung, Alan C.; Kostrewa, Dirk; Cramer, Patrick] Univ Munich, Gene Ctr, D-81377 Munich, Germany.
   [Engel, Christoph; Sainsbury, Sarah; Cheung, Alan C.; Kostrewa, Dirk; Cramer, Patrick] Univ Munich, Dept Biochem, Ctr Integrated Prot Sci Munich CIPSM, D-81377 Munich, Germany.
C3 University of Munich; University of Munich
RP Cramer, P (corresponding author), Univ Munich, Gene Ctr, Feodor Lynen Str 25, D-81377 Munich, Germany.
EM cramer@LMB.uni-muenchen.de
FU Boehringer Ingelheim Fonds; Elite Network Bavaria program 'Protein Dynamics in Health and Disease'; Graduate Research Academy 'RNA Biology' of SFB960; Alexander-von-Humboldt Foundation; Deutsche Forschungsgemeinschaft [SFB646, TR5, GraKo1721, SFB960, CIPSM, NIM]; European Research Council; Jung-Stiftung; Vallee Foundation
NR 63
TC 172
Z9 213
U1 0
U2 67
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 31
PY 2013
VL 502
IS 7473
BP 650
EP +
DI 10.1038/nature12712
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 243CC
UT WOS:000326293200040
PM 24153182
DA 2026-03-09
ER

PT J
AU Abdumalikov, AA
   Fink, JM
   Juliusson, K
   Pechal, M
   Berger, S
   Wallraff, A
   Filipp, S
AF Abdumalikov, A. A., Jr.
   Fink, J. M.
   Juliusson, K.
   Pechal, M.
   Berger, S.
   Wallraff, A.
   Filipp, S.
TI Experimental realization of non-Abelian non-adiabatic geometric gates
SO NATURE
LA English
DT Article
ID quantum computation; berrys phase
AB The geometric aspects of quantum mechanics are emphasized most prominently by the concept of geometric phases, which are acquired whenever a quantum system evolves along a path in Hilbert space, that is, the space of quantum states of the system. The geometric phase is determined only by the shape of this path(1-3) and is, in its simplest form, a real number. However, if the system has degenerate energy levels, then matrix-valued geometric state transformations, known as non-Abelian holonomies-the effect of which depends on the order of two consecutive paths-can be obtained(4). They are important, for example, for the creation of synthetic gauge fields in cold atomic gases(5) or the description of non-Abelian anyon statistics(6,7). Moreover, there are proposals(8,9) to exploit non-Abelian holonomic gates for the purposes of noise-resilient quantum computation. In contrast to Abelian geometric operations(10), non-Abelian ones have been observed only in nuclear quadrupole resonance experiments with a large number of spins, and without full characterization of the geometric process and its non-commutative nature(11,12). Here we realize non-Abelian non-adiabatic holonomic quantum operations(13,14) on a single, superconducting, artificial three-level atom(15) by applying a well-controlled, two-tone microwave drive. Using quantum process tomography, we determine fidelities of the resulting non-commuting gates that exceed 95 per cent. We show that two different quantum gates, originating from two distinct paths in Hilbert space, yield non-equivalent transformations when applied in different orders. This provides evidence for the non-Abelian character of the implemented holonomic quantum operations. In combination with a non-trivial two-quantum-bit gate, our method suggests a way to universal holonomic quantum computing.
C1 [Abdumalikov, A. A., Jr.; Fink, J. M.; Juliusson, K.; Pechal, M.; Berger, S.; Wallraff, A.; Filipp, S.] Swiss Fed Inst Technol, Dept Phys, CH-8093 Zurich, Switzerland.
C3 Swiss Federal Institutes of Technology Domain; ETH Zurich
RP Abdumalikov, AA (corresponding author), Swiss Fed Inst Technol, Dept Phys, CH-8093 Zurich, Switzerland.
EM abdumalikov@phys.ethz.ch
FU EU; GEOMDISS; Swiss National Science Foundation; ETH Zurich
NR 31
TC 319
Z9 340
U1 3
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 APR 25
PY 2013
VL 496
IS 7446
BP 482
EP 485
DI 10.1038/nature12010
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 131HU
UT WOS:000317984400036
PM 23594739
DA 2026-03-09
ER

PT J
AU Neculai, D
   Schwake, M
   Ravichandran, M
   Zunke, F
   Collins, RF
   Peters, J
   Neculai, M
   Plumb, J
   Loppnau, P
   Pizarro, JC
   Seitova, A
   Trimble, WS
   Saftig, P
   Grinstein, S
   Dhe-Paganon, S
AF Neculai, Dante
   Schwake, Michael
   Ravichandran, Mani
   Zunke, Friederike
   Collins, Richard F.
   Peters, Judith
   Neculai, Mirela
   Plumb, Jonathan
   Loppnau, Peter
   Pizarro, Juan Carlos
   Seitova, Alma
   Trimble, William S.
   Saftig, Paul
   Grinstein, Sergio
   Dhe-Paganon, Sirano
TI Structure of LIMP-2 provides functional insights with implications for SR-BI and CD36
SO NATURE
LA English
DT Article
ID high-density-lipoprotein; receptor class-b; scavenger receptor; binding; identification; phospholipids; inhibitors; lipids
AB Members of the CD36 superfamily of scavenger receptor proteins are important regulators of lipid metabolism and innate immunity. They recognize normal and modified lipoproteins, as well as pathogen-associated molecular patterns. The family consists of three members: SR-BI (which delivers cholesterol to the liver and steroidogenic organs and is a co-receptor for hepatitis C virus), LIMP-2/LGP85 (which mediates lysosomal delivery of beta-glucocerebrosidase and serves as a receptor for enterovirus 71 and coxsackieviruses) and CD36 (a fatty-acid transporter and receptor for phagocytosis of effete cells and Plasmodium-infected erythrocytes). Notably, CD36 is also a receptor for modified lipoproteins and beta-amyloid, and has been implicated in the pathogenesis of atherosclerosis and of Alzheimer's disease(1). Despite their prominent roles in health and disease, understanding the function and abnormalities of the CD36 family members has been hampered by the paucity of information about their structure. Here we determine the crystal structure of LIMP-2 and infer, by homology modelling, the structure of SR-BI and CD36. LIMP-2 shows a helical bundle where beta-glucocerebrosidase binds, and where ligands are most likely to bind to SR-BI and CD36. Remarkably, the crystal structure also shows the existence of a large cavity that traverses the entire length of the molecule. Mutagenesis of SR-BI indicates that the cavity serves as a tunnel through which cholesterol(esters) are delivered from the bound lipoprotein to the outer leaflet of the plasma membrane. We provide evidence supporting a model(2) whereby lipidic constituents of the ligands attached to the receptor surface are handed off to the membrane through the tunnel, accounting for the selective lipid transfer characteristic of SR-BI and CD36.
C1 [Neculai, Dante; Collins, Richard F.; Plumb, Jonathan; Trimble, William S.; Grinstein, Sergio] Hosp Sick Children, Cell Biol Program, Toronto, ON M5G 1X8, Canada.
   [Schwake, Michael; Zunke, Friederike; Peters, Judith; Saftig, Paul] Univ Kiel, Inst Biochem, D-24118 Kiel, Germany.
   [Schwake, Michael] Univ Bielefeld, Fak Chem, D-33615 Bielefeld, Germany.
   [Ravichandran, Mani; Neculai, Mirela; Loppnau, Peter; Pizarro, Juan Carlos; Seitova, Alma; Dhe-Paganon, Sirano] Univ Toronto, Struct Genom Consortium, Toronto, ON M5G 1L7, Canada.
   [Pizarro, Juan Carlos] Tulane Univ, Dept Trop Med, New Orleans, LA 70118 USA.
   [Trimble, William S.; Grinstein, Sergio] Univ Toronto, Dept Biochem, Toronto, ON M5S 1A8, Canada.
   [Grinstein, Sergio] St Michaels Hosp, Li Ka Shing Knowledge Inst, Keenan Res Ctr, Toronto, ON M5C 1N8, Canada.
   [Dhe-Paganon, Sirano] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA.
C3 University of Toronto; Hospital for Sick Children (SickKids); University of Kiel; University of Bielefeld; University of Toronto; Structural Genomics Consortium; Tulane University; University of Toronto; University of Toronto; Li Ka Shing Knowledge Institute; Saint Michaels Hospital Toronto; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute
RP Grinstein, S (corresponding author), Hosp Sick Children, Cell Biol Program, 555 Univ Ave, Toronto, ON M5G 1X8, Canada.
EM sergio.grinstein@sickkids.ca
FU Canadian Institutes for Health Research [MOP-102474, MOP-126069]; Deutsche Forschungsgemeinschaft [GRK1459, SFB877]; Bohringer Ingelheim Fonds; Canada Research Chair in Molecular Cell Biology; Canadian Institutes for Health Research; Canada Foundation for Innovation; Genome Canada through the Ontario Genomics Institute; GlaxoSmithKline; Karolinska Institutet; Knut and Alice Wallenberg Foundation; Ontario Innovation Trust; Ontario Ministry for Research and Innovation; Merck Co.; Novartis Research Foundation; Swedish Agency for Innovation Systems; Swedish Foundation for Strategic Research; Wellcome Trust
NR 21
TC 241
Z9 289
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 DEC 5
PY 2013
VL 504
IS 7478
BP 172
EP 176
DI 10.1038/nature12684
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 264BK
UT WOS:000327851700054
PM 24162852
DA 2026-03-09
ER

PT J
AU Sanders, TA
   Llagostera, E
   Barna, M
AF Sanders, Timothy A.
   Llagostera, Esther
   Barna, Maria
TI Specialized filopodia direct long-range transport of SHH during vertebrate tissue patterning
SO NATURE
LA English
DT Article
ID green fluorescent protein; sonic-hedgehog; myosin-x; f-actin; cholesterol modification; chick limb; in-vivo; cells; cytonemes; pathway
AB The ability of signalling proteins to traverse tissues containing tightly packed cells is of fundamental importance for cell specification and tissue development; however, how this is achieved at a cellular level remains poorly understood(1). For more than a century, the vertebrate limb bud has served as a model for studying cell signalling during embryonic development(2). Here we optimize single-cell real-time imaging to delineate the cellular mechanisms for how signalling proteins, such as sonic hedgehog (SHH), that possess membrane-bound covalent lipid modifications traverse long distances within the vertebrate limb bud in vivo. By directly imaging SHH ligand production under native regulatory control in chick (Gallus gallus) embryos, our findings show that SHH is unexpectedly produced in the form of a particle that remains associated with the cell via long cytoplasmic extensions that span several cell diameters. We show that these cellular extensions are a specialized class of actin-based filopodia with novel cytoskeletal features that have not been previously described. Notably, particles containing SHH travel along these extensions with a net anterograde movement within the field of SHH cell signalling. We further show that in SHH-responding cells, specific subsets of SHH co-receptors, including cell adhesion molecule downregulated by oncogenes (CDO) and brother of CDO (BOC), actively distribute and co-localize in specific micro-domains within filopodial extensions, far from the cell body. Stabilized interactions are formed between filopodia containing SHH ligand and those containing co-receptors over a long range. These results suggest that contact-mediated release propagated by specialized filopodia contributes to the delivery of SHH at a distance. Together, these studies identify an important mode of communication between cells that considerably extends our understanding of ligand movement and reception during vertebrate tissue patterning.
C1 [Sanders, Timothy A.; Llagostera, Esther; Barna, Maria] Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94158 USA.
   [Sanders, Timothy A.] Univ Calif San Francisco, Div Neonatol, Dept Pediat, San Francisco, CA 94158 USA.
   [Llagostera, Esther; Barna, Maria] Stanford Univ, Dept Dev Biol, Stanford, CA 94305 USA.
   [Llagostera, Esther; Barna, Maria] Stanford Univ, Dept Genet, Stanford, CA 94305 USA.
C3 University of California System; University of California San Francisco; University of California System; University of California San Francisco; Stanford University; Stanford University
RP Barna, M (corresponding author), Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94158 USA.
EM mbarna@stanford.edu
FU Spanish Ministry of Education and Science; Program for Breakthrough Biomedical Research, UCSF; March of Dimes Basil O'Connor Scholar Research Award; National Institute of Arthritis and Musculoskeletal and Skin Disease, part of NIH [NIH R21AR062262]
NR 57
TC 304
Z9 368
U1 2
U2 71
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 30
PY 2013
VL 497
IS 7451
BP 628
EP +
DI 10.1038/nature12157
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 152UF
UT WOS:000319556100046
PM 23624372
DA 2026-03-09
ER

PT J
AU Lukens, JR
   Vogel, P
   Johnson, GR
   Kelliher, MA
   Iwakura, Y
   Lamkanfi, M
   Kanneganti, TD
AF Lukens, John R.
   Vogel, Peter
   Johnson, Gordon R.
   Kelliher, Michelle A.
   Iwakura, Yoichiro
   Lamkanfi, Mohamed
   Kanneganti, Thirumala-Devi
TI RIP1-driven autoinflammation targets IL-1α independently of inflammasomes and RIP3
SO NATURE
LA English
DT Article
ID sterile inflammation; moth-eaten; cell; gene; activation; disease; mice; identification; autoimmunity; phosphatases
AB The protein-tyrosine phosphatase SHP-1 has critical roles in immune signalling, but how mutations in SHP-1 cause inflammatory disease in humans remains poorly defined(1). Mice homozygous for the Tyr208Asn amino acid substitution in the carboxy terminus of SHP-1 (referred to as Ptpn6(spin) mice) spontaneously develop a severe inflammatory syndrome that resembles neutrophilic dermatosis in humans and is characterized by persistent footpad swelling and suppurative inflammation(2,3). Here we report that receptor-interacting protein 1 (RIP1)-regulated interleukin (IL)-1 alpha production by haematopoietic cells critically mediates chronic inflammatory disease in Ptpn6(spin) mice, whereas inflammasome signalling and IL-1 beta-mediated events are dispensable. IL-1 alpha was also crucial for exacerbated inflammatory responses and unremitting tissue damage upon footpad microabrasion of Ptpn6(spin) mice. Notably, pharmacological and genetic blockade of the kinase RIP1 protected against wound-induced inflammation and tissue damage in Ptpn6(spin) mice, whereas RIP3 deletion failed to do so. Moreover, RIP1-mediated inflammatory cytokine production was attenuated by NF-kappa B and ERK inhibition. Together, our results indicate that wound-induced tissue damage and chronic inflammation in Ptpn6(spin) mice are critically dependent on RIP1-mediated IL-1 alpha production, whereas inflammasome signalling and RIP3-mediated necroptosis are dispensable. Thus, we have unravelled a novel inflammatory circuit in which RIP1-mediated IL-1 alpha secretion in response to deregulated SHP-1 activity triggers an inflammatory destructive disease that proceeds independently of inflammasomes and programmed necrosis.
C1 [Lukens, John R.; Johnson, Gordon 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.
   [Kelliher, Michelle A.] Univ Massachusetts, Sch Med, Dept Canc Biol, Worcester, MA 01605 USA.
   [Iwakura, Yoichiro] Univ Tokyo, Inst Med Sci, Ctr Med Expt, Tokyo 1088639, Japan.
   [Lamkanfi, Mohamed] Univ Ghent VIB, Dept Med Prot Res, B-9000 Ghent, Belgium.
   [Lamkanfi, Mohamed] Univ Ghent, Dept Biochem, B-9000 Ghent, Belgium.
C3 St Jude Children's Research Hospital; St Jude Children's Research Hospital; St Jude Children's Research Hospital; University of Massachusetts System; University of Massachusetts Worcester; University of Tokyo; Flanders Institute for Biotechnology (VIB); Ghent University; Ghent University
RP Kanneganti, TD (corresponding author), St Jude Childrens Res Hosp, Dept Immunol, 332 N Lauderdale St, Memphis, TN 38105 USA.
EM Thirumala-Devi.Kanneganti@StJude.org
FU European Union [256432]; ERC [281600]; Fund for Scientific Research-Flanders [G030212N, 1.2.201.10.N.00, 1.5.122.11.N.00]; National Institutes of Health [AR056296, CA163507, AI101935]; American Lebanese Syrian Associated Charities (ALSAC); National Institute of Allergy and Infectious Diseases [R01AI075118, 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 27
TC 147
Z9 166
U1 1
U2 48
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 13
PY 2013
VL 498
IS 7453
BP 224
EP +
DI 10.1038/nature12174
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 162RR
UT WOS:000320283400047
PM 23708968
DA 2026-03-09
ER

PT J
AU Stagno, V
   Ojwang, DO
   McCammon, CA
   Frost, DJ
AF Stagno, Vincenzo
   Ojwang, Dickson O.
   McCammon, Catherine A.
   Frost, Daniel J.
TI The oxidation state of the mantle and the extraction of carbon from Earth's interior
SO NATURE
LA English
DT Article
ID oxygen fugacity; ferric iron; olivine; garnet; melts; fe3+/sigma-fe; profile; beneath; phases; alloys
AB Determining the oxygen fugacity of Earth's silicate mantle is of prime importance because it affects the speciation and mobility of volatile elements in the interior and has controlled the character of degassing species from the Earth since the planet's formation(1). Oxygen fugacities recorded by garnet-bearing peridotite xenoliths from Archaean lithosphere are of particular interest, because they provide constraints on the nature of volatile-bearing metasomatic fluids and melts active in the oldest mantle samples, including those in which diamonds are found(2,3). Here we report the results of experiments to test garnet oxythermobarometry equilibria(4,5) under high-pressure conditions relevant to the deepest mantle xenoliths. We present a formulation for the most successful equilibrium and use it to determine an accurate picture of the oxygen fugacity through cratonic lithosphere. The oxygen fugacity of the deepest rocks is found to be at least one order of magnitude more oxidized than previously estimated. At depths where diamonds can form, the oxygen fugacity is not compatible with the stability of either carbonate-or methane-rich liquid but is instead compatible with a metasomatic liquid poor in carbonate and dominated by either water or silicate melt. The equilibrium also indicates that the relative oxygen fugacity of garnet-bearing rocks will increase with decreasing depth during adiabatic decompression. This implies that carbon in the asthenospheric mantle will be hosted as graphite or diamond but will be oxidized to produce carbonatemelt through the reduction of Fe3+ in silicate minerals during upwelling. The depth of carbonate melt formation will depend on the ratio of Fe3+ to total iron in the bulk rock. This 'redox melting' relationship has important implications for the onset of geophysically detectable incipient melting and for the extraction of carbon dioxide from the mantle through decompressive melting.
C1 [Stagno, Vincenzo; Ojwang, Dickson O.; McCammon, Catherine A.; Frost, Daniel J.] Univ Bayreuth, Bayer Geoinst, D-95440 Bayreuth, Germany.
C3 University of Bayreuth
RP Frost, DJ (corresponding author), Univ Bayreuth, Bayer Geoinst, POB 101251, D-95440 Bayreuth, Germany.
EM dan.frost@uni-bayreuth.de
FU European Commission under the Marie Curie Action for Early Stage Training of Researchers within the 6th Framework Programme [MEST-CT-2005-019700]; German Science Foundation [FR1555/5-1]
NR 43
TC 399
Z9 464
U1 10
U2 385
PU NATURE PUBLISHING 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 3
PY 2013
VL 493
IS 7430
BP 84
EP +
DI 10.1038/nature11679
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 062QC
UT WOS:000312933800035
PM 23282365
DA 2026-03-09
ER

PT J
AU Flood, TF
   Iguchi, S
   Gorczyca, M
   White, B
   Ito, K
   Yoshihara, M
AF Flood, Thomas F.
   Iguchi, Shinya
   Gorczyca, Michael
   White, Benjamin
   Ito, Kei
   Yoshihara, Motojiro
TI A single pair of interneurons commands the Drosophila feeding motor program
SO NATURE
LA English
DT Article
ID neuronal-synaptobrevin; expression; behavior; reveals; release; protein; brain; cells; gal4
AB Many feeding behaviours are the result of stereotyped, organized sequences of motor patterns. These patterns have been the subject of neuroethological studies(1,2), such as electrophysiological characterization of neurons governing prey capture in toads(1,3). However, technical limitations have prevented detailed study of the functional role of these neurons, a common problem for vertebrate organisms. Complexities involved in studies of whole-animal behaviour can be resolved in Drosophila, in which remote activation of brain cells by genetic means(4) enables us to examine the nervous system in freely moving animals to identify neurons that govern a specific behaviour, and then to repeatedly target and manipulate these neurons to characterize their function. Here we show neurons that generate the feeding motor program in Drosophila. We carried out an unbiased screen using remote neuronal activation and identified a critical pair of brain cells that induces the entire feeding sequence when activated. These 'feeding neurons' (here abbreviated to Fdg neurons for brevity) are also essential for normal feeding as their suppression or ablation eliminates sugar-induced feeding behaviour. Activation of a single Fdg neuron induces asymmetric feeding behaviour and ablation of a single Fdg neuron distorts the sugar-induced feeding behaviour to become asymmetric, indicating the direct role of these neurons in shaping motor-program execution. Furthermore, recording neuronal activity and calcium imaging simultaneously during feeding behaviour(5) reveals that the Fdg neurons respond to food presentation, but only in starved flies. Our results demonstrate that Fdg neurons operate firmly within the sensorimotor watershed, downstream of sensory and metabolic cues and at the top of the feeding motor hierarchy, to execute the decision to feed.
C1 [Flood, Thomas F.; Iguchi, Shinya; Gorczyca, Michael; Yoshihara, Motojiro] Univ Massachusetts, Sch Med, Dept Neurobiol, Worcester, MA 01605 USA.
   [White, Benjamin] NIMH, Mol Biol Lab, Bethesda, MD 20892 USA.
   [Ito, Kei] Univ Tokyo, Inst Mol & Cellular Biosci, Tokyo 1130032, Japan.
C3 University of Massachusetts System; University of Massachusetts Worcester; National Institutes of Health (NIH) - USA; NIH National Institute of Mental Health (NIMH); University of Tokyo
RP Yoshihara, M (corresponding author), Univ Massachusetts, Sch Med, Dept Neurobiol, Worcester, MA 01605 USA.
EM Motojiro.Yoshihara@umassmed.edu
FU National Institute of Mental Health [MH85958]; Worcester Foundation; National Institute of Mental Health Intramural Research Program; Japan Society for the Promotion of Science/National Science Foundation; Japan Science and Technology Agency CREST grant; National Institute of Mental Health [ZIAMH002800] Funding Source: NIH RePORTER
NR 46
TC 102
Z9 121
U1 0
U2 58
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 4
PY 2013
VL 499
IS 7456
BP 83
EP +
DI 10.1038/nature12208
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 176ED
UT WOS:000321285600038
PM 23748445
DA 2026-03-09
ER

PT J
AU Siria, A
   Poncharal, P
   Biance, AL
   Fulcrand, R
   Blase, X
   Purcell, ST
   Bocquet, L
AF Siria, Alessandro
   Poncharal, Philippe
   Biance, Anne -Laure
   Fulcrand, Remy
   Blase, Xavier
   Purcell, Stephen T.
   Bocquet, Lyderic
TI Giant osmotic energy conversion measured in a single transmembrane boron nitride nanotube
SO NATURE
LA English
DT Article
ID carbon nanotubes; reverse electrodialysis; power-generation; water transport; flow; membranes
AB New models of fluid transport are expected to emerge from the confinement of liquids at the nanoscale(1,2), with potential applications in ultrafiltration, desalination and energy conversion(3). Nevertheless, advancing our fundamental understanding of fluid transport on the smallest scales requires mass and ion dynamics to be ultimately characterized across an individual channel to avoid averaging over many pores. A major challenge for nanofluidics thus lies in building distinct and well-controlled nanochannels, amenable to the systematic exploration of their properties. Here we describe the fabrication and use of a hierarchical nanofluidic device made of a boron nitride nanotube that pierces an ultrathin membrane and connects two fluid reservoirs. Such a transmembrane geometry allows the detailed study of fluidic transport through a single nanotube under diverse forces, including electric fields, pressure drops and chemical gradients. Using this device, we discover very large, osmotically induced electric currents generated by salinity gradients, exceeding by two orders of magnitude their pressure-driven counterpart. We show that this result originates in the anomalously high surface charge carried by the nanotube's internal surface in water at large pH, which we independently quantify in conductance measurements. The nano-assembly route using nanostructures as building blocks opens the way to studying fluid, ionic and molecule transport on the nanoscale, and may lead to biomimetic functionalities. Our results furthermore suggest that boron nitride nanotubes could be used as membranes for osmotic power harvesting under salinity gradients.
C1 [Siria, Alessandro; Poncharal, Philippe; Biance, Anne -Laure; Fulcrand, Remy; Purcell, Stephen T.; Bocquet, Lyderic] Univ Lyon 1, CNRS, Inst Lumiere Mat, UMR5306, F-69622 Villeurbanne, France.
   [Blase, Xavier] CNRS, Inst Neel, UPR 2940, F-38042 Grenoble, France.
   [Blase, Xavier] Univ Grenoble 1, F-38042 Grenoble, France.
C3 Centre National de la Recherche Scientifique (CNRS); CNRS - Institute of Physics (INP); Universite Lyon 1; Communaute Universite Grenoble Alpes; Universite Grenoble Alpes (UGA); Centre National de la Recherche Scientifique (CNRS); CNRS - Institute of Physics (INP); Communaute Universite Grenoble Alpes; Universite Grenoble Alpes (UGA)
RP Bocquet, L (corresponding author), Univ Lyon 1, CNRS, Inst Lumiere Mat, UMR5306, F-69622 Villeurbanne, France.
EM lyderic.bocquet@univ-lyon1.fr
FU ERC-AG project Micromegas; French ANR under the programme P3N
NR 30
TC 1120
Z9 1206
U1 23
U2 1165
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 28
PY 2013
VL 494
IS 7438
BP 455
EP 458
DI 10.1038/nature11876
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 099YI
UT WOS:000315661500033
PM 23446417
DA 2026-03-09
ER

PT J
AU Evans, LDB
   Poulter, S
   Terentjev, EM
   Hughes, C
   Fraser, GM
AF Evans, Lewis D. B.
   Poulter, Simon
   Terentjev, Eugene M.
   Hughes, Colin
   Fraser, Gillian M.
TI A chain mechanism for flagellum growth
SO NATURE
LA English
DT Article
ID iii protein export; high-level expression; salmonella-typhimurium; escherichia-coli; substrate-specificity; bacterial flagellum; membrane atpase; hook; secretion; apparatus
AB Bacteria swim by means of long flagella extending from the cell surface. These are assembled from thousands of protein subunits translocated across the cell membrane by an export machinery at the base of each flagellum. Unfolded subunits(1-3) then transit through a narrow channel at the core of the growing flagellum to the tip, where they crystallize into the nascent structure. As the flagellum lengthens outside the cell, the rate of flagellum growth does not change(4). The mystery is how subunit transit is maintained at a constant rate without a discernible energy source in the channel of the external flagellum(5). We present evidence for a simple physical mechanism for flagellum growth that harnesses the entropic force of the unfolded subunits themselves. We show that a subunit docked at the export machinery can be captured by a free subunit through head-to-tail linkage of juxtaposed amino (N)- and carboxy (C)-terminal helices. We propose that sequential rounds of linkage would generate a multisubunit chain that pulls successive subunits into and through the channel to the flagellum tip, and by isolating filaments growing on bacterial cells we reveal the predicted chain of head-to-tail linked subunits in the transit channel of flagella. Thermodynamic analysis confirms that links in the subunit chain can withstand the pulling force generated by rounds of subunit crystallization at the flagellum tip, and polymer theory predicts that as the N terminus of each unfolded subunit crystallizes, the entropic force at the subunit C terminus would increase, rapidly overcoming the threshold required to pull the next subunit from the export machinery. This pulling force would adjust automatically over the increasing length of the growing flagellum, maintaining a constant rate of subunit delivery to the tip.
C1 [Evans, Lewis D. B.; Poulter, Simon; Hughes, Colin; Fraser, Gillian M.] Univ Cambridge, Dept Pathol, Cambridge CB2 1QP, England.
   [Terentjev, Eugene M.] Univ Cambridge, Cavendish Lab, Cambridge CB3 0HE, England.
C3 University of Cambridge; University of Cambridge
RP Fraser, GM (corresponding author), Univ Cambridge, Dept Pathol, Tennis Court Rd, Cambridge CB2 1QP, England.
EM gmf25@cam.ac.uk
FU Wellcome Trust; EPSRC [EP/F032773/1] Funding Source: UKRI; Engineering and Physical Sciences Research Council [EP/F032773/1] Funding Source: researchfish
NR 44
TC 72
Z9 81
U1 0
U2 73
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 12
PY 2013
VL 504
IS 7479
BP 287
EP +
DI 10.1038/nature12682
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 267TQ
UT WOS:000328121500038
PM 24213633
DA 2026-03-09
ER

PT J
AU Tierney, JE
   Smerdon, JE
   Anchukaitis, KJ
   Seager, R
AF Tierney, Jessica E.
   Smerdon, Jason E.
   Anchukaitis, Kevin J.
   Seager, Richard
TI Multidecadal variability in East African hydroclimate controlled by the Indian Ocean
SO NATURE
LA English
DT Article
ID rainfall variability; lake masoko; ice-age; drought; solar
AB The recent decades-long decline in East African rainfall(1) suggests that multidecadal variability is an important component of the climate of this vulnerable region. Prior work based on analysing the instrumental record implicates both Indian(2) and Pacific(1) ocean sea surface temperatures (SSTs) as possible drivers of East African multidecadal climate variability, but the short length of the instrumental record precludes a full elucidation of the underlying physical mechanisms. Here we show that on timescales beyond the decadal, the Indian Ocean drives East African rainfall variability by altering the local Walker circulation, whereas the influence of the Pacific Ocean is minimal. Our results, based on proxy indicators of relative moisture balance for the past millennium paired with long control simulations from coupled climate models, reveal that moist conditions in coastal East Africa are associated with cool SSTs (and related descending circulation) in the eastern Indian Ocean and ascending circulation over East Africa. The most prominent event identified in the proxy record-a coastal pluvial from 1680 to 1765-occurred when Indo-Pacific warm pool SSTs reached their minimum values of the past millennium. Taken together, the proxy and model evidence suggests that Indian Ocean SSTs are the primary influence on East African rainfall over multidecadal and perhaps longer timescales.
C1 [Tierney, Jessica E.; Anchukaitis, Kevin J.] Woods Hole Oceanog Inst, Woods Hole, MA 02543 USA.
   [Tierney, Jessica E.; Smerdon, Jason E.; Anchukaitis, Kevin J.; Seager, Richard] Columbia Univ, Lamont Doherty Earth Observ, Palisades, NY 10964 USA.
C3 Woods Hole Oceanographic Institution; Columbia University
RP Tierney, JE (corresponding author), Woods Hole Oceanog Inst, Woods Hole, MA 02543 USA.
EM tierney@whoi.edu
FU US NOAA; NSF [OCE-1203892]; NOAA [NA10OAR431037]; Office of Science, US Department of Energy; US NSF; Directorate For Geosciences; Division Of Ocean Sciences [1203892] Funding Source: National Science Foundation; Division Of Ocean Sciences; Directorate For Geosciences [1636445] Funding Source: National Science Foundation
NR 29
TC 279
Z9 313
U1 0
U2 139
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 17
PY 2013
VL 493
IS 7432
BP 389
EP 392
DI 10.1038/nature11785
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 071TA
UT WOS:000313615900048
PM 23325220
DA 2026-03-09
ER

PT J
AU Hollenstein, K
   Kean, J
   Bortolato, A
   Cheng, RKY
   Doré, AS
   Jazayeri, A
   Cooke, RM
   Weir, M
   Marshall, FH
AF Hollenstein, Kaspar
   Kean, James
   Bortolato, Andrea
   Cheng, Robert K. Y.
   Dore, Andrew S.
   Jazayeri, Ali
   Cooke, Robert M.
   Weir, Malcolm
   Marshall, Fiona H.
TI Structure of class B GPCR corticotropin-releasing factor receptor 1
SO NATURE
LA English
DT Article
ID protein-coupled receptors; crystal-structure; molecular recognition; parathyroid-hormone; peptide receptor; agonist; binding; thermostabilization; refinement; activation
AB Structural analysis of class B G-protein-coupled receptors (GPCRs), cell-surface proteins that respond to peptide hormones, has been restricted to the amino-terminal extracellular domain, thus providing little understanding of the membrane-spanning signal transduction domain. The corticotropin-releasing factor receptor type 1 is a class B receptor which mediates the response to stress and has been considered a drug target for depression and anxiety. Here we report the crystal structure of the transmembrane domain of the human corticotropin-releasing factor receptor type 1 incomplex with the small-molecule antagonist CP-376395. The structure provides detailed insight into the architecture of class B receptors. Atomic details of the interactions of the receptor with the non-peptide ligand that binds deep within the receptor are described. This structure provides a model for all class B GPCRs and may aid in the design of new small-molecule drugs for diseases of brain and metabolism.
C1 [Hollenstein, Kaspar; Kean, James; Bortolato, Andrea; Cheng, Robert K. Y.; Dore, Andrew S.; Jazayeri, Ali; Cooke, Robert M.; Weir, Malcolm; Marshall, Fiona H.] Heptares Therapeut Ltd, Welwyn Garden City AL7 3AX, Herts, England.
C3 Heptares Therapeutics Ltd.
RP Marshall, FH (corresponding author), Heptares Therapeut Ltd, BioPk,Broadwater Rd, Welwyn Garden City AL7 3AX, Herts, England.
EM fiona.marshall@heptares.com
NR 55
TC 364
Z9 423
U1 1
U2 114
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 25
PY 2013
VL 499
IS 7459
BP 438
EP +
DI 10.1038/nature12357
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 187YP
UT WOS:000322157900032
PM 23863939
DA 2026-03-09
ER

PT J
AU Yang, J
   Ortega-Hernández, J
   Butterfield, NJ
   Zhang, XG
AF Yang, Jie
   Ortega-Hernandez, Javier
   Butterfield, Nicholas J.
   Zhang, Xi-guang
TI Specialized appendages in fuxianhuiids and the head organization of early euarthropods
SO NATURE
LA English
DT Article
ID limulus-polyphemus chelicerata; arthropod head; nervous-system; evolution; origin; xiphosura; phylogeny; character; crustacea; region
AB The organization of the head provides critical data for resolving the phylogenetic relationships and evolutionary history of extinct and extant euarthropods(1,2). The early Cambrian-period fuxianhuiids are regarded as basal representatives of stem-group Euarthropode(3-7), and their anterior morphology therefore offers key insights for reconstructing the ancestral condition of the euarthropod head(1-3,8-11) However, the paired post-antennal structures in Fuxianhuia protensa remain controversial(3,8,10); they have been interpreted as both 'great appendages'(1,2) and as gut diverticulae(4,12,13). Here we describe Chengjiangocaris kunmingensis sp. nov. and Fuxianhuia xiaoshibaensis sp. nov. from a new early Cambrian (Stage 3) fossil Lagerstatte in Yunnan, China. Numerous specimens of both species show a unique 'taphonomic dissection' of the anterodorsal head shield, revealing the cephalic organization in detail. We demonstrate the presence of a pair of specialized post-antennal appendages (SPAs) in the fuxianhuiid head, which attach at either side of the posteriorly directed mouth, behind the hypostome. Preserved functional articulations indicate a well-defined but restricted range of limb movement, suggestive of a simple type of sweep feeding. The organization of the SPAs in fuxianhuiids is incompatible with the (deutocerebral) anterior raptorial appendages of megacheirans(2,9,14,15), and argue against the presence of protocerebral limbs in the fuxianhuiids(1,2,9). The positions of the fuxianhuiid antennae and SPAs indicate that they are segmentally homologous to the deutocerebral and tritocerebral appendages of crown-group Euarthropoda respectively(2,11,16,17). These findings indicate that antenniform deutocerebral appendages with many podomeres are a plesiomorphic feature of the ancestral euarthropod head.
C1 [Yang, Jie; Zhang, Xi-guang] Yunnan Univ, Key Lab Palaeobiol, Kunming 650091, Peoples R China.
   [Ortega-Hernandez, Javier; Butterfield, Nicholas J.] Univ Cambridge, Dept Earth Sci, Cambridge CB2 3EQ, England.
C3 Yunnan University; University of Cambridge
RP Zhang, XG (corresponding author), Yunnan Univ, Key Lab Palaeobiol, Kunming 650091, Peoples R China.
EM xgzhang@ynu.edu.cn
FU National Natural Science Foundation of China [41272027]; Ministry of Education of China [20115301110005]; CONACYT (Consejo Nacional de Ciencia y Tecnologia, Mexico); University of Cambridge Trusts; Darwin College, University of Cambridge
NR 29
TC 99
Z9 112
U1 0
U2 63
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 28
PY 2013
VL 494
IS 7438
BP 468
EP 471
DI 10.1038/nature11874
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 099YI
UT WOS:000315661500036
PM 23446418
DA 2026-03-09
ER

PT J
AU Posor, Y
   Eichhorn-Gruenig, M
   Puchkov, D
   Schöneberg, J
   Ullrich, A
   Lampe, A
   Müller, R
   Zarbakhsh, S
   Gulluni, F
   Hirsch, E
   Krauss, M
   Schultz, C
   Schmoranzer, J
   Noé, F
   Haucke, V
AF Posor, York
   Eichhorn-Gruenig, Marielle
   Puchkov, Dmytro
   Schoeneberg, Johannes
   Ullrich, Alexander
   Lampe, Andre
   Mueller, Rainer
   Zarbakhsh, Sirus
   Gulluni, Federico
   Hirsch, Emilio
   Krauss, Michael
   Schultz, Carsten
   Schmoranzer, Jan
   Noe, Frank
   Haucke, Volker
TI Spatiotemporal control of endocytosis by phosphatidylinositol-3,4-bisphosphate
SO NATURE
LA English
DT Article
ID clathrin-mediated endocytosis; phosphoinositide 3-kinase; coated vesicles; homology-domain; proteins; kinase; cells; phosphoinositide-3-kinase-c2-alpha; 4,5-bisphosphate; identification
AB Phosphoinositides serve crucial roles in cell physiology, ranging from cell signalling to membrane traffic(1,2). Among the seven eukaryotic phosphoinositides the best studied species is phosphatidylinositol-4,5-bisphosphate (PI(4,5)P-2), which is concentrated at the plasma membrane where, among other functions, it is required for the nucleation of endocytic clathrin-coated pits(3-6). No phosphatidylinositol other than PI(4,5)P-2 has been implicated in clathrin-mediated endocytosis, whereas the subsequent endosomal stages of the endocytic pathway are dominated by phosphatidylinositol-3-phosphates(PI(3)P)(7). How phosphatidylinositol conversion from PI(4,5)P-2-positive endocytic intermediates to PI(3)P-containing endosomes is achieved is unclear. Here we show that formation of phosphatidylinositol-3,4-bisphosphate (PI(3,4)P-2) by class II phosphatidylinositol-3-kinase C2 alpha (PI(3) K C2 alpha) spatiotemporally controls clathrin-mediated endocytosis. Depletion of PI(3,4)P-2 or PI(3)K C2 alpha impairs the maturation of late-stage clathrin-coated pits before fission. Timed formation of PI(3,4)P-2 by PI(3)K C2 alpha is required for selective enrichment of the BAR domain protein SNX9 at late-stage endocytic intermediates. These findings provide a mechanistic framework for the role of PI(3,4)P-2 in endocytosis and unravel a novel discrete function of PI(3,4)P-2 in a central cell physiological process.
C1 [Posor, York; Eichhorn-Gruenig, Marielle; Puchkov, Dmytro; Lampe, Andre; Krauss, Michael; Schmoranzer, Jan; Haucke, Volker] Leibniz Inst Mol Pharmakol FMP, D-13125 Berlin, Germany.
   [Posor, York; Eichhorn-Gruenig, Marielle; Puchkov, Dmytro; Lampe, Andre; Krauss, Michael; Schmoranzer, Jan; Haucke, Volker] Free Univ Berlin, D-13125 Berlin, Germany.
   [Schoeneberg, Johannes; Ullrich, Alexander; Noe, Frank] Free Univ Berlin, DFG Res Ctr MATHEON, D-14195 Berlin, Germany.
   [Mueller, Rainer; Zarbakhsh, Sirus; Schultz, Carsten] European Mol Biol Lab, Cell Biol & Biophys Unit, D-69117 Heidelberg, Germany.
   [Gulluni, Federico; Hirsch, Emilio] Univ Turin, Ctr Mol Biotechnol, Dept Genet, I-10126 Turin, Italy.
   [Gulluni, Federico; Hirsch, Emilio] Univ Turin, Ctr Mol Biotechnol, Dept Biol, I-10126 Turin, Italy.
   [Gulluni, Federico; Hirsch, Emilio] Univ Turin, Ctr Mol Biotechnol, Dept Biochem, I-10126 Turin, Italy.
   [Haucke, Volker] Charite, NeuroCure Cluster Excellence, D-10117 Berlin, Germany.
C3 Leibniz Association; Leibniz Forschungsinstitut furr Molekulare Pharmakologie (FMP); Free University of Berlin; German Research Foundation (DFG); Free University of Berlin; European Molecular Biology Laboratory (EMBL); University of Turin; University of Turin; University of Turin; Free University of Berlin; Humboldt University of Berlin; Charite Universitatsmedizin Berlin
RP Haucke, V (corresponding author), Leibniz Inst Mol Pharmakol FMP, Robert Roessle Str 10, D-13125 Berlin, Germany.
EM haucke@fmp-berlin.de
FU Deutsche Forschungsgemeinschaft [SFB 740/C8, SFB 740/D7, SFB 958/A04, SFB 958/A07, SFB 958/Z02]
NR 36
TC 327
Z9 394
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 JUL 11
PY 2013
VL 499
IS 7457
BP 233
EP +
DI 10.1038/nature12360
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 179YA
UT WOS:000321557600067
PM 23823722
DA 2026-03-09
ER

PT J
AU Erdmann, J
   Stark, K
   Esslinger, UB
   Rumpf, PM
   Koesling, D
   de Wit, C
   Kaiser, FJ
   Braunholz, D
   Medack, A
   Fischer, M
   Zimmermann, ME
   Tennstedt, S
   Graf, E
   Eck, S
   Aherrahrou, Z
   Nahrstaedt, J
   Willenborg, C
   Bruse, P
   Brænne, I
   Nöthen, MM
   Hofmann, P
   Braund, PS
   Mergia, E
   Reinhard, W
   Burgdorf, C
   Schreiber, S
   Balmforth, AJ
   Hall, AS
   Bertram, L
   Steinhagen-Thiessen, E
   Li, SC
   März, W
   Reilly, M
   Kathiresan, S
   McPherson, R
   Walter, U
   Ott, J
   Samani, NJ
   Strom, TM
   Meitinger, T
   Hengstenberg, C
   Schunkert, H
AF Erdmann, Jeanette
   Stark, Klaus
   Esslinger, Ulrike B.
   Rumpf, Philipp Moritz
   Koesling, Doris
   de Wit, Cor
   Kaiser, Frank J.
   Braunholz, Diana
   Medack, Anja
   Fischer, Marcus
   Zimmermann, Martina E.
   Tennstedt, Stephanie
   Graf, Elisabeth
   Eck, Sebastian
   Aherrahrou, Zouhair
   Nahrstaedt, Janja
   Willenborg, Christina
   Bruse, Petra
   Braenne, Ingrid
   Noethen, Markus M.
   Hofmann, Per
   Braund, Peter S.
   Mergia, Evanthia
   Reinhard, Wibke
   Burgdorf, Christof
   Schreiber, Stefan
   Balmforth, Anthony J.
   Hall, Alistair S.
   Bertram, Lars
   Steinhagen-Thiessen, Elisabeth
   Li, Shu-Chen
   Maerz, Winfried
   Reilly, Muredach
   Kathiresan, Sekar
   McPherson, Ruth
   Walter, Ulrich
   Ott, Jurg
   Samani, Nilesh J.
   Strom, Tim M.
   Meitinger, Thomas
   Hengstenberg, Christian
   Schunkert, Heribert
TI Dysfunctional nitric oxide signalling increases risk of myocardial infarction
SO NATURE
LA English
DT Article
ID soluble guanylate-cyclase; genome-wide association; susceptibility loci; disease
AB Myocardial infarction, a leading cause of death intheWesternworld(1), usually occurs when the fibrous cap overlying an atherosclerotic plaque in a coronary artery ruptures. The resulting exposure of blood to the atherosclerotic material then triggers thrombus formation, which occludes the artery(2). The importance of genetic predisposition to coronary artery disease and myocardial infarction is best documented by the predictive value of a positive family history(3). Nextgeneration sequencing in families with several affected individuals has revolutionized mutation identification(4). Here we report the segregation of two private, heterozygous mutations in two functionally relatedgenes, GUCY1A3 (p.Leu163Phefs*24) andCCT7 (p.Ser525Leu), in an extended myocardial infarction family. GUCY1A3 encodes the alpha 1 subunit of soluble guanylyl cyclase (alpha 1-sGC)(5), and CCT7 encodes CCT eta, a member of the tailless complex polypeptide 1 ring complex(6), which, among other functions, stabilizes soluble guanylyl cyclase. After stimulation with nitric oxide, soluble guanylyl cyclase generates cGMP, which induces vasodilation and inhibits platelet activation(7). Wedemonstratein vitro that mutations inbothGUCY1A3 and CCT7 severely reduce alpha 1-sGC as well as beta 1-sGC protein content, and impair soluble guanylyl cyclase activity. Moreover, platelets from digenic mutation carriers contained less soluble guanylyl cyclase protein and consequently displayed reduced nitric-oxideinduced cGMP formation. Mice deficient in alpha 1-sGC protein displayed accelerated thrombus formation in themicrocirculation after local trauma. Starting with a severely affected family, we have identified a link between impaired soluble-guanylyl-cyclase-dependent nitric oxide signalling and myocardial infarction risk, possibly through accelerated thrombus formation. Reversing this defect may provide a new therapeutic target for reducing the risk of myocardial infarction.
C1 [Erdmann, Jeanette; Medack, Anja; Tennstedt, Stephanie; Aherrahrou, Zouhair; Nahrstaedt, Janja; Willenborg, Christina; Bruse, Petra; Braenne, Ingrid] Med Univ Lubeck, Inst Integrat & Expt Genom, D-23562 Lubeck, Germany.
   [Erdmann, Jeanette; de Wit, Cor; Kaiser, Frank J.; Aherrahrou, Zouhair; Willenborg, Christina] German Ctr Cardiovasc Res DZHK, D-23562 Lubeck, Germany.
   [Stark, Klaus; Esslinger, Ulrike B.; Fischer, Marcus; Zimmermann, Martina E.] Univ Klinikum Regensburg, Klin & Poliklin Innere Med 2, D-93053 Regensburg, Germany.
   [Stark, Klaus] Univ Regensburg, Dept Genet Epidemiol, D-93053 Regensburg, Germany.
   [Esslinger, Ulrike B.] INSERM, UMR S937, Paris, France.
   [Rumpf, Philipp Moritz; Reinhard, Wibke; Burgdorf, Christof; Meitinger, Thomas; Hengstenberg, Christian; Schunkert, Heribert] Deutsch Herzzentrum Munich, D-80636 Munich, Germany.
   [Rumpf, Philipp Moritz; Reinhard, Wibke; Burgdorf, Christof; Meitinger, Thomas; Hengstenberg, Christian; Schunkert, Heribert] Tech Univ Munich, Klinikum Rechts Isar, Med Klin 1, D-80636 Munich, Germany.
   [Rumpf, Philipp Moritz; Reinhard, Wibke; Hengstenberg, Christian; Schunkert, Heribert] German Ctr Cardiovasc Res DZHK, D-80636 Munich, Germany.
   [Koesling, Doris; Mergia, Evanthia] Ruhr Univ Bochum, Dept Pharmacol & Toxicol, D-44801 Bochum, Germany.
   [de Wit, Cor] Med Univ Lubeck, Inst Physiol, D-23562 Lubeck, Germany.
   [Kaiser, Frank J.; Braunholz, Diana] Med Univ Lubeck, Inst Humangenet, D-23562 Lubeck, Germany.
   [Graf, Elisabeth; Eck, Sebastian; Strom, Tim M.; Meitinger, Thomas] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Human Genet, D-85764 Neuherberg, Germany.
   [Graf, Elisabeth; Eck, Sebastian; Strom, Tim M.; Meitinger, Thomas] Tech Univ Munich, Inst Human Genet, D-81675 Munich, Germany.
   [Noethen, Markus M.; Hofmann, Per] Univ Bonn, Inst Human Genet, D-53127 Bonn, Germany.
   [Noethen, Markus M.] Univ Bonn, Res Ctr Life & Brain, Dept Genom, D-53127 Bonn, Germany.
   [Hofmann, Per] Univ Basel Hosp, Div Med Genet, CH-4003 Basel, Switzerland.
   [Hofmann, Per] Univ Basel, Dept Biomed, CH-4003 Basel, Switzerland.
   [Braund, Peter S.; Samani, Nilesh J.] Univ Leicester, Dept Cardiovasc Sci, Leicester LE1 7RH, Leics, England.
   [Braund, Peter S.; Samani, Nilesh J.] Glenfield Gen Hosp, Leicester Natl Inst Hlth Res Biomed Res Unit Card, Leicester LE1 7RH, Leics, England.
   [Schreiber, Stefan] Univ Kiel, Inst Clin Mol Biol, D-24105 Kiel, Germany.
   [Balmforth, Anthony J.] Univ Leeds, Leeds Inst Genet Hlth & Therapeut, Multidisciplinary Cardiovasc Res Ctr, Div Cardiovasc & Diabet Res, Leeds LS2 9JT, W Yorkshire, England.
   [Hall, Alistair S.] Univ Leeds, Leeds Inst Genet Hlth & Therapeut, Multidisciplinary Cardiovasc Res Ctr, Div Cardiovasc & Neuronal Remodelling, Leeds LS2 9JT, W Yorkshire, England.
   [Bertram, Lars] Max Planck Inst Mol Genet, Dept Vertebrate Genom, D-14195 Berlin, Germany.
   [Steinhagen-Thiessen, Elisabeth] Charite, Charite Res Grp Geriatr, D-10117 Berlin, Germany.
   [Li, Shu-Chen] Max Planck Inst Human Dev, Ctr Lifespan Psychol, D-14195 Berlin, Germany.
   [Li, Shu-Chen] Tech Univ Dresden, Dept Psychol, D-01062 Dresden, Germany.
   [Maerz, Winfried] Synlab Serv GmbH, Synlab Acad, D-68165 Mannheim, Germany.
   [Maerz, Winfried] Synlab Serv GmbH, Business Dev, D-68165 Mannheim, Germany.
   [Maerz, Winfried] Med Univ Graz, Clin Inst Med & Chem Lab Diagnost, A-8036 Graz, Austria.
   [Maerz, Winfried] Heidelberg Univ, Med Fac Mannheim, Med Clin 5, D-68167 Mannheim, Germany.
   [Reilly, Muredach] Univ Penn, Cardiovasc Inst, Philadelphia, PA 19104 USA.
   [Kathiresan, Sekar] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02215 USA.
   [Kathiresan, Sekar] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02215 USA.
   [Kathiresan, Sekar] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02215 USA.
   [Kathiresan, Sekar] Broad Inst Harvard & Massachusetts Inst Technol M, Program Med & Populat Genet, Cambridge, MA 02215 USA.
   [McPherson, Ruth] Univ Ottawa, Inst Heart, Ottawa, ON K1Y 4W7, Canada.
   [Walter, Ulrich] Univ Med Mainz, CTH, D-55131 Mainz, Germany.
   [Walter, Ulrich] German Ctr Cardiovasc Res DZHK, D-55131 Mainz, Germany.
   [Ott, Jurg] Chinese Acad Sci, Inst Psychol, Beijing 100864, Peoples R China.
   [Ott, Jurg] Rockefeller Univ, Lab Stat Genet, New York, NY 10065 USA.
C3 University of Lubeck; German Centre for Cardiovascular Research; University of Regensburg; University of Regensburg; Institut National de la Sante et de la Recherche Medicale (Inserm); German Heart Centre Munich; Technical University of Munich; German Centre for Cardiovascular Research; Ruhr University Bochum; University of Lubeck; University of Lubeck; Helmholtz Association; Helmholtz-Center Munich - German Research Center for Environmental Health; Technical University of Munich; University of Bonn; University of Bonn; University of Basel; University of Basel; University of Leicester; University Hospitals of Leicester NHS Trust; University of Leicester; Glenfield Hospital; University of Kiel; University of Leeds; University of Leeds; Max Planck Society; Free University of Berlin; Humboldt University of Berlin; Charite Universitatsmedizin Berlin; Max Planck Society; Technische Universitat Dresden; SYNLAB Group; SYNLAB Group; Medical University of Graz; Ruprecht Karls University Heidelberg; University of Pennsylvania; 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; Massachusetts Institute of Technology (MIT); Broad Institute; University of Ottawa; University of Ottawa Heart Institute; Johannes Gutenberg University of Mainz; German Centre for Cardiovascular Research; Chinese Academy of Sciences; Institute of Psychology, CAS; Rockefeller University
RP Hengstenberg, C (corresponding author), Deutsch Herzzentrum Munich, D-80636 Munich, Germany.
EM jeanette.erdmann@iieg.uni-luebeck.de; hengstenberg@dhm.mhn.de
FU Deutsche Forschungsgemeinschaft; German Federal Ministry of Education and Research (BMBF) [01GS0417, 01GS0832]; EU [LSHM-CT-2006-037593]; ENGAGE [201413]; GEUVADIS [261123]; binational BMBF/ANR funded project CARDomics [01KU0908A]; Universitat zu Lubeck; University Hospital of Regensburg, Germany; The German Federal Ministry for Education and Research [16SV5538]; NSFC from Chinese Government [30730057]; British Heart Foundation; Leicester NIHR Biomedical Research Unit in Cardiovascular Disease; BMBF [01EO1003]; DFG; National Institute for Health Research [NF-SI-0611-10170] Funding Source: researchfish
NR 28
TC 228
Z9 243
U1 1
U2 98
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 19
PY 2013
VL 504
IS 7480
BP 432
EP +
DI 10.1038/nature12722
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 273ZR
UT WOS:000328575300051
PM 24213632
DA 2026-03-09
ER

PT J
AU Raj, VS
   Mou, HH
   Smits, SL
   Dekkers, DHW
   Müller, MA
   Dijkman, R
   Muth, D
   Demmers, JAA
   Zaki, A
   Fouchier, RAM
   Thiel, V
   Drosten, C
   Rottier, PJM
   Osterhaus, ADME
   Bosch, BJ
   Haagmans, BL
AF Raj, V. Stalin
   Mou, Huihui
   Smits, Saskia L.
   Dekkers, Dick H. W.
   Mueller, Marcel A.
   Dijkman, Ronald
   Muth, Doreen
   Demmers, Jeroen A. A.
   Zaki, Ali
   Fouchier, Ron A. M.
   Thiel, Volker
   Drosten, Christian
   Rottier, Peter J. M.
   Osterhaus, Albert D. M. E.
   Bosch, Berend Jan
   Haagmans, Bart L.
TI Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus-EMC
SO NATURE
LA English
DT Article
ID acute-respiratory-syndrome; angiotensin-converting enzyme-2; sars coronavirus; aminopeptidase-n; pathogenesis; mechanisms; reservoirs; bats
AB Most human coronaviruses cause mild upper respiratory tract disease but may be associated with more severe pulmonary disease in immunocompromised individuals'. However, SARS coronavirus caused severe lower respiratory disease with nearly 10% mortality and evidence of systemic spread(2). Recently, another coronavirus (human coronavirus-Erasmus Medical Center (hCoV-EMC)) was identified in patients with severe and sometimes lethal lower respiratory tract infection(3,4). Viral genome analysis revealed close relatedness to coronaviruses found in bats'. Here we identify dipeptidyl peptidase 4 (DPP4; also known as CD26) as a functional receptor for hCoV-EMC. DPP4 specifically co-purified with the receptor-binding Si domain of the hCoV-EMC spike protein from lysates of susceptible Huh-7 cells. Antibodies directed against DPP4 inhibited hCoV-EMC infection of primary human bronchial epithelial cells and Huh-7 cells. Expression of human and bat (Pipistrellus pipistrellus) DPP4 in non-susceptible COS-7 cells enabled infection by hCoV-EMC. The use of the evolutionarily conserved DPP4 protein from different species as a functional receptor provides clues about the host range potential of hCoV-EMC. In addition, it will contribute critically to our understanding of the pathogenesis and epidemiology of this emerging human coronavirus, and may facilitate the development of intervention strategies.
C1 [Raj, V. Stalin; Smits, Saskia L.; Fouchier, Ron A. M.; Osterhaus, Albert D. M. E.; Haagmans, Bart L.] Erasmus MC, Dept Virosci, NL-3000 CA Rotterdam, Netherlands.
   [Mou, Huihui; Rottier, Peter J. M.; Bosch, Berend Jan] Univ Utrecht, Fac Vet Med, Dept Infect Dis & Immunol, Div Virol, NL-3508 TD Utrecht, Netherlands.
   [Smits, Saskia L.] Viroclin Biosci BV, NL-3029 AK Rotterdam, Netherlands.
   [Dekkers, Dick H. W.; Demmers, Jeroen A. A.] Erasmus MC, Prote Dept, NL-3000 CA Rotterdam, Netherlands.
   [Mueller, Marcel A.; Muth, Doreen; Drosten, Christian] Univ Bonn, Med Ctr, Inst Virol, D-53105 Bonn, Germany.
   [Dijkman, Ronald; Thiel, Volker] Kantonal Hosp St Gallen, Inst Immunobiol, CH-9007 St Gallen, Switzerland.
   [Zaki, Ali] Dr Soliman Fakeeh Hosp, Virol Lab, Jeddah, Saudi Arabia.
   [Thiel, Volker] Univ Zurich, Vetsuisse Fac, CH-8057 Zurich, Switzerland.
C3 Erasmus University Rotterdam; Erasmus MC; Utrecht University; Erasmus University Rotterdam; Erasmus MC; University of Bonn; Kantonsspital St. Gallen; Institute of Immunobiology, St. Gallen; University of Zurich
RP Bosch, BJ (corresponding author), Univ Utrecht, Fac Vet Med, Dept Infect Dis & Immunol, Div Virol, NL-3508 TD Utrecht, Netherlands.
EM b.j.bosch@uu.nl; b.haagmans@erasmusmc.nl
FU European Union FP7 [223498]; ANTIGONE [278976]; Swiss National Science Foundation [31003A_132898]; 3R Research Foundation Switzerland [128-11]; German Research Foundation (DFG) [DR 772/3-1, KAl241/18-1]; German Ministry of Education and Research (BMBF SARS II); Swiss National Science Foundation (SNF) [31003A_132898] Funding Source: Swiss National Science Foundation (SNF)
CR Bermingham A, 2012, EUROSURVEILLANCE, V17, P6
   Boonacker E, 2003, EUR J CELL BIOL, V82, P53, DOI 10.1078/0171-9335-00302
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NR 23
TC 1558
Z9 1842
U1 0
U2 241
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 14
PY 2013
VL 495
IS 7440
BP 251
EP 254
DI 10.1038/nature12005
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 113FP
UT WOS:000316652300054
PM 23486063
DA 2026-03-09
ER

PT J
AU Deshmukh, VA
   Tardif, V
   Lyssiotis, CA
   Green, CC
   Kerman, B
   Kim, HJ
   Padmanabhan, K
   Swoboda, JG
   Ahmad, I
   Kondo, T
   Gage, FH
   Theofilopoulos, AN
   Lawson, BR
   Schultz, PG
   Lairson, LL
AF Deshmukh, Vishal A.
   Tardif, Virginie
   Lyssiotis, Costas A.
   Green, Chelsea C.
   Kerman, Bilal
   Kim, Hyung Joon
   Padmanabhan, Krishnan
   Swoboda, Jonathan G.
   Ahmad, Insha
   Kondo, Toru
   Gage, Fred H.
   Theofilopoulos, Argyrios N.
   Lawson, Brian R.
   Schultz, Peter G.
   Lairson, Luke L.
TI A regenerative approach to the treatment of multiple sclerosis
SO NATURE
LA English
DT Article
ID experimental autoimmune encephalomyelitis; muscarinic receptor subtypes; central-nervous-system; embryonic stem-cells; oligodendrocyte differentiation; progenitor cells; thyroid-hormone; precursor cells; myelin repair; spinal-cord
AB Progressive phases of multiple sclerosis are associated with inhibited differentiation of the progenitor cell population that generates the mature oligodendrocytes required for remyelination and disease remission. To identify selective inducers of oligodendrocyte differentiation, we performed an image-based screen for myelin basic protein (MBP) expression using primary rat optic-nerve-derived progenitor cells. Here we show that among the most effective compounds identifed was benztropine, which significantly decreases clinical severity in the experimental autoimmune encephalomyelitis (EAE) model of relapsing-remitting multiple sclerosis when administered alone or in combination with approved immunosuppressive treatments for multiple sclerosis. Evidence from a cuprizone-inducedmodel of demyelination, in vitro and in vivo T-cell assays and EAE adoptive transfer experiments indicated that the observed efficacy of this drug results directly from an enhancement of remyelination rather than immune suppression. Pharmacological studies indicate that benztropine functions by a mechanism that involves direct antagonism of M1 and/or M3 muscarinic receptors. These studies should facilitate the development of effective new therapies for the treatment of multiple sclerosis that complement established immunosuppressive approaches.
C1 [Deshmukh, Vishal A.; Lyssiotis, Costas A.; Green, Chelsea C.; Swoboda, Jonathan G.; Ahmad, Insha; Schultz, Peter G.; Lairson, Luke L.] Scripps Res Inst, Dept Chem, La Jolla, CA 92037 USA.
   [Tardif, Virginie; Theofilopoulos, Argyrios N.; Lawson, Brian R.] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA.
   [Kerman, Bilal; Kim, Hyung Joon; Padmanabhan, Krishnan; Gage, Fred H.] Salk Inst Biol Sci, Lab Genet, La Jolla, CA 92037 USA.
   [Kondo, Toru] Hokkaido Univ, Inst Med Genet, Div Stem Cell Biol, Kita Ku, Sapporo, Hokkaido 0600815, Japan.
   [Schultz, Peter G.; Lairson, Luke L.] Calif Inst Biomed Res, La Jolla, CA 92037 USA.
C3 Scripps Research Institute; Scripps Research Institute; Salk Institute; Hokkaido University
RP Lawson, BR (corresponding author), Scripps Res Inst, Dept Immunol & Microbial Sci, 10550 North Torrey Pines Rd, La Jolla, CA 92037 USA.
EM blawson@scripps.edu; schultz@scripps.edu; llairson@scripps.edu
FU Skaggs Institute for Chemical Biology; California Institute for Regenerative Medicine [TR3-05617, TG2-01165]; National Science Foundation
NR 54
TC 438
Z9 519
U1 1
U2 184
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 17
PY 2013
VL 502
IS 7471
BP 327
EP +
DI 10.1038/nature12647
PG 23
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 235GY
UT WOS:000325706300044
PM 24107995
DA 2026-03-09
ER

PT J
AU Jiang, L
   Liu, X
   Xiong, GS
   Liu, HH
   Chen, FL
   Wang, L
   Meng, XB
   Liu, GF
   Yu, H
   Yuan, YD
   Yi, W
   Zhao, LH
   Ma, HL
   He, YZ
   Wu, ZS
   Melcher, K
   Qian, Q
   Xu, HE
   Wang, YH
   Li, JY
AF Jiang, Liang
   Liu, Xue
   Xiong, Guosheng
   Liu, Huihui
   Chen, Fulu
   Wang, Lei
   Meng, Xiangbing
   Liu, Guifu
   Yu, Hong
   Yuan, Yundong
   Yi, Wei
   Zhao, Lihua
   Ma, Honglei
   He, Yuanzheng
   Wu, Zhongshan
   Melcher, Karsten
   Qian, Qian
   Xu, H. Eric
   Wang, Yonghong
   Li, Jiayang
TI DWARF 53 acts as a repressor of strigolactone signalling in rice
SO NATURE
LA English
DT Article
ID oryza-sativa-l; co-repressor; arabidopsis; topless; outgrowth; karrikin; ortholog; genes; max1; leaf
AB Strigolactones (SLs) are a group of newly identified plant hormones that control plant shoot branching. SL signalling requires the hormone-dependent interaction of DWARF14 (D14), a probable candidate SL receptor, with DWARF3 (D3), an F-box component of the Skp-Cullin-F-box (SCF) E3 ubiquitin ligase complex. Here we report the characterization of a dominant SL-insensitive rice (Oryza sativa) mutant dwarf 53 (d53) and the cloning of D53, which encodes a substrate of the SCFD3 ubiquitination complex and functions as a repressor of SL signalling. Treatments with GR24, a synthetic SL analogue, cause D53 degradation via the proteasome in a manner that requires D14 and the SCFD3 ubiquitin ligase, whereas the dominant form of D53 is resistant to SL-mediated degradation. Moreover, D53 can interact with transcriptional co-repressors known as TOPLESS-RELATED PROTEINS. Our results suggest a model of SL signalling that involves SL-dependent degradation of the D53 repressor mediated by the D14-D3 complex.
C1 [Jiang, Liang; Liu, Xue; Xiong, Guosheng; Liu, Huihui; Chen, Fulu; Wang, Lei; Meng, Xiangbing; Liu, Guifu; Yu, Hong; Yuan, Yundong; Wang, Yonghong; Li, Jiayang] Chinese Acad Sci, Inst Genet & Dev Biol, State Key Lab Plant Genom, Beijing 100101, Peoples R China.
   [Jiang, Liang; Liu, Xue; Xiong, Guosheng; Liu, Huihui; Chen, Fulu; Wang, Lei; Meng, Xiangbing; Liu, Guifu; Yu, Hong; Yuan, Yundong; Wang, Yonghong; Li, Jiayang] Chinese Acad Sci, Inst Genet & Dev Biol, Natl Ctr Plant Gene Res Beijing, Beijing 100101, Peoples R China.
   [Yi, Wei; Zhao, Lihua; Ma, Honglei; Xu, H. Eric] Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Ctr Struct & Funct Drug Targets,VARI SIMM Ctr, Shanghai 201203, Peoples R China.
   [He, Yuanzheng; Wu, Zhongshan; Melcher, Karsten; Xu, H. Eric] Van Andel Res Inst, Lab Struct Sci, Grand Rapids, MI 49503 USA.
   [Qian, Qian] Chinese Acad Agr Sci, China Natl Rice Res Inst, State Key Lab Rice Biol, Hangzhou 310006, Zhejiang, Peoples R China.
C3 Chinese Academy of Sciences; Institute of Genetics & Developmental Biology, CAS; Chinese Academy of Sciences; Institute of Genetics & Developmental Biology, CAS; Chinese Academy of Sciences; Shanghai Institute of Materia Medica, CAS; Van Andel Institute; Van Andel Research Institute; Chinese Academy of Agricultural Sciences; China National Rice Research Institute, CAAS
RP Li, JY (corresponding author), Chinese Acad Sci, Inst Genet & Dev Biol, State Key Lab Plant Genom, Beijing 100101, Peoples R China.
EM Eric.Xu@vai.org; yhwang@genetics.ac.cn; jyli@genetics.ac.cn
FU Ministry of Science and Technology of the People's Republic of China [2012AA10A301]; National Natural Science Foundation of China [31025004, 90817108, 91217311]
NR 50
TC 687
Z9 826
U1 10
U2 628
PU NATURE PUBLISHING 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 19
PY 2013
VL 504
IS 7480
BP 401
EP +
DI 10.1038/nature12870
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 273ZR
UT WOS:000328575300044
PM 24336200
DA 2026-03-09
ER

PT J
AU Libuda, DE
   Uzawa, S
   Meyer, BJ
   Villeneuve, AM
AF Libuda, Diana E.
   Uzawa, Satoru
   Meyer, Barbara J.
   Villeneuve, Anne M.
TI Meiotic chromosome structures constrain and respond to designation of crossover sites
SO NATURE
LA English
DT Article
ID synaptonemal complex; crossing-over; c-elegans; caenorhabditis-elegans; chiasma formation; strand-exchange; synapsis; meiosis; recombination; interference
AB Crossover recombination events between homologous chromosomes are required to form chiasmata, temporary connections between homologues that ensure their proper segregation at meiosis I-1. Despite this requirement for crossovers and an excess of the double-strand DNA breaks that are the initiating events for meiotic recombination, most organisms make very few crossovers per chromosome pair(2). Moreover, crossovers tend to inhibit the formation of other crossovers nearby on the same chromosome pair, a poorly understood phenomenon known as crossover interference(3,4). Here we show that the synaptonemal complex, a meiosis-specific structure that assembles between aligned homologous chromosomes, both constrains and is altered by crossover recombination events. Using a cytological marker of crossover sites in Caenorhabditis elegans(5), we show that partial depletion of the synaptonemal complex central region proteins attenuates crossover interference, increasing crossovers and reducing the effective distance over which interference operates, indicating that synaptonemal complex proteins limit crossovers. Moreover, we show that crossovers are associated with a local 0.4-0.5-micrometre increase in chromosome axis length. We propose that meiotic crossover regulation operates as a self-limiting system in which meiotic chromosome structures establish an environment that promotes crossover formation, which in turn alters chromosome structure to inhibit other crossovers at additional sites.
C1 [Libuda, Diana E.; Villeneuve, Anne M.] Stanford Univ, Dept Dev Biol, Sch Med, Stanford, CA 94305 USA.
   [Uzawa, Satoru; Meyer, Barbara J.] Univ Calif Berkeley, Howard Hughes Med Inst, Berkeley, CA 94720 USA.
   [Uzawa, Satoru; Meyer, Barbara J.] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA.
   [Villeneuve, Anne M.] Stanford Univ, Sch Med, Dept Genet, Stanford, CA 94305 USA.
C3 Stanford University; University of California System; University of California Berkeley; Howard Hughes Medical Institute; University of California System; University of California Berkeley; Stanford University
RP Villeneuve, AM (corresponding author), Stanford Univ, Dept Dev Biol, Sch Med, Stanford, CA 94305 USA.
EM annev@stanford.edu
FU National Institutes of Health (NIH) [P40 OD010440, K99 HD076165, R01 GM067268]; Helen Hay Whitney Foundation; Katharine McCormick Advanced Postdoctoral Fellowship; NIH Office of the Director; National Institute of General Medical Sciences [P40OD010440] Funding Source: NIH RePORTER
NR 32
TC 132
Z9 170
U1 0
U2 41
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 31
PY 2013
VL 502
IS 7473
BP 703
EP +
DI 10.1038/nature12577
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 243CC
UT WOS:000326293200052
PM 24107990
DA 2026-03-09
ER

PT J
AU Sanloup, C
   Drewitt, JWE
   Konôpková, Z
   Dalladay-Simpson, P
   Morton, DM
   Rai, N
   van Westrenen, W
   Morgenroth, W
AF Sanloup, Chrystele
   Drewitt, James W. E.
   Konopkova, Zuzana
   Dalladay-Simpson, Philip
   Morton, Donna M.
   Rai, Nachiketa
   van Westrenen, Wim
   Morgenroth, Wolfgang
TI Structural change in molten basalt at deep mantle conditions
SO NATURE
LA English
DT Article
ID earths lower mantle; high-pressure; magma ocean; coordination changes; liquid; metal; gpa; density; core; melt
AB Silicate liquids play a key part at all stages of deep Earth evolution, ranging from core and crust formation billions of years ago to present-day volcanic activity. Quantitative models of these processes require knowledge of the structural changes and compression mechanisms that take place in liquid silicates at the high pressures and temperatures in the Earth's interior. However, obtaining such knowledge has long been impeded by the challenging nature of the experiments. In recent years, structural and density information for silica glass was obtained at record pressures of up to 100 GPa (ref. 1), a major step towards obtaining data on the molten state. Here we report the structure of molten basalt up to 60 GPa by means of in situ X-ray diffraction. The coordination of silicon increases from four under ambient conditions to six at 35 GPa, similar to what has been reported in silica glass(1-3). The compressibility of the melt after the completion of the coordination change is lower than at lower pressure, implying that only a high-order equation of state can accurately describe the density evolution of silicate melts over the pressure range of the whole mantle. The transition pressure coincides with a marked change in the pressure-evolution of nickel partitioning between molten iron and molten silicates, indicating that melt compressibility controls siderophile-element partitioning.
C1 [Sanloup, Chrystele; Drewitt, James W. E.; Dalladay-Simpson, Philip; Morton, Donna M.] Univ Edinburgh, Scottish Univ Phys Alliance, Ctr Sci Extreme Condit, Edinburgh EH9 3JZ, Midlothian, Scotland.
   [Sanloup, Chrystele; Drewitt, James W. E.; Dalladay-Simpson, Philip; Morton, Donna M.] Univ Edinburgh, Scottish Univ Phys Alliance, Sch Phys & Astron, Edinburgh EH9 3JZ, Midlothian, Scotland.
   [Sanloup, Chrystele] Univ Paris 06, CNRS, UMR 7193, Inst Sci Terre Paris, F-75005 Paris, France.
   [Konopkova, Zuzana; Morgenroth, Wolfgang] DESY Photon Sci, D-22607 Hamburg, Germany.
   [Rai, Nachiketa; van Westrenen, Wim] Vrije Univ Amsterdam, Fac Earth & Life Sci, NL-1081 HV Amsterdam, Netherlands.
   [Morgenroth, Wolfgang] Goethe Univ Frankfurt, Inst Geowissensch, D-60438 Frankfurt, Germany.
C3 University of Edinburgh; University of Edinburgh; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Earth Sciences & Astronomy (INSU); Sorbonne Universite; Helmholtz Association; Deutsches Elektronen-Synchrotron (DESY); Vrije Universiteit Amsterdam; Goethe University Frankfurt
RP Sanloup, C (corresponding author), Univ Edinburgh, Scottish Univ Phys Alliance, Ctr Sci Extreme Condit, Edinburgh EH9 3JZ, Midlothian, Scotland.
EM chrystele.sanloup@ed.ac.uk
FU European Community under European Research Council [312284, 259649]; BMBF (the German Federal Ministry of Education and Research) [05K10RFA]; Engineering and Physical Sciences Research Council [1110865] Funding Source: researchfish; European Research Council (ERC) [259649] Funding Source: European Research Council (ERC)
CR Agee CB, 1998, PHYS EARTH PLANET IN, V107, P63, DOI 10.1016/S0031-9201(97)00124-6
   Asimow PD, 2010, J GEOPHYS RES-SOL EA, V115, P0, DOI 10.1029/2009JB007145
   Benmore CJ, 2010, PHYS REV B, V81, P0, DOI 10.1103/PhysRevB.81.054105
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   de Koker N, 2009, GEOPHYS J INT, V178, P162, DOI 10.1111/j.1365-246X.2009.04142.x
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NR 39
TC 153
Z9 163
U1 1
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 NOV 7
PY 2013
VL 503
IS 7474
BP 104
EP +
DI 10.1038/nature12668
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 247AS
UT WOS:000326585600040
PM 24201283
DA 2026-03-09
ER

PT J
AU Jakobsen, L
   Ratcliffe, JM
   Surlykke, A
AF Jakobsen, Lasse
   Ratcliffe, John M.
   Surlykke, Annemarie
TI Convergent acoustic field of view in echolocating bats
SO NATURE
LA English
DT Article
ID sound beam; brown bat; prey; vespertilionidae; size
AB Most echolocating bats exhibit a strong correlation between body size and the frequency of maximum energy in their echolocation calls (peak frequency), with smaller species using signals of higher frequency than larger ones(1,2). Size-signal allometry or acoustic detection constraints imposed on wavelength by preferred prey size have been used to explain this relationship(1,3). Here we propose the hypothesis that smaller bats emit higher frequencies to achieve directional sonar beams, and that variable beam width is critical for bats. Shorter wavelengths relative to the size of the emitter translate into more directional sound beams(4). Therefore, bats that emit their calls through their mouths should show a relationship between mouth size and wavelength, driving smaller bats to signals of higher frequency. We found that in a flight room mimicking a closed habitat, six aerial hawking vespertilionid species (ranging in size from 4 to 21 g, ref. 5) produced sonar beams of extraordinarily similar shape and volume. Each species had a directivity index of 11 +/- 1 dB (a half-amplitude angle of approximately 37 degrees) and an on-axis sound level of 108 +/- 4 dB sound pressure level referenced to 20 mu Pa root mean square at 10 cm. Thus all bats adapted their calls to achieve similar acoustic fields of view. We propose that the necessity for high directionality has been a key constraint on the evolution of echolocation, which explains the relationship between bat size and echolocation call frequency. Our results suggest that echolocation is a dynamic system that allows different species, regardless of their body size, to converge on optimal fields of view in response to habitat and task.
C1 [Jakobsen, Lasse; Ratcliffe, John M.; Surlykke, Annemarie] Univ So Denmark, Sound Commun Grp, Inst Biol, DK-5230 Odense M, Denmark.
C3 University of Southern Denmark
RP Surlykke, A (corresponding author), Univ So Denmark, Sound Commun Grp, Inst Biol, DK-5230 Odense M, Denmark.
EM ams@biology.sdu.dk
FU Danish Council for Natural Sciences (FNU), Carlsberg, Oticon; European Commission via the Seventh Framework Programme project ChiRoPing, Information Society Technologies [215370]
NR 29
TC 102
Z9 118
U1 2
U2 201
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 3
PY 2013
VL 493
IS 7430
BP 93
EP 96
DI 10.1038/nature11664
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 062QC
UT WOS:000312933800037
PM 23172147
DA 2026-03-09
ER

PT J
AU Zhang, YB
   Wong, CH
   Birnbaum, RY
   Li, GL
   Favaro, R
   Ngan, CY
   Lim, J
   Tai, E
   Poh, HM
   Wong, E
   Mulawadi, FH
   Sung, WK
   Nicolis, S
   Ahituv, N
   Ruan, YJ
   Wei, CL
AF Zhang, Yubo
   Wong, Chee-Hong
   Birnbaum, Ramon Y.
   Li, Guoliang
   Favaro, Rebecca
   Ngan, Chew Yee
   Lim, Joanne
   Tai, Eunice
   Poh, Huay Mei
   Wong, Eleanor
   Mulawadi, Fabianus Hendriyan
   Sung, Wing-Kin
   Nicolis, Silvia
   Ahituv, Nadav
   Ruan, Yijun
   Wei, Chia-Lin
TI Chromatin connectivity maps reveal dynamic promoter-enhancer long-range associations
SO NATURE
LA English
DT Article
ID neural stem-cells; regulatory sequences; gene-expression; mouse; pluripotent; vertebrate; circuitry
AB In multicellular organisms, transcription regulation is one of the central mechanisms modelling lineage differentiation and cell-fate determination(1). Transcription requires dynamic chromatin configurations between promoters and their corresponding distal regulatory elements(2). It is believed that their communication occurs within large discrete foci of aggregated RNA polymerases termed transcription factories in three-dimensional nuclear space(3). However, the dynamic nature of chromatin connectivity has not been characterized at the genome-wide level. Here, through a chromatin interaction analysis with paired-end tagging approach(3-5) using an antibody that primarily recognizes the pre-initiation complexes of RNA polymerase II6, we explore the transcriptional interactomes of three mouse cells of progressive lineage commitment, including pluripotent embryonic stem cells(7), neural stem cells(8) and neurosphere stem/progenitor cells(9). Our global chromatin connectivity maps reveal approximately 40,000 long-range interactions, suggest precise enhancer-promoter associations and delineate cell-type-specific chromatin structures. Analysis of the complex regulatory repertoire shows that there are extensive colocalizations among promoters and distal-acting enhancers. Most of the enhancers associate with promoters located beyond their nearest active genes, indicating that the linear juxtaposition is not the only guiding principle driving enhancer target selection. Although promoter-enhancer interactions exhibit high cell-type specificity, promoters involved in interactions are found to be generally common and mostly active among different cells. Chromatin connectivity networks reveal that the pivotal genes of reprogramming functions are transcribed within physical proximity to each other in embryonic stem cells, linking chromatin architecture to coordinated gene expression. Our study sets the stage for the full-scale dissection of spatial and temporal genome structures and their roles in orchestrating development.
C1 [Zhang, Yubo; Wong, Chee-Hong; Ngan, Chew Yee; Wei, Chia-Lin] Lawrence Berkeley Natl Lab, Joint Genome Inst, Sequencing Technol Grp, Walnut Creek, CA 94598 USA.
   [Birnbaum, Ramon Y.; Ahituv, Nadav] UCSF, Inst Human Genet, Dept Bioengn & Therapeut Sci, San Francisco, CA 94158 USA.
   [Li, Guoliang; Ruan, Yijun] Univ Connecticut, Jackson Lab Genom Med, Farmington, CT 06030 USA.
   [Li, Guoliang; Ruan, Yijun] Univ Connecticut, Dept Genet & Dev Biol, Farmington, CT 06030 USA.
   [Li, Guoliang; Lim, Joanne; Tai, Eunice; Poh, Huay Mei; Wong, Eleanor; Mulawadi, Fabianus Hendriyan; Sung, Wing-Kin; Wei, Chia-Lin] Genome Inst Singapore, Singapore 138672, Singapore.
   [Favaro, Rebecca; Nicolis, Silvia] Univ Milano Bicocca, Dept Biol Sci & Biotechnol, I-20126 Milan, Italy.
C3 United States Department of Energy (DOE); Joint Genome Institute - JGI; Lawrence Berkeley National Laboratory; Joint BioEnergy Institute - JBEI; University of California System; University of California San Francisco; Jackson Laboratory; University of Connecticut; University of Connecticut; Agency for Science Technology & Research (A*STAR); A*STAR - Genome Institute of Singapore (GIS); University of Milano-Bicocca
RP Wei, CL (corresponding author), Lawrence Berkeley Natl Lab, Joint Genome Inst, Sequencing Technol Grp, Walnut Creek, CA 94598 USA.
EM cwei@lbl.gov
FU ASTIL Regione Lombardia (SAL-19) [16874]; Telethon [GGP12152]; Cariplo [2010-0673]; AIRC [IG-5801]; NINDS [R01NS079231]; NICHD [R01HD059862]; NHGRI [R01HG005058, R01HG006768]; NIDDK [R01DK090382]; NIGMS [GM61390]; Simons Foundation SFARI [256769]; UCSF Program for Biomedical Breakthrough Research (PBBR); Agency for Science, Technology and Research (A*STAR), Singapore; Office of Science of the U.S. Department of Energy [DE-AC02-05CH11231]; National Institutes of Health ENCODE [R01 HG004456-01, R01HG003521-01, 1U54HG004557-01]
NR 30
TC 358
Z9 434
U1 0
U2 79
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 12
PY 2013
VL 504
IS 7479
BP 306
EP +
DI 10.1038/nature12716
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 267TQ
UT WOS:000328121500042
PM 24213634
DA 2026-03-09
ER

PT J
AU Muzerolle, J
   Furlan, E
   Flaherty, K
   Balog, Z
   Gutermuth, R
AF Muzerolle, James
   Furlan, Elise
   Flaherty, Kevin
   Balog, Zoltan
   Gutermuth, Robert
TI Pulsed accretion in a variable protostar
SO NATURE
LA English
DT Article
ID young stellar objects; binary dq tau; circumbinary disk; class-i; stars; variability; evolution; dynamics; a0538-66; auriga
AB Periodic increases in luminosity arising from variable accretion rates have been predicted for some pre-main-sequence close binary stars as they grow from circumbinary disks(1-3). The phenomenon is known as pulsed accretion and can affect the orbital evolution and mass distribution of young binaries(2,4), as well as the potential for planet formation(5,6). Accretion variability is a common feature of young stars, with a large range of amplitudes and timescales as measured from multi-epoch observations at optical(7,8) and infrared(9-13) wavelengths. Periodic variations consistent with pulsed accretion have been seen in only a few young binaries via optical accretion tracers(14-16), albeit intermittently with accretion luminosity variations ranging from zero to 50 per cent from orbit to orbit. Here we report that the infrared luminosity of a young protostar (of age about 10(5) years) increases by a factor of ten in roughly one week every 25.34 days. We attribute this to pulsed accretion associated with an unseen binary companion. The strength and regularity of this accretion signal is surprising; it may be related to the very young age of the system, which is a factor of ten younger than the other pulsed accretors previously studied.
C1 [Muzerolle, James] Space Telescope Sci Inst, Baltimore, MD 21218 USA.
   [Furlan, Elise] Natl Opt Astron Observ, Tucson, AZ 85719 USA.
   [Flaherty, Kevin] Univ Arizona, Steward Observ, Tucson, AZ 85721 USA.
   [Balog, Zoltan] Max Planck Inst Astron, D-69117 Heidelberg, Germany.
   [Gutermuth, Robert] Univ Massachusetts, Dept Astron, Amherst, MA 01003 USA.
C3 Space Telescope Science Institute; National Optical Astronomy Observatory; University of Arizona; Max Planck Society; University of Massachusetts System; University of Massachusetts Amherst
RP Muzerolle, J (corresponding author), Space Telescope Sci Inst, 3700 San Martin Dr, Baltimore, MD 21218 USA.
EM muzerol@stsci.edu
FU NASA
NR 27
TC 45
Z9 46
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 JAN 17
PY 2013
VL 493
IS 7432
BP 378
EP 380
DI 10.1038/nature11746
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 071TA
UT WOS:000313615900045
PM 23283175
DA 2026-03-09
ER

PT J
AU Liu, XJ
   Zhang, Y
   Han, WX
   Tang, AH
   Shen, JL
   Cui, ZL
   Vitousek, P
   Erisman, JW
   Goulding, K
   Christie, P
   Fangmeier, A
   Zhang, FS
AF Liu, Xuejun
   Zhang, Ying
   Han, Wenxuan
   Tang, Aohan
   Shen, Jianlin
   Cui, Zhenling
   Vitousek, Peter
   Erisman, Jan Willem
   Goulding, Keith
   Christie, Peter
   Fangmeier, Andreas
   Zhang, Fusuo
TI Enhanced nitrogen deposition over China
SO NATURE
LA English
DT Article
ID cycle; fertilizer; agroecosystems; environment; management; impacts; soil
AB China is experiencing intense air pollution caused in large part by anthropogenic emissions of reactive nitrogen(1,2). These emissions result in the deposition of atmospheric nitrogen (N) in terrestrial and aquatic ecosystems, with implications for human and ecosystem health, greenhouse gas balances and biological diversity(1,3-5). However, information on the magnitude and environmental impact of N deposition in China is limited. Here we use nationwide data sets on bulk N deposition, plant foliar N and crop N uptake (from long-term unfertilized soils) to evaluate N deposition dynamics and their effect on ecosystems across China between 1980 and 2010. We find that the average annual bulk deposition of N increased by approximately 8 kilograms of nitrogen per hectare (P < 0.001) between the 1980s (13.2 kilograms of nitrogen per hectare) and the 2000s (21.1 kilograms of nitrogen Per hectare). Nitrogen deposition rates in the industrialized and agriculturally intensified regions of China are as high as the peak levels of deposition in northwestern Europe in the 1980s(6), before the introduction of mitigation measures(7,8). Nitrogen from ammonium (NH4+) is the dominant form of N in bulk deposition, but the rate of increase is largest for deposition of N from nitrate (NO3-), in agreement with decreased ratios of NH3 to NOx emissions since 1980. We also find that the impact of N deposition on Chinese ecosystems includes significantly increased plant foliar N concentrations in natural and semi-natural (that is, non-agricultural) ecosystems and increased crop N uptake from long-term-unfertilized crop-lands. China and other economies are facing a continuing challenge to reduce emissions of reactive nitrogen, N deposition and their negative effects on human health and the environment.
C1 [Liu, Xuejun; Zhang, Ying; Han, Wenxuan; Tang, Aohan; Shen, Jianlin; Cui, Zhenling; Christie, Peter; Zhang, Fusuo] China Agr Univ, Coll Resources & Environm Sci, Beijing 100193, Peoples R China.
   [Vitousek, Peter] Stanford Univ, Dept Biol, Stanford, CA 94305 USA.
   [Erisman, Jan Willem] Vrije Univ Amsterdam, NL-1081 HV Amsterdam, Netherlands.
   [Erisman, Jan Willem] Louis Bolk Inst, NL-3972 LA Driebergen, Netherlands.
   [Goulding, Keith] Rothamsted Res, Sustainable Soils & Grassland Syst Dept, Harpenden AL5 2JQ, Herts, England.
   [Christie, Peter] Agri Food & Biosci Inst, Agri Environm Branch, Belfast BT9 5PX, Antrim, North Ireland.
   [Fangmeier, Andreas] Univ Hohenheim, Inst Landscape & Plant Ecol, D-70593 Stuttgart, Germany.
C3 China Agricultural University; Stanford University; Vrije Universiteit Amsterdam; UK Research & Innovation (UKRI); Biotechnology and Biological Sciences Research Council (BBSRC); Rothamsted Research; Agri-Food & Biosciences Institute; University Hohenheim
RP Zhang, FS (corresponding author), China Agr Univ, Coll Resources & Environm Sci, Beijing 100193, Peoples R China.
EM zhangfs@cau.edu.cn
FU Chinese National Basic Research Program [2009CB118606]; NSFC [31121062, 41071151, 40973054];  [GK 1070]; BBSRC [BBS/E/C/00005196, BBS/E/C/00005189] Funding Source: UKRI; Biotechnology and Biological Sciences Research Council [BBS/E/C/00005196, BBS/E/C/00005189] Funding Source: researchfish
NR 30
TC 2218
Z9 2972
U1 94
U2 3865
PU NATURE PUBLISHING 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 28
PY 2013
VL 494
IS 7438
BP 459
EP 462
DI 10.1038/nature11917
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 099YI
UT WOS:000315661500034
PM 23426264
DA 2026-03-09
ER

PT J
AU Ibarra-Laclette, E
   Lyons, E
   Hernández-Guzmán, G
   Pérez-Torres, CA
   Carretero-Paulet, L
   Chang, TH
   Lan, TY
   Welch, AJ
   Juárez, MJA
   Simpson, J
   Fernández-Cortes, A
   Arteaga-Vázquez, M
   Góngora-Castillo, E
   Acevedo-Hernández, G
   Schuster, SC
   Himmelbauer, H
   Minoche, AE
   Xu, S
   Lynch, M
   Oropeza-Aburto, A
   Cervantes-Pérez, SA
   Ortega-Estrada, MD
   Cervantes-Luevano, JI
   Michael, TP
   Mockler, T
   Bryant, D
   Herrera-Estrella, A
   Albert, VA
   Herrera-Estrella, L
AF Ibarra-Laclette, Enrique
   Lyons, Eric
   Hernandez-Guzman, Gustavo
   Anahi Perez-Torres, Claudia
   Carretero-Paulet, Lorenzo
   Chang, Tien-Hao
   Lan, Tianying
   Welch, Andreanna J.
   Abraham Juarez, Maria Jazmin
   Simpson, June
   Fernandez-Cortes, Araceli
   Arteaga-Vazquez, Mario
   Gongora-Castillo, Elsa
   Acevedo-Hernandez, Gustavo
   Schuster, Stephan C.
   Himmelbauer, Heinz
   Minoche, Andre E.
   Xu, Sen
   Lynch, Michael
   Oropeza-Aburto, Araceli
   Alan Cervantes-Perez, Sergio
   de Jesus Ortega-Estrada, Maria
   Israel Cervantes-Luevano, Jacob
   Michael, Todd P.
   Mockler, Todd
   Bryant, Douglas
   Herrera-Estrella, Alfredo
   Albert, Victor A.
   Herrera-Estrella, Luis
TI Architecture and evolution of a minute plant genome
SO NATURE
LA English
DT Article
ID bladderwort utricularia; arabidopsis; sequence; size; lentibulariaceae; identification; genes
AB It has been argued that the evolution of plant genome size is principally unidirectional and increasing owing to the varied action of whole-genome duplications (WGDs) and mobile element proliferation(1). However, extreme genome size reductions have been reported in the angiosperm family tree. Here we report the sequence of the 82-megabase genome of the carnivorous bladderwort plant Utricularia gibba. Despite its tiny size, the U. gibba genome accommodates a typical number of genes for a plant, with the main difference from other plant genomes arising from a drastic reduction in non-genic DNA. Unexpectedly, we identified at least three rounds of WGD in U. gibba since common ancestry with tomato (Solanum) and grape (Vitis). The compressed architecture of the U. gibba genome indicates that a small fraction of intergenic DNA, with few or no active retrotransposons, is sufficient to regulate and integrate all the processes required for the development and reproduction of a complex organism.
C1 [Ibarra-Laclette, Enrique; Hernandez-Guzman, Gustavo; Anahi Perez-Torres, Claudia; Fernandez-Cortes, Araceli; Oropeza-Aburto, Araceli; Alan Cervantes-Perez, Sergio; de Jesus Ortega-Estrada, Maria; Israel Cervantes-Luevano, Jacob; Herrera-Estrella, Alfredo; Herrera-Estrella, Luis] CINVESTAV, Lab Nacl Genom Biodiversidad LANGEBI, Guanajuato 36821, Mexico.
   [Lyons, Eric] Univ Arizona, Sch Plant Sci & iPlant Collaborat, Tucson, AZ 85721 USA.
   [Hernandez-Guzman, Gustavo] Univ Guanajuato, Dept Alimentos, Div Ciencias Vida, Guanajuato 36500, Mexico.
   [Carretero-Paulet, Lorenzo; Chang, Tien-Hao; Lan, Tianying; Welch, Andreanna J.; Albert, Victor A.] SUNY Buffalo, Dept Biol Sci, Buffalo, NY 14260 USA.
   [Lan, Tianying] Chongqing Univ Sci & Technol, Dept Biol, Chongqing 4000042, Peoples R China.
   [Abraham Juarez, Maria Jazmin; Simpson, June] CINVESTAV, Dept Genet, Unidad Irapuato, Guanajuato 36821, Mexico.
   [Arteaga-Vazquez, Mario] Univ Veracruzana, Inst Biotecnol & Ecol Aplicada, Xalapa 91090, Veracruz, Mexico.
   [Gongora-Castillo, Elsa] Michigan State Univ, Dept Plant Biol, E Lansing, MI 48824 USA.
   [Acevedo-Hernandez, Gustavo] Univ Guadalajara, Ctr Univ Cienega, Ocotlan 47840, Jalisco, Mexico.
   [Schuster, Stephan C.] Penn State Univ, Ctr Comparat Genom & Bioinformat, University Pk, PA 16802 USA.
   [Schuster, Stephan C.] Nanyang Technol Univ, Singapore Ctr Environm Life Sci Engn, Singapore 637551, Singapore.
   [Himmelbauer, Heinz; Minoche, Andre E.] CRG, Barcelona 08003, Spain.
   [Himmelbauer, Heinz; Minoche, Andre E.] UPF, Barcelona 08018, Spain.
   [Minoche, Andre E.] Max Planck Inst Mol Genet, D-14195 Berlin, Germany.
   [Xu, Sen; Lynch, Michael] Indiana Univ, Dept Biol, Bloomington, IN 47405 USA.
   [Michael, Todd P.] Rutgers State Univ, Waksman Inst Microbiol, Piscataway, NJ 08854 USA.
   [Michael, Todd P.] Rutgers State Univ, Dept Plant Biol & Pathol, Piscataway, NJ 08854 USA.
   [Mockler, Todd; Bryant, Douglas] Donald Danforth Plant Sci Ctr, St Louis, MO 63132 USA.
C3 CINVESTAV - Centro de Investigacion y de Estudios Avanzados del Instituto Politecnico Nacional; University of Arizona; Universidad de Guanajuato; State University of New York (SUNY) System; University at Buffalo, SUNY; Chongqing University of Science & Technology; CINVESTAV - Centro de Investigacion y de Estudios Avanzados del Instituto Politecnico Nacional; Universidad Veracruzana; Michigan State University; Universidad de Guadalajara; Pennsylvania Commonwealth System of Higher Education (PCSHE); Pennsylvania State University; Pennsylvania State University - University Park; Nanyang Technological University; Barcelona Institute of Science & Technology; Pompeu Fabra University; Centre de Regulacio Genomica (CRG); Pompeu Fabra University; Max Planck Society; Indiana University System; Indiana University Bloomington; Rutgers University System; Rutgers University New Brunswick; Rutgers University System; Rutgers University New Brunswick; Donald Danforth Plant Science Center
RP Albert, VA (corresponding author), SUNY Buffalo, Dept Biol Sci, Buffalo, NY 14260 USA.
EM vaalbert@buffalo.edu; lherrera@langebio.cinvestav.mx
FU CONACyT (Mexico) [4367]; College of Arts and Sciences, University at Buffalo; NSF [0922742]; CONACyT (Mexico); Direct For Biological Sciences; Division Of Integrative Organismal Systems [0922742] Funding Source: National Science Foundation
NR 25
TC 273
Z9 327
U1 3
U2 256
PU NATURE PUBLISHING 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 6
PY 2013
VL 498
IS 7452
BP 94
EP +
DI 10.1038/nature12132
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 158DC
UT WOS:000319947800040
PM 23665961
DA 2026-03-09
ER

PT J
AU Tanaka, G
   Hou, XG
   Ma, XY
   Edgecombe, GD
   Strausfeld, NJ
AF Tanaka, Gengo
   Hou, Xianguang
   Ma, Xiaoya
   Edgecombe, Gregory D.
   Strausfeld, Nicholas J.
TI Chelicerate neural ground pattern in a Cambrian great appendage arthropod
SO NATURE
LA English
DT Article
ID burgess shale; british-columbia; visual-systems; leanchoilia; brain; eyes; morphology; evolution; origin; spider
AB Preservation of neural tissue in early Cambrian arthropods has recently been demonstrated(1), to a degree that segmental structures of the head can be associated with individual brain neuromeres. This association provides novel data for addressing long-standing controversies about the segmental identities of specialized head appendages in fossil taxa(2,3). Here we document neuroanatomy in the head and trunk of a 'great appendage' arthropod, Alalcomenaeus sp., from the Chengjiang biota, southwest China, providing the most complete neuroanatomical profile known from a Cambrian animal. Micro-computed tomography reveals a configuration of one optic neuropil separate from a protocerebrum contiguous with four head ganglia, succeeded by eight contiguous ganglia in an eleven-segment trunk. Arrangements of optic neuropils, the brain and ganglia correspond most closely to the nervous system of Chelicerata of all extant arthropods, supporting the assignment of 'great appendage' arthropods to the chelicerate total group(4,5). The position of the deutocerebral neuromere aligns with the insertion of the great appendage, indicating its deutocerebral innervation and corroborating a homology between the 'great appendage' and chelicera indicated by morphological similarities(4,6,7). Alalcomenaeus and Fuxianhuia protensa(1) demonstrate that the two main configurations of the brain observed in modern arthropods, those of Chelicerata and Mandibulata, respectively(8), had evolved by the early Cambrian.
C1 [Tanaka, Gengo] Japan Agcy Marine Earth Sci & Technol, Yokosuka, Kanagawa 2370061, Japan.
   [Hou, Xianguang; Ma, Xiaoya] 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 Japan Agency for Marine-Earth Science & Technology (JAMSTEC); Yunnan University; Natural History Museum London; University of Arizona; University of Arizona
RP Hou, XG (corresponding author), Yunnan Univ, Yunnan Key Lab Palaeobiol, Kunming 650091, Peoples R China.
EM xghou@ynu.edu.cn; flybrain@email.arizona.edu
FU Natural Science Foundation of China [40730211]; Research in Education and Science from the Government of Japan [21740370]; Leverhulme Trust [F/00 696/T]; Center for Insect Science, University of Arizona; Air Force Research Laboratories [FA8651-10-1-0001]; Grants-in-Aid for Scientific Research [21740370, 24540501] Funding Source: KAKEN
NR 29
TC 124
Z9 133
U1 3
U2 74
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 17
PY 2013
VL 502
IS 7471
BP 364
EP +
DI 10.1038/nature12520
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 235GY
UT WOS:000325706300051
PM 24132294
DA 2026-03-09
ER

PT J
AU Le Sage, D
   Arai, K
   Glenn, DR
   DeVience, SJ
   Pham, LM
   Rahn-Lee, L
   Lukin, MD
   Yacoby, A
   Komeili, A
   Walsworth, RL
AF Le Sage, D.
   Arai, K.
   Glenn, D. R.
   DeVience, S. J.
   Pham, L. M.
   Rahn-Lee, L.
   Lukin, M. D.
   Yacoby, A.
   Komeili, A.
   Walsworth, R. L.
TI Optical magnetic imaging of living cells
SO NATURE
LA English
DT Article
ID magnetotactic bacteria; spin; resonance; electron
AB Magnetic imaging is a powerful tool for probing biological and physical systems. However, existing techniques either have poor spatial resolution compared to optical microscopy and are hence not generally applicable to imaging of sub-cellular structure (for example, magnetic resonance imaging(1)), or entail operating conditions that preclude application to living biological samples while providing submicrometre resolution (for example, scanning superconducting quantum interference device microscopy(2), electron holography(3) and magnetic resonance force microscopy(4)). Here we demonstrate magnetic imaging of living cells (magnetotactic bacteria) under ambient laboratory conditions and with sub-cellular spatial resolution (400 nanometres), using an optically detected magnetic field imaging array consisting of a nanometre-scale layer of nitrogen-vacancy colour centres implanted at the surface of a diamond chip. With the bacteria placed on the diamond surface, we optically probe the nitrogen-vacancy quantum spin states and rapidly reconstruct images of the vector components of the magnetic field created by chains of magnetic nanoparticles (magnetosomes) produced in the bacteria. We also spatially correlate these magnetic field maps with optical images acquired in the same apparatus. Wide-field microscopy allows parallel optical and magnetic imaging of multiple cells in a population with submicrometre resolution and a field of view in excess of 100 micrometres. Scanning electron microscope images of the bacteria confirm that the correlated optical and magnetic images can be used to locate and characterize the magnetosomes in each bacterium. Our results provide a new capability for imaging bio-magnetic structures in living cells under ambient conditions with high spatial resolution, and will enable the mapping of a wide range of magnetic signals within cells and cellular networks(5,6).
C1 [Le Sage, D.; Glenn, D. R.; Walsworth, R. L.] Harvard Smithsonian Ctr Astrophys, Cambridge, MA 02138 USA.
   [Le Sage, D.; Glenn, D. R.; Lukin, M. D.; Yacoby, A.; Walsworth, R. L.] Harvard Univ, Dept Phys, Cambridge, MA 02138 USA.
   [Arai, K.] MIT, Dept Phys, Cambridge, MA 02139 USA.
   [Glenn, D. R.; Walsworth, R. L.] Harvard Univ, Ctr Brain Sci, Cambridge, MA 02138 USA.
   [DeVience, S. J.] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA.
   [Pham, L. M.] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA.
   [Rahn-Lee, L.; Komeili, A.] Univ Calif Berkeley, Dept Plant & Microbial Biol, Berkeley, CA 94720 USA.
C3 Smithsonian Astrophysical Observatory; Harvard University; Smithsonian Institution; Harvard University; Massachusetts Institute of Technology (MIT); Harvard University; Harvard University; Harvard University; University of California System; University of California Berkeley
RP Walsworth, RL (corresponding author), Harvard Smithsonian Ctr Astrophys, 60 Garden St, Cambridge, MA 02138 USA.
EM rwalsworth@cfa.harvard.edu
FU David and Lucille Packard Foundation Fellowship in Science and Engineering; National Institutes of Health [R01GM084122]; NSF; DARPA QuASAR programme; Direct For Mathematical & Physical Scien; Division Of Physics [0969816] Funding Source: National Science Foundation
NR 32
TC 598
Z9 686
U1 11
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 25
PY 2013
VL 496
IS 7446
BP 486
EP U105
DI 10.1038/nature12072
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 131HU
UT WOS:000317984400037
PM 23619694
DA 2026-03-09
ER

PT J
AU Zhao, SW
   Kumar, R
   Sakai, A
   Vetting, MW
   Wood, BM
   Brown, S
   Bonanno, JB
   Hillerich, BS
   Seidel, RD
   Babbitt, PC
   Almo, SC
   Sweedler, JV
   Gerlt, JA
   Cronan, JE
   Jacobson, MP
AF Zhao, Suwen
   Kumar, Ritesh
   Sakai, Ayano
   Vetting, Matthew W.
   Wood, B. McKay
   Brown, Shoshana
   Bonanno, Jeffery B.
   Hillerich, Brandan S.
   Seidel, Ronald D.
   Babbitt, Patricia C.
   Almo, Steven C.
   Sweedler, Jonathan V.
   Gerlt, John A.
   Cronan, John E.
   Jacobson, Matthew P.
TI Discovery of new enzymes and metabolic pathways by using structure and genome context
SO NATURE
LA English
DT Article
ID proline betaine; enolase superfamily; glycine betaine; paracoccus-denitrificans; sinorhizobium-meliloti; divergent evolution; compatible solutes; protein-production; mass-spectrometry; gene-expression
AB Assigning valid functions to proteins identified in genome projects is challenging: overprediction and database annotation errors are the principal concerns(1). We and others(2) are developing computation-guided strategies for functional discovery with 'metabolite docking' to experimentally derived(3) or homology-based(4) three-dimensional structures. Bacterial metabolic pathways often are encoded by 'genome neighbourhoods' (gene clusters and/or operons), which can provide important clues for functional assignment. We recently demonstrated the synergy of docking and pathway context by 'predicting' the intermediates in the glycolytic pathway in Escherichia coli(5). Metabolite docking to multiple binding proteins and enzymes in the same pathway increases the reliability of in silico predictions of substrate specificities because the pathway intermediates are structurally similar. Here we report that structure-guided approaches for predicting the substrate specificities of several enzymes encoded by a bacterial gene cluster allowed the correct prediction of the in vitro activity of a structurally characterized enzyme of unknown function (PDB 2PMQ), 2-epimerization of trans-4-hydroxy-L-proline betaine (tHyp-B) and cis-4-hydroxy-D-proline betaine (cHyp-B), and also the correct identification of the catabolic pathway in which Hyp-B 2-epimerase participates. The substrate-liganded pose predicted by virtual library screening (docking) was confirmed experimentally. The enzymatic activities in the predicted pathway were confirmed by in vitro assays and genetic analyses; the intermediates were identified by metabolomics; and repression of the genes encoding the pathway by high salt concentrations was established by transcriptomics, confirming the osmolyte role of tHyp-B. This study establishes the utility of structure-guided functional predictions to enable the discovery of new metabolic pathways.
C1 [Zhao, Suwen; Jacobson, Matthew P.] Univ Calif San Francisco, Dept Pharmaceut Chem, San Francisco, CA 94143 USA.
   [Kumar, Ritesh; Sakai, Ayano; Wood, B. McKay; Sweedler, Jonathan V.; Gerlt, John A.; Cronan, John E.] Univ Illinois, Inst Genom Biol, Urbana, IL 61801 USA.
   [Vetting, Matthew W.; Bonanno, Jeffery B.; Hillerich, Brandan S.; Seidel, Ronald D.; Almo, Steven C.] Albert Einstein Coll Med, Dept Biochem, Bronx, NY 10461 USA.
   [Brown, Shoshana; Babbitt, Patricia C.] Univ Calif San Francisco, Dept Bioengn & Therapeut Sci, San Francisco, CA 94143 USA.
   [Sweedler, Jonathan V.; Gerlt, John A.] Univ Illinois, Dept Chem, Urbana, IL 61801 USA.
   [Gerlt, John A.; Cronan, John E.] Univ Illinois, Dept Biochem, Urbana, IL 61801 USA.
   [Cronan, John E.] Univ Illinois, Dept Microbiol, Urbana, IL 61801 USA.
C3 University of California System; University of California San Francisco; University of Illinois System; University of Illinois Urbana-Champaign; Montefiore Medical Center; Albert Einstein College of Medicine; Yeshiva University; University of California System; University of California San Francisco; University of Illinois System; University of Illinois Urbana-Champaign; University of Illinois System; University of Illinois Urbana-Champaign; University of Illinois System; University of Illinois Urbana-Champaign
RP Babbitt, PC (corresponding author), Univ Calif San Francisco, Dept Bioengn & Therapeut Sci, San Francisco, CA 94143 USA.
EM babbitt@cgl.ucsf.edu; steve.almo@einstein.yu.edu; jsweedle@illinois.edu; j-gerlt@illinois.edu; j-cronan@life.uiuc.edu; matt.jacobson@ucsf.edu
FU US National Institutes of Health [U54GM093342, U54GM074945, U54GM094662]; National Institutes of Health [P41-GM103311]; US DOE [DE-AC02-06CH11357]
NR 51
TC 118
Z9 140
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 OCT 31
PY 2013
VL 502
IS 7473
BP 698
EP +
DI 10.1038/nature12576
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 243CC
UT WOS:000326293200051
PM 24056934
DA 2026-03-09
ER

PT J
AU Patterson, D
   Schnell, M
   Doyle, JM
AF Patterson, David
   Schnell, Melanie
   Doyle, John M.
TI Enantiomer-specific detection of chiral molecules via microwave spectroscopy
SO NATURE
LA English
DT Article
ID parity violation; spectrometer; purification; spectrum; samples
AB Chirality plays a fundamental part in the activity of biological molecules and broad classes of chemical reactions, but detecting and quantifying it remains challenging(1). The spectroscopic methods of choice are usually circular dichroism and vibrational circular dichroism, methods that are forbidden in the electric dipole approximation(2). The resultant weak effects produce weak signals, and thus require high sample densities. In contrast, nonlinear techniques probing electric-dipole-allowed effects have been used for sensitive chiral analyses of liquid samples(3-7). Here we extend this class of approaches by carrying out nonlinear resonant phase-sensitive microwave spectroscopy of gas phase samples in the presence of an adiabatically switched non-resonant orthogonal electric field; we use this technique to map the enantiomer-dependent sign of an electric dipole Rabi frequency onto the phase of emitted microwave radiation. We outline theoretically how this results in a sensitive and species-selective method for determining the chirality of cold gas-phase molecules, and implement it experimentally to distinguish between the S and R enantiomers of 1,2-propanediol and their racemic mixture. This technique produces a large and definitive signature of chirality, and has the potential to determine the chirality of multiple species in a mixture.
C1 [Patterson, David; Doyle, John M.] Harvard Univ, Dept Phys, Cambridge, MA 02138 USA.
   [Schnell, Melanie] Ctr Free Elect Laser Sci, D-22607 Hamburg, Germany.
   [Schnell, Melanie] Max Planck Inst Kernphys, D-69117 Heidelberg, Germany.
C3 Harvard University; Max Planck Society
RP Patterson, D (corresponding author), Harvard Univ, Dept Phys, Cambridge, MA 02138 USA.
EM dave@cua.harvard.edu
FU Division Of Physics; Direct For Mathematical & Physical Scien [1125846] Funding Source: National Science Foundation
NR 25
TC 403
Z9 444
U1 4
U2 287
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 23
PY 2013
VL 497
IS 7450
BP 475
EP +
DI 10.1038/nature12150
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 148OG
UT WOS:000319254000044
PM 23698447
DA 2026-03-09
ER

PT J
AU Hondele, M
   Stuwe, T
   Hassler, M
   Halbach, F
   Bowman, A
   Zhang, ET
   Nijmeijer, B
   Kotthoff, C
   Rybin, V
   Amlacher, S
   Hurt, E
   Ladurner, AG
AF Hondele, Maria
   Stuwe, Tobias
   Hassler, Markus
   Halbach, Felix
   Bowman, Andrew
   Zhang, Elisa T.
   Nijmeijer, Bianca
   Kotthoff, Christiane
   Rybin, Vladimir
   Amlacher, Stefan
   Hurt, Ed
   Ladurner, Andreas G.
TI Structural basis of histone H2A-H2B recognition by the essential chaperone FACT
SO NATURE
LA English
DT Article
ID transcript elongation; dna; reveals; binding; domain; spt16; heterodimer; replication; initiation; complex
AB Facilitates chromatin transcription (FACT) is a conserved histone chaperone that reorganizes nucleosomes and ensures chromatin integrity during DNA transcription, replication and repair(1-6). Key to the broad functions of FACT is its recognition of histones H2A-H2B (ref. 2). However, the structural basis for how histones H2A-H2B are recognized and how this integrates with the other functions of FACT, including the recognition of histones H3-H4 and other nuclear factors, is unknown. Here we reveal the crystal structure of the evolutionarily conserved FACT chaperone domain Spt16M from Chaetomium thermophilum, in complex with the H2A-H2B heterodimer. A novel 'U-turn' motif scaffolded onto a Rtt106-like module(7-10) embraces the alpha 1 helix of H2B. Biochemical and in vivo assays validate the structure and dissect the contribution of histone tails and H3-H4 towards Spt16M binding. Furthermore, we report the structure of the FACT heterodimerization domain that connects FACT to replicative polymerases. Our results show that Spt16M makes several interactions with histones, which we suggest allow the module to invade the nucleosome gradually and block the strongest interaction of H2B with DNA. FACT would thus enhance 'nucleosome breathing' by re-organizing the first 30 base pairs of nucleosomal histone-DNA contacts. Our snapshot of the engagement of the chaperone with H2A-H2B and the structures of all globular FACT domains enable the high-resolution analysis of the vital chaperoning functions of FACT, shedding light on how the complex promotes the activity of enzymes that require nucleosome reorganization.
C1 [Hondele, Maria; Hassler, Markus; Bowman, Andrew; Kotthoff, Christiane; Ladurner, Andreas G.] Univ Munich, Butenandt Inst, Dept Physiol Chem, D-81377 Munich, Germany.
   [Hondele, Maria; Hassler, Markus; Bowman, Andrew; Kotthoff, Christiane; Ladurner, Andreas G.] Univ Munich, Fac Med, LMU Biomed Ctr, D-81377 Munich, Germany.
   [Hondele, Maria; Stuwe, Tobias; Hassler, Markus; Zhang, Elisa T.; Nijmeijer, Bianca; Rybin, Vladimir; Ladurner, Andreas G.] European Mol Biol Lab, Genome Biol Unit, D-69117 Heidelberg, Germany.
   [Hondele, Maria; Stuwe, Tobias; Hassler, Markus; Zhang, Elisa T.; Nijmeijer, Bianca; Rybin, Vladimir; Ladurner, Andreas G.] European Mol Biol Lab, Struct & Computat Biol Unit, D-69117 Heidelberg, Germany.
   [Halbach, Felix] Max Planck Inst Biochem, Dept Struct Cell Biol, D-82152 Martinsried, Germany.
   [Amlacher, Stefan; Hurt, Ed] Heidelberg Univ, Biochem Ctr, D-69120 Heidelberg, Germany.
   [Ladurner, Andreas G.] Munich Cluster Syst Neurol SyNergy, D-81377 Munich, Germany.
   [Ladurner, Andreas G.] Ctr Integrated Prot Sci Munich CIPSM, D-81377 Munich, Germany.
C3 University of Munich; University of Munich; European Molecular Biology Laboratory (EMBL); European Molecular Biology Laboratory (EMBL); Max Planck Society; Ruprecht Karls University Heidelberg; University of Munich
RP Ladurner, AG (corresponding author), Univ Munich, Butenandt Inst, Dept Physiol Chem, Butenandtstr 5, D-81377 Munich, Germany.
EM andreas.ladurner@med.lmu.de
FU EMBL; LMU Munich; EC FP6 Marie Curie RTN Chromatin Plasticity; Boehringer Ingelheim Fonds
NR 42
TC 148
Z9 187
U1 0
U2 55
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 4
PY 2013
VL 499
IS 7456
BP 111
EP +
DI 10.1038/nature12242
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 176ED
UT WOS:000321285600044
PM 23698368
DA 2026-03-09
ER

PT J
AU Santini, E
   Huynh, TN
   MacAskill, AF
   Carter, AG
   Pierre, P
   Ruggero, D
   Kaphzan, H
   Klann, E
AF Santini, Emanuela
   Huynh, Thu N.
   MacAskill, Andrew F.
   Carter, Adam G.
   Pierre, Philippe
   Ruggero, Davide
   Kaphzan, Hanoch
   Klann, Eric
TI Exaggerated translation causes synaptic and behavioural aberrations associated with autism
SO NATURE
LA English
DT Article
ID protein-synthesis; inhibition; memory; model; dysfunctions
AB Autism spectrum disorders (ASDs) are an early onset, heterogeneous group of heritable neuropsychiatric disorders with symptoms that include deficits in social interaction skills, impaired communication abilities, and ritualistic-like repetitive behaviours(1,2). One of the hypotheses for a common molecular mechanism underlying ASDs is altered translational control resulting in exaggerated protein synthesis(3). Genetic variants in chromosome 4q, which contains theEIF4E locus, have been described in patients with autism(4,5). Importantly, a rare single nucleotide polymorphism has been identified in autism that is associated with increased promoter activity in the EIF4E gene(6). Here we show that genetically increasing the levels of eukaryotic translation initiation factor 4E (eIF4E) in mice(7) results in exaggerated cap-dependent translation and aberrant behaviours reminiscent of autism, including repetitive and perseverative behaviours and social interaction deficits. Moreover, these autistic-like behaviours are accompanied by synaptic pathophysiology in the medial prefrontal cortex, striatumand hippocampus. The autistic-like behaviours displayed by the eIF4E-transgenic mice are corrected by intracerebroventricular infusions of the cap-dependent translation inhibitor 4EGI-1. Our findings demonstrate a causal relationship between exaggerated cap-dependent translation, synaptic dysfunction and aberrant behaviours associated with autism.
C1 [Santini, Emanuela; Huynh, Thu N.; MacAskill, Andrew F.; Carter, Adam G.; Kaphzan, Hanoch; Klann, Eric] NYU, Ctr Neural Sci, New York, NY 10003 USA.
   [Pierre, Philippe] Aix Marseille Univ, Ctr Immunol Marseille Luminy, F-13288 Marseille, France.
   [Pierre, Philippe] INSERM, U1104, F-13288 Marseille, France.
   [Pierre, Philippe] CNRS, URM 7280, F-13288 Marseille, France.
   [Ruggero, Davide] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, Sch Med, Dept Urol, San Francisco, CA 94143 USA.
C3 New York University; Aix-Marseille Universite; Institut National de la Sante et de la Recherche Medicale (Inserm); Institut National de la Sante et de la Recherche Medicale (Inserm); Aix-Marseille Universite; Centre National de la Recherche Scientifique (CNRS); University of California System; University of California San Francisco; UCSF Medical Center; UCSF Helen Diller Family Comprehensive Cancer Center
RP Klann, E (corresponding author), NYU, Ctr Neural Sci, New York, NY 10003 USA.
EM eklann@cns.nyu.edu
FU National Institutes of Health (NIH) [NS034007, NS047384, NS078718]; Department of Defense CDMRP [W81XWH-11-1-0389]; NIH [CA154916]; Wellcome Trust
NR 38
TC 305
Z9 371
U1 1
U2 90
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 17
PY 2013
VL 493
IS 7432
BP 411
EP U158
DI 10.1038/nature11782
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 071TA
UT WOS:000313615900053
PM 23263185
DA 2026-03-09
ER

PT J
AU Jiang, P
   Du, WJ
   Mancuso, A
   Wellen, KE
   Yang, XL
AF Jiang, Peng
   Du, Wenjing
   Mancuso, Anthony
   Wellen, Kathryn E.
   Yang, Xiaolu
TI Reciprocal regulation of p53 and malic enzymes modulates metabolism and senescence
SO NATURE
LA English
DT Article
ID activated protein-kinase; atp-citrate lyase; cellular senescence; oncogenic ras; premature senescence; insulin-secretion; tumor suppression; cells; restoration; acetylation
AB Cellular senescence both protects multicellular organisms from cancer and contributes to their ageing(1). The pre-eminent tumour suppressor p53 has an important role in the induction and maintenance of senescence, but how it carries out this function remains poorly understood(1-3). In addition, although increasing evidence supports the idea that metabolic changes underlie many cell-fate decisions and p53-mediated tumour suppression, few connections between metabolic enzymes and senescence have been established. Here we describe a new mechanism by which p53 links these functions. We show that p53 represses the expression of the tricarboxylic-acid-cycle-associated malic enzymes ME1 and ME2 in human and mouse cells. Both malic enzymes are important for NADPH production, lipogenesis and glutamine metabolism, but ME2 has a more profound effect. Through the inhibition of malic enzymes, p53 regulates cell metabolism and proliferation. Downregulation of ME1 and ME2 reciprocally activates p53 through distinct MDM2- and AMP-activated protein kinase-mediated mechanisms in a feed-forward manner, bolstering this pathway and enhancing p53 activation. Downregulation of ME1 and ME2 also modulates the outcome of p53 activation, leading to strong induction of senescence, but not apoptosis, whereas enforced expression of either malic enzyme suppresses senescence. Our findings define physiological functions of malic enzymes, demonstrate a positive-feedback mechanism that sustains p53 activation, and reveal a connection between metabolism and senescence mediated by p53.
C1 [Jiang, Peng; Du, Wenjing; Mancuso, Anthony; Wellen, Kathryn E.; Yang, Xiaolu] Univ Penn, Sch Med, Dept Canc Biol, Philadelphia, PA 19104 USA.
   [Jiang, Peng; Du, Wenjing; Mancuso, Anthony; Wellen, Kathryn E.; Yang, Xiaolu] Univ Penn, Sch Med, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA.
C3 University of Pennsylvania; University of Pennsylvania
RP Yang, XL (corresponding author), Univ Penn, Sch Med, Dept Canc Biol, Philadelphia, PA 19104 USA.
EM xyang@mail.med.upenn.edu
FU National Institutes of Health [CA088868]; US Department of Defense [W81XWH-10-1-0468]; National Cancer Institute [P30CA016520] Funding Source: NIH RePORTER
NR 33
TC 418
Z9 497
U1 2
U2 180
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 31
PY 2013
VL 493
IS 7434
BP 689
EP +
DI 10.1038/nature11776
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 080CU
UT WOS:000314219600060
PM 23334421
DA 2026-03-09
ER

PT J
AU Mochizuki, K
   Matsumoto, M
   Ohmine, I
AF Mochizuki, Kenji
   Matsumoto, Masakazu
   Ohmine, Iwao
TI Defect pair separation as the controlling step in homogeneous ice melting
SO NATURE
LA English
DT Article
ID molecular-dynamics; hexagonal ice; water; nucleation; growth; temperature; simulations; stability
AB On being heated, ice melts into liquid water. Although in practice this process tends to be heterogeneous, it can occur homogeneously inside bulk ice(1). The thermally induced homogeneous melting of solids is fairly well understood, and involves the formation and growth of melting nuclei(1-5). But in the case of water, resilient hydrogen bonds render ice melting more complex. We know that the first defects appearing during homogeneous ice melting are pairs of five-and seven-membered rings, which appear and disappear repeatedly and randomly in space and time in the crystalline ice structure(6-8). However, the accumulation of these defects to form an aggregate is nearly additive in energy, and results in a steep free energy increase that suppresses further growth. Here we report molecular dynamics simulations of homogeneous ice melting that identify as a crucial first step not the formation but rather the spatial separation of a defect pair. We find that once it is separated, the defect pair-either an interstitial (I) and a vacancy (V) defect pair (a Frenkel pair), or an L and a D defect pair (a Bjerrum pair)(9) - is entropically stabilized, or 'entangled'. In this state, defects with threefold hydrogen-bond coordination persist and grow, and thereby prepare the system for subsequent rapid melting.
C1 [Mochizuki, Kenji] Grad Univ Adv Studies SOKENDAI, Sch Phys Sci, Okazaki, Aichi 4448585, Japan.
   [Matsumoto, Masakazu] Okayama Univ, Grad Sch Nat Sci & Technol, Okayama 7008530, Japan.
   [Ohmine, Iwao] Natl Inst Nat Sci, Inst Mol Sci, Okazaki, Aichi 4448585, Japan.
C3 Graduate University for Advanced Studies - Japan; Okayama University; National Institutes of Natural Sciences (NINS) - Japan; Institute for Molecular Science (IMS)
RP Mochizuki, K (corresponding author), Grad Univ Adv Studies SOKENDAI, Sch Phys Sci, Okazaki, Aichi 4448585, Japan.
EM kmochi@ims.ac.jp
FU Grants-in-Aid for Scientific Research [24550025] Funding Source: KAKEN
NR 26
TC 60
Z9 65
U1 1
U2 129
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 20
PY 2013
VL 498
IS 7454
BP 350
EP 354
DI 10.1038/nature12190
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 166XI
UT WOS:000320592900037
PM 23783630
DA 2026-03-09
ER

PT J
AU Iqbal, MJ
   Levy, R
   Koop, EJ
   Dekker, JB
   de Jong, JP
   van der Velde, JHM
   Reuter, D
   Wieck, AD
   Aguado, R
   Meir, Y
   van der Wal, CH
AF Iqbal, M. J.
   Levy, Roi
   Koop, E. J.
   Dekker, J. B.
   de Jong, J. P.
   van der Velde, J. H. M.
   Reuter, D.
   Wieck, A. D.
   Aguado, Ramon
   Meir, Yigal
   van der Wal, C. H.
TI Odd and even Kondo effects from emergent localization in quantum point contacts
SO NATURE
LA English
DT Article
ID quantized conductance; dot; transport; signatures; field
AB A quantum point contact (QPC) is a basic nanometre-scale electronic device: a short and narrow transport channel between two electron reservoirs. In clean channels, electron transport is ballistic and the conductance is then quantized as a function of channel width(1,2) with plateaux at integer multiples of 2e(2)/h (where e is the electron charge and h is Planck's constant). This can be understood in a picture where the electron states are propagating waves, without the need to account for electron-electron interactions. Quantized conductance could thus be the signature of ultimate control over nanoscale electron transport. However, even studies with the cleanest QPCs generically show significant anomalies in the quantized conductance traces, and there is consensus that these result from electron many-body effects(3,4). Despite extensive experimental and theoretical studies(4-11), understanding these anomalies is an open problem. Here we report that the many-body effects have their origin in one or more spontaneously localized states that emerge from Friedel oscillations in the electron charge density within the QPC channel. These localized states will have electron spins associated with them, and the Kondo effect-related to electron transport through such localized electron spins-contributes to the formation of the many-body state(5-7). We present evidence for such localization, with Kondo effects of odd or even character, directly reflecting the parity of the number of localized states; the evidence is obtained from experiments with length-tunable QPCs that show a periodic modulation of the many-body properties with Kondo signatures that alternate between odd and even Kondo effects. Our results are of importance for assessing the role of QPCs in more complex hybrid devices(12,13) and for proposals for spintronic and quantum information applications(14,15). In addition, our results show that tunable QPCs offer a versatile platform for investigating many-body effects in nanoscale systems, with the ability to probe such physics at the level of a single site.
C1 [Iqbal, M. J.; Koop, E. J.; Dekker, J. B.; de Jong, J. P.; van der Velde, J. H. M.; van der Wal, C. H.] Univ Groningen, Zernike Inst Adv Mat, NL-9747 AG Groningen, Netherlands.
   [Levy, Roi; Meir, Yigal] Ben Gurion Univ Negev, Dept Phys, IL-84105 Beer Sheva, Israel.
   [Reuter, D.; Wieck, A. D.] Ruhr Univ Bochum, D-44780 Bochum, Germany.
   [Aguado, Ramon] CSIC, ICMM, E-28049 Madrid, Spain.
   [Meir, Yigal] Ben Gurion Univ Negev, Ilse Katz Inst Nanoscale Sci & Technol, IL-84105 Beer Sheva, Israel.
C3 University of Groningen; Ben-Gurion University of the Negev; Ruhr University Bochum; Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Instituto de Ciencia de Materiales de Madrid (ICMM); Ben-Gurion University of the Negev
RP Iqbal, MJ (corresponding author), Univ Groningen, Zernike Inst Adv Mat, NL-9747 AG Groningen, Netherlands.
EM m.j.iqbal@rug.nl; c.h.van.der.wal@rug.nl
FU Research School Ruhr-Universitat Bochum; BMBF QuaHL-Rep [16BQ1035]; Spanish Ministry of Economy and Innovation [FIS2009-08744, FIS2012-33521]; Higher Education Commission of Pakistan; ISF;  [DFG-SPP 1285]
NR 30
TC 68
Z9 73
U1 0
U2 112
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 5
PY 2013
VL 501
IS 7465
BP 79
EP +
DI 10.1038/nature12491
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 211ER
UT WOS:000323888300035
PM 23995683
DA 2026-03-09
ER

PT J
AU Rellergert, WG
   Sullivan, ST
   Schowalter, SJ
   Kotochigova, S
   Chen, K
   Hudson, ER
AF Rellergert, Wade G.
   Sullivan, Scott T.
   Schowalter, Steven J.
   Kotochigova, Svetlana
   Chen, Kuang
   Hudson, Eric R.
TI Evidence for sympathetic vibrational cooling of translationally cold molecules
SO NATURE
LA English
DT Article
ID ions; chemistry; collisions
AB Compared with atoms, molecules have a rich internal structure that offers many opportunities for technological and scientific advancement. The study of this structure could yield critical insights into quantum chemistry(1-3), new methods for manipulating quantum information(4,5), and improved tests of discrete symmetry violation(6,7) and fundamental constant variation(8-10). Harnessing this potential typically requires the preparation of cold molecules in their quantum rovibrational ground state. However, the molecular internal structure severely complicates efforts to produce such samples. Removal of energy stored in long-lived vibrational levels is particularly problematic because optical transitions between vibrational levels are not governed by strict selection rules, which makes laser cooling difficult. Additionally, traditional collisional, or sympathetic, cooling methods are inefficient at quenching molecular vibrational motion(11). Here we experimentally demonstrate that the vibrational motion of trapped BaCl+ molecules is quenched by collisions with ultracold calcium atoms at a rate comparable to the classical scattering, or Langevin, rate. This is over four orders of magnitude more efficient than traditional sympathetic cooling schemes(11). The high cooling rate, a consequence of a strong interaction potential (due to the high polarizability of calcium), along with the low collision energies involved(12), leads to molecular samples with a vibrational ground-state occupancy of at least 90 per cent. Our demonstration uses a novel thermometry technique that relies on relative photodissociation yields. Although the decrease in vibrational temperature is modest, with straightforward improvements it should be possible to produce molecular samples with a vibrational ground-state occupancy greater than 99 per cent in less than 100 milliseconds. Because sympathetic cooling of molecular rotational motion is much more efficient than vibrational cooling in traditional systems, we expect that the method also allows efficient cooling of the rotational motion of the molecules. Moreover, the technique should work for many different combinations of ultracold atoms and molecules.
C1 [Rellergert, Wade G.; Sullivan, Scott T.; Schowalter, Steven J.; Chen, Kuang; Hudson, Eric R.] Univ Calif Los Angeles, Dept Phys & Astron, Los Angeles, CA 90095 USA.
   [Kotochigova, Svetlana] Temple Univ, Dept Phys, Philadelphia, PA 19122 USA.
C3 University of California System; University of California Los Angeles; Pennsylvania Commonwealth System of Higher Education (PCSHE); Temple University
RP Rellergert, WG (corresponding author), Univ Calif Los Angeles, Dept Phys & Astron, Los Angeles, CA 90095 USA.
EM wgr6@ucla.edu
FU ARO [W911NF-10-1-0505]; US NSF [PHY-1005453, PHY-1205311]; AFOSR [FA 9550-11-1-0243]; Direct For Mathematical & Physical Scien; Division Of Physics [1005453, 1255526] Funding Source: National Science Foundation
NR 32
TC 102
Z9 127
U1 5
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 28
PY 2013
VL 495
IS 7442
BP 490
EP +
DI 10.1038/nature11937
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 113QN
UT WOS:000316682800041
PM 23538830
DA 2026-03-09
ER

PT J
AU Xu, K
   Zhang, MH
   Zhao, Q
   Yu, F
   Guo, H
   Wang, CY
   He, FY
   Ding, JP
   Zhang, P
AF Xu, Ke
   Zhang, Minhua
   Zhao, Qin
   Yu, Fang
   Guo, Hui
   Wang, Chengyuan
   He, Fangyuan
   Ding, Jianping
   Zhang, Peng
TI Crystal structure of a folate energy-coupling factor transporter from Lactobacillus brevis
SO NATURE
LA English
DT Article
ID abc transporter; maltose transporter; binding-protein; prokaryotes; mechanism; intermediate; complex
AB ATP-binding cassette (ABC) transporters, composed of importers and exporters, form one of the biggest protein superfamilies that transport a variety of substrates across the membrane, powered by ATP hydrolysis. Most ABC transporters are composed of two transmembrane domains and two cytoplasmic nucleotide-binding domains. Also, importers from prokaryotes usually have extra solute-binding proteins in the periplasm that are responsible for the binding of substrates(1,2). Structures of importers have been reported that suggested a two-state model for the transport mechanism(3-11). Energy-coupling factor (ECF) transporters belong to a new class of ATP-binding cassette importers. Each ECF transporter comprises an energy-coupling module consisting of a transmembrane T protein (EcfT), two nucleotide-binding proteins (EcfA and EcfA'), and another transmembrane substrate-specific binding S protein(12-14) (EcfS). Despite the similarities with ABC transporters, ECF transporters have different organizational and functional properties. The lack of solute-binding proteins in ECF transporters differentiates them clearly from the canonical ABC importers(15). Previously reported structures of the EcfS proteins RibU and ThiT clearly demonstrated the binding site of substrate riboflavin and thiamine, respectively(16,17). However, the organization of the four different components and the transport mechanism of ECF transporters remain unknown. Here we present the structure of an intact folate ECF transporter from Lactobacillus brevis at a resolution of 3 angstrom. This structure was captured in an inward-facing, nucleotide-free conformation with no bound substrate. The folate-binding protein FolT is nearly parallel to the membrane and is bound almost entirely by EcfT, which adopts an L shape and connects to EcfA and EcfA' through two coupling helices. Two conserved XRX motifs from the coupling helices of EcfT have a vital role in energy coupling by docking into EcfA-EcfA'. We propose a transport model that involves a substantial conformational change of FolT.
C1 [Xu, Ke; Zhang, Minhua; Zhao, Qin; Guo, Hui; Wang, Chengyuan; He, Fangyuan; Zhang, Peng] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Plant Physiol & Ecol, Natl Key Lab Plant Mol Genet, Shanghai 200032, Peoples R China.
   [Yu, Fang; Ding, Jianping] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, State Key Lab Mol Biol, Shanghai 200031, Peoples R China.
   [Zhang, Peng] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Plant Physiol & Ecol, CAS Key Lab Synthet Biol, Shanghai 200032, Peoples R China.
C3 Chinese Academy of Sciences; Chinese Academy of Sciences; Center for Excellence in Molecular Cell Science, CAS; Chinese Academy of Sciences
RP Zhang, P (corresponding author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Plant Physiol & Ecol, Natl Key Lab Plant Mol Genet, 300 Fenglin Rd, Shanghai 200032, Peoples R China.
EM pengzhang01@sibs.ac.cn
FU Ministry of Science and Technology of China [2013CB127000]; Shanghai Institutes for Biological Sciences; Chinese Academy of Sciences [2012OHTP, 2009CSP001, 2011KIP101, KSCX2-EW-J-12]; Shanghai 'Pujiang Talent' programme [11PJ1411300]
NR 27
TC 83
Z9 104
U1 0
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 MAY 9
PY 2013
VL 497
IS 7448
BP 268
EP +
DI 10.1038/nature12046
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 139CD
UT WOS:000318558200042
PM 23584589
DA 2026-03-09
ER

PT J
AU Weber, JN
   Peterson, BK
   Hoekstra, HE
AF Weber, Jesse N.
   Peterson, Brant K.
   Hoekstra, Hopi E.
TI Discrete genetic modules are responsible for complex burrow evolution in Peromyscus mice
SO NATURE
LA English
DT Article
ID genome-wide association; architecture; relatedness
AB Relative to morphological traits, we know little about how genetics influence the evolution of complex behavioural differences in nature(1). It is unclear how the environment influences natural variation in heritable behaviour(2), and whether complex behavioural differences evolve through few genetic changes, each affecting many aspects of behaviour, or through the accumulation of several genetic changes that, when combined, give rise to behavioural complexity(3). Here we show that in nature, oldfield mice (Pero-myscus polionotus) build complex burrows with long entrance and escape tunnels, and that burrow length is consistent across populations, although burrow depth varies with soil composition. This burrow architecture is in contrast with the small, simple burrows of its sister species, deer mice (P. maniculatus). When investigated under laboratory conditions, both species recapitulate their natural burrowing behaviour. Genetic crosses between the two species reveal that the derived burrows of oldfield mice are dominant and evolved through the addition of multiple genetic changes. In burrows built by first-generation backcross mice, entrancetunnel length and the presence of an escape tunnel can be uncoupled, suggesting that these traits are modular. Quantitative trait locus analysis also indicates that tunnel length segregates as a complex trait, affected by at least three independent genetic regions, whereas the presence of an escape tunnel is associated with only a single locus. Together, these results suggest that complex behaviours-in this case, a classic 'extended phenotype'(4)-can evolve through multiple genetic changes each affecting distinct behaviour modules.
C1 [Weber, Jesse N.; Peterson, Brant K.; Hoekstra, Hopi E.] Museum Comparat Zool, Dept Organism & Evolutionary Biol, Cambridge, MA 02138 USA.
   [Peterson, Brant K.; Hoekstra, Hopi E.] Ctr Brain Sci, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA.
RP Hoekstra, HE (corresponding author), Museum Comparat Zool, Dept Organism & Evolutionary Biol, 26 Oxford St, Cambridge, MA 02138 USA.
EM hoekstra@oeb.harvard.edu
FU Chapman Funds for Vertebrate Locomotion; National Science Foundation [IOS-0910164]; Arnold and Mabel Beckman Young Investigator Award
NR 34
TC 178
Z9 229
U1 7
U2 348
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 17
PY 2013
VL 493
IS 7432
BP 402
EP U145
DI 10.1038/nature11816
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 071TA
UT WOS:000313615900051
PM 23325221
DA 2026-03-09
ER

PT J
AU Dvinge, H
   Git, A
   Gräf, S
   Salmon-Divon, M
   Curtis, C
   Sottoriva, A
   Zhao, YJ
   Hirst, M
   Armisen, J
   Miska, EA
   Chin, SF
   Provenzano, E
   Turashvili, G
   Green, A
   Ellis, I
   Aparicio, S
   Caldas, C
AF Dvinge, Heidi
   Git, Anna
   Graef, Stefan
   Salmon-Divon, Mali
   Curtis, Christina
   Sottoriva, Andrea
   Zhao, Yongjun
   Hirst, Martin
   Armisen, Javier
   Miska, Eric A.
   Chin, Suet-Feung
   Provenzano, Elena
   Turashvili, Gulisa
   Green, Andrew
   Ellis, Ian
   Aparicio, Sam
   Caldas, Carlos
TI The shaping and functional consequences of the microRNA landscape in breast cancer
SO NATURE
LA English
DT Article
ID gene-expression; estrogen-receptor; messenger-rna; metastasis; reveals; induce; tumors
AB MicroRNAs (miRNAs) show differential expression across breast cancer subtypes, and have both oncogenic and tumour-suppressive roles(1-6). Here we report the miRNA expression profiles of 1,302 breast tumours with matching detailed clinical annotation, long-term follow-up and genomic and messenger RNA expression data(7). This provides a comprehensive overview of the quantity, distribution and variation of the miRNA population and provides information on the extent to which genomic, transcriptional and post-transcriptional events contribute to miRNA expression architecture, suggesting an important role for post-transcriptional regulation. The key clinical parameters and cellular pathways related to the miRNA landscape are characterized, revealing context-dependent interactions, for example with regards to cell adhesion and Wnt signalling. Notably, only prognostic miRNA signatures derived from breast tumours devoid of somatic copy-number aberrations (CNA-devoid) are consistently prognostic across several other subtypes and can be validated in external cohorts. We then use a data-driven approach(8) to seek the effects of miRNAs associated with differential co-expression of mRNAs, and find that miRNAs act as modulators of mRNA-mRNA interactions rather than as on-off molecular switches. We demonstrate such an important modulatory role for miRNAs in the biology of CNA-devoid breast cancers, a common subtype in which the immune response is prominent. These findings represent a new framework for studying the biology of miRNAs in human breast cancer.
C1 [Dvinge, Heidi; Git, Anna; Graef, Stefan; Chin, Suet-Feung; Caldas, Carlos] Canc Res UK Cambridge Inst, Cambridge CB2 0RE, England.
   [Dvinge, Heidi; Git, Anna; Graef, Stefan; Chin, Suet-Feung; Caldas, Carlos] Univ Cambridge, Li Ka Shing Ctr, Dept Oncol, Cambridge CB2 0RE, England.
   [Salmon-Divon, Mali] European Bioinformat Inst, European Mol Biol Lab, Cambridge CB10 1SD, England.
   [Salmon-Divon, Mali] Ariel Univ, Ctr Samaria, Dept Mol Biol, IL-40700 Ariel, Israel.
   [Curtis, Christina; Sottoriva, Andrea] Univ So Calif, Dept Prevent Med, Los Angeles, CA 90033 USA.
   [Zhao, Yongjun; Hirst, Martin] BC Canc Agcy, Genome Sci Ctr, Vancouver, BC V5Z 1L3, Canada.
   [Zhao, Yongjun; Hirst, Martin; Turashvili, Gulisa; Aparicio, Sam] Univ British Columbia, Dept Pathol & Lab Med, Vancouver, BC V6T 2B5, Canada.
   [Armisen, Javier; Miska, Eric A.] Univ Cambridge, Wellcome Trust Canc Res UK Gurdon Inst, Cambridge CB2 1QN, England.
   [Armisen, Javier; Miska, Eric A.] Univ Cambridge, Dept Biochem, Cambridge CB2 1QN, England.
   [Provenzano, Elena; Caldas, Carlos] Cambridge Univ Hosp NHS Fdn Trust, Addenbrookes Hosp, Cambridge Breast Unit, Cambridge CB2 2QQ, England.
   [Provenzano, Elena; Caldas, Carlos] NIHR Cambridge Biomed Res Ctr, Cambridge CB2 2QQ, England.
   [Turashvili, Gulisa; Aparicio, Sam] British Columbia Canc Res Ctr, Vancouver, BC V5Z 1L3, Canada.
   [Green, Andrew; Ellis, Ian] Univ Nottingham, Sch Mol Med Sci, Dept Histopathol, Nottingham NG5 1PB, England.
   [Caldas, Carlos] Cambridge Expt Canc Med Ctr, Cambridge CB2 0RE, England.
C3 Cancer Research UK; CRUK Cambridge Institute; University of Cambridge; CRUK Cambridge Institute; European Molecular Biology Laboratory (EMBL); European Bioinformatics Institute; Ariel University; University of Southern California; British Columbia Cancer Agency; University of British Columbia; University of Cambridge; University of Cambridge; University of Cambridge; Cambridge University Hospitals NHS Foundation Trust; Addenbrooke's Hospital; University of Cambridge; British Columbia Cancer Agency; University of Nottingham
RP Git, A (corresponding author), Canc Res UK Cambridge Inst, Robinson Way, Cambridge CB2 0RE, England.
EM anna.git@cruk.cam.ac.uk; saparicio@bccrc.ca; carlos.caldas@cruk.cam.ac.uk
FU Cancer Research UK; British Columbia Cancer Foundation; University of Cambridge; Hutchinson Whampoa; NIHR Cambridge Biomedical Research Centre; Cambridge Experimental Cancer Medicine Centre; Cancer Research UK [11832, 16942] Funding Source: researchfish; National Institute for Health Research [NF-SI-0611-10154] Funding Source: researchfish
NR 30
TC 345
Z9 391
U1 0
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 16
PY 2013
VL 497
IS 7449
BP 378
EP 382
DI 10.1038/nature12108
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 144PN
UT WOS:000318952000040
PM 23644459
DA 2026-03-09
ER

PT J
AU Toyoshima, C
   Iwasawa, S
   Ogawa, H
   Hirata, A
   Tsueda, J
   Inesi, G
AF Toyoshima, Chikashi
   Iwasawa, Shiho
   Ogawa, Haruo
   Hirata, Ayami
   Tsueda, Junko
   Inesi, Giuseppe
TI Crystal structures of the calcium pump and sarcolipin in the Mg2+-bound E1 state
SO NATURE
LA English
DT Article
ID sarcoplasmic-reticulum; skeletal-muscle; ca2+; phospholamban; binding; atpase; ca2+-atpase; absence; expression; regulator
AB P-type ATPases are ATP-powered ion pumps that establish ion concentration gradients across biological membranes, and are distinct from other ATPases in that the reaction cycle includes an autophosphorylation step. The best studied is Ca2+-ATPase from muscle sarcoplasmic reticulum (SERCA1a), a Ca2+ pump that relaxes muscle cells after contraction, and crystal structures have been determined for most of the reaction intermediates(1,2). An important outstanding structure is that of the El intermediate, which has empty high-affinity Ca2+-binding sites ready to accept new cytosolic Ca2+. In the absence of Ca2+ and at pH 7 or higher, the ATpase is predominantly in El, not in E2 (low affinity for ce(2+), and if millimolar Mg2+ is present, one Mg2+ is expected to occupy one of the Ca2+-binding sites with a millimolar dissociation constant(4,5). This Mg2+ accelerates the reaction cycle(4), not permitting phosphorylation without Ca2+ binding. Here we describe the crystal structure of native SERCA1a (from rabbit) in this El-Mg2+ state at 3.0 A resolution in addition to crystal structures of SERCA1a in E2 free from exogenous inhibitors, and address the structural basis of the activation signal for phosphoryl transfer. Unexpectedly, sarcolipin(6), a small regulatory membrane protein of Ca2+-ATPase, is bound, stabilizing the El Mg2+ state. Sarcolipin is a close homologue of phospholamban, which is a critical mediator of P-adrenergic signal in Ca2+ regulation in heart (for reviews, see, for example, refs 8-10), and seems to play an important role in muscle-based thermogenesis(11). We also determined the crystal structure of recombinant SERCA1a devoid of sarcolipin, and describe the structural basis of inhibition by sarcolipim/phospholamban. Thus, the crystal structures reported here fill a gap in the structural elucidation of the reaction cycle and provide a solid basis for understanding the physiological regulation of the calcium pump.
C1 [Toyoshima, Chikashi; Iwasawa, Shiho; Ogawa, Haruo; Hirata, Ayami; Tsueda, Junko] Univ Tokyo, Inst Mol & Cellular Biosci, Bunkyo Ku, Tokyo 1130032, Japan.
   [Inesi, Giuseppe] Calif Pacific Med Ctr, Res Inst, San Francisco, CA 94107 USA.
C3 University of Tokyo; California Pacific Medical Center; California Pacific Medical Center Research Institute
RP Toyoshima, C (corresponding author), Univ Tokyo, Inst Mol & Cellular Biosci, Bunkyo Ku, Tokyo 1130032, Japan.
EM ct@iam.u-tokyo.ac.jp
FU Ministry of Education, Culture, Sports, Science and Technology of Japan [2009B0025]; Grants-in-Aid for Scientific Research [25650020, 23000014] Funding Source: KAKEN
NR 30
TC 187
Z9 209
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 MAR 14
PY 2013
VL 495
IS 7440
BP 260
EP 264
DI 10.1038/nature11899
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 113FP
UT WOS:000316652300056
PM 23455422
DA 2026-03-09
ER

PT J
AU Burnaevskiy, N
   Fox, TG
   Plymire, DA
   Ertelt, JM
   Weigele, BA
   Selyunin, AS
   Way, SS
   Patrie, SM
   Alto, NM
AF Burnaevskiy, Nikolay
   Fox, Thomas G.
   Plymire, Daniel A.
   Ertelt, James M.
   Weigele, Bethany A.
   Selyunin, Andrey S.
   Way, Sing Sing
   Patrie, Steven M.
   Alto, Neal M.
TI Proteolytic elimination of N-myristoyl modifications by the Shigella virulence factor IpaJ
SO NATURE
LA English
DT Article
ID protein; effector; complex; gtpase; identification; inactivation; autophagy; sequence; glycine; family
AB Protein N-myristoylation is a 14-carbon fatty-acid modification that is conserved across eukaryotic species and occurs on nearly 1% of the cellular proteome(1,2). The ability of the myristoyl group to facilitate dynamic protein-protein and protein-membrane interactions (known as the myristoyl switch) makes it an essential feature of many signal transduction systems(3). Thus pathogenic strategies that facilitate protein demyristoylation would markedly alter the signalling landscape of infected host cells. Here we describe an irreversible mechanism of protein demyristoylation catalysed by invasion plasmid antigen J (IpaJ), a previously uncharacterized Shigella flexneri type III effector protein with cysteine protease activity. A yeast genetic screen for IpaJ substrates identified ADP-ribosylation factor (ARF)1p and ARF2p, small molecular mass GTPases that regulate cargo transport through the Golgi apparatus(4). Mass spectrometry showed that IpaJ cleaved the peptide bond between N-myristoylated glycine-2 and asparagine-3 of human ARF1, thereby providing a new mechanism for host secretory inhibition by a bacterial pathogen(5,6). We further demonstrate that IpaJ cleaves an array of N-myristoylated proteins involved in cellular growth, signal transduction, autophagasome maturation and organelle function. Taken together, these findings show a previously unrecognized pathogenic mechanism for the site-specific elimination of N-myristoyl protein modification.
C1 [Burnaevskiy, Nikolay; Weigele, Bethany A.; Selyunin, Andrey S.; Alto, Neal M.] Univ Texas SW Med Ctr Dallas, Dept Microbiol, Dallas, TX 75390 USA.
   [Fox, Thomas G.] Indiana Univ Sch Med, Sect Pediat Infect Dis, Dept Pediat, Indianapolis, IN 46202 USA.
   [Plymire, Daniel A.; Patrie, Steven M.] Univ Texas SW Med Ctr Dallas, Dept Pathol, Dallas, TX 75390 USA.
   [Ertelt, James M.; Way, Sing Sing] Cincinnati Childrens Hosp Med Ctr, Div Infect Dis, Cincinnati, OH 45229 USA.
C3 University of Texas System; University of Texas Southwestern Medical Center; Indiana University System; Indiana University Bloomington; University of Texas System; University of Texas Southwestern Medical Center; University System of Ohio; University of Cincinnati; Cincinnati Children's Hospital Medical Center
RP Alto, NM (corresponding author), Univ Texas SW Med Ctr Dallas, Dept Microbiol, 5323 Harry Hines Blvd, Dallas, TX 75390 USA.
EM neal.alto@utsouthwestern.edu
FU Cancer Prevention and Research Institute of Texas [RP120613]; Howard Hughes Medical Institute; National Institutes of Health (NIAID) [5T32AI007520, RO1AI083359]; Burroughs Wellcome Fund; National Institutes of Health (NIGMS) [R01GM100486]; Welch Foundation [I-1704]; National Institute of Allergy and Infectious Diseases [T32AI007520, R01AI083359] Funding Source: NIH RePORTER
NR 36
TC 128
Z9 151
U1 2
U2 65
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 4
PY 2013
VL 496
IS 7443
BP 106
EP +
DI 10.1038/nature12004
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 117ZZ
UT WOS:000316993400034
PM 23535599
DA 2026-03-09
ER

PT J
AU Shneider, MM
   Buth, SA
   Ho, BT
   Basler, M
   Mekalanos, JJ
   Leiman, PG
AF Shneider, Mikhail M.
   Buth, Sergey A.
   Ho, Brian T.
   Basler, Marek
   Mekalanos, John J.
   Leiman, Petr G.
TI PAAR-repeat proteins sharpen and diversify the type VI secretion system spike
SO NATURE
LA English
DT Article
ID bacteriophage-t4 baseplate; 3-dimensional structure; vibrio-cholerae; identification; competition; expression; apparatus; software; homology; server
AB The bacterial type VI secretion system (T6SS) is a large multicomponent, dynamic macromolecular machine that has an important role in the ecology of many Gram-negative bacteria. T6SS is responsible for translocation of a wide range of toxic effector molecules, allowing predatory cells to kill both prokaryotic as well as eukaryotic prey cells(1-5). The T6SS organelle is functionally analogous to contractile tails of bacteriophages and is thought to attack cells by initially penetrating them with a trimeric protein complex called the VgrG spike(6,7). Neither the exact protein composition of the T6SS organelle nor the mechanisms of effector selection and delivery are known. Here we report that proteins from the PAAR (proline-alanine-alanine-arginine) repeat superfamily form a sharp conical extension on the VgrG spike, which is further involved in attaching effector domains to the spike. The crystal structures of two PAAR-repeat proteins bound to VgrG-like partners show that these proteins sharpen the tip of the T6SS spike complex. We demonstrate that PAAR proteins are essential for T6SS-mediated secretion and target cell killing by Vibrio cholerae and Acinetobacter baylyi. Our results indicate a new model of the T6SS organelle in which the VgrG-PAAR spike complex is decorated with multiple effectors that are delivered simultaneously into target cells in a single contraction-driven translocation event.
C1 [Shneider, Mikhail M.; Buth, Sergey A.; Leiman, Petr G.] Ecole Polytech Fed Lausanne, CH-1015 Lausanne, Switzerland.
   [Shneider, Mikhail M.] Shemyakin Ovchinnikov Inst Bioorgan Chem, Lab Mol Bioengn, Moscow 117997, Russia.
   [Ho, Brian T.; Basler, Marek; Mekalanos, John J.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA 02115 USA.
C3 Swiss Federal Institutes of Technology Domain; Ecole Polytechnique Federale de Lausanne; Russian Academy of Sciences; Pushchino Scientific Center for Biological Research (PSCBI) of the Russian Academy of Sciences; Institute of Bioorganic Chemistry of the Russian Academy of Sciences; Harvard University; Harvard Medical School
RP Leiman, PG (corresponding author), Ecole Polytech Fed Lausanne, BSP 415, CH-1015 Lausanne, Switzerland.
EM john_mekalanos@hms.harvard.edu; petr.leiman@epfl.ch
FU Swiss National Science Foundation [31003A_127092]; EPFL; NIAID [AI-026289, AI-01845]; Swiss National Science Foundation (SNF) [31003A_127092] Funding Source: Swiss National Science Foundation (SNF)
NR 36
TC 425
Z9 495
U1 3
U2 130
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 15
PY 2013
VL 500
IS 7462
BP 350
EP +
DI 10.1038/nature12453
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 201AF
UT WOS:000323112400036
PM 23925114
DA 2026-03-09
ER

PT J
AU Amaral, M
   Levy, C
   Heyes, DJ
   Lafite, P
   Outeiro, TF
   Giorgini, F
   Leys, D
   Scrutton, NS
AF Amaral, Marta
   Levy, Colin
   Heyes, Derren J.
   Lafite, Pierre
   Outeiro, Tiago F.
   Giorgini, Flaviano
   Leys, David
   Scrutton, Nigel S.
TI Structural basis of kynurenine 3-monooxygenase inhibition
SO NATURE
LA English
DT Article
ID 3-hydroxylase inhibition; endogenous metabolite; quinolinic acid; pathway; model; brain; hydroxylase; microglia; catalysis; flavin
AB Inhibition of kynurenine 3-monooxygenase (KMO), an enzyme in the eukaryotic tryptophan catabolic pathway (that is, kynurenine pathway), leads to amelioration of Huntington's-disease-relevant phenotypes in yeast, fruitfly and mouse models(1-5), as well as in a mouse model of Alzheimer's disease(3). KMO is a flavin adenine dinucleotide (FAD)-dependent monooxygenase and is located in the outer mitochondrial membrane where it converts L-kynurenine to 3-hydroxykynurenine. Perturbations in the levels of kynurenine pathway metabolites have been linked to the pathogenesis of a spectrum of brain disorders(6), as well as cancer(7,8) and several peripheral inflammatory conditions(9). Despite the importance of KMO as a target for neurodegenerative disease, the molecular basis of KMO inhibition by available lead compounds has remained unknown. Here we report the first crystal structure of Saccharomyces cerevisiae KMO, in the free form and in complex with the tight-binding inhibitor UPF 648. UPF 648 binds close to the FAD cofactor and perturbs the local active-site structure, preventing productive binding of the substrate L-kynurenine. Functional assays and targeted mutagenesis reveal that the active-site architecture and UPF 648 binding are essentially identical in human KMO, validating the yeast KMO-UPF 648 structure as a template for structure-based drug design. This will inform the search for new KMO inhibitors that are able to cross the blood-brain barrier in targeted therapies against neurodegenerative diseases such as Huntington's, Alzheimer's and Parkinson's diseases.
C1 [Amaral, Marta; Levy, Colin; Heyes, Derren J.; Leys, David; Scrutton, Nigel S.] Univ Manchester, Manchester Inst Biotechnol, Manchester M1 7DN, Lancs, England.
   [Amaral, Marta; Giorgini, Flaviano] Univ Leicester, Dept Genet, Leicester LE1 7RH, Leics, England.
   [Amaral, Marta; Outeiro, Tiago F.] Inst Mol Med, Cell & Mol Neurosci Unit, P-1659028 Lisbon, Portugal.
   [Amaral, Marta; Outeiro, Tiago F.] Univ Lisbon, Fac Med, Inst Fisiol, P-1649028 Lisbon, Portugal.
   [Lafite, Pierre] Univ Orleans, Inst Chim Organ & Analyt, CNRS, UMR7311, F-45067 Orleans 2, France.
   [Outeiro, Tiago F.] Univ Med Ctr Gottingen, Ctr Nanoscale Microscopy & Mol Physiol Brain, Dept Neurodegenerat & Restorat Res, D-37073 Gottingen, Germany.
C3 University of Manchester; University of Leicester; Universidade de Lisboa; Universidade de Lisboa; Universite de Orleans; Centre National de la Recherche Scientifique (CNRS); University of Gottingen; University of Gottingen Hospital
RP Scrutton, NS (corresponding author), Univ Manchester, Manchester Inst Biotechnol, 131 Princess St, Manchester M1 7DN, Lancs, England.
EM nigel.scrutton@manchester.ac.uk
FU BBSRC [BB/D01963X/1] Funding Source: UKRI; EPSRC [EP/I037253/1, EP/J020192/1] Funding Source: UKRI; Biotechnology and Biological Sciences Research Council [BB/D01963X/1] Funding Source: researchfish; Engineering and Physical Sciences Research Council [EP/J020192/1, EP/I037253/1] Funding Source: researchfish; Biotechnology and Biological Sciences Research Council [BB/D01963X/1] Funding Source: Medline
NR 40
TC 120
Z9 133
U1 2
U2 126
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 18
PY 2013
VL 496
IS 7445
BP 382
EP +
DI 10.1038/nature12039
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 126FV
UT WOS:000317599200042
PM 23575632
DA 2026-03-09
ER

PT J
AU Haroon, MF
   Hu, SH
   Shi, Y
   Imelfort, M
   Keller, J
   Hugenholtz, P
   Yuan, ZG
   Tyson, GW
AF Haroon, Mohamed F.
   Hu, Shihu
   Shi, Ying
   Imelfort, Michael
   Keller, Jurg
   Hugenholtz, Philip
   Yuan, Zhiguo
   Tyson, Gene W.
TI Anaerobic oxidation of methane coupled to nitrate reduction in a novel archaeal lineage
SO NATURE
LA English
DT Article
ID in-situ hybridization; coenzyme-m reductase; oxidizing archaea; bacteria; community; microorganisms; nitrite; genome; metatranscriptomics; methanogenesis
AB Anaerobic oxidation of methane (AOM) is critical for controlling the flux of methane from anoxic environments. AOM coupled to iron(1), manganese(1) and sulphate(2) reduction have been demonstrated in consortia containing anaerobic methanotrophic (ANME) archaea. More recently it has been shown that the bacterium Candidatus 'Methylomirabilis oxyfera' can couple AOM to nitrite reduction through an intra-aerobic methane oxidation pathway(3). Bioreactors capable of AOM coupled to denitrification have resulted in the enrichment of 'M. oxyfera' and a novel ANME lineage, ANME-2d(4,5). However, as 'M. oxyfera' can independently couple AOM to denitrification, the role of ANME-2d in the process is unresolved. Here, a bioreactor fed with nitrate, ammonium and methane was dominated by a single ANME-2d population performing nitrate-driven AOM. Metagenomic, single-cell genomic and metatranscriptomic analyses combined with bioreactor performance and C-13- and N-15-labelling experiments show that ANME-2d is capable of independent AOM through reverse methanogenesis using nitrate as the terminal electron acceptor. Comparative analyses reveal that the genes for nitrate reduction were transferred laterally from a bacterial donor, suggesting selection for this novel process within ANME-2d. Nitrite produced by ANME-2d is reduced to dinitrogen gas through a syntrophic relationship with an anaerobic ammonium-oxidizing bacterium, effectively outcompeting 'M. oxyfera' in the system. We propose the name Candidatus 'Methanoperedens nitror-educens' for the ANME-2d population and the family Candidatus 'Methanoperedenaceae' for the ANME-2d lineage. We predict that 'M. nitroreducens' and other members of the 'Methanoperedenaceae' have an important role in linking the global carbon and nitrogen cycles in anoxic environments.
C1 [Haroon, Mohamed F.; Imelfort, Michael; Hugenholtz, Philip; Tyson, Gene W.] Univ Queensland, Sch Chem & Mol Biosci, Australian Ctr Ecogen, Brisbane, Qld 4072, Australia.
   [Hu, Shihu; Shi, Ying; Imelfort, Michael; Keller, Jurg; Yuan, Zhiguo; Tyson, Gene W.] Univ Queensland, Adv Water Management Ctr, Fac Engn Architecture & Informat Technol, Brisbane, Qld 4072, Australia.
   [Hugenholtz, Philip] Univ Queensland, Inst Mol Biosci, Brisbane, Qld 4072, Australia.
C3 University of Queensland; University of Queensland; University of Queensland
RP Tyson, GW (corresponding author), Univ Queensland, Sch Chem & Mol Biosci, Australian Ctr Ecogen, Brisbane, Qld 4072, Australia.
EM z.yuan@awmc.uq.edu.au; g.tyson@uq.edu.au
FU Australian Research Council (ARC) [DP0666762, DP0987204]; Australian Centre for Ecogenomics; ARC Queen Elizabeth II Fellowship [DP1093175]; ARC Discovery Outstanding Researcher Award [DP120103498]; China Scholarship Council; Australian Research Council [DP0987204, DP0666762] Funding Source: Australian Research Council
NR 47
TC 1071
Z9 1261
U1 36
U2 1638
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 29
PY 2013
VL 500
IS 7464
BP 567
EP +
DI 10.1038/nature12375
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 207TD
UT WOS:000323625900032
PM 23892779
DA 2026-03-09
ER

PT J
AU Zhang, LB
   Prak, L
   Rayon-Estrada, V
   Thiru, P
   Flygare, J
   Lim, B
   Lodish, HF
AF Zhang, Lingbo
   Prak, Lina
   Rayon-Estrada, Violeta
   Thiru, Prathapan
   Flygare, Johan
   Lim, Bing
   Lodish, Harvey F.
TI ZFP36L2 is required for self-renewal of early burst-forming unit erythroid progenitors
SO NATURE
LA English
DT Article
ID glucocorticoid-receptor; transcription factor; differentiation; erythropoietin; proteins; cells; gene; red
AB Stem cells and progenitors in many lineages undergo self-renewing divisions, but the extracellular and intracellular proteins that regulate this process are largely unknown. Glucocorticoids stimulate red blood cell formation by promoting self-renewal of early burst-forming unit-erythroid (BFU-E) progenitors(1-4). Here we show that the RNA-binding protein ZFP36L2 is a transcriptional target of the glucocorticoid receptor (GR) in BFU-Es and is required for BFU-E self-renewal. ZFP36L2 is normally downregulated during erythroid differentiation from the BFU-E stage, but its expression is maintained by all tested GR agonists that stimulate BFU-E self-renewal, and the GR binds to several potential enhancer regions of ZFP36L2. Knockdown of ZFP36L2 in cultured BFU-E cells did not affect the rate of cell division but disrupted glucocorticoid-induced BFU-E self-renewal, and knockdown of ZFP36L2 in transplanted erythroid progenitors prevented expansion of erythroid lineage progenitors normally seen following induction of anaemia by phenylhydrazine treatment. ZFP36L2 preferentially binds to messenger RNAs that are induced or maintained at high expression levels during terminal erythroid differentiation and negatively regulates their expression levels. ZFP36L2 therefore functions as part of a molecular switch promoting BFU-E self-renewal and a subsequent increase in the total numbers of colony-forming unit-erythroid (CFU-E) progenitors and erythroid cells that are generated.
C1 [Zhang, Lingbo; Prak, Lina; Rayon-Estrada, Violeta; Thiru, Prathapan; Flygare, Johan; Lodish, Harvey F.] MIT, Whitehead Inst Biomed Res, Cambridge, MA 02142 USA.
   [Zhang, Lingbo; Prak, Lina; Rayon-Estrada, Violeta; Thiru, Prathapan; Flygare, Johan; Lodish, Harvey F.] MIT, Dept Biol, Cambridge, MA 02142 USA.
   [Zhang, Lingbo; Lim, Bing; Lodish, Harvey F.] Singapore Massachusetts Inst Technol Alliance, Singapore 117576, Singapore.
   [Zhang, Lingbo; Lim, Bing] ASTAR, Genome Inst Singapore, Singapore 138627, Singapore.
   [Lim, Bing] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA.
C3 Massachusetts Institute of Technology (MIT); Whitehead Institute; Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); National University of Singapore; Nanyang Technological University; Agency for Science Technology & Research (A*STAR); A*STAR - Genome Institute of Singapore (GIS); Harvard University; Harvard University Medical Affiliates; Beth Israel Deaconess Medical Center; Harvard Medical School
RP Lodish, HF (corresponding author), MIT, Whitehead Inst Biomed Res, Cambridge, MA 02142 USA.
EM lodish@wi.mit.edu
FU NIH [P01 HL 32262]; Singapore-Massachusetts Institute of Technology Alliance; National Cancer Institute [P30CA014051] Funding Source: NIH RePORTER; National Heart Lung and Blood Institute [P01HL032262] Funding Source: NIH RePORTER
NR 22
TC 94
Z9 120
U1 0
U2 28
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 4
PY 2013
VL 499
IS 7456
BP 92
EP +
DI 10.1038/nature12215
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 176ED
UT WOS:000321285600040
PM 23748442
DA 2026-03-09
ER

PT J
AU Pearson, JS
   Giogha, C
   Ong, SY
   Kennedy, CL
   Kelly, M
   Robinson, KS
   Lung, TWF
   Mansell, A
   Riedmaier, P
   Oates, CVL
   Zaid, A
   Mühlen, S
   Crepin, VF
   Marches, O
   Ang, CS
   Williamson, NA
   O'Reilly, LA
   Bankovacki, A
   Nachbur, U
   Infusini, G
   Webb, AI
   Silke, J
   Strasser, A
   Frankel, G
   Hartland, EL
AF Pearson, Jaclyn S.
   Giogha, Cristina
   Ong, Sze Ying
   Kennedy, Catherine L.
   Kelly, Michelle
   Robinson, Keith S.
   Lung, Tania Wong Fok
   Mansell, Ashley
   Riedmaier, Patrice
   Oates, Clare V. L.
   Zaid, Ali
   Muehlen, Sabrina
   Crepin, Valerie F.
   Marches, Olivier
   Ang, Ching-Seng
   Williamson, Nicholas A.
   O'Reilly, Lorraine A.
   Bankovacki, Aleksandra
   Nachbur, Ueli
   Infusini, Giuseppe
   Webb, Andrew I.
   Silke, John
   Strasser, Andreas
   Frankel, Gad
   Hartland, Elizabeth L.
TI A type III effector antagonizes death receptor signalling during bacterial gut infection
SO NATURE
LA English
DT Article
ID apoptosis; virulence; proteins; roles; nleb
AB Successful infection by enteric bacterial pathogens depends on the ability of the bacteria to colonize the gut, replicate in host tissues and disseminate to other hosts. Pathogens such as Salmonella, Shigella and enteropathogenic and enterohaemorrhagic (EPEC and EHEC, respectively) Escherichia coli use a type III secretion system(T3SS) to deliver virulence effector proteins into host cells during infection that promote colonization and interfere with antimicrobial host responses(1-3). Here we report that the T3SS effector NleB1 from EPEC binds to host cell death-domain-containing proteins and thereby inhibits death receptor signalling. Protein interaction studies identified FADD, TRADD and RIPK1 as binding partners of NleB1. NleB1 expressed ectopically or injected by the bacterial T3SS prevented Fas ligand or TNF-induced formation of the canonical death-inducing signalling complex (DISC) and proteolytic activation of caspase-8, an essential step in death-receptor-induced apoptosis. This inhibition depended on the N-acetylglucosamine transferase activity of NleB1, which specifically modified Arg 117 in the death domain of FADD. The importance of the death receptor apoptotic pathway to host defence was demonstrated using mice deficient in the FAS signalling pathway, which showed delayed clearance of the EPEC-like mouse pathogen Citrobacter rodentium and reversion to virulence of an nleB mutant. The activity of NleB suggests that EPEC and other attaching and effacing pathogens antagonize death-receptor-induced apoptosis of infected cells, thereby blocking a major antimicrobial host response.
C1 [Pearson, Jaclyn S.; Giogha, Cristina; Ong, Sze Ying; Kennedy, Catherine L.; Kelly, Michelle; Lung, Tania Wong Fok; Riedmaier, Patrice; Oates, Clare V. L.; Zaid, Ali; Muehlen, Sabrina; Hartland, Elizabeth L.] Univ Melbourne, Dept Microbiol & Immunol, Melbourne, Vic 3010, Australia.
   [Robinson, Keith S.; Crepin, Valerie F.; Frankel, Gad] Univ London Imperial Coll Sci Technol & Med, MRC Ctr Mol Bacteriol & Infect, Dept Life Sci, London SW7 2AZ, England.
   [Mansell, Ashley] Monash Inst Med Res, Ctr Innate Immun & Infect Dis, Melbourne, Vic 3010, Australia.
   [Marches, Olivier] Queen Mary Univ London, Barts & London Sch Med & Dent, Blizard Inst, Ctr Immunol & Infect Dis, London E1 2AT, England.
   [Ang, Ching-Seng; Williamson, Nicholas A.] Univ Melbourne, Mol Sci & Biotechnol Inst Bio21, Melbourne, Vic 3010, Australia.
   [O'Reilly, Lorraine A.; Bankovacki, Aleksandra; Nachbur, Ueli; Infusini, Giuseppe; Webb, Andrew I.; Silke, John; Strasser, Andreas] Walter & Eliza Hall Inst Med Res, Parkville, Vic 3052, Australia.
   [O'Reilly, Lorraine A.; Webb, Andrew I.; Silke, John; Strasser, Andreas] Univ Melbourne, Dept Med Biol, Melbourne, Vic 3010, Australia.
   [Hartland, Elizabeth L.] Royal Childrens Hosp, Murdoch Childrens Res Inst, Parkville, Vic 3052, Australia.
C3 University of Melbourne; Imperial College London; University of London; Queen Mary University London; University of Melbourne; Walter & Eliza Hall Institute; University of Melbourne; Royal Children's Hospital Melbourne; Murdoch Children's Research Institute
RP Hartland, EL (corresponding author), Univ Melbourne, Dept Microbiol & Immunol, Melbourne, Vic 3010, Australia.
EM hartland@unimelb.edu.au
FU Australian National Health and Medical Research Council [606788, 637332, 1009145]; Wellcome Trust; Juvenile Diabetes Foundation; Leukaemia; Lymphoma Society (New York; SCOR grant) [7413]; Australian Research Council Future Fellowship; Australian Postgraduate Awards; MRC [MR/J006874/1] Funding Source: UKRI; Medical Research Council [MR/J006874/1] Funding Source: researchfish; National Health and Medical Research Council (NHMRC) [637332, 1009145] Funding Source: National Health and Medical Research Council (NHMRC)
NR 24
TC 230
Z9 266
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 SEP 12
PY 2013
VL 501
IS 7466
BP 247
EP +
DI 10.1038/nature12524
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 215XR
UT WOS:000324244900046
PM 24025841
DA 2026-03-09
ER

PT J
AU Johnston, SE
   Gratten, J
   Berenos, C
   Pilkington, JG
   Clutton-Brock, TH
   Pemberton, JM
   Slate, J
AF Johnston, Susan E.
   Gratten, Jacob
   Berenos, Camillo
   Pilkington, Jill G.
   Clutton-Brock, Tim H.
   Pemberton, Josephine M.
   Slate, Jon
TI Life history trade-offs at a single locus maintain sexually selected genetic variation
SO NATURE
LA English
DT Article
ID antagonistic selection; population; weaponry; fitness; polymorphism; association; resistance; reveals; capture
AB Sexual selection, through intra-male competition or female choice, is assumed to be a source of strong and sustained directional selection in the wild(1,2). In the presence of such strong directional selection, alleles enhancing a particular trait are predicted to become fixed within a population, leading to a decrease in the underlying genetic variation(3). However, there is often considerable genetic variation underlying sexually selected traits in wild populations, and consequently, this phenomenon has become a long-discussed issue in the field of evolutionary biology(1,4,5). In wild Soay sheep, large horns confer an advantage in strong intra-sexual competition, yet males show an inherited polymorphism for horn type and have substantial genetic variation in their horn size(6). Here we show that most genetic variation in this trait is maintained by a trade-off between natural and sexual selection at a single gene, relaxin-like receptor 2 (RXFP2). We found that an allele conferring larger horns, Ho+, is associated with higher reproductive success, whereas a smaller horn allele, Ho-P, confers increased survival, resulting in a net effect of overdominance (that is, heterozygote advantage) for fitness at RXFP2. The nature of this trade-off is simple relative to commonly proposed explanations for the maintenance of sexually selected traits, such as genic capture(7,8) ('good genes') and sexually antagonistic selection(5,9). Our results demonstrate that by identifying the genetic architecture of trait variation, we can determine the principal mechanisms maintaining genetic variation in traits under strong selection and explain apparently counter-evolutionary observations.
C1 [Johnston, Susan E.; Gratten, Jacob; Slate, Jon] Univ Sheffield, Dept Anim & Plant Sci, Sheffield S10 2TN, S Yorkshire, England.
   [Johnston, Susan E.; Berenos, Camillo; Pilkington, Jill G.; Pemberton, Josephine M.] Univ Edinburgh, Inst Evolutionary Biol, Edinburgh EH9 3JT, Midlothian, Scotland.
   [Gratten, Jacob] Univ Queensland, Queensland Brain Inst, Brisbane, Qld 4072, Australia.
   [Clutton-Brock, Tim H.] Univ Cambridge, Dept Zool, Cambridge CB2 3EJ, England.
C3 University of Sheffield; University of Edinburgh; University of Queensland; University of Cambridge
RP Johnston, SE (corresponding author), Univ Edinburgh, Inst Evolutionary Biol, Edinburgh EH9 3JT, Midlothian, Scotland.
EM Susan.Johnston@ed.ac.uk; j.slate@shef.ac.uk
FU Natural Environment Research Council (NERC); NERC; European Research Council (ERC); Biotechnology and Biological Sciences Research Council CASE studentship; Natural Environment Research Council [NE/B504314/1, NE/G004854/1] Funding Source: researchfish; NERC [NE/G004854/1] Funding Source: UKRI
NR 34
TC 245
Z9 269
U1 2
U2 298
PU NATURE PUBLISHING 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 3
PY 2013
VL 502
IS 7469
BP 93
EP +
DI 10.1038/nature12489
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 227IM
UT WOS:000325106000037
PM 23965625
DA 2026-03-09
ER

PT J
AU Hatzivassiliou, G
   Haling, JR
   Chen, HF
   Song, K
   Price, S
   Heald, R
   Hewitt, JFM
   Zak, M
   Peck, A
   Orr, C
   Merchant, M
   Hoeflich, KP
   Chan, J
   Luoh, SM
   Anderson, DJ
   Ludlam, MJC
   Wiesmann, C
   Ultsch, M
   Friedman, LS
   Malek, S
   Belvin, M
AF Hatzivassiliou, Georgia
   Haling, Jacob R.
   Chen, Huifen
   Song, Kyung
   Price, Steve
   Heald, Robert
   Hewitt, Joanne F. M.
   Zak, Mark
   Peck, Ariana
   Orr, Christine
   Merchant, Mark
   Hoeflich, Klaus P.
   Chan, Jocelyn
   Luoh, Shiuh-Ming
   Anderson, Daniel J.
   Ludlam, Mary J. C.
   Wiesmann, Christian
   Ultsch, Mark
   Friedman, Lori S.
   Malek, Shiva
   Belvin, Marcia
TI Mechanism of MEK inhibition determines efficacy in mutant KRAS- versus BRAF-driven cancers
SO NATURE
LA English
DT Article
ID wild-type; kinase activation; c-raf; b-raf; mutations; pathways; pi3k
AB KRAS and BRAF activating mutations drive tumorigenesis through constitutive activation of the MAPK pathway. As these tumours represent an area of high unmet medical need, multiple allosteric MEK inhibitors, which inhibit MAPK signalling in both genotypes, are being tested in clinical trials. Impressive single-agent activity in BRAF-mutant melanoma has been observed; however, efficacy has been far less robust in KRAS-mutant disease(1). Here we show that, owing to distinct mechanisms regulating MEK activation in KRAS-versus BRAF-driven tumours(2,3), different mechanisms of inhibition are required for optimal antitumour activity in each genotype. Structural and functional analysis illustrates that MEK inhibitors with superior efficacy in KRAS-driven tumours (GDC-0623 and G-573, the former currently in phase I clinical trials) form a strong hydrogen-bond interaction with S212 in MEK that is critical for blocking MEK feedback phosphorylation by wild-type RAF. Conversely, potent inhibition of active, phosphorylated MEK is required for strong inhibition of the MAPK pathway in BRAF-mutant tumours, resulting in superior efficacy in this genotype with GDC-0973 (also known as cobimetinib), a MEK inhibitor currently in phase III clinical trials. Our study highlights that differences in the activation state of MEK in KRAS-mutant tumours versus BRAF-mutant tumours can be exploited through the design of inhibitors that uniquely target these distinct activation states of MEK. These inhibitors are currently being evaluated in clinical trials to determine whether improvements in therapeutic index within KRAS versus BRAF preclinical models translate to improved clinical responses in patients.
C1 [Hatzivassiliou, Georgia; Song, Kyung; Orr, Christine; Merchant, Mark; Hoeflich, Klaus P.; Chan, Jocelyn; Luoh, Shiuh-Ming; Friedman, Lori S.; Belvin, Marcia] Genentech Inc, Dept Translat Oncol, San Francisco, CA 94080 USA.
   [Haling, Jacob R.; Peck, Ariana; Malek, Shiva] Genentech Inc, Dept Biochem & Cellular Pharmacol, San Francisco, CA 94080 USA.
   [Chen, Huifen; Zak, Mark] Genentech Inc, Dept Discovery Chem, San Francisco, CA 94080 USA.
   [Price, Steve; Heald, Robert; Hewitt, Joanne F. M.] Argenta, Harlow CM19 5TR, Essex, England.
   [Anderson, Daniel J.; Ludlam, Mary J. C.] Genentech Inc, Dept Discovery Oncol, San Francisco, CA 94080 USA.
   [Wiesmann, Christian; Ultsch, Mark] Genentech Inc, Dept Biol Struct, San Francisco, CA 94080 USA.
C3 Roche Holding; Genentech; Roche Holding USA; Roche Holding; Genentech; Roche Holding USA; Roche Holding; Roche Holding USA; Genentech; Roche Holding; Roche Holding USA; Genentech; Roche Holding; Genentech; Roche Holding USA
RP Belvin, M (corresponding author), Genentech Inc, Dept Translat Oncol, 1 DNA Way, San Francisco, CA 94080 USA.
EM hatzivassiliou.georgia@gene.com; belvin.marcia@gene.com
FU Department of Energy; National Institutes of Health; National Institute of General Medical Sciences; National Center for Research Resources
NR 29
TC 256
Z9 311
U1 0
U2 89
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 12
PY 2013
VL 501
IS 7466
BP 232
EP 236
DI 10.1038/nature12441
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 215XR
UT WOS:000324244900043
PM 23934108
DA 2026-03-09
ER

PT J
AU Liu, B
   Baskin, RJ
   Kowalczykowski, SC
AF Liu, Bian
   Baskin, Ronald J.
   Kowalczykowski, Stephen C.
TI DNA unwinding heterogeneity by RecBCD results from static molecules able to equilibrate
SO NATURE
LA English
DT Article
ID recombination hotspot chi; single-molecule; enzyme; recognition; translocation; helicase; protein; energy; dynamics; motor
AB Single-molecule studies can overcome the complications of asynchrony and ensemble-averaging in bulk-phase measurements, provide mechanistic insights into molecular activities, and reveal interesting variations between individual molecules(1-3). The application of these techniques to the RecBCD helicase of Escherichia coli has resolved some long-standing discrepancies, and has provided otherwise unattainable mechanistic insights into its enzymatic behaviour(4-6). Enigmatically, the DNA unwinding rates of individual enzyme molecules are seen to vary considerably(6-8), but the origin of this heterogeneity remains unknown. Here we investigate the physical basis for this behaviour. Although any individual RecBCD molecule unwound DNA at a constant rate for an average of approximately 30,000 steps, we discover that transiently halting a single enzyme-DNA complex by depleting Mg2+-ATP could change the subsequent rates of DNA unwinding by that enzyme after reintroduction to ligand. The proportion of molecules that changed rate increased exponentially with the duration of the interruption, with a half-life of approximately 1 second, suggesting that a conformational change occurred during the time that the molecule was arrested. The velocity after pausing an individual molecule was any velocity found in the starting distribution of the ensemble. We suggest that substrate binding stabilizes the enzyme in one of many equilibrium conformational sub-states that determine the rate-limiting translocation behaviour of each RecBCD molecule. Each stabilized sub-state can persist for the duration (approximately 1 minute) of processive unwinding of a DNA molecule, comprising tens of thousands of catalytic steps, each of which is much faster than the time needed for the conformational change required to alter kinetic behaviour. This ligand-dependent stabilization of rate-defining conformational sub-states results in seemingly static molecule-to-molecule variation in RecBCD helicase activity, but in fact reflects one microstate from the equilibrium ensemble that a single molecule manifests during an individual processive translocation event.
C1 [Liu, Bian; Kowalczykowski, Stephen C.] Univ Calif Davis, Dept Microbiol & Mol Genet, Davis, CA 95616 USA.
   [Liu, Bian; Baskin, Ronald J.; Kowalczykowski, Stephen C.] Univ Calif Davis, Dept Mol & Cellular Biol, Davis, CA 95616 USA.
   [Liu, Bian; Kowalczykowski, Stephen C.] Univ Calif Davis, Biophys 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 & Mol Genet, Davis, CA 95616 USA.
EM sckowalczykowski@ucdavis.edu
FU National Institutes of Health [GM-62653, GM-64745]
NR 35
TC 68
Z9 81
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 AUG 22
PY 2013
VL 500
IS 7463
BP 482
EP +
DI 10.1038/nature12333
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 203TJ
UT WOS:000323316100040
PM 23851395
DA 2026-03-09
ER

PT J
AU Wilson, MA
   Kwon, Y
   Xu, YY
   Chung, WH
   Chi, P
   Niu, HY
   Mayle, R
   Chen, XF
   Malkova, A
   Sung, P
   Ira, G
AF Wilson, Marenda A.
   Kwon, YoungHo
   Xu, Yuanyuan
   Chung, Woo-Hyun
   Chi, Peter
   Niu, Hengyao
   Mayle, Ryan
   Chen, Xuefeng
   Malkova, Anna
   Sung, Patrick
   Ira, Grzegorz
TI Pif1 helicase and Polδ promote recombination-coupled DNA synthesis via bubble migration
SO NATURE
LA English
DT Article
ID break-induced replication; saccharomyces-cerevisiae; polymerase-delta; homologous recombination; rad51-mediated recombination; mitotic recombination; half-crossovers; yeast; proteins; rad51
AB During DNA repair by homologous recombination (HR), DNA synthesis copies information from a template DNA molecule. Multiple DNA polymerases have been implicated in repair-specific DNA synthesis(1-3), but it has remained unclear whether a DNA helicase is involved in this reaction. A good candidate DNA helicase is Pif1, an evolutionarily conserved helicase in Saccharomyces cerevisiae important for break-induced replication (BIR)(4) as well as HR-dependent telomere maintenance in the absence of telomerase(5) found in 10-15% of all cancers(6). Pif1 has a role in DNA synthesis across hard-to-replicate sites(7,8) and in lagging-strand synthesis with polymerase delta (Pol delta)(9-11). Here we provide evidence that Pif1 stimulates DNA synthesis during BIR and crossover recombination. The initial steps of BIR occur normally in Pif1-deficient cells, but Pol delta recruitment and DNA synthesis are decreased, resulting in premature resolution of DNA intermediates into half-crossovers. Purified Pif1 protein strongly stimulates Pol delta-mediated DNA synthesis from a D-loop made by the Rad51 recombinase. Notably, Pif1 liberates the newly synthesized strand to prevent the accumulation of topological constraint and to facilitate extensive DNA synthesis via the establishment of a migrating D-loop structure. Our results uncover a novel function of Pif1 and provide insights into the mechanism of HR.
C1 [Wilson, Marenda A.; Chung, Woo-Hyun; Mayle, Ryan; Chen, Xuefeng; Ira, Grzegorz] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA.
   [Kwon, YoungHo; Xu, Yuanyuan; Niu, Hengyao; Sung, Patrick] Yale Univ, Sch Med, Dept Mol Biophys & Biochem, New Haven, CT 06520 USA.
   [Chung, Woo-Hyun] Duksung Womens Univ, Coll Pharm, Seoul 132714, South Korea.
   [Chi, Peter] Natl Taiwan Univ, Inst Biochem Sci, Taipei 10617, Taiwan.
   [Chi, Peter] Acad Sinica, Inst Biol Chem, Taipei 115, Taiwan.
   [Malkova, Anna] IUPUI, Sch Sci, Dept Biol, Indianapolis, IN 46202 USA.
C3 Baylor College of Medicine; Yale University; Duksung Women's University; National Taiwan University; Academia Sinica - Taiwan; Indiana University System; Indiana University Indianapolis
RP Ira, G (corresponding author), Baylor Coll Med, Dept Mol & Human Genet, 1 Baylor Plaza, Houston, TX 77030 USA.
EM patrick.sung@yale.edu; gira@bcm.edu
FU US National Institutes of Health [GM080600, ES007061, GM057814, ES015632, GM084242, T32GM07526-34]; National Research Foundation of Korea [NRF-2012R1A1A1009917]; Academia Sinica; National Taiwan University; National Science Council of Taiwan; National Institute of Environmental Health Sciences [R01ES007061] Funding Source: NIH RePORTER; National Institute of General Medical Sciences [R01GM080600, T32GM007526] Funding Source: NIH RePORTER
NR 38
TC 259
Z9 323
U1 0
U2 67
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 17
PY 2013
VL 502
IS 7471
BP 393
EP +
DI 10.1038/nature12585
PG 20
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 235GY
UT WOS:000325706300058
PM 24025768
DA 2026-03-09
ER

PT J
AU Axelsson, E
   Ratnakumar, A
   Arendt, ML
   Maqbool, K
   Webster, MT
   Perloski, M
   Liberg, O
   Arnemo, JM
   Hedhammar, Å
   Lindblad-Toh, K
AF Axelsson, Erik
   Ratnakumar, Abhirami
   Arendt, Maja-Louise
   Maqbool, Khurram
   Webster, Matthew T.
   Perloski, Michele
   Liberg, Olof
   Arnemo, Jon M.
   Hedhammar, Ake
   Lindblad-Toh, Kerstin
TI The genomic signature of dog domestication reveals adaptation to a starch-rich diet
SO NATURE
LA English
DT Article
ID maltase-glucoamylase gene; glucose; transporters; selection; history; sperm
AB The domestication of dogs. was an important episode in the development of human civilization. The precise timing and location of this event is debated(1-5) and little is known about the genetic changes that accompanied the transformation of ancient wolves into domestic dogs. Here we conduct whole-genome resequencimg of dogs and wolves to identify 3.8 million genetic variants used to identify 36 genomic regions that probably represent targets for selection during dog domestication. Nineteen of these regions contain genes important in brain function, eight of which belong to nervous system development pathways and potentially underlie behavioural changes central to dog domestication(6). Ten genes with key roles in starch digestion and fat metabolism also show signals of selection. We identify candidate mutations in key genes and provide functional support for an increased starch digestion in dogs relative to wolves. Our results indicate that novel adaptations allowing the early ancestors of modern dogs to thrive on a diet rich in starch, relative to the carnivorous diet of wolves, constituted a crucial step in the early domestication of dogs.
C1 [Axelsson, Erik; Ratnakumar, Abhirami; Arendt, Maja-Louise; Maqbool, Khurram; Webster, Matthew T.; Lindblad-Toh, Kerstin] Uppsala Univ, Dept Med Biochem & Microbiol, Sci Life Lab, S-75237 Uppsala, Sweden.
   [Perloski, Michele; Lindblad-Toh, Kerstin] Broad Inst Massachusetts Inst Technol & Harvard, Cambridge, MA 02139 USA.
   [Liberg, Olof] Swedish Univ Agr Sci, Dept Ecol, Grimso Wildlife Res Stn, S-73091 Riddarhyttan, Sweden.
   [Arnemo, Jon M.] Hedmark Univ Coll, Fac Appl Ecol & Agr Sci, Dept Forestry & Wildlife Management, NO-2418 Elverum, Norway.
   [Arnemo, Jon M.] Swedish Univ Agr Sci, Fac Forest Sci, Dept Wildlife Fish & Environm Studies, S-90183 Umea, Sweden.
   [Hedhammar, Ake] Swedish Univ Agr Sci, Dept Clin Sci, Sci Life Lab, S-75651 Uppsala, Sweden.
C3 Uppsala University; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Swedish University of Agricultural Sciences; Inland Norway University of Applied Sciences; Swedish University of Agricultural Sciences; Swedish University of Agricultural Sciences
RP Axelsson, E (corresponding author), Uppsala Univ, Dept Med Biochem & Microbiol, Sci Life Lab, S-75237 Uppsala, Sweden.
EM Erik.Axelsson@imbim.uu.se; kersli@broadinstitute.org
FU SSF; Swedish Research Council; Swedish Research Council Formas; Uppsala University; EURYI; ESF; Higher Education Commission, Pakistan
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NR 30
TC 705
Z9 843
U1 10
U2 717
PU NATURE PUBLISHING 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 21
PY 2013
VL 495
IS 7441
BP 360
EP 364
DI 10.1038/nature11837
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 113EY
UT WOS:000316650500041
PM 23354050
DA 2026-03-09
ER

PT J
AU Kim, HJ
   Kim, NC
   Wang, YD
   Scarborough, EA
   Moore, J
   Diaz, Z
   MacLea, KS
   Freibaum, B
   Li, SQ
   Molliex, A
   Kanagaraj, AP
   Carter, R
   Boylan, KB
   Wojtas, AM
   Rademakers, R
   Pinkus, JL
   Greenberg, SA
   Trojanowski, JQ
   Traynor, BJ
   Smith, BN
   Topp, S
   Gkazi, AS
   Miller, J
   Shaw, CE
   Kottlors, M
   Kirschner, J
   Pestronk, A
   Li, YR
   Ford, AF
   Gitler, AD
   Benatar, M
   King, OD
   Kimonis, VE
   Ross, ED
   Weihl, CC
   Shorter, J
   Taylor, JP
AF Kim, Hong Joo
   Kim, Nam Chul
   Wang, Yong-Dong
   Scarborough, Emily A.
   Moore, Jennifer
   Diaz, Zamia
   MacLea, Kyle S.
   Freibaum, Brian
   Li, Songqing
   Molliex, Amandine
   Kanagaraj, Anderson P.
   Carter, Robert
   Boylan, Kevin B.
   Wojtas, Aleksandra M.
   Rademakers, Rosa
   Pinkus, Jack L.
   Greenberg, Steven A.
   Trojanowski, John Q.
   Traynor, Bryan J.
   Smith, Bradley N.
   Topp, Simon
   Gkazi, Athina-Soragia
   Miller, Jack
   Shaw, Christopher E.
   Kottlors, Michael
   Kirschner, Janbernd
   Pestronk, Alan
   Li, Yun R.
   Ford, Alice Flynn
   Gitler, Aaron D.
   Benatar, Michael
   King, Oliver D.
   Kimonis, Virginia E.
   Ross, Eric D.
   Weihl, Conrad C.
   Shorter, James
   Taylor, J. Paul
TI Mutations in prion-like domains in hnRNPA2B1 and hnRNPA1 cause multisystem proteinopathy and ALS
SO NATURE
LA English
DT Article
ID amyotrophic-lateral-sclerosis; rna-binding proteins; drosophila model; saccharomyces-cerevisiae; frontotemporal dementia; multiple alignment; stress granules; vcp mutations; tdp-43; disease
AB Algorithms designed to identify canonical yeast prions predict that around 250 human proteins, including several RNA-binding proteins associated with neurodegenerative disease, harbour a distinctive prion-like domain (PrLD) enriched in uncharged polar amino acids and glycine. PrLDs in RNA-binding proteins are essential for the assembly of ribonucleoprotein granules. However, the interplay between human PrLD function and disease is not understood. Here we define pathogenic mutations in PrLDs of heterogeneous nuclear ribonucleoproteins (hnRNPs) A2B1 and A1 in families with inherited degeneration affecting muscle, brain, motor neuron and bone, and in one case of familial amyotrophic lateral sclerosis. Wild-type hnRNPA2 (the most abundant isoform of hnRNPA2B1) and hnRNPA1 show an intrinsic tendency to assemble into self-seeding fibrils, which is exacerbated by the disease mutations. Indeed, the pathogenic mutations strengthen a 'steric zipper' motif in the PrLD, which accelerates the formation of self-seeding fibrils that cross-seed polymerization of wild-type hnRNP. Notably, the disease mutations promote excess incorporation of hnRNPA2 and hnRNPA1 into stress granules and drive the formation of cytoplasmic inclusions in animal models that recapitulate the human pathology. Thus, dysregulated polymerization caused by a potent mutant steric zipper motif in a PrLD can initiate degenerative disease. Related proteins with PrLDs should therefore be considered candidates for initiating and perhaps propagating proteinopathies of muscle, brain, motor neuron and bone.
C1 [Kim, Hong Joo; Kim, Nam Chul; Moore, Jennifer; Freibaum, Brian; Li, Songqing; Molliex, Amandine; Kanagaraj, Anderson P.; Taylor, J. Paul] St Jude Childrens Res Hosp, Dept Dev Neurobiol, Memphis, TN 38120 USA.
   [Wang, Yong-Dong] St Jude Childrens Res Hosp, Hartwell Ctr Bioinformat & Biotechnol, Memphis, TN 38120 USA.
   [Scarborough, Emily A.; Diaz, Zamia; Ford, Alice Flynn; Shorter, James] Univ Penn, Dept Biochem & Biophys, Perelman Sch Med, Philadelphia, PA 19104 USA.
   [MacLea, Kyle S.; Ross, Eric D.] Colorado State Univ, Dept Biochem & Mol Biol, Ft Collins, CO 80523 USA.
   [Carter, Robert] St Jude Childrens Res Hosp, Dept Computat Biol, Memphis, TN 38120 USA.
   [Boylan, Kevin B.; Wojtas, Aleksandra M.; Rademakers, Rosa] Mayo Clin, Dept Neurosci, Jacksonville, FL 32224 USA.
   [Pinkus, Jack L.; Greenberg, Steven A.] Harvard Univ, Brigham & Womens Hosp, Dept Neurol, Sch Med, Boston, MA 02115 USA.
   [Trojanowski, John Q.; Smith, Bradley N.] Univ Penn, Dept Pathol & Lab Med, Inst Aging, Philadelphia, PA 19104 USA.
   [Trojanowski, John Q.; Smith, Bradley N.] Univ Penn, Ctr Neurodegenerat Dis Res, Perelman Sch Med, Philadelphia, PA 19104 USA.
   [Traynor, Bryan J.] NIA, Neuromuscular Dis Res Grp, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
   [Topp, Simon; Gkazi, Athina-Soragia; Miller, Jack; Shaw, Christopher E.] Kings Coll London, Ctr Neurodegenerat Res, Dept Clin Neurosci, Inst Psychiat, London SE5 8AF, England.
   [Kottlors, Michael; Kirschner, Janbernd] Univ Childrens Hosp Freiburg, Div Neuropediat & Muscle Disorders, D-79106 Freiburg, Germany.
   [Pestronk, Alan; Weihl, Conrad C.] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA.
   [Li, Yun R.] Univ Penn, Med Sci Training Program, Perelman Sch Med, Philadelphia, PA 19104 USA.
   [Gitler, Aaron D.] Stanford Univ, Dept Genet, Sch Med, Stanford, CA 94305 USA.
   [Benatar, Michael] Univ Miami, Neurol Dept, Miller Sch Med, Miami, FL 33136 USA.
   [King, Oliver D.] Boston Biomed Res Inst, Watertown, MA 02472 USA.
   [Kimonis, Virginia E.] Univ Calif Irvine, Dept Pediat, Div Genet & Metab, Irvine, CA 92696 USA.
C3 St Jude Children's Research Hospital; St Jude Children's Research Hospital; University of Pennsylvania; Colorado State University System; Colorado State University Fort Collins; St Jude Children's Research Hospital; Mayo Clinic; Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Brigham & Women's Hospital; University of Pennsylvania; University of Pennsylvania; National Institutes of Health (NIH) - USA; NIH National Institute on Aging (NIA); University of London; King's College London; University of Freiburg; Washington University (WUSTL); University of Pennsylvania; Stanford University; University of Miami; Boston Biomedical Research Institute; University of California System; University of California Irvine
RP Taylor, JP (corresponding author), St Jude Childrens Res Hosp, Dept Dev Neurobiol, Memphis, TN 38120 USA.
EM jshorter@mail.med.upenn.edu; JPaul.Taylor@STJUDE.ORG
FU ALSAC; Packard Foundation; National Institutes of Health (NIH) [NS053825]; ALS Association; NIH [AG032953, DP2OD002177, NS067354, AG031867]; Ellison Medical Foundation; National Science Foundation [MCB-1023771]; Div Of Molecular and Cellular Bioscience; Direct For Biological Sciences [1023771] Funding Source: National Science Foundation; Medical Research Council [G0500289B, MC_G1000733, G0900688] Funding Source: researchfish; MRC [G0900688, MC_G1000733] Funding Source: UKRI; National Institute on Aging [ZIAAG000933, R01AG031867] Funding Source: NIH RePORTER
NR 37
TC 1186
Z9 1413
U1 3
U2 316
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 28
PY 2013
VL 495
IS 7442
BP 467
EP +
DI 10.1038/nature11922
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 113QN
UT WOS:000316682800037
PM 23455423
DA 2026-03-09
ER

PT J
AU Gaudry, Q
   Hong, EJ
   Kain, J
   de Bivort, BL
   Wilson, RI
AF Gaudry, Quentin
   Hong, Elizabeth J.
   Kain, Jamey
   de Bivort, Benjamin L.
   Wilson, Rachel I.
TI Asymmetric neurotransmitter release enables rapid odour lateralization in Drosophila
SO NATURE
LA English
DT Article
ID olfactory local interneurons; antennal lobe; melanogaster; circuit; neurons; osmotropotaxis; information; marker; system; gene
AB In Drosophila, most individual olfactory receptor neurons (ORNs) project bilaterally to both sides of the brain(1,2). Having bilateral rather than unilateral projections may represent a useful redundancy. However, bilateral ORN projections to the brain should also compromise the ability to lateralize odours. Nevertheless, walking or flying Drosophila reportedly turn towards the antenna that is more strongly stimulated by odour(3-5). Here we show that each ORN spike releases approximately 40% more neurotransmitter from the axon branch ipsilateral to the soma than from the contralateral branch. As a result, when an odour activates the antennae asymmetrically, ipsilateral central neurons begin to spike a few milliseconds before contralateral neurons, and at a 30 to 50% higher rate than contralateral neurons. We show that a walking fly can detect a 5% asymmetry in total ORN input to its left and right antennal lobes, and can turn towards the odour in less time than it requires the fly to complete a stride. These results demonstrate that neurotransmitter release properties can be tuned independently at output synapses formed by a single axon onto two target cells with identical functions and morphologies. Our data also show that small differences in spike timing and spike rate can produce reliable differences in olfactory behaviour.
C1 [Gaudry, Quentin; Hong, Elizabeth J.; Wilson, Rachel I.] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA.
   [Kain, Jamey; de Bivort, Benjamin L.] Harvard Univ, Rowland Inst, Cambridge, MA 02142 USA.
   [de Bivort, Benjamin L.] Harvard Univ, Dept Organism & Evolutionary Biol, Cambridge, MA 02138 USA.
   [de Bivort, Benjamin L.] Harvard Univ, Ctr Brain Sci, Cambridge, MA 02138 USA.
C3 Harvard University; Harvard Medical School; Harvard University; Harvard University; Harvard University
RP Wilson, RI (corresponding author), Harvard Univ, Sch Med, Dept Neurobiol, 220 Longwood Ave, Boston, MA 02115 USA.
EM rachel_wilson@hms.harvard.edu
FU National Institutes of Health [R01DC008174]; Rowland Junior Fellows Program; National Institute on Deafness and Other Communication Disorders [R01DC008174] Funding Source: NIH RePORTER
NR 36
TC 106
Z9 129
U1 0
U2 57
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 17
PY 2013
VL 493
IS 7432
BP 424
EP U175
DI 10.1038/nature11747
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 071TA
UT WOS:000313615900056
PM 23263180
DA 2026-03-09
ER

PT J
AU Lomakin, IB
   Steitz, TA
AF Lomakin, Ivan B.
   Steitz, Thomas A.
TI The initiation of mammalian protein synthesis and mRNA scanning mechanism
SO NATURE
LA English
DT Article
ID eukaryotic translation initiation; 40s ribosomal-subunit; start codon selection; crystal-structure; site selection; 70s ribosome; eif1a; position; complex; fidelity
AB During translation initiation in eukaryotes, the small ribosomal subunit binds messenger RNA at the 5' end and scans in the 5' to 3' direction to locate the initiation codon, form the 80S initiation complex and start protein synthesis. This simple, yet intricate, process is guided by multiple initiation factors. Here we determine the structures of three complexes of the small ribosomal subunit that represent distinct steps in mammalian translation initiation. These structures reveal the locations of eIF1, eIF1A, mRNA and initiator transfer RNA bound to the small ribosomal subunit and provide insights into the details of translation initiation specific to eukaryotes. Conformational changes associated with the captured functional states reveal the dynamics of the interactions in the P site of the ribosome. These results have functional implications for the mechanism of mRNA scanning.
C1 [Lomakin, Ivan B.; Steitz, Thomas A.] Yale Univ, Dept Mol Biophys & Biochem, New Haven, CT 06520 USA.
   [Steitz, Thomas A.] Yale Univ, Howard Hughes Med Inst, New Haven, CT 06520 USA.
C3 Yale University; Yale University; Howard Hughes Medical Institute
RP Steitz, TA (corresponding author), Yale Univ, Dept Mol Biophys & Biochem, POB 6666, New Haven, CT 06520 USA.
EM ivan.lomakin@yale.edu; thomas.steitz@yale.edu
FU National Institutes of Health (NIH) [GM022778]
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NR 50
TC 146
Z9 220
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 AUG 15
PY 2013
VL 500
IS 7462
BP 307
EP +
DI 10.1038/nature12355
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 201AF
UT WOS:000323112400026
PM 23873042
DA 2026-03-09
ER

PT J
AU Yang, LQ
   Lin, CR
   Jin, CY
   Yang, JC
   Tanasa, B
   Li, WB
   Merkurjev, D
   Ohgi, KA
   Meng, D
   Zhang, J
   Evans, CP
   Rosenfeld, MG
AF Yang, Liuqing
   Lin, Chunru
   Jin, Chunyu
   Yang, Joy C.
   Tanasa, Bogdan
   Li, Wenbo
   Merkurjev, Daria
   Ohgi, Kenneth A.
   Meng, Da
   Zhang, Jie
   Evans, Christopher P.
   Rosenfeld, Michael G.
TI lncRNA-dependent mechanisms of androgen-receptor-regulated gene activation programs
SO NATURE
LA English
DT Article
ID long noncoding rna; prostate-cancer; cell-growth; expression; transcription; enhancers; identification; acetylation; methylation; macrophage
AB Although recent studies have indicated roles of long non-coding RNAs (lncRNAs) in physiological aspects of cell-type determination and tissue homeostasis(1), their potential involvement in regulated gene transcription programs remains rather poorly understood. The androgen receptor regulates a large repertoire of genes central to the identity and behaviour of prostate cancer cells(2), and functions in a ligand-independent fashion in many prostate cancers when they become hormone refractory after initial androgen deprivation therapy(3). Here we report that two lncRNAs highly overexpressed in aggressive prostate cancer, PRNCR1 (also known as PCAT8) and PCGEM1, bind successively to the androgen receptor and strongly enhance both ligand-dependent and ligand-independent androgen-receptor-mediated gene activation programs and proliferation in prostate cancer cells. Binding of PRNCR1 to the carboxy-terminally acetylated androgen receptor on enhancers and its association with DOT1L appear to be required for recruitment of the second lncRNA, PCGEM1, to the androgen receptor amino terminus that is methylated by DOT1L. Unexpectedly, recognition of specific protein marks by PCGEM1-recruited pygopus 2 PHD domain enhances selective looping of androgen-receptor-bound enhancers to target gene promoters in these cells. In 'resistant' prostate cancer cells, these overexpressed lncRNAs can interact with, and are required for, the robust activation of both truncated and full-length androgen receptor, causing ligand-independent activation of the androgen receptor transcriptional program and cell proliferation. Conditionally expressed short hairpin RNA targeting these lncRNAs in castration-resistant prostate cancer cell lines strongly suppressed tumour xenograft growth in vivo. Together, these results indicate that these overexpressed lncRNAs can potentially serve as a required component of castration-resistance in prostatic tumours.
C1 [Yang, Liuqing; Lin, Chunru; Jin, Chunyu; Tanasa, Bogdan; Li, Wenbo; Merkurjev, Daria; Ohgi, Kenneth A.; Zhang, Jie; Rosenfeld, Michael G.] Univ Calif San Diego, Dept Med, Howard Hughes Med Inst, La Jolla, CA 92093 USA.
   [Yang, Liuqing; Lin, Chunru] Univ Texas MD Anderson Canc Ctr, Dept Mol & Cellular Oncol, Houston, TX 77030 USA.
   [Yang, Joy C.; Evans, Christopher P.] Univ Calif Davis, Sch Med, Dept Urol, Sacramento, CA 95817 USA.
   [Tanasa, Bogdan] Scripps Res Inst, Grad Program, Kellogg Sch Sci & Technol, La Jolla, CA 92037 USA.
   [Merkurjev, Daria] Univ Calif San Diego, Dept Bioengn, Bioinformat & Syst Biol Program, La Jolla, CA 92093 USA.
   [Meng, Da] Univ Calif San Diego, Dept Biol Sci, Neurosci Grad Program, La Jolla, CA 92093 USA.
C3 Howard Hughes Medical Institute; University of California System; University of California San Diego; University of Texas System; UTMD Anderson Cancer Center; University of California System; University of California Davis; Scripps Research Institute; University of California System; University of California San Diego; University of California System; University of California San Diego
RP Rosenfeld, MG (corresponding author), Univ Calif San Diego, Dept Med, Howard Hughes Med Inst, La Jolla, CA 92093 USA.
EM lyang7@mdanderson.org; clin2@mdanderson.org; mrosenfeld@ucsd.edu
FU National Institutes of Health (NIH) [DK039949, DK18477, NS034934, CA173903]; Department of Defense [PC111467, SV2C-AACR-DT0812]; Prostate Cancer Foundation; NIH Pathway to Independence Award [1K99DK094981-01, 4R00CA166527-02]; US Army Medical Research and Material Command Era of Hope Postdoctoral award [W81XWH-08-1-0554]; Cancer Prevention Research Institute of Texas First-time Faculty Recruitment Award [R1218]; Cancer Research Institute Postdoctoral Fellowship; National Cancer Institute [P30CA023100] Funding Source: NIH RePORTER; National Institute of Diabetes and Digestive and Kidney Diseases [R01DK018477, R01DK039949, T32DK007541] Funding Source: NIH RePORTER
NR 30
TC 552
Z9 658
U1 2
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 AUG 29
PY 2013
VL 500
IS 7464
BP 598
EP +
DI 10.1038/nature12451
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 207TD
UT WOS:000323625900039
PM 23945587
DA 2026-03-09
ER

PT J
AU Yang, HJ
   Rudge, DG
   Koos, JD
   Vaidialingam, B
   Yang, HJ
   Pavletich, NP
AF Yang, Haijuan
   Rudge, Derek G.
   Koos, Joseph D.
   Vaidialingam, Bhamini
   Yang, Hyo J.
   Pavletich, Nikola P.
TI mTOR kinase structure, mechanism and regulation
SO NATURE
LA English
DT Article
ID p70 s6 kinase; mammalian target; cell-growth; binding partner; rag gtpases; rapamycin; raptor; tor; rheb; pathway
AB The mammalian target of rapamycin (mTOR), a phosphoinositide 3-kinase-related protein kinase, controls cell growth in response to nutrients and growth factors and is frequently deregulated in cancer. Here we report co-crystal structures of a complex of truncated mTOR and mammalian lethal with SEC13 protein 8 (mLST8) with an ATP transition state mimic and with ATP-site inhibitors. The structures reveal an intrinsically active kinase conformation, with catalytic residues and a catalytic mechanism remarkably similar to canonical protein kinases. The active site is highly recessed owing to the FKBP12-rapamycin-binding (FRB) domain and an inhibitory helix protruding from the catalytic cleft. mTOR-activating mutations map to the structural framework that holds these elements in place, indicating that the kinase is controlled by restricted access. In vitro biochemistry shows that the FRB domain acts as a gatekeeper, with its rapamycin-binding site interacting with substrates to grant them access to the restricted active site. Rapamycin-FKBP12 inhibits the kinase by directly blocking substrate recruitment and by further restricting active-site access. The structures also reveal active-site residues and conformational changes that underlie inhibitor potency and specificity.
C1 [Yang, Haijuan; Rudge, Derek G.; Koos, Joseph D.; Vaidialingam, Bhamini; Yang, Hyo J.; Pavletich, Nikola P.] Mem Sloan Kettering Canc Ctr, Struct Biol Program, New York, NY 10065 USA.
   [Pavletich, Nikola P.] Mem Sloan Kettering Canc Ctr, Howard Hughes Med Inst, New York, NY 10065 USA.
C3 Memorial Sloan Kettering Cancer Center; Memorial Sloan Kettering Cancer Center; Howard Hughes Medical Institute
RP Pavletich, NP (corresponding author), Mem Sloan Kettering Canc Ctr, Struct Biol Program, New York, NY 10065 USA.
EM pavletin@mskcc.org
FU Howard Hughes Medical Institute; National Cancer Institute [P30CA008748] Funding Source: NIH RePORTER
NR 53
TC 883
Z9 1077
U1 4
U2 252
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 9
PY 2013
VL 497
IS 7448
BP 217
EP +
DI 10.1038/nature12122
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 139CD
UT WOS:000318558200031
PM 23636326
DA 2026-03-09
ER

PT J
AU Qin, J
   Wu, SP
   Creighton, CJ
   Dai, FY
   Xie, X
   Cheng, CM
   Frolov, A
   Ayala, G
   Lin, X
   Feng, XH
   Ittmann, MM
   Tsai, SJ
   Tsai, MJ
   Tsai, SY
AF Qin, Jun
   Wu, San-Pin
   Creighton, Chad J.
   Dai, Fangyan
   Xie, Xin
   Cheng, Chiang-Min
   Frolov, Anna
   Ayala, Gustavo
   Lin, Xia
   Feng, Xin-Hua
   Ittmann, Michael M.
   Tsai, Shaw-Jenq
   Tsai, Ming-Jer
   Tsai, Sophia Y.
TI COUP-TFII inhibits TGF-β-induced growth barrier to promote prostate tumorigenesis
SO NATURE
LA English
DT Article
ID transcription factor-ii; gene-expression; cancer; orphan; angiogenesis; suppression; metastasis; recurrence; mouse
AB Mutations in phosphatase and tensin homologue (PTEN) or genomic alterations in the phosphatidylinositol-3-OH kinase-signalling pathway are the most common genetic alterations reported in human prostate cancer(1-4). However, the precise mechanism underlying how indolent tumours with PTEN alterations acquire metastatic potential remains poorly understood. Recent studies suggest that upregulation of transforming growth factor (TGF)-beta signalling triggered by PTEN loss will form a growth barrier as a defence mechanism to constrain prostate cancer progression(5), underscoring that TGF-beta signalling might represent a pre-invasive checkpoint to prevent PTEN-mediated prostate tumorigenesis. Here we show that COUP transcription factor II (COUP-TFII, also known as NR2F2)(6-9), a member of the nuclear receptor superfamily, serves as a key regulator to inhibit SMAD4-dependent transcription, and consequently overrides the TGF-beta-dependent checkpoint for PTEN-null indolent tumours. Overexpression of COUP-TFII in the mouse prostate epithelium cooperates with PTEN deletion to augment malignant progression and produce an aggressive metastasis-prone tumour. The functional counteraction between COUP-TFII and SMAD4 is reinforced by genetically engineered mouse models in which conditional loss of SMAD4 diminishes the inhibitory effects elicited by COUP-TFII ablation. The biological significance of COUP-TFII in prostate carcinogenesis is substantiated by patient sample analysis, in which COUP-TFII expression or activity is tightly correlated with tumour recurrence and disease progression, whereas it is inversely associated with TGF-beta signalling. These findings reveal that the destruction of the TGF-beta-dependent barrier by COUP-TFII is crucial for the progression of PTEN-mutant prostate cancer into a life-threatening disease, and supports COUP-TFII as a potential drug target for the intervention of metastatic human prostate cancer.
C1 [Qin, Jun; Wu, San-Pin; Dai, Fangyan; Xie, Xin; Cheng, Chiang-Min; Feng, Xin-Hua; Tsai, Shaw-Jenq; Tsai, Ming-Jer; Tsai, Sophia Y.] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA.
   [Creighton, Chad J.] Baylor Coll Med, Dan L Duncan Canc Ctr, Houston, TX 77030 USA.
   [Dai, Fangyan; Lin, Xia; Feng, Xin-Hua] Baylor Coll Med, Michael E DeBakey Dept Surg, Houston, TX 77030 USA.
   [Frolov, Anna; Ayala, Gustavo; Ittmann, Michael M.] Baylor Coll Med, Dept Pathol & Immunol, Houston, TX 77030 USA.
   [Tsai, Shaw-Jenq] Natl Cheng Kung Univ, Dept Physiol, Coll Med, Tainan 701, Taiwan.
   [Tsai, Ming-Jer; Tsai, Sophia Y.] Baylor Coll Med, Program Dev Biol, Houston, TX 77030 USA.
C3 Baylor College of Medicine; Baylor College of Medicine; Baylor College of Medicine; Baylor College of Medicine; National Cheng Kung University; Baylor College of Medicine
RP Tsai, MJ (corresponding author), Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA.
EM mtsai@bcm.edu; stsai@bcm.edu
FU DERC Center [P30 DK079638]; National Institutes of Health [DK62434, DK59820, DK45641, HL76448]; Dan L. Duncan Cancer Center; National Cancer Institute [P30CA125123] Funding Source: NIH RePORTER
NR 37
TC 158
Z9 182
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 JAN 10
PY 2013
VL 493
IS 7431
BP 236
EP U252
DI 10.1038/nature11674
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 066YY
UT WOS:000313259600042
PM 23201680
DA 2026-03-09
ER

PT J
AU Liu, J
   Wang, B
   Cane, MA
   Yim, SY
   Lee, JY
AF Liu, Jian
   Wang, Bin
   Cane, Mark A.
   Yim, So-Young
   Lee, June-Yi
TI Divergent global precipitation changes induced by natural versus anthropogenic forcing
SO NATURE
LA English
DT Article
ID northern-hemisphere temperatures; sea-surface temperature; tropical pacific; climate-change; past millennium; oscillation; patterns
AB As a result of global warming, precipitation is likely to increase in high latitudes and the tropics and to decrease in already dry subtropical regions(1). The absolute magnitude and regional details of such changes, however, remain intensely debated(2,3). As is well known from El Nino studies, sea-surface-temperature gradients across the tropical Pacific Ocean can strongly influence global rainfall(4,5). Palaeoproxy evidence indicates that the difference between the warm west Pacific and the colder east Pacific increased in past periods when the Earth warmed as a result of increased solar radiation(6-9). In contrast, in most model projections of future greenhouse warming this gradient weakens(2,10,11). It has not been clear how to reconcile these two findings. Here we show in climate model simulations that the tropical Pacific sea-surface-temperature gradient increases when the warming is due to increased solar radiation and decreases when it is due to increased greenhouse-gas forcing. For the same global surface temperature increase the latter pattern produces less rainfall, notably over tropical land, which explains why in the model the late twentieth century is warmer than in the Medieval Warm Period (around AD 1000-1250) but precipitation is less. This difference is consistent with the global tropospheric energy budget(12), which requires a balance between the latent heat released in precipitation and radiative cooling. The tropospheric cooling is less for increased greenhouse gases, which add radiative absorbers to the troposphere, than for increased solar heating, which is concentrated at the Earth's surface. Thus warming due to increased greenhouse gases produces a climate signature different from that of warming due to solar radiation changes.
C1 [Liu, Jian] Nanjing Normal Univ, Sch Geog Sci, Minist Educ, Key Lab Virtual Geog Environm, Nanjing 210023, Jiangsu, Peoples R China.
   [Liu, Jian] Chinese Acad Sci, Nanjing Inst Geog & Limnol, State Key Lab Lake Sci & Environm, Nanjing 210008, Jiangsu, Peoples R China.
   [Wang, Bin; Yim, So-Young; Lee, June-Yi] Univ Hawaii Manoa, Int Pacific Res Ctr, Honolulu, HI 96825 USA.
   [Wang, Bin; Yim, So-Young; Lee, June-Yi] Univ Hawaii Manoa, Dept Meteorol, Honolulu, HI 96825 USA.
   [Cane, Mark A.] Columbia Univ, Lamont Doherty Earth Observ, Palisades, NY 10964 USA.
C3 Nanjing Normal University; Chinese Academy of Sciences; Nanjing Institute of Geography & Limnology, CAS; University of Hawaii System; University of Hawaii Manoa; University of Hawaii System; University of Hawaii Manoa; Columbia University
RP Cane, MA (corresponding author), Columbia Univ, Lamont Doherty Earth Observ, Palisades, NY 10964 USA.
EM jliu@njnu.edu.cn; mcane@ldeo.columbia.edu
FU National Basic Research Program [2010CB950102, XDA05080800]; Natural Science Foundation of China [40871007]; Korean Ministry of Education, Science and Technology (MEST) [2011-0021927]; Department of Energy and NOAA [DE-SC0005108, NA08OAR4320912]; International Pacific Research Center; JAMSTEC; NOAA; NASA
NR 30
TC 176
Z9 231
U1 7
U2 304
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 31
PY 2013
VL 493
IS 7434
BP 656
EP 659
DI 10.1038/nature11784
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 080CU
UT WOS:000314219600053
PM 23364744
DA 2026-03-09
ER

PT J
AU Howe, K
   Clark, MD
   Torroja, CF
   Torrance, J
   Berthelot, C
   Muffato, M
   Collins, JE
   Humphray, S
   McLaren, K
   Matthews, L
   McLaren, S
   Sealy, I
   Caccamo, M
   Churcher, C
   Scott, C
   Barrett, JC
   Koch, R
   Rauch, GJ
   White, S
   Chow, W
   Kilian, B
   Quintais, LT
   Guerra-Assunçao, JA
   Zhou, Y
   Gu, Y
   Yen, J
   Vogel, JH
   Eyre, T
   Redmond, S
   Banerjee, R
   Chi, JX
   Fu, BY
   Langley, E
   Maguire, SF
   Laird, GK
   Lloyd, D
   Kenyon, E
   Donaldson, S
   Sehra, H
   Almeida-King, J
   Loveland, J
   Trevanion, S
   Jones, M
   Quail, M
   Willey, D
   Hunt, A
   Burton, J
   Sims, S
   McLay, K
   Plumb, B
   Davis, J
   Clee, C
   Oliver, K
   Clark, R
   Riddle, C
   Eliott, D
   Threadgold, G
   Harden, G
   Ware, D
   Mortimer, B
   Kerry, G
   Heath, P
   Phillimore, B
   Tracey, A
   Corby, N
   Dunn, M
   Johnson, C
   Wood, J
   Clark, S
   Pelan, S
   Griffiths, G
   Smith, M
   Glithero, R
   Howden, P
   Barker, N
   Stevens, C
   Harley, J
   Holt, K
   Panagiotidis, G
   Lovell, J
   Beasley, H
   Henderson, C
   Gordon, D
   Auger, K
   Wright, D
   Collins, J
   Raisen, C
   Dyer, L
   Leung, K
   Robertson, L
   Ambridge, K
   Leongamornlert, D
   McGuire, S
   Gilderthorp, R
   Griffiths, C
   Manthravadi, D
   Nichol, S
   Barker, G
   Whitehead, S
   Kay, M
   Brown, J
   Murnane, C
   Gray, E
   Humphries, M
   Sycamore, N
   Barker, D
   Saunders, D
   Wallis, J
   Babbage, A
   Hammond, S
   Mashreghi-Mohammadi, M
   Barr, L
   Martin, S
   Wray, P
   Ellington, A
   Matthews, N
   Ellwood, M
   Woodmansey, R
   Clark, G
   Cooper, J
   Tromans, A
   Grafham, D
   Skuce, C
   Pandian, R
   Andrews, R
   Harrison, E
   Kimberley, A
   Garnett, J
   Fosker, N
   Hall, R
   Garner, P
   Kelly, D
   Bird, C
   Palmer, S
   Gehring, I
   Berger, A
   Dooley, CM
   Ersan-Ürün, Z
   Eser, C
   Geiger, H
   Geisler, M
   Karotki, L
   Kirn, A
   Konantz, J
   Konantz, M
   Oberländer, M
   Rudolph-Geiger, S
   Teucke, M
   Osoegawa, K
   Zhu, BL
   Rapp, A
   Widaa, S
   Langford, C
   Yang, FT
   Carter, NP
   Harrow, J
   Ning, ZM
   Herrero, J
   Searle, SMJ
   Enright, A
   Geisler, R
   Plasterk, RHA
   Lee, C
   Westerfield, M
   de Jong, PJ
   Zon, LI
   Postlethwait, JH
   Nüsslein-Volhard, C
   Hubbard, TJP
   Roest Crollius, H
   Rogers, J
   Stemple, DL
AF Howe, Kerstin
   Clark, Matthew D.
   Torroja, Carlos F.
   Torrance, James
   Berthelot, Camille
   Muffato, Matthieu
   Collins, John E.
   Humphray, Sean
   McLaren, Karen
   Matthews, Lucy
   McLaren, Stuart
   Sealy, Ian
   Caccamo, Mario
   Churcher, Carol
   Scott, Carol
   Barrett, Jeffrey C.
   Koch, Romke
   Rauch, Gerd-Joerg
   White, Simon
   Chow, William
   Kilian, Britt
   Quintais, Leonor T.
   Guerra-Assuncao, Jose A.
   Zhou, Yi
   Gu, Yong
   Yen, Jennifer
   Vogel, Jan-Hinnerk
   Eyre, Tina
   Redmond, Seth
   Banerjee, Ruby
   Chi, Jianxiang
   Fu, Beiyuan
   Langley, Elizabeth
   Maguire, Sean F.
   Laird, Gavin K.
   Lloyd, David
   Kenyon, Emma
   Donaldson, Sarah
   Sehra, Harminder
   Almeida-King, Jeff
   Loveland, Jane
   Trevanion, Stephen
   Jones, Matt
   Quail, Mike
   Willey, Dave
   Hunt, Adrienne
   Burton, John
   Sims, Sarah
   McLay, Kirsten
   Plumb, Bob
   Davis, Joy
   Clee, Chris
   Oliver, Karen
   Clark, Richard
   Riddle, Clare
   Eliott, David
   Threadgold, Glen
   Harden, Glenn
   Ware, Darren
   Mortimer, Beverly
   Kerry, Giselle
   Heath, Paul
   Phillimore, Benjamin
   Tracey, Alan
   Corby, Nicole
   Dunn, Matthew
   Johnson, Christopher
   Wood, Jonathan
   Clark, Susan
   Pelan, Sarah
   Griffiths, Guy
   Smith, Michelle
   Glithero, Rebecca
   Howden, Philip
   Barker, Nicholas
   Stevens, Christopher
   Harley, Joanna
   Holt, Karen
   Panagiotidis, Georgios
   Lovell, Jamieson
   Beasley, Helen
   Henderson, Carl
   Gordon, Daria
   Auger, Katherine
   Wright, Deborah
   Collins, Joanna
   Raisen, Claire
   Dyer, Lauren
   Leung, Kenric
   Robertson, Lauren
   Ambridge, Kirsty
   Leongamornlert, Daniel
   McGuire, Sarah
   Gilderthorp, Ruth
   Griffiths, Coline
   Manthravadi, Deepa
   Nichol, Sarah
   Barker, Gary
   Whitehead, Siobhan
   Kay, Michael
   Brown, Jacqueline
   Murnane, Clare
   Gray, Emma
   Humphries, Matthew
   Sycamore, Neil
   Barker, Darren
   Saunders, David
   Wallis, Justene
   Babbage, Anne
   Hammond, Sian
   Mashreghi-Mohammadi, Maryam
   Barr, Lucy
   Martin, Sancha
   Wray, Paul
   Ellington, Andrew
   Matthews, Nicholas
   Ellwood, Matthew
   Woodmansey, Rebecca
   Clark, Graham
   Cooper, James
   Tromans, Anthony
   Grafham, Darren
   Skuce, Carl
   Pandian, Richard
   Andrews, Robert
   Harrison, Elliot
   Kimberley, Andrew
   Garnett, Jane
   Fosker, Nigel
   Hall, Rebekah
   Garner, Patrick
   Kelly, Daniel
   Bird, Christine
   Palmer, Sophie
   Gehring, Ines
   Berger, Andrea
   Dooley, Christopher M.
   Ersan-Ueruen, Zuebeyde
   Eser, Cigdem
   Geiger, Horst
   Geisler, Maria
   Karotki, Lena
   Kirn, Anette
   Konantz, Judith
   Konantz, Martina
   Oberlaender, Martina
   Rudolph-Geiger, Silke
   Teucke, Mathias
   Osoegawa, Kazutoyo
   Zhu, Baoli
   Rapp, Amanda
   Widaa, Sara
   Langford, Cordelia
   Yang, Fengtang
   Carter, Nigel P.
   Harrow, Jennifer
   Ning, Zemin
   Herrero, Javier
   Searle, Steve M. J.
   Enright, Anton
   Geisler, Robert
   Plasterk, Ronald H. A.
   Lee, Charles
   Westerfield, Monte
   de Jong, Pieter J.
   Zon, Leonard I.
   Postlethwait, John H.
   Nuesslein-Volhard, Christiane
   Hubbard, Tim J. P.
   Roest Crollius, Hugues
   Rogers, Jane
   Stemple, Derek L.
TI The zebrafish reference genome sequence and its relationship to the human genome
SO NATURE
LA English
DT Article
ID gene; duplication; mutations; evolution; reveals
AB Zebrafish have become a popular organism for the study of vertebrate gene function(1,2). The virtually transparent embryos of this species, and the ability to accelerate genetic studies by gene knockdown or overexpression, have led to the widespread use of zebrafish in the detailed investigation of vertebrate gene function and increasingly, the study of human genetic disease(3-5). However, for effective modelling of human genetic disease it is important to understand the extent to which zebrafish genes and gene structures are related to orthologous human genes. To examine this, we generated a high-quality sequence assembly of the zebrafish genome, made up of an overlapping set of completely sequenced large-insert clones that were ordered and oriented using a high-resolution high-density meiotic map. Detailed automatic and manual annotation provides evidence of more than 26,000 protein-coding genes(6), the largest gene set of any vertebrate so far sequenced. Comparison to the human reference genome shows that approximately 70% of human genes have at least one obvious zebrafish orthologue. In addition, the high quality of this genome assembly provides a clearer understanding of key genomic features such as a unique repeat content, a scarcity of pseudogenes, an enrichment of zebrafish-specific genes on chromosome 4 and chromosomal regions that influence sex determination.
C1 [Howe, Kerstin; Clark, Matthew D.; Torroja, Carlos F.; Torrance, James; Collins, John E.; Humphray, Sean; McLaren, Karen; Matthews, Lucy; McLaren, Stuart; Sealy, Ian; Churcher, Carol; Scott, Carol; Barrett, Jeffrey C.; White, Simon; Chow, William; Kilian, Britt; Gu, Yong; Yen, Jennifer; Vogel, Jan-Hinnerk; Eyre, Tina; Redmond, Seth; Banerjee, Ruby; Chi, Jianxiang; Fu, Beiyuan; Langley, Elizabeth; Maguire, Sean F.; Laird, Gavin K.; Lloyd, David; Kenyon, Emma; Donaldson, Sarah; Sehra, Harminder; Almeida-King, Jeff; Loveland, Jane; Trevanion, Stephen; Jones, Matt; Quail, Mike; Willey, Dave; Hunt, Adrienne; Burton, John; Sims, Sarah; McLay, Kirsten; Plumb, Bob; Davis, Joy; Clee, Chris; Oliver, Karen; Clark, Richard; Riddle, Clare; Eliott, David; Threadgold, Glen; Harden, Glenn; Ware, Darren; Mortimer, Beverly; Kerry, Giselle; Heath, Paul; Phillimore, Benjamin; Tracey, Alan; Corby, Nicole; Dunn, Matthew; Johnson, Christopher; Wood, Jonathan; Clark, Susan; Pelan, Sarah; Griffiths, Guy; Smith, Michelle; Glithero, Rebecca; Howden, Philip; Barker, Nicholas; Stevens, Christopher; Harley, Joanna; Holt, Karen; Panagiotidis, Georgios; Lovell, Jamieson; Beasley, Helen; Henderson, Carl; Gordon, Daria; Auger, Katherine; Wright, Deborah; Collins, Joanna; Raisen, Claire; Dyer, Lauren; Leung, Kenric; Robertson, Lauren; Ambridge, Kirsty; Leongamornlert, Daniel; McGuire, Sarah; Gilderthorp, Ruth; Griffiths, Coline; Manthravadi, Deepa; Nichol, Sarah; Barker, Gary; Whitehead, Siobhan; Kay, Michael; Brown, Jacqueline; Murnane, Clare; Gray, Emma; Humphries, Matthew; Sycamore, Neil; Barker, Darren; Saunders, David; Wallis, Justene; Babbage, Anne; Hammond, Sian; Mashreghi-Mohammadi, Maryam; Barr, Lucy; Martin, Sancha; Wray, Paul; Ellington, Andrew; Matthews, Nicholas; Ellwood, Matthew; Woodmansey, Rebecca; Clark, Graham; Cooper, James; Tromans, Anthony; Grafham, Darren; Skuce, Carl; Pandian, Richard; Andrews, Robert; Harrison, Elliot; Kimberley, Andrew; Garnett, Jane; Fosker, Nigel; Hall, Rebekah; Garner, Patrick; Kelly, Daniel; Bird, Christine; Palmer, Sophie; Berger, Andrea; Dooley, Christopher M.; Widaa, Sara; Langford, Cordelia; Yang, Fengtang; Carter, Nigel P.; Harrow, Jennifer; Ning, Zemin; Searle, Steve M. J.; Hubbard, Tim J. P.; Rogers, Jane; Stemple, Derek L.] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England.
   [Clark, Matthew D.; Caccamo, Mario; Rogers, Jane] Genome Anal Ctr, Norwich NR4 7UH, Norfolk, England.
   [Torroja, Carlos F.] Ctr Nacl Invest Cardiovasc, Bioinformat Unit, Madrid 28029, Spain.
   [Berthelot, Camille; Roest Crollius, Hugues] ENS, Inst Biol, IBENS, F-75005 Paris, France.
   [Berthelot, Camille; Roest Crollius, Hugues] INSERM, U1024, F-75005 Paris, France.
   [Berthelot, Camille; Roest Crollius, Hugues] CNRS, UMR 8197, F-75005 Paris, France.
   [Muffato, Matthieu; Quintais, Leonor T.; Guerra-Assuncao, Jose A.; Herrero, Javier; Enright, Anton] EMBL European Bioinformat Inst, Cambridge CB10 1SD, England.
   [Humphray, Sean] Illumina Cambridge, Saffron Walden CB10 1XL, Essex, England.
   [Koch, Romke; Plasterk, Ronald H. A.] Hubrecht Lab, NL-3584 CT Utrecht, Netherlands.
   [Rauch, Gerd-Joerg; Gehring, Ines; Berger, Andrea; Dooley, Christopher M.; Ersan-Ueruen, Zuebeyde; Eser, Cigdem; Geiger, Horst; Geisler, Maria; Karotki, Lena; Kirn, Anette; Konantz, Judith; Konantz, Martina; Oberlaender, Martina; Rudolph-Geiger, Silke; Teucke, Mathias; Geisler, Robert; Nuesslein-Volhard, Christiane] Max Planck Inst Dev Biol, D-72076 Tubingen, Germany.
   [Zhou, Yi; Zon, Leonard I.] Childrens Hosp, Stem Cell Program, Boston, MA 02115 USA.
   [Zhou, Yi; Zon, Leonard I.] Childrens Hosp, Div Hematol & Oncol, Boston, MA 02115 USA.
   [Zhou, Yi; Zon, Leonard I.] Dana Farber Canc Inst, Boston, MA 02115 USA.
   [Osoegawa, Kazutoyo; Zhu, Baoli; de Jong, Pieter J.] Childrens Hosp Oakland, Oakland, CA 94609 USA.
   [Rapp, Amanda; Westerfield, Monte; Postlethwait, John H.] Univ Oregon, Inst Neurosci, Eugene, OR 97403 USA.
   [Geisler, Robert] KIT, ITG, D-76344 Eggenstein Leopoldshafen, Germany.
   [Lee, Charles] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
   [Lee, Charles] Harvard Univ, Sch Med, Boston, MA 02115 USA.
C3 Wellcome Trust Sanger Institute; UK Research & Innovation (UKRI); Biotechnology and Biological Sciences Research Council (BBSRC); Earlham Institute; Centro Nacional de Investigaciones Cardiovasculares (CNIC); Universite PSL; Ecole Normale Superieure (ENS); Institut National de la Sante et de la Recherche Medicale (Inserm); Institut National de la Sante et de la Recherche Medicale (Inserm); Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB); European Molecular Biology Laboratory (EMBL); European Bioinformatics Institute; Illumina; Royal Netherlands Academy of Arts & Sciences; Hubrecht Institute (KNAW); Max Planck Society; 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; Dana-Farber Cancer Institute; University of California System; University of California San Francisco; UCSF Medical Center; UCSF Benioff Children's Hospital Oakland; University of Oregon; Helmholtz Association; Karlsruhe Institute of Technology; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard University; Harvard Medical School
RP Stemple, DL (corresponding author), Wellcome Trust Sanger Inst, Wellcome Trust Genome Campus, Cambridge CB10 1SA, England.
EM ds4@sanger.ac.uk
FU National Institutes of Health (NIH) [R01 GM085318, P01 HD22486, R01 OD011116, R01 RR020833, 1 R01 DK55377-01A1]; European Commission [LSHG-CT-2003-503496, HEALTH-F4-2010-242048]; German Human Genome Project (DHGP) [01 KW 9627, 01 KW 9919]; Wellcome Trust [098051]; NCRR NIH HHS [R01 RR020833, R01 RR010715] Funding Source: Medline; NICHD NIH HHS [P01 HD022486, P01 HD22486] Funding Source: Medline; NIDDK NIH HHS [R01 DK055377, 1 R01 DK55377-01A1] Funding Source: Medline; NIGMS NIH HHS [R01 GM085318] Funding Source: Medline; NIH HHS [R01 OD011116] Funding Source: Medline; Wellcome Trust [098051, 095908] Funding Source: Medline
NR 30
TC 3632
Z9 4419
U1 39
U2 230
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 25
PY 2013
VL 496
IS 7446
BP 498
EP 503
DI 10.1038/nature12111
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 131HU
UT WOS:000317984400040
PM 33365218
DA 2026-03-09
ER

PT J
AU Fernández, IS
   Ng, CL
   Kelley, AC
   Wu, GW
   Yu, YT
   Ramakrishnan, V
AF Fernandez, Israel S.
   Chyan Leong Ng
   Kelley, Ann C.
   Wu, Guowei
   Yu, Yi-Tao
   Ramakrishnan, V.
TI Unusual base pairing during the decoding of a stop codon by the ribosome
SO NATURE
LA English
DT Article
ID transfer-rna; mechanism; pseudouridine; refinement; tu
AB During normal translation, the binding of a release factor to one of the three stop codons (UGA, UAA or UAG) results in the termination of protein synthesis. However, modification of the initial uridine to a pseudouridine (Psi) allows efficient recognition and readthrough of these stop codons by a transfer RNA(tRNA), although it requires the formation of two normally forbidden purine-purine base pairs(1). Here we determined the crystal structure at 3.1 angstrom resolution of the 30S ribosomal subunit in complex with the anticodon stem loop of tRNA(Ser) bound to the Psi AG stop codon in the A site. The Psi A base pair at the first position is accompanied by the formation of purine-purine base pairs at the second and third positions of the codon, which show an unusual Watson-Crick/Hoogsteen geometry. The structure shows a previously unsuspected ability of the ribosomal decoding centre to accommodate non-canonical base pairs.
C1 [Fernandez, Israel S.; Chyan Leong Ng; Kelley, Ann C.; Ramakrishnan, V.] MRC Lab Mol Biol, Cambridge CB2 0QH, England.
   [Wu, Guowei; Yu, Yi-Tao] Univ Rochester, Med Ctr, Dept Biochem & Biophys, Rochester, NY 14642 USA.
C3 MRC Laboratory Molecular Biology; University of Rochester
RP Ramakrishnan, V (corresponding author), MRC Lab Mol Biol, Cambridge CB2 0QH, England.
EM YiTao_Yu@URMC.Rochester.edu; ramak@mrc-lmb.cam.ac.uk
FU UK Medical Research Council [U105184332]; Wellcome Trust; Agouron Institute; Louis-Jeantet Foundation; National Institutes of Health [GM104077]; University of Rochester CTSA from the National Center for Advancing Translational Sciences of the National Institutes of Health [UL1TR000042]; Fundacion Ramon Areces; Medical Research Council [MC_U105184332] Funding Source: researchfish; MRC [MC_U105184332] Funding Source: UKRI
NR 20
TC 139
Z9 186
U1 3
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 1
PY 2013
VL 500
IS 7460
BP 107
EP U136
DI 10.1038/nature12302
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 192VK
UT WOS:000322514800038
PM 23812587
DA 2026-03-09
ER

PT J
AU Nakaki, F
   Hayashi, K
   Ohta, H
   Kurimoto, K
   Yabuta, Y
   Saitou, M
AF Nakaki, Fumio
   Hayashi, Katsuhiko
   Ohta, Hiroshi
   Kurimoto, Kazuki
   Yabuta, Yukihiro
   Saitou, Mitinori
TI Induction of mouse germ-cell fate by transcription factors in vitro
SO NATURE
LA English
DT Article
ID ground-state; specification; expression; dynamics; lineage; transplantation; prdm14; blimp1; mice
AB The germ-cell lineage ensures the continuity of life through the generation of male and female gametes, which unite to form a totipotent zygote. We have previously demonstrated that, by using cytokines, embryonic stem cells and induced pluripotent stem cells can be induced into epiblast-like cells (EpiLCs) and then into primordial germcell (PGC)-like cells with the capacity for both spermatogenesis and oogenesis(1,2), creating an opportunity for understanding and regulating mammalian germ-cell development in both sexes in vitro. Here we show that, without cytokines, simultaneous overexpression of three transcription factors, Blimp1 (also known as Prdm1), Prdm14 and Tfap2c (also known as AP2c), directs EpiLCs, but not embryonic stem cells, swiftly and efficiently into a PGC state. Notably, Prdm14 alone, but not Blimp1 or Tfap2c, suffices for the induction of the PGC state in EpiLCs. The transcription-factor-induced PGC state, irrespective of the transcription factors used, reconstitutes key transcriptome and epigenetic reprogramming in PGCs, but bypasses a mesodermal program that accompanies PGC or PGC-like-cell specification by cytokines including bone morphogenetic protein 4. Notably, the transcription-factor-induced PGC-like cells contribute to spermatogenesis and fertile offspring. Our findings provide a new insight into the transcriptional logic for PGC specification, and create a foundation for the transcription-factor-based reconstitution and regulation of mammalian gametogenesis.
C1 [Nakaki, Fumio; Hayashi, Katsuhiko; Ohta, Hiroshi; Kurimoto, Kazuki; Yabuta, Yukihiro; Saitou, Mitinori] Kyoto Univ, Grad Sch Med, Dept Anat & Cell Biol, Sakyo Ku, Kyoto 6068501, Japan.
   [Hayashi, Katsuhiko; Saitou, Mitinori] Kyoto Univ, Ctr iPS Cell Res & Applicat, Sakyo Ku, Kyoto 6068507, Japan.
   [Hayashi, Katsuhiko] JST, PRESTO, Sakyo Ku, Kyoto 6068501, Japan.
   [Ohta, Hiroshi; Kurimoto, Kazuki; Yabuta, Yukihiro; Saitou, Mitinori] JST, ERATO, Sakyo Ku, Kyoto 6068501, Japan.
   [Saitou, Mitinori] Kyoto Univ, Inst Integrated Cell Mat Sci, Sakyo Ku, Kyoto 6068501, Japan.
C3 Kyoto University; Kyoto University; Japan Science & Technology Agency (JST); Japan Science & Technology Agency (JST); Kyoto University
RP Saitou, M (corresponding author), Kyoto Univ, Grad Sch Med, Dept Anat & Cell Biol, Sakyo Ku, Yoshida Konoe Cho, Kyoto 6068501, Japan.
EM saitou@anat2.med.kyoto-u.ac.jp
FU Ministry of Education, Culture, Sports, Science, and Technology of Japan; JST-CREST/ERATO; Takeda Science Foundation; Academia for Repro-regenerative Medicine; Grants-in-Aid for Scientific Research [24680045, 24681039, 25650065, 21677003] Funding Source: KAKEN
NR 30
TC 239
Z9 274
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 SEP 12
PY 2013
VL 501
IS 7466
BP 222
EP +
DI 10.1038/nature12417
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 215XR
UT WOS:000324244900041
PM 23913270
DA 2026-03-09
ER

PT J
AU Nakamura, Y
   Oscherwitz, J
   Cease, KB
   Chan, SM
   Muñoz-Planillo, R
   Hasegawa, M
   Villaruz, AE
   Cheung, GYC
   McGavin, MJ
   Travers, JB
   Otto, M
   Inohara, N
   Nuñez, G
AF Nakamura, Yuumi
   Oscherwitz, Jon
   Cease, Kemp B.
   Chan, Susana M.
   Munoz-Planillo, Raul
   Hasegawa, Mizuho
   Villaruz, Amer E.
   Cheung, Gordon Y. C.
   McGavin, Martin J.
   Travers, Jeffrey B.
   Otto, Michael
   Inohara, Naohiro
   Nunez, Gabriel
TI Staphylococcus δ-toxin induces allergic skin disease by activating mast cells
SO NATURE
LA English
DT Article
ID aureus; virulence; ige; mice; identification; deficient; responses; release; growth; phase
AB Atopic dermatitis is a chronic inflammatory skin disease that affects 15-30% of children and approximately 5% of adults in industrialized countries(1). Although the pathogenesis of atopic dermatitis is not fully understood, the disease is mediated by an abnormal immunoglobulin E immune response in the setting of skin barrier dysfunction(2). Mast cells contribute to immunoglobulin-E-mediated allergic disorders including atopic dermatitis(3). Upon activation, mast cells release their membrane-bound cytosolic granules leading to the release of several molecules that are important in the pathogenesis of atopic dermatitis and host defence(4). More than 90% of patients with atopic dermatitis are colonized with Staphylococcus aureus in the lesional skin whereas most healthy individuals do not harbour the pathogen(5). Several staphylococcal exotoxins can act as superantigens and/or antigens in models of atopic dermatitis(6). However, the role of these staphylococcal exotoxins in disease pathogenesis remains unclear. Here we report that culture supernatants of S. aureus contain potent mast-cell degranulation activity. Biochemical analysis identified delta-toxin as the mast cell degranulation-inducing factor produced by S. aureus. Mast cell degranulation induced by delta-toxin depended on phosphoinositide 3-kinase and calcium (Ca2+) influx; however, unlike that mediated by immunoglobulin-E crosslinking, it did not require the spleen tyrosine kinase. In addition, immunoglobulin-E enhanced delta-toxin-induced mast cell degranulation in the absence of antigen. Furthermore, S. aureus isolates recovered from patients with atopic dermatitis produced large amounts of delta-toxin. Skin colonization with S. aureus, but not a mutant deficient in delta-toxin, promoted immunoglobulin-E and interleukin-4 production, as well as inflammatory skin disease. Furthermore, enhancement of immunoglobulin E production and dermatitis by delta-toxin was abrogated in Kit(W-sh/W-sh) mast-cell-deficient mice and restored by mast cell reconstitution. These studies identify delta-toxin as a potent inducer of mast cell degranulation and suggest a mechanistic link between S. aureus colonization and allergic skin disease.
C1 [Nakamura, Yuumi; Chan, Susana M.; Munoz-Planillo, Raul; Hasegawa, Mizuho; Inohara, Naohiro; Nunez, Gabriel] Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI 48109 USA.
   [Nakamura, Yuumi; Chan, Susana M.; Munoz-Planillo, Raul; Hasegawa, Mizuho; Inohara, Naohiro; Nunez, Gabriel] Univ Michigan, Sch Med, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA.
   [Oscherwitz, Jon; Cease, Kemp B.] Univ Michigan, Sch Med, Dept Internal Med, Div Hematol Oncol, Ann Arbor, MI 48109 USA.
   [Oscherwitz, Jon; Cease, Kemp B.] VA Ann Arbor Healthcare Syst, Ann Arbor, MI 48105 USA.
   [Villaruz, Amer E.; Cheung, Gordon Y. C.; Otto, Michael] NIAID, Lab Human Bacterial Pathogenesis, US Natl Inst Hlth, Bethesda, MD 20892 USA.
   [McGavin, Martin J.] Univ Western Ontario, Dept Microbiol & Immunol, London, ON N6A 5C1, Canada.
   [McGavin, Martin J.] Univ Western Ontario, Ctr Human Immunol, London, ON N6A 5C1, Canada.
   [Travers, Jeffrey B.] Indiana Univ Sch Med, Dept Dermatol, Indianapolis, IN 46202 USA.
C3 University of Michigan System; University of Michigan; University of Michigan System; University of Michigan; University of Michigan System; University of Michigan; US Department of Veterans Affairs; Veterans Health Administration (VHA); VA Ann Arbor Healthcare System; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID); Western University (University of Western Ontario); Western University (University of Western Ontario); Indiana University System; Indiana University Bloomington
RP Nuñez, G (corresponding author), Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI 48109 USA.
EM gabriel.nunez@umich.edu
FU Chiba University Global COE Program; Cell Science Research Foundation; Kanae Foundation for the Promotion of Medical Science; Department of Veterans Affairs [I01BX000429]; National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH); NIH [R01AR059688, R01HL062996]; University of Michigan's Cancer Center; National Heart Lung and Blood Institute [R01HL062996] Funding Source: NIH RePORTER; National Institute of Allergy and Infectious Diseases [ZIAAI000904] Funding Source: NIH RePORTER
NR 34
TC 437
Z9 517
U1 6
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 21
PY 2013
VL 503
IS 7476
BP 397
EP +
DI 10.1038/nature12655
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 254KG
UT WOS:000327163200041
PM 24172897
DA 2026-03-09
ER

PT J
AU Hashem, Y
   des Georges, A
   Dhote, V
   Langlois, R
   Liao, HY
   Grassucci, RA
   Pestova, TV
   Hellen, CUT
   Frank, J
AF Hashem, Yaser
   des Georges, Amedee
   Dhote, Vidya
   Langlois, Robert
   Liao, Hstau Y.
   Grassucci, Robert A.
   Pestova, Tatyana V.
   Hellen, Christopher U. T.
   Frank, Joachim
TI Hepatitis-C-virus-like internal ribosome entry sites displace eIF3 to gain access to the 40S subunit
SO NATURE
LA English
DT Article
ID eukaryotic translation initiation; swine-fever virus; electron-microscopy; molecular-dynamics; domain-ii; macromolecular complexes; crystal-structure; 80s ribosome; rna; ires
AB Hepatitis C virus (HCV) and classical swine fever virus (CSFV) messenger RNAs contain related (HCV-like) internal ribosome entry sites (IRESs) that promote 5'-end independent initiation of translation, requiring only a subset of the eukaryotic initiation factors (eIFs) needed for canonical initiation on cellular mRNAs(1). Initiation on HCV-like IRESs relies on their specific interaction with the 40S subunit(2-8), which places the initiation codon into the P site, where it directly base-pairs with eIF2-bound initiator methionyl transfer RNA to form a 48S initiation complex. However, all HCV-like IRESs also specifically interact with eIF3 (refs 2, 5-7, 9-12), but the role of this interaction in IRES-mediated initiation has remained unknown. During canonical initiation, eIF3 binds to the 40S subunit as a component of the 43S pre-initiation complex, and comparison of the ribosomal positions of eIF3(13) and the HCV IRES8 revealed that they overlap, so that their rearrangement would be required for formation of ribosomal complexes containing both components(13). Here we present a cryo-electron microscopy reconstruction of a 40S ribosomal complex containing eIF3 and the CSFV IRES. Remarkably, although the position and interactions of the CSFV IRES with the 40S subunit in this complex are similar to those of the HCV IRES in the 40S-IRES binary complex(8), eIF3 is completely displaced from its ribosomal position in the 43S complex, and instead interacts through its ribosome-binding surface exclusively with the apical region of domain III of the IRES. Our results suggest a role for the specific interaction of HCV-like IRESs with eIF3 in preventing ribosomal association of eIF3, which could serve two purposes: relieving the competition between the IRES and eIF3 for a common binding site on the 40S subunit, and reducing formation of 43S complexes, thereby favouring translation of viral mRNAs.
C1 [Hashem, Yaser; des Georges, Amedee; Frank, Joachim] Columbia Univ, Dept Biochem & Mol Biophys, Howard Hughes Med Inst, New York, NY 10032 USA.
   [Hashem, Yaser; des Georges, Amedee; Langlois, Robert; Liao, Hstau Y.; Grassucci, Robert A.; Frank, Joachim] Columbia Univ, Dept Biochem & Mol Biophys, New York, NY 10032 USA.
   [Dhote, Vidya; Pestova, Tatyana V.; Hellen, Christopher U. T.] Suny Downstate Med Ctr, Dept Cell Biol, Brooklyn, NY 11203 USA.
   [Grassucci, Robert A.; Frank, Joachim] Columbia Univ, Dept Biol Sci, New York, NY 10032 USA.
C3 Columbia University; Howard Hughes Medical Institute; Columbia University; State University of New York (SUNY) System; SUNY Downstate Health Sciences University; Columbia University
RP Hellen, CUT (corresponding author), Suny Downstate Med Ctr, Dept Cell Biol, Brooklyn, NY 11203 USA.
EM christopher.hellen@downstate.edu; jf2192@columbia.edu
FU HHMI; National Institutes of Health (NIH) [R01 GM29169, R01 AI51340, R01 GM59660]
NR 55
TC 157
Z9 183
U1 1
U2 46
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 28
PY 2013
VL 503
IS 7477
BP 539
EP +
DI 10.1038/nature12658
PG 20
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 258MU
UT WOS:000327464200046
PM 24185006
DA 2026-03-09
ER

PT J
AU Zhou, HH
   Sun, LT
   Yang, XL
   Schimmel, P
AF Zhou, Huihao
   Sun, Litao
   Yang, Xiang-Lei
   Schimmel, Paul
TI ATP-directed capture of bioactive herbal-based medicine on human tRNA synthetase
SO NATURE
LA English
DT Article
ID halofuginone; adenylate; assays
AB Febrifugine is the active component of the Chinese herb Chang Shan (Dichroa febrifuga Lour.)(1,2), which has been used for treating malaria-induced fever for about 2,000 years. Halofuginone (HF), the halogenated derivative of febrifugine, has been tested in clinical trials for potential therapeutic applications in cancer and fibrotic disease(3-6). Recently, HF was reported to inhibit T(H)17 cell differentiation by activating the amino acid response pathway(7), through inhibiting human prolyl-transfer RNA synthetase (ProRS) to cause intracellular accumulation of uncharged tRNA(8,9). Curiously, inhibition requires the presence of unhydrolysed ATP. Here we report an unusual 2.0 angstrom structure showing that ATP directly locks onto and orients two parts of HF onto human ProRS, so that one part of HF mimics bound proline and the other mimics the 3' end of bound tRNA. Thus, HF is a new type of ATP-dependent inhibitor that simultaneously occupies two different substrate binding sites on ProRS. Moreover, our structure indicates a possible similar mechanism of action for febrifugine in malaria treatment. Finally, the elucidation here of a two-site modular targeting activity of HF raises the possibility that substrate-directed capture of similar inhibitors might be a general mechanism that could be applied to other synthetases.
C1 [Zhou, Huihao; Sun, Litao; Yang, Xiang-Lei; Schimmel, Paul] Scripps Res Inst, Dept Mol Biol, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA.
C3 Scripps Research Institute
RP Schimmel, P (corresponding author), Scripps Res Inst, Dept Mol Biol, Skaggs Inst Chem Biol, 10550 N Torrey Pines Rd, La Jolla, CA 92037 USA.
EM schimmel@scripps.edu
FU National Institutes of Health [GM15539, GM23562, GM88278]; National Foundation for Cancer Research
NR 21
TC 141
Z9 166
U1 0
U2 122
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 7
PY 2013
VL 494
IS 7435
BP 121
EP 124
DI 10.1038/nature11774
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 087DJ
UT WOS:000314741200046
PM 23263184
DA 2026-03-09
ER

PT J
AU Smalley, DE
   Smithwick, QYJ
   Bove, VM
   Barabas, J
   Jolly, S
AF Smalley, D. E.
   Smithwick, Q. Y. J.
   Bove, V. M., Jr.
   Barabas, J.
   Jolly, S.
TI Anisotropic leaky-mode modulator for holographic video displays
SO NATURE
LA English
DT Article
ID wave
AB Every holographic video display is built on a spatial light modulator, which directs light by diffraction to form points in three-dimensional space. The modulators currently used for holographic video displays are challenging to use for several reasons: they have relatively low bandwidth, high cost, low diffraction angle, poor scalability, and the presence of quantization noise, unwanted diffractive orders and zero-order light. Here we present modulators for holographic video displays based on anisotropic leaky-mode couplers, which have the potential to address all of these challenges. These modulators can be fabricated simply, monolithically and at low cost. Additionally, these modulators are capable of new functionalities, such as wavelength division multiplexing for colour display. We demonstrate three enabling properties of particular interest-polarization rotation, enlarged angular diffraction, and frequency domain colour filtering-and suggest that this technology can be used as a platform for low-cost, high-performance holographic video displays.
C1 [Smalley, D. E.; Smithwick, Q. Y. J.; Bove, V. M., Jr.; Barabas, J.; Jolly, S.] MIT, Media Lab, Cambridge, MA 02139 USA.
C3 Massachusetts Institute of Technology (MIT)
RP Smalley, DE (corresponding author), MIT, Media Lab, Cambridge, MA 02139 USA.
EM desmalley@gmail.com
FU NVIDIA
NR 20
TC 183
Z9 239
U1 2
U2 110
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 20
PY 2013
VL 498
IS 7454
BP 313
EP +
DI 10.1038/nature12217
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 166XI
UT WOS:000320592900030
PM 23783627
DA 2026-03-09
ER

PT J
AU Bali, E
   Audétat, A
   Keppler, H
AF Bali, Eniko
   Audetat, Andreas
   Keppler, Hans
TI Water and hydrogen are immiscible in Earth's mantle
SO NATURE
LA English
DT Article
ID oxidation-state; fluid inclusions; carbon; solubility; quartz; gases
AB In the deep, chemically reducing parts of Earth's mantle(1), hydrous fluids contain significant amounts of molecular hydrogen (H-2). Thermodynamic models of fluids in Earth's mantle so far have always assumed that molecular hydrogen and water are completely miscible. Here we show experimental evidence that water and hydrogen can coexist as two separate, immiscible phases. Immiscibility between water and hydrogen may be the cause of the formation of enigmatic, ultra-reducing domains in the mantle that contain moissanite (SiC) and other phases indicative of extremely reducing conditions(2,3). Moreover, the immiscibility between water and hydrogen may provide a mechanism for the rapid oxidation of Earth's upper mantle immediately following core formation(4).
C1 [Bali, Eniko; Audetat, Andreas; Keppler, Hans] Univ Bayreuth, Bayer Geoinst, D-95440 Bayreuth, Germany.
   [Bali, Eniko] Univ Gottingen, Geowissensch Zentrum, D-37077 Gottingen, Germany.
C3 University of Bayreuth; University of Gottingen
RP Bali, E (corresponding author), Univ Bayreuth, Bayer Geoinst, POB 101251, D-95440 Bayreuth, Germany.
EM enikoe.bali@geo.uni-goettingen.de
NR 30
TC 79
Z9 90
U1 1
U2 159
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 14
PY 2013
VL 495
IS 7440
BP 220
EP 222
DI 10.1038/nature11908
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 113FP
UT WOS:000316652300047
PM 23486061
DA 2026-03-09
ER

PT J
AU Mundell, CG
   Kopac, D
   Arnold, DM
   Steele, IA
   Gomboc, A
   Kobayashi, S
   Harrison, RM
   Smith, RJ
   Guidorzi, C
   Virgili, FJ
   Melandri, A
   Japelj, J
AF Mundell, C. G.
   Kopac, D.
   Arnold, D. M.
   Steele, I. A.
   Gomboc, A.
   Kobayashi, S.
   Harrison, R. M.
   Smith, R. J.
   Guidorzi, C.
   Virgili, F. J.
   Melandri, A.
   Japelj, J.
TI Highly polarized light from stable ordered magnetic fields in GRB 120308A
SO NATURE
LA English
DT Article
ID gamma-ray bursts; optical polarization; afterglow; emission; shock; reconnection; model; jets
AB After the initial burst of gamma-rays that defines a gamma-ray burst (GRB), expanding ejecta collide with the circumburst medium and begin to decelerate at the onset of the afterglow, during which a forward shock travels outwards and a reverse shock propagates backwards into the oncoming collimated flow, or 'jet'(1,2). Light from the reverse shock should be highly polarized if the jet's magnetic field is globally ordered and advected from the central engine(3,4), with a position angle that is predicted to remain stable in magnetized baryonic jet models(5) or vary randomly with time if the field is produced locally by plasma or magnetohydrodynamic instabilities(6,7). Degrees of linear polarization of P approximate to 10 per cent in the optical band have previously been detected in the early afterglow(6,8), but the lack of temporal measurements prevented definitive tests of competing jet models(9-14). Hours to days after the gamma-ray burst, polarization levels are low (P<4 per cent), when emission from the shocked ambient medium dominates(15-17). Here we report the detection of P=28(-4)(+4) per cent in the immediate afterglow of Swift gamma-ray burst GRB 120308A, four minutes after its discovery in the gamma-ray band, decreasing to P = 16(-4)(+5) per cent over the subsequent ten minutes. The polarization position angle remains stable, changing by no more than 15 degrees over this time, with a possible trend suggesting gradual rotation and ruling out plasma or magnetohydrodynamic instabilities. Instead, the polarization properties show that GRBs contain magnetized baryonic jets with large-scale uniform fields that can survive long after the initial explosion.
C1 [Mundell, C. G.; Arnold, D. M.; Steele, I. A.; Kobayashi, S.; Harrison, R. M.; Smith, R. J.; Virgili, F. J.] Liverpool John Moores Univ, Astrophys Res Inst, Liverpool L3 5RF, Merseyside, England.
   [Kopac, D.; Gomboc, A.; Japelj, J.] Univ Ljubljana, Fac Math & Phys, Ljubljana 1000, Slovenia.
   [Gomboc, A.] Ctr Excellence SPACE SI, Ljubljana 1000, Slovenia.
   [Guidorzi, C.] Univ Ferrara, Dept Phys, I-44122 Ferrara, Italy.
   [Melandri, A.] Brera Astron Observ, INAF, I-23807 Merate, LC, Italy.
C3 Liverpool John Moores University; University of Ljubljana; University of Ferrara; Istituto Nazionale Astrofisica (INAF)
RP Mundell, CG (corresponding author), Liverpool John Moores Univ, Astrophys Res Inst, IC2,Liverpool Sci Pk,146 Brownlow Hill, Liverpool L3 5RF, Merseyside, England.
EM c.mundell@ljmu.ac.uk
FU Royal Society; Wolfson Foundation; Science and Technology Facilities Council; Slovenian Research Agency; Centre of Excellence for Space Sciences and Technologies SPACE-SI; European Union; European Regional Development Fund; Republic of Slovenia, Ministry of Education, Science and Sport; STFC [ST/I505821/1, ST/J500732/1, ST/J001465/1] Funding Source: UKRI; Science and Technology Facilities Council [ST/J001465/1, ST/I505821/1, ST/J500732/1, 1096028] Funding Source: researchfish
NR 27
TC 120
Z9 125
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 DEC 5
PY 2013
VL 504
IS 7478
BP 119
EP +
DI 10.1038/nature12814
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 264BK
UT WOS:000327851700042
PM 24305162
DA 2026-03-09
ER

PT J
AU Ritz, R
   Halder, M
   Wagner, M
   Franz, C
   Bauer, A
   Pfleiderer, C
AF Ritz, R.
   Halder, M.
   Wagner, M.
   Franz, C.
   Bauer, A.
   Pfleiderer, C.
TI Formation of a topological non-Fermi liquid in MnSi
SO NATURE
LA English
DT Article
ID quantum phase-transition; state; breakdown
AB Fermi liquid theory provides a remarkably powerful framework for the description of the conduction electrons in metals and their ordering phenomena, such as superconductivity, ferromagnetism, and spin-and charge-density-wave order. A different class of ordering phenomena of great interest concerns spin configurations that are topologically protected, that is, their topology can be destroyed only by forcing the average magnetization locally to zero(1). Examples of such configurations are hedgehogs (points at which all spins are either pointing inwards or outwards) and vortices. A central question concerns the nature of the metallic state in the presence of such topologically distinct spin textures. Here we report a high-pressure study of the metallic state at the border of the skyrmion lattice in MnSi, which represents a new form of magnetic order composed of topologically non-trivial vortices(2). When long-range magnetic order is suppressed under pressure, the key characteristic of the skyrmion lattice-that is, the topological Hall signal due to the emergent magnetic flux associated with the topological winding-is unaffected in sign or magnitude and becomes an important characteristic of the metallic state. The regime of the topological Hall signal in temperature, pressure and magnetic field coincides thereby with the exceptionally extended regime of a pronounced non-Fermi-liquid resistivity(3,30). The observation of this topological Hall signal in the regime of the NFL resistivity suggests empirically that spin correlations with non-trivial topological character may drive a breakdown of Fermi liquid theory in pure metals.
C1 [Ritz, R.; Halder, M.; Wagner, M.; Franz, C.; Bauer, A.; Pfleiderer, C.] Tech Univ Munich, Phys Dept E21, D-85748 Garching, Germany.
C3 Technical University of Munich
RP Ritz, R (corresponding author), Tech Univ Munich, Phys Dept E21, D-85748 Garching, Germany.
EM robert.ritz@frm2.tum.de; christian.pfleiderer@frm2.tum.de
FU TUM Graduate School; DFG [TRR80, FOR960]; ERC-AdG [291079 TOPFIT]
NR 30
TC 114
Z9 122
U1 4
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 MAY 9
PY 2013
VL 497
IS 7448
BP 231
EP 234
DI 10.1038/nature12023
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 139CD
UT WOS:000318558200034
PM 23636328
DA 2026-03-09
ER

PT J
AU Keestra, AM
   Winter, MG
   Auburger, JJ
   Frässle, SP
   Xavier, MN
   Winter, SE
   Kim, A
   Poon, V
   Ravesloot, MM
   Waldenmaier, JFT
   Tsolis, RM
   Eigenheer, RA
   Baümler, AJ
AF Keestra, A. Marijke
   Winter, Maria G.
   Auburger, Josef J.
   Fraessle, Simon P.
   Xavier, Mariana N.
   Winter, Sebastian E.
   Kim, Anita
   Poon, Victor
   Ravesloot, Marietta M.
   Waldenmaier, Julian F. T.
   Tsolis, Renee M.
   Eigenheer, Richard A.
   Bauemler, Andreas J.
TI Manipulation of small Rho GTPases is a pathogen-induced process detected by NOD1
SO NATURE
LA English
DT Article
ID nf-kappa-b; serovar typhimurium colitis; salmonella-typhimurium; chemokine expression; nuclear responses; signaling pathway; epithelial-cells; host-cells; activation; model
AB Our innate immune system distinguishes microbes from self by detecting conserved pathogen-associated molecular patterns(1). However, these are produced by all microbes, regardless of their pathogenic potential. To distinguish virulent microbes from those with lower disease-causing potential the innate immune system detects conserved pathogen-induced processes(2), such as the presence of microbial products in the host cytosol, by mechanisms that are not fully resolved. Here we show that NOD1 senses cytosolic microbial products by monitoring the activation state of small Rho GTPases. Activation of RAC1 and CDC42 by bacterial delivery or ectopic expression of SopE, a virulence factor of the enteric pathogen Salmonella, triggered the NOD1 signalling pathway, with consequent RIP2 (also known as RIPK2)-mediated induction of NF-kappa B-dependent inflammatory responses. Similarly, activation of the NOD1 signalling pathway by peptidoglycan required RAC1 activity. Furthermore, constitutively active forms of RAC1, CDC42 and RHOA activated the NOD1 signalling pathway. Our data identify the activation of small Rho GTPases as a pathogen-induced process sensed through the NOD1 signalling pathway.
C1 [Keestra, A. Marijke; Winter, Maria G.; Auburger, Josef J.; Fraessle, Simon P.; Xavier, Mariana N.; Winter, Sebastian E.; Kim, Anita; Poon, Victor; Ravesloot, Marietta M.; Waldenmaier, Julian F. T.; Tsolis, Renee M.; Bauemler, Andreas J.] Univ Calif Davis, Sch Med, Dept Med Microbiol & Immunol, Davis, CA 95616 USA.
   [Eigenheer, Richard A.] Univ Calif Davis, UC Davis Genome Ctr, Prote Core Facil, Davis, CA 95616 USA.
C3 University of California System; University of California Davis; University of California System; University of California Davis
RP Baümler, AJ (corresponding author), Univ Calif Davis, Sch Med, Dept Med Microbiol & Immunol, 1 Shields Ave, Davis, CA 95616 USA.
EM ajbaumler@ucdavis.edu
FU Public Health Service Grants [AI044170, AI076246]; American Heart Association [12SDG12220022]; American Heart Association (AHA) [12SDG12220022] Funding Source: American Heart Association (AHA); National Institute of Allergy and Infectious Diseases [R01AI044170] Funding Source: NIH RePORTER
NR 33
TC 191
Z9 223
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 APR 11
PY 2013
VL 496
IS 7444
BP 233
EP +
DI 10.1038/nature12025
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 122VM
UT WOS:000317346300044
PM 23542589
DA 2026-03-09
ER

PT J
AU Miyazaki, T
   Sueyoshi, K
   Hiraga, T
AF Miyazaki, Tomonori
   Sueyoshi, Kenta
   Hiraga, Takehiko
TI Olivine crystals align during diffusion creep of Earth's upper mantle
SO NATURE
LA English
DT Article
ID grain-boundary; seismic anisotropy; forsterite; temperature; growth; size; flow; deformation; segregation; transitions
AB The crystallographic preferred orientation (CPO) of olivine produced during dislocation creep is considered to be the primary cause of elastic anisotropy in Earth's upper mantle and is often used to determine the direction of mantle flow. A fundamental question remains, however, as to whether the alignment of olivine crystals is uniquely produced by dislocation creep. Here we report the development of CPO in iron-free olivine (that is, forsterite) during diffusion creep; the intensity and pattern of CPO depend on temperature and the presence of melt, which control the appearance of crystallographic planes on grain boundaries. Grain boundary sliding on these crystallography-controlled boundaries accommodated by diffusion contributes to grain rotation, resulting in a CPO. We show that strong radial anisotropy is anticipated at temperatures corresponding to depths where melting initiates to depths where strongly anisotropic and low seismic velocities are detected. Conversely, weak anisotropy is anticipated at temperatures corresponding to depths where almost isotropic mantle is found. We propose diffusion creep to be the primary means of mantle flow.
C1 [Miyazaki, Tomonori; Sueyoshi, Kenta; Hiraga, Takehiko] Univ Tokyo, Earthquake Res Inst, Bunkyo Ku, Tokyo 1130032, Japan.
C3 University of Tokyo
RP Hiraga, T (corresponding author), Univ Tokyo, Earthquake Res Inst, Bunkyo Ku, 1-1-1 Yayoi, Tokyo 1130032, Japan.
EM hiraga@eri.u-tokyo.ac.jp
FU Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan; JSPS [23684043, 22000003, 21109005]; Earthquake Research Institute's cooperative research programme; Grants-in-Aid for Scientific Research [21109005, 23684043] Funding Source: KAKEN
NR 43
TC 132
Z9 153
U1 0
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 OCT 17
PY 2013
VL 502
IS 7471
BP 321
EP +
DI 10.1038/nature12570
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 235GY
UT WOS:000325706300043
PM 24132289
DA 2026-03-09
ER

PT J
AU Rigotti, M
   Barak, O
   Warden, MR
   Wang, XJ
   Daw, ND
   Miller, EK
   Fusi, S
AF Rigotti, Mattia
   Barak, Omri
   Warden, Melissa R.
   Wang, Xiao-Jing
   Daw, Nathaniel D.
   Miller, Earl K.
   Fusi, Stefano
TI The importance of mixed selectivity in complex cognitive tasks
SO NATURE
LA English
DT Article
ID information; cortex; model
AB Single-neuron activity in the prefrontal cortex (PFC) is tuned to mixtures of multiple task-related aspects. Such mixed selectivity is highly heterogeneous, seemingly disordered and therefore difficult to interpret. We analysed the neural activity recorded in monkeys during an object sequence memory task to identify a role of mixed selectivity in subserving the cognitive functions ascribed to the PFC. We show that mixed selectivity neurons encode distributed information about all task-relevant aspects. Each aspect can be decoded from the population of neurons even when single-cell selectivity to that aspect is eliminated. Moreover, mixed selectivity offers a significant computational advantage over specialized responses in terms of the repertoire of input-output functions implementable by readout neurons. This advantage originates from the highly diverse nonlinear selectivity to mixtures of task-relevant variables, a signature of high-dimensional neural representations. Crucially, this dimensionality is predictive of animal behaviour as it collapses in error trials. Our findings recommend a shift of focus for future studies from neurons that have easily interpretable response tuning to the widely observed, but rarely analysed, mixed selectivity neurons.
C1 [Rigotti, Mattia; Barak, Omri; Fusi, Stefano] Columbia Univ Coll Phys & Surg, Ctr Theoret Neurosci, New York, NY 10032 USA.
   [Rigotti, Mattia; Wang, Xiao-Jing; Daw, Nathaniel D.] NYU, Ctr Neural Sci, New York, NY 10003 USA.
   [Rigotti, Mattia; Daw, Nathaniel D.] NYU, Dept Psychol, New York, NY 10003 USA.
   [Warden, Melissa R.; Miller, Earl K.] MIT, Picower Inst Learning & Memory, Cambridge, MA 02139 USA.
   [Warden, Melissa R.; Miller, Earl K.] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA.
   [Warden, Melissa R.] Stanford Univ, Dept Bioengn, Stanford, CA 94305 USA.
   [Wang, Xiao-Jing] Yale Univ, Sch Med, Dept Neurobiol, Kavli Inst Neurosci, New Haven, CT 06525 USA.
C3 Columbia University; New York University; New York University; Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); Stanford University; Yale University
RP Fusi, S (corresponding author), Columbia Univ Coll Phys & Surg, Ctr Theoret Neurosci, 630 W 168th St, New York, NY 10032 USA.
EM sf2237@columbia.edu
FU Gatsby Foundation; Swartz Foundation; Kavli Foundation; Swiss National Science Foundation [PBSKP3-133357]; Janggen-Poehn Foundation; McKnight Foundation; McDonnell Foundation; NIMH [5-R37-MH087027-04]; Picower Foundation; Brain & Behavior Research Foundation; NARSAD; Swiss National Science Foundation (SNF) [PBSKP3_133357] Funding Source: Swiss National Science Foundation (SNF)
NR 23
TC 1058
Z9 1307
U1 4
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 30
PY 2013
VL 497
IS 7451
BP 585
EP 590
DI 10.1038/nature12160
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 152UF
UT WOS:000319556100036
PM 23685452
DA 2026-03-09
ER

PT J
AU Campbell, CS
   Desai, A
AF Campbell, Christopher S.
   Desai, Arshad
TI Tension sensing by Aurora B kinase is independent of survivin-based centromere localization
SO NATURE
LA English
DT Article
ID proper chromosome segregation; saccharomyces-cerevisiae; spindle checkpoint; budding yeast; protein-kinase; complex; incenp; phosphorylation; orientation; biorientation
AB Accurate segregation of the replicated genome requires chromosome biorientation on the spindle. Biorientation is ensured by Aurora B kinase (Ipl1), a member of the four-subunit chromosomal passenger complex (CPC)(1,2). Localization of the CPC to the inner centromere is central to the current model for how tension ensures chromosome biorientation: kinetochore-spindle attachments that are not under tension remain close to the inner centromere and are destabilized by Aurora B phosphorylation, whereas kinetochores under tension are pulled away from the influence of Aurora B, stabilizing their microtubule attachments(3-5). Here we show that an engineered truncation of the Sli15 (known as INCENP in humans) subunit of budding yeast CPC that eliminates association with the inner centromere nevertheless supports proper chromosome segregation during both mitosis and meiosis. Truncated Sli15 suppresses the deletion phenotypes of the innercentromere-targeting proteins survivin (Bir1), borealin (Nbl1), Bub1 and Sgo1 (ref. 6). Unlike wild-type Sli15, truncated Sli15 localizes to pre-anaphase spindle microtubules. Premature targeting of full-length Sli15 to microtubules by preventing Cdk1 (also known as Cdc28) phosphorylation also suppresses the inviability of Bir1 deletion. These results suggest that activation of Aurora B kinase by clustering either on chromatin or on microtubules is sufficient for chromosome biorientation.
C1 [Campbell, Christopher S.; Desai, Arshad] Univ Calif San Diego, Ludwig Inst Canc Res, La Jolla, CA 92037 USA.
   [Campbell, Christopher S.; Desai, Arshad] Univ Calif San Diego, Dept Cellular & Mol Med, La Jolla, CA 92037 USA.
C3 University of California System; University of California San Diego; Ludwig Institute for Cancer Research; University of California System; University of California San Diego
RP Desai, A (corresponding author), Univ Calif San Diego, Ludwig Inst Canc Res, La Jolla, CA 92037 USA.
EM abdesai@ucsd.edu
FU National Institutes of Health (NIH) [GM074215]; Damon Runyon Cancer Research Foundation Fellowship [DRG 2007-09]; Ludwig Institute for Cancer Research; National Institute of General Medical Sciences [R01GM074215] Funding Source: NIH RePORTER
NR 30
TC 111
Z9 141
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 MAY 2
PY 2013
VL 497
IS 7447
BP 118
EP +
DI 10.1038/nature12057
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 134OK
UT WOS:000318221500045
PM 23604256
DA 2026-03-09
ER

PT J
AU Shoji-Kawata, S
   Sumpter, R
   Leveno, M
   Campbell, GR
   Zou, ZJ
   Kinch, L
   Wilkins, AD
   Sun, QH
   Pallauf, K
   MacDuff, D
   Huerta, C
   Virgin, HW
   Helms, JB
   Eerland, R
   Tooze, SA
   Xavier, R
   Lenschow, DJ
   Yamamoto, A
   King, D
   Lichtarge, O
   Grishin, NV
   Spector, SA
   Kaloyanova, DV
   Levine, B
AF Shoji-Kawata, Sanae
   Sumpter, Rhea, Jr.
   Leveno, Matthew
   Campbell, Grant R.
   Zou, Zhongju
   Kinch, Lisa
   Wilkins, Angela D.
   Sun, Qihua
   Pallauf, Kathrin
   MacDuff, Donna
   Huerta, Carlos
   Virgin, Herbert W.
   Helms, J. Bernd
   Eerland, Ruud
   Tooze, Sharon A.
   Xavier, Ramnik
   Lenschow, Deborah J.
   Yamamoto, Ai
   King, David
   Lichtarge, Olivier
   Grishin, Nick V.
   Spector, Stephen A.
   Kaloyanova, Dora V.
   Levine, Beth
TI Identification of a candidate therapeutic autophagy-inducing peptide
SO NATURE
LA English
DT Article
ID protein; disease; pathogenesis; macrophages; localizes; infection; beclin-1; pathway; complex; binding
AB The lysosomal degradation pathway of autophagy has a crucial role in defence against infection, neurodegenerative disorders, cancer and ageing. Accordingly, agents that induce autophagy may have broad therapeutic applications. One approach to developing such agents is to exploit autophagy manipulation strategies used by microbial virulence factors. Here we show that a peptide, Tat-beclin 1-derived from a region of the autophagy protein, beclin 1, which binds human immunodeficiency virus (HIV)-1 Nef-is a potent inducer of autophagy, and interacts with a newly identified negative regulator of autophagy, GAPR-1 (also called GLIPR2). Tat-beclin 1 decreases the accumulation of polyglutamine expansion protein aggregates and the replication of several pathogens (including HIV-1) in vitro, and reduces mortality in mice infected with chikungunya or West Nile virus. Thus, through the characterization of a domain of beclin 1 that interacts with HIV-1 Nef, we have developed an autophagy-inducing peptide that has potential efficacy in the treatment of human diseases.
C1 [Shoji-Kawata, Sanae; Sumpter, Rhea, Jr.; Leveno, Matthew; Zou, Zhongju; Sun, Qihua; Pallauf, Kathrin; Levine, Beth] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Dallas, TX 75390 USA.
   [Shoji-Kawata, Sanae; Sumpter, Rhea, Jr.; Leveno, Matthew; Zou, Zhongju; Sun, Qihua; Levine, Beth] Univ Texas SW Med Ctr Dallas, Ctr Autophagy Res, Dallas, TX 75390 USA.
   [Campbell, Grant R.; Spector, Stephen A.] Univ Calif San Diego, Dept Pediat, La Jolla, CA 92093 USA.
   [Campbell, Grant R.; Spector, Stephen A.] Rady Childrens Hosp, San Diego, CA 92123 USA.
   [Zou, Zhongju; Kinch, Lisa; Grishin, Nick V.; Levine, Beth] Univ Texas SW Med Ctr Dallas, Howard Hughes Med Inst, Dallas, TX 75390 USA.
   [Kinch, Lisa; Huerta, Carlos; Grishin, Nick V.] Univ Texas SW Med Ctr Dallas, Dept Biochem, Dallas, TX 75390 USA.
   [Wilkins, Angela D.; Lichtarge, Olivier] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA.
   [MacDuff, Donna; Virgin, Herbert W.; Lenschow, Deborah J.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA.
   [Helms, J. Bernd; Eerland, Ruud; Kaloyanova, Dora V.] Univ Utrecht, Dept Biochem & Cell Biol, NL-3508 TD Utrecht, Netherlands.
   [Helms, J. Bernd; Eerland, Ruud; Kaloyanova, Dora V.] Univ Utrecht, Inst Biomembranes, NL-3508 TD Utrecht, Netherlands.
   [Tooze, Sharon A.] Canc Res UK, London Res Inst, London EC1V 4AD, England.
   [Xavier, Ramnik] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Computat & Integrat Biol, Boston, MA 02114 USA.
   [Xavier, Ramnik] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA 02114 USA.
   [Xavier, Ramnik] Broad Inst Harvard & Massachusetts Inst Technol, Cambridge, MA 02142 USA.
   [Lenschow, Deborah J.] Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA.
   [Yamamoto, Ai] Columbia Univ Coll Phys & Surg, Dept Neurol, New York, NY 10032 USA.
   [King, David] Univ Calif Berkeley, Howard Hughes Med Inst, Berkeley, CA 94720 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 California System; University of California San Diego; Rady Childrens Hospital San Diego; University of Texas System; University of Texas Southwestern Medical Center; Howard Hughes Medical Institute; University of Texas System; University of Texas Southwestern Medical Center; Baylor College of Medicine; Washington University (WUSTL); Utrecht University; Utrecht University; Cancer Research UK; Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard Medical School; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Washington University (WUSTL); Columbia University; Howard Hughes Medical Institute; University of California System; University of California Berkeley; University of Texas System; University of Texas Southwestern Medical Center
RP Levine, B (corresponding author), Univ Texas SW Med Ctr Dallas, Dept Internal Med, Dallas, TX 75390 USA.
EM beth.levine@utsouthwestern.edu
FU NIH [U54AI057156, K08 AI099150, ROI NS077874, RO1 GM094575, ROI GM066099, ROI GM079656, ROI NS063973, ROI NS050199, U54AI057160, ROI DK083756, ROI DK086502, T32 GM008297]; NSF [CCF-0905536]; NWO-ALW Open Program [817.02.023]; Cancer Research UK; Welch Foundation [I-15-5]; Cancer Research UK [15153] Funding Source: researchfish; Direct For Biological Sciences; Div Of Biological Infrastructure [1062455] Funding Source: National Science Foundation; National Cancer Institute [P30CA142543] Funding Source: NIH RePORTER; National Institute of General Medical Sciences [R01GM066099] Funding Source: NIH RePORTER; National Institute of Neurological Disorders and Stroke [R01NS077111] Funding Source: NIH RePORTER
NR 27
TC 658
Z9 746
U1 1
U2 238
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 14
PY 2013
VL 494
IS 7436
BP 201
EP 206
DI 10.1038/nature11866
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 092QS
UT WOS:000315137700032
PM 23364696
DA 2026-03-09
ER

PT J
AU Xiong, Y
   McCormack, M
   Li, L
   Hall, Q
   Xiang, CB
   Sheen, J
AF Xiong, Yan
   McCormack, Matthew
   Li, Lei
   Hall, Qi
   Xiang, Chengbin
   Sheen, Jen
TI Glucose-TOR signalling reprograms the transcriptome and activates meristems
SO NATURE
LA English
DT Article
ID e2f target genes; arabidopsis; root; growth; rapamycin; proliferation; expression; nutrient; energy; differentiation
AB Meristems encompass stem/progenitor cells that sustain postembryonic growth of all plant organs. How meristems are activated and sustained by nutrient signalling remains enigmatic in photosynthetic plants. Combining chemical manipulations and chemical genetics at the photoautotrophic transition checkpoint, we reveal that shoot photosynthesis-derived glucose drives target-of-rapamycin (TOR) signalling relays through glycolysis and mitochondrial bioenergetics to control root meristem activation, which is decoupled from direct glucose sensing, growth-hormone signalling and stem-cell maintenance. Surprisingly, glucose-TOR signalling dictates transcriptional reprogramming of remarkable gene sets involved in central and secondary metabolism, cell cycle, transcription, signalling, transport and protein folding. Systems, cellular and genetic analyses uncover TOR phosphorylation of E2Fa transcription factor for an unconventional activation of S-phase genes, and glucose-signalling defects in e2fa root meristems. Our findings establish pivotal roles of glucose-TOR signalling in unprecedented transcriptional networks wiring central metabolism and biosynthesis for energy and biomass production, and integrating localized stem/progenitor-cell proliferation through inter-organ nutrient coordination to control developmental transition and growth.
C1 [Xiong, Yan; McCormack, Matthew; Li, Lei; Hall, Qi; Sheen, Jen] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
   [Xiong, Yan; McCormack, Matthew; Li, Lei; Hall, Qi; Sheen, Jen] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA.
   [Xiong, Yan; McCormack, Matthew; Li, Lei; Hall, Qi; Sheen, Jen] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA.
   [Xiang, Chengbin] Univ Sci & Technol China, Sch Life Sci, Hefei 230023, Peoples R China.
C3 Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard Medical School; Chinese Academy of Sciences; University of Science & Technology of China, CAS
RP Xiong, Y (corresponding author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
EM xiong@molbio.mgh.harvard.edu; sheen@molbio.mgh.harvard.edu
FU MGH Tosteson Postdoctoral Fellowship; Chinese Academy of Sciences [KSCX3-YW-N-007]; NSF; NIH; WJC Special Project RDA-Korea [PJ009106]
NR 42
TC 663
Z9 749
U1 14
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 APR 11
PY 2013
VL 496
IS 7444
BP 181
EP +
DI 10.1038/nature12030
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 122VM
UT WOS:000317346300033
PM 23542588
DA 2026-03-09
ER

PT J
AU Moum, JN
   Perlin, A
   Nash, JD
   McPhaden, MJ
AF Moum, James N.
   Perlin, Alexander
   Nash, Jonathan D.
   McPhaden, Michael J.
TI Seasonal sea surface cooling in the equatorial Pacific cold tongue controlled by ocean mixing
SO NATURE
LA English
DT Article
ID tropical pacific; annual cycle; shear-flow; temperature; turbulence; instability; balance; models; budget
AB Sea surface temperature (SST) is a critical control on the atmosphere(1), and numerical models of atmosphere-ocean circulation emphasize its accurate prediction. Yet many models demonstrate large, systematic biases in simulated SST in the equatorial 'cold tongues' (expansive regions of net heat uptake from the atmosphere) of the Atlantic(2) and Pacific(3) oceans, particularly with regard to a central but little-understood feature of tropical oceans: a strong seasonal cycle. The biases may be related to the inability of models to constrain turbulent mixing realistically(4), given that turbulent mixing, combined with seasonal variations in atmospheric heating, determines SST. In temperate oceans, the seasonal SST cycle is clearly related to varying solar heating(5); in the tropics, however, SSTs vary seasonally in the absence of similar variations in solar inputs(6). Turbulent mixing has long been a likely explanation, but firm, long-term observational evidence has been absent. Here we show the existence of a distinctive seasonal cycle of subsurface cooling via mixing in the equatorial Pacific cold tongue, using multi-year measurements of turbulence in the ocean. In boreal spring, SST rises by 2 kelvin when heating of the upper ocean by the atmosphere exceeds cooling by mixing from below. In boreal summer, SST decreases because cooling from below exceeds heating from above. When the effects of lateral advection are considered, the magnitude of summer cooling via mixing (4 kelvin per month) is equivalent to that required to counter the heating terms. These results provide quantitative assessment of how mixing varies on timescales longer than a few weeks, clearly showing its controlling influence on seasonal cooling of SST in a critical oceanic regime.
C1 [Moum, James N.; Perlin, Alexander; Nash, Jonathan D.] Oregon State Univ, Coll Earth Ocean & Atmospher Sci, Corvallis, OR 97331 USA.
   [McPhaden, Michael J.] NOAA, Pacific Marine Environm Lab, Seattle, WA 98115 USA.
C3 Oregon State University; National Oceanic Atmospheric Admin (NOAA) - USA
RP Moum, JN (corresponding author), Oregon State Univ, Coll Earth Ocean & Atmospher Sci, Corvallis, OR 97331 USA.
EM moum@coas.oregonstate.edu
FU National Science Foundation [0424133, 0728375, 1256620]; Division Of Ocean Sciences; Directorate For Geosciences [0424133, 0728375, 1256620] Funding Source: National Science Foundation
NR 28
TC 126
Z9 137
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 AUG 1
PY 2013
VL 500
IS 7460
BP 64
EP 67
DI 10.1038/nature12363
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 192VK
UT WOS:000322514800028
PM 23883934
DA 2026-03-09
ER

PT J
AU Tannahill, GM
   Curtis, AM
   Adamik, J
   Palsson-McDermott, EM
   McGettrick, AF
   Goel, G
   Frezza, C
   Bernard, NJ
   Kelly, B
   Foley, NH
   Zheng, L
   Gardet, A
   Tong, Z
   Jany, SS
   Corr, SC
   Haneklaus, M
   Caffrey, BE
   Pierce, K
   Walmsley, S
   Beasley, FC
   Cummins, E
   Nizet, V
   Whyte, M
   Taylor, CT
   Lin, H
   Masters, SL
   Gottlieb, E
   Kelly, VP
   Clish, C
   Auron, PE
   Xavier, RJ
   O'Neill, LAJ
AF Tannahill, G. M.
   Curtis, A. M.
   Adamik, J.
   Palsson-McDermott, E. M.
   McGettrick, A. F.
   Goel, G.
   Frezza, C.
   Bernard, N. J.
   Kelly, B.
   Foley, N. H.
   Zheng, L.
   Gardet, A.
   Tong, Z.
   Jany, S. S.
   Corr, S. C.
   Haneklaus, M.
   Caffrey, B. E.
   Pierce, K.
   Walmsley, S.
   Beasley, F. C.
   Cummins, E.
   Nizet, V.
   Whyte, M.
   Taylor, C. T.
   Lin, H.
   Masters, S. L.
   Gottlieb, E.
   Kelly, V. P.
   Clish, C.
   Auron, P. E.
   Xavier, R. J.
   O'Neill, L. A. J.
TI Succinate is an inflammatory signal that induces IL-1β through HIF-1α
SO NATURE
LA English
DT Article
ID receptor gpr91; hypoxia; activation; links; inhibition; metabolism; mechanism; promoter; mutation; provides
AB Macrophages activated by the Gram-negative bacterial product lipopolysaccharide switch their core metabolism from oxidative phosphorylation to glycolysis(1). Here we show that inhibition of glycolysis with 2-deoxyglucose suppresses lipopolysaccharide-induced interleukin-1 beta but not tumour-necrosis factor-a in mouse macrophages. A comprehensive metabolic map of lipopolysaccharide-activated macrophages shows upregulation of glycolytic and down-regulation of mitochondrial genes, which correlates directly with the expression profiles of altered metabolites. Lipopolysaccharide strongly increases the levels of the tricarboxylic-acid cycle intermediate succinate. Glutamine-dependent anerplerosis is the principal source of succinate, although the 'GABA (gamma-aminobutyric acid) shunt' pathway also has a role. Lipopolysaccharide-induced succinate stabilizes hypoxia-inducible factor-1 alpha, an effect that is inhibited by 2-deoxyglucose, with interleukin-1 beta as an important target. Lipopolysaccharide also increases succinylation of several proteins. We therefore identify succinate as a metabolite in innate immune signalling, which enhances interleukin-1 beta production during inflammation.
C1 [Tannahill, G. M.; Curtis, A. M.; Palsson-McDermott, E. M.; McGettrick, A. F.; Bernard, N. J.; Kelly, B.; Foley, N. H.; Jany, S. S.; Corr, S. C.; Haneklaus, M.; Kelly, V. P.; O'Neill, L. A. J.] Trinity Coll Dublin, Sch Biochem & Immunol, Trinity Biomed Sci Inst, Dublin 2, Ireland.
   [Adamik, J.; Auron, P. E.] Duquesne Univ, Dept Biol Sci, Pittsburgh, PA 15282 USA.
   [Goel, G.; Xavier, R. J.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Richard B Simches Res Ctr, Boston, MA 02114 USA.
   [Frezza, C.; Zheng, L.; Gottlieb, E.] Beatson Inst Canc Res, Apoptosis & Tumour Physiol Lab, Glasgow G61 1BD, Lanark, Scotland.
   [Frezza, C.; Xavier, R. J.] Hutchison MRC Res Ctr, Med Res Council Canc Cell Unit, Cambridge CB2 0X2, England.
   [Gardet, A.; Pierce, K.; Clish, C.] Broad Inst MIT & Harvard, Cambridge Ctr 7, Cambridge, MA 02142 USA.
   [Tong, Z.; Lin, H.] Cornell Univ, Dept Chem & Chem Biol, Ithaca, NY 14853 USA.
   [Caffrey, B. E.] Trinity Coll Dublin, Smurfit Inst Genet, Dublin 2, Ireland.
   [Walmsley, S.; Whyte, M.] Univ Sheffield, Dept Infect & Immun, Acad Unit Resp Med, Sheffield S10 2RX, S Yorkshire, England.
   [Beasley, F. C.; Nizet, V.] Univ Calif San Diego, Ctr Neural Circuits & Behav, Div Pediat, V Nizet Lab, La Jolla, CA 92093 USA.
   [Cummins, E.; Taylor, C. T.] Univ Coll Dublin, Conway Inst, Dublin 4, Ireland.
   [Masters, S. L.] Walter & Eliza Hall Inst Med Res, Inflammat Div, Parkville, Vic 3052, Australia.
C3 Trinity College Dublin; Duquesne University; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Beatson Institute; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Cornell University; Trinity College Dublin; University of Sheffield; University of California System; University of California San Diego; University College Dublin; Walter & Eliza Hall Institute
RP O'Neill, LAJ (corresponding author), Trinity Coll Dublin, Sch Biochem & Immunol, Trinity Biomed Sci Inst, Dublin 2, Ireland.
EM laoneill@tcd.ie
FU European Research Council; Science Foundation Ireland; Health Research Board; European Union FP7 programme 'TIMER'; Wellcome Trust; National Institutes of Health; Helmsley Trust; Nestle Research Centre; VESKI; Duquesne University Hunkele Dreaded Disease Award; Interleukin Foundation; National Health and Medical Research Council; Medical Research Council [MC_UP_1101/3] Funding Source: researchfish; MRC [MC_UP_1101/3] Funding Source: UKRI
NR 30
TC 3251
Z9 3678
U1 26
U2 570
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 11
PY 2013
VL 496
IS 7444
BP 238
EP +
DI 10.1038/nature11986
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 122VM
UT WOS:000317346300045
PM 23535595
DA 2026-03-09
ER

PT J
AU MacDougall, AS
   McCann, KS
   Gellner, G
   Turkington, R
AF MacDougall, A. S.
   McCann, K. S.
   Gellner, G.
   Turkington, R.
TI Diversity loss with persistent human disturbance increases vulnerability to ecosystem collapse
SO NATURE
LA English
DT Article
ID biodiversity; stability; shifts
AB Long-term and persistent human disturbances have simultaneously altered the stability and diversity of ecological systems, with disturbances directly reducing functional attributes such as invasion resistance, while eliminating the buffering effects of high species diversity(1-4). Theory predicts that this combination of environmental change and diversity loss increases the risk of abrupt and potentially irreversible ecosystem collapse(1-3,5-7), but long-term empirical evidence from natural systems is lacking. Here we demonstrate this relationship in a degraded but species-rich pyrogenic grassland in which the combined effects of fire suppression, invasion and trophic collapse have created a species-poor grassland that is highly productive, resilient to yearly climatic fluctuations, and resistant to invasion, but vulnerable to rapid collapse after the re-introduction of fire. We initially show how human disturbance has created a negative relationship between diversity and function, contrary to theoretical predictions(3,4). Fire prevention since the mid-nineteenth century is associated with the loss of plant species but it has stabilized high-yield annual production and invasion resistance, comparable to a managed high-yield low-diversity agricultural system. In managing for fire suppression, however, a hidden vulnerability to sudden environmental change emerges that is explained by the elimination of the buffering effects of high species diversity. With the re-introduction of fire, grasslands only persist in areas with remnant concentrations of native species, in which a range of rare and mostly functionally redundant plants proliferate after burning and prevent extensive invasion including a rapid conversion towards woodland. This research shows how biodiversity can be crucial for ecosystem stability despite appearing functionally insignificant beforehand, a relationship probably applicable to many ecosystems given the globally prevalent combination of intensive long-term land management and species loss.
C1 [MacDougall, A. S.; McCann, K. S.; Gellner, G.] Univ Guelph, Dept Integrat Biol, Guelph, ON N1G 2W1, Canada.
   [Turkington, R.] Univ British Columbia, Dept Bot, Vancouver, BC V6T 1Z4, Canada.
   [Turkington, R.] Univ British Columbia, Biodivers Res Ctr, Vancouver, BC V6T 1Z4, Canada.
C3 University of Guelph; University of British Columbia; University of British Columbia
RP MacDougall, AS (corresponding author), Univ Guelph, Dept Integrat Biol, Guelph, ON N1G 2W1, Canada.
EM amacdo02@uoguelph.ca
FU NSERC; World Wildlife Fund Endangered Species Recovery Fund; Mountain Equipment Co-Op Environmental Research Fund; University of Guelph
NR 25
TC 280
Z9 354
U1 9
U2 618
PU NATURE PUBLISHING 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 7
PY 2013
VL 494
IS 7435
BP 86
EP 89
DI 10.1038/nature11869
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 087DJ
UT WOS:000314741200039
PM 23389543
DA 2026-03-09
ER

PT J
AU Carretti, E
   Crocker, RM
   Staveley-Smith, L
   Haverkorn, M
   Purcell, C
   Gaensler, BM
   Bernardi, G
   Kesteven, MJ
   Poppi, S
AF Carretti, Ettore
   Crocker, Roland M.
   Staveley-Smith, Lister
   Haverkorn, Marijke
   Purcell, Cormac
   Gaensler, B. M.
   Bernardi, Gianni
   Kesteven, Michael J.
   Poppi, Sergio
TI Giant magnetized outflows from the centre of the Milky Way
SO NATURE
LA English
DT Article
ID x-ray-emission; galactic-center; fermi bubbles; cosmic-rays; gamma-rays; field; wind; nucleus; galaxy; bulge
AB The nucleus of the Milky Way is known to harbour regions of intense star formation activity as well as a supermassive black hole(1). Recent observations have revealed regions of gamma-ray emission reaching far above and below the Galactic Centre (relative to the Galactic plane), the so-called 'Fermi bubbles'(2). It is uncertain whether these were generated by nuclear star formation or by quasar-like outbursts of the central black hole(3-6) and no information on the structures' magnetic field has been reported. Here we report observations of two giant, linearly polarized radio lobes, containing three ridgelike substructures, emanating from the Galactic Centre. The lobes each extend about 60 degrees in the Galactic bulge, closely corresponding to the Fermi bubbles, and are permeated by strong magnetic fields of up to 15 microgauss. We conclude that the radio lobes originate in a biconical, star-formation-driven (rather than black-hole-driven) outflow from the Galaxy's central 200 parsecs that transports a huge amount of magnetic energy, about 10(55) ergs, into the Galactic halo. The ridges wind around this outflow and, we suggest, constitute a 'phonographic' record of nuclear star formation activity over at least ten million years.
C1 [Carretti, Ettore] CSIRO Astron & Space Sci, Parkes, NSW 2870, Australia.
   [Crocker, Roland M.] Max Planck Inst Kernphys, D-69029 Heidelberg, Germany.
   [Crocker, Roland M.] Australian Natl Univ, Res Sch Astron & Astrophys, Weston, ACT 2611, Australia.
   [Staveley-Smith, Lister] Univ Western Australia, Int Ctr Radio Astron Res, Crawley, WA 6009, Australia.
   [Staveley-Smith, Lister] Univ Western Australia, ARC Ctr Excellence All sky Astrophys CAASTRO, Crawley, WA 6009, Australia.
   [Haverkorn, Marijke] Radboud Univ Nijmegen, Dept Astrophys IMAPP, NL-6500 GL Nijmegen, Netherlands.
   [Haverkorn, Marijke] Leiden Univ, Leiden Observ, NL-2300 RA Leiden, Netherlands.
   [Purcell, Cormac; Gaensler, B. M.] Univ Sydney, Sydney Inst Astron, Sch Phys, Sydney, NSW 2006, Australia.
   [Bernardi, Gianni] Harvard Smithsonian Ctr Astrophys, Cambridge, MA 02138 USA.
   [Kesteven, Michael J.] CSIRO Astron & Space Sci, Epping, NSW 1710, Australia.
   [Poppi, Sergio] INAF Osservatorio Astron Cagliari, I-09012 Capoterra, CA, Italy.
C3 Commonwealth Scientific & Industrial Research Organisation (CSIRO); CSIRO Astronomy & Space; Max Planck Society; Australian National University; University of Western Australia; University of Western Australia; Radboud University Nijmegen; Leiden University - Excl LUMC; Leiden University; University of Sydney; Smithsonian Astrophysical Observatory; Smithsonian Institution; Harvard University; Commonwealth Scientific & Industrial Research Organisation (CSIRO); CSIRO Astronomy & Space; Istituto Nazionale Astrofisica (INAF)
RP Carretti, E (corresponding author), CSIRO Astron & Space Sci, POB 276, Parkes, NSW 2870, Australia.
EM Ettore.Carretti@csiro.au
FU Max-Planck-Institut fur Kernphysik; Australian Research Council [FT110100108]; Australian Laureate Fellowship from the Australian Research Council [FL100100114]; Netherlands Organisation for Scientific Research (NWO) [639.042.915]; Australian Research Council [FT110100108] Funding Source: Australian Research Council
NR 29
TC 189
Z9 204
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 3
PY 2013
VL 493
IS 7430
BP 66
EP 69
DI 10.1038/nature11734
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 062QC
UT WOS:000312933800031
PM 23282363
DA 2026-03-09
ER

PT J
AU Zhou, F
   Lin, QB
   Zhu, LH
   Ren, YL
   Zhou, KN
   Shabek, N
   Wu, FQ
   Mao, HB
   Dong, W
   Gan, L
   Ma, WW
   Gao, H
   Chen, J
   Yang, C
   Wang, D
   Tan, JJ
   Zhang, X
   Guo, XP
   Wang, JL
   Jiang, L
   Liu, X
   Chen, WQ
   Chu, JF
   Yan, CY
   Ueno, K
   Ito, S
   Asami, T
   Cheng, ZJ
   Wang, J
   Lei, CL
   Zhai, HQ
   Wu, CY
   Wang, HY
   Zheng, N
   Wan, JM
AF Zhou, Feng
   Lin, Qibing
   Zhu, Lihong
   Ren, Yulong
   Zhou, Kunneng
   Shabek, Nitzan
   Wu, Fuqing
   Mao, Haibin
   Dong, Wei
   Gan, Lu
   Ma, Weiwei
   Gao, He
   Chen, Jun
   Yang, Chao
   Wang, Dan
   Tan, Junjie
   Zhang, Xin
   Guo, Xiuping
   Wang, Jiulin
   Jiang, Ling
   Liu, Xi
   Chen, Weiqi
   Chu, Jinfang
   Yan, Cunyu
   Ueno, Kotomi
   Ito, Shinsaku
   Asami, Tadao
   Cheng, Zhijun
   Wang, Jie
   Lei, Cailin
   Zhai, Huqu
   Wu, Chuanyin
   Wang, Haiyang
   Zheng, Ning
   Wan, Jianmin
TI D14-SCFD3-dependent degradation of D53 regulates strigolactone signalling
SO NATURE
LA English
DT Article
ID box protein tir1; gene-expression; arabidopsis; rice; perception; outgrowth; max2; germination; inhibition; karrikin
AB Strigolactones (SLs), a newly discovered class of carotenoid-derived phytohormones, are essential for developmental processes that shape plant architecture and interactions with parasitic weeds and symbiotic arbuscular mycorrhizal fungi. Despite the rapid progress in elucidating the SL biosynthetic pathway, the perception and signalling mechanisms of SL remain poorly understood. Here we show that DWARF 53 (D53) acts as a repressor of SL signalling and that SLs induce its degradation. We find that the rice (Oryza sativa) d53 mutant, which produces an exaggerated number of tillers compared to wild-type plants, is caused by a gain-of-function mutation and is insensitive to exogenous SL treatment. The D53 gene product shares predicted features with the class I Clp ATPase proteins and can form a complex with the a/b hydrolase protein DWARF 14 (D14) and the F-box protein DWARF 3 (D3), two previously identified signalling components potentially responsible for SL perception. We demonstrate that, in a D14- and D3-dependent manner, SLs induce D53 degradation by the proteasome and abrogate its activity in promoting axillary bud outgrowth. Our combined genetic and biochemical data reveal that D53 acts as a repressor of the SL signalling pathway, whose hormone-induced degradation represents a key molecular link between SL perception and responses.
C1 [Zhou, Feng; Zhu, Lihong; Zhou, Kunneng; Gao, He; Yang, Chao; Jiang, Ling; Liu, Xi; Wan, Jianmin] Nanjing Agr Univ, Jiangsu Plant Gene Engn Res Ctr, Natl Key Lab Crop Genet & Germplasm Enhancement, Nanjing 210095, Jiangsu, Peoples R China.
   [Zhou, Feng; Lin, Qibing; Ren, Yulong; Wu, Fuqing; Dong, Wei; Gan, Lu; Ma, Weiwei; Chen, Jun; Wang, Dan; Tan, Junjie; Zhang, Xin; Guo, Xiuping; Wang, Jiulin; Cheng, Zhijun; Wang, Jie; Lei, Cailin; Zhai, Huqu; Wu, Chuanyin; Wang, Haiyang; Wan, Jianmin] Chinese Acad Agr Sci, Inst Crop Sci, Natl Key Facil Crop Gene Resources & Genet Improv, Beijing 100081, Peoples R China.
   [Shabek, Nitzan; Mao, Haibin; Zheng, Ning] Univ Washington, Dept Pharmacol, Seattle, WA 98195 USA.
   [Shabek, Nitzan; Mao, Haibin; Zheng, Ning] Univ Washington, Howard Hughes Med Inst, Seattle, WA 98195 USA.
   [Chen, Weiqi; Chu, Jinfang; Yan, Cunyu] Chinese Acad Sci, Inst Genet & Dev Biol, Natl Ctr Plant Gene Res Beijing, Beijing 100101, Peoples R China.
   [Ueno, Kotomi; Ito, Shinsaku; Asami, Tadao] Univ Tokyo, Dept Appl Biol Chem, Bunkyo Ku, Tokyo 1138657, Japan.
C3 Nanjing Agricultural University; Chinese Academy of Agricultural Sciences; Institute of Crop Sciences, CAAS; University of Washington; University of Washington Seattle; University of Washington; University of Washington Seattle; Howard Hughes Medical Institute; Chinese Academy of Sciences; Institute of Genetics & Developmental Biology, CAS; University of Tokyo
RP Wan, JM (corresponding author), Nanjing Agr Univ, Jiangsu Plant Gene Engn Res Ctr, Natl Key Lab Crop Genet & Germplasm Enhancement, Nanjing 210095, Jiangsu, Peoples R China.
EM wanghaiyang@caas.cn; nzheng@u.washington.edu; wanjm@njau.edu.cn
FU National Transgenic Science and Technology Program [2011ZX08009-003]; 863 National High-tech R&D Program of China [2012AA101100, 2012AA10A301]; Jiangsu Province 333 Program [BRA2012126]; National Natural Science Foundation of China [90917017]; National Science Foundation; Div Of Molecular and Cellular Bioscience; Direct For Biological Sciences [0929100] Funding Source: National Science Foundation
NR 50
TC 719
Z9 845
U1 12
U2 598
PU NATURE PUBLISHING 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 19
PY 2013
VL 504
IS 7480
BP 406
EP +
DI 10.1038/nature12878
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 273ZR
UT WOS:000328575300045
PM 24336215
DA 2026-03-09
ER

PT J
AU Balanoff, AM
   Bever, GS
   Rowe, TB
   Norell, MA
AF Balanoff, Amy M.
   Bever, Gabe S.
   Rowe, Timothy B.
   Norell, Mark A.
TI Evolutionary origins of the avian brain
SO NATURE
LA English
DT Article
ID organization; theropod; ear; china; birds
AB Features that were once considered exclusive to modern birds, such as feathers and a furcula, are now known to have first appeared in non-avian dinosaurs(1). However, relatively little is known of the early evolutionary history of the hyperinflated brain that distinguishes birds from other living reptiles and provides the important neurological capablities required by flight(2). Here we use high-resolution computed tomography to estimate and compare cranial volumes of extant birds, the early avialan Archaeopteryx lithographica, and a number of non-avian maniraptoran dinosaurs that are phylogenetically close to the origins of both Avialae and avian flight. Previous work established that avian cerebral expansion began early in theropod history and that the cranial cavity of Archaeopteryx was volumetrically intermediate between these early forms and modern birds(3,4). Our new data indicate that the relative size of the cranial cavity of Archaeopteryx is reflective of a more generalized maniraptoran volumetric signature and in several instances is actually smaller than that of other non-avian dinosaurs. Thus, bird-like encephalization indices evolved multiple times, supporting the conclusion that if Archaeopteryx had the neurological capabilities required of flight, so did at least some other non-avian maniraptorans. This is congruent with recent findings that avialans were not unique among maniraptorans in their ability to fly in some form(5,6).
C1 [Balanoff, Amy M.; Bever, Gabe S.; Norell, Mark A.] Amer Museum Nat Hist, Div Paleontol, New York, NY 10024 USA.
   [Balanoff, Amy M.] Columbia Univ, Dept Earth & Environm Sci, New York, NY 10027 USA.
   [Bever, Gabe S.] SUNY Coll Old Westbury, New York Inst Technol, Old Westbury, NY 11568 USA.
   [Rowe, Timothy B.] Univ Texas Austin, Jackson Sch Geosci, Austin, TX 78712 USA.
C3 American Museum of Natural History (AMNH); Columbia University; New York Institute Technology; State University of New York (SUNY) System; SUNY Old Westbury; University of Texas System; University of Texas Austin
RP Balanoff, AM (corresponding author), SUNY Stony Brook, Sch Med, Dept Anat Sci, Stony Brook, NY 11794 USA.
EM abalanoff@gmail.com
FU NSF DDIG [DEB 0909970]; NSF [IIS-0208675, EAR-0948842]; Columbia University International Travel Fellowship
NR 30
TC 146
Z9 170
U1 2
U2 151
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 5
PY 2013
VL 501
IS 7465
BP 93
EP +
DI 10.1038/nature12424
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 211ER
UT WOS:000323888300038
PM 23903660
DA 2026-03-09
ER

PT J
AU Wienholtz, F
   Beck, D
   Blaum, K
   Borgmann, C
   Breitenfeldt, M
   Cakirli, RB
   George, S
   Herfurth, F
   Holt, JD
   Kowalska, M
   Kreim, S
   Lunney, D
   Manea, V
   Menéndez, J
   Neidherr, D
   Rosenbusch, M
   Schweikhard, L
   Schwenk, A
   Simonis, J
   Stanja, J
   Wolf, RN
   Zuber, K
AF Wienholtz, F.
   Beck, D.
   Blaum, K.
   Borgmann, Ch.
   Breitenfeldt, M.
   Cakirli, R. B.
   George, S.
   Herfurth, F.
   Holt, J. D.
   Kowalska, M.
   Kreim, S.
   Lunney, D.
   Manea, V.
   Menendez, J.
   Neidherr, D.
   Rosenbusch, M.
   Schweikhard, L.
   Schwenk, A.
   Simonis, J.
   Stanja, J.
   Wolf, R. N.
   Zuber, K.
TI Masses of exotic calcium isotopes pin down nuclear forces
SO NATURE
LA English
DT Article
ID shell-model; spectrometry; physics
AB The properties of exotic nuclei on the verge of existence play a fundamental part in our understanding of nuclear interactions(1). Exceedingly neutron-rich nuclei become sensitive to new aspects of nuclear forces(2). Calcium, with its doubly magic isotopes Ca-40 and Ca-48, is an ideal test for nuclear shell evolution, from the valley of stability to the limits of existence. With a closed proton shell, the calcium isotopes mark the frontier for calculations with three-nucleon forces from chiral effective field theory(3-6). Whereas predictions for the masses of Ca-51 and Ca-52 have been validated by direct measurements(4), it is an open question as to how nuclear masses evolve for heavier calcium isotopes. Here we report the mass determination of the exotic calcium isotopes Ca-53 and Ca-54, using the multi-reflection time-of-flight mass spectrometer(7) of ISOLTRAP at CERN. The measured masses unambiguously establish a prominent shell closure at neutron number N = 32, in excellent agreement with our theoretical calculations. These results increase our understanding of neutron-rich matter and pin down the subtle components of nuclear forces that are at the forefront of theoretical developments constrained by quantum chromodynamics(8).
C1 [Wienholtz, F.; George, S.; Rosenbusch, M.; Schweikhard, L.; Wolf, R. N.] Ernst Moritz Arndt Univ Greifswald, Inst Phys, Felix Hausdorff Str 6, D-17489 Greifswald, Germany.
   [Beck, D.; Herfurth, F.; Neidherr, D.] GSI Helmholtzzentrum Schwerionenforsch GmbH, D-64291 Darmstadt, Germany.
   [Blaum, K.; Borgmann, Ch.; Cakirli, R. B.; Kreim, S.] Max Planck Inst Kernphys, D-69117 Heidelberg, Germany.
   [Breitenfeldt, M.] Katholieke Univ Leuven, Inst Kern & Stralingsfys, B-3001 Heverlee, Belgium.
   [Cakirli, R. B.] Istanbul Univ, Dept Phys, TR-34134 Istanbul, Turkey.
   [Holt, J. D.; Menendez, J.; Schwenk, A.; Simonis, J.] Tech Univ Darmstadt, Inst Kernphys, D-64289 Darmstadt, Germany.
   [Holt, J. D.; Menendez, J.; Schwenk, A.; Simonis, J.] GSI Helmholtzzentrum Schwerionenforsch GmbH, ExtreMe Matter Inst EMMI, D-64291 Darmstadt, Germany.
   [Kowalska, M.; Kreim, S.] CERN, CH-1211 Geneva 23, Switzerland.
   [Lunney, D.; Manea, V.] Univ Paris Sud, CNRS, IN2P3, CSNSM, F-91405 Orsay, France.
   [Stanja, J.; Zuber, K.] Tech Univ Dresden, Inst Kern & Teilchenphys, D-01069 Dresden, Germany.
C3 Universitat Greifswald; Helmholtz Association; GSI Helmholtz-Center for Heavy Ion Research; Max Planck Society; KU Leuven; Istanbul University; Technical University of Darmstadt; Helmholtz Association; GSI Helmholtz-Center for Heavy Ion Research; European Organization for Nuclear Research (CERN); Universite Paris Saclay; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute of Nuclear and Particle Physics (IN2P3); Technische Universitat Dresden
RP Wienholtz, F (corresponding author), Ernst Moritz Arndt Univ Greifswald, Inst Phys, Felix Hausdorff Str 6, D-17489 Greifswald, Germany.
EM wienholtz@physik.uni-greifswald.de
FU BMBF [06GF9102, 05P12HGCI1, 05P12HGFNE, 06DA70471, 06DD9054]; DFG [SFB 634, GE2183/2-1]; ERC [307986 STRONGINT]; EU through ENSAR [262010]; Helmholtz Alliance [HA216/EMMI]; French IN2P3; ISOLDE Collaboration; Max-Planck Society
NR 30
TC 431
Z9 489
U1 3
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 JUN 20
PY 2013
VL 498
IS 7454
BP 346
EP 349
DI 10.1038/nature12226
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 166XI
UT WOS:000320592900036
PM 23783629
DA 2026-03-09
ER

PT J
AU Dubois, J
   Jullien, T
   Portier, F
   Roche, P
   Cavanna, A
   Jin, Y
   Wegscheider, W
   Roulleau, P
   Glattli, DC
AF Dubois, J.
   Jullien, T.
   Portier, F.
   Roche, P.
   Cavanna, A.
   Jin, Y.
   Wegscheider, W.
   Roulleau, P.
   Glattli, D. C.
TI Minimal-excitation states for electron quantum optics using levitons
SO NATURE
LA English
DT Article
ID coherent states; hanbury-brown; interference; noise
AB The on-demand generation of pure quantum excitations is important for the operation of quantum systems, but it is particularly difficult for a system of fermions. This is because any perturbation affects all states below the Fermi energy, resulting in a complex superposition of particle and hole excitations. However, it was predicted nearly 20 years ago(1-3) that a Lorentzian time-dependent potential with quantized flux generates a minimal excitation with only one particle and no hole. Here we report that such quasiparticles (hereafter termed levitons) can be generated on demand in a conductor by applying voltage pulses to a contact. Partitioning the excitations with an electronic beam splitter generates a current noise that we use to measure their number. Minimal-excitation states are observed for Lorentzian pulses, whereas for other pulse shapes there are significant contributions from holes. Further identification of levitons is provided in the energy domain with shot-noise spectroscopy, and in the time domain with electronic Hong-Ou-Mandel noise correlations(4-8). The latter, obtained by colliding synchronized levitons on a beam splitter, exemplifies the potential use of levitons for quantum information: using linear electron quantum optics(9) in ballistic conductors, it is possible to imagine flying-qubit(10,11) operation in which the Fermi statistics are exploited(12-14) to entangle synchronized electrons emitted by distinct sources(15-18). Compared with electron sources based on quantum dots(19-21), the generation of levitons does not require delicate nanolithography, considerably simplifying the circuitry for scalability. Levitons are not limited to carrying a single charge, and so in a broader context n-particle levitons could find application in the study of full electron counting statistics(22-25). But they can also carry a fraction of charge if they are implemented in Luttinger liquids(3) or in fractional quantum Hall edge channels(26); this allows the study of Abelian and non-Abelian quasiparticles in the time domain. Finally, the generation technique could be applied to cold atomic gases(27,28), leading to the possibility of atomic levitons.
C1 [Dubois, J.; Jullien, T.; Portier, F.; Roche, P.; Roulleau, P.; Glattli, D. C.] CEA Saclay, Serv Phys Etat Condense, Nanoelect Grp, IRAMIS,DSM,CNRS,URA 2464, F-91191 Gif Sur Yvette, France.
   [Cavanna, A.; Jin, Y.] Univ Paris Diderot, CNRS, Lab Photon & Nanostruct LPN, Sorbonne Paris Cite, F-91460 Marcoussis, France.
   [Wegscheider, W.] ETH, Lab Solid State Phys, CH-8093 Zurich, Switzerland.
C3 CEA; Centre National de la Recherche Scientifique (CNRS); Universite Paris Saclay; Centre National de la Recherche Scientifique (CNRS); Universite Paris Cite; Swiss Federal Institutes of Technology Domain; ETH Zurich
RP Glattli, DC (corresponding author), CEA Saclay, Serv Phys Etat Condense, Nanoelect Grp, IRAMIS,DSM,CNRS,URA 2464, F-91191 Gif Sur Yvette, France.
EM christian.glattli@cea.fr
FU ERC [228273 MeQuaNo]
NR 31
TC 308
Z9 325
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 OCT 31
PY 2013
VL 502
IS 7473
BP 659
EP 663
DI 10.1038/nature12713
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 243CC
UT WOS:000326293200042
PM 24153178
DA 2026-03-09
ER

PT J
AU Pujol, M
   Marty, B
   Burgess, R
   Turner, G
   Philippot, P
AF Pujol, Magali
   Marty, Bernard
   Burgess, Ray
   Turner, Grenville
   Philippot, Pascal
TI Argon isotopic composition of Archaean atmosphere probes early Earth geodynamics
SO NATURE
LA English
DT Article
ID continental-crust; western-australia; pilbara craton; quartz veins; north-pole; evolution; growth; xenon; differentiation; helium
AB Understanding the growth rate of the continental crust through timeis a fundamental issue inEarth sciences(1-8). The isotopic signatures of noble gases in the silicate Earth (mantle, crust) and in the atmosphere afford exceptional insight into the evolution through time of these geochemical reservoirs(9). However, no data for the compositions of these reservoirs exists for the distant past, and temporal exchange rates between Earth's interior and its surface are severely under-constrained owing to a lack of samples preserving the original signature of the atmosphere at the time of their formation. Here, we report the analysis of argon in Archaean (3.5-billion-year-old) hydrothermal quartz. Noble gases are hosted in primary fluid inclusions containing a mixture of Archaean freshwater and hydrothermal fluid. Our analysis reveals Archaean atmospheric argon with a Ar-40/Ar-36 value of 143 +/- 24, lower than the present-day value of 298.6 (for which Ar-40 has been produced by the radioactive decay of the potassium isotope K-40, with a half-life of 1.25 billion years; Ar-36 is primordial in origin). This ratio is consistent with an early development of the felsic crust, which might have had an important role in climate variability during the first half of Earth's history.
C1 [Pujol, Magali; Marty, Bernard] Univ Lorraine, CRPG CNRS, F-54501 Vandoeuvre Les Nancy, France.
   [Burgess, Ray; Turner, Grenville] Univ Manchester, Sch Earth Atmospher & Environm Sci, Manchester M13 9PL, Lancs, England.
   [Philippot, Pascal] Univ Paris Diderot, CNRS, Inst Phys Globe Paris, Sorbonne Paris Cite, F-75238 Paris 5, France.
C3 Universite de Lorraine; Centre National de la Recherche Scientifique (CNRS); University of Manchester; Centre National de la Recherche Scientifique (CNRS); Universite Paris Cite
RP Marty, B (corresponding author), Univ Lorraine, CRPG CNRS, 15 Rue Notre Dame Pauvres, F-54501 Vandoeuvre Les Nancy, France.
EM bmarty@crpg.cnrs-nancy.fr
FU CNRS; Region Lorraine; ANR (Agence Nationale pour la Recherche); European Research Council under the European Community [267255]; Institut de Physique du Globe de Paris (IPGP); Geological Survey of Western Australia (GSWA); STFC [ST/J001643/1] Funding Source: UKRI; Science and Technology Facilities Council [ST/J001643/1] Funding Source: researchfish
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NR 39
TC 90
Z9 111
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 JUN 6
PY 2013
VL 498
IS 7452
BP 87
EP +
DI 10.1038/nature12152
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 158DC
UT WOS:000319947800038
PM 23739427
DA 2026-03-09
ER

PT J
AU Bloom, JS
   Ehrenreich, IM
   Loo, WT
   Lite, TLV
   Kruglyak, L
AF Bloom, Joshua S.
   Ehrenreich, Ian M.
   Loo, Wesley T.
   Thuy-Lan Vo Lite
   Kruglyak, Leonid
TI Finding the sources of missing heritability in a yeast cross
SO NATURE
LA English
DT Article
ID genetic interactions; complex diseases; human height; variants; traits; expression; evolution
AB For many traits, including susceptibility to common diseases in humans, causal loci uncovered by genetic-mapping studies explain only a minority of the heritable contribution to trait variation. Multiple explanations for this 'missing heritability' have been proposed(1). Here we use a large cross between two yeast strains to accurately estimate different sources of heritable variation for 46 quantitative traits, and to detect underlying loci with high statistical power. We find that the detected loci explain nearly the entire additive contribution to heritable variation for the traits studied. We also show that the contribution to heritability of gene-gene interactions varies among traits, from near zero to approximately 50 per cent. Detected two-locus interactions explain only a minority of this contribution. These results substantially advance our understanding of the missing heritability problem and have important implications
C1 [Bloom, Joshua S.; Ehrenreich, Ian M.; Loo, Wesley T.; Thuy-Lan Vo Lite; Kruglyak, Leonid] Princeton Uniyers, Lewis Sigler Inst Integrat Genom, Princeton, NJ 08540 USA.
   [Bloom, Joshua S.; Loo, Wesley T.; Thuy-Lan Vo Lite] Princeton Univ, Dept Mol Biol, Princeton, NJ 08540 USA.
   [Ehrenreich, Ian M.] Univ So Calif, Mol & Computat Biol Sect, Los Angeles, CA 90089 USA.
   [Kruglyak, Leonid] Princeton Univ, Dept Ecol & Evolutionary Biol, Princeton, NJ 08540 USA.
   [Kruglyak, Leonid] Princeton Univ, Howard Hughes Med Inst, Princeton, NJ 08540 USA.
C3 Princeton University; University of Southern California; Princeton University; Howard Hughes Medical Institute; Princeton University
RP Kruglyak, L (corresponding author), Princeton Uniyers, Lewis Sigler Inst Integrat Genom, Princeton, NJ 08540 USA.
EM leonid@genomics.princeton.edu
FU National Institutes of Health (NIH) [R37 MH59520, R01 GM102308]; James S. McDonnell Centennial Fellowship; Howard Hughes Medical Institute; National Science Foundation (NSF); NIH postdoctoral fellowship [F32 HG51762]; NIH grant [P50 GM071508]; National Institute of General Medical Sciences [R01GM102308] Funding Source: NIH RePORTER
NR 30
TC 313
Z9 374
U1 1
U2 99
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 14
PY 2013
VL 494
IS 7436
BP 234
EP 237
DI 10.1038/nature11867
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 092QS
UT WOS:000315137700039
PM 23376951
DA 2026-03-09
ER

PT J
AU Lee, MT
   Bonneau, AR
   Takacs, CM
   Bazzini, AA
   DiVito, KR
   Fleming, ES
   Giraldez, AJ
AF Lee, Miler T.
   Bonneau, Ashley R.
   Takacs, Carter M.
   Bazzini, Ariel A.
   DiVito, Kate R.
   Fleming, Elizabeth S.
   Giraldez, Antonio J.
TI Nanog, Pou5f1 and SoxB1 activate zygotic gene expression during the maternal-to-zygotic transition
SO NATURE
LA English
DT Article
ID endoderm formation; human fibroblasts; pluripotency; genome; oct4; network; identification; translation; dynamics; protein
AB After fertilization, maternal factors direct development and trigger zygotic genome activation (ZGA) at the maternal-to-zygotic transition (MZT). In zebrafish, ZGA is required for gastrulation and clearance of maternal messenger RNAs, which is in part regulated by the conserved microRNA miR-430. However, the factors that activate the zygotic program in vertebrates are unknown. Here we show that Nanog, Pou5f1 (also called Oct4) and SoxB1 regulate zygotic gene activation in zebrafish. We identified several hundred genes directly activated by maternal factors, constituting the first wave of zygotic transcription. Ribosome profiling revealed that nanog, sox19b and pou5f1 are the most highly translated transcription factors pre-MZT. Combined loss of these factors resulted in developmental arrest before gastrulation and a failure to activate >75% of zygotic genes, including miR-430. Our results demonstrate that maternal Nanog, Pou5f1 and SoxB1 are required to initiate the zygotic developmental program and induce clearance of the maternal program by activating miR-430 expression.
C1 [Lee, Miler T.; Bonneau, Ashley R.; Takacs, Carter M.; Bazzini, Ariel A.; DiVito, Kate R.; Fleming, Elizabeth S.; Giraldez, Antonio J.] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06510 USA.
   [Giraldez, Antonio J.] Yale Univ, Sch Med, Yale Stem Cell Ctr, New Haven, CT 06520 USA.
C3 Yale University; Yale University
RP Giraldez, AJ (corresponding author), Yale Univ, Sch Med, Dept Genet, New Haven, CT 06510 USA.
EM antonio.giraldez@yale.edu
FU NIH [F32HD071697-02, T32GM007499, F32HD061194-03]; Pew Fellows Program in Biomedical Sciences; Pew Scholars Program in the Biomedical Sciences; Yale Scholars Program;  [R01GM081602-06];  [R01GM103789-01];  [R01HD074078-02]; National Institute of General Medical Sciences [T32GM007499] Funding Source: NIH RePORTER
NR 59
TC 384
Z9 462
U1 0
U2 93
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 21
PY 2013
VL 503
IS 7476
BP 360
EP +
DI 10.1038/nature12632
PG 24
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 254KG
UT WOS:000327163200033
PM 24056933
DA 2026-03-09
ER

PT J
AU Tuff, J
   Wade, J
   Wood, BJ
AF Tuff, J.
   Wade, J.
   Wood, B. J.
TI Volcanism on Mars controlled by early oxidation of the upper mantle
SO NATURE
LA English
DT Article
ID iron-rich mantle; martian meteorites; sulfide saturation; sulfur-content; petrogenesis; constraints; origin; rocks; crust; melt
AB Detailed information about the chemical composition and evolution of Mars has been derived principally from the SNC (shergottite-nakhlite-chassignite) meteorites, which are genetically related igneous rocks of Martian origin(1,2). They are chemically and texturally similar to terrestrial basalts and cumulates, except that they have higher concentrations of iron and volatile elements such as phosphorus and chlorine and lower concentrations of nickel and other chalcophile (sulphur-loving) elements(3). Most Martian meteorites have relatively young crystallization ages (1.4 billion years to 180 million years ago(4)) and are considered to be derived from young, lightly cratered volcanic regions, such as the Tharsis plateau(4,5). Surface rocks from the Gusev crater analysed by the Spirit rover are much older (about 3.7 billion years old(6)) and exhibit marked compositional differences from the meteorites(7). Although also basaltic in composition, the surface rocks are richer in nickel and sulphur and have lower manganese/iron ratios than the meteorites. This has led to doubts that Mars can be described adequately using the 'SNC model'. Here we show, however, that the differences between the compositions of meteorites and surface rocks can be explained by differences in the oxygen fugacity duringmelting of the same sulphur-rich mantle. This ties the sources of Martian meteorites to those of the surface rocks through an early (>3.7 billion years ago) oxidation of the uppermost mantle that had less influence on the deeper regions, which produce the more recent volcanic rocks.
C1 [Tuff, J.; Wade, J.; Wood, B. J.] Univ Oxford, Dept Earth Sci, Oxford OX1 3AN, England.
C3 University of Oxford
RP Wood, BJ (corresponding author), Univ Oxford, Dept Earth Sci, S Parks Rd, Oxford OX1 3AN, England.
EM berniew@earth.ox.ac.uk
FU UK Science and Technology Facilities Council [ST/G00272X/1]; European Research Council [267764]; European Research Council (ERC) [267764] Funding Source: European Research Council (ERC); Science and Technology Facilities Council [ST/G00272X/1] Funding Source: researchfish; STFC [ST/G00272X/1] Funding Source: UKRI
NR 37
TC 58
Z9 64
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 JUN 20
PY 2013
VL 498
IS 7454
BP 342
EP +
DI 10.1038/nature12225
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 166XI
UT WOS:000320592900035
PM 23783628
DA 2026-03-09
ER

PT J
AU Cheung, WWL
   Watson, R
   Pauly, D
AF Cheung, William W. L.
   Watson, Reg
   Pauly, Daniel
TI Signature of ocean warming in global fisheries catch
SO NATURE
LA English
DT Article
ID climate-change; fish assemblage; impacts; shifts; vulnerability; sea
AB Marine fishes and invertebrates respond to ocean warming through distribution shifts, generally to higher latitudes and deeper waters. Consequently, fisheries should be affected by 'tropicalization' of catch(1-4) (increasing dominance of warm-water species). However, a signature of such climate-change effects on global fisheries catch has so far not been detected. Here we report such an index, the mean temperature of the catch (MTC), that is calculated from the average inferred temperature preference of exploited species weighted by their annual catch. Our results show that, after accounting for the effects of fishing and large-scale oceanographic variability, global MTC increased at a rate of 0.19 degrees Celsius per decade between 1970 and 2006, and non-tropical MTC increased at a rate of 0.23 degrees Celsius per decade. In tropical areas, MTC increased initially because of the reduction in the proportion of subtropical species catches, but subsequently stabilized as scope for further tropicalization of communities became limited. Changes in MTC in 52 large marine ecosystems, covering the majority of the world's coastal and shelf areas, are significantly and positively related to regional changes in sea surface temperature(5). This study shows that ocean warming has already affected global fisheries in the past four decades, highlighting the immediate need to develop adaptation plans to minimize the effect of such warming on the economy and food security of coastal communities, particularly in tropical regions(6,7).
C1 [Cheung, William W. L.] Univ British Columbia, Changing Ocean Res Unit, Fisheries Ctr, Vancouver, BC V6T 1Z4, Canada.
   [Watson, Reg] Univ Tasmania, Inst Marine & Antarctic Studies, Taroona, Tas 7001, Australia.
   [Pauly, Daniel] Univ British Columbia, Sea Us Project, Vancouver, BC V6T 1Z4, Canada.
C3 University of British Columbia; University of Tasmania; University of British Columbia
RP Cheung, WWL (corresponding author), Univ British Columbia, Changing Ocean Res Unit, Fisheries Ctr, Vancouver, BC V6T 1Z4, Canada.
EM w.cheung@fisheries.ubc.ca
FU National Geographic Society; Natural Sciences and Engineering Research Council of Canada; Pew Charitable Trust through the Sea Around Us project
NR 30
TC 694
Z9 798
U1 8
U2 619
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 16
PY 2013
VL 497
IS 7449
BP 365
EP +
DI 10.1038/nature12156
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 144PN
UT WOS:000318952000037
PM 23676754
DA 2026-03-09
ER

PT J
AU Richard, M
   Schrauwen, EJA
   de Graaf, M
   Bestebroer, TM
   Spronken, MIJ
   van Boheemen, S
   de Meulder, D
   Lexmond, P
   Linster, M
   Herfst, S
   Smith, DJ
   van den Brand, JM
   Burke, DF
   Kuiken, T
   Rimmelzwaan, GF
   Osterhaus, ADME
   Fouchier, RAM
AF Richard, Mathilde
   Schrauwen, Eefje J. A.
   de Graaf, Miranda
   Bestebroer, Theo M.
   Spronken, Monique I. J.
   van Boheemen, Sander
   de Meulder, Dennis
   Lexmond, Pascal
   Linster, Martin
   Herfst, Sander
   Smith, Derek J.
   van den Brand, Judith M.
   Burke, David F.
   Kuiken, Thijs
   Rimmelzwaan, Guus F.
   Osterhaus, Albert D. M. E.
   Fouchier, Ron A. M.
TI Limited airborne transmission of H7N9 influenza A virus between ferrets
SO NATURE
LA English
DT Article
ID single amino-acid; human infections; poultry; origin; hemagglutinin; replication; adaptation; generation; diversity
AB Wild waterfowl form the main reservoir of influenza A viruses, from which transmission occurs directly or indirectly to various secondary hosts, including humans(1). Direct avian-to-human transmission has been observed for viruses of subtypes A(H5N1), A(H7N2), A(H7N3), A(H7N7), A(H9N2) and A(H10N7) upon human exposure to poultry(2-7), but a lack of sustained human-to-human transmission has prevented these viruses from causing new pandemics. Recently, avian A(H7N9) viruses were transmitted to humans, causing severe respiratory disease and deaths in China(8). Because transmission via respiratory droplets and aerosols (hereafter referred to as airborne transmission) is the main route for efficient transmission between humans, it is important to gain an insight into airborne transmission of the A(H7N9) virus. Here we show that although the A/Anhui/1/2013 A(H7N9) virus harbours determinants associated with human adaptation and transmissibility between mammals, its airborne transmissibility in ferrets is limited, and it is intermediate between that of typical human and avian influenza viruses. Multiple A(H7N9) virus genetic variants were transmitted. Upon ferret passage, variants with higher avian receptor binding, higher pH of fusion, and lower thermostability were selected, potentially resulting in reduced transmissibility. This A(H7N9) virus outbreak highlights the need for increased understanding of the determinants of efficient airborne transmission of avian influenza viruses between mammals.
C1 [Richard, Mathilde; Schrauwen, Eefje J. A.; de Graaf, Miranda; Bestebroer, Theo M.; Spronken, Monique I. J.; van Boheemen, Sander; de Meulder, Dennis; Lexmond, Pascal; Linster, Martin; Herfst, Sander; van den Brand, Judith M.; Kuiken, Thijs; Rimmelzwaan, Guus F.; Osterhaus, Albert D. M. E.; Fouchier, Ron A. M.] Erasmus MC, Dept Virosci, NL-3015 GE Rotterdam, Netherlands.
   [Smith, Derek J.; Burke, David F.] Univ Cambridge, Dept Zool, Cambridge CB2 3EJ, England.
C3 Erasmus University Rotterdam; Erasmus MC; University of Cambridge
RP Fouchier, RAM (corresponding author), Erasmus MC, Dept Virosci, NL-3015 GE Rotterdam, Netherlands.
EM r.fouchier@erasmusmc.nl
FU NIAID-NIH [HHSN266200700010C]; EU program EMPERIE; EU program ANTIGONE
NR 37
TC 170
Z9 191
U1 0
U2 79
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 26
PY 2013
VL 501
IS 7468
BP 560
EP +
DI 10.1038/nature12476
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 223RP
UT WOS:000324826300061
PM 23925116
DA 2026-03-09
ER

PT J
AU Roychoudhuri, R
   Hirahara, K
   Mousavi, K
   Clever, D
   Klebanoff, CA
   Bonelli, M
   Sciumè, G
   Zare, H
   Vahedi, G
   Dema, B
   Yu, ZY
   Liu, H
   Takahashi, H
   Rao, M
   Muranski, P
   Crompton, JG
   Punkosdy, G
   Bedognetti, D
   Wang, E
   Hoffmann, V
   Rivera, J
   Marincola, FM
   Nakamura, A
   Sartorelli, V
   Kanno, Y
   Gattinoni, L
   Muto, A
   Igarashi, K
   O'Shea, JJ
   Restifo, NP
AF Roychoudhuri, Rahul
   Hirahara, Kiyoshi
   Mousavi, Kambiz
   Clever, David
   Klebanoff, Christopher A.
   Bonelli, Michael
   Sciume, Giuseppe
   Zare, Hossein
   Vahedi, Golnaz
   Dema, Barbara
   Yu, Zhiya
   Liu, Hui
   Takahashi, Hayato
   Rao, Mahadev
   Muranski, Pawel
   Crompton, Joseph G.
   Punkosdy, George
   Bedognetti, Davide
   Wang, Ena
   Hoffmann, Victoria
   Rivera, Juan
   Marincola, Francesco M.
   Nakamura, Atsushi
   Sartorelli, Vittorio
   Kanno, Yuka
   Gattinoni, Luca
   Muto, Akihiko
   Igarashi, Kazuhiko
   O'Shea, John J.
   Restifo, Nicholas P.
TI BACH2 represses effector programs to stabilize Treg-mediated immune homeostasis
SO NATURE
LA English
DT Article
ID genome-wide association; gene-expression; cell-differentiation; susceptibility loci; risk loci; b-cells; transcription; disease; interleukin-4; metaanalysis
AB Through their functional diversification, distinct lineages of CD4(+) T cells can act to either drive or constrain immune-mediated pathology. Transcription factors are critical in the generation of cellular diversity, and negative regulators antagonistic to alternate fates often act in conjunction with positive regulators to stabilize lineage commitment(1). Genetic polymorphisms within a single locus encoding the transcription factor BACH2 are associated with numerous autoimmune and allergic diseases including asthma(2), Crohn's disease(3,4), coeliac disease(5), vitiligo(6), multiple sclerosis(7) and type 1 diabetes(8). Although these associations point to a shared mechanism underlying susceptibility to diverse immune-mediated diseases, a function for BACH2 in the maintenance of immune homeostasis has not been established. Here, by studying mice in which the Bach2 gene is disrupted, we define BACH2 as a broad regulator of immune activation that stabilizes immunoregulatory capacity while repressing the differentiation programs of multiple effector lineages in CD4(+) T cells. BACH2 was required for efficient formation of regulatory (T-reg) cells and consequently for suppression of lethal inflammation in a manner that was T-reg-cell-dependent. Assessment of the genome-wide function of BACH2, however, revealed that it represses genes associated with effector cell differentiation. Consequently, its absence during T-reg polarization resulted in inappropriate diversion to effector lineages. In addition, BACH2 constrained full effector differentiation within T(H)1, T(H)2 and T(H)17 cell lineages. These findings identify BACH2 as a key regulator of CD4(+) T-cell differentiation that prevents inflammatory disease by controlling the balance between tolerance and immunity.
C1 [Roychoudhuri, Rahul; Clever, David; Klebanoff, Christopher A.; Yu, Zhiya; Rao, Mahadev; Muranski, Pawel; Crompton, Joseph G.; Gattinoni, Luca; Restifo, Nicholas P.] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
   [Hirahara, Kiyoshi; Bonelli, Michael; Sciume, Giuseppe; Vahedi, Golnaz; Takahashi, Hayato; Kanno, Yuka; O'Shea, John J.] NIAMSD, Mol Immunol & Inflammat Branch, Bethesda, MD 20892 USA.
   [Mousavi, Kambiz; Zare, Hossein; Sartorelli, Vittorio] NIAMS, Lab Muscle Stem Cells & Gene Regulat, NIH, Bethesda, MD 20892 USA.
   [Dema, Barbara; Rivera, Juan] NIAMS, Lab Mol Immunogenet, NIH, Bethesda, MD 20892 USA.
   [Liu, Hui; Bedognetti, Davide; Wang, Ena; Marincola, Francesco M.] NIH, Dept Transfus Med, Bethesda, MD 20892 USA.
   [Punkosdy, George] NIAID, NIH, Bethesda, MD 20892 USA.
   [Hoffmann, Victoria] NIH, Div Vet Resources, Bethesda, MD 20892 USA.
   [Marincola, Francesco M.] Sidra Med & Res Ctr, Doha, Qatar.
   [Nakamura, Atsushi; Muto, Akihiko; Igarashi, Kazuhiko] Tohoku Univ, Grad Sch Med, Dept Biochem, Sendai, Miyagi 9808575, Japan.
   [Muto, Akihiko; Igarashi, Kazuhiko] Japan Sci & Technol Agcy, CREST, Sendai, Miyagi 9808575, Japan.
   [Restifo, Nicholas P.] NIH, Ctr Regenerat Med, Bethesda, MD 20892 USA.
C3 National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); National Institutes of Health (NIH) - USA; NIH National Institute of Arthritis & Musculoskeletal & Skin Diseases (NIAMS); National Institutes of Health (NIH) - USA; NIH National Institute of Arthritis & Musculoskeletal & Skin Diseases (NIAMS); National Institutes of Health (NIH) - USA; NIH National Institute of Arthritis & Musculoskeletal & Skin Diseases (NIAMS); National Institutes of Health (NIH) - USA; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID); National Institutes of Health (NIH) - USA; Sidra Medical & Research Center; Tohoku University; Japan Science & Technology Agency (JST); National Institutes of Health (NIH) - USA
RP Roychoudhuri, R (corresponding author), NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM roychoudhuri@mail.nih.gov; osheajo@mail.nih.gov; restifo@nih.gov
FU Intramural Research Programs of the National Cancer Institute (NIH); National Institute of Arthritis and Musculoskeletal and Skin Diseases; NIH Center for Regenerative Medicine; JSPS Research Fellowship for Japanese Biomedical and Behavioural Researchers at NIH; National Institute of Allergy and Infectious Diseases [ZIAAI001045] Funding Source: NIH RePORTER; National Institute of Arthritis and Musculoskeletal and Skin Diseases [ZIAAR041159, ZIAAR041164] Funding Source: NIH RePORTER
NR 35
TC 339
Z9 378
U1 1
U2 54
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 27
PY 2013
VL 498
IS 7455
BP 506
EP +
DI 10.1038/nature12199
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 171LH
UT WOS:000320929400057
PM 23728300
DA 2026-03-09
ER

PT J
AU Almeida, J
   Schobesberger, S
   Kürten, A
   Ortega, IK
   Kupiainen-Määttä, O
   Praplan, AP
   Adamov, A
   Amorim, A
   Bianchi, F
   Breitenlechner, M
   David, A
   Dommen, J
   Donahue, NM
   Downard, A
   Dunne, E
   Duplissy, J
   Ehrhart, S
   Flagan, RC
   Franchin, A
   Guida, R
   Hakala, J
   Hansel, A
   Heinritzi, M
   Henschel, H
   Jokinen, T
   Junninen, H
   Kajos, M
   Kangasluoma, J
   Keskinen, H
   Kupc, A
   Kurtén, T
   Kvashin, AN
   Laaksonen, A
   Lehtipalo, K
   Leiminger, M
   Leppä, J
   Loukonen, V
   Makhmutov, V
   Mathot, S
   McGrath, MJ
   Nieminen, T
   Olenius, T
   Onnela, A
   Petäjä, T
   Riccobono, F
   Riipinen, I
   Rissanen, M
   Rondo, L
   Ruuskanen, T
   Santos, FD
   Sarnela, N
   Schallhart, S
   Schnitzhofer, R
   Seinfeld, JH
   Simon, M
   Sipilä, M
   Stozhkov, Y
   Stratmann, F
   Tomé, A
   Tröstl, J
   Tsagkogeorgas, G
   Vaattovaara, P
   Viisanen, Y
   Virtanen, A
   Vrtala, A
   Wagner, PE
   Weingartner, E
   Wex, H
   Williamson, C
   Wimmer, D
   Ye, PL
   Yli-Juuti, T
   Carslaw, KS
   Kulmala, M
   Curtius, J
   Baltensperger, U
   Worsnop, DR
   Vehkamäki, H
   Kirkby, J
AF Almeida, Joao
   Schobesberger, Siegfried
   Kuerten, Andreas
   Ortega, Ismael K.
   Kupiainen-Maatta, Oona
   Praplan, Arnaud P.
   Adamov, Alexey
   Amorim, Antonio
   Bianchi, Federico
   Breitenlechner, Martin
   David, Andre
   Dommen, Josef
   Donahue, Neil M.
   Downard, Andrew
   Dunne, Eimear
   Duplissy, Jonathan
   Ehrhart, Sebastian
   Flagan, Richard C.
   Franchin, Alessandro
   Guida, Roberto
   Hakala, Jani
   Hansel, Armin
   Heinritzi, Martin
   Henschel, Henning
   Jokinen, Tuija
   Junninen, Heikki
   Kajos, Maija
   Kangasluoma, Juha
   Keskinen, Helmi
   Kupc, Agnieszka
   Kurten, Theo
   Kvashin, Alexander N.
   Laaksonen, Ari
   Lehtipalo, Katrianne
   Leiminger, Markus
   Leppa, Johannes
   Loukonen, Ville
   Makhmutov, Vladimir
   Mathot, Serge
   McGrath, Matthew J.
   Nieminen, Tuomo
   Olenius, Tinja
   Onnela, Antti
   Petaja, Tuukka
   Riccobono, Francesco
   Riipinen, Ilona
   Rissanen, Matti
   Rondo, Linda
   Ruuskanen, Taina
   Santos, Filipe D.
   Sarnela, Nina
   Schallhart, Simon
   Schnitzhofer, Ralf
   Seinfeld, John H.
   Simon, Mario
   Sipila, Mikko
   Stozhkov, Yuri
   Stratmann, Frank
   Tome, Antonio
   Troestl, Jasmin
   Tsagkogeorgas, Georgios
   Vaattovaara, Petri
   Viisanen, Yrjo
   Virtanen, Annele
   Vrtala, Aron
   Wagner, Paul E.
   Weingartner, Ernest
   Wex, Heike
   Williamson, Christina
   Wimmer, Daniela
   Ye, Penglin
   Yli-Juuti, Taina
   Carslaw, Kenneth S.
   Kulmala, Markku
   Curtius, Joachim
   Baltensperger, Urs
   Worsnop, Douglas R.
   Vehkamaki, Hanna
   Kirkby, Jasper
TI Molecular understanding of sulphuric acid-amine particle nucleation in the atmosphere
SO NATURE
LA English
DT Article
ID mass-spectrometer; formation events; aerosol; dimethylamine; ammonia; water
AB Nucleation of aerosol particles from trace atmospheric vapours is thought to provide up to half of global cloud condensation nuclei(1). Aerosols can cause a net cooling of climate by scattering sunlight and by leading to smaller but more numerous cloud droplets, which makes clouds brighter and extends their lifetimes(2). Atmospheric aerosols derived from human activities are thought to have compensated for a large fraction of the warming caused by greenhouse gases(2). However, despite its importance for climate, atmospheric nucleation is poorly understood. Recently, it has been shown that sulphuric acid and ammonia cannot explain particle formation rates observed in the lower atmosphere(3). It is thought that amines may enhance nucleation(4-16), but until now there has been no direct evidence for amine ternary nucleation under atmospheric conditions. Here we use the CLOUD (Cosmics Leaving OUtdoor Droplets) chamber at CERN and find that dimethylamine above three parts per trillion by volume can enhance particle formation rates more than 1,000-fold compared with ammonia, sufficient to account for the particle formation rates observed in the atmosphere. Molecular analysis of the clusters reveals that the faster nucleation is explained by a base-stabilization mechanism involving acid-amine pairs, which strongly decrease evaporation. The ion-induced contribution is generally small, reflecting the high stability of sulphuric acid-dimethylamine clusters and indicating that galactic cosmic rays exert only a small influence on their formation, except at low overall formation rates. Our experimental measurements are well reproduced by a dynamical model based on quantum chemical calculations of binding energies of molecular clusters, without any fitted parameters. These results show that, in regions of the atmosphere near amine sources, both amines and sulphur dioxide should be considered when assessing the impact of anthropogenic activities on particle formation.
C1 [Almeida, Joao; Kuerten, Andreas; Ehrhart, Sebastian; Leiminger, Markus; Rondo, Linda; Simon, Mario; Williamson, Christina; Wimmer, Daniela; Curtius, Joachim; Kirkby, Jasper] Goethe Univ Frankfurt, Inst Atmospher & Environm Sci, D-60438 Frankfurt, Germany.
   [Almeida, Joao; David, Andre; Guida, Roberto; Mathot, Serge; Onnela, Antti; Kirkby, Jasper] CERN, CH-1211 Geneva, Switzerland.
   [Schobesberger, Siegfried; Ortega, Ismael K.; Kupiainen-Maatta, Oona; Adamov, Alexey; Duplissy, Jonathan; Franchin, Alessandro; Hakala, Jani; Henschel, Henning; Jokinen, Tuija; Junninen, Heikki; Kajos, Maija; Kangasluoma, Juha; Lehtipalo, Katrianne; Loukonen, Ville; Nieminen, Tuomo; Olenius, Tinja; Petaja, Tuukka; Rissanen, Matti; Ruuskanen, Taina; Sarnela, Nina; Schallhart, Simon; Sipila, Mikko; Wimmer, Daniela; Yli-Juuti, Taina; Kulmala, Markku; Worsnop, Douglas R.; Vehkamaki, Hanna] Univ Helsinki, Dept Phys, FI-00014 Helsinki, Finland.
   [Praplan, Arnaud P.; Bianchi, Federico; Dommen, Josef; Riccobono, Francesco; Troestl, Jasmin; Weingartner, Ernest; Baltensperger, Urs] Paul Scherrer Inst, Lab Atmospher Chem, CH-5232 Villigen, Switzerland.
   [Amorim, Antonio; Santos, Filipe D.; Tome, Antonio] Univ Lisbon, SIM, P-1749016 Lisbon, Portugal.
   [Amorim, Antonio; Santos, Filipe D.; Tome, Antonio] Univ Beira Interior, P-1749016 Lisbon, Portugal.
   [Breitenlechner, Martin; Hansel, Armin; Heinritzi, Martin; Schnitzhofer, Ralf] Ionicon Analyt GmbH, A-6020 Innsbruck, Austria.
   [Breitenlechner, Martin; Hansel, Armin; Heinritzi, Martin; Schnitzhofer, Ralf] Univ Innsbruck, Inst Ion & Appl Phys, A-6020 Innsbruck, Austria.
   [Donahue, Neil M.; Ye, Penglin] Carnegie Mellon Univ, Ctr Atmospher Particle Studies, Pittsburgh, PA 15213 USA.
   [Downard, Andrew; Flagan, Richard C.; Seinfeld, John H.] CALTECH, Div Chem & Chem Engn, Pasadena, CA 91125 USA.
   [Dunne, Eimear; Carslaw, Kenneth S.] Univ Leeds, Sch Earth & Environm, Leeds LS2 9JT, W Yorkshire, England.
   [Keskinen, Helmi; Laaksonen, Ari; Vaattovaara, Petri; Virtanen, Annele; Worsnop, Douglas R.] Univ Eastern Finland, FI-70211 Kuopio, Finland.
   [Kupc, Agnieszka; Vrtala, Aron; Wagner, Paul E.] Univ Vienna, Fac Phys, A-1090 Vienna, Austria.
   [Kurten, Theo] Univ Helsinki, Dept Chem, FI-00014 Helsinki, Finland.
   [Kvashin, Alexander N.; Makhmutov, Vladimir; Stozhkov, Yuri] PN Lebedev Phys Inst, Solar & Cosm Ray Res Lab, Moscow 119991, Russia.
   [Laaksonen, Ari; Leppa, Johannes; Viisanen, Yrjo; Worsnop, Douglas R.] Finnish Meteorol Inst, FI-00101 Helsinki, Finland.
   [McGrath, Matthew J.] Kyoto Univ, Grad Sch Sci, Dept Biophys, Kyoto 6068502, Japan.
   [Nieminen, Tuomo; Sipila, Mikko; Kulmala, Markku] Univ Helsinki, Helsinki Inst Phys, FI-00014 Helsinki, Finland.
   [Riipinen, Ilona] Univ Stockholm, Dept Appl Environm Sci, SE-10961 Stockholm, Sweden.
   [Stratmann, Frank; Tsagkogeorgas, Georgios; Wex, Heike] Leibniz Inst Tropospher Res, D-04318 Leipzig, Germany.
   [Worsnop, Douglas R.] Aerodyne Res Inc, Billerica, MA 01821 USA.
C3 Goethe University Frankfurt; European Organization for Nuclear Research (CERN); University of Helsinki; Swiss Federal Institutes of Technology Domain; Paul Scherrer Institute; Universidade de Lisboa; Universidade da Beira Interior; University of Innsbruck; Carnegie Mellon University; California Institute of Technology; University of Leeds; University of Eastern Finland; University of Vienna; University of Helsinki; Russian Academy of Sciences; Russian Academy of Science Lebedev Physical Institute; Finnish Meteorological Institute; Kyoto University; University of Helsinki; Helsinki Institute of Physics; Stockholm University; Leibniz Association; Leibniz Institut fur Tropospharenforschung (TROPOS); Aerodyne Research
RP Kirkby, J (corresponding author), Goethe Univ Frankfurt, Inst Atmospher & Environm Sci, D-60438 Frankfurt, Germany.
EM jasper.kirkby@cern.ch
FU EC [215072, 316662, 57360, 227463]; German Federal Ministry of Education and Research [01LK0902A, 01LK1222A]; Swiss National Science Foundation [200020_135307, 206620_130527]; Academy of Finland [1118615, 135054, 133872, 251427, 139656, 139995, 137749, 141217, 141451]; Finnish Funding Agency for Technology and Innovation; Vaisala Foundation; Nessling Foundation; Austrian Science Fund (FWF) [P19546, L593]; Portuguese Foundation for Science and Technology [CERN/FP/116387/2010]; Swedish Research Council, Vetenskapsradet [2011-5120]; Presidium of the Russian Academy of Sciences; Russian Foundation for Basic Research [08-02-91006-CERN, 12-02-91522-CERN]; US National Science Foundation [AGS1136479, CHE1012293]; Austrian Science Fund (FWF) [L 593] Funding Source: researchfish; Div Atmospheric & Geospace Sciences; Directorate For Geosciences [1136479] Funding Source: National Science Foundation; Division Of Chemistry; Direct For Mathematical & Physical Scien [1012293] Funding Source: National Science Foundation
NR 42
TC 780
Z9 869
U1 14
U2 825
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 17
PY 2013
VL 502
IS 7471
BP 359
EP +
DI 10.1038/nature12663
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 235GY
UT WOS:000325706300050
PM 24097350
DA 2026-03-09
ER

PT J
AU Turner, L
   Lavstsen, T
   Berger, SS
   Wang, CW
   Petersen, JEV
   Avril, M
   Brazier, AJ
   Freeth, J
   Jespersen, JS
   Nielsen, MA
   Magistrado, P
   Lusingu, J
   Smith, JD
   Higgins, MK
   Theander, TG
AF Turner, Louise
   Lavstsen, Thomas
   Berger, Sanne S.
   Wang, Christian W.
   Petersen, Jens E. V.
   Avril, Marion
   Brazier, Andrew J.
   Freeth, Jim
   Jespersen, Jakob S.
   Nielsen, Morten A.
   Magistrado, Pamela
   Lusingu, John
   Smith, Joseph D.
   Higgins, Matthew K.
   Theander, Thor G.
TI Severe malaria is associated with parasite binding to endothelial protein C receptor
SO NATURE
LA English
DT Article
ID erythrocyte-membrane protein-1; falciparum-infected erythrocytes; var genes; drotrecogin-alpha; expression; acquisition; antibody; adhesion; subset
AB Sequestration of Plasmodium falciparum-infected erythrocytes in host blood vessels is a key triggering event in the pathogenesis of severe childhood malaria, which is responsible for about one million deaths every year(1). Sequestration is mediated by specific interactions between members of the P. falciparum erythrocyte membrane protein 1 (PfEMP1) family and receptors on the endothelial lining(2). Severe childhood malaria is associated with expression of specific PfEMP1 subtypes containing domain cassettes (DCs) 8 and 13 (ref. 3), but the endothelial receptor for parasites expressing these proteins was unknown(4,5). Here we identify endothelial protein C receptor (EPCR), which mediates the cytoprotective effects of activated protein C-6, as the endothelial receptor for DC8 and DC13 PfEMP1. We show that EPCR binding is mediated through the amino-terminal cysteine-rich interdomain region (CIDRa1) of DC8 and group A PfEMP1 subfamilies, and that CIDRa1 interferes with protein C binding to EPCR. This PfEMP1 adhesive property links P. falciparum cytoadhesion to a host receptor involved in anticoagulation and endothelial cytoprotective pathways, and has implications for understanding malaria pathology and the development of new malaria interventions.
C1 [Turner, Louise; Lavstsen, Thomas; Berger, Sanne S.; Wang, Christian W.; Petersen, Jens E. V.; Jespersen, Jakob S.; Nielsen, Morten A.; Theander, Thor G.] Univ Copenhagen, Ctr Med Parasitol, Dept Int Hlth Immunol & Microbiol, Copenhagen, Denmark.
   [Turner, Louise; Lavstsen, Thomas; Berger, Sanne S.; Wang, Christian W.; Petersen, Jens E. V.; Jespersen, Jakob S.; Nielsen, Morten A.; Theander, Thor G.] Rigshosp, Dept Infect Dis, DK-2100 Copenhagen, Denmark.
   [Avril, Marion; Brazier, Andrew J.; Smith, Joseph D.] Seattle Biomed Res Inst, Seattle, WA 98109 USA.
   [Freeth, Jim] Retrogenix, Whaley Bridge SK23 7LY, High Peak, England.
   [Magistrado, Pamela; Lusingu, John] Natl Inst Med Res, Tanga Ctr, Tanga, Tanzania.
   [Smith, Joseph D.] Univ Washington, Dept Global Hlth, Seattle, WA 98195 USA.
   [Higgins, Matthew K.] Univ Oxford, Dept Biochem, Oxford OX1 3QU, England.
C3 University of Copenhagen; University of Copenhagen; Copenhagen University Hospital; Rigshospitalet; Center for Infectious Disease Research; National Institute of Medical Research; University of Washington; University of Washington Seattle; University of Oxford
RP Lavstsen, T (corresponding author), Univ Copenhagen, Ctr Med Parasitol, Dept Int Hlth Immunol & Microbiol, Copenhagen, Denmark.
EM lturner@sund.ku.dk; thomasl@sund.ku.dk
FU University of Copenhagen Program of Excellence; Lundbeck Foundation; Danish International Development Agency; Augustinus Fonden; Malaria Capacity Development Consortium; Danish Medical Research Council; National Institutes of Health [R01 AI47953, U19 AI089688]; Medical Research Council; MRC [G0901062] Funding Source: UKRI; Lundbeck Foundation [R108-2012-10328] Funding Source: researchfish; Medical Research Council [G0901062] Funding Source: researchfish; National Institute of Allergy and Infectious Diseases [U19AI089688] Funding Source: NIH RePORTER
NR 30
TC 439
Z9 522
U1 1
U2 69
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 27
PY 2013
VL 498
IS 7455
BP 502
EP +
DI 10.1038/nature12216
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 171LH
UT WOS:000320929400056
PM 23739325
DA 2026-03-09
ER

PT J
AU Caron, SJC
   Ruta, V
   Abbott, LF
   Axel, R
AF Caron, Sophie J. C.
   Ruta, Vanessa
   Abbott, L. F.
   Axel, Richard
TI Random convergence of olfactory inputs in the Drosophila mushroom body
SO NATURE
LA English
DT Article
ID imaging reveals; neurons; map; representation; ablation
AB The mushroom body in the fruitfly Drosophila melanogaster is an associative brain centre that translates odour representations into learned behavioural responses(1). Kenyon cells, the intrinsic neurons of the mushroom body, integrate input from olfactory glomeruli to encode odours as sparse distributed patterns of neural activity(2,3). We have developed anatomic tracing techniques to identify the glomerular origin of the inputs that converge onto 200 individual Kenyon cells. Here we show that each Kenyon cell integrates input from a different and apparently random combination of glomeruli. The glomerular inputs to individual Kenyon cells show no discernible organization with respect to their odour tuning, anatomic features or developmental origins. Moreover, different classes of Kenyon cells do not seem to preferentially integrate inputs from specific combinations of glomeruli. This organization of glomerular connections to the mushroom body could allow the fly to contextualize novel sensory experiences, a feature consistent with the role of this brain centre in mediating learned olfactory associations and behaviours.
C1 [Caron, Sophie J. C.; Abbott, L. F.; Axel, Richard] Columbia Univ, Coll Phys & Surg, Dept Neurosci, New York, NY 10032 USA.
   [Ruta, Vanessa] Rockefeller Univ, Lab Neurophysiol & Behav, New York, NY 10065 USA.
   [Abbott, L. F.] Columbia Univ, Coll Phys & Surg, Dept Physiol & Cellular Biophys, New York, NY 10032 USA.
   [Axel, Richard] Columbia Univ, Coll Phys & Surg, Dept Biochem & Mol Biophys, New York, NY 10032 USA.
   [Axel, Richard] Columbia Univ, Howard Hughes Med Inst, New York, NY 10032 USA.
C3 Columbia University; Rockefeller University; Columbia University; Columbia University; Columbia University; Howard Hughes Medical Institute
RP Axel, R (corresponding author), Columbia Univ, Coll Phys & Surg, Dept Neurosci, New York, NY 10032 USA.
EM ra27@columbia.edu
FU Foundation for the National Institutes of Health through the Grand Challenges in Global Health Initiative; Howard Hughes Medical Institute; Swartz Foundation; Gatsby Foundation; Pew Charitable Trusts; McKnight Foundation; New York Stem Cell Foundation
NR 28
TC 285
Z9 349
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 MAY 2
PY 2013
VL 497
IS 7447
BP 113
EP +
DI 10.1038/nature12063
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 134OK
UT WOS:000318221500044
PM 23615618
DA 2026-03-09
ER

PT J
AU Lee, SJ
   McCormick, MS
   Lippard, SJ
   Cho, US
AF Lee, Seung Jae
   McCormick, Michael S.
   Lippard, Stephen J.
   Cho, Uhn-Soo
TI Control of substrate access to the active site in methane monooxygenase
SO NATURE
LA English
DT Article
ID methylococcus-capsulatus bath; methylosinus-trichosporium ob3b; regulatory protein-b; hydroxylase component; dioxygen activation; crystal-structure; oxygen activation; oxidation
AB Methanotrophs consume methane as their major carbon source and have an essential role in the global carbon cycle by limiting escape of this greenhouse gas to the atmosphere(1-3). These bacteria oxidize methane to methanol by soluble and particulate methane monooxygenases (MMOs)(1-4). Soluble MMO contains three protein components, a 251-kilodalton hydroxylase (MMOH), a 38.6-kilodalton reductase (MMOR), and a 15.9-kilodalton regulatory protein (MMOB), required to couple electron consumption with substrate hydroxylation at the catalytic diiron centre of MMOH2. Until now, the role of MMOB has remained ambiguous owing to a lack of atomic-level information about the MMOH-MMOB (hereafter termed H-B) complex. Here we remedy this deficiency by providing a crystal structure of H-B, which reveals the manner by which MMOB controls the conformation of residues in MMOH crucial for substrate access to the active site. MMOB docks at the alpha(2)beta(2) interface of alpha(2)beta(2)gamma(2) MMOH, and triggers simultaneous conformational changes in the alpha-subunit that modulate oxygen and methane access as well as proton delivery to the diiron centre. Without such careful control by MMOB of these substrate routes to the diiron active site, the enzyme operates as an NADH oxidase rather than a monooxygenases(5). Biological catalysis involving small substrates is often accomplished in nature by large proteins and protein complexes. The structure presented in this work provides an elegant example of this principle.
C1 [Lee, Seung Jae; McCormick, Michael S.; Lippard, Stephen J.] MIT, Dept Chem, Cambridge, MA 02139 USA.
   [Cho, Uhn-Soo] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
C3 Massachusetts Institute of Technology (MIT); Harvard University; Harvard Medical School
RP Lippard, SJ (corresponding author), MIT, Dept Chem, Cambridge, MA 02139 USA.
EM lippard@mit.edu; uhnsoo@med.umich.edu
FU National Institute of General Medical Sciences [GM 32114]
NR 30
TC 114
Z9 148
U1 3
U2 280
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 21
PY 2013
VL 494
IS 7437
BP 380
EP 384
DI 10.1038/nature11880
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 095CS
UT WOS:000315312900044
PM 23395959
DA 2026-03-09
ER

PT J
AU Moore, S
   Evans, CD
   Page, SE
   Garnett, MH
   Jones, TG
   Freeman, C
   Hooijer, A
   Wiltshire, AJ
   Limin, SH
   Gauci, V
AF Moore, Sam
   Evans, Chris D.
   Page, Susan E.
   Garnett, Mark H.
   Jones, Tim G.
   Freeman, Chris
   Hooijer, Aljosja
   Wiltshire, Andrew J.
   Limin, Suwido H.
   Gauci, Vincent
TI Deep instability of deforested tropical peatlands revealed by fluvial organic carbon fluxes
SO NATURE
LA English
DT Article
ID environment simulator jules; model description; forest; export; peat; kalimantan; indonesia; accumulation; vegetation; emissions
AB Tropical peatlands contain one of the largest pools of terrestrial organic carbon, amounting to about 89,000 teragrams(1) (1 Tg is a billion kilograms). Approximately 65 per cent of this carbon store is in Indonesia, where extensive anthropogenic degradation in the form of deforestation, drainage and fire are converting it into a globally significant source of atmospheric carbon dioxide(1-3). Here we quantify the annual export of fluvial organic carbon from both intact peat swamp forest and peat swamp forest subject to past anthropogenic disturbance. We find that the total fluvial organic carbon flux from disturbed peat swamp forest is about 50 per cent larger than that from intact peat swamp forest. By carbon-14 dating of dissolved organic carbon (which makes up over 91 per cent of total organic carbon), we find that leaching of dissolved organic carbon from intact peat swamp forest is derived mainly from recent primary production (plant growth). In contrast, dissolved organic carbon from disturbed peat swamp forest consists mostly of much older (centuries to millennia) carbon from deep within the peat column. When we include the fluvial carbon loss term, which is often ignored, in the peatland carbon budget, we find that it increases the estimate of total carbon lost from the disturbed peatlands in our study by 22 per cent. We further estimate that since 1990 peatland disturbance has resulted in a 32 per cent increase in fluvial organic carbon flux from southeast Asia-an increase that is more than half of the entire annual fluvial organic carbon flux from all European peatlands. Our findings emphasize the need to quantify fluvial carbon losses in order to improve estimates of the impact of deforestation and drainage on tropical peatland carbon balances.
C1 [Moore, Sam; Gauci, Vincent] Open Univ, Dept Environm Earth & Ecosyst, CEPSAR, Milton Keynes MK7 6AA, Bucks, England.
   [Evans, Chris D.] Environm Ctr Wales, Ctr Ecol & Hydrol, Bangor LL57 2UW, Gwynedd, Wales.
   [Page, Susan E.] Univ Leicester, Dept Geog, Leicester LE1 7RH, Leics, England.
   [Garnett, Mark H.] Nat Environm Res Council Radiocarbon Facil, E Kilbride G75 0QF, Lanark, Scotland.
   [Jones, Tim G.; Freeman, Chris] Bangor Univ, Sch Biol Sci, Bangor LL57 2UW, Gwynedd, Wales.
   [Hooijer, Aljosja] Deltares, NL-2600 MH Delft, Netherlands.
   [Wiltshire, Andrew J.] Met Off Hadley Ctr, Exeter EX1 3PB, Devon, England.
   [Limin, Suwido H.] Univ Palangka Raya, CIMTROP, Palangka Raya 73112, Central Kaliman, Indonesia.
C3 Open University - UK; UK Centre for Ecology & Hydrology (UKCEH); University of Leicester; UK Research & Innovation (UKRI); Natural Environment Research Council (NERC); NERC British Geological Survey; Bangor University; Deltares; Met Office - UK; Hadley Centre; Universitas Palangka Raya (UPR)
RP Gauci, V (corresponding author), Open Univ, Dept Environm Earth & Ecosyst, CEPSAR, Walton Hall, Milton Keynes MK7 6AA, Bucks, England.
EM v.gauci@open.ac.uk
FU NERC [NE/F008813/1]; Natural Environment Research Council (NERC); Open University (CEPSAR) via the NERC Radiocarbon Facility (Environment) [1323.1008, 15.91]; DECC/Defra Met Office Hadley Centre Programme [GA01101]; Royal Society; British Council; Natural Environment Research Council [earth010003, NRCF010001] Funding Source: researchfish; NERC [earth010003, NRCF010001] Funding Source: UKRI
NR 42
TC 249
Z9 284
U1 5
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 JAN 31
PY 2013
VL 493
IS 7434
BP 660
EP +
DI 10.1038/nature11818
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 080CU
UT WOS:000314219600054
PM 23364745
DA 2026-03-09
ER

PT J
AU Carter, ME
   Soden, ME
   Zweifel, LS
   Palmiter, RD
AF Carter, Matthew E.
   Soden, Marta E.
   Zweifel, Larry S.
   Palmiter, Richard D.
TI Genetic identification of a neural circuit that suppresses appetite
SO NATURE
LA English
DT Article
ID canine adenovirus vectors; fos-like immunoreactivity; parabrachial nucleus; thermosensory pathway; rat-brain; neurons; expression; immune; amygdala; peptide
AB Appetite suppression occurs after a meal and in conditions when it is unfavourable to eat, such as during illness or exposure to toxins. A brain region proposed to play a role in appetite suppression is the parabrachial nucleus(1-3), a heterogeneous population of neurons surrounding the superior cerebellar peduncle in the brainstem. The parabrachial nucleus is thought to mediate the suppression of appetite induced by the anorectic hormones amylin and cholecystokinin(2), as well as by lithium chloride and lipopolysaccharide, compounds that mimic the effects of toxic foods and bacterial infections, respectively(4-6). Hyperactivity of the parabrachial nucleus is also thought to cause starvation after ablation of orexigenic agouti-related peptide neurons in adult mice(1,7). However, the identities of neurons in the parabrachial nucleus that regulate feeding are unknown, as are the functionally relevant downstream projections. Here we identify calcitonin gene-related peptide-expressing neurons in the outer external lateral subdivision of the parabrachial nucleus that project to the laterocapsular division of the central nucleus of the amygdala as forming a functionally important circuit for suppressing appetite. Using genetically encoded anatomical, optogenetic(8) and pharmacogenetic(9) tools, we demonstrate that activation of these neurons projecting to the central nucleus of the amygdala suppresses appetite. In contrast, inhibition of these neurons increases food intake in circumstances when mice do not normally eat and prevents starvation in adult mice whose agouti-related peptide neurons are ablated. Taken together, our data demonstrate that this neural circuit from the parabrachial nucleus to the central nucleus of the amygdala mediates appetite suppression in conditions when it is unfavourable to eat. This neural circuit may provide targets for therapeutic intervention to overcome or promote appetite.
C1 [Carter, Matthew E.; Palmiter, Richard D.] Univ Washington, Howard Hughes Med Inst, Seattle, WA 98195 USA.
   [Carter, Matthew E.; Palmiter, Richard D.] Univ Washington, Dept Biochem, Seattle, WA 98195 USA.
   [Soden, Marta E.; Zweifel, Larry S.] Univ Washington, Dept Pharmacol, Seattle, WA 98195 USA.
   [Soden, Marta E.; Zweifel, Larry S.] Univ Washington, Dept Psychiat, 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; University of Washington; University of Washington Seattle
RP Palmiter, RD (corresponding author), Univ Washington, Howard Hughes Med Inst, Seattle, WA 98195 USA.
EM palmiter@uw.edu
FU Hilda and Preston Davis Foundation; National Institutes of Health [R01MH094536, R01DA024908]; Klarman Family Foundation; National Institute on Drug Abuse [R01DA024908] Funding Source: NIH RePORTER
NR 34
TC 464
Z9 550
U1 1
U2 123
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 7
PY 2013
VL 503
IS 7474
BP 111
EP +
DI 10.1038/nature12596
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 247AS
UT WOS:000326585600042
PM 24121436
DA 2026-03-09
ER

PT J
AU Li, Q
   Bohin, N
   Wen, T
   Ng, V
   Magee, J
   Chen, SC
   Shannon, K
   Morrison, SJ
AF Li, Qing
   Bohin, Natacha
   Wen, Tiffany
   Ng, Victor
   Magee, Jeffrey
   Chen, Shann-Ching
   Shannon, Kevin
   Morrison, Sean J.
TI Oncogenic Nras has bimodal effects on stem cells that sustainably increase competitiveness
SO NATURE
LA English
DT Article
ID hematopoietic stem; self-renewal; ras; activation; proliferation; inactivation; mutations; leukemia; stat5; kras
AB 'Pre-leukaemic' mutations are thought to promote clonal expansion of haematopoietic stem cells (HSCs) by increasing self-renewal and competitiveness(1); however, mutations that increase HSC proliferation tend to reduce competitiveness and self-renewal potential, raising the question of how a mutant HSC can sustainably outcompete wild-type HSCs. Activating mutations in NRAS are prevalent in human myeloproliferative neoplasms and leukaemia(2). Here we show that a single allele of oncogenic Nras(G12D) increases HSC proliferation but also increases reconstituting and self-renewal potential upon serial transplantation in irradiated mice, all prior to leukaemia initiation. Nras(G12D) also confers long-term self-renewal potential to multipotent progenitors. To explore the mechanism by which Nras(G12D) promotes HSC proliferation and self-renewal, we assessed cell-cycle kinetics using H2B-GFP label retention and 5-bromodeoxyuridine (BrdU) incorporation. Nras(G12D) had a bimodal effect on HSCs, increasing the frequency with which some HSCs divide and reducing the frequency with which others divide. This mirrored bimodal effects on reconstituting potential, as rarely dividing Nras(G12D) HSCs outcompeted wild-type HSCs, whereas frequently dividing Nras(G12D) HSCs did not. Nras(G12D) caused these effects by promoting STAT5 signalling, inducing different transcriptional responses in different subsets of HSCs. One signal can therefore increase HSC proliferation, competitiveness and self-renewal through bimodal effects on HSC gene expression, cycling and reconstituting potential.
C1 [Li, Qing; Bohin, Natacha; Wen, Tiffany; Ng, Victor] Univ Michigan, Dept Med, Ann Arbor, MI 48109 USA.
   [Magee, Jeffrey; Morrison, Sean J.] Univ Texas SW Med Ctr Dallas, Dept Pediat, Howard Hughes Med Inst, Dallas, TX 75390 USA.
   [Magee, Jeffrey; Morrison, Sean J.] Univ Texas SW Med Ctr Dallas, Childrens Res Inst, Dallas, TX 75390 USA.
   [Chen, Shann-Ching] St Jude Childrens Res Hosp, Dept Pathol, Memphis, TN 38105 USA.
   [Shannon, Kevin] Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94158 USA.
C3 University of Michigan System; University of Michigan; Howard Hughes Medical Institute; University of Texas System; University of Texas Southwestern Medical Center; University of Texas System; University of Texas Southwestern Medical Center; St Jude Children's Research Hospital; University of California System; University of California San Francisco
RP Li, Q (corresponding author), Univ Michigan, Dept Med, Ann Arbor, MI 48109 USA.
EM lqing@umich.edu; Sean.Morrison@UTSouthwestern.edu
FU Cancer Prevention and Research Institute of Texas; NIH [K08-CA-134649]; V Foundation V Scholar award; National Cancer Institute [P30CA046592, T32CA128583] Funding Source: NIH RePORTER
NR 34
TC 98
Z9 113
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 DEC 5
PY 2013
VL 504
IS 7478
BP 143
EP +
DI 10.1038/nature12830
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 264BK
UT WOS:000327851700048
PM 24284627
DA 2026-03-09
ER

PT J
AU Johannessen, CM
   Johnson, LA
   Piccioni, F
   Townes, A
   Frederick, DT
   Donahue, MK
   Narayan, R
   Flaherty, KT
   Wargo, JA
   Root, DE
   Garraway, LA
AF Johannessen, Cory M.
   Johnson, Laura A.
   Piccioni, Federica
   Townes, Aisha
   Frederick, Dennie T.
   Donahue, Melanie K.
   Narayan, Rajiv
   Flaherty, Keith T.
   Wargo, Jennifer A.
   Root, David E.
   Garraway, Levi A.
TI A melanocyte lineage program confers resistance to MAP kinase pathway inhibition (Publication with Expression of Concern. See APR, 2025)
SO NATURE
LA English
DT Article; Publication with Expression of Concern
ID improved survival; mek inhibition; braf; expression; microphthalmia; transcription; mutations; oncogene; reveals; raf-1
AB Malignant melanomas harbouring point mutations (Val600Glu) in the serine/threonine-protein kinase BRAF (BRAF(V600E)) depend on RAF-MEK-ERK signalling for tumour cell growth(1). RAF and MEK inhibitors show remarkable clinical efficacy in BRAF(V600E) melanoma(2,3); however, resistance to these agents remains a formidable challenge(2,4). Global characterization of resistance mechanisms may inform the development of more effective therapeutic combinations. Here we carried out systematic gain-of-function resistance studies by expressing more than 15,500 genes individually in a BRAF(V600E) melanoma cell line treated with RAF, MEK, ERK or combined RAF-MEK inhibitors. These studies revealed a cyclic-AMP-dependent melanocytic signalling network not previously associated with drug resistance, including G-protein-coupled receptors, adenyl cyclase, protein kinase A and cAMP response element binding protein(CREB). Preliminary analysis of biopsies from BRAF (V600E) melanoma patients revealed that phosphorylated (active) CREB was suppressed by RAF-MEK inhibition but restored in relapsing tumours. Expression of transcription factors activated downstream of MAP kinase and cAMP pathways also conferred resistance, including c-FOS, NR4A1, NR4A2 and MITF. Combined treatment with MAPK-pathway and histone-deacetylase inhibitors suppressed MITF expression and cAMP-mediated resistance. Collectively, these data suggest that oncogenic dysregulation of a melanocyte lineage dependency can cause resistance to RAF-MEK-ERK inhibition, which may be overcome by combining signalling-and chromatin-directed therapeutics.
C1 [Johannessen, Cory M.; Johnson, Laura A.; Piccioni, Federica; Townes, Aisha; Donahue, Melanie K.; Narayan, Rajiv; Root, David E.; Garraway, Levi A.] Broad Inst Harvard Univ & Massachusetts Inst Tech, Cambridge, MA 02142 USA.
   [Johannessen, Cory M.; Johnson, Laura A.; Garraway, Levi A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
   [Johannessen, Cory M.; Garraway, Levi A.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
   [Frederick, Dennie T.; Flaherty, Keith T.; Wargo, Jennifer A.] Massachusetts Gen Hosp, Dept Surg Oncol Med Oncol & Dermatol, Boston, MA 02114 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; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital
RP Garraway, LA (corresponding author), Broad Inst Harvard Univ & Massachusetts Inst Tech, 7 Cambridge Ctr, Cambridge, MA 02142 USA.
EM Levi_Garraway@dfci.harvard.edu
FU National Institutes of Health (NIH) [DP2 OD002750]; Melanoma Research Alliance; Starr Cancer Consortium; Dr. Miriam and Sheldon G. Adelson Medical Research Foundation; NCI Skin Cancer SPORE [P50CA93683]; LINCS Program [U54 HG006093]; National Cancer Institute [P01CA163222] Funding Source: NIH RePORTER
CR Ahn S, 1998, MOL CELL BIOL, V18, P967, DOI 10.1128/MCB.18.2.967
   Aronov AM, 2009, J MED CHEM, V52, P6362, DOI 10.1021/jm900630q
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NR 26
TC 376
Z9 446
U1 0
U2 53
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 5
PY 2013
VL 504
IS 7478
BP 138
EP +
DI 10.1038/nature12688
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 264BK
UT WOS:000327851700047
PM 24185007
DA 2026-03-09
ER

PT J
AU Miyamachi, T
   Schuh, T
   Märkl, T
   Bresch, C
   Balashov, T
   Stöhr, A
   Karlewski, C
   André, S
   Marthaler, M
   Hoffmann, M
   Geilhufe, M
   Ostanin, S
   Hergert, W
   Mertig, I
   Schön, G
   Ernst, A
   Wulfhekel, W
AF Miyamachi, Toshio
   Schuh, Tobias
   Maerkl, Tobias
   Bresch, Christopher
   Balashov, Timofey
   Stoehr, Alexander
   Karlewski, Christian
   Andre, Stephan
   Marthaler, Michael
   Hoffmann, Martin
   Geilhufe, Matthias
   Ostanin, Sergey
   Hergert, Wolfram
   Mertig, Ingrid
   Schoen, Gerd
   Ernst, Arthur
   Wulfhekel, Wulf
TI Stabilizing the magnetic moment of single holmium atoms by symmetry
SO NATURE
LA English
DT Article
ID spin; anisotropy; surface
AB Single magnetic atoms, and assemblies of such atoms, on nonmagnetic surfaces have recently attracted attention owing to their potential use in high-density magnetic data storage and as a platform for quantum computing(1-8). A fundamental problem resulting from their quantum mechanical nature is that the localized magnetic moments of these atoms are easily destabilized by interactions with electrons, nuclear spins and lattice vibrations of the substrate(3-5). Even when large magnetic fields are applied to stabilize the magnetic moment, the observed lifetimes remain rather short(5,6) (less than a microsecond). Several routes for stabilizing the magnetic moment against fluctuations have been suggested, such as using thin insulating layers between the magnetic atom and the substrate to suppress the interactions with the substrate's conduction electrons(2,3,5), or coupling several magnetic moments together to reduce their quantum mechanical fluctuations(7,8). Here we show that the magnetic moments of single holmium atoms on a highly conductive metallic substrate can reach lifetimes of the order of minutes. The necessary decoupling from the thermal bath of electrons, nuclear spins and lattice vibrations is achieved by a remarkable combination of several symmetries intrinsic to the system: time reversal symmetry, the internal symmetries of the total angular momentum and the point symmetry of the local environment of the magnetic atom.
C1 [Miyamachi, Toshio; Schuh, Tobias; Maerkl, Tobias; Bresch, Christopher; Balashov, Timofey; Stoehr, Alexander; Wulfhekel, Wulf] Karlsruhe Inst Technol KIT, Inst Phys, D-76131 Karlsruhe, Germany.
   [Miyamachi, Toshio] Univ Tokyo, Inst Solid State Phys, Kashiwa, Chiba 2778581, Japan.
   [Stoehr, Alexander] Max Planck Inst Festkorperforsch, D-70569 Stuttgart, Germany.
   [Karlewski, Christian; Andre, Stephan; Marthaler, Michael; Schoen, Gerd] Karlsruhe Inst Technol KIT, Inst Theoret Festkorperphys, D-76131 Karlsruhe, Germany.
   [Hoffmann, Martin; Geilhufe, Matthias; Ostanin, Sergey; Mertig, Ingrid; Ernst, Arthur] Max Planck Inst Mikrostrukturphys, D-06120 Halle, Germany.
   [Hoffmann, Martin; Hergert, Wolfram; Mertig, Ingrid] Univ Halle Wittenberg, Inst Phys, D-06099 Halle, Germany.
   [Ernst, Arthur] Univ Leipzig, Wilhelm Ostwald Inst Phys & Theoret Chem, D-04103 Leipzig, Germany.
C3 Helmholtz Association; Karlsruhe Institute of Technology; University of Tokyo; Max Planck Society; Helmholtz Association; Karlsruhe Institute of Technology; Max Planck Society; Martin Luther University Halle Wittenberg; Leipzig University
RP Wulfhekel, W (corresponding author), Karlsruhe Inst Technol KIT, Inst Phys, Wolfgang Gaede Str 1, D-76131 Karlsruhe, Germany.
EM wulf.wulfhekel@kit.edu
FU German Science Foundation (DFG) [Wu349/4-2, SPP 1538]; DFG Collaborative Research Centre [SFB 762]
NR 25
TC 126
Z9 129
U1 0
U2 152
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 14
PY 2013
VL 503
IS 7475
BP 242
EP 246
DI 10.1038/nature12759
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 250YX
UT WOS:000326894200047
PM 24226888
DA 2026-03-09
ER

PT J
AU Zhang, R
   Zhang, Y
   Dong, ZC
   Jiang, S
   Zhang, C
   Chen, LG
   Zhang, L
   Liao, Y
   Aizpurua, J
   Luo, Y
   Yang, JL
   Hou, JG
AF Zhang, R.
   Zhang, Y.
   Dong, Z. C.
   Jiang, S.
   Zhang, C.
   Chen, L. G.
   Zhang, L.
   Liao, Y.
   Aizpurua, J.
   Luo, Y.
   Yang, J. L.
   Hou, J. G.
TI Chemical mapping of a single molecule by plasmon-enhanced Raman scattering
SO NATURE
LA English
DT Article
ID spectroscopy; microscopy; resolution
AB Visualizing individual molecules with chemical recognition is a longstanding target in catalysis, molecular nanotechnology and biotechnology. Molecular vibrations provide a valuable 'finger-print' for such identification. Vibrational spectroscopy based on tip-enhanced Raman scattering allows us to access the spectral signals of molecular species very efficiently via the strong localized plasmonic fields produced at the tip apex(1-11). However, the best spatial resolution of the tip-enhanced Raman scattering imaging is still limited to 3-15 nanometres(5,12-16), which is not adequate for resolving a single molecule chemically. Here we demonstrate Raman spectral imaging with spatial resolution below one nanometre, resolving the inner structure and surface configuration of a single molecule. This is achieved by spectrally matching the resonance of the nanocavity plasmon to the molecular vibronic transitions, particularly the downward transition responsible for the emission of Raman photons. This matching is made possible by the extremely precise tuning capability provided by scanning tunnelling microscopy. Experimental evidence suggests that the highly confined and broadband nature of the nanocavity plasmon field in the tunnelling gap is essential for ultrahigh-resolution imaging through the generation of an efficient double-resonance enhancement for both Raman excitation and Raman emission. Our technique not only allows for chemical imaging at the single-molecule level, but also offers a new way to study the optical processes and photochemistry of a single molecule.
C1 [Zhang, R.; Zhang, Y.; Dong, Z. C.; Jiang, S.; Zhang, C.; Chen, L. G.; Zhang, L.; Liao, Y.; Luo, Y.; Yang, J. L.; Hou, J. G.] Univ Sci & Technol China, Hefei Natl Lab Phys Sci Microscale, Hefei 230026, Anhui, Peoples R China.
   [Aizpurua, J.] Mat Phys Ctr CSIC UPV EHU, Donostia San Sebastian 20018, Spain.
   [Aizpurua, J.] Donostia Int Phys Ctr DIPC, Donostia San Sebastian 20018, Spain.
   [Luo, Y.] Royal Inst Technol, Sch Biotechnol, S-10691 Stockholm, Sweden.
C3 Chinese Academy of Sciences; University of Science & Technology of China, CAS; University of Basque Country; Consejo Superior de Investigaciones Cientificas (CSIC); Royal Institute of Technology
RP Dong, ZC (corresponding author), Univ Sci & Technol China, Hefei Natl Lab Phys Sci Microscale, Hefei 230026, Anhui, Peoples R China.
EM zcdong@ustc.edu.cn; jghou@ustc.edu.cn
FU National Basic Research Program of China; Strategic Priority Research Program of the Chinese Academy of Sciences; Natural Science Foundation of China; Basque Government Project of Excellence (ETORTEK)
NR 30
TC 1558
Z9 1754
U1 14
U2 1910
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 6
PY 2013
VL 498
IS 7452
BP 82
EP 86
DI 10.1038/nature12151
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 158DC
UT WOS:000319947800037
PM 23739426
DA 2026-03-09
ER

PT J
AU Bolatto, AD
   Warren, SR
   Leroy, AK
   Walter, F
   Veilleux, S
   Ostriker, EC
   Ott, J
   Zwaan, M
   Fisher, DB
   Weiss, A
   Rosolowsky, E
   Hodge, J
AF Bolatto, Alberto D.
   Warren, Steven R.
   Leroy, Adam K.
   Walter, Fabian
   Veilleux, Sylvain
   Ostriker, Eve C.
   Ott, Juergen
   Zwaan, Martin
   Fisher, David B.
   Weiss, Axel
   Rosolowsky, Erik
   Hodge, Jacqueline
TI Suppression of star formation in the galaxy NGC 253 by a starburst-driven molecular wind
SO NATURE
LA English
DT Article
ID chandra observations; mass function; ngc-253; outflows; feedback; gas; m82; superwinds; emission; origin
AB The under-abundance of very massive galaxies(1,2) in the Universe is frequently attributed to the effect of galactic winds(3-6). Although ionized galactic winds are readily observable, most of the expelled mass (that is, the total mass flowing out from the nuclear region) is likely to be in atomic(7,8) and molecular phases(9-11) that are cooler than the ionized phases. Expanding molecular shells observed in starburst systems such as NGC 253 (ref. 12) and M 82 (refs 13, 14) may facilitate the entrainment of molecular gas in the wind. Although shell properties are well constrained(12), determining the amount of outflowing gas emerging from such shells and the connection between this gas and the ionized wind requires spatial resolution better than 100 parsecs coupled with sensitivity to a wide range of spatial scales, a combination hitherto not available. Here we report observations of NGC 253, a nearby(15) starburst galaxy (distance similar to 3.4 megaparsecs) known to possess a wind(16-20), that trace the cool molecular wind at 50-parsec resolution. At this resolution, the extraplanar molecular gas closely tracks the Ha filaments, and it appears to be connected to expanding molecular shells located in the starburst region. These observations allow us to determine that the molecular outflow rate is greater than 3 solar masses per year and probably about 9 solar masses per year. This implies a ratio of mass-outflow rate to star-formation rate of at least 1, and probably similar to 3, indicating that the starburst-driven wind limits the star-formation activity and the final stellar content.
C1 [Bolatto, Alberto D.; Warren, Steven R.; Veilleux, Sylvain; Fisher, David B.] Univ Maryland, Dept Astron, Lab Millimeter Wave Astron, College Pk, MD 20742 USA.
   [Bolatto, Alberto D.; Warren, Steven R.; Veilleux, Sylvain; Fisher, David B.] Univ Maryland, Joint Space Inst, College Pk, MD 20742 USA.
   [Leroy, Adam K.] Natl Radio Astron Observ, Charlottesville, VA 22903 USA.
   [Walter, Fabian; Hodge, Jacqueline] Max Planck Inst Astron, D-69117 Heidelberg, Germany.
   [Ostriker, Eve C.] Princeton Univ, Dept Astrophys Sci, Princeton, NJ 08544 USA.
   [Ott, Juergen] Natl Radio Astron Observ, Socorro, NM 87801 USA.
   [Zwaan, Martin] European So Observ, D-85748 Garching, Germany.
   [Weiss, Axel] Max Planck Inst Radioastron, D-53121 Bonn, Germany.
   [Rosolowsky, Erik] Univ British Columbia, Dept Phys & Astron, Kelowna, BC V1V 1V7, Canada.
C3 University System of Maryland; University of Maryland College Park; University System of Maryland; University of Maryland College Park; National Radio Astronomy Observatory (NRAO); Max Planck Society; Princeton University; National Radio Astronomy Observatory (NRAO); European Southern Observatory; Max Planck Society; University of British Columbia
RP Bolatto, AD (corresponding author), Univ Maryland, Dept Astron, Lab Millimeter Wave Astron, College Pk, MD 20742 USA.
EM bolatto@astro.umd.edu
FU CAREER [NSF-AST0955836, NSF-AST1139998]; Research Corporation for Science Advancement Cottrell Scholar award; NSF [AST-0908185];  [NSF-AST100958]; Division Of Astronomical Sciences; Direct For Mathematical & Physical Scien [1009583, 0955836, 1318309] Funding Source: National Science Foundation
NR 30
TC 256
Z9 273
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 JUL 25
PY 2013
VL 499
IS 7459
BP 450
EP 453
DI 10.1038/nature12351
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 187YP
UT WOS:000322157900034
PM 23887428
DA 2026-03-09
ER

PT J
AU Rao, A
   Chow, PCY
   Gélinas, S
   Schlenker, CW
   Li, CZ
   Yip, HL
   Jen, AKY
   Ginger, DS
   Friend, RH
AF Rao, Akshay
   Chow, Philip C. Y.
   Gelinas, Simon
   Schlenker, Cody W.
   Li, Chang-Zhi
   Yip, Hin-Lap
   Jen, Alex K. -Y.
   Ginger, David S.
   Friend, Richard H.
TI The role of spin in the kinetic control of recombination in organic photovoltaics
SO NATURE
LA English
DT Article
ID heterojunction solar-cells; charge-transfer excitons; open-circuit voltage; efficiency; energy; morphology; separation; additives; polymers; geminate
AB In biological complexes, cascade structures promote the spatial separation of photogenerated electrons and holes, preventing their recombination(1). In contrast, the photogenerated excitons in organic photovoltaic cells are dissociated at a single donor-acceptor heterojunction formed within a de-mixed blend of the donor and acceptor semiconductors(2). The nanoscale morphology and high charge densities give a high rate of electron-hole encounters, which should in principle result in the formation of spin-triplet excitons, as in organic light-emitting diodes(3). Although organic photovoltaic cells would have poor quantum efficiencies if every encounter led to recombination, state-of-the-art examples nevertheless demonstrate near-unity quantum efficiency(4). Here we show that this suppression of recombination arises through the interplay between spin, energetics and delocalization of electronic excitations in organic semiconductors. We use time-resolved spectroscopy to study a series of model high-efficiency polymer-fullerene systems in which the lowest-energy molecular triplet exciton (T-1) for the polymer is lower in energy than the intermolecular charge transfer state. We observe the formation of T-1 states following bimolecular recombination, indicating that encounters of spin-uncorrelated electrons and holes generate charge transfer states with both spin-singlet ((CT)-C-1) and spin-triplet ((CT)-C-3) characters. We show that the formation of triplet excitons can be the main loss mechanism in organic photovoltaic cells. But we also find that, even when energetically favoured, the relaxation of (CT)-C-3 states to T-1 states can be strongly suppressed by wavefunction delocalization, allowing for the dissociation of (CT)-C-3 states back to free charges, thereby reducing recombination and enhancing device performance. Our results point towards new design rules both for photo-conversion systems, enabling the suppression of electron-hole recombination, and for organic light-emitting diodes, avoiding the formation of triplet excitons and enhancing fluorescence efficiency.
C1 [Rao, Akshay; Chow, Philip C. Y.; Gelinas, Simon; Friend, Richard H.] Univ Cambridge, Cavendish Lab, Cambridge CB3 0HE, England.
   [Schlenker, Cody W.; Jen, Alex K. -Y.; Ginger, David S.] Univ Washington, Dept Chem, Seattle, WA 98195 USA.
   [Li, Chang-Zhi; Yip, Hin-Lap; Jen, Alex K. -Y.] Univ Washington, Dept Mat Sci & Engn, Seattle, WA 98195 USA.
C3 University of Cambridge; University of Washington; University of Washington Seattle; University of Washington; University of Washington Seattle
RP Friend, RH (corresponding author), Univ Cambridge, Cavendish Lab, Cambridge CB3 0HE, England.
EM rhf10@cam.ac.uk
FU Corpus Christi College, Cambridge; Fonds Quebecois de Recherche sur la Nature et les Technologies; EPSRC; Winton Programme for the Physics of Sustainability; National Science Foundation [DMR-1215753]; Office of Naval Research [N00014-11-1-0300]; Direct For Mathematical & Physical Scien; Division Of Materials Research [1215753] Funding Source: National Science Foundation; EPSRC [EP/G060738/1] Funding Source: UKRI; Engineering and Physical Sciences Research Council [EP/G060738/1] Funding Source: researchfish
NR 30
TC 508
Z9 551
U1 6
U2 738
PU NATURE PUBLISHING 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 22
PY 2013
VL 500
IS 7463
BP 435
EP +
DI 10.1038/nature12339
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 203TJ
UT WOS:000323316100030
PM 23925118
DA 2026-03-09
ER

PT J
AU Lang, GI
   Rice, DP
   Hickman, MJ
   Sodergren, E
   Weinstock, GM
   Botstein, D
   Desai, MM
AF Lang, Gregory I.
   Rice, Daniel P.
   Hickman, Mark J.
   Sodergren, Erica
   Weinstock, George M.
   Botstein, David
   Desai, Michael M.
TI Pervasive genetic hitchhiking and clonal interference in forty evolving yeast populations
SO NATURE
LA English
DT Article
ID integrative genomics viewer; long-term experiment; asexual populations; beneficial mutations; saccharomyces-cerevisiae; adaptive mutations; escherichia-coli; viral adaptation; evolution; alignment
AB The dynamics of adaptation determine which mutations fix in a population, and hence how reproducible evolution will be. This is central to understanding the spectra of mutations recovered in the evolution of antibiotic resistance(1), the response of pathogens to immune selection(2,3), and the dynamics of cancer progression(4,5). In laboratory evolution experiments, demonstrably beneficial mutations are found repeatedly(6-8), but are often accompanied by other mutations with no obvious benefit. Here we use whole-genome whole-population sequencing to examine the dynamics of genome sequence evolution at high temporal resolution in 40 replicate Saccharomyces cerevisiae populations growing in rich medium for 1,000 generations. We find pervasive genetic hitchhiking: multiple mutations arise and move synchronously through the population as mutational 'cohorts'. Multiple clonal cohorts are often present simultaneously, competing with each other in the same population. Our results show that patterns of sequence evolution are driven by a balance between these chance effects of hitchhiking and interference, which increase stochastic variation in evolutionary outcomes, and the deterministic action of selection on individual mutations, which favours parallel evolutionary solutions in replicate populations.
C1 [Lang, Gregory I.; Botstein, David] Princeton Univ, Lewis Sigler Inst Integrat Genom, Princeton, NJ 08544 USA.
   [Lang, Gregory I.; Botstein, David] Princeton Univ, Dept Mol Biol, Princeton, NJ 08544 USA.
   [Rice, Daniel P.; Desai, Michael M.] Harvard Univ, Dept Organism & Evolutionary Biol, Cambridge, MA 02138 USA.
   [Rice, Daniel P.; Desai, Michael M.] Harvard Univ, Dept Phys, Cambridge, MA 02138 USA.
   [Rice, Daniel P.; Desai, Michael M.] Harvard Univ, FAS Ctr Syst Biol, Cambridge, MA 02138 USA.
   [Hickman, Mark J.] Rowan Univ, Dept Biol Sci, Glassboro, NJ 08028 USA.
   [Hickman, Mark J.] Rowan Univ, Dept Chem & Biochem, Glassboro, NJ 08028 USA.
   [Sodergren, Erica; Weinstock, George M.] Washington Univ, Sch Med, Genome Inst, St Louis, MO 63108 USA.
C3 Princeton University; Princeton University; Harvard University; Harvard University; Harvard University; Rowan University; Rowan University; Washington University (WUSTL)
RP Lang, GI (corresponding author), Lehigh Univ, Dept Biol Sci, Bethlehem, PA 18015 USA.
EM glang@lehigh.edu; mmdesai@fas.harvard.edu
FU NSF; NIGMS Centers of Excellence [GM071508]; NIH [GM046406]; James S. McDonnell Foundation; Alfred P. Sloan Foundation; Harvard Milton Fund
NR 36
TC 407
Z9 523
U1 0
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 AUG 29
PY 2013
VL 500
IS 7464
BP 571
EP +
DI 10.1038/nature12344
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 207TD
UT WOS:000323625900033
PM 23873039
DA 2026-03-09
ER

PT J
AU Yosef, N
   Shalek, AK
   Gaublomme, JT
   Jin, HL
   Lee, YJ
   Awasthi, A
   Wu, C
   Karwacz, K
   Xiao, S
   Jorgolli, M
   Gennert, D
   Satija, R
   Shakya, A
   Lu, DY
   Trombetta, JJ
   Pillai, MR
   Ratcliffe, PJ
   Coleman, ML
   Bix, M
   Tantin, D
   Park, H
   Kuchroo, VK
   Regev, A
AF Yosef, Nir
   Shalek, Alex K.
   Gaublomme, Jellert T.
   Jin, Hulin
   Lee, Youjin
   Awasthi, Amit
   Wu, Chuan
   Karwacz, Katarzyna
   Xiao, Sheng
   Jorgolli, Marsela
   Gennert, David
   Satija, Rahul
   Shakya, Arvind
   Lu, Diana Y.
   Trombetta, John J.
   Pillai, Meenu R.
   Ratcliffe, Peter J.
   Coleman, Mathew L.
   Bix, Mark
   Tantin, Dean
   Park, Hongkun
   Kuchroo, Vijay K.
   Regev, Aviv
TI Dynamic regulatory network controlling TH17 cell differentiation
SO NATURE
LA English
DT Article
ID genome-wide analysis; transcription-factor; gene-expression; t-cells; target genes; platform; gamma; induction; discovery; database
AB Despite their importance, the molecular circuits that control the differentiation of naive T cells remain largely unknown. Recent studies that reconstructed regulatory networks in mammalian cells have focused on short-term responses and relied on perturbation-based approaches that cannot be readily applied to primary T cells. Here we combine transcriptional profiling at high temporal resolution, novel computational algorithms, and innovative nanowire-based perturbation tools to systematically derive and experimentally validate a model of the dynamic regulatory network that controls the differentiation of mouse T(H)17 cells, a proinflammatory T-cell subset that has been implicated in the pathogenesis of multiple autoimmune diseases. The T(H)17 transcriptional network consists of two self-reinforcing, but mutually antagonistic, modules, with 12 novel regulators, the coupled action of which may be essential for maintaining the balance between T(H)17 and other CD41 T-cell subsets. Our study identifies and validates 39 regulatory factors, embeds them within a comprehensive temporal network and reveals its organizational principles; it also highlights novel drug targets for controlling T(H)17 cell differentiation.
C1 [Yosef, Nir; Gennert, David; Satija, Rahul; Lu, Diana Y.; Trombetta, John J.; Park, Hongkun; Kuchroo, Vijay K.; Regev, Aviv] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.
   [Yosef, Nir; Jin, Hulin; Lee, Youjin; Awasthi, Amit; Wu, Chuan; Karwacz, Katarzyna; Xiao, Sheng; Kuchroo, Vijay K.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Ctr Neurol Dis, Boston, MA 02115 USA.
   [Shalek, Alex K.; Gaublomme, Jellert T.; Jorgolli, Marsela; Park, Hongkun] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA.
   [Shalek, Alex K.; Gaublomme, Jellert T.; Jorgolli, Marsela; Park, Hongkun] Harvard Univ, Dept Phys, Cambridge, MA 02138 USA.
   [Shakya, Arvind; Tantin, Dean] Univ Utah, Sch Med, Dept Pathol, Salt Lake City, UT 84132 USA.
   [Pillai, Meenu R.; Bix, Mark] St Jude Childrens Res Hosp, Dept Immunol, Memphis, TN 38105 USA.
   [Ratcliffe, Peter J.; Coleman, Mathew L.] Univ Oxford, Oxford OX3 7BN, England.
   [Regev, Aviv] MIT, Howard Hughes Med Inst, Dept Biol, Cambridge, MA 02140 USA.
C3 Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard University; Harvard University; Utah System of Higher Education; University of Utah; St Jude Children's Research Hospital; University of Oxford; Howard Hughes Medical Institute; Massachusetts Institute of Technology (MIT)
RP Park, H (corresponding author), Broad Inst MIT & Harvard, 7 Cambridge Ctr, Cambridge, MA 02142 USA.
EM Hongkun_Park@harvard.edu; vkuchroo@rics.bwh.harvard.edu; aregev@broad.mit.edu
FU NHGRI [1P50HG006193-01]; NIH Pioneer Awards [5DP1OD003893-03, DP1OD003958-01]; NIH [NS 30843, NS045937, AI073748, AI45757]; National MS Society [RG2571]; HHMI; Klarman Cell Observatory; National Institute of Allergy and Infectious Diseases [R01AI100873] Funding Source: NIH RePORTER; British Heart Foundation [RG/11/1/28684] Funding Source: researchfish
NR 65
TC 543
Z9 669
U1 0
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 APR 25
PY 2013
VL 496
IS 7446
BP 461
EP +
DI 10.1038/nature11981
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 131HU
UT WOS:000317984400033
PM 23467089
DA 2026-03-09
ER

PT J
AU Jiang, JS
   Miracco, EJ
   Hong, K
   Eckert, B
   Chan, H
   Cash, DD
   Min, BS
   Zhou, ZH
   Collins, K
   Feigon, J
AF Jiang, Jiansen
   Miracco, Edward J.
   Hong, Kyungah
   Eckert, Barbara
   Chan, Henry
   Cash, Darian D.
   Min, Bosun
   Zhou, Z. Hong
   Collins, Kathleen
   Feigon, Juli
TI The architecture of Tetrahymena telomerase holoenzyme
SO NATURE
LA English
DT Article
ID rna-binding domain; stem-loop iv; molecular-structure determination; catalytic subunit tert; n-terminal domain; reverse-transcriptase; electron-microscopy; structural basis; protein p65; xplor-nih
AB Telomerase adds telomeric repeats to chromosome ends using an internal RNA template and a specialized telomerase reverse transcriptase (TERT), thereby maintaining genome integrity. Little is known about the physical relationships among protein and RNA subunits within a biologically functional holoenzyme. Here we describe the architecture of Tetrahymena thermophila telomerase holoenzyme determined by electron microscopy. Six of the seven proteins and the TERT-binding regions of telomerase RNA (TER) have been localized by affinity labelling. Fitting with high-resolution structures reveals the organization of TERT, TER and p65 in the ribonucleoprotein (RNP) catalytic core. p50 has an unanticipated role as a hub between the RNP catalytic core, p75-p19-p45 subcomplex, and the DNA-binding Teb1. A complete in vitro holoenzyme reconstitution assigns function to these interactions in processive telomeric repeat synthesis. These studies provide the first view of the extensive network of subunit associations necessary for telomerase holoenzyme assembly and physiological function.
C1 [Jiang, Jiansen; Zhou, Z. Hong] Univ Calif Los Angeles, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA 90095 USA.
   [Jiang, Jiansen; Miracco, Edward J.; Chan, Henry; Cash, Darian D.; Feigon, Juli] Univ Calif Los Angeles, Dept Chem & Biochem, Los Angeles, CA 90095 USA.
   [Jiang, Jiansen; Zhou, Z. Hong; Feigon, Juli] Univ Calif Los Angeles, Calif Nanosyst Inst, Los Angeles, CA 90095 USA.
   [Hong, Kyungah; Eckert, Barbara; Min, Bosun; Collins, Kathleen] Univ Calif Berkeley, Dept Mol & Cell Biol, 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 Los Angeles; University of California System; University of California Berkeley
RP Feigon, J (corresponding author), Univ Calif Los Angeles, Dept Chem & Biochem, Los Angeles, CA 90095 USA.
EM hong.zhou@ucla.edu; kcollins@berkeley.edu; feigon@mbi.ucla.edu
FU NSF [MCB1022379]; NIH [GM48123, GM54198, GM071940, AI069015, 1S10RR23057]; Ruth L. Kirschstein NRSA postdoctoral fellowship [GM101874]; Ruth L. Kirschstein NRSA pre-doctoral training grant fellowship [GM007185]; CNSI; UCLA; Direct For Biological Sciences [1022379] Funding Source: National Science Foundation; Div Of Molecular and Cellular Bioscience [1022379] Funding Source: National Science Foundation; National Institute of General Medical Sciences [R01GM071940] Funding Source: NIH RePORTER
NR 65
TC 97
Z9 122
U1 0
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 APR 11
PY 2013
VL 496
IS 7444
BP 187
EP +
DI 10.1038/nature12062
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 122VM
UT WOS:000317346300034
PM 23552895
DA 2026-03-09
ER

PT J
AU D'Angelo, G
   Uemura, T
   Chuang, CC
   Polishchuk, E
   Santoro, M
   Ohvo-Rekilä, H
   Sato, T
   Di Tullio, G
   Varriale, A
   D'Auria, S
   Daniele, T
   Capuani, F
   Johannes, L
   Mattjus, P
   Monti, M
   Pucci, P
   Williams, RL
   Burke, JE
   Platt, FM
   Harada, A
   De Matteis, MA
AF D'Angelo, Giovanni
   Uemura, Takefumi
   Chuang, Chia-Chen
   Polishchuk, Elena
   Santoro, Michele
   Ohvo-Rekila, Henna
   Sato, Takashi
   Di Tullio, Giuseppe
   Varriale, Antonio
   D'Auria, Sabato
   Daniele, Tiziana
   Capuani, Fabrizio
   Johannes, Ludger
   Mattjus, Peter
   Monti, Maria
   Pucci, Piero
   Williams, Roger L.
   Burke, John E.
   Platt, Frances M.
   Harada, Akihiro
   De Matteis, Maria Antonietta
TI Vesicular and non-vesicular transport feed distinct glycosylation pathways in the Golgi
SO NATURE
LA English
DT Article
ID glycosphingolipid synthesis; glucosylceramide; toxin; binding; surface; sphingolipids; 4-phosphate; ptdins(4)p; proteins; synthase
AB Newly synthesized proteins and lipids are transported across the Golgi complex via different mechanisms whose respective roles are not completely clear. We previously identified a non-vesicular intra-Golgi transport pathway for glucosylceramide (GlcCer)-the common precursor of the different series of glycosphingolipids-that is operated by the cytosolic GlcCer-transfer protein FAPP2 (also known as PLEKHA8) (ref. 1). However, the molecular determinants of the FAPP2-mediated transfer of GlcCer from the cis-Golgi to the trans-Golgi network, as well as the physiological relevance of maintaining two parallel transport pathways of GlcCer-vesicular and non-vesicular-through the Golgi, remain poorly defined. Here, using mouse and cell models, we clarify the molecular mechanisms underlying the intra-Golgi vectorial transfer of GlcCer by FAPP2 and show that GlcCer is channelled by vesicular and non-vesicular transport to two topologically distinct glycosylation tracks in the Golgi cisternae and the trans-Golgi network, respectively. Our results indicate that the transport modality across the Golgi complex is a key determinant for the glycosylation pattern of a cargo and establish a new paradigm for the branching of the glycosphingolipid synthetic pathway.
C1 [D'Angelo, Giovanni; Polishchuk, Elena; Santoro, Michele; Capuani, Fabrizio; De Matteis, Maria Antonietta] Telethon Inst Genet & Med, I-80131 Naples, Italy.
   [D'Angelo, Giovanni; Varriale, Antonio; D'Auria, Sabato] CNR, Inst Prot Biochem, I-80131 Naples, Italy.
   [Uemura, Takefumi; Sato, Takashi; Harada, Akihiro] Gunma Univ, Inst Mol & Cellular Regulat, Dept Mol & Cellular Biol, Lab Mol Traff, Gunma 3718512, Japan.
   [Chuang, Chia-Chen; Platt, Frances M.] Univ Oxford, Dept Pharmacol, Oxford OX1 3QT, England.
   [Ohvo-Rekila, Henna; Mattjus, Peter] Abo Akad Univ, Dept Biosci, FI-20520 Turku, Finland.
   [Di Tullio, Giuseppe; Daniele, Tiziana] Ist Ric Farmacol Mario Negri, Consorzio Mario Negri Sud, Dept Cell Biol & Oncol, I-66030 Chieti, Italy.
   [Johannes, Ludger] Inst Curie, Ctr Rech, F-75248 Paris 05, France.
   [Johannes, Ludger] CNRS, UMR144, F-75248 Paris, France.
   [Monti, Maria; Pucci, Piero] Univ Naples Federico II, Dipartimento Sci Chim, I-80145 Naples, Italy.
   [Monti, Maria; Pucci, Piero] Univ Naples Federico II, CEINGE Biotecnol Avanzate, I-80145 Naples, Italy.
   [Williams, Roger L.; Burke, John E.] MRC Lab Mol Biol, Cambridge CB2 0QH, England.
   [Harada, Akihiro] Osaka Univ, Dept Cell Biol, Suita, Osaka 5650871, Japan.
C3 Fondazione Telethon; Telethon Institute of Genetics & Medicine (TIGEM); Consiglio Nazionale delle Ricerche (CNR); Istituto di Biochimica delle Proteine (IBP-CNR); Gunma University; University of Oxford; Abo Akademi University; Istituto di Ricerche Farmacologiche Mario Negri IRCCS; Consorzio Mario Negri Sud; UNICANCER; Universite PSL; Institut Curie; Sorbonne Universite; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB); Universite PSL; UNICANCER; Institut Curie; University of Naples Federico II; University of Naples Federico II; CEINGE Biotecnologie Avanzate; MRC Laboratory Molecular Biology; University of Osaka
RP De Matteis, MA (corresponding author), Telethon Inst Genet & Med, Via Pietro Castellino 111, I-80131 Naples, Italy.
EM dematteis@tigem.it
FU Telethon [GSP08002, GGP06166]; Associazione Italiana per la Ricerca sul Cancro (AIRC) [IG 8623]; EU (FP7 Lipidomicnet); AIRC [MFAG 10585]; Academy of Finland; Sigrid Juselius Foundation; Study Abroad Scholarship from the Taiwan Ministry of Education; MRC [MC_U105184308] Funding Source: UKRI; Grants-in-Aid for Scientific Research [25113517, 23591347, 24659084, 24390046] Funding Source: KAKEN; British Heart Foundation [PG/11/109/29247] Funding Source: researchfish; Medical Research Council [MC_U105184308] Funding Source: researchfish
NR 30
TC 129
Z9 141
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 SEP 5
PY 2013
VL 501
IS 7465
BP 
EP 
DI 10.1038/nature12423
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AL8YC
UT WOS:000339424700002
PM 23913272
DA 2026-03-09
ER

PT J
AU Le Chatelier, E
   Nielsen, T
   Qin, JJ
   Prifti, E
   Hildebrand, F
   Falony, G
   Almeida, M
   Arumugam, M
   Batto, JM
   Kennedy, S
   Leonard, P
   Li, JH
   Burgdorf, K
   Grarup, N
   Jorgensen, T
   Brandslund, I
   Nielsen, HB
   Juncker, AS
   Bertalan, M
   Levenez, F
   Pons, N
   Rasmussen, S
   Sunagawa, S
   Tap, J
   Tims, S
   Zoetendal, EG
   Brunak, S
   Clément, K
   Doré, J
   Kleerebezem, M
   Kristiansen, K
   Renault, P
   Sicheritz-Ponten, T
   de Vos, WM
   Zucker, JD
   Raes, J
   Hansen, T
   Bork, P
   Wang, J
   Ehrlich, SD
   Pedersen, O
AF Le Chatelier, Emmanuelle
   Nielsen, Trine
   Qin, Junjie
   Prifti, Edi
   Hildebrand, Falk
   Falony, Gwen
   Almeida, Mathieu
   Arumugam, Manimozhiyan
   Batto, Jean-Michel
   Kennedy, Sean
   Leonard, Pierre
   Li, Junhua
   Burgdorf, Kristoffer
   Grarup, Niels
   Jorgensen, Torben
   Brandslund, Ivan
   Nielsen, Henrik Bjorn
   Juncker, Agnieszka S.
   Bertalan, Marcelo
   Levenez, Florence
   Pons, Nicolas
   Rasmussen, Simon
   Sunagawa, Shinichi
   Tap, Julien
   Tims, Sebastian
   Zoetendal, Erwin G.
   Brunak, Soren
   Clement, Karine
   Dore, Joel
   Kleerebezem, Michiel
   Kristiansen, Karsten
   Renault, Pierre
   Sicheritz-Ponten, Thomas
   de Vos, Willem M.
   Zucker, Jean-Daniel
   Raes, Jeroen
   Hansen, Torben
   Bork, Peer
   Wang, Jun
   Ehrlich, S. Dusko
   Pedersen, Oluf
TI Richness of human gut microbiome correlates with metabolic markers
SO NATURE
LA English
DT Article
ID body-mass index; diet-induced obesity; wide association; weight; inflammation; loci; resistance; childhood; variants; bacteria
AB We are facing a global metabolic health crisis provoked by an obesity epidemic. Here we report the human gut microbial composition in a population sample of 123 non-obese and 169 obese Danish individuals. We find two groups of individuals that differ by the number of gut microbial genes and thus gut bacterial richness. They contain known and previously unknown bacterial species at different proportions; individuals with a low bacterial richness (23% of the population) are characterized by more marked overall adiposity, insulin resistance and dyslipidaemia and a more pronounced inflammatory phenotype when compared with high bacterial richness individuals. The obese individuals among the lower bacterial richness group also gain more weight over time. Only a few bacterial species are sufficient to distinguish between individuals with high and low bacterial richness, and even between lean and obese participants. Our classifications based on variation in the gut microbiome identify subsets of individuals in the general white adult population who may be at increased risk of progressing to adiposity-associated co-morbidities.
C1 [Le Chatelier, Emmanuelle; Prifti, Edi; Almeida, Mathieu; Batto, Jean-Michel; Kennedy, Sean; Leonard, Pierre; Levenez, Florence; Pons, Nicolas; Tap, Julien; Dore, Joel] INRA, Metagenopolis US1367, F-78350 Jouy En Josas, France.
   [Nielsen, Trine; Arumugam, Manimozhiyan; Burgdorf, Kristoffer; Grarup, Niels; Hansen, Torben; Pedersen, Oluf] Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn, Ctr Basic Metab Res, DK-2200 Copenhagen, Denmark.
   [Qin, Junjie; Arumugam, Manimozhiyan; Li, Junhua] BGI Shenzhen, Shenzhen 518083, Peoples R China.
   [Hildebrand, Falk; Falony, Gwen; Raes, Jeroen] VIB, Dept Biol Struct, B-1050 Brussels, Belgium.
   [Hildebrand, Falk; Falony, Gwen; Raes, Jeroen] Vrije Univ Brussel, Dept Biosci Engn, B-1050 Brussels, Belgium.
   [Arumugam, Manimozhiyan; Sunagawa, Shinichi; Tap, Julien; Bork, Peer] European Mol Biol Lab, D-69117 Heidelberg, Germany.
   [Li, Junhua] S China Univ Technol, Sch Biosci & Biotechnol, Guangzhou 510006, Guangdong, Peoples R China.
   [Jorgensen, Torben] Glostrup Univ Hosp, Res Ctr Prevent & Hlth, DK-2900 Glostrup, Denmark.
   [Jorgensen, Torben] Univ Copenhagen, Fac Hlth & Med Sci, DK-2200 Copenhagen, Denmark.
   [Jorgensen, Torben] Aalborg Univ, Fac Med, Inst Publ Hlth, DK-9100 Aalborg, Denmark.
   [Brandslund, Ivan] Vejle Hosp, Dept Clin Biochem, DK-7100 Vejle, Denmark.
   [Brandslund, Ivan] Univ Southern Denmark, Inst Reg Hlth Res, DK-8200 Odense, Denmark.
   [Nielsen, Henrik Bjorn; Juncker, Agnieszka S.; Bertalan, Marcelo; Rasmussen, Simon; Brunak, Soren; Sicheritz-Ponten, Thomas] Tech Univ Denmark, Ctr Biol Sequence Anal, DK-2800 Lyngby, Denmark.
   [Nielsen, Henrik Bjorn; Juncker, Agnieszka S.; Bertalan, Marcelo; Rasmussen, Simon; Brunak, Soren; Sicheritz-Ponten, Thomas] Tech Univ Denmark, Novo Nordisk Fdn, Ctr Biosustainabil, DK-2800 Lyngby, Denmark.
   [Tims, Sebastian; Zoetendal, Erwin G.; Kleerebezem, Michiel; de Vos, Willem M.] Wageningen Univ, Lab Microbiol, NL-6710 BA Ede, Netherlands.
   [Clement, Karine] Ctr Rech Cordeliers, Inst Natl Sante & Rech Med, U872, Equipe 7, F-75006 Paris, France.
   [Clement, Karine; Zucker, Jean-Daniel] Univ Paris 06, F-75006 Paris, France.
   [Clement, Karine] CRNH Ile France, Inst Cardiometab & Nutr, AP HP, F-75013 Paris, France.
   [Dore, Joel; Renault, Pierre] INRA, MICALIS, UMR14121, F-78350 Jouy En Josas, France.
   [Kristiansen, Karsten] Univ Copenhagen, Dept Biol, DK-2200 Copenhagen, Denmark.
   [de Vos, Willem M.] Univ Helsinki, Dept Bacteriol & Immunol, FIN-00014 Helsinki, Finland.
   [Zucker, Jean-Daniel] Inst Rech Dev, UMI 209, Unite Modelisat Math & Informat Syst Complexes, F-93143 Bondy, France.
   [Hansen, Torben] Univ Southern Denmark, Fac Hlth Sci, DK-8200 Odense, Denmark.
   [Wang, Jun] King Abdulaziz Univ, Jeddah 21589, Saudi Arabia.
   [Wang, Jun] Univ Copenhagen, Novo Nordisk Fdn, Ctr Basic Metab Res, DK-2200 Copenhagen, Denmark.
   [Wang, Jun] Aarhus Univ, Ctr Sequencing, DK-8000 Aarhus C, Denmark.
   [Pedersen, Oluf] Hagedorn Res Inst, DK-2820 Gentofte, Denmark.
   [Pedersen, Oluf] Univ Copenhagen, Fac Hlth & Med Sci, Inst Biomed Sci, DK-2200 Copenhagen, Denmark.
   [Pedersen, Oluf] Aarhus Univ, Fac Hlth, DK-8000 Aarhus, Denmark.
C3 INRAE; Universite Paris Saclay; Novo Nordisk Foundation; University of Copenhagen; Beijing Genomics Institute (BGI); Flanders Institute for Biotechnology (VIB); Vrije Universiteit Brussel; European Molecular Biology Laboratory (EMBL); South China University of Technology; University of Copenhagen; Copenhagen University Hospital; University of Copenhagen; Aalborg University; University of Southern Denmark; Lillebaelt Hospital; University of Southern Denmark; Technical University of Denmark; Novo Nordisk Foundation; Technical University of Denmark; Wageningen University & Research; Sorbonne Universite; Universite Paris Cite; Institut National de la Sante et de la Recherche Medicale (Inserm); Sorbonne Universite; Sorbonne Universite; Assistance Publique Hopitaux Paris (APHP); Universite Paris Saclay; INRAE; AgroParisTech; University of Copenhagen; University of Helsinki; Institut de Recherche pour le Developpement (IRD); Sorbonne Universite; University of Southern Denmark; King Abdulaziz University; University of Copenhagen; Novo Nordisk Foundation; Aarhus University; Novo Nordisk; Hagedorn Research Institute; University of Copenhagen; Aarhus University
RP Bork, P (corresponding author), European Mol Biol Lab, Meyerhofstr 1, D-69117 Heidelberg, Germany.
EM bork@embl.de; wangj@genomics.org.cn; dusko.ehrlich@jouy.inra.fr; oluf@sund.ku.dk
FU European Community [HEALTH-F4-2007-201052]; Lundbeck Foundation Centre for Applied Medical Genomics in Personalized Disease Prediction, Prevention and Care (LuCamp); ANR MicroObes, the Metagenopolis grant [ANR-11-DPBS-0001]; Region Ile de France (CODDIM); Fondacoeur; Novo Nordisk Foundation; Novo Nordisk Fonden [NNF10CC1016517] Funding Source: researchfish; Agence Nationale de la Recherche (ANR) [ANR-11-DPBS-0001] Funding Source: Agence Nationale de la Recherche (ANR)
NR 56
TC 3554
Z9 4064
U1 9
U2 1160
PU NATURE PUBLISHING 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 29
PY 2013
VL 500
IS 7464
BP 541
EP +
DI 10.1038/nature12506
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 207TD
UT WOS:000323625900026
PM 23985870
DA 2026-03-09
ER

PT J
AU Goddeeris, MM
   Wu, BM
   Venzke, D
   Yoshida-Moriguchi, T
   Saito, F
   Matsumura, K
   Moore, SA
   Campbell, KP
AF Goddeeris, Matthew M.
   Wu, Biming
   Venzke, David
   Yoshida-Moriguchi, Takako
   Saito, Fumiaki
   Matsumura, Kiichiro
   Moore, Steven A.
   Campbell, Kevin P.
TI LARGE glycans on dystroglycan function as a tunable matrix scaffold to prevent dystrophy
SO NATURE
LA English
DT Article
ID congenital muscular-dystrophy; alpha-dystroglycan; abnormal glycosylation; laminin-binding; disruption; mutations; expression; membrane; complex; cells
AB The dense glycan coat that surrounds every cell is essential for cellular development and physiological function(1), and it is becoming appreciated that its composition is highly dynamic. Post-translational addition of the polysaccharide repeating unit [-3-xylose-alpha 1,3-glucuronic acid-beta 1-](n) by like-acetylglucosaminyltransferase (LARGE) is required for the glycoprotein dystroglycan to function as a receptor for proteins in the extracellular matrix(2,3). Reductions in the amount of [-3-xylose-alpha 1,3-glucuronic acid-beta 1-](n) (hereafter referred to as LARGE-glycan) on dystroglycan result in heterogeneous forms of muscular dystrophy(4). However, neither patient nor mouse studies has revealed a clear correlation between glycosylation status and phenotype(5,6). This disparity can be attributed to our lack of knowledge of the cellular function of the LARGE-glycan repeat. Here we show that coordinated upregulation of Large and dystroglycan in differentiating mouse muscle facilitates rapid extension of LARGE-glycan repeat chains. Using synthesized LARGE-glycan repeats we show a direct correlation between LARGE-glycan extension and its binding capacity for extracellular matrix ligands. Blocking Large upregulation during muscle regeneration results in the synthesis of dystroglycan with minimal LARGE-glycan repeats in association with a less compact basement membrane, immature neuromuscular junctions and dysfunctional muscle predisposed to dystrophy. This was consistent with the finding that patients with increased clinical severity of disease have fewer LARGE-glycan repeats. Our results reveal that the LARGE-glycan of dystroglycan serves as a tunable extracellular matrix protein scaffold, the extension of which is required for normal skeletal muscle function.
C1 [Goddeeris, Matthew M.; Wu, Biming; Venzke, David; Yoshida-Moriguchi, Takako; Campbell, Kevin P.] Univ Iowa, Howard Hughes Med Inst, Roy J & Lucille A Carver Coll Med, Iowa City, IA 52242 USA.
   [Goddeeris, Matthew M.; Wu, Biming; Venzke, David; Yoshida-Moriguchi, Takako; Campbell, Kevin P.] Univ Iowa, Roy J & Lucille A Carver Coll Med, Dept Mol Physiol, Iowa City, IA 52242 USA.
   [Saito, Fumiaki; Matsumura, Kiichiro] Teikyo Univ, Sch Med, Dept Neurol & Neurosci, Itabashi Ku, Tokyo 1738605, Japan.
   [Moore, Steven A.] Univ Iowa, Roy J & Lucille A Carver Coll Med, Dept Pathol, Iowa City, IA 52242 USA.
   [Campbell, Kevin P.] Univ Iowa, Roy J & Lucille A Carver Coll Med, Dept Neurol, Iowa City, IA 52242 USA.
   [Campbell, Kevin P.] Univ Iowa, Roy J & Lucille A Carver Coll Med, Dept Internal Med, Iowa City, IA 52242 USA.
C3 University of Iowa; Howard Hughes Medical Institute; University of Iowa; Teikyo University; University of Iowa; University of Iowa; University of Iowa
RP Campbell, KP (corresponding author), Univ Iowa, Howard Hughes Med Inst, Roy J & Lucille A Carver Coll Med, Iowa City, IA 52242 USA.
EM kevin-campbell@uowa.edu
FU NIH/NIAMS Ruth L. Kirschstein National Research Science Award [F32 AR057289-01]; NIH [T32-DK07690-16]; American Reinvestment and Recovery Act Grant [1RC2NS069521-01]; Muscular Dystrophy Association Research Grant [157538]; Paul D. Wellstone Muscular Dystrophy Cooperative Research Center Grant [1U54NS053672]; NCNP (Ministry of Health and Welfare, Japan); MEXT [23591256, 24501357, 25430075]; National Institute of Diabetes and Digestive and Kidney Diseases [T32DK007690] Funding Source: NIH RePORTER; Grants-in-Aid for Scientific Research [24501357, 25430075, 23591256] Funding Source: KAKEN
NR 46
TC 101
Z9 117
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 NOV 7
PY 2013
VL 503
IS 7474
BP 136
EP +
DI 10.1038/nature12605
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 247AS
UT WOS:000326585600047
PM 24132234
DA 2026-03-09
ER

PT J
AU Cao, EH
   Liao, MF
   Cheng, YF
   Julius, D
AF Cao, Erhu
   Liao, Maofu
   Cheng, Yifan
   Julius, David
TI TRPV1 structures in distinct conformations reveal activation mechanisms
SO NATURE
LA English
DT Article
ID species-specific sensitivity; c-type inactivation; capsaicin receptor; ion-channel; k+ channel; tarantula toxin; voltage-sensor; selectivity; binding; domain
AB Transient receptor potential (TRP) channels are polymodal signal detectors that respond to a wide range of physical and chemical stimuli. Elucidating how these channels integrate and convert physiological signals into channel opening is essential to understanding how they regulate cell excitability under normal and pathophysiological conditions. Here we exploit pharmacological probes (a peptide toxin and small vanilloid agonists) to determine structures of two activated states of the capsaicin receptor, TRPV1. A domain (consisting of transmembrane segments 1-4) that moves during activation of voltage-gated channels remains stationary in TRPV1, highlighting differences in gating mechanisms for these structurally related channel superfamilies. TRPV1 opening is associated with major structural rearrangements in the outer pore, including the pore helix and selectivity filter, as well as pronounced dilation of a hydrophobic constriction at the lower gate, suggesting a dual gating mechanism. Allosteric coupling between upper and lower gates may account for rich physiological modulation exhibited by TRPV1 and other TRP channels.
C1 [Cao, Erhu; Julius, David] Univ Calif San Francisco, Dept Physiol, San Francisco, CA 94158 USA.
   [Liao, Maofu; Cheng, Yifan] Univ Calif San Francisco, Dept Biochem & Biophys, Keck Adv Microscopy Lab, San Francisco, CA 94158 USA.
C3 University of California System; University of California San Francisco; University of California System; University of California San Francisco
RP Julius, D (corresponding author), Univ Calif San Francisco, Dept Physiol, San Francisco, CA 94158 USA.
EM ycheng@ucsf.edu; david.julius@ucsf.edu
FU National Institutes of Health [R01GM098672, S10RR026814, R01NS065071, R01NS047723]; National Science Foundation [DBI-0960271]; University of California, San Francisco Program for Breakthrough Biomedical Research
NR 55
TC 853
Z9 998
U1 4
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 DEC 5
PY 2013
VL 504
IS 7478
BP 113
EP +
DI 10.1038/nature12823
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 264BK
UT WOS:000327851700041
PM 24305161
DA 2026-03-09
ER

PT J
AU Desireddy, A
   Conn, BE
   Guo, JS
   Yoon, B
   Barnett, RN
   Monahan, BM
   Kirschbaum, K
   Griffith, WP
   Whetten, RL
   Landman, U
   Bigioni, TP
AF Desireddy, Anil
   Conn, Brian E.
   Guo, Jingshu
   Yoon, Bokwon
   Barnett, Robert N.
   Monahan, Bradley M.
   Kirschbaum, Kristin
   Griffith, Wendell P.
   Whetten, Robert L.
   Landman, Uzi
   Bigioni, Terry P.
TI Ultrastable silver nanoparticles
SO NATURE
LA English
DT Article
ID crystal-structure; growth; plasmonics; cluster
AB Noble-metal nanoparticles have had a substantial impact across a diverse range of fields, including catalysis(1), sensing(2), photochemistry(3), optoelectronics(4,5), energy conversion(6) andmedicine(7). Although silver has very desirable physical properties, good relative abundance and low cost, gold nanoparticles have been widely favoured owing to their proved stability and ease of use. Unlike gold, silver is notorious for its susceptibility to oxidation (tarnishing), which has limited the development of important silver-based nanomaterials. Despite two decades of synthetic efforts, silver nanoparticles that are inert or have long-term stability remain unrealized. Here we report a simple synthetic protocol for producing ultrastable silver nanoparticles, yielding a single-sized molecular product in very large quantities with quantitative yield and without the need for size sorting. The stability, purity and yield are substantially better than those for other metal nanoparticles, including gold, owing to an effective stabilization mechanism. The particular size and stoichiometry of the product were found to be insensitive to variations in synthesis parameters. The chemical stability and structural, electronic and optical properties can be understood using first-principles electronic structure theory based on an experimental single-crystal X-ray structure. Although several structures have been determined for protected gold nanoclusters(8-12), none has been reported so far for silver nanoparticles. The total structure of a thiolate-protected silver nanocluster reported here uncovers the unique structure of the silver thiolate protecting layer, consisting of Ag2S5 capping structures. The outstanding stability of the nanoparticle is attributed to a closed-shell 18-electron configuration with a large energy gap between the highest occupied molecular orbital and the lowest unoccupied molecular orbital, an ultrastable 32-silver-atom excavated-dodecahedral(13) core consisting of a hollow 12-silver-atom icosahedron encapsulated by a 20-silver-atom dodecahedron, and the choice of protective coordinating ligands. The straightforward synthesis of large quantities of pure molecular product promises to make this class of materials widely available for further research and technology development(14-18).
C1 [Desireddy, Anil; Conn, Brian E.; Guo, Jingshu; Monahan, Bradley M.; Kirschbaum, Kristin; Griffith, Wendell P.; Bigioni, Terry P.] Univ Toledo, Dept Chem, Toledo, OH 43606 USA.
   [Yoon, Bokwon; Barnett, Robert N.; Landman, Uzi] Georgia Inst Technol, Sch Phys, Atlanta, GA 30332 USA.
   [Whetten, Robert L.] Georgia Inst Technol, Sch Chem & Biochem, Atlanta, GA 30332 USA.
   [Whetten, Robert L.] Univ Texas San Antonio, Dept Phys & Astron, San Antonio, TX 78249 USA.
   [Bigioni, Terry P.] Univ Toledo, Sch Solar & Adv Renewable Energy, Toledo, OH 43606 USA.
C3 University System of Ohio; University of Toledo; University System of Georgia; Georgia Institute of Technology; University System of Georgia; Georgia Institute of Technology; University of Texas System; University of Texas at San Antonio; University System of Ohio; University of Toledo
RP Bigioni, TP (corresponding author), Univ Toledo, Dept Chem, Toledo, OH 43606 USA.
EM Terry.Bigioni@utoledo.edu
FU NSF [CBET-0955148, CRIF-0840474]; Wright Center for Photovoltaics Innovation and Commercialization; School of Solar and Advanced Renewable Energy; Office of Basic Energy Sciences of the US Department of Energy [FG05-86ER45234]; Air Force Office of Scientific Research; Directorate For Engineering; Div Of Chem, Bioeng, Env, & Transp Sys [0955148] Funding Source: National Science Foundation
NR 33
TC 1029
Z9 1104
U1 19
U2 1652
PU NATURE PUBLISHING 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 19
PY 2013
VL 501
IS 7467
BP 399
EP 402
DI 10.1038/nature12523
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 219XT
UT WOS:000324545700041
PM 24005327
DA 2026-03-09
ER

PT J
AU Blomberg, R
   Kries, H
   Pinkas, DM
   Mittl, PRE
   Grütter, MG
   Privett, HK
   Mayo, SL
   Hilvert, D
AF Blomberg, Rebecca
   Kries, Hajo
   Pinkas, Daniel M.
   Mittl, Peer R. E.
   Gruetter, Markus G.
   Privett, Heidi K.
   Mayo, Stephen L.
   Hilvert, Donald
TI Precision is essential for efficient catalysis in an evolved Kemp eliminase
SO NATURE
LA English
DT Article
ID triosephosphate isomerase; enzyme catalysis; transition-state; base catalysis; antibody; design; orientation; specificity; mutagenesis; evolution
AB Linus Pauling established the conceptual framework for understanding and mimicking enzymes more than six decades ago(1). The notion that enzymes selectively stabilize the rate-limiting transition state of the catalysed reaction relative to the bound ground state reduces the problem of design to one of molecular recognition. Nevertheless, past attempts to capitalize on this idea, for example by using transition state analogues to elicit antibodies with catalytic activities(2), have generally failed to deliver true enzymatic rates. The advent of computational design approaches, combined with directed evolution, has provided an opportunity to revisit this problem. Starting from a computationally designed catalyst for the Kemp elimination(3)-a well-studied model system for proton transfer from carbon-we show that an artificial enzyme can be evolved that accelerates an elementary chemical reaction 6 x 10(8)-fold, approaching the exceptional efficiency of highly optimized natural enzymes such as triosephosphate isomerase. A 1.09 angstrom resolution crystal structure of the evolved enzyme indicates that familiar catalytic strategies such as shape complementarity and precisely placed catalytic groups can be successfully harnessed to afford such high rate accelerations, making us optimistic about the prospects of designing more sophisticated catalysts.
C1 [Blomberg, Rebecca; Kries, Hajo; Pinkas, Daniel M.; Hilvert, Donald] ETH, Organ Chem Lab, CH-8093 Zurich, Switzerland.
   [Mittl, Peer R. E.; Gruetter, Markus G.] Univ Zurich, Dept Biochem, CH-8057 Zurich, Switzerland.
   [Privett, Heidi K.] CALTECH, Div Chem & Chem Engn, Pasadena, CA 91125 USA.
   [Mayo, Stephen L.] CALTECH, Div Biol & Biol Engn, Pasadena, CA 91125 USA.
C3 Swiss Federal Institutes of Technology Domain; ETH Zurich; University of Zurich; California Institute of Technology; California Institute of Technology
RP Hilvert, D (corresponding author), ETH, Organ Chem Lab, CH-8093 Zurich, Switzerland.
EM hilvert@org.chem.ethz.ch
FU Swiss National Science Foundation (SNSF); National Center of Excellence in Research (NCCR) Structural Biology program of the SNSF; ETH Zurich; Defense Advanced Research Projects Agency (DARPA); Fonds des Verbandes der chemischen Industrie; Stipendienfonds der Schweizer Chemischen Industrie; Studienstiftung des deutschen Volkes; National Security Science and Engineering Faculty Fellowship
NR 47
TC 272
Z9 307
U1 4
U2 196
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 21
PY 2013
VL 503
IS 7476
BP 418
EP +
DI 10.1038/nature12623
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 254KG
UT WOS:000327163200046
PM 24132235
DA 2026-03-09
ER

PT J
AU Liu, SH
   Brown, JD
   Stanya, KJ
   Homan, E
   Leidl, M
   Inouye, K
   Bhargava, P
   Gangl, MR
   Dai, LL
   Hatano, B
   Hotamisligil, GS
   Saghatelian, A
   Plutzky, J
   Lee, CH
AF Liu, Sihao
   Brown, Jonathan D.
   Stanya, Kristopher J.
   Homan, Edwin
   Leidl, Mathias
   Inouye, Karen
   Bhargava, Prerna
   Gangl, Matthew R.
   Dai, Lingling
   Hatano, Ben
   Hotamisligil, Goekhan S.
   Saghatelian, Alan
   Plutzky, Jorge
   Lee, Chih-Hao
TI A diurnal serum lipid integrates hepatic lipogenesis and peripheral fatty acid use
SO NATURE
LA English
DT Article
ID circadian behavior; adipose-tissue; metabolism; identification; mass; alpha; glucose; mice
AB Food intake increases the activity of hepatic de novo lipogenesis, which mediates the conversion of glucose to fats for storage or use. In mice, this program follows a circadian rhythm that peaks with nocturnal feeding(1,2) and is repressed by Rev-erb alpha/beta and an HDAC3-containing complex(3-5) during the day. The transcriptional activators controlling rhythmic lipid synthesis in the dark cycle remain poorly defined. Disturbances in hepatic lipogenesis are also associated with systemic metabolic phenotypes(6-8), suggesting that lipogenesis in the liver communicates with peripheral tissues to control energy substrate homeostasis. Here we identify a PPAR delta-dependent de novo lipogenic pathway in the liver that modulates fat use by muscle via a circulating lipid. The nuclear receptor PPAR delta controls diurnal expression of lipogenic genes in the dark/feeding cycle. Liver-specific PPAR delta activation increases, whereas hepatocyte-Ppard deletion reduces, muscle fatty acid uptake. Unbiased metabolite profiling identifies phosphatidylcholine 18:0/18:1 (PC(18:0/18:1) as a serum lipid regulated by diurnal hepatic PPAR delta activity. PC(18:0/18:1) reduces postprandial lipid levels and increases fatty acid use through muscle PPAR alpha. High-fat feeding diminishes rhythmic production of PC(18:0/18:1), whereas PC(18:0/18:1) administration in db/db mice (also known as Lepr(-/-)) improves metabolic homeostasis. These findings reveal an integrated regulatory circuit coupling lipid synthesis in the liver to energy use in muscle by coordinating the activity of two closely related nuclear receptors. These data implicate alterations in diurnal hepatic PPAR delta-PC(18:0/18:1) signalling in metabolic disorders, including obesity.
C1 [Liu, Sihao; Stanya, Kristopher J.; Inouye, Karen; Bhargava, Prerna; Gangl, Matthew R.; Dai, Lingling; Hatano, Ben; Hotamisligil, Goekhan S.; Lee, Chih-Hao] Harvard Univ, Sch Publ Hlth, Div Biol Sci, Dept Genet & Complex Dis, Boston, MA 02115 USA.
   [Brown, Jonathan D.; Plutzky, Jorge] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiovasc,Dept Med, Boston, MA 02115 USA.
   [Homan, Edwin; Leidl, Mathias; Saghatelian, Alan] Harvard Univ, Dept Chem, Cambridge, MA 02138 USA.
   [Dai, Lingling] Cent South Univ, XiangYa Hosp, Good Clin Practice Off, Changsha 410000, Hunan, Peoples R China.
   [Dai, Lingling] Cent South Univ, Inst Clin Pharmacol, Changsha 410000, Hunan, Peoples R China.
C3 Harvard University; Harvard T.H. Chan School of Public Health; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard Medical School; Harvard University; Central South University; Central South University
RP Lee, CH (corresponding author), Harvard Univ, Sch Publ Hlth, Div Biol Sci, Dept Genet & Complex Dis, 665 Huntington Ave, Boston, MA 02115 USA.
EM clee@hsph.harvard.edu
FU American Heart Association; American Diabetes Association; National Institutes of Health [R01DK075046, R01HL048743, K08HL105678]
NR 40
TC 197
Z9 219
U1 0
U2 99
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 24
PY 2013
VL 502
IS 7472
BP 550
EP +
DI 10.1038/nature12710
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 238YN
UT WOS:000325988400054
PM 24153306
DA 2026-03-09
ER

PT J
AU Raman, KV
   Kamerbeek, AM
   Mukherjee, A
   Atodiresei, N
   Sen, TK
   Lazic, P
   Caciuc, V
   Michel, R
   Stalke, D
   Mandal, SK
   Blügel, S
   Münzenberg, M
   Moodera, JS
AF Raman, Karthik V.
   Kamerbeek, Alexander M.
   Mukherjee, Arup
   Atodiresei, Nicolae
   Sen, Tamal K.
   Lazic, Predrag
   Caciuc, Vasile
   Michel, Reent
   Stalke, Dietmar
   Mandal, Swadhin K.
   Bluegel, Stefan
   Muenzenberg, Markus
   Moodera, Jagadeesh S.
TI Interface-engineered templates for molecular spin memory devices
SO NATURE
LA English
DT Article
ID single-molecule; surface; spintronics; bistability; anisotropy; chemistry; magnet
AB The use of molecular spin state as a quantum of information for storage, sensing and computing has generated considerable interest in the context of next-generation data storage and communication devices(1,2), opening avenues for developing multifunctional molecular spintronics(3). Such ideas have been researched extensively, using single-molecule magnets(4,5) and molecules with a metal ion(6) or nitrogen vacancy(7) as localized spin-carrying centres for storage and for realizing logic operations(8). However, the electronic coupling between the spin centres of these molecules is rather weak, which makes construction of quantum memory registers a challenging task(9). In this regard, delocalized carbon-based radical species with unpaired spin, such as phenalenyl(10), have shown promise. These phenalenyl moieties, which can be regarded as graphene fragments, are formed by the fusion of three benzene rings and belong to the class of open-shell systems. The spin structure of these molecules responds to external stimuli(11,12) (such as light, and electric and magnetic fields), which provides novel schemes for performing spin memory and logic operations. Here we construct a molecular device using such molecules as templates to engineer interfacial spin transfer resulting from hybridization and magnetic exchange interaction with the surface of a ferromagnet; the device shows an unexpected interfacial magnetoresistance of more than 20 per cent near room temperature. Moreover, we successfully demonstrate the formation of a nanoscale magnetic molecule with a well-defined magnetic hysteresis on ferromagnetic surfaces. Owing to strong magnetic coupling with the ferromagnet, such independent switching of an adsorbed magnetic molecule has been unsuccessful with single-molecule magnets(13). Our findings suggest the use of chemically amenable phenalenyl-based molecules as a viable and scalable platform for building molecular-scale quantum spin memory and processors for technological development.
C1 [Raman, Karthik V.; Kamerbeek, Alexander M.; Moodera, Jagadeesh S.] MIT, Francis Bitter Natl Magnet Lab, Cambridge, MA 02139 USA.
   [Raman, Karthik V.] MIT, Dept Mat Sci & Engn, Cambridge, MA 02139 USA.
   [Mukherjee, Arup; Sen, Tamal K.; Mandal, Swadhin K.] Indian Inst Sci Educ & Res IISER Kolkata, Dept Chem Sci, Mohanpur 741252, India.
   [Atodiresei, Nicolae; Caciuc, Vasile; Bluegel, Stefan] Forschungszentrum Julich, Peter Grunberg Inst, D-52425 Julich, Germany.
   [Atodiresei, Nicolae; Caciuc, Vasile; Bluegel, Stefan] Forschungszentrum Julich, Inst Adv Simulat, D-52425 Julich, Germany.
   [Atodiresei, Nicolae; Caciuc, Vasile; Bluegel, Stefan] JARA, D-52425 Julich, Germany.
   [Lazic, Predrag] Rudjer Boskovic Inst, Div Theoret Phys, HR-10002 Zagreb, Croatia.
   [Michel, Reent; Stalke, Dietmar] Univ Gottingen, Inst Anorgan Chem, D-37077 Gottingen, Germany.
   [Muenzenberg, Markus] Univ Gottingen, Inst Phys 1, D-37077 Gottingen, Germany.
   [Moodera, Jagadeesh S.] MIT, Dept Phys, Cambridge, MA 02139 USA.
C3 Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); Indian Institute of Science Education & Research (IISER) - Kolkata; Helmholtz Association; Julich Research Centre; Helmholtz Association; Julich Research Centre; Rudjer Boskovic Institute; University of Gottingen; University of Gottingen; Massachusetts Institute of Technology (MIT)
RP Raman, KV (corresponding author), IBM India Res Lab, Bangalore 560045, Karnataka, India.
EM vkarthik@mit.edu; n.atodiresei@fz-juelich.de; swadhin.mandal@iiserkol.ac.in; moodera@mit.edu
FU Office of Naval Research (ONR) [N00014-09-1-0177]; National Science Foundation [DMR 0504158, ULFR 09-0532-01]; University of Groningen; IISER-Kolkata; CSIR, India [01(2369)/10/EMR-II]; German Science foundation [SFB 602, SPP 1538]; Deutsche Forschungsgemeinschaft (DFG) [1178]; Danish National Research Foundation (DNRF); Land Niedersachsen
NR 30
TC 434
Z9 460
U1 2
U2 756
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 24
PY 2013
VL 493
IS 7433
BP 509
EP 513
DI 10.1038/nature11719
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 075GF
UT WOS:000313871400033
PM 23344361
DA 2026-03-09
ER

PT J
AU Campos, GEP
   Moran, MS
   Huete, A
   Zhang, YG
   Bresloff, C
   Huxman, TE
   Eamus, D
   Bosch, DD
   Buda, AR
   Gunter, SA
   Scalley, TH
   Kitchen, SG
   McClaran, MP
   McNab, WH
   Montoya, DS
   Morgan, JA
   Peters, DPC
   Sadler, EJ
   Seyfried, MS
   Starks, PJ
AF Campos, Guillermo E. Ponce
   Moran, M. Susan
   Huete, Alfredo
   Zhang, Yongguang
   Bresloff, Cynthia
   Huxman, Travis E.
   Eamus, Derek
   Bosch, David D.
   Buda, Anthony R.
   Gunter, Stacey A.
   Scalley, Tamara Heartsill
   Kitchen, Stanley G.
   McClaran, Mitchel P.
   McNab, W. Henry
   Montoya, Diane S.
   Morgan, Jack A.
   Peters, Debra P. C.
   Sadler, E. John
   Seyfried, Mark S.
   Starks, Patrick J.
TI Ecosystem resilience despite large-scale altered hydroclimatic conditions
SO NATURE
LA English
DT Article
ID rain-use efficiency; climate-change; drought; water; evapotranspiration; bim
AB Climate change is predicted to increase both drought frequency and duration, and when coupled with substantial warming, will establish a new hydroclimatological model for many regions(1). Large-scale, warm droughts have recently occurred in North America, Africa, Europe, Amazonia and Australia, resulting in major effects on terrestrial ecosystems, carbon balance and food security(2,3). Here we compare the functional response of above-ground net primary production to contrasting hydroclimatic periods in the late twentieth century (1975-1998), and drier, warmer conditions in the early twenty-first century (2000-2009) in the Northern and Southern Hemispheres. We find a common ecosystem water-use efficiency (WUEe: above-ground net primary production/evapotranspiration) across biomes ranging from grassland to forest that indicates an intrinsic system sensitivity to water availability across rainfall regimes, regardless of hydroclimatic conditions. We found higher WUEe in drier years that increased significantly with drought to a maximum WUEe across all biomes; and a minimum native state in wetter years that was common across hydroclimatic periods. This indicates biome-scale resilience to the interannual variability associated with the early twenty-first century drought-that is, the capacity to tolerate low, annual precipitation and to respond to subsequent periods of favourable water balance. These findings provide a conceptual model of ecosystem properties at the decadal scale applicable to the widespread altered hydroclimatic conditions that are predicted for later this century. Understanding the hydroclimatic threshold that will break down ecosystem resilience and alter maximum WUEe may allow us to predict land-surface consequences as large regions become more arid, starting with water-limited, low-productivity grasslands.
C1 [Campos, Guillermo E. Ponce; Moran, M. Susan; Zhang, Yongguang] ARS SW Watershed Res, USDA, Tucson, AZ 85719 USA.
   [Campos, Guillermo E. Ponce; Bresloff, Cynthia] Univ Arizona, Tucson, AZ 85721 USA.
   [Huete, Alfredo; Eamus, Derek] Univ Technol Sydney, Sydney, NSW 2007, Australia.
   [Huxman, Travis E.] Univ Calif Irvine, Irvine, CA USA.
   [Huxman, Travis E.] Univ Calif Irvine, Ctr Environm Biol, Irvine, CA 92697 USA.
   [Bosch, David D.] ARS, USDA, SE Watershed Res Lab, Tifton, GA 31793 USA.
   [Buda, Anthony R.] ARS, USDA, Pasture Syst & Watershed Management Res Unit, University Pk, PA 16802 USA.
   [Gunter, Stacey A.] ARS, USDA, So Plains Range Res Stn, Woodward, OK 73801 USA.
   [Scalley, Tamara Heartsill] USDA FS Int Inst Trop Forestry, Rio Piedras, PR 00926 USA.
   [Kitchen, Stanley G.] USDA, FS Rocky Mt Res Stn, Shrub Sci Lab, Provo, UT 84606 USA.
   [McClaran, Mitchel P.] Univ Arizona, Sch Nat Resources & Environm, Tucson, AZ 85721 USA.
   [McNab, W. Henry] USDA FS So Res Stn, Asheville, NC 28806 USA.
   [Montoya, Diane S.] USDA FS Pacific SW Res Stn, Arcata, CA 95521 USA.
   [Morgan, Jack A.] ARS, USDA, Rangeland Resources Res Unit, Ft Collins, CO 80526 USA.
   [Peters, Debra P. C.] New Mexico State Univ, USDA ARS Jornada Expt Range & Jornada Basin Long, Las Cruces, NM 88012 USA.
   [Sadler, E. John] ARS, USDA, Cropping Syst & Water Qual Res Unit, Columbia, MO 65211 USA.
   [Seyfried, Mark S.] ARS, USDA, NW Watershed Res Ctr, Boise, ID 83712 USA.
   [Starks, Patrick J.] ARS, USDA, Grazinglands Res Lab, El Reno, OK 73036 USA.
C3 United States Department of Agriculture (USDA); University of Arizona; University of Technology Sydney; University of California System; University of California Irvine; University of California System; University of California Irvine; United States Department of Agriculture (USDA); United States Department of Agriculture (USDA); United States Department of Agriculture (USDA); United States Department of Agriculture (USDA); United States Department of Agriculture (USDA); University of Arizona; United States Department of Agriculture (USDA); United States Forest Service; United States Department of Agriculture (USDA); New Mexico State University; United States Department of Agriculture (USDA); University of Missouri System; University of Missouri Columbia; United States Department of Agriculture (USDA); United States Department of Agriculture (USDA)
RP Campos, GEP (corresponding author), ARS SW Watershed Res, USDA, Tucson, AZ 85719 USA.
EM geponce@gmail.com; susan.moran@ars.usda.gov
FU NASA SMAP Science Definition Team [08-SMAPSDT08-0042]; Australian Research Council (ARC) [DP1115479]; Terrestrial Ecosystem Research Network (TERN) EIF: AusCover; Direct For Biological Sciences; Emerging Frontiers [1065699] Funding Source: National Science Foundation; Division Of Environmental Biology; Direct For Biological Sciences [1235828] Funding Source: National Science Foundation
NR 22
TC 504
Z9 576
U1 7
U2 751
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 21
PY 2013
VL 494
IS 7437
BP 349
EP 352
DI 10.1038/nature11836
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 095CS
UT WOS:000315312900037
PM 23334410
DA 2026-03-09
ER

PT J
AU Zhang, J
   Li, DH
   Chen, RJ
   Xiong, QH
AF Zhang, Jun
   Li, Dehui
   Chen, Renjie
   Xiong, Qihua
TI Laser cooling of a semiconductor by 40 kelvin
SO NATURE
LA English
DT Article
ID recombination; luminescence
AB Optical irradiation accompanied by spontaneous anti-Stokes emission can lead to cooling of matter, in a phenomenon known as laser cooling, or optical refrigeration, which was proposed by Pringsheim in 1929(1). In gaseous matter, an extremely low temperature can be obtained in diluted atomic gases by Doppler cooling(2), and laser cooling of ultradense gas has been demonstrated by collisional redistribution of radiation(3). In solid-state materials, laser cooling is achieved by the annihilation of phonons, which are quanta of lattice vibrations, during anti-Stokes luminescence. Since the first experimental demonstration in glasses doped with rare-earth metals(4), considerable progress has been made, particularly in ytterbium-doped glasses or crystals: recently a record was set of cooling to about 110 kelvin from the ambient temperature, surpassing the thermoelectric Peltier cooler(5,6). It would be interesting to realize laser cooling in semiconductors, in which excitonic resonances dominate(7-9), rather than in systems doped with rare-earth metals, where atomic resonances dominate. However, so far no net cooling in semiconductors has been achieved despite much experimental(10-12) and theoretical(7-9,13,14) work, mainly on group-III-V gallium arsenide quantum wells. Here we report a net cooling by about 40 kelvin in a semiconductor using group-II-VI cadmium sulphide nanoribbons, or nanobelts, starting from 290 kelvin. We use a pump laser with a wavelength of 514 nanometres, and obtain an estimated cooling efficiency of about 1.3 per cent and an estimated cooling power of 180 microwatts. At 100 kelvin, 532-nm pumping leads to a net cooling of about 15 kelvin with a cooling efficiency of about 2.0 per cent. We attribute the net laser cooling in cadmium sulphide nanobelts to strong coupling between excitons and longitudinal optical phonons (LOPs), which allows the resonant annihilation of multiple LOPs in luminescence up-conversion processes, high external quantum efficiency and negligible background absorption. Our findings suggest that, alternatively, group-II-VI semiconductors with strong exciton-LOP coupling could be harnessed to achieve laser cooling and open the way to optical refrigeration based on semiconductors.
C1 [Zhang, Jun; Li, Dehui; Chen, Renjie; Xiong, Qihua] Nanyang Technol Univ, Sch Phys & Math Sci, Div Phys & Appl Phys, Singapore 637371, Singapore.
   [Xiong, Qihua] Nanyang Technol Univ, Sch Elect & Elect Engn, Div Microelect, Singapore 639798, Singapore.
C3 Nanyang Technological University; Nanyang Technological University
RP Xiong, QH (corresponding author), Nanyang Technol Univ, Sch Phys & Math Sci, Div Phys & Appl Phys, Singapore 637371, Singapore.
EM qihua@ntu.edu.sg
FU Singapore National Research Foundation [NRF-RF2009-06]; Singapore Ministry of Education [MOE2011-T2-2-051]; Nanyang Technological University [M58113004]
NR 29
TC 282
Z9 333
U1 6
U2 469
PU NATURE PUBLISHING 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 24
PY 2013
VL 493
IS 7433
BP 504
EP 508
DI 10.1038/nature11721
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 075GF
UT WOS:000313871400032
PM 23344360
DA 2026-03-09
ER

PT J
AU Vieira-Pires, RS
   Szollosi, A
   Morais-Cabral, JH
AF Vieira-Pires, Ricardo S.
   Szollosi, Andras
   Morais-Cabral, Joao H.
TI The structure of the KtrAB potassium transporter
SO NATURE
LA English
DT Article
ID k+-uptake system; crystal-structure; glycine residues; gating ring; channel; selectivity; mechanism; adaptation; pcc-6803; complex
AB In bacteria, archaea, fungi and plants the Trk, Ktr and HKT ion transporters are key components of osmotic regulation, pH homeostasis and resistance to drought and high salinity. These ion transporters are functionally diverse: they can function as Na+ or K+ channels and possibly as cation/K+ symporters. They are closely related to potassium channels both at the level of the membrane protein and at the level of the cytosolic regulatory domains. Here we describe the crystal structure of a Ktr K+ transporter, the KtrAB complex from Bacillus subtilis. The structure shows the dimeric membrane protein KtrB assembled with a cytosolic octameric KtrA ring bound to ATP, an activating ligand. A comparison between the structure of KtrAB-ATP and the structures of the isolated full-length KtrA protein with ATP or ADP reveals a ligand-dependent conformational change in the octameric ring, raising new ideas about the mechanism of activation in these transporters.
C1 [Vieira-Pires, Ricardo S.; Szollosi, Andras; Morais-Cabral, Joao H.] Univ Porto, IBMC, P-4150180 Oporto, Portugal.
C3 Universidade do Porto
RP Morais-Cabral, JH (corresponding author), Univ Porto, IBMC, Rua Campo Alegre 823, P-4150180 Oporto, Portugal.
EM jcabral@ibmc.up.pt
FU FEBS; EMBO; FEDER funds through the Operational Competitiveness Program-COMPETE; FCT-Fundacao para a Ciencia e a Tecnologia [FCOMP-01-0124-FEDER-022718 (PEst-C/SAU/LA0002/2011), FCOMP-01-0124-FEDER-009028 (PTDC/BIA-PRO/099861/2008) FCOMP-01-0124-FEDER-010781 (PTDC/QUI-BIQ/105342/2008)]; Fundação para a Ciência e a Tecnologia [PTDC/BIA-PRO/099861/2008, PTDC/QUI-BIQ/105342/2008] Funding Source: FCT
NR 42
TC 103
Z9 124
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 APR 18
PY 2013
VL 496
IS 7445
BP 323
EP +
DI 10.1038/nature12055
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 126FV
UT WOS:000317599200029
PM 23598340
DA 2026-03-09
ER

PT J
AU Chen, SS
   Oldham, ML
   Davidson, AL
   Chen, J
AF Chen, Shanshuang
   Oldham, Michael L.
   Davidson, Amy L.
   Chen, Jue
TI Carbon catabolite repression of the maltose transporter revealed by X-ray crystallography
SO NATURE
LA English
DT Article
ID glucose phosphotransferase system; signal-transducing protein; phosphoryl transfer complex; escherichia-coli; salmonella-typhimurium; inducer exclusion; abc transporter; regulatory protein; crystal-structure; lactose permease
AB Efficient carbon utilization is critical to the survival of microorganisms in competitive environments. To optimize energy usage, bacteria have developed an integrated control system to preferentially uptake carbohydrates that support rapid growth. The availability of a preferred carbon source, such as glucose, represses the synthesis and activities of proteins necessary for the transport and metabolism of secondary carbon sources. This regulatory phenomenon is defined as carbon catabolite repression(1). In enteric bacteria, the key player of carbon catabolite repression is a component of the glucose-specific phosphotransferase system, enzyme IIA (EIIA(Glc))(1,2). It is known that unphosphorylated EIIA(Glc) binds to and inhibits a variety of transporters when glucose is available(1,2). However, understanding the underlying molecular mechanism has been hindered by the complete absence of structures for any EIIA(Glc)-transporter complexes. Here we present the 3.9 angstrom crystal structure of Escherichia coli EIIA(Glc) in complex with the maltose transporter, an ATP-binding cassette (ABC) transporter. The structure shows that two EIIA(Glc) molecules bind to the cytoplasmic ATPase subunits, stabilizing the transporter in an inward-facing conformation and preventing the structural rearrangements necessary for ATP hydrolysis. We also show that the half-maximal inhibitory concentrations of the full-length EIIA(Glc) and an amino-terminal truncation mutant differ by 60-fold, consistent with the hypothesis that the amino-terminal region, disordered in the crystal structure, functions as a membrane anchor to increase the effective EIIA(Glc) concentration at the membrane(3,4). Together these data suggest a model of how the central regulatory protein EIIAGlc allosterically inhibits maltose uptake in E. coli.
C1 [Chen, Shanshuang; Chen, Jue] Purdue Univ, Dept Biol Sci, W Lafayette, IN 47907 USA.
   [Oldham, Michael L.; Chen, Jue] Howard Hughes Med Inst, W Lafayette, IN 47907 USA.
   [Davidson, Amy L.] Purdue Univ, Dept Chem, W Lafayette, IN 47907 USA.
C3 Purdue University System; Purdue University; Howard Hughes Medical Institute; Purdue University System; Purdue University
RP Chen, J (corresponding author), Purdue Univ, Dept Biol Sci, W Lafayette, IN 47907 USA.
EM chenjue@purdue.edu
FU National Institutes of Health [GM070515]
NR 41
TC 81
Z9 102
U1 2
U2 62
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 18
PY 2013
VL 499
IS 7458
BP 364
EP U147
DI 10.1038/nature12232
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 184RJ
UT WOS:000321910700042
PM 23770568
DA 2026-03-09
ER

PT J
AU Dewan, A
   Pacifico, R
   Zhan, R
   Rinberg, D
   Bozza, T
AF Dewan, Adam
   Pacifico, Rodrigo
   Zhan, Ross
   Rinberg, Dmitry
   Bozza, Thomas
TI Non-redundant coding of aversive odours in the main olfactory pathway
SO NATURE
LA English
DT Article
ID amine-associated receptors; chemosensory receptors; mouse; subsystem; evolution; odorants; neurons; mice; bulb
AB Many species are critically dependent on olfaction for survival. In the main olfactory system of mammals, odours are detected by sensory neurons that express a large repertoire of canonical odorant receptors and a much smaller repertoire of trace amine-associated receptors (TAARs)(1-4). Odours are encoded in a combinatorial fashion across glomeruli in the main olfactory bulb, with each glomerulus corresponding to a specific receptor(5-7). The degree to which individual receptor genes contribute to odour perception is unclear. Here we show that genetic deletion of the olfactory Taar gene family, or even a single Taar gene (Taar4), eliminates the aversion that mice display to low concentrations of volatile amines and to the odour of predator urine. Our findings identify a role for the TAARs in olfaction, namely, in the high-sensitivity detection of innately aversive odours. In addition, our data reveal that aversive amines are represented in a non-redundant fashion, and that individual main olfactory receptor genes can contribute substantially to odour perception.
C1 [Dewan, Adam; Pacifico, Rodrigo; Zhan, Ross; Bozza, Thomas] Northwestern Univ, Dept Neurobiol, Evanston, IL 60208 USA.
   [Rinberg, Dmitry] HHMI, Ashburn, VA USA.
C3 Northwestern University; Howard Hughes Medical Institute
RP Bozza, T (corresponding author), Northwestern Univ, Dept Neurobiol, Evanston, IL 60208 USA.
EM bozza@northwestern.edu
FU NIH/NIDCD [R01DC009640, F32DC012004]; Whitehall Foundation; Brain Research Foundation
NR 27
TC 148
Z9 201
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 MAY 23
PY 2013
VL 497
IS 7450
BP 486
EP +
DI 10.1038/nature12114
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 148OG
UT WOS:000319254000047
PM 23624375
DA 2026-03-09
ER

PT J
AU Sharma, S
   Quintana, A
   Findlay, GM
   Mettlen, M
   Baust, B
   Jain, M
   Nilsson, R
   Rao, A
   Hogan, PG
AF Sharma, Sonia
   Quintana, Ariel
   Findlay, Gregory M.
   Mettlen, Marcel
   Baust, Beate
   Jain, Mohit
   Nilsson, Roland
   Rao, Anjana
   Hogan, Patrick G.
TI An siRNA screen for NFAT activation identifies septins as coordinators of store-operated Ca2+ entry
SO NATURE
LA English
DT Article
ID channel activation; orai1; stim1; calcium; cytoskeleton; release; crac; forchlorfenuron; organization; domains
AB The STIM1-ORAI1 pathway of store-operated Ca2+ entry is an essential component of cellular Ca2+ signalling(1). STIM1 senses depletion of intracellular Ca2+ stores in response to physiological stimuli, and relocalizes within the endoplasmic reticulum to plasma-membrane-apposed junctions, where it recruits and gates open plasma membrane ORAI1 Ca2+ channels. Here we use a genome-wide RNA interference screen in HeLa cells to identify filamentous septin proteins as crucial regulators of store-operated Ca2+ entry. Septin filaments and phosphatidylinositol-4,5-bisphosphate (also known as PtdIns(4,5)P-2) rearrange locally at endoplasmic reticulum-plasma membrane junctions before and during formation of STIM1-ORAI1 clusters, facilitating STIM1 targeting to these junctions and promoting the stable recruitment of ORAI1. Septin rearrangement at junctions is required for PtdIns(4,5) P2 reorganization and efficient STIM1-ORAI1 communication. Septins are known to demarcate specialized membrane regions such as dendritic spines, the yeast bud and the primary cilium, and to serve as membrane diffusion barriers and/or signalling hubs in cellular processes such as vesicle trafficking, cell polarity and cytokinesis2-4. Our data show that septins also organize the highly localized plasma membrane domains that are important in STIM1-ORAI1 signalling, and indicate that septins may organize membrane microdomains relevant to other signalling processes.
C1 [Sharma, Sonia; Quintana, Ariel; Rao, Anjana; Hogan, Patrick G.] La Jolla Inst Allergy & Immunol, La Jolla, CA 92037 USA.
   [Sharma, Sonia; Quintana, Ariel; Findlay, Gregory M.; Baust, Beate; Rao, Anjana; Hogan, Patrick G.] Harvard Univ, Sch Med, Childrens Hosp Boston, Program Cellular & Mol Med, Boston, MA 02115 USA.
   [Mettlen, Marcel] Scripps Res Inst, La Jolla, CA 92037 USA.
   [Jain, Mohit] Broad Inst, Cambridge, MA 02142 USA.
   [Jain, Mohit] Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA.
   [Nilsson, Roland] Karolinska Inst, S-17176 Stockholm, Sweden.
C3 La Jolla Institute for Immunology; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Program in Cellular & Molecular Medicine (PCMM); Harvard Medical School; Scripps Research Institute; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Karolinska Institutet
RP Rao, A (corresponding author), La Jolla Inst Allergy & Immunol, La Jolla, CA 92037 USA.
EM arao@liai.org; phogan@liai.org
FU National Institutes of Health (NIH) [AI040127, AI084167]; NIH [AI092763, K08 HL107451, R01GM73165]; Canadian Institutes for Health Research; Leukemia & Lymphoma Society; Deutsche Forschungsgemeinschaft [QU298/1-1]; Knut & Alice Wallenberg Foundation; National Institute of Allergy and Infectious Diseases [R01AI040127] Funding Source: NIH RePORTER; National Institute of General Medical Sciences [R01GM073165] Funding Source: NIH RePORTER
NR 30
TC 195
Z9 211
U1 0
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 JUL 11
PY 2013
VL 499
IS 7457
BP 238
EP +
DI 10.1038/nature12229
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 179YA
UT WOS:000321557600068
PM 23792561
DA 2026-03-09
ER

PT J
AU Hochreiter-Hufford, AE
   Lee, CS
   Kinchen, JM
   Sokolowski, JD
   Arandjelovic, S
   Call, JA
   Klibanov, AL
   Yan, Z
   Mandell, JW
   Ravichandran, KS
AF Hochreiter-Hufford, Amelia E.
   Lee, Chang Sup
   Kinchen, Jason M.
   Sokolowski, Jennifer D.
   Arandjelovic, Sanja
   Call, Jarrod A.
   Klibanov, Alexander L.
   Yan, Zhen
   Mandell, James W.
   Ravichandran, Kodi S.
TI Phosphatidylserine receptor BAI1 and apoptotic cells as new promoters of myoblast fusion
SO NATURE
LA English
DT Article
ID duchenne muscular-dystrophy; skeletal-muscle; engulfment receptor; in-vivo; find-me; expression; drosophila; mouse; protein; gene
AB Skeletal muscle arises from the fusion of precursor myoblasts into multinucleated myofibres(1,2). Although conserved transcription factors and signalling proteins involved in myogenesis have been identified, upstream regulators are less well understood. Here we report an unexpected discovery that the membrane protein BAI1, previously linked to recognition of apoptotic cells by phagocytes(3), promotes myoblast fusion. Endogenous BAI1 expression increased during myoblast fusion, and BAI1 overexpression enhanced myoblast fusion by means of signalling through ELMO/Dock180/Rac1 proteins(4). During myoblast fusion, a fraction of myoblasts within the population underwent apoptosis and exposed phosphatidylserine, an established ligand for BAI1 (ref. 3). Blocking apoptosis potently impaired myoblast fusion, and adding back apoptotic myoblasts restored fusion. Furthermore, primary human myoblasts could be induced to form myotubes by adding apoptotic myoblasts, even under normal growth conditions. Mechanistically, apoptotic cells did not directly fuse with the healthy myoblasts, rather the apoptotic cells induced a contact-dependent signalling with neighbours to promote fusion among the healthy myoblasts. In vivo, myofibres from Bai1(-/-) mice are smaller than those from wild-type littermates. Muscle regeneration after injury was also impaired in Bai1(-/-) mice, highlighting a role for BAI1 in mammalian myogenesis. Collectively, these data identify apoptotic cells as a new type of cue that induces signalling via the phosphatidylserine receptor BAI1 to promote fusion of healthy myoblasts, with important implications for muscle development and repair.
C1 [Hochreiter-Hufford, Amelia E.; Lee, Chang Sup; Kinchen, Jason M.; Arandjelovic, Sanja; Ravichandran, Kodi S.] Univ Virginia, Dept Microbiol Immunol & Canc Biol, Charlottesville, VA 22908 USA.
   [Hochreiter-Hufford, Amelia E.; Lee, Chang Sup; Kinchen, Jason M.; Arandjelovic, Sanja; Ravichandran, Kodi S.] Univ Virginia, Beirne B Carter Immunol Ctr, Charlottesville, VA 22908 USA.
   [Hochreiter-Hufford, Amelia E.; Lee, Chang Sup; Kinchen, Jason M.; Sokolowski, Jennifer D.; Arandjelovic, Sanja; Mandell, James W.; Ravichandran, Kodi S.] Univ Virginia, Ctr Cell Clearance, Charlottesville, VA 22908 USA.
   [Sokolowski, Jennifer D.; Mandell, James W.] Univ Virginia, Dept Pathol, Charlottesville, VA 22908 USA.
   [Call, Jarrod A.; Klibanov, Alexander L.; Yan, Zhen] Univ Virginia, Robert M Berne Cardiovasc Res Ctr, Charlottesville, VA 22908 USA.
   [Call, Jarrod A.; Klibanov, Alexander L.; Yan, Zhen] Univ Virginia, Dept Med, Charlottesville, VA 22908 USA.
C3 University of Virginia; University of Virginia; University of Virginia; University of Virginia; University of Virginia; University of Virginia
RP Ravichandran, KS (corresponding author), Univ Virginia, Dept Microbiol Immunol & Canc Biol, Charlottesville, VA 22908 USA.
EM Ravi@virginia.edu
FU National Institute of General Medical Sciences/National Institutes of Health; Center for Cell Clearance at the University of Virginia; National Cancer Institute [P30CA044579] Funding Source: NIH RePORTER; National Institute of Allergy and Infectious Diseases [T32AI007496] Funding Source: NIH RePORTER; National Institute of Arthritis and Musculoskeletal and Skin Diseases [T32AR007612] Funding Source: NIH RePORTER; National Institute of General Medical Sciences [T32GM007267] Funding Source: NIH RePORTER
NR 31
TC 250
Z9 296
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 MAY 9
PY 2013
VL 497
IS 7448
BP 263
EP +
DI 10.1038/nature12135
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 139CD
UT WOS:000318558200041
PM 23615608
DA 2026-03-09
ER

PT J
AU Chen, JL
   Carta, S
   Soldado-Magraner, J
   Schneider, BL
   Helmchen, F
AF Chen, Jerry L.
   Carta, Stefano
   Soldado-Magraner, Joana
   Schneider, Bernard L.
   Helmchen, Fritjof
TI Behaviour-dependent recruitment of long-range projection neurons in somatosensory cortex
SO NATURE
LA English
DT Article
ID primary motor cortex; barrel cortex; tactile discrimination; object localization; sensorimotor system; neural activity; rat primary; whisker; mice; awake
AB In the mammalian neocortex, segregated processing streams are thought to be important for forming sensory representations of the environment(1,2), but how local information in primary sensory cortex is transmitted to other distant cortical areas during behaviour is unclear. Here we show task-dependent activation of distinct, largely non-overlapping long-range projection neurons in the whisker region of primary somatosensory cortex (S1) in awake, behaving mice. Using two-photon calcium imaging, we monitored neuronal activity in anatomically identified S1 neurons projecting to secondary somatosensory (S2) or primary motor (M1) cortex in mice using their whiskers to perform a texture-discrimination task or a task that required them to detect the presence of an object at a certain location. Whisking-related cells were found among S2-projecting (S2P) but not M1-projecting (M1P) neurons. A higher fraction of S2P than M1P neurons showed touch-related responses during texture discrimination, whereas a higher fraction of M1P than S2P neurons showed touch-related responses during the detection task. In both tasks, S2P and M1P neurons could discriminate similarly between trials producing different behavioural decisions. However, in trials producing the same decision, S2P neurons performed better at discriminating texture, whereas M1P neurons were better at discriminating location. Sensory stimulus features alone were not sufficient to elicit these differences, suggesting that selective transmission of S1 information to S2 and M1 is driven by behaviour.
C1 [Chen, Jerry L.; Carta, Stefano; Soldado-Magraner, Joana; Helmchen, Fritjof] Univ Zurich, Brain Res Inst, CH-8057 Zurich, Switzerland.
   [Carta, Stefano; Helmchen, Fritjof] Univ Zurich, ETH Zurich, Neurosci Ctr Zurich, CH-8057 Zurich, Switzerland.
   [Soldado-Magraner, Joana] Univ Zurich, ETH Zurich, Inst Neuroinformat, CH-8057 Zurich, Switzerland.
   [Schneider, Bernard L.] Ecole Polytech Fed Lausanne, Brain Mind Inst, EPFL SV BMI LEN, CH-1015 Lausanne, Switzerland.
C3 University of Zurich; Swiss Federal Institutes of Technology Domain; ETH Zurich; University of Zurich; Swiss Federal Institutes of Technology Domain; ETH Zurich; University of Zurich; Swiss Federal Institutes of Technology Domain; Ecole Polytechnique Federale de Lausanne
RP Helmchen, F (corresponding author), Univ Zurich, Brain Res Inst, Winterthurerstr 190, CH-8057 Zurich, Switzerland.
EM helmchen@hifo.uzh.ch
FU Swiss National Science Foundation [310030-127091]; EU [223524, 243914]; Swiss SystemsX.ch initiative; National Center of Competence in Research 'Neural Plasticity and Repair'; Forschungskredit of the University of Zurich [541541808]; US National Science Foundation [1158914]; Office Of The Director; Office Of Internatl Science &Engineering [1158914] Funding Source: National Science Foundation; Swiss National Science Foundation (SNF) [310030_127091] Funding Source: Swiss National Science Foundation (SNF)
NR 39
TC 239
Z9 276
U1 2
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 JUL 18
PY 2013
VL 499
IS 7458
BP 336
EP +
DI 10.1038/nature12236
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 184RJ
UT WOS:000321910700036
PM 23792559
DA 2026-03-09
ER

PT J
AU Riechers, DA
   Bradford, CM
   Clements, DL
   Dowell, CD
   Pérez-Fournon, I
   Ivison, RJ
   Bridge, C
   Conley, A
   Fu, H
   Vieira, JD
   Wardlow, J
   Calanog, J
   Cooray, A
   Hurley, P
   Neri, R
   Kamenetzky, J
   Aguirre, JE
   Altieri, B
   Arumugam, V
   Benford, DJ
   Béthermin, M
   Bock, J
   Burgarella, D
   Cabrera-Lavers, A
   Chapman, SC
   Cox, P
   Dunlop, JS
   Earle, L
   Farrah, D
   Ferrero, P
   Franceschini, A
   Gavazzi, R
   Glenn, J
   Solares, EAG
   Gurwell, MA
   Halpern, M
   Hatziminaoglou, E
   Hyde, A
   Ibar, E
   Kovács, A
   Krips, M
   Lupu, RE
   Maloney, PR
   Martinez-Navajas, P
   Matsuhara, H
   Murphy, EJ
   Naylor, BJ
   Nguyen, HT
   Oliver, SJ
   Omont, A
   Page, MJ
   Petitpas, G
   Rangwala, N
   Roseboom, IG
   Scott, D
   Smith, AJ
   Staguhn, JG
   Streblyanska, A
   Thomson, AP
   Valtchanov, I
   Viero, M
   Wang, L
   Zemcov, M
   Zmuidzinas, J
AF Riechers, Dominik A.
   Bradford, C. M.
   Clements, D. L.
   Dowell, C. D.
   Perez-Fournon, I.
   Ivison, R. J.
   Bridge, C.
   Conley, A.
   Fu, Hai
   Vieira, J. D.
   Wardlow, J.
   Calanog, J.
   Cooray, A.
   Hurley, P.
   Neri, R.
   Kamenetzky, J.
   Aguirre, J. E.
   Altieri, B.
   Arumugam, V.
   Benford, D. J.
   Bethermin, M.
   Bock, J.
   Burgarella, D.
   Cabrera-Lavers, A.
   Chapman, S. C.
   Cox, P.
   Dunlop, J. S.
   Earle, L.
   Farrah, D.
   Ferrero, P.
   Franceschini, A.
   Gavazzi, R.
   Glenn, J.
   Solares, E. A. Gonzalez
   Gurwell, M. A.
   Halpern, M.
   Hatziminaoglou, E.
   Hyde, A.
   Ibar, E.
   Kovacs, A.
   Krips, M.
   Lupu, R. E.
   Maloney, P. R.
   Martinez-Navajas, P.
   Matsuhara, H.
   Murphy, E. J.
   Naylor, B. J.
   Nguyen, H. T.
   Oliver, S. J.
   Omont, A.
   Page, M. J.
   Petitpas, G.
   Rangwala, N.
   Roseboom, I. G.
   Scott, D.
   Smith, A. J.
   Staguhn, J. G.
   Streblyanska, A.
   Thomson, A. P.
   Valtchanov, I.
   Viero, M.
   Wang, L.
   Zemcov, M.
   Zmuidzinas, J.
TI A dust-obscured massive maximum-starburst galaxy at a redshift of 6.34
SO NATURE
LA English
DT Article
ID star-forming galaxy; molecular gas; submillimeter galaxy; host galaxy; quasars; disks
AB Massive present-day early-type (elliptical and lenticular) galaxies probably gained the bulk of their stellar mass and heavy elements through intense, dust-enshrouded starbursts-that is, increased rates of star formation-in the most massive dark-matter haloes at early epochs. However, it remains unknown how soon after the Big Bang massive starburst progenitors exist. The measured redshift (z) distribution of dusty, massive starbursts has long been suspected to be biased low in z owing to selection effects(1), as confirmed by recent findings of systems with redshifts as high as similar to 5 (refs 2-4). Here we report the identification of a massive starburst galaxy at z = 6.34 through a submillimetre colour-selection technique. We unambiguously determined the redshift from a suite of molecular and atomic fine-structure cooling lines. These measurements reveal a hundred billion solar masses of highly excited, chemically evolved interstellar medium in this galaxy, which constitutes at least 40 per cent of the baryonic mass. A 'maximum starburst' converts the gas into stars at a rate more than 2,000 times that of the Milky Way, a rate among the highest observed at any epoch. Despite the overall downturn in cosmic star formation towards the highest redshifts(5), it seems that environments mature enough to form the most massive, intense starbursts existed at least as early as 880 million years after the Big Bang.
C1 [Riechers, Dominik A.; Bradford, C. M.; Dowell, C. D.; Bridge, C.; Vieira, J. D.; Cooray, A.; Bock, J.; Kovacs, A.; Murphy, E. J.; Nguyen, H. T.; Viero, M.; Zemcov, M.; Zmuidzinas, J.] CALTECH, 1200 East Calif Blvd,MC 249-17, Pasadena, CA 91125 USA.
   [Riechers, Dominik A.] Cornell Univ, Ithaca, NY 14853 USA.
   [Bradford, C. M.; Dowell, C. D.; Bock, J.; Naylor, B. J.; Nguyen, H. T.; Zemcov, M.; Zmuidzinas, J.] CALTECH, Jet Prop Lab, Pasadena, CA 91109 USA.
   [Clements, D. L.; Hyde, A.] Univ London Imperial Coll Sci Technol & Med, Blackett Lab, Astrophys Grp, London SW7 2AZ, England.
   [Perez-Fournon, I.; Cabrera-Lavers, A.; Ferrero, P.; Martinez-Navajas, P.; Streblyanska, A.] Inst Astrofis Canarias, E-38200 Tenerife, Spain.
   [Perez-Fournon, I.; Cabrera-Lavers, A.; Ferrero, P.; Martinez-Navajas, P.; Streblyanska, A.] Univ La Laguna, Dept Astrofis, E-38205 Tenerife, Spain.
   [Ivison, R. J.; Ibar, E.] Royal Observ, UK Astron Technol Ctr, Edinburgh EH9 3HJ, Midlothian, Scotland.
   [Ivison, R. J.; Arumugam, V.; Dunlop, J. S.; Roseboom, I. G.; Thomson, A. P.] Univ Edinburgh, Royal Observ, Inst Astron, Edinburgh EH9 3HJ, Midlothian, Scotland.
   [Conley, A.; Earle, L.; Glenn, J.; Maloney, P. R.] Univ Colorado, Ctr Astrophys & Space Astron UCB 389, Boulder, CO 80309 USA.
   [Fu, Hai; Wardlow, J.; Calanog, J.; Cooray, A.] Univ Calif Irvine, Dept Phys & Astron, Irvine, CA 92697 USA.
   [Hurley, P.; Oliver, S. J.; Roseboom, I. G.; Smith, A. J.; Wang, L.] Univ Sussex, Dept Phys & Astron, Ctr Astron, Brighton BN1 9QH, E Sussex, England.
   [Neri, R.; Cox, P.; Krips, M.] Inst Radio Astron Millimetr, F-38406 St Martin Dheres, France.
   [Kamenetzky, J.; Glenn, J.; Rangwala, N.] Univ Colorado, Dept Astrophys & Planetary Sci, CASA UCB 389, Boulder, CO 80309 USA.
   [Aguirre, J. E.; Lupu, R. E.] Univ Penn, Dept Phys & Astron, Philadelphia, PA 19104 USA.
   [Altieri, B.; Valtchanov, I.] European Space Astron Ctr, Herschel Sci Ctr, Madrid 28691, Spain.
   [Benford, D. J.; Staguhn, J. G.] NASA, Observat Cosmol Lab, Goddard Space Flight Ctr, Greenbelt, MD 20771 USA.
   [Bethermin, M.] Univ Paris Diderot, CEA Saclay, Lab AIM Paris Saclay, CEA,DSM,Irfu,CNRS, F-91191 Gif Sur Yvette, France.
   [Bethermin, M.] Univ Paris Sud, Univ Pris 11, Inst Astrophys Spatiale IAS, F-91405 Orsay, France.
   [Bethermin, M.] CNRS, UMR 8617, F-91405 Orsay, France.
   [Burgarella, D.] Aix Marseille Univ, CNRS, Lab Astrophys Marseille, UMR7326, F-13388 Marseille, France.
   [Cabrera-Lavers, A.] Grantecan SA, Ctr Astrofis La Palma, E-38712 Brena Baja, La Palma, Spain.
   [Chapman, S. C.; Solares, E. A. Gonzalez] Univ Cambridge, Inst Astron, Cambridge CB3 0HA, England.
   [Farrah, D.] Virginia Tech, Dept Phys, Blacksburg, VA 24061 USA.
   [Franceschini, A.] Univ Padua, Dipartimento Fis & Astron, I-35122 Padua, Italy.
   [Gavazzi, R.; Omont, A.] Univ Paris 06, CNRS, Inst Astrophys Paris, UMR 7095, F-75014 Paris, France.
   [Gurwell, M. A.; Petitpas, G.] Harvard Smithsonian Ctr Astrophys, Cambridge, MA 02138 USA.
   [Halpern, M.; Scott, D.] Univ British Columbia, Dept Phys & Astron, Vancouver, BC V6T 1Z1, Canada.
   [Hatziminaoglou, E.] ESO, D-85748 Garching, Germany.
   [Kovacs, A.] Univ Minnesota, Inst Astrophys, Minneapolis, MN 55455 USA.
   [Matsuhara, H.] Japan Aerosp & Explorat Agcy, Inst Space & Astronaut Sci, Sagamihara, Kanagawa 2298510, Japan.
   [Murphy, E. J.] CALTECH, Infrared Proc & Anal Ctr, Pasadena, CA 91125 USA.
   [Page, M. J.] Univ Coll London, Mullard Space Sci Lab, Dorking RH5 6NT, Surrey, England.
   [Staguhn, J. G.] Johns Hopkins Univ, Dept Phys & Astron, Baltimore, MD 21218 USA.
C3 California Institute of Technology; Cornell University; National Aeronautics & Space Administration (NASA); NASA Jet Propulsion Laboratory (JPL); California Institute of Technology; Imperial College London; Instituto de Astrofisica de Canarias; Universidad de la Laguna; University of Edinburgh; University of Edinburgh; University of Colorado System; University of Colorado Boulder; University of California System; University of California Irvine; University of Sussex; University of Colorado System; University of Colorado Boulder; University of Pennsylvania; European Space Agency; European Space Astronomy Center; National Aeronautics & Space Administration (NASA); NASA Goddard Space Flight Center; Universite Paris Saclay; CEA; Centre National de la Recherche Scientifique (CNRS); Universite Paris Cite; Sorbonne Universite; Universite Paris Saclay; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Earth Sciences & Astronomy (INSU); Universite Paris Saclay; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Earth Sciences & Astronomy (INSU); Aix-Marseille Universite; University of Cambridge; Virginia Polytechnic Institute & State University; University of Padua; Sorbonne Universite; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Earth Sciences & Astronomy (INSU); Harvard University; Smithsonian Astrophysical Observatory; Smithsonian Institution; University of British Columbia; University of Minnesota System; University of Minnesota Twin Cities; Japan Aerospace Exploration Agency (JAXA); Institute of Space & Astronautical Science (ISAS); California Institute of Technology; University of London; University College London; Johns Hopkins University
RP Riechers, DA (corresponding author), CALTECH, 1200 East Calif Blvd,MC 249-17, Pasadena, CA 91125 USA.
EM dr@astro.cornell.edu
FU STFC [ST/I000976/1, ST/J001422/1, ST/L001314/1, ST/F007027/1, ST/F006977/1, ST/I005765/1, ST/J000647/1, ST/K000977/1] Funding Source: UKRI; Science and Technology Facilities Council [ST/K000977/1, ST/L001314/1, ST/F006977/1, ST/H00243X/1, ST/J001422/1, ST/J000647/1, ST/I000976/1, ST/F007027/1, ST/I005765/1] Funding Source: researchfish; UK Space Agency [ST/J004812/1, ST/G003874/1] Funding Source: researchfish; Direct For Mathematical & Physical Scien; Division Of Astronomical Sciences [1140063] Funding Source: National Science Foundation; Division Of Astronomical Sciences; Direct For Mathematical & Physical Scien [1106284] Funding Source: National Science Foundation; Grants-in-Aid for Scientific Research [20001003, 23244040] Funding Source: KAKEN
NR 30
TC 487
Z9 518
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 APR 18
PY 2013
VL 496
IS 7445
BP 329
EP 333
DI 10.1038/nature12050
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 126FV
UT WOS:000317599200030
PM 23598341
DA 2026-03-09
ER

PT J
AU Liu, JF
   Bregman, JN
   Bai, Y
   Justham, S
   Crowther, P
AF Liu, Ji-Feng
   Bregman, Joel N.
   Bai, Yu
   Justham, Stephen
   Crowther, Paul
TI Puzzling accretion onto a black hole in the ultraluminous X-ray source M 101 ULX-1
SO NATURE
LA English
DT Article
ID mass; m101; metallicity; constraints; abundance; emission; binary; systems; chandra; stars
AB There are two proposed explanations for ultraluminous X-ray sources(1,2) (ULXs) with luminosities in excess of 10(39) erg s(-1). They could be intermediate-mass black holes (more than 100-1,000 solar masses, M-circle dot) radiating at sub-maximal (sub-Eddington) rates, as in Galactic black-hole X-ray binaries but with larger, cooler accretion disks(3-5). Alternatively, they could be stellar-mass black holes radiating at Eddington or super-Eddington rates(2,6). On its discovery, M 101 ULX-1(4,7) had a luminosity of 3 x 10(39) erg s(-1) and a supersoft thermal disk spectrum with an exceptionally low temperature-uncomplicated by photons energized by a corona of hot electrons-more consistent with the expected appearance of an accreting intermediate-mass black hole(3,4). Here we report optical spectroscopic monitoring of M 101 ULX-1. We confirm the previous suggestion(8) that the system contains a Wolf-Rayet star, and reveal that the orbital period is 8.2 days. The black hole has a minimum mass of 5 M-circle dot, and more probably a mass of 20 M-circle dot-30 M-circle dot, but we argue that it is very unlikely to be an intermediate-mass black hole. Therefore, its exceptionally soft spectra at high Eddington ratios violate the expectations for accretion onto stellar-mass black holes(9-11). Accretion must occur from captured stellar wind, which has hitherto been thought to be so inefficient that it could not power an ultraluminous source(12,13).
C1 [Liu, Ji-Feng; Bai, Yu; Justham, Stephen] Chinese Acad Sci, Natl Astron Observ, Key Lab Opt Astron, Beijing 100012, Peoples R China.
   [Bregman, Joel N.] Univ Michigan, Dept Astron, Ann Arbor, MI 48105 USA.
   [Crowther, Paul] Univ Sheffield, Dept Phys & Astron, Sheffield S3 7RH, S Yorkshire, England.
C3 Chinese Academy of Sciences; National Astronomical Observatory, CAS; University of Michigan System; University of Michigan; University of Sheffield
RP Liu, JF (corresponding author), Chinese Acad Sci, Natl Astron Observ, Key Lab Opt Astron, 20A Datun Rd, Beijing 100012, Peoples R China.
EM jfliu@nao.cas.cn
FU NASA [PF6-70043]; Chinese Academy of Sciences [KJCX2-EW-T01]; National Science Foundation of China [NSFC-11273028, NSFC-11333004]; Science and Technology Facilities Council [ST/J001589/1] Funding Source: researchfish; STFC [ST/J001589/1] Funding Source: UKRI
NR 48
TC 148
Z9 159
U1 0
U2 33
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 28
PY 2013
VL 503
IS 7477
BP 500
EP +
DI 10.1038/nature12762
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 258MU
UT WOS:000327464200037
PM 24284727
DA 2026-03-09
ER

PT J
AU Fu, H
   Cooray, A
   Feruglio, C
   Ivison, RJ
   Riechers, DA
   Gurwell, M
   Bussmann, RS
   Harris, AI
   Altieri, B
   Aussel, H
   Baker, AJ
   Bock, J
   Boylan-Kolchin, M
   Bridge, C
   Calanog, JA
   Casey, CM
   Cava, A
   Chapman, SC
   Clements, DL
   Conley, A
   Cox, P
   Farrah, D
   Frayer, D
   Hopwood, R
   Jia, J
   Magdis, G
   Marsden, G
   Martínez-Navajas, P
   Negrello, M
   Neri, R
   Oliver, SJ
   Omont, A
   Page, MJ
   Pérez-Fournon, I
   Schulz, B
   Scott, D
   Smith, A
   Vaccari, M
   Valtchanov, I
   Vieira, JD
   Viero, M
   Wang, L
   Wardlow, JL
   Zemcov, M
AF Fu, Hai
   Cooray, Asantha
   Feruglio, C.
   Ivison, R. J.
   Riechers, D. A.
   Gurwell, M.
   Bussmann, R. S.
   Harris, A. I.
   Altieri, B.
   Aussel, H.
   Baker, A. J.
   Bock, J.
   Boylan-Kolchin, M.
   Bridge, C.
   Calanog, J. A.
   Casey, C. M.
   Cava, A.
   Chapman, S. C.
   Clements, D. L.
   Conley, A.
   Cox, P.
   Farrah, D.
   Frayer, D.
   Hopwood, R.
   Jia, J.
   Magdis, G.
   Marsden, G.
   Martinez-Navajas, P.
   Negrello, M.
   Neri, R.
   Oliver, S. J.
   Omont, A.
   Page, M. J.
   Perez-Fournon, I.
   Schulz, B.
   Scott, D.
   Smith, A.
   Vaccari, M.
   Valtchanov, I.
   Vieira, J. D.
   Viero, M.
   Wang, L.
   Wardlow, J. L.
   Zemcov, M.
TI The rapid assembly of an elliptical galaxy of 400 billion solar masses at a redshift of 2.3
SO NATURE
LA English
DT Article
ID h-2 conversion factor; star-formation; submillimeter galaxy; molecular gas; model; co
AB Stellar archaeology(1) shows that massive elliptical galaxies formed rapidly about ten billion years ago with star-formation rates of above several hundred solar masses per year. Their progenitors are probably the submillimetre bright galaxies(2) at redshifts z greater than 2. Although the mean molecular gas mass(3) (5 x 10(10) solar masses) of the submillimetre bright galaxies can explain the formation of typical elliptical galaxies, it is inadequate to form elliptical galaxies(4) that already have stellar masses above 2 x 10(11) solar masses at z approximate to 2. Here we report multi-wavelength high-resolution observations of a rare merger of two massive submillimetre bright galaxies at z approximate to 2.3. The system is seen to be forming stars at a rate of 2,000 solar masses per year. The star-formation efficiency is an order of magnitude greater than that of normal galaxies, so the gas reservoir will be exhausted and star formation will be quenched in only around 200 million years. At a projected separation of 19 kiloparsecs, the two massive starbursts are about to merge and form a passive elliptical galaxy with a stellar mass of about 4 x 10(11) solar masses. We conclude that gas-rich major galaxy mergers with intense star formation can form the most massive elliptical galaxies by z approximate to 1.5.
C1 [Fu, Hai; Cooray, Asantha; Boylan-Kolchin, M.; Calanog, J. A.; Jia, J.; Wardlow, J. L.] Univ Calif Irvine, Dept Phys & Astron, Irvine, CA 92697 USA.
   [Feruglio, C.; Cox, P.; Neri, R.] Inst Radio Astron Millimetr, F-38406 St Martin Dheres, France.
   [Ivison, R. J.] Royal Observ, UK Astron Technol Ctr, Edinburgh EH9 3HJ, Midlothian, Scotland.
   [Riechers, D. A.] Cornell Univ, Dept Astron, Ithaca, NY 14853 USA.
   [Gurwell, M.; Bussmann, R. S.] Harvard Smithsonian Ctr Astrophys, Cambridge, MA 02138 USA.
   [Harris, A. I.] Univ Maryland, Dept Astron, College Pk, MD 20742 USA.
   [Altieri, B.; Valtchanov, I.] European Space Astron Ctr, Herschel Sci Ctr, Madrid 28691, Spain.
   [Aussel, H.] Univ Paris Diderot, Lab AIM Paris Saclay, CEA Saclay, CEA,DSM,Irfu,SAp,CNRS, F-91191 Gif Sur Yvette, France.
   [Baker, A. J.] Rutgers State Univ, Dept Phys & Astron, Piscataway, NJ 08854 USA.
   [Bock, J.; Zemcov, M.] CALTECH, Jet Prop Lab, Pasadena, CA 91109 USA.
   [Bock, J.; Bridge, C.; Vieira, J. D.; Viero, M.] CALTECH, Pasadena, CA 91125 USA.
   [Casey, C. M.] Univ Hawaii, Inst Astron, Honolulu, HI 96822 USA.
   [Cava, A.] Univ Complutense Madrid, Fac Ciencias Fis, Dept Astrofis, E-28040 Madrid, Spain.
   [Chapman, S. C.] Dalhousie Univ, Dept Phys & Atmospher Sci, Halifax, NS B3H 4R2, Canada.
   [Clements, D. L.; Hopwood, R.] Univ London Imperial Coll Sci Technol & Med, Blackett Lab, Astrophys Grp, London SW7 2AZ, England.
   [Conley, A.] Univ Colorado, Ctr Astrophys & Space Astron UCB 389, Boulder, CO 80309 USA.
   [Farrah, D.] Virginia Tech, Dept Phys, Blacksburg, VA 24061 USA.
   [Frayer, D.] Natl Radio Astron Observ, Green Bank, WV 24944 USA.
   [Magdis, G.] Univ Oxford, Dept Phys, Oxford OX1 3RH, England.
   [Marsden, G.; Scott, D.] Univ British Columbia, Dept Phys & Astron, Vancouver, BC V6T 1Z1, Canada.
   [Martinez-Navajas, P.; Perez-Fournon, I.] Inst Astrofis Canarias, E-38200 Tenerife, Spain.
   [Martinez-Navajas, P.; Perez-Fournon, I.] Univ La Laguna, Dept Astrofis, E-38205 Tenerife, Spain.
   [Negrello, M.] Osserv Astron Padova, INAF, I-35122 Padua, Italy.
   [Oliver, S. J.; Smith, A.; Wang, L.] Univ Sussex, Dept Phys & Astron, Ctr Astron, Brighton BN1 9QH, E Sussex, England.
   [Omont, A.] Univ Paris 06, CNRS, Inst Astrophys Paris, UMR 7095, F-75014 Paris, France.
   [Page, M. J.] Univ Coll London, Mullard Space Sci Lab, Dorking RH5 6NT, Surrey, England.
   [Schulz, B.] CALTECH, Jet Prop Lab, Infrared Proc & Anal Ctr, Pasadena, CA 91125 USA.
   [Vaccari, M.] Univ Western Cape, Dept Phys, Astrophys Grp, ZA-7535 Cape Town, South Africa.
C3 University of California System; University of California Irvine; University of Edinburgh; Cornell University; Smithsonian Institution; Smithsonian Astrophysical Observatory; Harvard University; University System of Maryland; University of Maryland College Park; European Space Agency; European Space Astronomy Center; Universite Paris Saclay; CEA; Centre National de la Recherche Scientifique (CNRS); Universite Paris Cite; Rutgers University System; Rutgers University New Brunswick; California Institute of Technology; National Aeronautics & Space Administration (NASA); NASA Jet Propulsion Laboratory (JPL); California Institute of Technology; University of Hawaii System; Complutense University of Madrid; Dalhousie University; Imperial College London; University of Colorado System; University of Colorado Boulder; Virginia Polytechnic Institute & State University; National Radio Astronomy Observatory (NRAO); University of Oxford; University of British Columbia; Instituto de Astrofisica de Canarias; Universidad de la Laguna; University of Padua; Istituto Nazionale Astrofisica (INAF); University of Sussex; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Earth Sciences & Astronomy (INSU); Sorbonne Universite; University of London; University College London; National Aeronautics & Space Administration (NASA); NASA Jet Propulsion Laboratory (JPL); California Institute of Technology; University of the Western Cape
RP Fu, H (corresponding author), Univ Calif Irvine, Dept Phys & Astron, Irvine, CA 92697 USA.
EM haif@uci.edu; acooray@uci.edu
FU CSA (Canada); NAOC (China); CEA (France); CNES (France); CNRS (France); ASI (Italy); MCINN (Spain); SNSB (Sweden); STFC (UK); NASA (USA); Science and Technology Facilities Council [ST/K000977/1, ST/I005765/1, ST/L001314/1, ST/I000976/1] Funding Source: researchfish; UK Space Agency [ST/J004812/1, ST/G003874/1] Funding Source: researchfish; Direct For Mathematical & Physical Scien; Division Of Astronomical Sciences [1140063, 1139950, 1140019] Funding Source: National Science Foundation; Direct For Mathematical & Physical Scien; Division Of Astronomical Sciences [1140031] Funding Source: National Science Foundation; STFC [ST/I000976/1, ST/L001314/1, ST/I005765/1, ST/K000977/1] Funding Source: UKRI
NR 30
TC 125
Z9 132
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 JUN 20
PY 2013
VL 498
IS 7454
BP 338
EP 341
DI 10.1038/nature12184
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 166XI
UT WOS:000320592900034
PM 23698363
DA 2026-03-09
ER

PT J
AU Kabeche, L
   Compton, DA
AF Kabeche, Lilian
   Compton, Duane A.
TI Cyclin A regulates kinetochore microtubules to promote faithful chromosome segregation
SO NATURE
LA English
DT Article
ID error-correction; cell-cycle; mitosis; orientation; anaphase; destruction; aneuploidy; attachment; metaphase; dynamics
AB The most conspicuous event in the cell cycle is the alignment of chromosomes in metaphase. Chromosome alignment fosters faithful segregation through the formation of bi-oriented attachments of kinetochores to spindle microtubules. Notably, numerous kinetochore-microtubule (k-MT) attachment errors are present in early mitosis (prometaphase) 1, and the persistence of those errors is the leading cause of chromosome mis-segregation in aneuploid human tumour cells that continually mis-segregate whole chromosomes and display chromosomal instability(2-7). How robust error correction is achieved in prometaphase to ensure error-free mitosis remains unknown. Here we show that k-MT attachments in prometaphase cells are considerably less stable than in metaphase cells. The switch to more stable k-MT attachments in metaphase requires the proteasome-dependent destruction of cyclin A in prometaphase. Persistent cyclin A expression prevents k-MT stabilization even in cells with aligned chromosomes. By contrast, k-MTs are prematurely stabilized in cyclin-A-deficient cells. Consequently, cells lacking cyclin A display higher rates of chromosome mis-segregation. Thus, the stability of k-MT attachments increases decisively in a coordinated fashion among all chromosomes as cells transit from prometaphase to metaphase. Cyclin A creates a cellular environment that promotes microtubule detachment from kinetochores in prometaphase to ensure efficient error correction and faithful chromosome segregation.
C1 [Kabeche, Lilian; Compton, Duane A.] Geisel Sch Med Dartmouth, Dept Biochem, Hanover, NH 03755 USA.
   [Kabeche, Lilian; Compton, Duane A.] Norris Cotton Canc Ctr, Lebanon, NH 03756 USA.
C3 Dartmouth College; Dartmouth Cancer Center
RP Compton, DA (corresponding author), Geisel Sch Med Dartmouth, Dept Biochem, Hanover, NH 03755 USA.
EM duane.a.compton@dartmouth.edu
FU National Institutes of Health [GM51542, GM008704]; John H. Copenhaver Jr and William H. Thomas, MD 1952 Junior Fellowship; National Institute of General Medical Sciences [R37GM051542] Funding Source: NIH RePORTER
NR 28
TC 111
Z9 144
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 OCT 3
PY 2013
VL 502
IS 7469
BP 110
EP +
DI 10.1038/nature12507
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 227IM
UT WOS:000325106000041
PM 24013174
DA 2026-03-09
ER

PT J
AU Posé, D
   Verhage, L
   Ott, F
   Yant, L
   Mathieu, J
   Angenent, GC
   Immink, RGH
   Schmid, M
AF Pose, David
   Verhage, Leonie
   Ott, Felix
   Yant, Levi
   Mathieu, Johannes
   Angenent, Gerco C.
   Immink, Richard G. H.
   Schmid, Markus
TI Temperature-dependent regulation of flowering by antagonistic FLM variants
SO NATURE
LA English
DT Article
ID mads-box gene; circadian clock; functional-analysis; floral transition; arabidopsis; identification; repressor; time; vernalization; responses
AB The appropriate timing of flowering is crucial for plant reproductive success. It is therefore not surprising that intricate genetic networks have evolved to perceive and integrate both endogenous and environmental signals, such as carbohydrate and hormonal status, photoperiod and temperature(1,2). In contrast to our detailed understanding of the vernalization pathway, little is known about how flowering time is controlled in response to changes in the ambient growth temperature. In Arabidopsis thaliana, the MADS-box transcription factor genes FLOWERING LOCUS M (FLM) and SHORT VEGETATIVE PHASE (SVP) have key roles in this process(3,4). FLM is subject to temperature-dependent alternative splicing(3). Here we report that the two main FLM protein splice variants, FLM-beta and FLM-delta, compete for interaction with the floral repressor SVP. The SVP-FLM-beta complex is predominately formed at low temperatures and prevents precocious flowering. By contrast, the competing SVP-FLM-delta complex is impaired in DNA binding and acts as a dominant-negative activator of flowering at higher temperatures. Our results show a new mechanism that controls the timing of the floral transition in response to changes in ambient temperature. A better understanding of how temperature controls the molecular mechanisms of flowering will be important to cope with current changes in global climate(5,6).
C1 [Pose, David; Ott, Felix; Yant, Levi; Mathieu, Johannes; Schmid, Markus] Max Planck Inst Dev Biol, Dept Mol Biol, D-72076 Tubingen, Germany.
   [Verhage, Leonie; Angenent, Gerco C.; Immink, Richard G. H.] Plant Res Int, Biosci, NL-6708 PB Wageningen, Netherlands.
   [Verhage, Leonie; Angenent, Gerco C.] Wageningen Univ, Mol Biol Lab, NL-6708 PB Wageningen, Netherlands.
C3 Max Planck Society; Wageningen University & Research
RP Schmid, M (corresponding author), Max Planck Inst Dev Biol, Dept Mol Biol, Spemannstr 35, D-72076 Tubingen, Germany.
EM markus.schmid@tuebingen.mpg.de
FU ERA-NET PLANT GENOMICS collaborative project BLOOM-NET; Deutsche Forschungsgemeinschaft [SCHM 1560/7-1]; MPI for Developmental Biology; BLOOM-NET related NWO grant; NWO/TTI-Green Genetics THERMOFLOW grant
NR 35
TC 385
Z9 435
U1 6
U2 271
PU NATURE PUBLISHING 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 21
PY 2013
VL 503
IS 7476
BP 414
EP +
DI 10.1038/nature12633
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 254KG
UT WOS:000327163200045
PM 24067612
DA 2026-03-09
ER

PT J
AU Zheng, XT
   Bi, SD
   Wang, XL
   Meng, J
AF Zheng, Xiaoting
   Bi, Shundong
   Wang, Xiaoli
   Meng, Jin
TI A new arboreal haramiyid shows the diversity of crown mammals in the Jurassic period
SO NATURE
LA English
DT Article
ID allotherian mammals; diversification; evolution; origins; teeth; tail
AB A major unsolved problem in mammalian evolution is the origin of Allotheria, including Multituberculata and Haramiyida(1-5). Multituberculates are the most diverse and best known Mesozoic era mammals and ecologically resemble rodents, but haramiyids are known mainly from isolated teeth, hampering our search for their phylogenetic relationships. Here we report a new haramiyid from the Jurassic period of China, which is, to our knowledge the largest reported so far. It has a novel dentition, a mandible resembling advanced multituberculates and postcranial features adapted for arboreal life. Our phylogenetic analysis places Haramiyida within crown Mammalia, suggesting the origin of crown Mammalia in the Late Triassic period and diversification in the Jurassic, which contrasts other estimated divergence times of crown Mammalia(6-8). The new haramiyid reveals additional mammalian features of the group, helps to identify other haramiyids represented by isolated teeth, and shows again that, regardless of various phylogenetic scenarios, a complex pattern of evolution involving many convergences and/or reversals existed in Mesozoic mammals. [GRAPHICS] .
C1 [Zheng, Xiaoting; Wang, Xiaoli] Linyi Univ, Inst Geol & Paleontol, Linyi 276005, Shandong, Peoples R China.
   [Zheng, Xiaoting; Wang, Xiaoli] Shandong Tianyu Museum Nat, Pingyi 273300, Shandong, Peoples R China.
   [Bi, Shundong; Meng, Jin] Chinese Acad Sci, Inst Vertebrate Paleontol & Paleoanthropol, Key Lab Vertebrate Evolut & Human Origin, Beijing 100044, Peoples R China.
   [Bi, Shundong] Indiana Univ Penn, Dept Biol, Indiana, PA 15705 USA.
   [Meng, Jin] Amer Museum Nat Hist, Div Paleontol, New York, NY 10024 USA.
C3 Linyi University; Chinese Academy of Sciences; Institute of Vertebrate Paleontology & Paleoanthropology, CAS; Pennsylvania State System of Higher Education (PASSHE); Indiana University of Pennsylvania; American Museum of Natural History (AMNH)
RP Bi, SD (corresponding author), Chinese Acad Sci, Inst Vertebrate Paleontol & Paleoanthropol, Key Lab Vertebrate Evolut & Human Origin, Beijing 100044, Peoples R China.
EM bishundong@ivpp.ac.cn; jmeng@amnh.org
FU National Basic Research Program of China 973 Program [2012CB821906]; National Natural Science Foundation of China [41172016, 41128002]; Hundred Talents Programs of the Chinese Academy of Sciences
NR 30
TC 107
Z9 129
U1 1
U2 71
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 8
PY 2013
VL 500
IS 7461
BP 199
EP 202
DI 10.1038/nature12353
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 197CH
UT WOS:000322825500033
PM 23925244
DA 2026-03-09
ER

PT J
AU Singh, R
   Low, ETL
   Ooi, LCL
   Ong-Abdullah, M
   Ting, NC
   Nagappan, J
   Nookiah, R
   Amiruddin, MD
   Rosli, R
   Manaf, MAA
   Chan, KL
   Halim, MA
   Azizi, N
   Lakey, N
   Smith, SW
   Budiman, MA
   Hogan, M
   Bacher, B
   Van Brunt, A
   Wang, CY
   Ordway, JM
   Sambanthamurthi, R
   Martienssen, RA
AF Singh, Rajinder
   Low, Eng-Ti Leslie
   Ooi, Leslie Cheng-Li
   Ong-Abdullah, Meilina
   Ting, Ngoot-Chin
   Nagappan, Jayanthi
   Nookiah, Rajanaidu
   Amiruddin, Mohd Din
   Rosli, Rozana
   Manaf, Mohamad Arif Abdul
   Chan, Kuang-Lim
   Halim, Mohd Amin
   Azizi, Norazah
   Lakey, Nathan
   Smith, Steven W.
   Budiman, Muhammad A.
   Hogan, Michael
   Bacher, Blaire
   Van Brunt, Andrew
   Wang, Chunyan
   Ordway, Jared M.
   Sambanthamurthi, Ravigadevi
   Martienssen, Robert A.
TI The oil palm SHELL gene controls oil yield and encodes a homologue of SEEDSTICK
SO NATURE
LA English
DT Article
ID mads-box genes; elaeis-guineensis; agamous subfamily; linkage map; diversification; conservation; arabidopsis; carpel; fruit; locus
AB A key event in the domestication and breeding of the oil palm Elaeis guineensis was loss of the thick coconut-like shell surrounding the kernel. Modern E. guineensis has three fruit forms, dura (thick-shelled), pisifera (shell-less) and tenera (thin-shelled), a hybrid between dura and pisifera(1-4). The pisifera palm is usually female-sterile. The tenera palm yields far more oil than dura, and is the basis for commercial palm oil production in all of southeast Asia(5). Here we describe the mapping and identification of the SHELL gene responsible for the different fruit forms. Using homozygosity mapping by sequencing, we found two independent mutations in the DNA-binding domain of a homologue of the MADS-box gene SEEDSTICK (STK, also known as AGAMOUS-LIKE 11), which controls ovule identity and seed development in Arabidopsis. The SHELL gene is responsible for the tenera phenotype in both cultivated and wild palms from sub-Saharan Africa, and our findings provide a genetic explanation for the single gene hybrid vigour (or heterosis) attributed to SHELL, via heterodimerization. This gene mutation explains the single most important economic trait in oil palm, and has implications for the competing interests of global edible oil production, biofuels and rainforest conservation(6).
C1 [Singh, Rajinder; Low, Eng-Ti Leslie; Ooi, Leslie Cheng-Li; Ong-Abdullah, Meilina; Ting, Ngoot-Chin; Nagappan, Jayanthi; Nookiah, Rajanaidu; Amiruddin, Mohd Din; Rosli, Rozana; Manaf, Mohamad Arif Abdul; Chan, Kuang-Lim; Halim, Mohd Amin; Azizi, Norazah; Sambanthamurthi, Ravigadevi] Persiaran Inst, Malaysian Palm Oil Board, Kajang 43000, Selangor, Malaysia.
   [Lakey, Nathan; Smith, Steven W.; Budiman, Muhammad A.; Hogan, Michael; Bacher, Blaire; Van Brunt, Andrew; Wang, Chunyan; Ordway, Jared M.] Orion Genom, St Louis, MO 63108 USA.
   [Martienssen, Robert A.] Cold Spring Harbor Lab, Howard Hughes Med Inst, Gordon & Betty Moore Fdn, Cold Spring Harbor, NY 11724 USA.
C3 Malaysian Palm Oil Board; Cold Spring Harbor Laboratory; Howard Hughes Medical Institute
RP Sambanthamurthi, R (corresponding author), Persiaran Inst, Malaysian Palm Oil Board, Kajang 43000, Selangor, Malaysia.
EM raviga@mpob.gov.my; martiens@cshl.edu
FU Malaysian Palm Oil Board; National Science Foundation [0421604]; Division Of Integrative Organismal Systems; Direct For Biological Sciences [0421604] Funding Source: National Science Foundation
NR 30
TC 162
Z9 185
U1 1
U2 122
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 15
PY 2013
VL 500
IS 7462
BP 340
EP +
DI 10.1038/nature12356
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 201AF
UT WOS:000323112400034
PM 23883930
DA 2026-03-09
ER

PT J
AU DeGennaro, M
   McBride, CS
   Seeholzer, L
   Nakagawa, T
   Dennis, EJ
   Goldman, C
   Jasinskiene, N
   James, AA
   Vosshall, LB
AF DeGennaro, Matthew
   McBride, Carolyn S.
   Seeholzer, Laura
   Nakagawa, Takao
   Dennis, Emily J.
   Goldman, Chloe
   Jasinskiene, Nijole
   James, Anthony A.
   Vosshall, Leslie B.
TI orco mutant mosquitoes lose strong preference for humans and are not repelled by volatile DEET
SO NATURE
LA English
DT Article
ID drosophila odorant receptors; aedes-aegypti; anopheles-gambiae; channels; female
AB Female mosquitoes of some species are generalists and will blood-feed on a variety of vertebrate hosts, whereas others display marked host preference. Anopheles gambiae and Aedes aegypti have evolved a strong preference for humans, making them dangerously efficient vectors of malaria and Dengue haemorrhagic fever(1). Specific host odours probably drive this strong preference because other attractive cues, including body heat and exhaled carbon dioxide (CO2), are common to all warm-blooded hosts(2,3). Insects sense odours via several chemosensory receptor families, including the odorant receptors (ORs), membrane proteins that form heteromeric odour-gated ion channels(4,5) comprising a variable ligand-selective subunit and an obligate co-receptor called Orco (ref. 6). Here we use zinc-finger nucleases to generate targeted mutations in the orco gene of A. aegypti to examine the contribution of Orco and the odorant receptor pathway to mosquito host selection and sensitivity to the insect repellent DEET (N,N-diethyl-meta-toluamide). orco mutant olfactory sensory neurons have greatly reduced spontaneous activity and lack odour-evoked responses. Behaviourally, orco mutant mosquitoes have severely reduced attraction to honey, an odour cue related to floral nectar, and do not respond to human scent in the absence of CO2. However, in the presence of CO2, female orco mutant mosquitoes retain strong attraction to both human and animal hosts, but no longer strongly prefer humans. orco mutant females are attracted to human hosts even in the presence of DEET, but are repelled upon contact, indicating that olfactory- and contact-mediated effects of DEET are mechanistically distinct. We conclude that the odorant receptor pathway is crucial for an anthropophilic vector mosquito to discriminate human from non-human hosts and to be effectively repelled by volatile DEET.
C1 [DeGennaro, Matthew; McBride, Carolyn S.; Seeholzer, Laura; Nakagawa, Takao; Dennis, Emily J.; Goldman, Chloe; Vosshall, Leslie B.] Rockefeller Univ, Lab Neurogenet & Behav, New York, NY 10065 USA.
   [DeGennaro, Matthew; Vosshall, Leslie B.] Rockefeller Univ, Howard Hughes Med Inst, New York, NY 10065 USA.
   [Jasinskiene, Nijole; James, Anthony A.] Univ Calif Irvine, Dept Mol Biol & Biochem, Irvine, CA 92697 USA.
   [James, Anthony A.] Univ Calif Irvine, Dept Microbiol & Mol Genet & Mol Biol & Biochem, Irvine, CA 92697 USA.
C3 Rockefeller University; Rockefeller University; Howard Hughes Medical Institute; University of California System; University of California Irvine; University of California System; University of California Irvine
RP Vosshall, LB (corresponding author), Rockefeller Univ, Lab Neurogenet & Behav, New York, NY 10065 USA.
EM Leslie.Vosshall@rockefeller.edu
FU Foundation for the National Institutes of Health through the Grand Challenges in Global Health Initiative; National Institutes of Health [DC012069, AI29746]
NR 29
TC 336
Z9 399
U1 2
U2 261
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 27
PY 2013
VL 498
IS 7455
BP 487
EP 491
DI 10.1038/nature12206
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 171LH
UT WOS:000320929400053
PM 23719379
DA 2026-03-09
ER

PT J
AU Abad, M
   Mosteiro, L
   Pantoja, C
   Cañamero, M
   Rayon, T
   Ors, I
   Graña, O
   Megías, D
   Domínguez, O
   Martínez, D
   Manzanares, M
   Ortega, S
   Serrano, M
AF Abad, Maria
   Mosteiro, Lluc
   Pantoja, Cristina
   Canamero, Marta
   Rayon, Teresa
   Ors, Inmaculada
   Grana, Osvaldo
   Megias, Diego
   Dominguez, Orlando
   Martinez, Dolores
   Manzanares, Miguel
   Ortega, Sagrario
   Serrano, Manuel
TI Reprogramming in vivo produces teratomas and iPS cells with totipotency features
SO NATURE
LA English
DT Article
ID embryonic stem-cells; transcription factors; direct conversion; mouse; expression; fibroblasts; generation; gene; differentiation; neurons
AB Reprogramming of adult cells to generate induced pluripotent stem cells (iPS cells) has opened new therapeutic opportunities; however, little is known about the possibility of in vivo reprogramming within tissues. Here we show that transitory induction of the four factors Oct4, Sox2, Klf4 and c-Myc in mice results in teratomas emerging from multiple organs, implying that full reprogramming can occur in vivo. Analyses of the stomach, intestine, pancreas and kidney reveal groups of dedifferentiated cells that express the pluripotency marker NANOG, indicative of in situ reprogramming. By bone marrow transplantation, we demonstrate that haematopoietic cells can also be reprogrammed in vivo. Notably, reprogrammable mice present circulating iPS cells in the blood and, at the transcriptome level, these in vivo generated iPS cells are closer to embryonic stem cells (ES cells) than standard in vitro generated iPS cells. Moreover, in vivo iPS cells efficiently contribute to the trophectoderm lineage, suggesting that they achieve a more plastic or primitive state than ES cells. Finally, intraperitoneal injection of in vivo iPS cells generates embryo-like structures that express embryonic and extraembryonic markers. We conclude that reprogramming in vivo is feasible and confers totipotency features absent in standard iPS or ES cells. These discoveries could be relevant for future applications of reprogramming in regenerative medicine.
C1 [Abad, Maria; Mosteiro, Lluc; Pantoja, Cristina; Serrano, Manuel] Spanish Natl Canc Res Ctr CNIO, Tumour Suppress Grp, E-28029 Madrid, Spain.
   [Canamero, Marta] Spanish Natl Canc Res Ctr CNIO, Histopathol Unit, E-28029 Madrid, Spain.
   [Rayon, Teresa; Ors, Inmaculada; Manzanares, Miguel] Spanish Natl Cardiovasc Res Ctr CNIC, Cardiovasc Dev & Repair Dept, E-28029 Madrid, Spain.
   [Grana, Osvaldo] Spanish Natl Canc Res Ctr CNIO, Bioinformat Unit, E-28029 Madrid, Spain.
   [Megias, Diego] Spanish Natl Canc Res Ctr CNIO, Confocal Microscopy Unit, E-28029 Madrid, Spain.
   [Dominguez, Orlando] Spanish Natl Canc Res Ctr CNIO, Genom Unit, E-28029 Madrid, Spain.
   [Martinez, Dolores] Spanish Natl Canc Res Ctr CNIO, Flow Cytometry Unit, E-28029 Madrid, Spain.
   [Ortega, Sagrario] Spanish Natl Canc Res Ctr CNIO, Transgen Mice Unit, E-28029 Madrid, Spain.
C3 Centro Nacional de Investigaciones Oncologicas (CNIO); Centro Nacional de Investigaciones Oncologicas (CNIO); Centro Nacional de Investigaciones Cardiovasculares (CNIC); Centro Nacional de Investigaciones Oncologicas (CNIO); Centro Nacional de Investigaciones Oncologicas (CNIO); Centro Nacional de Investigaciones Oncologicas (CNIO); Centro Nacional de Investigaciones Oncologicas (CNIO); Centro Nacional de Investigaciones Oncologicas (CNIO)
RP Serrano, M (corresponding author), Spanish Natl Canc Res Ctr CNIO, Tumour Suppress Grp, E-28029 Madrid, Spain.
EM mserrano@cnio.es
FU CNIO; Spanish Ministry of Economy (MINECO, SAF); Regional Government of Madrid (ReCaRe); European Union (RISK-IR); Botin Foundation; Ramon Areces Foundation; AXA Foundation; MINECO(BFU); Regional Government of Madrid (Cell-DD); ProCNIC Foundation
NR 44
TC 414
Z9 479
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 OCT 17
PY 2013
VL 502
IS 7471
BP 340
EP +
DI 10.1038/nature12586
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 235GY
UT WOS:000325706300046
PM 24025773
DA 2026-03-09
ER

PT J
AU Brown, PG
   Assink, JD
   Astiz, L
   Blaauw, R
   Boslough, MB
   Borovicka, J
   Brachet, N
   Brown, D
   Campbell-Brown, M
   Ceranna, L
   Cooke, W
   de Groot-Hedlin, C
   Drob, DP
   Edwards, W
   Evers, LG
   Garces, M
   Gill, J
   Hedlin, M
   Kingery, A
   Laske, G
   Le Pichon, A
   Mialle, P
   Moser, DE
   Saffer, A
   Silber, E
   Smets, P
   Spalding, RE
   Spurny, P
   Tagliaferri, E
   Uren, D
   Weryk, RJ
   Whitaker, R
   Krzeminski, Z
AF Brown, P. G.
   Assink, J. D.
   Astiz, L.
   Blaauw, R.
   Boslough, M. B.
   Borovicka, J.
   Brachet, N.
   Brown, D.
   Campbell-Brown, M.
   Ceranna, L.
   Cooke, W.
   de Groot-Hedlin, C.
   Drob, D. P.
   Edwards, W.
   Evers, L. G.
   Garces, M.
   Gill, J.
   Hedlin, M.
   Kingery, A.
   Laske, G.
   Le Pichon, A.
   Mialle, P.
   Moser, D. E.
   Saffer, A.
   Silber, E.
   Smets, P.
   Spalding, R. E.
   Spurny, P.
   Tagliaferri, E.
   Uren, D.
   Weryk, R. J.
   Whitaker, R.
   Krzeminski, Z.
TI A 500-kiloton airburst over Chelyabinsk and an enhanced hazard from small impactors
SO NATURE
LA English
DT Article
ID earth; asteroids; explosion
AB Most large (over a kilometre in diameter) near-Earth asteroids are now known, but recognition that airbursts (or fireballs resulting from nuclear-weapon-sized detonations of meteoroids in the atmosphere) have the potential to do greater damage(1) than previously thought has shifted an increasing portion of the residual impact risk (the risk of impact from an unknown object) to smaller objects(2). Above the threshold size of impactor at which the atmosphere absorbs sufficient energy to prevent a ground impact, most of the damage is thought to be caused by the airburst shock wave(3), but owing to lack of observations this is uncertain(4,5). Here we report an analysis of the damage from the airburst of an asteroid about 19 metres (17 to 20 metres) in diameter southeast of Chelyabinsk, Russia, on 15 February 2013, estimated to have an energy equivalent of approximately 500 (+/- 100) kilotons of trinitrotoluene (TNT, where 1 kiloton of TNT = 4.185x10(12) joules). We show that a widely referenced technique(4-6) of estimating airburst damage does not reproduce the observations, and that the mathematical relations(7) based on the effects of nuclear weapons-almost always used with this technique-overestimate blast damage. This suggests that earlier damage estimates(5,6) near the threshold impactor size are too high. We performed a global survey of airbursts of a kiloton or more (including Chelyabinsk), and find that the number of impactors with diameters of tens of metres may be an order of magnitude higher than estimates based on other techniques(8,9). This suggests a non-equilibrium(if the population were in a long-term collisional steady state the size-frequency distribution would either follow a single power law or there must be a size-dependent bias in other surveys) in the near-Earth asteroid population for objects 10 to 50 metres in diameter, and shifts more of the residual impact risk to these sizes.
C1 [Brown, P. G.; Campbell-Brown, M.; Gill, J.; Silber, E.; Uren, D.; Weryk, R. J.; Krzeminski, Z.] Univ Western Ontario, Dept Phys & Astron, London, ON N6A 3K7, Canada.
   [Brown, P. G.] Univ Western Ontario, Ctr Planetary Sci & Explorat, London, ON N6A 5B7, Canada.
   [Assink, J. D.; Brachet, N.; Le Pichon, A.] Commissariat Energie Atom, Dept Anal Surveillance Environm CEA DAM DIF, F-91297 Bruyeres Le Chatel, Arpajon, France.
   [Astiz, L.; de Groot-Hedlin, C.; Hedlin, M.; Laske, G.] Univ Calif San Diego, Inst Geophys & Planetary Phys, Lab Atmospher Acoust, La Jolla, CA 92093 USA.
   [Blaauw, R.; Moser, D. E.] NASA, Marshall Informat Technol Serv MITS, Dynet Tech Serv, Marshall Space Flight Ctr, Huntsville, CA 35812 USA.
   [Boslough, M. B.; Spalding, R. E.] Sandia Natl Labs, Albuquerque, NM 87185 USA.
   [Borovicka, J.; Spurny, P.] Acad Sci Czech Republ, Astron Inst, CZ-25165 Ondrejov, Czech Republic.
   [Brown, D.; Mialle, P.] Comprehens Test Ban Treaty Org, Provis Tech Secretariat, Int Data Ctr, A-1400 Vienna, Austria.
   [Ceranna, L.] Bundesanstalt Geowissensch & Rohstoffe, D-30655 Hannover, Germany.
   [Cooke, W.; Saffer, A.] Marshall Space Flight Ctr, Meteoroid Environm Off, Space Environm Team, Huntsville, AL 35812 USA.
   [Drob, D. P.] Naval Res Lab, Space Sci Div, Washington, DC 20375 USA.
   [Edwards, W.] Nat Resources Canada, Canadian Hazard Informat Serv, Ottawa, ON K1A 0Y3, Canada.
   [Evers, L. G.; Smets, P.] Royal Netherlands Meteorol Inst, Seismol Div, NL-3732 GK De Bilt, Netherlands.
   [Evers, L. G.; Smets, P.] Delft Univ Technol, Fac Civil Engn & Geosci, Dept Geosci & Engn, NL-2628 CN Delft, Netherlands.
   [Garces, M.] Univ Hawaii, Infrasound Lab, Honolulu, HI 96740 USA.
   [Kingery, A.] NASA, ERC Inc Jacobs ESSSA Grp, Marshall Space Flight Ctr, Huntsville, AL 35812 USA.
   [Tagliaferri, E.] ET Space Syst, Camarillo, CA 93012 USA.
   [Whitaker, R.] Los Alamos Natl Lab, Los Alamos, NM 87545 USA.
C3 Western University (University of Western Ontario); Western University (University of Western Ontario); Communaute Universite Grenoble Alpes; Universite Grenoble Alpes (UGA); CEA; University of California System; University of California San Diego; National Aeronautics & Space Administration (NASA); United States Department of Energy (DOE); Sandia National Laboratories; Czech Academy of Sciences; Astronomical Institute of the Czech Academy of Sciences; National Aeronautics & Space Administration (NASA); NASA Marshall Space Flight Center; United States Department of Defense; United States Navy; United States Naval Research Laboratory; Natural Resources Canada; Royal Netherlands Meteorological Institute; Delft University of Technology; University of Hawaii System; National Aeronautics & Space Administration (NASA); ERC Inc; United States Department of Energy (DOE); Los Alamos National Laboratory
RP Brown, PG (corresponding author), Univ Western Ontario, Dept Phys & Astron, London, ON N6A 3K7, Canada.
EM pbrown@uwo.ca
FU NASA [NNX11AB76A]; Office of Naval Research;  [67985815]; Division Of Earth Sciences; Directorate For Geosciences [1147962] Funding Source: National Science Foundation
CR BENMENAHEM A, 1975, PHYS EARTH PLANET IN, V11, P1, DOI 10.1016/0031-9201(75)90072-2
   Bland PA, 2006, METEORIT PLANET SCI, V41, P607, DOI 10.1111/j.1945-5100.2006.tb00485.x
   Borovicka J, 2013, METEORIT PLANET SCI, V0, P0
   Boslough MBE, 2008, INT J IMPACT ENG, V35, P1441, DOI 10.1016/j.ijimpeng.2008.07.053
   Boslough MBE, 1997, ANN NY ACAD SCI, V822, P236, DOI 10.1111/j.1749-6632.1997.tb48345.x
   Brachet N, 2010, INFRASOUND MONITORING FOR ATMOSPHERIC STUDIES, V0, PP77, DOI 10.1007/978-1-4020-9508-5_3
   Brown P, 2011, METEORIT PLANET SCI, V46, P339, DOI 10.1111/j.1945-5100.2010.01167.x
   Brown P, 2002, NATURE, V420, P294, DOI 10.1038/nature01238
   Brown P, 2008, J GEOPHYS RES-PLANET, V113, P0, DOI 10.1029/2008JE003105
   CEPLECHA Z, 1992, ASTRON ASTROPHYS, V263, P361
   CHAPMAN CR, 1994, NATURE, V367, P33, DOI 10.1038/367033a0
   CHYBA CF, 1993, NATURE, V361, P40, DOI 10.1038/361040a0
   Collins GS, 2005, METEORIT PLANET SCI, V40, P817, DOI 10.1111/j.1945-5100.2005.tb00157.x
   Ens TA, 2012, J ATMOS SOL-TERR PHY, V80, P208, DOI 10.1016/j.jastp.2012.01.018
   Glasstone S, 1977, EFFECTS NUCL WEAPONS, V0, P100
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   Harris A, 2008, NATURE, V453, P1178, DOI 10.1038/4531178a
   HILLS JG, 1993, ASTRON J, V105, P1114, DOI 10.1086/116499
   Rabinowitz D, 2000, NATURE, V403, P165, DOI 10.1038/35003128
   ReVelle DO, 2007, P INT ASTRON UNION S, V0, P95
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   Silber EA, 2009, J GEOPHYS RES-PLANET, V114, P0, DOI 10.1029/2009JE003334
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   Toon OB, 1997, REV GEOPHYS, V35, P41, DOI 10.1029/96RG03038
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   Werner SC, 2002, ICARUS, V156, P287
NR 26
TC 367
Z9 421
U1 2
U2 83
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 14
PY 2013
VL 503
IS 7475
BP 238
EP 241
DI 10.1038/nature12741
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 250YX
UT WOS:000326894200046
PM 24196713
DA 2026-03-09
ER

PT J
AU Conrad, CP
   Steinberger, B
   Torsvik, TH
AF Conrad, Clinton P.
   Steinberger, Bernhard
   Torsvik, Trond H.
TI Stability of active mantle upwelling revealed by net characteristics of plate tectonics
SO NATURE
LA English
DT Article
ID true polar wander; earths mantle; deep mantle; slab pull; dynamics; velocity; motions; tomography; convection; rotation
AB Viscous convection within the mantle is linked to tectonic plate motions(1-3) and deforms Earth's surface across wide areas(4-6). Such close links between surface geology and deep mantle dynamics presumably operated throughout Earth's history, but are difficult to investigate for past times because the history of mantle flow is poorly known(7). Here we show that the time dependence of global-scale mantle flow can be deduced from the net behaviour of surface plate motions. In particular, we tracked the geographic locations of net convergence and divergence for harmonic degrees 1 and 2 by computing the dipole and quadrupole moments of plate motions from tectonic reconstructions(8,9) extended back to the early Mesozoic era. For present-day plate motions, we find dipole convergence in eastern Asia and quadrupole divergence in both central Africa and the central Pacific. These orientations are nearly identical to the dipole and quadrupole orientations of underlying mantle flow, which indicates that these 'net characteristics' of plate motions reveal deeper flow patterns. The positions of quadrupole divergence have not moved significantly during the past 250 million years, which suggests long-term stability of mantle upwelling beneath Africa and the Pacific Ocean. These upwelling locations are positioned above two compositionally and seismologically distinct(10) regions of the lowermost mantle, which may organize global mantle flow(11) as they remain stationary over geologic time(12).
C1 [Conrad, Clinton P.] Univ Hawaii Manoa, SOEST, Dept Geol & Geophys, Honolulu, HI 96822 USA.
   [Steinberger, Bernhard] GFZ German Res Ctr Geosci, Helmholtz Ctr Potsdam, D-14473 Potsdam, Germany.
   [Steinberger, Bernhard; Torsvik, Trond H.] Univ Oslo, CEED, N-0316 Oslo, Norway.
   [Torsvik, Trond H.] Geol Survey Norway, NO-7491 Trondheim, Norway.
   [Torsvik, Trond H.] Univ Witwatersrand, Sch Geosci, ZA-2050 Johannesburg, South Africa.
C3 University of Hawaii System; University of Hawaii Manoa; Helmholtz Association; GFZ Helmholtz Centre for Geosciences; University of Oslo; Geological Survey of Norway; University of Witwatersrand
RP Conrad, CP (corresponding author), Univ Hawaii Manoa, SOEST, Dept Geol & Geophys, Honolulu, HI 96822 USA.
EM clintc@hawaii.edu
FU NSF [EAR-1151241]; ERC [267631]; European Research Council (ERC) [267631] Funding Source: European Research Council (ERC); Directorate For Geosciences [1151241] Funding Source: National Science Foundation; Division Of Earth Sciences [1151241] Funding Source: National Science Foundation
NR 30
TC 77
Z9 90
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 JUN 27
PY 2013
VL 498
IS 7455
BP 479
EP 482
DI 10.1038/nature12203
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 171LH
UT WOS:000320929400051
PM 23803848
DA 2026-03-09
ER

PT J
AU Cebula, A
   Seweryn, M
   Rempala, GA
   Pabla, SS
   McIndoe, RA
   Denning, TL
   Bry, L
   Kraj, P
   Kisielow, P
   Ignatowicz, L
AF Cebula, Anna
   Seweryn, Michal
   Rempala, Grzegorz A.
   Pabla, Simarjot Singh
   McIndoe, Richard A.
   Denning, Timothy L.
   Bry, Lynn
   Kraj, Piotr
   Kisielow, Pawel
   Ignatowicz, Leszek
TI Thymus-derived regulatory T cells contribute to tolerance to commensal microbiota
SO NATURE
LA English
DT Article
ID self; selection; antigen
AB Peripheral mechanisms preventing autoimmunity and maintaining tolerance to commensal microbiota involve CD4(+) Foxp3(+) regulatory T (T-reg) cells(1,2) generated in the thymus or extrathymically by induction of naive CD4(+) Foxp3(-) T cells. Previous studies suggested that the T-cell receptor repertoires of thymic T-reg cells and induced T-reg cells are biased towards self and non-self antigens, respectively(3-6), but their relative contribution in controlling immunopathology, such as colitis and other untoward inflammatory responses triggered by different types of antigens, remains unresolved(7). The intestine, and especially the colon, is a particularly suitable organ to study this question, given the variety of self-, microbiota- and food-derived antigens to which T-reg cells and other T-cell populations are exposed. Intestinal environments can enhance conversion to a regulatory lineage(8,9) and favour tolerogenic presentation of antigens to naive CD4(+) T cells(10,11), suggesting that intestinal homeostasis depends on microbiota-specific induced T-reg cells(12-15). Here, to identify the origin and antigen-specificity of intestinal T-reg cells, we performed single-cell and high-throughput sequencing of the T-cell receptor repertoires of CD4(+) Foxp3(+) and CD4(+) Foxp3(-) T cells, and analysed their reactivity against specific commensal species. We show that thymus-derived T-reg cells constitute most T-reg cells in all lymphoid and intestinal organs, including the colon, where their repertoire is heavily influenced by the composition of the microbiota. Our results suggest that thymic T-reg cells, and not induced T-reg cells, dominantly mediate tolerance to antigens produced by intestinal commensals.
C1 [Cebula, Anna; Pabla, Simarjot Singh; McIndoe, Richard A.; Kraj, Piotr; Ignatowicz, Leszek] Georgia Regents Univ, Ctr Biotechnol & Genom Med, Augusta, GA 30912 USA.
   [Seweryn, Michal; Rempala, Grzegorz A.] Ohio State Univ, Coll Publ Hlth, Math Biosci Inst, Columbus, OH 43210 USA.
   [Seweryn, Michal] Univ Lodz, Fac Math & Comp Sci, PL-90238 Lodz, Poland.
   [Denning, Timothy L.] Emory Univ, Dept Pediat, Atlanta, GA 30329 USA.
   [Bry, Lynn] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA.
   [Kisielow, Pawel] Ludwik Hirszfeld Inst Immunol & Expt Therapy, Dept Tumor Immunol, PL-53114 Wroclaw, Poland.
C3 University System of Georgia; Augusta University; University System of Ohio; Ohio State University; University of Lodz; Emory University; Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Brigham & Women's Hospital; Polish Academy of Sciences; Hirszfeld Institute of Immunology & Experimental Therapy of the Polish Academy of Sciences
RP Ignatowicz, L (corresponding author), Georgia Regents Univ, Ctr Biotechnol & Genom Med, Augusta, GA 30912 USA.
EM lignatowicz@gru.edu
FU National Institutes of Health (NIH) [AI 5R01AI079277, DMS1106485, R01CA152158]; Brigham and Women's Hospital in Boston, Massachusetts;  [P30-DK034854]; National Institute of Diabetes and Digestive and Kidney Diseases [P30DK034854] Funding Source: NIH RePORTER; Direct For Mathematical & Physical Scien; Division Of Mathematical Sciences [1318886] Funding Source: National Science Foundation
NR 30
TC 307
Z9 368
U1 0
U2 67
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 9
PY 2013
VL 497
IS 7448
BP 258
EP +
DI 10.1038/nature12079
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 139CD
UT WOS:000318558200040
PM 23624374
DA 2026-03-09
ER

PT J
AU Reinhard, CT
   Planavsky, NJ
   Lyons, TW
AF Reinhard, Christopher T.
   Planavsky, Noah J.
   Lyons, Timothy W.
TI Long-term sedimentary recycling of rare sulphur isotope anomalies
SO NATURE
LA English
DT Article
ID mass-independent sulfur; modeling atmospheric o-2; oxygen; co2; evolution; earth; fluctuations; proportions; oxidation; cycles
AB The accumulation of substantial quantities of O-2 in the atmosphere has come to control the chemistry and ecological structure of Earth's surface. Non-mass-dependent (NMD) sulphur isotope anomalies in the rock record(1) are the central tool used to reconstruct the redox history of the early atmosphere. The generation and initial delivery of these anomalies to marine sediments requires low partial pressures of atmospheric O-2 (p(O2); refs 2, 3), and the disappearance of NMD anomalies from the rock record 2.32 billion years ago(1,4) is thought to have signalled a departure from persistently low atmospheric oxygen levels (less than about 10(-5) times the present atmospheric level) during approximately the first two billion years of Earth's history. Here we present a model study designed to describe the long-term surface recycling of crustal NMD anomalies, and show that the record of this geochemical signal is likely to display a 'crustalmemory effect' following increases in atmospheric p(O2) above this threshold. Once NMD anomalies have been buried in the upper crust they are extremely resistant to removal, and can be erased only through successive cycles of weathering, dilution and burial on an oxygenated Earth surface. This recycling results in the residual incorporation ofNMDanomalies into the sedimentary record long after synchronous atmospheric generation of the isotopic signal has ceased, with dynamic and measurable signals probably surviving for as long as 10-100 million years subsequent to an increase in atmospheric p(O2) to more than 10(-5) times the present atmospheric level. Our results can reconcile geochemical evidence for oxygen production and transient accumulation with the maintenance of NMD anomalies on the early Earth(5-8), and suggest that future work should investigate the notion that temporally continuous generation of new NMD sulphur isotope anomalies in the atmosphere was likely to have ceased long before their ultimate disappearance from the rock record.
C1 [Reinhard, Christopher T.; Planavsky, Noah J.] CALTECH, Div Geol & Planetary Sci, Pasadena, CA 91126 USA.
   [Reinhard, Christopher T.; Planavsky, Noah J.; Lyons, Timothy W.] Univ Calif Riverside, Dept Earth Sci, Riverside, CA 92521 USA.
C3 California Institute of Technology; University of California System; University of California Riverside
RP Reinhard, CT (corresponding author), CALTECH, Div Geol & Planetary Sci, Pasadena, CA 91126 USA.
EM reinhard@caltech.edu
FU NSF-EAR; NASA Exobiology Program; O. K. Earl Postdoctoral Fellowship in Geological and Planetary Sciences at the California Institute of Technology; NSF-EAR-PDF; Directorate For Geosciences; Division Of Earth Sciences [1144317, 0951998] Funding Source: National Science Foundation
NR 52
TC 86
Z9 97
U1 1
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 MAY 2
PY 2013
VL 497
IS 7447
BP 100
EP +
DI 10.1038/nature12021
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 134OK
UT WOS:000318221500041
PM 23615613
DA 2026-03-09
ER

PT J
AU McShane, LM
   Cavenagh, MM
   Lively, TG
   Eberhard, DA
   Bigbee, WL
   Williams, PM
   Mesirov, JP
   Polley, MYC
   Kim, KY
   Tricoli, JV
   Taylor, JMG
   Shuman, DJ
   Simon, RM
   Doroshow, JH
   Conley, BA
AF McShane, Lisa M.
   Cavenagh, Margaret M.
   Lively, Tracy G.
   Eberhard, David A.
   Bigbee, William L.
   Williams, P. Mickey
   Mesirov, Jill P.
   Polley, Mei-Yin C.
   Kim, Kelly Y.
   Tricoli, James V.
   Taylor, Jeremy M. G.
   Shuman, Deborah J.
   Simon, Richard M.
   Doroshow, James H.
   Conley, Barbara A.
TI Criteria for the use of omics-based predictors in clinical trials
SO NATURE
LA English
DT Article
ID microarray; biomarkers
AB The US National Cancer Institute (NCI), in collaboration with scientists representing multiple areas of expertise relevant to 'omics'-based test development, has developed a checklist of criteria that can be used to determine the readiness of omics-based tests for guiding patient care in clinical trials. The checklist criteria cover issues relating to specimens, assays, mathematical modelling, clinical trial design, and ethical, legal and regulatory aspects. Funding bodies and journals are encouraged to consider the checklist, which they may find useful for assessing study quality and evidence strength. The checklist will be used to evaluate proposals for NCI-sponsored clinical trials in which omics tests will be used to guide therapy.
C1 [McShane, Lisa M.; Cavenagh, Margaret M.; Lively, Tracy G.; Polley, Mei-Yin C.; Kim, Kelly Y.; Tricoli, James V.; Shuman, Deborah J.; Simon, Richard M.; Doroshow, James H.; Conley, Barbara A.] NCI, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA.
   [Eberhard, David A.] Univ N Carolina, Dept Pathol, Chapel Hill, NC 27599 USA.
   [Eberhard, David A.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA.
   [Bigbee, William L.] Univ Pittsburgh, Sch Med, Dept Pathol, Pittsburgh, PA 15213 USA.
   [Bigbee, William L.] Univ Pittsburgh, Sch Med, Inst Canc, Hillman Canc Ctr, Pittsburgh, PA 15213 USA.
   [Williams, P. Mickey] NCI, Frederick Natl Lab Canc Res, NIH, Frederick, MD 21702 USA.
   [Mesirov, Jill P.] MIT, Broad Inst, Cambridge, MA 02142 USA.
   [Mesirov, Jill P.] Harvard Univ, Cambridge, MA 02142 USA.
   [Taylor, Jeremy M. G.] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.
C3 National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); NIH Division of Cancer Treatment & Diagnosis; University of North Carolina; University of North Carolina Chapel Hill; University of North Carolina; University of North Carolina Chapel Hill; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); Frederick National Laboratory for Cancer Research; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Harvard University; University of Michigan System; University of Michigan
RP McShane, LM (corresponding author), NCI, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA.
EM mcshanel@ctep.nci.nih.gov
FU National Cancer Institute [R01CA129102, P30CA046592, ZIABC011078] Funding Source: NIH RePORTER; NCI NIH HHS [P30 CA046592, R01 CA129102] Funding Source: Medline; Intramural NIH HHS [Z99 CA999999] Funding Source: Medline
NR 18
TC 172
Z9 193
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 OCT 17
PY 2013
VL 502
IS 7471
BP 317
EP 320
DI 10.1038/nature12564
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 235GY
UT WOS:000325706300042
PM 24132288
DA 2026-03-09
ER

PT J
AU Zaidi, S
   Choi, M
   Wakimoto, H
   Ma, LJ
   Jiang, JM
   Overton, JD
   Romano-Adesman, A
   Bjornson, RD
   Breitbart, RE
   Brown, KK
   Carriero, NJ
   Cheung, YH
   Deanfield, J
   DePalma, S
   Fakhro, KA
   Glessner, J
   Hakonarson, H
   Italia, MJ
   Kaltman, JR
   Kaski, J
   Kim, R
   Kline, JK
   Lee, T
   Leipzig, J
   Lopez, A
   Mane, SM
   Mitchell, LE
   Newburger, JW
   Parfenov, M
   Pe'er, I
   Porter, G
   Roberts, AE
   Sachidanandam, R
   Sanders, SJ
   Seiden, HS
   State, MW
   Subramanian, S
   Tikhonova, IR
   Wang, W
   Warburton, D
   White, PS
   Williams, IA
   Zhao, HY
   Seidman, JG
   Brueckner, M
   Chung, WK
   Gelb, BD
   Goldmuntz, E
   Seidman, CE
   Lifton, RP
AF Zaidi, Samir
   Choi, Murim
   Wakimoto, Hiroko
   Ma, Lijiang
   Jiang, Jianming
   Overton, John D.
   Romano-Adesman, Angela
   Bjornson, Robert D.
   Breitbart, Roger E.
   Brown, Kerry K.
   Carriero, Nicholas J.
   Cheung, Yee Him
   Deanfield, John
   DePalma, Steve
   Fakhro, Khalid A.
   Glessner, Joseph
   Hakonarson, Hakon
   Italia, Michael J.
   Kaltman, Jonathan R.
   Kaski, Juan
   Kim, Richard
   Kline, Jennie K.
   Lee, Teresa
   Leipzig, Jeremy
   Lopez, Alexander
   Mane, Shrikant M.
   Mitchell, Laura E.
   Newburger, Jane W.
   Parfenov, Michael
   Pe'er, Itsik
   Porter, George
   Roberts, Amy E.
   Sachidanandam, Ravi
   Sanders, Stephan J.
   Seiden, Howard S.
   State, Mathew W.
   Subramanian, Sailakshmi
   Tikhonova, Irina R.
   Wang, Wei
   Warburton, Dorothy
   White, Peter S.
   Williams, Ismee A.
   Zhao, Hongyu
   Seidman, Jonathan G.
   Brueckner, Martina
   Chung, Wendy K.
   Gelb, Bruce D.
   Goldmuntz, Elizabeth
   Seidman, Christine E.
   Lifton, Richard P.
TI De novo mutations in histone-modifying genes in congenital heart disease
SO NATURE
LA English
DT Article
ID copy-number variants; autism spectrum; family; risk
AB Congenital heart disease (CHD) is the most frequent birth defect, affecting 0.8% of live births(1). Many cases occur sporadically and impair reproductive fitness, suggesting a role for de novo mutations. Here we compare the incidence of de novo mutations in 362 severe CHD cases and 264 controls by analysing exome sequencing of parent-offspring trios. CHD cases show a significant excess of protein-altering de novo mutations in genes expressed in the developing heart, with an odds ratio of 7.5 for damaging (premature termination, frameshift, splice site) mutations. Similar odds ratios are seen across the main classes of severe CHD. We find a marked excess of de novo mutations in genes involved in the production, removal or reading of histone 3 lysine 4 (H3K4) methylation, or ubiquitination of H2BK120, which is required for H3K4 methylation(2-4). There are also two de novo mutations in SMAD2, which regulates H3K27 methylation in the embryonic left-right organizer(5). The combination of both activating (H3K4 methylation) and inactivating (H3K27 methylation) chromatin marks characterizes 'poised' promoters and enhancers, which regulate expression of key developmental genes(6). These findings implicate de novo point mutations in several hundreds of genes that collectively contribute to approximately 10% of severe CHD.
C1 [Zaidi, Samir; Choi, Murim; Overton, John D.; Fakhro, Khalid A.; Lopez, Alexander; Mane, Shrikant M.; Sanders, Stephan J.; State, Mathew W.; Tikhonova, Irina R.; Zhao, Hongyu; Brueckner, Martina; Lifton, Richard P.] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06504 USA.
   [Zaidi, Samir; Choi, Murim; Fakhro, Khalid A.; Lifton, Richard P.] Yale Univ, Howard Hughes Med Inst, New Haven, CT 06510 USA.
   [Wakimoto, Hiroko; Jiang, Jianming; Brown, Kerry K.; DePalma, Steve; Parfenov, Michael; Seidman, Jonathan G.; Seidman, Christine E.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
   [Ma, Lijiang; Lee, Teresa; Warburton, Dorothy; Williams, Ismee A.; Chung, Wendy K.] Columbia Univ, Med Ctr, Dept Pediat, New York, NY 10032 USA.
   [Jiang, Jianming; Seidman, Christine E.] Harvard Univ, Howard Hughes Med Inst, Boston, MA 02115 USA.
   [Overton, John D.; Lopez, Alexander; Mane, Shrikant M.; Tikhonova, Irina R.; Lifton, Richard P.] Yale Ctr Mendelian Genom, New Haven, CT 06510 USA.
   [Overton, John D.; Bjornson, Robert D.; Carriero, Nicholas J.; Lopez, Alexander; Mane, Shrikant M.; Tikhonova, Irina R.; Lifton, Richard P.] Yale Univ, Yale Ctr Genome Anal, New Haven, CT 06511 USA.
   [Romano-Adesman, Angela] Steven & Alexandra Cohen Childrens Med Ctr New Yo, New Hyde Pk, NY 11040 USA.
   [Bjornson, Robert D.; Carriero, Nicholas J.] Yale Univ, Dept Comp Sci, New Haven, CT 06511 USA.
   [Breitbart, Roger E.; Newburger, Jane W.; Roberts, Amy E.] Childrens Hosp, Dept Cardiol, Boston, MA 02115 USA.
   [Cheung, Yee Him] Columbia Univ, Mailman Sch Publ Hlth, Dept Biostat, New York, NY 10032 USA.
   [Deanfield, John; Kaski, Juan] Great Ormond St Hosp Sick Children, Univ Coll London, Dept Cardiol, London WC1N 3JH, England.
   [Glessner, Joseph; Hakonarson, Hakon] Childrens Hosp Philadelphia, Ctr Appl Genom, Philadelphia, PA 19104 USA.
   [Hakonarson, Hakon; White, Peter S.; Goldmuntz, Elizabeth] Univ Penn, Perelman Sch Med, Dept Pediat, Philadelphia, PA 19104 USA.
   [Italia, Michael J.; Leipzig, Jeremy; Wang, Wei; White, Peter S.] Childrens Hosp Philadelphia, Ctr Biomed Informat, Philadelphia, PA 19104 USA.
   [Kaltman, Jonathan R.] NHLBI, NIH, Bethesda, MD 20892 USA.
   [Kim, Richard] Univ So Calif, Keck Sch Med, Sect Cardiothorac Surg, Los Angeles, CA 90089 USA.
   [Kline, Jennie K.] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY 10032 USA.
   [Mitchell, Laura E.] Univ Texas Sch Publ Hlth, Div Epidemiol Human Genet & Environm Sci, Houston, TX 77030 USA.
   [Pe'er, Itsik] Columbia Univ, Dept Comp Sci, New York, NY 10032 USA.
   [Porter, George] Univ Rochester, Sch Med & Dent, Med Ctr, Dept Pediat, Rochester, NY 14611 USA.
   [Sachidanandam, Ravi; Subramanian, Sailakshmi; Gelb, Bruce D.] Icahn Sch Med Mt Sinai, New York, NY 10029 USA.
   [Sanders, Stephan J.; State, Mathew W.] Yale Univ, Dept Psychiat, Ctr Child Study, Program Neurogenet, New Haven, CT 06510 USA.
   [Seiden, Howard S.; Gelb, Bruce D.] Icahn Sch Med Mt Sinai, Dept Pediat, New York, NY 10029 USA.
   [Wang, Wei] New Jersey Inst Technol, Dept Comp Sci, Newark, NJ 07102 USA.
   [Warburton, Dorothy] Columbia Univ, Med Ctr, Dept Pathol, New York, NY 10032 USA.
   [Zhao, Hongyu] Yale Univ, Sch Publ Hlth, Dept Biostat, New Haven, CT 06510 USA.
   [Brueckner, Martina] Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06510 USA.
   [Chung, Wendy K.] Columbia Univ, Med Ctr, Dept Med, New York, NY 10032 USA.
   [Gelb, Bruce D.] Icahn Sch Med Mt Sinai, Mindich Child Hlth & Dev Inst, New York, NY 10029 USA.
   [Goldmuntz, Elizabeth] Univ Penn, Perelman Sch Med, Childrens Hosp Philadelphia, Div Cardiol, Philadelphia, PA 19104 USA.
   [Seidman, Christine E.] Harvard Univ, Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA.
   [Lifton, Richard P.] Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06510 USA.
C3 Yale University; Howard Hughes Medical Institute; Yale University; Harvard University; Harvard Medical School; Columbia University; Howard Hughes Medical Institute; Harvard University; Yale University; Northwell Health; North Shore University Hospital; Steven & Alexandra Cohen Children's Medical Center of New York; Yale University; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Columbia University; University of London; University College London; Great Ormond Street Hospital for Children NHS Foundation Trust; University of Pennsylvania; Pennsylvania Medicine; Childrens Hospital of Philadelphia; University of Pennsylvania; University of Pennsylvania; Pennsylvania Medicine; Childrens Hospital of Philadelphia; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI); University of Southern California; Columbia University; University of Texas System; University of Texas Health Science Center Houston; University of Texas School Public Health; Columbia University; University of Rochester; Icahn School of Medicine at Mount Sinai; Yale University; Icahn School of Medicine at Mount Sinai; New Jersey Institute of Technology; Columbia University; Yale University; Yale University; Columbia University; Icahn School of Medicine at Mount Sinai; University of Pennsylvania; Pennsylvania Medicine; Childrens Hospital of Philadelphia; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Yale University
RP Brueckner, M (corresponding author), Yale Univ, Sch Med, Dept Genet, 333 Cedar St, New Haven, CT 06504 USA.
EM martina.brueckner@yale.edu; wkc15@cumc.columbia.edu; bruce.gelb@mssm.edu; goldmuntz@email.chop.edu; csediman@genetics.med.harvard.edu; richard.lifton@yale.edu
FU National Institutes of Health (NIH) National Heart, Lung, and Blood Institute (NHLBI) Pediatric Cardiac Genomics Consortium [U01-HL098188, U01-HL098147, U01-HL098153, U01-HL098163, U01-HL098123, U01-HL098162]; Simons Foundation for Autism Research; NIH Centers for Mendelian Genomics [5U54HG006504]; National Heart Lung and Blood Institute [U01HL098147, U01HL098162] Funding Source: NIH RePORTER; National Institute of Diabetes and Digestive and Kidney Diseases [P30DK079310] Funding Source: NIH RePORTER
NR 30
TC 754
Z9 883
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 JUN 13
PY 2013
VL 498
IS 7453
BP 220
EP +
DI 10.1038/nature12141
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 162RR
UT WOS:000320283400046
PM 23665959
DA 2026-03-09
ER

PT J
AU Kretz, M
   Siprashvili, Z
   Chu, C
   Webster, DE
   Zehnder, A
   Qu, K
   Lee, CS
   Flockhart, RJ
   Groff, AF
   Chow, J
   Johnston, D
   Kim, GE
   Spitale, RC
   Flynn, RA
   Zheng, GXY
   Aiyer, S
   Raj, A
   Rinn, JL
   Chang, HY
   Khavari, PA
AF Kretz, Markus
   Siprashvili, Zurab
   Chu, Ci
   Webster, Dan E.
   Zehnder, Ashley
   Qu, Kun
   Lee, Carolyn S.
   Flockhart, Ross J.
   Groff, Abigail F.
   Chow, Jennifer
   Johnston, Danielle
   Kim, Grace E.
   Spitale, Robert C.
   Flynn, Ryan A.
   Zheng, Grace X. Y.
   Aiyer, Subhadra
   Raj, Arjun
   Rinn, John L.
   Chang, Howard Y.
   Khavari, Paul A.
TI Control of somatic tissue differentiation by the long non-coding RNA TINCR
SO NATURE
LA English
DT Article
ID gene; chromatin; complexes; repression; expression; mutations; staufen; suite; shape
AB Several of the thousands of human long non-coding RNAs (lncRNAs) have been functionally characterized(1-4); however, potential roles for lncRNAs in somatic tissue differentiation remain poorly understood. Here we show that a 3.7-kilobase lncRNA, terminal differentiation-induced ncRNA (TINCR), controls human epidermal differentiation by a post-transcriptional mechanism. TINCR is required for high messenger RNA abundance of key differentiation genes, many of which are mutated in human skin diseases, including FLG, LOR, ALOXE3, ALOX12B, ABCA12, CASP14 and ELOVL3. TINCR-deficient epidermis lacked terminal differentiation ultrastructure, including keratohyalin granules and intact lamellar bodies. Genome-scale RNA interactome analysis revealed that TINCR interacts with a range of differentiation mRNAs. TINCR-mRNA interaction occurs through a 25-nucleotide 'TINCR box' motif that is strongly enriched in interacting mRNAs and required for TINCR binding. A high-throughput screen to analyse TINCR binding capacity to approximately 9,400 human recombinant proteins revealed direct binding of TINCR RNA to the staufen1 (STAU1) protein. STAU1-deficient tissue recapitulated the impaired differentiation seen with TINCR depletion. Loss of UPF1 and UPF2, both of which are required for STAU1-mediated RNA decay, however, did not have differentiation effects. Instead, the TINCR-STAU1 complex seems to mediate stabilization of differentiation mRNAs, such as KRT80. These data identify TINCR as a key lncRNA required for somatic tissue differentiation, which occurs through lncRNA binding to differentiation mRNAs to ensure their expression.
C1 [Kretz, Markus; Siprashvili, Zurab; Chu, Ci; Webster, Dan E.; Zehnder, Ashley; Qu, Kun; Lee, Carolyn S.; Flockhart, Ross J.; Groff, Abigail F.; Chow, Jennifer; Johnston, Danielle; Kim, Grace E.; Spitale, Robert C.; Flynn, Ryan A.; Zheng, Grace X. Y.; Chang, Howard Y.; Khavari, Paul A.] Stanford Univ, Sch Med, Program Epithelial Biol, Stanford, CA 94305 USA.
   [Aiyer, Subhadra; Raj, Arjun] Univ Penn, Dept Bioengn, Philadelphia, PA 19104 USA.
   [Rinn, John L.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA.
   [Chang, Howard Y.] Howard Hughes Med Inst, Stanford, CA 94305 USA.
   [Khavari, Paul A.] Vet Affairs Palo Alto Healthcare Syst, Palo Alto, CA 94304 USA.
C3 Stanford University; University of Pennsylvania; Harvard University; Howard Hughes Medical Institute; US Department of Veterans Affairs; Veterans Health Administration (VHA); VA Palo Alto Health Care System
RP Chang, HY (corresponding author), Stanford Univ, Sch Med, Program Epithelial Biol, Stanford, CA 94305 USA.
EM howchang@stanford.edu; khavari@stanford.edu
FU US Veterans Affairs Office of Research and Development; National Institutes of Health (National Institute of Arthritis and Musculoskeletal and Skin Diseases) [AR49737]; NIH [R01-HG004361]; California Institute for Regenerative Medicine; National Cancer Institute [T32CA009302] Funding Source: NIH RePORTER; National Institute of Arthritis and Musculoskeletal and Skin Diseases [R01AR049737, T32AR007422] Funding Source: NIH RePORTER
NR 37
TC 785
Z9 937
U1 1
U2 204
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 10
PY 2013
VL 493
IS 7431
BP 231
EP U245
DI 10.1038/nature11661
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 066YY
UT WOS:000313259600041
PM 23201690
DA 2026-03-09
ER

PT J
AU Kosaka, Y
   Xie, SP
AF Kosaka, Yu
   Xie, Shang-Ping
TI Recent global-warming hiatus tied to equatorial Pacific surface cooling
SO NATURE
LA English
DT Article
ID atmospheric bridge; precipitation; variability; climatology
AB Despite the continued increase in atmospheric greenhouse gas concentrations, the annual-mean global temperature has not risen in the twenty-first century(1,2), challenging the prevailing view that anthropogenic forcing causes climate warming. Various mechanisms have been proposed for this hiatus in global warming(3-6), but their relative importance has not been quantified, hampering observational estimates of climate sensitivity. Here we show that accounting for recent cooling in the eastern equatorial Pacific reconciles climate simulations and observations. We present a novel method of uncovering mechanisms for global temperature change by prescribing, in addition to radiative forcing, the observed history of sea surface temperature over the central to eastern tropical Pacific in a climate model. Although the surface temperature prescription is limited to only 8.2% of the global surface, our model reproduces the annual-mean global temperature remarkably well with correlation coefficient r = 0.97 for 1970-2012 (which includes the current hiatus and a period of accelerated global warming). Moreover, our simulation captures major seasonal and regional characteristics of the hiatus, including the intensified Walker circulation, the winter cooling in northwestern North America and the prolonged drought in the southern USA. Our results show that the current hiatus is part of natural climate variability, tied specifically to a La-Nina-like decadal cooling. Although similar decadal hiatus events may occur in the future, the multi-decadal warming trend is very likely to continue with greenhouse gas increase.
C1 [Kosaka, Yu; Xie, Shang-Ping] Univ Calif San Diego, Scripps Inst Oceanog, La Jolla, CA 92093 USA.
   [Xie, Shang-Ping] Ocean Univ China, Phys Oceanog Lab, Qingdao 266100, Peoples R China.
   [Xie, Shang-Ping] Ocean Univ China, Ocean Atmosphere Interact & Climate Lab, Qingdao 266100, Peoples R China.
   [Xie, Shang-Ping] Univ Hawaii Manoa, SOEST, Int Pacific Res Ctr, Honolulu, HI 96822 USA.
C3 University of California System; University of California San Diego; Scripps Institution of Oceanography; Ocean University of China; Ocean University of China; University of Hawaii System; University of Hawaii Manoa
RP Xie, SP (corresponding author), Univ Calif San Diego, Scripps Inst Oceanog, 9500 Gilman Dr MC206, La Jolla, CA 92093 USA.
EM sxie@ucsd.edu
FU NSF [ATM-0854365]; National Basic Research Program of China [2012CB955600]; NOAA [NA10OAR4310250]; Grants-in-Aid for Scientific Research [25287120] Funding Source: KAKEN; Div Atmospheric & Geospace Sciences; Directorate For Geosciences [1305719] Funding Source: National Science Foundation
NR 30
TC 1369
Z9 1583
U1 7
U2 774
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 19
PY 2013
VL 501
IS 7467
BP 403
EP +
DI 10.1038/nature12534
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 219XT
UT WOS:000324545700042
PM 23995690
DA 2026-03-09
ER

PT J
AU Fang, LH
   Choi, SH
   Baek, JS
   Liu, C
   Almazan, F
   Ulrich, F
   Wiesner, P
   Taleb, A
   Deer, E
   Pattison, J
   Torres-Vázquez, J
   Li, AC
   Miller, YI
AF Fang, Longhou
   Choi, Soo-Ho
   Baek, Ji Sun
   Liu, Chao
   Almazan, Felicidad
   Ulrich, Florian
   Wiesner, Philipp
   Taleb, Adam
   Deer, Elena
   Pattison, Jennifer
   Torres-Vazquez, Jesus
   Li, Andrew C.
   Miller, Yury I.
TI Control of angiogenesis by AIBP-mediated cholesterol efflux
SO NATURE
LA English
DT Article
ID embryonic vascular development; cassette transporter 1; i binding-protein; endothelial-cells; tangier-disease; zebrafish; expression; abcg1; gene; activation
AB Cholesterol is a structural component of the cell and is indispensable for normal cellular function, although its excess often leads to abnormal proliferation, migration, inflammatory responses and/or cell death. To prevent cholesterol overload, ATP-binding cassette (ABC) transporters mediate cholesterol efflux from the cells to apolipoprotein A-I (apoA-I) and the apoA-I-containing high-density lipoprotein (HDL)(1-3). Maintaining efficient cholesterol efflux is essential for normal cellular function(4-6). However, the role of cholesterol efflux in angiogenesis and the identity of its local regulators are poorly understood. Here we show that apoA-I binding protein (AIBP) accelerates cholesterol efflux from endothelial cells to HDL and thereby regulates angiogenesis. AIBP- and HDL-mediated cholesterol depletion reduces lipid rafts, interferes with VEGFR2 (also known as KDR) dimerization and signalling and inhibits vascular endothelial growth factor-induced angiogenesis in vitro and mouse aortic neovascularization ex vivo. Notably, Aibp, a zebrafish homologue of human AIBP, regulates the membrane lipid order in embryonic zebrafish vasculature and functions as a non-cell-autonomous regulator of angiogenesis. aibp knockdown results in dysregulated sprouting/branching angiogenesis, whereas forced Aibp expression inhibits angiogenesis. Dysregulated angiogenesis is phenocopied in Abca1 (also known as Abca1a) Abcg1-deficient embryos, and cholesterol levels are increased in Aibp-deficient and Abca1Abcg1-deficient embryos. Our findings demonstrate that secreted AIBP positively regulates cholesterol efflux from endothelial cells and that effective cholesterol efflux is critical for proper angiogenesis.
C1 [Fang, Longhou; Choi, Soo-Ho; Baek, Ji Sun; Liu, Chao; Almazan, Felicidad; Wiesner, Philipp; Taleb, Adam; Deer, Elena; Pattison, Jennifer; Li, Andrew C.; Miller, Yury I.] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA.
   [Ulrich, Florian; Torres-Vazquez, Jesus] NYU, Langone Med Ctr, Skirball Inst Biomol Med, Helen L & Martin S Kimmel Ctr Biol & Med, New York, NY 10016 USA.
C3 University of California System; University of California San Diego; New York University; NYU Langone Medical Center
RP Miller, YI (corresponding author), Univ Calif San Diego, Dept Med, 9500 Gilman Dr, La Jolla, CA 92093 USA.
EM yumiller@ucsd.edu
FU NIH [HL093767, HL055798, HL114734]; UC Tobacco-Related Disease Program [18FT-0137]; UCSD [P30NS047101]; National Institute of Neurological Disorders and Stroke [P30NS047101] Funding Source: NIH RePORTER
NR 42
TC 173
Z9 194
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 JUN 6
PY 2013
VL 498
IS 7452
BP 118
EP +
DI 10.1038/nature12166
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 158DC
UT WOS:000319947800045
PM 23719382
DA 2026-03-09
ER

PT J
AU Blaschke, K
   Ebata, KT
   Karimi, MM
   Zepeda-Martínez, JA
   Goyal, P
   Mahapatra, S
   Tam, A
   Laird, DJ
   Hirst, M
   Rao, A
   Lorincz, MC
   Ramalho-Santos, M
AF Blaschke, Kathryn
   Ebata, Kevin T.
   Karimi, Mohammad M.
   Zepeda-Martinez, Jorge A.
   Goyal, Preeti
   Mahapatra, Sahasransu
   Tam, Angela
   Laird, Diana J.
   Hirst, Martin
   Rao, Anjana
   Lorincz, Matthew C.
   Ramalho-Santos, Miguel
TI Vitamin C induces Tet-dependent DNA demethylation and a blastocyst-like state in ES cells
SO NATURE
LA English
DT Article
ID ground-state; methylation; 5-hydroxymethylcytosine; dynamics; genes; pluripotency; dioxygenase; generation; parallel; tool
AB DNA methylation is a heritable epigenetic modification involved in gene silencing, imprinting, and the suppression of retrotransposons(1). Global DNA demethylation occurs in the early embryo and the germ line(2,3), and may be mediated by Tet (ten eleven translocation) enzymes(4-6), which convert 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC)(7). Tet enzymes have been studied extensively in mouse embryonic stem (ES) cells(8-12), which are generally cultured in the absence of vitamin C, a potential cofactor for Fe(II) 2-oxoglutarate dioxygenase enzymes such as Tet enzymes. Here we report that addition of vitamin C to mouse ES cells promotes Tet activity, leading to a rapid and global increase in 5hmC. This is followed by DNA demethylation of many gene promoters and upregulation of demethylated germline genes. Tet1 binding is enriched near the transcription start site of genes affected by vitamin C treatment. Importantly, vitamin C, but not other antioxidants, enhances the activity of recombinant Tet1 in a biochemical assay, and the vitamin-C-induced changes in 5hmC and 5mC are entirely suppressed in Tet1 and Tet2 double knockout ES cells. Vitamin C has a stronger effect on regions that gain methylation in cultured ES cells compared to blastocysts, and in vivo are methylated only after implantation. In contrast, imprinted regions and intracisternal A particle retroelements, which are resistant to demethylation in the early embryo(2,13), are resistant to vitamin-C-induced DNA demethylation. Collectively, the results of this study establish vitamin C as a direct regulator of Tet activity and DNA methylation fidelity in ES cells.
C1 [Blaschke, Kathryn; Ebata, Kevin T.; Laird, Diana J.; Ramalho-Santos, Miguel] Univ Calif San Francisco, Dept Obstet & Gynecol, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, San Francisco, CA 94143 USA.
   [Blaschke, Kathryn; Ebata, Kevin T.; Laird, Diana J.; Ramalho-Santos, Miguel] Univ Calif San Francisco, Ctr Reprod Sci, San Francisco, CA 94143 USA.
   [Karimi, Mohammad M.; Goyal, Preeti; Lorincz, Matthew C.] Univ British Columbia, Dept Med Genet, Inst Life Sci, Vancouver, BC V6T 1Z3, Canada.
   [Karimi, Mohammad M.; Tam, Angela; Hirst, Martin] British Columbia Canc Agcy, Canadas Michael Smith Genome Sci Ctr, Vancouver, BC V5Z 1L3, Canada.
   [Zepeda-Martinez, Jorge A.; Mahapatra, Sahasransu; Rao, Anjana] La Jolla Inst Allergy & Immunol, La Jolla, CA 92037 USA.
   [Zepeda-Martinez, Jorge A.; Mahapatra, Sahasransu; Rao, Anjana] Sanford Consortium Regenerat Med, La Jolla, CA 92037 USA.
   [Hirst, Martin] Univ British Columbia, Dept Microbiol & Immunol, Inst Life Sci, Vancouver, BC V6T 1Z3, Canada.
C3 University of California System; University of California San Francisco; University of California System; University of California San Francisco; University of British Columbia; British Columbia Cancer Agency; La Jolla Institute for Immunology; University of British Columbia
RP Lorincz, MC (corresponding author), Univ British Columbia, Dept Med Genet, Inst Life Sci, Vancouver, BC V6T 1Z3, Canada.
EM mlorincz@mail.ubc.ca; mrsantos@diabetes.ucsf.edu
FU NSF; California Institute of Regenerative Medicine postdoctoral training grant [TG2-01153]; Michael Smith Foundation for Health Research; CIHR [92093]; NIH [HD065812, CA151535, DP2OD004698, OD012204]; California Institute of Regenerative Medicine
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NR 42
TC 697
Z9 803
U1 3
U2 266
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 8
PY 2013
VL 500
IS 7461
BP 222
EP +
DI 10.1038/nature12362
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 197CH
UT WOS:000322825500038
PM 23812591
DA 2026-03-09
ER

PT J
AU Pirkkalainen, JM
   Cho, SU
   Li, J
   Paraoanu, GS
   Hakonen, PJ
   Sillanpää, MA
AF Pirkkalainen, J. -M.
   Cho, S. U.
   Li, Jian
   Paraoanu, G. S.
   Hakonen, P. J.
   Sillanpaa, M. A.
TI Hybrid circuit cavity quantum electrodynamics with a micromechanical resonator
SO NATURE
LA English
DT Article
ID ground-state; superconducting qubit; flux qubit; entanglement; oscillator; dynamics; motion
AB Hybrid quantum systems with inherently distinct degrees of freedom have a key role in many physical phenomena. Well-known examples include cavity quantum electrodynamics(1), trapped ions(2), and electrons and phonons in the solid state. In those systems, strong coupling makes the constituents lose their individual character and form dressed states, which represent a collective form of dynamics. As well as having fundamental importance, hybrid systems also have practical applications, notably in the emerging field of quantum information control. A promising approach is to combine long-lived atomic states(2,3) with the accessible electrical degrees of freedom in superconducting cavities and quantum bits(4,5) (qubits). Here we integrate circuit cavity quantum electrodynamics(6,7) with phonons. Apart from coupling to a microwave cavity, our superconducting transmon qubit(8), consisting of tunnel junctions and a capacitor, interacts with a phonon mode in a micromechanical resonator, and thus acts like an atom coupled to two different cavities. We measure the phonon Stark shift, as well as the splitting of the qubit spectral line into motional sidebands, which feature transitions between the dressed electromechanical states. In the time domain, we observe coherent conversion of qubit excitation to phonons as sideband Rabi oscillations. This is a model system with potential for a quantum interface, which may allow for storage of quantum information in long-lived phonon states, coupling to optical photons or for investigations of strongly coupled quantum systems near the classical limit.
C1 [Pirkkalainen, J. -M.; Cho, S. U.; Li, Jian; Paraoanu, G. S.; Hakonen, P. J.; Sillanpaa, M. A.] Aalto Univ, Low Temp Lab, FI-00076 Aalto, Finland.
C3 Aalto University
RP Pirkkalainen, JM (corresponding author), Aalto Univ, Low Temp Lab, POB 15100, FI-00076 Aalto, Finland.
EM juha.pirkkalainen@aalto.fi
FU Academy of Finland under CoE in Low Temperature Quantum Phenomena and Devices [141559]; European Research Council [240387-NEMSQED]; Vaisala Foundation; Emil Aaltonen Foundation; Kaute Foundation; NGSMP;  [EU-FP7-NMP-246026]; Academy of Finland (AKA) [141559] Funding Source: Academy of Finland (AKA)
NR 30
TC 249
Z9 274
U1 0
U2 176
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 14
PY 2013
VL 494
IS 7436
BP 211
EP 215
DI 10.1038/nature11821
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 092QS
UT WOS:000315137700034
PM 23407536
DA 2026-03-09
ER

PT J
AU Leconte, J
   Forget, F
   Charnay, B
   Wordsworth, R
   Pottier, A
AF Leconte, Jeremy
   Forget, Francois
   Charnay, Benjamin
   Wordsworth, Robin
   Pottier, Alizee
TI Increased insolation threshold for runaway greenhouse processes on Earth-like planets
SO NATURE
LA English
DT Article
ID general-circulation model; habitable zones; climate; atmosphere; temperatures; scattering; water; equilibrium; sensitivity; simulation
AB The increase in solar luminosity over geological timescales should warm the Earth's climate, increasing water evaporation, which will in turn enhance the atmospheric greenhouse effect. Above a certain critical insolation, this destabilizing greenhouse feedback can 'run away' until the oceans have completely evaporated(1-4). Through increases in stratospheric humidity, warming may also cause evaporative loss of the oceans to space before the runaway greenhouse state occurs(5,6). The critical insolation thresholds for these processes, however, remain uncertain because they have so far been evaluated using one-dimensional models that cannot account for the dynamical and cloud feedback effects that are key stabilizing features of the Earth's climate. Here we use a three-dimensional global climate model to show that the insolation threshold for the runaway greenhouse state to occur is about 375 W m(-2), which is significantly higher than previously thought(6,7). Our model is specifically developed to quantify the climate response of Earth-like planets to increased insolation in hot and extremely moist atmospheres. In contrast with previous studies, we find that clouds have a destabilizing feedback effect on the long-term warming. However, subsident, unsaturated regions created by the Hadley circulation have a stabilizing effect that is strong enough to shift the runaway greenhouse limit to higher values of insolation than are inferred from one-dimensional models. Furthermore, because of wavelength-dependent radiative effects, the stratosphere remains sufficiently cold and dry to hamper the escape of atmospheric water, even at large fluxes. This has strong implications for the possibility of liquid water existing on Venus early in its history, and extends the size of the habitable zone around other stars.
C1 [Leconte, Jeremy; Forget, Francois; Charnay, Benjamin; Pottier, Alizee] Inst Pierre Simon Laplace, Meteorol Dynam Lab, F-75252 Paris, France.
   [Wordsworth, Robin] Univ Chicago, Dept Geol Sci, Chicago, IL 60637 USA.
C3 Institut Polytechnique de Paris; Ecole Polytechnique; Universite Paris Saclay; Sorbonne Universite; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Earth Sciences & Astronomy (INSU); University of Chicago
RP Leconte, J (corresponding author), Inst Pierre Simon Laplace, Meteorol Dynam Lab, 4 Pl Jussieu,BP 99, F-75252 Paris, France.
EM jeremy.leconte@lmd.jussieu.fr
FU Region Ile-de-France; Div Atmospheric & Geospace Sciences; Directorate For Geosciences [0933936] Funding Source: National Science Foundation
NR 45
TC 236
Z9 267
U1 0
U2 80
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 12
PY 2013
VL 504
IS 7479
BP 268
EP +
DI 10.1038/nature12827
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 267TQ
UT WOS:000328121500034
PM 24336285
DA 2026-03-09
ER

PT J
AU Geibel, S
   Procko, E
   Hultgren, SJ
   Baker, D
   Waksman, G
AF Geibel, Sebastian
   Procko, Erik
   Hultgren, Scott J.
   Baker, David
   Waksman, Gabriel
TI Structural and energetic basis of folded-protein transport by the FimD usher
SO NATURE
LA English
DT Article
ID bacterial outer-membrane; crystal-structure; pilus; crystallography; refinement
AB Type 1 pili, produced by uropathogenic Escherichia coli, are multi-subunit fibres crucial in recognition of and adhesion to host tissues(1). During pilus biogenesis, subunits are recruited to an outer membrane assembly platform, the FimD usher, which catalyses their polymerization and mediates pilus secretion(2). The recent determination of the crystal structure of an initiation complex provided insight into the initiation step of pilus biogenesis resulting in pore activation, but very little is known about the elongation steps that follow(3). Here, to address this question, we determine the structure of an elongation complex in which the tip complex assembly composed of FimC, FimF, FimG and FimH passes through FimD. This structure demonstrates the conformational changes required to prevent backsliding of the nascent pilus through the FimD pore and also reveals unexpected properties of the usher pore. We show that the circular binding interface between the pore lumen and the folded substrate participates in transport by defining a low-energy pathway along which the nascent pilus polymer is guided during secretion.
C1 [Geibel, Sebastian; Waksman, Gabriel] UCL, Inst Struct & Mol Biol, London WC1E 7HX, England.
   [Geibel, Sebastian; Waksman, Gabriel] Univ London Birkbeck Coll, London WC1E 7HX, England.
   [Procko, Erik; Baker, David] Univ Washington, Howard Hughes Med Inst, Seattle, WA 98195 USA.
   [Procko, Erik; Baker, David] Univ Washington, Dept Biochem, Seattle, WA 98195 USA.
   [Hultgren, Scott J.] Washington Univ, Sch Med, Ctr Womens Infect Dis Res, St Louis, MO 63011 USA.
   [Hultgren, Scott J.] Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO 63011 USA.
C3 University of London; University College London; Birkbeck University London; University of London; Birkbeck University London; University of Washington; University of Washington Seattle; Howard Hughes Medical Institute; University of Washington; University of Washington Seattle; Washington University (WUSTL); Washington University (WUSTL)
RP Waksman, G (corresponding author), UCL, Inst Struct & Mol Biol, Malet St, London WC1E 7HX, England.
EM dabaker@u.washington.edu; g.waksman@ucl.ac.uk
FU Medical Research Council [85602]; National Institute of General Medical Studies at the US National Institutes of Health (NIH) [P41 GM103533]; National Institute of Allergy and Infectious Disease at the NIH [AI029549]; MRC [G0800002, MR/K018434/1] Funding Source: UKRI; Medical Research Council [G0800002, MR/K018434/1] Funding Source: researchfish; National Institute of Allergy and Infectious Diseases [R01AI029549] Funding Source: NIH RePORTER; National Institute of General Medical Sciences [P41GM103533] Funding Source: NIH RePORTER
NR 26
TC 80
Z9 95
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 APR 11
PY 2013
VL 496
IS 7444
BP 243
EP +
DI 10.1038/nature12007
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 122VM
UT WOS:000317346300046
PM 23579681
DA 2026-03-09
ER

PT J
AU Satoh, T
   Kidoya, H
   Naito, H
   Yamamoto, M
   Takemura, N
   Nakagawa, K
   Yoshioka, Y
   Morii, E
   Takakura, N
   Takeuchi, O
   Akira, S
AF Satoh, Takashi
   Kidoya, Hiroyasu
   Naito, Hisamichi
   Yamamoto, Masahiro
   Takemura, Naoki
   Nakagawa, Katsuhiro
   Yoshioka, Yoshichika
   Morii, Eiichi
   Takakura, Nobuyuki
   Takeuchi, Osamu
   Akira, Shizuo
TI Critical role of Trib1 in differentiation of tissue-resident M2-like macrophages
SO NATURE
LA English
DT Article
ID tribbles homolog; alternative activation; myeloid leukemogenesis; glucose-homeostasis; insulin-resistance; adipose-tissue; inflammation; obesity; polarization; association
AB Macrophages consist of at least two subgroups, M1 and M2 (refs 1-3). Whereas M1 macrophages are proinflammatory and have a central role in host defence against bacterial and viral infections(4,5), M2 macrophages are associated with responses to anti-inflammatory reactions, helminth infection, tissue remodelling, fibrosis and tumour progression(6). Trib1 is an adaptor protein involved in protein degradation by interacting with COP1 ubiquitin ligase(7). Genome-wide association studies in humans have implicated TRIB1 in lipid metabolism(8-10). Here we show that Trib1 is critical for the differentiation of F4/80(+)MR(+) tissue-resident macrophages-that share characteristics with M2 macrophages (which we term M2-like macrophages)-and eosinophils but not for the differentiation of M1 myeloid cells. Trib1 deficiency results in a severe reduction of M2-like macrophages in various organs, including bone marrow, spleen, lung and adipose tissues. Aberrant expression of C/EBP alpha in Trib1-deficient bone marrow cells is responsible for the defects in macrophage differentiation. Unexpectedly, mice lacking Trib1 in haematopoietic cells show diminished adipose tissue mass accompanied by evidence of increased lipolysis, even when fed a normal diet. Supplementation of M2-like macrophages rescues the pathophysiology, indicating that a lack of these macrophages is the cause of lipolysis. In response to a high-fat diet, mice lacking Trib1 in haematopoietic cells develop hypertriglyceridaemia and insulin resistance, together with increased proinflammatory cytokine gene induction. Collectively, these results demonstrate that Trib1 is critical for adipose tissue maintenance and suppression of metabolic disorders by controlling the differentiation of tissue-resident M2-like macrophages.
C1 [Satoh, Takashi; Takemura, Naoki; Nakagawa, Katsuhiro; Takeuchi, Osamu; Akira, Shizuo] Osaka Univ, Lab Host Def, WPI Immunol Frontier Res Ctr WPI IFReC, Suita, Osaka 5650871, Japan.
   [Satoh, Takashi; Takemura, Naoki; Nakagawa, Katsuhiro; Takeuchi, Osamu; Akira, Shizuo] Osaka Univ, Dept Host Def, Microbial Dis Res Inst, Suita, Osaka 5650871, Japan.
   [Kidoya, Hiroyasu; Naito, Hisamichi; Takakura, Nobuyuki] Osaka Univ, Dept Signal Transduct, Microbial Dis Res Inst, Suita, Osaka 5650871, Japan.
   [Yamamoto, Masahiro] Osaka Univ, Lab Immunoparasitol, WPI Immunol Frontier Res Ctr WPI IFReC, Suita, Osaka 5650871, Japan.
   [Yamamoto, Masahiro] Osaka Univ, Dept Immunoparasitol, Microbial Dis Res Inst, Suita, Osaka 5650871, Japan.
   [Yoshioka, Yoshichika] Osaka Univ, Lab Biofunct Imaging, WPI Immunol Frontier Res Ctr WPI IFReC, Suita, Osaka 5650871, Japan.
   [Morii, Eiichi] Osaka Univ, Dept Pathol, Grad Sch Med, Suita, Osaka 5650871, Japan.
   [Takeuchi, Osamu] Kyoto Univ, Lab Infect & Prevent, Inst Virus Res, Sakyo Ku, Kyoto 6068507, Japan.
C3 University of Osaka; University of Osaka; University of Osaka; University of Osaka; University of Osaka; University of Osaka; University of Osaka; Kyoto University
RP Akira, S (corresponding author), Osaka Univ, Lab Host Def, WPI Immunol Frontier Res Ctr WPI IFReC, 3-1 Yamada Oka, Suita, Osaka 5650871, Japan.
EM sakira@biken.osaka-u.ac.jp
FU Special Coordination Funds of the Japanese Ministry of Education, Culture, Sports, Science and Technology; Ministry of Health, Labour and Welfare in Japan; Japan Society for the Promotion of Science through the Funding Program for World-Leading Innovative R&D on Science and Technology (FIRST Program); Grants-in-Aid for Scientific Research [22689016, 22112005, 22613004, 20002008, 23701054] Funding Source: KAKEN
NR 30
TC 270
Z9 310
U1 1
U2 123
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 28
PY 2013
VL 495
IS 7442
BP 524
EP +
DI 10.1038/nature11930
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 113QN
UT WOS:000316682800049
PM 23515163
DA 2026-03-09
ER

PT J
AU Mahmoud, AI
   Kocabas, F
   Muralidhar, SA
   Kimura, W
   Koura, AS
   Thet, S
   Porrello, ER
   Sadek, HA
AF Mahmoud, Ahmed I.
   Kocabas, Fatih
   Muralidhar, Shalini A.
   Kimura, Wataru
   Koura, Ahmed S.
   Thet, Suwannee
   Porrello, Enzo R.
   Sadek, Hesham A.
TI Meis1 regulates postnatal cardiomyocyte cell cycle arrest
SO NATURE
LA English
DT Article
ID zebrafish heart regeneration; hematopoietic stem-cells; cardiac myocytes; proliferation; injury; phenotype; proteins; renewal; humans; growth
AB The neonatal mammalian heart is capable of substantial regeneration following injury through cardiomyocyte proliferation(1,2). However, this regenerative capacity is lost by postnatal day 7 and the mechanisms of cardiomyocyte cell cycle arrest remain unclear. The homeodomain transcription factor Meis1 is required for normal cardiac development but its role in cardiomyocytes is unknown(3,4). Here we identify Meis1 as a critical regulator of the cardiomyocyte cell cycle. Meis1 deletion in mouse cardiomyocytes was sufficient for extension of the postnatal proliferative window of cardiomyocytes, and for re-activation of cardiomyocyte mitosis in the adult heart with no deleterious effect on cardiac function. In contrast, overexpression of Meis1 in cardiomyocytes decreased neonatal myocyte proliferation and inhibited neonatal heart regeneration. Finally, we show that Meis1 is required for transcriptional activation of the synergistic CDK inhibitors p15, p16 and p21. These results identify Meis1 as a critical transcriptional regulator of cardiomyocyte proliferation and a potential therapeutic target for heart regeneration.
C1 [Mahmoud, Ahmed I.; Kocabas, Fatih; Muralidhar, Shalini A.; Kimura, Wataru; Thet, Suwannee; Sadek, Hesham A.] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Div Cardiol, Dallas, TX 75390 USA.
   [Koura, Ahmed S.] Ain Shams Univ, Sch Med, Cairo 1156, Egypt.
   [Porrello, Enzo R.] Univ Queensland, Sch Biomed Sci, St Lucia, Qld 4072, Australia.
C3 University of Texas System; University of Texas Southwestern Medical Center; Egyptian Knowledge Bank (EKB); Ain Shams University; University of Queensland
RP Sadek, HA (corresponding author), Univ Texas SW Med Ctr Dallas, Dept Internal Med, Div Cardiol, Dallas, TX 75390 USA.
EM hesham.sadek@utsouthwestern.edu
FU American Heart Association; Gilead Research Scholars Program in Cardiovascular Disease; Foundation for Heart Failure Research, NY; National Institutes of Health [1R01HL115275-01]
NR 28
TC 461
Z9 549
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 MAY 9
PY 2013
VL 497
IS 7448
BP 249
EP 253
DI 10.1038/nature12054
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 139CD
UT WOS:000318558200038
PM 23594737
DA 2026-03-09
ER

PT J
AU Takeda, S
   Mizuta, T
   Fuwa, M
   van Loock, P
   Furusawa, A
AF Takeda, Shuntaro
   Mizuta, Takahiro
   Fuwa, Maria
   van Loock, Peter
   Furusawa, Akira
TI Deterministic quantum teleportation of photonic quantum bits by a hybrid technique
SO NATURE
LA English
DT Article
ID podolsky-rosen channels; experimental realization; state; computation; operations; qubits
AB Quantum teleportation(1) allows for the transfer of arbitrary unknown quantum states from a sender to a spatially distant receiver, provided that the two parties share an entangled state and can communicate classically. It is the essence of many sophisticated protocols for quantum communication and computation(2-5). Photons are an optimal choice for carrying information in the form of 'flying qubits', but the teleportation of photonic quantum bits(6-11) (qubits) has been limited by experimental inefficiencies and restrictions. Main disadvantages include the fundamentally probabilistic nature of linear-optics Bell measurements(12), as well as the need either to destroy the teleported qubit or attenuate the input qubit when the detectors do not resolve photon numbers(13). Here we experimentally realize fully deterministic quantum teleportation of photonic qubits without post-selection. The key step is to make use of a hybrid technique involving continuous-variable teleportation(14-16) of a discrete-variable, photonic qubit. When the receiver's feedforward gain is optimally tuned, the continuous-variable teleporter acts as a pure loss channel(17,18), and the input dual-rail-encoded qubit, based on a single photon, represents a quantum error detection code against photon loss(19) and hence remains completely intact for most teleportation events. This allows for a faithful qubit transfer even with imperfect continuous-variable entangled states: for four qubits the overall transfer fidelities range from 0.79 to 0.82 and all of them exceed the classical limit of teleportation. Furthermore, even for a relatively low level of the entanglement, qubits are teleported much more efficiently than in previous experiments, albeit post-selectively (taking into account only the qubit subspaces), and with a fidelity comparable to the previously reported values.
C1 [Takeda, Shuntaro; Mizuta, Takahiro; Fuwa, Maria; Furusawa, Akira] Univ Tokyo, Sch Engn, Dept Appl Phys, Bunkyo Ku, Tokyo 1138656, Japan.
   [van Loock, Peter] Johannes Gutenberg Univ Mainz, Inst Phys, D-55128 Mainz, Germany.
C3 University of Tokyo; Johannes Gutenberg University of Mainz
RP Furusawa, A (corresponding author), Univ Tokyo, Sch Engn, Dept Appl Phys, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1138656, Japan.
EM akiraf@ap.t.u-tokyo.ac.jp
FU PDIS; GIA; G-COE; APSA; FIRST; SCOPE programme; ASCR-JSPS; ALPS; Grants-in-Aid for Scientific Research [12J04889, 23244080] Funding Source: KAKEN
NR 30
TC 234
Z9 258
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 AUG 15
PY 2013
VL 500
IS 7462
BP 315
EP 318
DI 10.1038/nature12366
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 201AF
UT WOS:000323112400028
PM 23955230
DA 2026-03-09
ER

PT J
AU Frigola, J
   Remus, D
   Mehanna, A
   Diffley, JFX
AF Frigola, Jordi
   Remus, Dirk
   Mehanna, Amina
   Diffley, John F. X.
TI ATPase-dependent quality control of DNA replication origin licensing
SO NATURE
LA English
DT Article
ID re-replication; complex; helicase; cdt1; initiation; mechanism; sequence; binding; cells; orc6
AB The regulated loading of the Mcm2-7 DNA helicase (comprising six related subunits, Mcm2 to Mcm7) into pre-replicative complexes at multiple replication origins ensures precise once per cell cycle replication in eukaryotic cells. The origin recognition complex (ORC), Cdc6 and Cdt1 load Mcm2-7 into a double hexamer bound around duplex DNA in an ATP-dependent reaction, but the molecular mechanism of this origin 'licensing' is still poorly understood. Here we show that both Mcm2-7 hexamers in Saccharomyces cerevisiae are recruited to origins by an essential, conserved carboxy-terminal domain of Mcm3 that interacts with and stimulates the ATPase activity of ORC-Cdc6. ATP hydrolysis can promote Mcm2-7 loading, but can also promote Mcm2-7 release if components are missing or if ORC has been inactivated by cyclin-dependent kinase phosphorylation. Our work provides new insights into how origins are licensed and reveals a novel ATPase-dependent mechanism contributing to precise once per cell cycle replication.
C1 [Frigola, Jordi; Remus, Dirk; Mehanna, Amina; Diffley, John F. X.] Canc Res UK London Res Inst, Clare Hall Labs, S Mimms EN6 3LD, Herts, England.
C3 Cancer Research UK
RP Diffley, JFX (corresponding author), Canc Res UK London Res Inst, Clare Hall Labs, S Mimms EN6 3LD, Herts, England.
EM John.Diffley@cancer.org.uk
FU Cancer Research UK; Association for International Cancer Research [10-0270]; European Research Council [249883 - EUKDNAREP]; Cancer Research UK [15669] Funding Source: researchfish
NR 26
TC 186
Z9 217
U1 0
U2 52
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 21
PY 2013
VL 495
IS 7441
BP 339
EP 343
DI 10.1038/nature11920
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 113EY
UT WOS:000316650500036
PM 23474987
DA 2026-03-09
ER

PT J
AU Li, XC
   Dang, SY
   Yan, CY
   Gong, XQ
   Wang, JW
   Shi, YG
AF Li, Xiaochun
   Dang, Shangyu
   Yan, Chuangye
   Gong, Xinqi
   Wang, Jiawei
   Shi, Yigong
TI Structure of a presenilin family intramembrane aspartate protease
SO NATURE
LA English
DT Article
ID gamma-secretase reveals; crystal-structure; 3-dimensional structure; catalytic pore; transmembrane domain-4; complex; proteolysis; binding; pen-2; model
AB Presenilin and signal peptide peptidase (SPP) are intramembrane aspartyl proteases that regulate important biological functions in eukaryotes. Mechanistic understanding of presenilin and SPP has been hamperedby lack of relevant structural information. Here we report the crystal structure of a presenilin/SPP homologue (PSH) from the archaeon Methanoculleus marisnigri JR1. The protease, comprising nine transmembrane segments (TMs), adopts a previously unreported protein fold. The amino-terminal domain, consisting of TM1-6, forms a horseshoe-shaped structure, surrounding TM7-9 of the carboxy-terminal domain. The two catalytic aspartate residues are located on the cytoplasmic side of TM6 and TM7, spatially close to each other and approximately 8 angstrom into the lipid membrane surface. Water molecules gain constant access to the catalytic aspartates through a large cavity between the amino-and carboxy-terminal domains. Structural analysis reveals insights into the presenilin/SPP family of intramembrane proteases.
C1 [Li, Xiaochun; Dang, Shangyu; Yan, Chuangye; Gong, Xinqi; Shi, Yigong] Tsinghua Univ, Minist Educ, Key Lab Prot Sci, Sch Life Sci,Ctr Struct Biol, Beijing 100084, Peoples R China.
   [Li, Xiaochun; Dang, Shangyu; Yan, Chuangye; Gong, Xinqi; Wang, Jiawei; Shi, Yigong] Tsinghua Univ, Sch Med, Beijing 100084, Peoples R China.
   [Li, Xiaochun; Dang, Shangyu; Yan, Chuangye; Gong, Xinqi; Wang, Jiawei; Shi, Yigong] Tsinghua Univ, Tsinghua Peking Joint Ctr Life Sci, Struct Biol Ctr, Sch Life Sci, Beijing 100084, Peoples R China.
   [Wang, Jiawei] Tsinghua Univ, State Key Lab Biomembrane & Membrane Biotechnol, Struct Biol Ctr, Sch Life Sci, Beijing 100084, Peoples R China.
C3 Tsinghua University; Tsinghua University; Tsinghua University; Tsinghua University
RP Shi, YG (corresponding author), Tsinghua Univ, Minist Educ, Key Lab Prot Sci, Sch Life Sci,Ctr Struct Biol, Beijing 100084, Peoples R China.
EM shi-lab@tsinghua.edu.cn
FU Ministry of Science and Technology [2009CB918801]; National Natural Science Foundation of China [30888001]
NR 60
TC 170
Z9 197
U1 1
U2 214
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 3
PY 2013
VL 493
IS 7430
BP 56
EP +
DI 10.1038/nature11801
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 062QC
UT WOS:000312933800029
PM 23254940
DA 2026-03-09
ER

PT J
AU Chang, JB
   Ferrell, JE
AF Chang, Jeremy B.
   Ferrell, James E., Jr.
TI Mitotic trigger waves and the spatial coordination of the Xenopus cell cycle
SO NATURE
LA English
DT Article
ID surface contraction waves; nuclear division; localization; activation; eggs; propagation; bistability; hysteresis; oscillator; extracts
AB Despite the large size of the Xenopus laevis egg (approximately 1.2 mm diameter), a fertilized egg rapidly proceeds through mitosis in a spatially coordinated fashion. Mitosis is initiated by a bistable system of regulatory proteins centred on Cdk1 (refs 1, 2), raising the possibility that this spatial coordination could be achieved through trigger waves of Cdk1 activity(3). Using an extract system that performs cell cycles in vitro, here we show that mitosis does spread through Xenopus cytoplasm via trigger waves, propagating at a linear speed of approximately 60 mu m min(-1). Perturbing the feedback loops that give rise to the bistability of Cdk1 changes the speed and dynamics of the waves. Time-lapse imaging of intact eggs argues that trigger waves of Cdk1 activation are responsible for surface contraction waves, ripples in the cell cortex that precede cytokinesis(4,5). These findings indicate that Cdk1 trigger waves help ensure the spatiotemporal coordination of mitosis in large eggs. Trigger waves may be an important general mechanism for coordinating biochemical events over large distances.
C1 [Chang, Jeremy B.; Ferrell, James E., Jr.] Stanford Univ, Sch Med, Dept Chem & Syst Biol, Stanford, CA 94305 USA.
   [Ferrell, James E., Jr.] Stanford Univ, Sch Med, Dept Biochem, Stanford, CA 94305 USA.
C3 Stanford University; Stanford University
RP Chang, JB (corresponding author), Stanford Univ, Sch Med, Dept Chem & Syst Biol, Stanford, CA 94305 USA.
EM jbchang@stanford.edu; james.ferrell@stanford.edu
FU National Institutes of Health [GM046383, GM077544]; National Science Foundation; National Cancer Institute [P30CA124435] Funding Source: NIH RePORTER
CR Bonnet J, 2008, CELL CYCLE, V7, P1991, DOI 10.4161/cc.7.13.6095
   CLUTTERBUCK AJ, 1970, J GEN MICROBIOL, V60, P133, DOI 10.1099/00221287-60-1-133
   FOE VE, 1983, J CELL SCI, V61, P31
   Gerhart JC, 1980, BIOLOGICAL REGULATION AND DEVELOPMENT, V2, P133
   Gladfelter AS, 2006, J CELL BIOL, V172, P347, DOI 10.1083/jcb.200507003
   HARA K, 1971, ROUX ARCH DEV BIOL, V167, P183, DOI 10.1007/BF00577039
   HARA K, 1980, P NATL ACAD SCI-BIOL, V77, P462, DOI 10.1073/pnas.77.1.462
   Haskins EF, 1974, PUB WISS FILM SEKT B, V8, P1
   Hausen P, 1991, EARLY DEV XENOPUS LA, V0, P0
   Jackman M, 2003, NAT CELL BIOL, V5, P143, DOI 10.1038/ncb918
   Luther R, 1906, Z ELKTROCHEM ANGEW P, V12, P596, DOI 10.1002/bbpc.19060123208
   Markevich NI, 2006, MOL SYST BIOL, V2, P0, DOI 10.1038/msb4100108
   MURRAY AW, 1991, METHOD CELL BIOL, V36, P581
   Nakamura N, 2005, MOL REPROD DEV, V72, P336, DOI 10.1002/mrd.20348
   NEWPORT J, 1982, CELL, V30, P675, DOI 10.1016/0092-8674(82)90272-0
   NOVAK B, 1993, J THEOR BIOL, V165, P101, DOI 10.1006/jtbi.1993.1179
   Pérez-Mongiovi D, 1998, J CELL SCI, V111, P385
   Pomerening JR, 2003, NAT CELL BIOL, V5, P346, DOI 10.1038/ncb954
   Rankin S, 1997, CURR BIOL, V7, P451, DOI 10.1016/S0960-9822(06)00192-8
   Reynolds AR, 2003, NAT CELL BIOL, V5, P447, DOI 10.1038/ncb981
   Sha W, 2003, P NATL ACAD SCI USA, V100, P975, DOI 10.1073/pnas.0235349100
   SHINAGAWA A, 1989, DEV GROWTH DIFFER, V31, P249, DOI 10.1111/j.1440-169X.1989.00249.x
   Trunnell NB, 2011, MOL CELL, V41, P263, DOI 10.1016/j.molcel.2011.01.012
   TYSON JJ, 1988, PHYSICA D, V32, P327, DOI 10.1016/0167-2789(88)90062-0
   Wang YL, 2001, CANCER RES, V61, P8211
   Winfree AT, 1974, FARADAY S CHEM SOC, V9, P38
   Yang Q, 2013, NAT CELL BIOL, V15, P519, DOI 10.1038/ncb2737
NR 27
TC 149
Z9 188
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 AUG 29
PY 2013
VL 500
IS 7464
BP 603
EP 607
DI 10.1038/nature12321
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 207TD
UT WOS:000323625900040
PM 23863935
DA 2026-03-09
ER

PT J
AU Ross, JM
   Stewart, JB
   Hagström, E
   Brené, S
   Mourier, A
   Coppotelli, G
   Freyer, C
   Lagouge, M
   Hoffer, BJ
   Olson, L
   Larsson, NG
AF Ross, Jaime M.
   Stewart, James B.
   Hagstrom, Erik
   Brene, Stefan
   Mourier, Arnaud
   Coppotelli, Giuseppe
   Freyer, Christoph
   Lagouge, Marie
   Hoffer, Barry J.
   Olson, Lars
   Larsson, Nils-Goran
TI Germline mitochondrial DNA mutations aggravate ageing and can impair brain development
SO NATURE
LA English
DT Article
ID purifying selection; mtdna; heteroplasmy; frequency; deletions; reveals; tissue
AB Ageing is due to an accumulation of various types of damage(1,2), and mitochondrial dysfunction has long been considered to be important in this process(3-8). There is substantial sequence variation in mammalian mitochondrial DNA (mtDNA)(9), and the high mutation rate is counteracted by different mechanisms that decrease maternal transmission of mutated mtDNA(10-13). Despite these protective mechanisms(14), it is becoming increasingly clear that lowlevel mtDNA heteroplasmy is quite common and often inherited in humans(15,16). We designed a series of mouse mutants to investigate the extent to which inherited mtDNA mutations can contribute to ageing. Here we report that maternally transmitted mtDNA mutations can induce mild ageing phenotypes in mice with a wild-type nuclear genome. Furthermore, maternally transmittedmtDNAmutations lead to anticipation of reduced fertility in mice that are heterozygous for themtDNAmutator allele (PolgAwt/mut) and aggravate premature ageing phenotypes inmtDNAmutatormice (PolgAmut/mut). Unexpectedly, a combination of maternally transmitted and somatic mtDNA mutations also leads to stochastic brain malformations. Our findings show that a pre-existing mutation load will not only allow somatic mutagenesis to create a critically high total mtDNA mutation load sooner but will also increase clonal expansionofmtDNA mutations(17) to enhance the normally occurring mosaic respiratory chain deficiency in ageing tissues(18,19). Our findings suggest that maternally transmitted mtDNA mutations may have a similar role in aggravating aspects of normal human ageing.
C1 [Ross, Jaime M.; Coppotelli, Giuseppe; Olson, Lars] Karolinska Inst, Dept Neurosci, S-17177 Stockholm, Sweden.
   [Stewart, James B.; Mourier, Arnaud; Freyer, Christoph; Lagouge, Marie] Max Planck Inst Biol Ageing, D-50931 Cologne, Germany.
   [Hagstrom, Erik; Freyer, Christoph; Larsson, Nils-Goran] Karolinska Inst, Dept Lab Med, S-17177 Stockholm, Sweden.
   [Brene, Stefan] Karolinska Inst, KERIC, Dept Neurobiol Care Sci & Soc, S-17176 Stockholm, Sweden.
   [Hoffer, Barry J.] Univ Hosp, Case Western Reserve Med Ctr, Dept Neurosurg, Cleveland, OH 44106 USA.
C3 Karolinska Institutet; Max Planck Society; Karolinska Institutet; Karolinska Institutet; University System of Ohio; Case Western Reserve University; Case Western Reserve University Hospital; University Hospitals of Cleveland
RP Olson, L (corresponding author), Karolinska Inst, Dept Neurosci, Retzius Vag 8, S-17177 Stockholm, Sweden.
EM lars.olson@ki.se; larsson@age.mpg.de
FU ERC [268897, 322744]; Swedish Research Council [K2011-62X-21870-01-6, K2012-62X-03185-42-4]; Swedish Brain Foundation; Swedish Brain Power; Swedish Parkinson Foundation; Karolinska Distinguished Professor Award; Swedish Alzheimer Foundation; National Institutes of Health [AG04418, NS070825]; National Institute on Drug Abuse; National Institutes of Health/Karolinska Institutet Graduate Partnerships Program; Swedish Society for Medical Research; United Mitochondrial Disease Foundation; European Research Council (ERC) [268897] Funding Source: European Research Council (ERC)
NR 33
TC 235
Z9 267
U1 0
U2 67
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 19
PY 2013
VL 501
IS 7467
BP 412
EP +
DI 10.1038/nature12474
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 219XT
UT WOS:000324545700044
PM 23965628
DA 2026-03-09
ER

PT J
AU Rambo, RP
   Tainer, JA
AF Rambo, Robert P.
   Tainer, John A.
TI Accurate assessment of mass, models and resolution by small-angle scattering
SO NATURE
LA English
DT Article
ID x-ray-scattering; biological macromolecules; structural-analyses; saxs; rna; crystallography; computation; proteins; quality; scale
AB Modern small-angle scattering (SAS) experiments with X-rays or neutrons provide a comprehensive, resolution-limited observation of the thermodynamic state. However, methods for evaluating mass and validating SAS-based models and resolution have been inadequate. Here we define the volume of correlation, V-c, a SAS invariant derived from the scattered intensities that is specific to the structural state of the particle, but independent of concentration and the requirements of a compact, folded particle. We show that V-c defines a ratio, Q(R), that determines the molecular mass of proteins or RNA ranging from 10 to 1,000 kilodaltons. Furthermore, we propose a statistically robust method for assessing model-data agreements (chi(2)(free)) akin to cross-validation. Our approach prevents over-fitting of the SAS data and can be used with a newly defined metric, R-SAS, for quantitative evaluation of resolution. Together, these metrics (V-c, Q(R), chi(2)(free) and R-SAS) provide analytical tools for unbiased and accurate macromolecular structural characterizations in solution.
C1 [Rambo, Robert P.; Tainer, John A.] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Adv Light Source, Div Life Sci, Berkeley, CA 94720 USA.
   [Tainer, John A.] Scripps Res Inst, Skaggs Inst Chem Biol, Dept Integrat Struct & Computat Biol, La Jolla, CA 92037 USA.
C3 University of California System; University of California Berkeley; United States Department of Energy (DOE); Lawrence Berkeley National Laboratory; Scripps Research Institute
RP Rambo, RP (corresponding author), Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Adv Light Source, Div Life Sci, Berkeley, CA 94720 USA.
EM rprambo@lbl.gov; jat@scripps.edu
FU Office of Science, US Department of Energy on Novel Technology for Structural Biology; United States Department of Energy program Integrated Diffraction Analysis Technologies [DEAC02-05CH11231]; National Institutes of Health [R01GM105404]
NR 32
TC 641
Z9 734
U1 2
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 APR 25
PY 2013
VL 496
IS 7446
BP 477
EP +
DI 10.1038/nature12070
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 131HU
UT WOS:000317984400035
PM 23619693
DA 2026-03-09
ER

PT J
AU Znamenskiy, P
   Zador, AM
AF Znamenskiy, Petr
   Zador, Anthony M.
TI Corticostriatal neurons in auditory cortex drive decisions during auditory discrimination
SO NATURE
LA English
DT Article
ID superior colliculus; basal ganglia; substantia nigra; overlying areas; albino-rat; in-vivo; striatum; microstimulation; organization; performance
AB The neural pathways by which information about the acoustic world reaches the auditory cortex are well characterized, but how auditory representations are transformed into motor commands is not known. Here we use a perceptual decision-making task in rats to study this transformation. We demonstrate the role of corticostriatal projection neurons in auditory decisions by manipulating the activity of these neurons in rats performing an auditory frequency-discriminationtask. Targeted channelrhodopsin-2(ChR2)(1,2)-mediated stimulation of corticostriatal neurons during the task biased decisions in the direction predicted by the frequency tuning of the stimulated neurons, whereas archaerhodopsin-3 (Arch)(3)-mediated inactivation biased decisions in the opposite direction. Striatal projections are widespread in cortex and may provide a general mechanism for the control of motor decisions by sensory cortex.
C1 [Znamenskiy, Petr] Cold Spring Harbor Lab, Watson Sch Biol Sci, Cold Spring Harbor, NY 11724 USA.
   [Znamenskiy, Petr; Zador, Anthony M.] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA.
C3 Cold Spring Harbor Laboratory; Cold Spring Harbor Laboratory
RP Zador, AM (corresponding author), Cold Spring Harbor Lab, 1 Bungtown Rd, Cold Spring Harbor, NY 11724 USA.
EM zador@cshl.edu
FU Swartz Foundation; National Institutes of Health [25041001, 55120101]
NR 29
TC 267
Z9 324
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 MAY 23
PY 2013
VL 497
IS 7450
BP 482
EP +
DI 10.1038/nature12077
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 148OG
UT WOS:000319254000046
PM 23636333
DA 2026-03-09
ER

PT J
AU Fedorov, AV
   Brierley, CM
   Lawrence, KT
   Liu, Z
   Dekens, PS
   Ravelo, AC
AF Fedorov, A. V.
   Brierley, C. M.
   Lawrence, K. T.
   Liu, Z.
   Dekens, P. S.
   Ravelo, A. C.
TI Patterns and mechanisms of early Pliocene warmth
SO NATURE
LA English
DT Article
ID equatorial pacific thermocline; carbon-dioxide concentration; permanent el-nino; surface temperatures; thermal structure; western pacific; climate-change; ice volume; atlantic; circulation
AB About five to four million years ago, in the early Pliocene epoch, Earth had a warm, temperate climate. The gradual cooling that followed led to the establishment of modern temperature patterns, possibly in response to a decrease in atmospheric CO2 concentration, of the order of 100 parts per million, towards preindustrial values. Here we synthesize the available geochemical proxy records of sea surface temperature and show that, compared with that of today, the early Pliocene climate had substantially lower meridional and zonal temperature gradients but similar maximum ocean temperatures. Using an Earth system model, we show that none of the mechanisms currently proposed to explain Pliocene warmth can simultaneously reproduce all three crucial features. We suggest that a combination of several dynamical feedbacks underestimated in the models at present, such as those related to ocean mixing and cloud albedo, may have been responsible for these climate conditions.
C1 [Fedorov, A. V.; Brierley, C. M.] Yale Univ, Dept Geol & Geophys, New Haven, CT 06511 USA.
   [Brierley, C. M.] Univ London Univ Coll, Dept Geog, London WC1E 6BT, England.
   [Lawrence, K. T.] Lafayette Coll, Dept Geol & Environm Geosci, Easton, PA 18042 USA.
   [Liu, Z.] Univ Hong Kong, Dept Earth Sci, Hong Kong, Hong Kong, Peoples R China.
   [Dekens, P. S.] San Francisco State Univ, Dept Geosci, San Francisco, CA 94132 USA.
   [Ravelo, A. C.] Univ Calif Santa Cruz, Dept Ocean Sci, Santa Cruz, CA 95064 USA.
C3 Yale University; University of London; University College London; Lafayette College; University of Hong Kong; California State University System; San Francisco State University; University of California System; University of California Santa Cruz
RP Fedorov, AV (corresponding author), Yale Univ, Dept Geol & Geophys, POB 6666, New Haven, CT 06511 USA.
EM alexey.fedorov@yale.edu
FU US National Science Foundation [OCE-0901921, OCE-0623310]; US Department of Energy Office of Science [DE-SC0007037]; David and Lucile Packard Foundation; National Science Foundation; Yale University Faculty of Arts and Sciences High Performance Computing facility; Directorate For Geosciences; Division Of Ocean Sciences [1204254] Funding Source: National Science Foundation
NR 92
TC 321
Z9 381
U1 2
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 APR 4
PY 2013
VL 496
IS 7443
BP 43
EP +
DI 10.1038/nature12003
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 117ZZ
UT WOS:000316993400022
PM 23552943
DA 2026-03-09
ER

PT J
AU Chatzigeorgiou, M
   Bang, S
   Hwang, SW
   Schafer, WR
AF Chatzigeorgiou, Marios
   Bang, Sangsu
   Hwang, Sun Wook
   Schafer, William R.
TI tmc-1 encodes a sodium-sensitive channel required for salt chemosensation in C. elegans
SO NATURE
LA English
DT Article
ID nucleotide-gated channel; ash neurons; hearing-loss; gene family; hair-cells; taste; avoidance; adaptation; behaviors; mutations
AB Transmembrane channel-like (TMC) genes encode a broadly conserved family of multipass integral membrane proteins in animals(1,2). Human TMC1 and TMC2 genes are linked to human deafness and required for hair-cell mechanotransduction; however, the molecular functions of these and other TMC proteins have not been determined(3-6). Here we show that the Caenorhabditis elegans tmc-1 gene encodes a sodium sensor that functions specifically in salt taste chemosensation. tmc-1 is expressed in the ASH polymodal avoidance neurons, where it is required for salt-evoked neuronal activity and behavioural avoidance of high concentrations of NaCl. However, tmc-1 has no effect on responses to other stimuli sensed by the ASH neurons including high osmolarity and chemical repellents, indicating a specific role in salt sensation. When expressed in mammalian cell culture, C. elegans TMC-1 generates a predominantly cationic conductance activated by high extracellular sodium but not by other cations or uncharged small molecules. Thus, TMC-1 is both necessary for salt sensation in vivo and sufficient to generate a sodium-sensitive channel in vitro, identifying it as a probable ionotropic sensory receptor.
C1 [Chatzigeorgiou, Marios; Schafer, William R.] MRC Lab Mol Biol, Div Cell Biol, Cambridge CB2 0QH, England.
   [Bang, Sangsu; Hwang, Sun Wook] Korea Univ, Coll Med, Dept Biomed Sci, Seoul 136705, South Korea.
C3 MRC Laboratory Molecular Biology; Korea University; Korea University Medicine (KU Medicine)
RP Hwang, SW (corresponding author), Korea Univ, Coll Med, Dept Biomed Sci, Seoul 136705, South Korea.
EM sunhwang@korea.ac.kr; wschafer@mrc-lmb.cam.ac.uk
FU Medical Research Council; National Research Foundation of Korea [2012000540]; Ministry of Health Welfare [A111373]; MRC [MC_U105185857] Funding Source: UKRI; Medical Research Council [MC_U105185857] Funding Source: researchfish
NR 30
TC 114
Z9 152
U1 0
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 FEB 7
PY 2013
VL 494
IS 7435
BP 95
EP 99
DI 10.1038/nature11845
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 087DJ
UT WOS:000314741200041
PM 23364694
DA 2026-03-09
ER

PT J
AU Chaudhury, D
   Walsh, JJ
   Friedman, AK
   Juarez, B
   Ku, SM
   Koo, JW
   Ferguson, D
   Tsai, HC
   Pomeranz, L
   Christoffel, DJ
   Nectow, AR
   Ekstrand, M
   Domingos, A
   Mazei-Robison, MS
   Mouzon, E
   Lobo, MK
   Neve, RL
   Friedman, JM
   Russo, SJ
   Deisseroth, K
   Nestler, EJ
   Han, MH
AF Chaudhury, Dipesh
   Walsh, Jessica J.
   Friedman, Allyson K.
   Juarez, Barbara
   Ku, Stacy M.
   Koo, Ja Wook
   Ferguson, Deveroux
   Tsai, Hsing-Chen
   Pomeranz, Lisa
   Christoffel, Daniel J.
   Nectow, Alexander R.
   Ekstrand, Mats
   Domingos, Ana
   Mazei-Robison, Michelle S.
   Mouzon, Ezekiell
   Lobo, Mary Kay
   Neve, Rachael L.
   Friedman, Jeffrey M.
   Russo, Scott J.
   Deisseroth, Karl
   Nestler, Eric J.
   Han, Ming-Hu
TI Rapid regulation of depression-related behaviours by control of midbrain dopamine neurons
SO NATURE
LA English
DT Article
ID ventral tegmental area; social defeat stress; antidepressant action; reward circuit; in-vivo; susceptibility; stimulation; inhibition; expression; responses
AB Ventral tegmental area(VTA) dopamine neurons in the brain's reward circuit have a crucial role in mediating stress responses(1-4), including determining susceptibility versus resilience to social-stress-induced behavioural abnormalities(5). VTA dopamine neurons show two in vivo patterns of firing: low frequency tonic firing and high frequency phasic firing(6-8). Phasic firing of the neurons, which is well known to encode reward signals(6,7,9), is upregulated by repeated social-defeat stress, a highly validated mouse model of depression(5,8,10-13). Surprisingly, this pathophysiological effect is seen in susceptible mice only, with no apparent change in firing rate in resilient individuals(5,8). However, direct evidence-in real time-linking dopamine neuron phasic firing in promoting the susceptible (depression-like) phenotype is lacking. Here we took advantage of the temporal precision and cell-type and projection-pathway specificity of optogenetics to show that enhanced phasic firing of these neurons mediates susceptibility to social-defeat stress in freely behaving mice. We show that optogenetic induction of phasic, but not tonic, firing in VTA dopamine neurons of mice undergoing a subthreshold social-defeat paradigm rapidly induced a susceptible phenotype as measured by social avoidance and decreased sucrose preference. Optogenetic phasic stimulation of these neurons also quickly induced a susceptible phenotype in previously resilient mice that had been subjected to repeated social-defeat stress. Furthermore, we show differences in projection-pathway specificity in promoting stress susceptibility: phasic activation of VTA neurons projecting to the nucleus accumbens (NAc), but not to the medial prefrontal cortex (mPFC), induced susceptibility to social-defeat stress. Conversely, optogenetic inhibition of the VTA-NAc projection induced resilience, whereas inhibition of the VTA-mPFC projection promoted susceptibility. Overall, these studies reveal novel firing-pattern-and neural-circuit-specific mechanisms of depression.
C1 [Chaudhury, Dipesh; Walsh, Jessica J.; Friedman, Allyson K.; Juarez, Barbara; Ku, Stacy M.; Nestler, Eric J.; Han, Ming-Hu] Mt Sinai Sch Med, Friedman Brain Inst, Dept Pharmacol & Syst Therapeut, New York, NY 10029 USA.
   [Walsh, Jessica J.; Juarez, Barbara; Ku, Stacy M.; Koo, Ja Wook; Ferguson, Deveroux; Christoffel, Daniel J.; Mazei-Robison, Michelle S.; Mouzon, Ezekiell; Lobo, Mary Kay; Russo, Scott J.; Nestler, Eric J.; Han, Ming-Hu] Mt Sinai Sch Med, Friedman Brain Inst, Fishberg Dept Neurosci, New York, NY 10029 USA.
   [Tsai, Hsing-Chen; Deisseroth, Karl] Stanford Univ, Dept Bioengn, Stanford, CA 94305 USA.
   [Tsai, Hsing-Chen; Deisseroth, Karl] Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA.
   [Pomeranz, Lisa; Nectow, Alexander R.; Ekstrand, Mats; Domingos, Ana; Friedman, Jeffrey M.] Rockefeller Univ, Howard Hughes Med Inst, Mol Genet Lab, New York, NY 10056 USA.
   [Neve, Rachael L.] MIT, McGovern Inst Brain Res, Cambridge, MA 02139 USA.
C3 Icahn School of Medicine at Mount Sinai; Icahn School of Medicine at Mount Sinai; Stanford University; Stanford University; Howard Hughes Medical Institute; Rockefeller University; Massachusetts Institute of Technology (MIT)
RP Han, MH (corresponding author), Mt Sinai Sch Med, Friedman Brain Inst, Dept Pharmacol & Syst Therapeut, New York, NY 10029 USA.
EM ming-hu.han@mssm.edu
FU National Institute of Mental Health [R01 MH092306]; Johnson & Johnson IMHRO Rising Star Translational Research Award; National Research Service Awards [F31 MH095425, F32 MH096464]; Mount Sinai PREP [R25 GM064118]; National Institute of General Medical Sciences [R25GM064118] Funding Source: NIH RePORTER; National Institute of General Medical Sciences; National Institute on Aging; National Institute of Mental Health [T32MH020016] Funding Source: NIH RePORTER; National Institute of Mental Health [T32MH087004, P50MH096890] Funding Source: NIH RePORTER
NR 37
TC 931
Z9 1110
U1 8
U2 482
PU NATURE PUBLISHING 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 24
PY 2013
VL 493
IS 7433
BP 532
EP +
DI 10.1038/nature11713
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 075GF
UT WOS:000313871400038
PM 23235832
DA 2026-03-09
ER

PT J
AU Yin, P
   Li, QX
   Yan, CY
   Liu, Y
   Liu, JJ
   Yu, F
   Wang, Z
   Long, JF
   He, JH
   Wang, HW
   Wang, JW
   Zhu, JK
   Shi, YG
   Yan, NE
AF Yin, Ping
   Li, Quanxiu
   Yan, Chuangye
   Liu, Ying
   Liu, Junjie
   Yu, Feng
   Wang, Zheng
   Long, Jiafu
   He, Jianhua
   Wang, Hong-Wei
   Wang, Jiawei
   Zhu, Jian-Kang
   Shi, Yigong
   Yan, Nieng
TI Structural basis for the modular recognition of single-stranded RNA by PPR proteins
SO NATURE
LA English
DT Article
ID pentatricopeptide repeat proteins; cytoplasmic male-sterility; restores fertility; binding; identification; mechanism; reveals; insight; termini; rice
AB Pentatricopeptide repeat (PPR) proteins represent a large family of sequence-specific RNA-binding proteins that are involved in multiple aspects of RNA metabolism. PPR proteins, which are found in exceptionally large numbers in the mitochondria and chloroplasts of terrestrial plants(1-5), recognize single-stranded RNA (ssRNA) in a modular fashion(6-8). The maize chloroplast protein PPR10 binds to two similar RNA sequences from the ATPI-ATPH and PSAJ-RPL33 intergenic regions, referred to as ATPH and PSAJ, respectively(9,10). By protecting the target RNA elements from 5' or 3' exonucleases, PPR10 defines the corresponding 5' and 3' messenger RNA termini(9-11). Despite rigorous functional characterizations, the structural basis of sequence-specific ssRNA recognition by PPR proteins remains to be elucidated. Here we report the crystal structures of PPR10 in RNA-free and RNA-bound states at resolutions of 2.85 and 2.45 angstrom, respectively. In the absence of RNA binding, the nineteen repeats of PPR10 are assembled into a right-handed superhelical spiral. PPR10 forms an antiparallel, intertwined homodimer and exhibits considerable conformational changes upon binding to its target ssRNA, an 18-nucleotide PSAJ element. Six nucleotides of PSAJ are specifically recognized by six corresponding PPR10 repeats following the predicted code. The molecular basis for the specific and modular recognition of RNA bases A, G and U is revealed. The structural elucidation of RNA recognition by PPR proteins provides an important framework for potential biotechnological applications of PPR proteins in RNA-related research areas.
C1 [Yin, Ping; Li, Quanxiu; Liu, Ying; Wang, Jiawei; Yan, Nieng] Tsinghua Univ, State Key Lab Biomembrane & Membrane Biotechnol, Beijing 100084, Peoples R China.
   [Yin, Ping; Li, Quanxiu; Yan, Chuangye; Liu, Ying; Liu, Junjie; Wang, Hong-Wei; Wang, Jiawei; Shi, Yigong; Yan, Nieng] Tsinghua Univ, Ctr Struct Biol, Sch Life Sci, Beijing 100084, Peoples R China.
   [Yin, Ping; Li, Quanxiu; Yan, Chuangye; Liu, Ying; Liu, Junjie; Wang, Hong-Wei; Wang, Jiawei; Shi, Yigong; Yan, Nieng] Tsinghua Univ, Sch Med, Tsinghua Peking Ctr Life Sci, Beijing 100084, Peoples R China.
   [Yan, Chuangye; Liu, Junjie; Wang, Hong-Wei; Shi, Yigong] Tsinghua Univ, Minist Educ, Key Lab Prot Sci, Beijing 100084, Peoples R China.
   [Yu, Feng; He, Jianhua] Chinese Acad Sci, Shanghai Inst Appl Phys, Shanghai 201204, Peoples R China.
   [Wang, Zheng; Long, Jiafu] Nankai Univ, State Key Lab Med Chem Biol, Tianjin 300071, Peoples R China.
   [Wang, Zheng; Long, Jiafu] Nankai Univ, Coll Life Sci, Tianjin 300071, Peoples R China.
   [Zhu, Jian-Kang] Chinese Acad Sci, Shanghai Inst Biol Sci, Shanghai Ctr Plant Stress Biol, Shanghai 200032, Peoples R China.
   [Zhu, Jian-Kang] Purdue Univ, Dept Hort & Landscape Architecture, W Lafayette, IN 47907 USA.
C3 Tsinghua University; Tsinghua University; Tsinghua University; Tsinghua University; Chinese Academy of Sciences; Shanghai Institute of Applied Physics, CAS; Nankai University; Nankai University; Chinese Academy of Sciences; Purdue University System; Purdue University
RP Yan, NE (corresponding author), Tsinghua Univ, State Key Lab Biomembrane & Membrane Biotechnol, Beijing 100084, Peoples R China.
EM nyan@tsinghua.edu.cn
FU Ministry of Science and Technology [2011CB910501]; National Natural Science Foundation of China [91017011, 31070644, 31021002, 31200567]; Howard Hughes Medical Institute
NR 37
TC 287
Z9 337
U1 10
U2 321
PU NATURE PUBLISHING 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 5
PY 2013
VL 504
IS 7478
BP 168
EP +
DI 10.1038/nature12651
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 264BK
UT WOS:000327851700053
PM 24162847
DA 2026-03-09
ER

PT J
AU Feng, ZD
   Hensley, L
   McKnight, KL
   Hu, FY
   Madden, V
   Ping, LF
   Jeong, SH
   Walker, C
   Lanford, RE
   Lemon, SM
AF Feng, Zongdi
   Hensley, Lucinda
   McKnight, Kevin L.
   Hu, Fengyu
   Madden, Victoria
   Ping, LiFang
   Jeong, Sook-Hyang
   Walker, Christopher
   Lanford, Robert E.
   Lemon, Stanley M.
TI A pathogenic picornavirus acquires an envelope by hijacking cellular membranes
SO NATURE
LA English
DT Article
ID hepatitis-a virus; culture-adapted variant; lysosomal degradation; alix; mechanisms; infection; regions; antigen
AB Animal viruses are broadly categorized structurally by the presence or absence of an envelope composed of a lipid-bilayer membrane(1), attributes that profoundly affect stability, transmission and immune recognition. Among those lacking an envelope, the Picornaviridae are a large and diverse family of positive-strand RNA viruses that includes hepatitis A virus (HAV), an ancient human pathogen that remains a common cause of enterically transmitted hepatitis(2-4). HAV infects in a stealth-like manner and replicates efficiently in the liver(5). Virus-specific antibodies appear only after 3-4 weeks of infection, and typically herald its resolution(3,4). Although unexplained mechanistically, both anti-HAV antibody and inactivated whole-virus vaccines prevent disease when administered as late as 2 weeks after exposure(6), when virus replication is well established in the liver(5). Here we show that HAV released from cells is cloaked in host-derived membranes, thereby protecting the virion from antibody-mediated neutralization. These enveloped viruses ('eHAV') resemble exosomes(7), small vesicles that are increasingly recognized to be important in intercellular communications. They are fully infectious, sensitive to extraction with chloroform, and circulate in the blood of infected humans. Their biogenesis is dependent on host proteins associated with endosomal-sorting complexes required for transport (ESCRT)(8), namely VPS4B and ALIX. Whereas the hijacking of membranes by HAV facilitates escape from neutralizing antibodies and probably promotes virus spread within the liver, anti-capsid antibodies restrict replication after infection with eHAV, suggesting a possible explanation for prophylaxis after exposure. Membrane hijacking by HAV blurs the classic distinction between 'enveloped' and 'non-enveloped' viruses and has broad implications for mechanisms of viral egress from infected cells as well as host immune responses.
C1 [Feng, Zongdi; Hensley, Lucinda; McKnight, Kevin L.; Hu, Fengyu; Ping, LiFang; Lemon, Stanley M.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA.
   [Madden, Victoria] Univ N Carolina, Dept Pathol & Lab Med, Chapel Hill, NC 27599 USA.
   [Jeong, Sook-Hyang] Seoul Natl Univ, Bundang Hosp, Dept Internal Med, Songnam 463707, Gyeonggi Do, South Korea.
   [Walker, Christopher] Nationwide Childrens Hosp, Res Inst, Ctr Vaccines & Immun, Columbus, OH 43205 USA.
   [Walker, Christopher] Ohio State Univ, Dept Pediat, Coll Med, Columbus, OH 43205 USA.
   [Lanford, Robert E.] Texas Biomed Res Inst, Dept Virol & Immunol, San Antonio, TX 78227 USA.
   [Lemon, Stanley M.] Univ N Carolina, Dept Med, Div Infect Dis, Chapel Hill, NC 27599 USA.
   [Lemon, Stanley M.] Univ N Carolina, Dept Microbiol & Immunol, 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; Seoul National University (SNU); University System of Ohio; Ohio State University; Nationwide Childrens Hospital; Research Institute at Nationwide Children's Hospital; Center for Vaccines & Immunity; University System of Ohio; Ohio State University; Texas Biomedical Research Institute; University of North Carolina; University of North Carolina Chapel Hill; University of North Carolina; University of North Carolina Chapel Hill
RP Lemon, SM (corresponding author), Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA.
EM smlemon@med.unc.edu
FU National Institutes of Health [R01-AI103083]; University Cancer Research Fund; National Cancer Institute [P30CA016086] Funding Source: NIH RePORTER; National Institute of Allergy and Infectious Diseases [R01AI103083] Funding Source: NIH RePORTER; NIH Office of the Director [P51OD011133] Funding Source: NIH RePORTER
NR 33
TC 593
Z9 687
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 18
PY 2013
VL 496
IS 7445
BP 367
EP +
DI 10.1038/nature12029
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 126FV
UT WOS:000317599200039
PM 23542590
DA 2026-03-09
ER

PT J
AU Lindsey, HA
   Gallie, J
   Taylor, S
   Kerr, B
AF Lindsey, Haley A.
   Gallie, Jenna
   Taylor, Susan
   Kerr, Benjamin
TI Evolutionary rescue from extinction is contingent on a lower rate of environmental change
SO NATURE
LA English
DT Article
ID escherichia-coli; pseudomonas-aeruginosa; rifampicin-resistance; prevent extinction; natural-selection; sign epistasis; climate-change; adaptation; mutations; model
AB The extinction rate of populations is predicted to rise under increasing rates of environmental change(1-3). If a population experiencing increasingly stressful conditions lacks appropriate phenotypic plasticity or access to more suitable habitats, then genetic change may be the only way to avoid extinction(1). Evolutionary rescue from extinction occurs when natural selection enriches a population for more stress-tolerant genetic variants(1,3). Some experimental studies have shown that lower rates of environmental change lead to more adapted populations or fewer extinctions(4-9). However, there has been little focus on the genetic changes that underlie evolutionary rescue. Here we demonstrate that some evolutionary trajectories are contingent on a lower rate of environmental change. We allowed hundreds of populations of Escherichia coli to evolve under variable rates of increase in concentration of the antibiotic rifampicin. We then genetically engineered all combinations of mutations from isolates evolved under lower rates of environmental change. By assessing fitness of these engineered strains across a range of drug concentrations, we show that certain genotypes are evolutionarily inaccessible under rapid environmental change. Rapidly deteriorating environments not only limit mutational opportunities by lowering population size, but they can also eliminate sets of mutations as evolutionary options. As anthropogenic activities are leading to environmental change at unprecedented rapidity(1), it is critical to understand how the rate of environmental change affects both demographic and genetic underpinnings of evolutionary rescue.
C1 [Lindsey, Haley A.; Gallie, Jenna; Taylor, Susan; Kerr, Benjamin] Univ Washington, Dept Biol, Seattle, WA 98195 USA.
   [Lindsey, Haley A.; Gallie, Jenna; Taylor, Susan; Kerr, Benjamin] Univ Washington, BEACON Ctr Study Evolut Act, Seattle, WA 98195 USA.
   [Gallie, Jenna] Eawag, Dept Environm Microbiol, CH-8600 Dubendorf, Switzerland.
   [Gallie, Jenna] ETH, Dept Environm Syst Sci, CH-8092 Zurich, Switzerland.
C3 University of Washington; University of Washington Seattle; University of Washington; University of Washington Seattle; Swiss Federal Institutes of Technology Domain; Swiss Federal Institute of Aquatic Science & Technology (EAWAG); Swiss Federal Institutes of Technology Domain; ETH Zurich
RP Kerr, B (corresponding author), Univ Washington, Dept Biol, Seattle, WA 98195 USA.
EM kerrb@uw.edu
FU National Science Foundation [DBI-0939454]; NSF CAREER [DEB0952825]; UW Royalty Research Fund [A74107]; Division Of Environmental Biology; Direct For Biological Sciences [0952825] Funding Source: National Science Foundation
NR 30
TC 223
Z9 267
U1 1
U2 224
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 28
PY 2013
VL 494
IS 7438
BP 463
EP 467
DI 10.1038/nature11879
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 099YI
UT WOS:000315661500035
PM 23395960
DA 2026-03-09
ER

PT J
AU Burschka, J
   Pellet, N
   Moon, SJ
   Humphry-Baker, R
   Gao, P
   Nazeeruddin, MK
   Grätzel, M
AF Burschka, Julian
   Pellet, Norman
   Moon, Soo-Jin
   Humphry-Baker, Robin
   Gao, Peng
   Nazeeruddin, Mohammad K.
   Graetzel, Michael
TI Sequential deposition as a route to high-performance perovskite-sensitized solar cells
SO NATURE
LA English
DT Article
ID efficient; intercalation; exchange; raman
AB Following pioneering work(1), solution-processable organic-inorganic hybrid perovskites-such as CH3NH3PbX3 (X = Cl, Br, I)-have attracted attention as light-harvesting materials for mesoscopic solar cells(2-15). So far, the perovskite pigment has been deposited in a single step onto mesoporous metal oxide films using a mixture of PbX2 and CH3NH3X in a common solvent. However, the uncontrolled precipitation of the perovskite produces large morphological variations, resulting in a wide spread of photovoltaic performance in the resulting devices, which hampers the prospects for practical applications. Here we describe a sequential deposition method for the formation of the perovskite pigment within the porous metal oxide film. PbI2 is first introduced from solution into a nanoporous titanium dioxide film and subsequently transformed into the perovskite by exposing it to a solution of CH3NH3I. We find that the conversion occurs within the nanoporous host as soon as the two components come into contact, permitting much better control over the perovskite morphology than is possible with the previously employed route. Using this technique for the fabrication of solid-state mesoscopic solar cells greatly increases the reproducibility of their performance and allows us to achieve a power conversion efficiency of approximately 15 per cent (measured under standard AM1.5G test conditions on solar zenith angle, solar light intensity and cell temperature). This two-step method should provide new opportunities for the fabrication of solution-processed photovoltaic cells with unprecedented power conversion efficiencies and high stability equal to or even greater than those of today's best thin-film photovoltaic devices.
C1 [Burschka, Julian; Pellet, Norman; Moon, Soo-Jin; Humphry-Baker, Robin; Gao, Peng; Nazeeruddin, Mohammad K.; Graetzel, Michael] Swiss Fed Inst Technol, Dept Chem & Chem Engn, Lab Photon & Interfaces, CH-1015 Lausanne, Switzerland.
   [Pellet, Norman] Max Planck Inst Solid State Res, D-70569 Stuttgart, Germany.
C3 Swiss Federal Institutes of Technology Domain; Ecole Polytechnique Federale de Lausanne; Max Planck Society
RP Grätzel, M (corresponding author), Swiss Fed Inst Technol, Dept Chem & Chem Engn, Lab Photon & Interfaces, Stn 6, CH-1015 Lausanne, Switzerland.
EM michael.graetzel@epfl.ch
FU Aisin Cosmos R&D Co., Ltd, Japan; European Community [ENERGY.2012.10.2.1]; NANOMATCELL [308997]; Global Research Laboratory Program, Korea; Center for Advanced Molecular Photovoltaics of King Abdullah University of Science and Technology [KUS-C1-015-21]; Solvay S.A.; Ministry of Education, Science and Technology through the National Research Foundation of Korea [R31-2008-000-10035-0]; Max Planck Society; King Abdulaziz University, Jeddah; Nanyang Technolocal University, Singapore; European Research Council [ARG 247404]
NR 25
TC 8699
Z9 9523
U1 96
U2 11782
PU NATURE PUBLISHING 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 18
PY 2013
VL 499
IS 7458
BP 316
EP +
DI 10.1038/nature12340
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 184RJ
UT WOS:000321910700031
PM 23842493
DA 2026-03-09
ER

PT J
AU Delgado-Baquerizo, M
   Maestre, FT
   Gallardol, A
   Bowker, MA
   Wallenstein, MD
   Quero, JL
   Ochoa, V
   Gozalo, B
   Garcia-Gomez, M
   Soliveres, S
   Garcia-Palacios, P
   Berdugo, M
   Valencia, E
   Escolar, C
   Arredondol, T
   Barraza-Zepeda, C
   Bran, D
   Carreiral, JA
   Chaiebll, M
   Conceicao, AA
   Derak, M
   Eldridge, DL
   Escudero, A
   Espinosa, CI
   Gaitan, J
   Gatica, MG
   Gomez-Gonzalez, S
   Guzman, E
   Gutierrez, JR
   Florentino, A
   Hepper, E
   Hernandez, RM
   Huber-Sannwald, E
   Jankju, M
   Liu, JS
   Mau, RL
   Miriti, M
   Monerris, J
   Naseri, K
   Noumi, Z
   Polo, V
   Prina, A
   Pucheta, E
   Ramirez, E
   Ramirez-Collantes, DA
   Romao, R
   Tighe, M
   Torres, D
   Torres-Diaz, C
   Ungar, ED
   Val, J
   Wamiti, W
   Wang, DL
   Zaady, E
AF Delgado-Baquerizo, Manuel
   Maestre, Fernando T.
   Gallardol, Antonio
   Bowker, Matthew A.
   Wallenstein, Matthew D.
   Luis Quero, Jose
   Ochoa, Victoria
   Gozalo, Beatriz
   Garcia-Gomez, Miguel
   Soliveres, Santiago
   Garcia-Palacios, Pablo
   Berdugo, Miguel
   Valencia, Enrique
   Escolar, Cristina
   Arredondo, Turin
   Barraza-Zepeda, Claudia
   Bran, Donald
   Antonio Carreiral, Jose
   Chaieb, Mohamed
   Conceicao, Abel A.
   Derak, Mchich
   Eldridge, David J.
   Escudero, Adrian
   Espinosa, Carlos I.
   Gaitan, Juan
   Gatica, M. Gabriel
   Gomez-Gonzalez, Susana
   Guzman, Elizabeth
   Gutierrez, Julio R.
   Florentino, Adriana
   Hepper, Estela
   Hernandez, Rosa M.
   Huber-Sannwald, Elisabeth
   Jankju, Mohammad
   Liu, Jushan
   Mau, Rebecca L.
   Miriti, Maria
   Monerris, Jorge
   Naseri, Kamal
   Noumi, Zouhaier
   Polo, Vicente
   Prina, Anibal
   Pucheta, Eduardo
   Ramirez, Elizabeth
   Ramirez-Collantes, David A.
   Romao, Roberto
   Tighe, Matthew
   Torres, Duiio
   Torres-Diaz, Cristian
   Ungar, Eugene D.
   Val, James
   Wamiti, Wanyoike
   Wang, Deli
   Zaady, Eli
TI Decoupling of soil nutrient cycles as a function of aridity in global drylands
SO NATURE
LA English
DT Article
ID dissolved organic nitrogen; biogeochemical cycles; phosphorus; carbon; matter; transformations; shrublands; retention; feedbacks; responses
AB The biogeochemical cycles of carbon (C), nitrogen (N) and phosphorus (P) are interlinked by primary production, respiration and decomposition in terrestrial ecosystems(1). It has been suggested that the C, N and P cycles could become uncoupled under rapid climate change because of the different degrees of control exerted on the supply of these elements by biological and geochemical processes(1-5). Climatic controls on biogeochemical cycles are particularly relevant in arid, semi-arid and dry sub-humid ecosystems (drylands) because their biological activity is mainly driven by water availability(6-8). The increase in aridity predicted for the twenty-first century in many drylands worldwide(9-11) may therefore threaten the balance between these cycles, differentially affecting the availability of essential nutrients(12-14). Here we evaluate how aridity affects the balance between C, N and P in soils collected from 224 dryland sites from all continents except Antarctica. We find a negative effect of aridity on the concentration of soil organic C and total N, but a positive effect on the concentration of inorganic P. Aridity is negatively related to plant cover, which may favour the dominance of physical processes such as rock weathering, a major source of P to ecosystems, over biological processes that provide more C and N, such as litter decomposition(12-14). Our findings suggest that any predicted increase in aridity with climate change will probably reduce the concentrations of N and C in global drylands, but increase that of P. These changes would uncouple the C, N and P cycles in drylands and could negatively affect the provision of key services provided by these ecosystems.
C1 [Delgado-Baquerizo, Manuel; Gallardol, Antonio] Univ Pablo Olavide, Dept Sistemas Fis Quim & Nat, Seville 41013, Spain.
   [Delgado-Baquerizo, Manuel; Maestre, Fernando T.; Luis Quero, Jose; Ochoa, Victoria; Gozalo, Beatriz; Garcia-Gomez, Miguel; Soliveres, Santiago; Berdugo, Miguel; Valencia, Enrique; Escolar, Cristina; Escudero, Adrian; Polo, Vicente] Univ Rey Juan Carlos, Dept Biol & Geol, Area Biodiversidad & Conservac, Escuela Super Ciencias Expt & Tecnol, Mostoles 28933, Spain.
   [Bowker, Matthew A.] No Arizona Univ, Sch Forestry, Flagstaff, AZ 86011 USA.
   [Wallenstein, Matthew D.; Garcia-Palacios, Pablo] Colorado State Univ, Nat Resource Ecol Lab, Ft Collins, CO 80523 USA.
   [Luis Quero, Jose] Univ Cordoba, Dept Ingn Forestal, E-14071 Cordoba, Spain.
   [Garcia-Palacios, Pablo] Colorado State Univ, Dept Biol, Ft Collins, CO 80523 USA.
   [Arredondo, Turin; Huber-Sannwald, Elisabeth] Inst Potosino Invest Cient Tecnol, Div Ciencias Ambientales, San Luis Potosi 78210, Mexico.
   [Barraza-Zepeda, Claudia; Gutierrez, Julio R.] Univ La Serena, Dept Biol, Coquimbo Region 1700000, Chile.
   [Bran, Donald; Gaitan, Juan] Inst Nacl Tecnol Agropecuaria, Estn Expt San Carlos Bariloche 277, RA-8400 San Carlos De Bariloche, Rio Negro, Argentina.
   [Antonio Carreiral, Jose] Univ Jaen, Dept Biol Anim Biol Vegetal & Ecol, Jaen 23071, Spain.
   [Chaieb, Mohamed; Noumi, Zouhaier] Univ Sfax, Fac Sci, Unite Rech Plant Divers & Ecosyst Arid Environm, Sfax 3018, Tunisia.
   [Conceicao, Abel A.; Romao, Roberto] Univ Estadual Feira de Santana, Dept Ciencias Biol, Bairro Novo Horizonte 44036, Feira De Santan, Brazil.
   [Derak, Mchich] Direct Reg Eaux & Forets & Lutte Desertificat Rif, Tetouan 93000, Morocco.
   [Eldridge, David J.] Univ New S Wales, Sch Biol Earth Environm Sci, Sydney, NSW 2052, Australia.
   [Espinosa, Carlos I.; Guzman, Elizabeth] Univ Tecn Particular Loja, Inst Ecol, Marcelino Champagnat, Loja, Ecuador.
   [Gatica, M. Gabriel; Pucheta, Eduardo] Univ Nacl San Juan, Dept Biol, Fac Ciencias Exactas Fis & Nat, Rivadavia, San Juan, Argentina.
   [Gomez-Gonzalez, Susana; Torres-Diaz, Cristian] Univ Bio Bio 447, Dept Ciencias Basicas, Lab Genom & Biodiversidad, Chillan 3780000, Chile.
   [Florentino, Adriana] Cent Univ Venezuela, Fac Agron, Inst Edafol, Caracas 1051, Venezuela.
   [Hepper, Estela; Prina, Anibal] Univ Nacl La Pampa, Fac Agron, RA-6300 Santa Rosa, La Pampa, Argentina.
   [Hernandez, Rosa M.; Ramirez, Elizabeth] Univ Expt Simon Rodriguez, Ctr Agroecol Trop, Lab Biogeoquim, Caracas 47925, Venezuela.
   [Jankju, Mohammad; Naseri, Kamal] Ferdowsi Univ Mashhad, Dept Range & Watershed Management, Fac Nat Resources & Environm, Mashhad 917751363, Iran.
   [Liu, Jushan; Wang, Deli] NE Normal Univ, Inst Grassland Sci, Changchun 130024, Jilin Province, Peoples R China.
   [Liu, Jushan; Wang, Deli] Minist Educ, Key Lab Vegetat Ecol, Changchun 130024, Jilin Province, Peoples R China.
   [Mau, Rebecca L.] No Arizona Univ, Dept Biol Sci, Flagstaff, AZ 36011 USA.
   [Miriti, Maria] Ohio State Univ, Dept Evolut Ecol & Organismal Biol, Columbus, OH 43210 USA.
   [Monerris, Jorge] Univ Quebec, Dept Sci Biol, Montreal, PQ H2X 3Y5, Canada.
   [Ramirez-Collantes, David A.] Int Potato Ctr, Prod Syst & Environm Sub Program, Lima, Peru.
   [Tighe, Matthew] Univ New England, Sch Environm & Rural Sci, Dept Agron & Soil Sci, Armidale, NSW 2351, Australia.
   [Torres, Duiio] Univ Centroccidental Lisandro Alvarado, Dept Quim & Suelos, Barquisimeto 3001, Venezuela.
   [Ungar, Eugene D.] Agr Res Org, Volcani Ctr, Inst Plant Sci, Dept Agron & Nat Resources, IL-50250 Bet Dagan, Israel.
   [Val, James] Off Environm & Heritage, Buronga, NSW 2739, Australia.
   [Wamiti, Wanyoike] Natl Museums Kenya, Dept Zool, Nairobi 7842000500, Kenya.
   [Zaady, Eli] Agr Res Org, Dept Nat Resources & Agron, Minist Agr, IL-85280 Negev, Israel.
C3 Universidad Pablo de Olavide; Universidad Rey Juan Carlos; Northern Arizona University; Colorado State University System; Colorado State University Fort Collins; Universidad de Cordoba; Colorado State University System; Colorado State University Fort Collins; Instituto Potosino Investigacion Cientifica y Tecnologica; Universidad de La Serena; Instituto Nacional de Tecnologia Agropecuaria (INTA); Universidad de Jaen; Universite de Sfax; Faculty of Sciences Sfax; Universidade Estadual de Feira de Santana; University of New South Wales Sydney; Universidad Tecnica Particular de Loja; Universidad Nacional de San Juan; University of Central Venezuela; Ferdowsi University Mashhad; Northeast Normal University - China; Northern Arizona University; University System of Ohio; Ohio State University; University of Quebec; University of Quebec Montreal; CGIAR; International Potato Center (CIP); University of New England; Volcani Institute of Agricultural Research; Office of Environment & Heritage - New South Wales
RP Delgado-Baquerizo, M (corresponding author), Univ Pablo Olavide, Dept Sistemas Fis Quim & Nat, Carretera Utrera,Kilometro 1, Seville 41013, Spain.
EM mdelbaq@upo.es
FU European Research Council (ERC) under the European Community [242658]; Ministry of Science and Innovation of the Spanish Government [CGL2010-21381]; CYTED [Accion 407AC0323]; Pablo de Olavide University; Division Of Environmental Biology; Direct For Biological Sciences [1020540] Funding Source: National Science Foundation
NR 72
TC 892
Z9 1026
U1 41
U2 1544
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 31
PY 2013
VL 502
IS 7473
BP 672
EP +
DI 10.1038/nature12670
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 243CC
UT WOS:000326293200045
PM 24172979
DA 2026-03-09
ER

PT J
AU Lister, AM
AF Lister, Adrian M.
TI The role of behaviour in adaptive morphological evolution of African proboscideans
SO NATURE
LA English
DT Article
ID environmental-change; isotopic evidence; afar-depression; elephas-recki; late miocene; kenya; hypsodonty; paleoenvironments; ecosystems; carbonates
AB The fossil record richly illustrates the origin of morphological adaptation through time. However, our understanding of the selective forces responsible in a given case, and the role of behaviour in the process, is hindered by assumptions of synchrony between environmental change, behavioural innovation and morphological response. Here I show, from independent proxy data through a 20-million-year sequence of fossil proboscideans in East Africa, that changes in environment, diet and morphology are often significantly offset chronologically, allowing dissection of the roles of behaviour and different selective drivers. These findings point the way to hypothesis-driven testing of the interplay between habitat change, behaviour and morphological adaptation with the use of independent proxies in the fossil record(1).
C1 Nat Hist Museum, Dept Earth Sci, London SW7 5BD, England.
C3 Natural History Museum London
RP Lister, AM (corresponding author), Nat Hist Museum, Dept Earth Sci, Cromwell Rd, London SW7 5BD, England.
EM a.lister@nhm.ac.uk
NR 71
TC 73
Z9 75
U1 1
U2 69
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 15
PY 2013
VL 500
IS 7462
BP 331
EP +
DI 10.1038/nature12275
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 201AF
UT WOS:000323112400032
DA 2026-03-09
ER

PT J
AU Thorne, RM
   Li, W
   Ni, B
   Ma, Q
   Bortnik, J
   Chen, L
   Baker, DN
   Spence, HE
   Reeves, GD
   Henderson, MG
   Kletzing, CA
   Kurth, WS
   Hospodarsky, GB
   Blake, JB
   Fennell, JF
   Claudepierre, SG
   Kanekal, SG
AF Thorne, R. M.
   Li, W.
   Ni, B.
   Ma, Q.
   Bortnik, J.
   Chen, L.
   Baker, D. N.
   Spence, H. E.
   Reeves, G. D.
   Henderson, M. G.
   Kletzing, C. A.
   Kurth, W. S.
   Hospodarsky, G. B.
   Blake, J. B.
   Fennell, J. F.
   Claudepierre, S. G.
   Kanekal, S. G.
TI Rapid local acceleration of relativistic radiation-belt electrons by magnetospheric chorus
SO NATURE
LA English
DT Article
ID whistler-mode chorus; waves; energization; scattering; diffusion
AB Recent analysis of satellite data obtained during the 9 October 2012 geomagnetic storm identified the development of peaks in electron phase space density(1), which are compelling evidence for local electron acceleration in the heart of the outer radiation belt(2,3), but are inconsistent with acceleration by inward radial diffusive transport(4,5). However, the precise physical mechanism responsible for the acceleration on 9 October was not identified. Previous modelling has indicated that a magnetospheric electromagnetic emission known as chorus could be a potential candidate for local electron acceleration(6-10), but a definitive resolution of the importance of chorus for radiation-belt acceleration was not possible because of limitations in the energy range and resolution of previous electron observations and the lack of a dynamic global wave model. Here we report high-resolution electron observations(11) obtained during the 9 October storm and demonstrate, using a two-dimensional simulation performed with a recently developed time-varying data-driven model(12), that chorus scattering explains the temporal evolution of both the energy and angular distribution of the observed relativistic electron flux increase. Our detailed modelling demonstrates the remarkable efficiency of wave acceleration in the Earth's outer radiation belt, and the results presented have potential application to Jupiter, Saturn and other magnetized astrophysical objects.
C1 [Thorne, R. M.; Li, W.; Ni, B.; Ma, Q.; Bortnik, J.; Chen, L.] Univ Calif Los Angeles, Dept Atmospher & Ocean Sci, Los Angeles, CA 90095 USA.
   [Baker, D. N.] Univ Colorado, Lab Atmospher & Space Res, Boulder, CO 80303 USA.
   [Spence, H. E.] Univ New Hampshire, Each Inst Study Earth Oceans & Space, Durham, NH 03824 USA.
   [Reeves, G. D.; Henderson, M. G.] Los Alamos Natl Lab, Space Sci & Applicat Grp, Los Alamos, NM 87544 USA.
   [Kletzing, C. A.; Kurth, W. S.; Hospodarsky, G. B.] Univ Iowa, Dept Phys & Astron, Iowa City, IA 52242 USA.
   [Blake, J. B.; Fennell, J. F.; Claudepierre, S. G.] Aerosp Corp, Los Angeles, CA 90245 USA.
   [Kanekal, S. G.] NASA, Goddard Space Flight Ctr, Greenbelt, MD 20771 USA.
C3 University of California System; University of California Los Angeles; University of Colorado System; University of Colorado Boulder; University System Of New Hampshire; University of New Hampshire; United States Department of Energy (DOE); Los Alamos National Laboratory; University of Iowa; Aerospace Corporation - USA; National Aeronautics & Space Administration (NASA); NASA Goddard Space Flight Center
RP Thorne, RM (corresponding author), Univ Calif Los Angeles, Dept Atmospher & Ocean Sci, Los Angeles, CA 90095 USA.
EM rmt@atmos.ucla.edu
FU JHU/APL under NASA [967399, 921647, NAS5-01072]; EMFISIS [1001057397:01]; ECT [13-041]
NR 30
TC 722
Z9 769
U1 3
U2 91
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 19
PY 2013
VL 504
IS 7480
BP 411
EP +
DI 10.1038/nature12889
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 273ZR
UT WOS:000328575300046
PM 24352287
DA 2026-03-09
ER

PT J
AU Kuhlman, SJ
   Olivas, ND
   Tring, E
   Ikrar, T
   Xu, XM
   Trachtenberg, JT
AF Kuhlman, Sandra J.
   Olivas, Nicholas D.
   Tring, Elaine
   Ikrar, Taruna
   Xu, Xiangmin
   Trachtenberg, Joshua T.
TI A disinhibitory microcircuit initiates critical-period plasticity in the visual cortex
SO NATURE
LA English
DT Article
ID experience-dependent plasticity; remote-control; responses; organization; inhibition; mechanisms; resolution; amblyopia; neocortex; network
AB Early sensory experience instructs the maturation of neural circuitry in the cortex(1,2). This has been studied extensively in the primary visual cortex, in which loss of vision to one eye permanently degrades cortical responsiveness to that eye(3,4), a phenomenon known as ocular dominance plasticity (ODP). Cortical inhibition mediates this process(4-6), but the precise role of specific classes of inhibitory neurons in ODP is controversial. Here we report that evoked firing rates of binocular excitatory neurons in the primary visual cortex immediately drop by half when vision is restricted to one eye, but gradually return to normal over the following twenty-four hours, despite the fact that vision remains restricted to one eye. This restoration of binocular-like excitatory firing rates after monocular deprivation results from a rapid, although transient, reduction in the firing rates of fast-spiking, parvalbumin-positive (PV) interneurons, which in turn can be attributed to a decrease in local excitatory circuit input onto PV interneurons. This reduction in PV-cell-evoked responses after monocular lid suture is restricted to the critical period for ODP and appears to be necessary for subsequent shifts in excitatory ODP. Pharmacologically enhancing inhibition at the time of sight deprivation blocks ODP and, conversely, pharmacogenetic reduction of PV cell firing rates can extend the critical period for ODP. These findings define the microcircuit changes initiating competitive plasticity during critical periods of cortical development. Moreover, they show that the restoration of evoked firing rates of layer 2/3 pyramidal neurons by PV-specific disinhibition is a key step in the progression of ODP.
C1 [Kuhlman, Sandra J.; Tring, Elaine; Trachtenberg, Joshua T.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurobiol, Los Angeles, CA 90048 USA.
   [Olivas, Nicholas D.; Ikrar, Taruna; Xu, Xiangmin] Univ Calif Irvine, Dept Anat & Neurobiol, Irvine, CA 92697 USA.
   [Xu, Xiangmin] Univ Calif Irvine, Dept Biomed Engn, Irvine, CA 92697 USA.
C3 University of California System; University of California Los Angeles; University of California Los Angeles Medical Center; David Geffen School of Medicine at UCLA; University of California System; University of California Irvine; University of California System; University of California Irvine
RP Xu, XM (corresponding author), Univ Calif Irvine, Dept Anat & Neurobiol, Irvine, CA 92697 USA.
EM xiangmix@uci.edu; joshua.trachtenberg@gmail.com
FU US National Eye Institute [EY016052]; US National Institute of Neurological Disorders and Stroke [NS078434]; NARSAD; National Eye Institute [R01EY023871] Funding Source: NIH RePORTER
NR 46
TC 311
Z9 384
U1 1
U2 90
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 26
PY 2013
VL 501
IS 7468
BP 543
EP +
DI 10.1038/nature12485
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 223RP
UT WOS:000324826300057
PM 23975100
DA 2026-03-09
ER

PT J
AU Ruark, E
   Snape, K
   Humburg, P
   Loveday, C
   Bajrami, I
   Brough, R
   Rodrigues, DN
   Renwick, A
   Seal, S
   Ramsay, E
   Duarte, SD
   Rivas, MA
   Warren-Perry, M
   Zachariou, A
   Campion-Flora, A
   Hanks, S
   Murray, A
   Pour, NA
   Douglas, J
   Gregory, L
   Rimmer, A
   Walker, NM
   Yang, TP
   Adlard, JW
   Barwell, J
   Berg, J
   Brady, AF
   Brewer, C
   Brice, G
   Chapman, C
   Cook, J
   Davidson, R
   Donaldson, A
   Douglas, F
   Eccles, D
   Evans, DG
   Greenhalgh, L
   Henderson, A
   Izatt, L
   Kumar, A
   Lalloo, F
   Miedzybrodzka, Z
   Morrison, PJ
   Paterson, J
   Porteous, M
   Rogers, MT
   Shanley, S
   Walker, L
   Gore, M
   Houlston, R
   Brown, MA
   Caufield, MJ
   Deloukas, P
   McCarthy, MI
   Todd, JA
   Turnbull, C
   Reis, JS
   Ashworth, A
   Antoniou, AC
   Lord, CJ
   Donnelly, P
   Rahman, N
AF Ruark, Elise
   Snape, Katie
   Humburg, Peter
   Loveday, Chey
   Bajrami, Ilirjana
   Brough, Rachel
   Rodrigues, Daniel Nava
   Renwick, Anthony
   Seal, Sheila
   Ramsay, Emma
   Duarte, Silvana Del Vecchio
   Rivas, Manuel A.
   Warren-Perry, Margaret
   Zachariou, Anna
   Campion-Flora, Adriana
   Hanks, Sandra
   Murray, Anne
   Pour, Naser Ansari
   Douglas, Jenny
   Gregory, Lorna
   Rimmer, Andrew
   Walker, Neil M.
   Yang, Tsun-Po
   Adlard, Julian W.
   Barwell, Julian
   Berg, Jonathan
   Brady, Angela F.
   Brewer, Carole
   Brice, Glen
   Chapman, Cyril
   Cook, Jackie
   Davidson, Rosemarie
   Donaldson, Alan
   Douglas, Fiona
   Eccles, Diana
   Evans, D. Gareth
   Greenhalgh, Lynn
   Henderson, Alex
   Izatt, Louise
   Kumar, Ajith
   Lalloo, Fiona
   Miedzybrodzka, Zosia
   Morrison, Patrick J.
   Paterson, Joan
   Porteous, Mary
   Rogers, Mark T.
   Shanley, Susan
   Walker, Lisa
   Gore, Martin
   Houlston, Richard
   Brown, Matthew A.
   Caufield, Mark J.
   Deloukas, Panagiotis
   McCarthy, Mark I.
   Todd, John A.
   Turnbull, Clare
   Reis-Filho, Jorge S.
   Ashworth, Alan
   Antoniou, Antonis C.
   Lord, Christopher J.
   Donnelly, Peter
   Rahman, Nazneen
TI Mosaic PPM1D mutations are associated with predisposition to breast and ovarian cancer
SO NATURE
LA English
DT Article
ID detectable clonal mosaicism; confer susceptibility; germline mutations; tumor-suppressor; rare variants; wip1; phosphatase; protein; amplification; inhibitor
AB Improved sequencing technologies offer unprecedented opportunities for investigating the role of rare genetic variation in common disease. However, there are considerable challenges with respect to study design, data analysis and replication(1). Using pooled next-generation sequencing of 507 genes implicated in the repair of DNA in 1,150 samples, an analytical strategy focused on protein-truncating variants (PTVs) and a large-scale sequencing case-control replication experiment in 13,642 individuals, here we show that rare PTVs in the p53-inducible protein phosphatase PPM1D are associated with predisposition to breast cancer and ovarian cancer. PPM1D PTV mutations were present in 25 out of 7,781 cases versus 1 out of 5,861 controls (P = 1.12 x 10(-5)), including 18 mutations in 6,912 individuals with breast cancer (P = 2.42 x 10(-4)) and 12 mutations in 1,121 individuals with ovarian cancer (P = 3.10 x 10(-9)). Notably, all of the identified PPM1D PTVs were mosaic in lymphocyte DNA and clustered within a 370-base-pair region in the final exon of the gene, carboxy-terminal to the phosphatase catalytic domain. Functional studies demonstrate that the mutations result in enhanced suppression of p53 in response to ionizing radiation exposure, suggesting that the mutant alleles encode hyperactive PPM1D isoforms. Thus, although the mutations cause premature protein truncation, they do not result in the simple loss-of-function effect typically associated with this class of variant, but instead probably have a gain-of-function effect. Our results have implications for the detection and management of breast and ovarian cancer risk. More generally, these data provide new insights into the role of rare and of mosaic genetic variants in common conditions, and the use of sequencing in their identification.
C1 [Ruark, Elise; Snape, Katie; Loveday, Chey; Renwick, Anthony; Seal, Sheila; Ramsay, Emma; Duarte, Silvana Del Vecchio; Warren-Perry, Margaret; Zachariou, Anna; Hanks, Sandra; Murray, Anne; Pour, Naser Ansari; Douglas, Jenny; Houlston, Richard; Turnbull, Clare; Rahman, Nazneen] Inst Canc Res, Div Genet & Epidemiol, Sutton SM2 5NG, Surrey, England.
   [Humburg, Peter; Rivas, Manuel A.; Gregory, Lorna; Rimmer, Andrew] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.
   [Bajrami, Ilirjana; Brough, Rachel; Rodrigues, Daniel Nava; Campion-Flora, Adriana; Reis-Filho, Jorge S.; Ashworth, Alan; Lord, Christopher J.] Inst Canc Res, Breakthrough Breast Canc Res Ctr, London SW3 6JB, England.
   [Brough, Rachel] Inst Canc Res, Canc Res UK Gene Funct Lab, London SW3 6JB, England.
   [Rivas, Manuel A.] Univ Oxford, Nuffield Dept Clin Med, Oxford OX3 7LD, England.
   [Walker, Neil M.; Todd, John A.] Univ Cambridge, Addenbrookes Hosp, Cambridge Inst Med Res, Juvenile Diabet Res Fdn,Wellcome Trust Diabet & I, Cambridge CB2 0XY, England.
   [Yang, Tsun-Po] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England.
   [Adlard, Julian W.] Chapel Allerton Hosp, Yorkshire Reg Genet Serv, Leeds LS7 4SA, W Yorkshire, England.
   [Barwell, Julian] Univ Hosp Leicester NHS Trust, Leicestershire Genet Ctr, Leicester LE1 5WW, Leics, England.
   [Berg, Jonathan] Univ Dundee, Div Med Sci, Dundee DD1 9SY, Scotland.
   [Brady, Angela F.] Kennedy Galton Ctr, NW Thames Reg Genet Serv, London HA1 3UJ, England.
   [Brewer, Carole] Royal Devon & Exeter Hosp, Peninsula Reg Genet Serv, Exeter EX1 2ED, Devon, England.
   [Brice, Glen] St George Hosp, SW Thames Reg Genet Serv, London SW17 0RE, England.
   [Chapman, Cyril] Birmingham Womens Hosp, W Midlands Reg Genet Serv, Birmingham B15 2TG, W Midlands, England.
   [Cook, Jackie] Sheffield Childrens NHS Fdn Trust, Sheffield Reg Genet Serv, Sheffield S10 2TH, S Yorkshire, England.
   [Davidson, Rosemarie] So Gen Hosp, Lab Med, W Scotland Reg Genet Serv, Glasgow G51 4TF, Lanark, Scotland.
   [Donaldson, Alan] Univ Hosp Bristol NHS Fdn Trust, SW Reg Genet Serv, Bristol BS2 8EG, Avon, England.
   [Douglas, Fiona; Henderson, Alex] Newcastle Upon Tyne Hosp NHS Fdn Trust, No Genet Serv, Newcastle Upon Tyne NE1 3BZ, Tyne & Wear, England.
   [Eccles, Diana] Univ Southampton, Southampton Univ Hosp NHS Trust, Fac Med, Southampton SO16 5YA, Hants, England.
   [Evans, D. Gareth] St Marys Hosp, Manchester Acad Hlth Sci Ctr, Manchester M13 9WL, Lancs, England.
   [Greenhalgh, Lynn] Liverpool Womens NHS Fdn Trust, Merseyside & Cheshire Clin Genet Serv, Liverpool L8 7SS, Merseyside, England.
   [Izatt, Louise] Guys & St Thomas NHS Fdn Trust, SE Thames Reg Genet Serv, London SE1 9RT, England.
   [Kumar, Ajith] Great Ormond St Hosp Sick Children, NE Thames Reg Genet Serv, London WC1N 3JH, England.
   [Lalloo, Fiona] St Marys Hosp, Univ Dept Med Genet & Reg Genet Serv, Manchester M13 9WL, Lancs, England.
   [Miedzybrodzka, Zosia] Aberdeen Royal Infirm, Aberdeen & N Scotland Clin Genet Serv, Aberdeen AB25 2ZA, Scotland.
   [Morrison, Patrick J.] Queens Univ Belfast, Dept Med Genet, Belfast HSC Trust, No Ireland Reg Genet Serv, Belfast BT9 7AB, Antrim, North Ireland.
   [Paterson, Joan] Cambridge Univ Hosp NHS Fdn Trust, E Anglian Reg Genet Serv, Cambridge CB2 0QQ, England.
   [Porteous, Mary] Western Gen Hosp, SE Scotland Clin Genet Serv, Edinburgh EH4 2XU, Midlothian, Scotland.
   [Rogers, Mark T.] Univ Wales Hosp, All Wales Med Genet Serv, Cardiff CF14 4XW, S Glam, Wales.
   [Shanley, Susan] Royal Marsden NHS Fdn Trust, Dept Canc Genet, Sutton SM2 5PT, Surrey, England.
   [Walker, Lisa] Oxford Univ Hosp NHS Trust, Oxford Reg Genet Serv, Oxford OX3 7LJ, England.
   [Gore, Martin] Royal Marsden NHS Fdn, Dept Gynaecol Oncol, London SW3 6JJ, England.
   [Brown, Matthew A.] Univ Queensland, Princess Alexandra Hosp, Diamantina Inst, Brisbane, Qld 4102, Australia.
   [Caufield, Mark J.] Queen Mary Univ London, London Sch Med & Dent, William Harvey Res Inst, Clin Pharmacol & Barts & London Genome Ctr, London EC1M 6BQ, England.
   [McCarthy, Mark I.] Univ Oxford, Churchill Hosp, Oxford Ctr Diabet Endocrinol & Med, Oxford OX3 7LI, England.
   [McCarthy, Mark I.] Churchill Hosp, Oxford NIHR Biomed Res Ctr, Oxford OX3 7LI, England.
   [Antoniou, Antonis C.] Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge CB1 8RN, England.
   [Donnelly, Peter] Univ Oxford, Dept Stat, Oxford OX1 3TG, England.
C3 University of London; Institute of Cancer Research - UK; University of Oxford; Wellcome Centre for Human Genetics; University of London; Institute of Cancer Research - UK; Royal Marsden NHS Foundation Trust; Cancer Research UK; Royal Marsden NHS Foundation Trust; University of London; Institute of Cancer Research - UK; University of Oxford; Cambridge University Hospitals NHS Foundation Trust; Addenbrooke's Hospital; University of Cambridge; Wellcome Trust Sanger Institute; Chapel Allerton Hospital; University Hospitals of Leicester NHS Trust; University of Leicester; University of Dundee; University of Exeter; City St Georges, University of London; Birmingham Women's Hospital; Sheffield Children's NHS Foundation Trust; University of Glasgow; University of Bristol; Newcastle University - UK; Newcastle Upon Tyne Hospitals NHS Foundation Trust; University of Southampton; University Hospital Southampton NHS Foundation Trust; University of Manchester; Guy's & St Thomas' NHS Foundation Trust; University of London; University College London; Great Ormond Street Hospital for Children NHS Foundation Trust; University of Manchester; University of Aberdeen; Queens University Belfast; University of Cambridge; University of Edinburgh; Cardiff University; Royal Marsden NHS Foundation Trust; Oxford University Hospitals NHS Foundation Trust; Royal Marsden NHS Foundation Trust; Princess Alexandra Hospital; University of Queensland; University of London; Queen Mary University London; University of Oxford; University of Cambridge; University of Oxford
RP Rahman, N (corresponding author), Inst Canc Res, Div Genet & Epidemiol, Sutton SM2 5NG, Surrey, England.
EM nazneen.rahman@icr.ac.uk
FU Wellcome Trust [090532/Z/09/Z]; Medical Research Council (MRC) Hub grant [G0900747 91070]; Institute of Cancer Research; Cancer Research UK; RMH-ICR National Institute for Health Research (NIHR) Specialist Biomedical Research Centre for Cancer; MRC [G0000934]; Cancer Research UK Senior Cancer Research Fellow [C12292/A11174]; Wolfson-Royal Society Merit Award; Michael and Betty Kadoorie Cancer Genetics Research Programme; MRC [G9521010, G0800759, G0000934, G0800675, G0600329, G0700491] Funding Source: UKRI; Cancer Research UK [15106, 11174, 14276] Funding Source: researchfish; Chief Scientist Office [CZB/4/540, ETM/137, ETM/75] Funding Source: researchfish; Medical Research Council [MR/K006584/1, G0900747, G0000934, G0600329, G0800759, G0700491, G0800675, G9521010] Funding Source: researchfish; National Institute for Health Research [NF-SI-0611-10219, NF-SI-0508-10275] Funding Source: researchfish; Wellcome Trust [095552/Z/11/Z] Funding Source: researchfish
NR 40
TC 212
Z9 240
U1 0
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 JAN 17
PY 2013
VL 493
IS 7432
BP 406
EP U152
DI 10.1038/nature11725
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 071TA
UT WOS:000313615900052
PM 23242139
DA 2026-03-09
ER

PT J
AU Anderson, JS
   Rittle, J
   Peters, JC
AF Anderson, John S.
   Rittle, Jonathan
   Peters, Jonas C.
TI Catalytic conversion of nitrogen to ammonia by an iron model complex
SO NATURE
LA English
DT Article
ID molecular nitrogen; reduction; molybdenum; dinitrogen; n-2; hydrogenation; mechanism; transformation; cleavage; carbon
AB The reduction of nitrogen (N-2) to ammonia (NH3) is a requisite transformation for life(1). Although it is widely appreciated that the iron-rich cofactors of nitrogenase enzymes facilitate this transformation(2-5), how they do so remains poorly understood. A central element of debate has been the exact site or sites of N-2 coordination and reduction(6,7). In synthetic inorganic chemistry, an early emphasis was placed on molybdenum(8) because it was thought to be an essential element of nitrogenases(3) and because it had been established that well-defined molybdenum model complexes could mediate the stoichiometric conversion of N-2 to NH3 (ref. 9). This chemical transformation can be performed in a catalytic fashion by two well-defined molecular systems that feature molybdenum centres(10,11). However, it is now thought that iron is the only transition metal essential to all nitrogenases(3), and recent biochemical and spectroscopic data have implicated iron instead of molybdenum as the site of N-2 binding in the FeMo-cofactor(12). Here we describe a tris(phosphine) borane-supported iron complex that catalyses the reduction of N-2 to NH3 under mild conditions, and in which more than 40 per cent of the proton and reducing equivalents are delivered to N-2. Our results indicate that a single iron site may be capable of stabilizing the various NxHy intermediates generated during catalytic NH3 formation. Geometric tunability at iron imparted by a flexible iron-boron interaction in our model system seems to be important for efficient catalysis(13-15). We propose that the interstitial carbon atom recently assigned in the nitrogenase cofactor may have a similar role(16,17), perhaps by enabling a single iron site to mediate the enzymatic catalysis through a flexible iron-carbon interaction(18).
C1 [Anderson, John S.; Rittle, Jonathan; Peters, Jonas C.] CALTECH, Div Chem & Chem Engn, Pasadena, CA 91125 USA.
C3 California Institute of Technology
RP Peters, JC (corresponding author), CALTECH, Div Chem & Chem Engn, Pasadena, CA 91125 USA.
EM jpeters@caltech.edu
FU NIH [GM 070757]; Gordon and Betty Moore Foundation; National Institute of General Medical Sciences [R01GM070757] Funding Source: NIH RePORTER
NR 35
TC 851
Z9 977
U1 11
U2 1107
PU NATURE PUBLISHING 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 5
PY 2013
VL 501
IS 7465
BP 84
EP +
DI 10.1038/nature12435
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 211ER
UT WOS:000323888300036
PM 24005414
DA 2026-03-09
ER

PT J
AU Bogorad, IW
   Lin, TS
   Liao, JC
AF Bogorad, Igor W.
   Lin, Tzu-Shyang
   Liao, James C.
TI Synthetic non-oxidative glycolysis enables complete carbon conservation
SO NATURE
LA English
DT Article
ID escherichia-coli; pathway; flux; assimilation; metabolism; catabolism; expression; conversion; products; glucose
AB Glycolysis, or its variations, is a fundamental metabolic pathway in life that functions in almost all organisms to decompose external or intracellular sugars. The pathway involves the partial oxidation and splitting of sugars to pyruvate, which in turn is decarboxylated to produce acetyl-coenzyme A (CoA) for various biosynthetic purposes. The decarboxylation of pyruvate loses a carbon equivalent, and limits the theoretical carbon yield to only two moles of two-carbon (C2) metabolites per mole of hexose. This native route is a major source of carbon loss in biorefining and microbial carbon metabolism. Here we design and construct a non-oxidative, cyclic pathway that allows the production of stoichiometric amounts of C2 metabolites from hexose, pentose and triose phosphates without carbon loss. We tested this pathway, termed non-oxidative glycolysis (NOG), in vitro and in vivo in Escherichia coli. NOG enables complete carbon conservation in sugar catabolism to acetyl-CoA, and can be used in conjunction with CO2 fixation(1) and other one-carbon (C1) assimilation pathways(2) to achieve a 100% carbon yield to desirable fuels and chemicals.
C1 [Bogorad, Igor W.; Lin, Tzu-Shyang; Liao, James C.] Univ Calif Los Angeles, Dept Chem & Biomol Engn, Los Angeles, CA 90095 USA.
   [Bogorad, Igor W.] Univ Calif Los Angeles, Dept Bioengn, Los Angeles, CA 90095 USA.
   [Liao, James C.] Univ Calif Los Angeles, Inst Genom & Prote, Los Angeles, CA 90095 USA.
C3 University of California System; University of California Los Angeles; University of California System; University of California Los Angeles; University of California System; University of California Los Angeles
RP Liao, JC (corresponding author), Univ Calif Los Angeles, Dept Chem & Biomol Engn, 420 Westwood Plaza, Los Angeles, CA 90095 USA.
EM liaoj@ucla.edu
FU National Science Foundation (NSF) [MCB-1139318]; Department of Energy (DOE) [DE0-SC0006698]; NSF Integrative Graduate Education and Research Traineeship (IGERT) [0903720]; Direct For Education and Human Resources [0903720] Funding Source: National Science Foundation; Division Of Graduate Education [0903720] Funding Source: National Science Foundation
NR 31
TC 325
Z9 415
U1 9
U2 294
PU NATURE PUBLISHING 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 31
PY 2013
VL 502
IS 7473
BP 693
EP +
DI 10.1038/nature12575
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 243CC
UT WOS:000326293200050
PM 24077099
DA 2026-03-09
ER

PT J
AU Berggren, G
   Adamska, A
   Lambertz, C
   Simmons, TR
   Esselborn, J
   Atta, M
   Gambarelli, S
   Mouesca, JM
   Reijerse, E
   Lubitz, W
   Happe, T
   Artero, V
   Fontecave, M
AF Berggren, G.
   Adamska, A.
   Lambertz, C.
   Simmons, T. R.
   Esselborn, J.
   Atta, M.
   Gambarelli, S.
   Mouesca, J. -M.
   Reijerse, E.
   Lubitz, W.
   Happe, T.
   Artero, V.
   Fontecave, M.
TI Biomimetic assembly and activation of [FeFe]-hydrogenases
SO NATURE
LA English
DT Article
ID fe-only hydrogenase; active-site; h-cluster; desulfovibrio-desulfuricans; chlamydomonas-reinhardtii; s-adenosylmethionine; linkage isomerism; biofuel cell; iron; coordination
AB Hydrogenases are the most active molecular catalysts for hydrogen production and uptake(1,2), and could therefore facilitate the development of new types of fuel cell(3-5). In [FeFe]-hydrogenases, catalysis takes place at a unique di-iron centre (the [2Fe] subsite), which contains a bridging dithiolate ligand, three CO ligands and two CN- ligands(6,7). Through a complex multienzymatic biosynthetic process, this [2Fe] subsite is first assembled on a maturation enzyme, HydF, and then delivered to the apo-hydrogenase for activation(8). Synthetic chemistry has been used to prepare remarkably similar mimics of that subsite(1), but it has failed to reproduce the natural enzymatic activities thus far. Here we show that three synthetic mimics (containing different bridging dithiolate ligands) can be loaded onto bacterial Thermotoga maritima HydF and then transferred to apo-HydA1, one of the hydrogenases of Chlamy-domonas reinhardtii algae. Full activation of HydA1 was achieved only when using the HydF hybrid protein containing the mimic with an azadithiolate bridge, confirming the presence of this ligand in the active site of native [FeFe]-hydrogenases(9,10). This is an example of controlled metalloenzyme activation using the combination of a specific protein scaffold and active-site synthetic analogues. This simple methodology provides both new mechanistic and structural insight into hydrogenase maturation and a unique tool for producing recombinant wild-type and variant [FeFe]-hydrogenases, with no requirement for the complete maturation machinery.
C1 [Berggren, G.; Simmons, T. R.; Atta, M.; Artero, V.; Fontecave, M.] Univ Grenoble 1, CNRS, CEA, Lab Chim & Biol Met, F-38054 Grenoble 9, France.
   [Berggren, G.; Fontecave, M.] Coll France, F-75231 Paris 5, France.
   [Adamska, A.; Reijerse, E.; Lubitz, W.] Max Planck Inst Chem Energiekonvers, D-45470 Mulheim, Germany.
   [Lambertz, C.; Esselborn, J.; Happe, T.] Ruhr Univ Bochum, AG Photobiotechnol, Lehrstuhl Biochem Pflanzen, D-44801 Bochum, Germany.
   [Gambarelli, S.; Mouesca, J. -M.] Univ Grenoble 1, CEA INAC, Lab Chim Inorgan & Biol, UMR E 3, F-38054 Grenoble 9, France.
C3 Centre National de la Recherche Scientifique (CNRS); CEA; Communaute Universite Grenoble Alpes; Universite Grenoble Alpes (UGA); Universite PSL; College de France; Max Planck Society; Ruhr University Bochum; Communaute Universite Grenoble Alpes; Universite Grenoble Alpes (UGA)
RP Fontecave, M (corresponding author), Univ Grenoble 1, CNRS, CEA, Lab Chim & Biol Met, 17 Rue Martyrs, F-38054 Grenoble 9, France.
EM marc.fontecave@cea.fr
FU Bengt Lundqvist Minnesfond, FORMAS [213-2010-563]; Swedish Royal Academy of Sciences; French National Research Agency (ANR) [07-BLAN-0298-01]; Labex programme (ARCANE) [11-LABX-003]; European Research Council under the European Union's Seventh Framework Programme [306398]; Deutsche Forschungsgemeinschaft [HA 255/2-1]; BMBF [Bio-H2]; Volkswagen foundation [LigH2t]; Max Planck Society
NR 36
TC 584
Z9 660
U1 4
U2 620
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 4
PY 2013
VL 499
IS 7456
BP 66
EP +
DI 10.1038/nature12239
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 176ED
UT WOS:000321285600034
PM 23803769
DA 2026-03-09
ER

PT J
AU Song, YT
   Chen, X
   Dabade, V
   Shield, TW
   James, RD
AF Song, Yintao
   Chen, Xian
   Dabade, Vivekanand
   Shield, Thomas W.
   James, Richard D.
TI Enhanced reversibility and unusual microstructure of a phase-transforming material
SO NATURE
LA English
DT Article
ID shape-memory alloys; x-ray-diffraction; hysteresis; alchemi; driven; strain
AB Materials undergoing reversible solid-to-solid martensitic phase transformations are desirable for applications in medical sensors and actuators(1), eco-friendly refrigerators(2,3) and energy conversion devices(4). The ability to pass back and forth through the phase transformation many times without degradation of properties (termed 'reversibility') is critical for these applications. Materials tuned to satisfy a certain geometric compatibility condition have been shown(2,5-14) to exhibit high reversibility, measured by low hysteresis and small migration of transformation temperature under cycling(6,9,12,15). Recently, stronger compatibility conditions called the 'cofactor conditions'(5,15) have been proposed theoretically to achieve even better reversibility. Here we report the enhanced reversibility and unusual microstructure of the first martensitic material, Zn45Au30Cu25, that closely satisfies the cofactor conditions. We observe four striking properties of thismaterial. (1) Despite a transformation strain of 8%, the transformation temperature shifts less than 0.5 degrees C after more than 16,000 thermal cycles. For comparison, the transformation temperature of the ubiquitous NiTi alloy shifts up to 20 degrees C in the first 20 cycles(9,16). (2) The hysteresis remains approximately 2 degrees C during this cycling. For comparison, the hysteresis of the NiTi alloy is up to 70 degrees C (refs 9, 12). (3) The alloy exhibits an unusual riverine microstructure of martensite not seen in other martensites. (4) Unlike that of typical polycrystal martensites, its microstructure changes drastically in consecutive transformation cycles, whereas macroscopic properties such as transformation temperature and latent heat are nearly reproducible. These results promise a concrete strategy for seeking ultra-reliable martensitic materials.
C1 [Song, Yintao; Chen, Xian; Dabade, Vivekanand; Shield, Thomas W.; James, Richard D.] Univ Minnesota, Dept Aerosp Engn & Mech, Minneapolis, MN 55455 USA.
C3 University of Minnesota System; University of Minnesota Twin Cities
RP James, RD (corresponding author), Univ Minnesota, Dept Aerosp Engn & Mech, Minneapolis, MN 55455 USA.
EM james@umn.edu
FU MURI [FA9550-12-1-0458, W911NF-07-1-0410]; NSF-PIRE [OISE-0967140]; Graduate School of the University of Minnesota; Office Of Internatl Science &Engineering; Office Of The Director [0967140] Funding Source: National Science Foundation
NR 30
TC 389
Z9 432
U1 5
U2 422
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 3
PY 2013
VL 502
IS 7469
BP 85
EP 88
DI 10.1038/nature12532
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 227IM
UT WOS:000325106000035
PM 24091977
DA 2026-03-09
ER

PT J
AU Cotillard, A
   Kennedy, SP
   Kong, LC
   Prifti, E
   Pons, N
   Le Chatelier, E
   Almeida, M
   Quinquis, B
   Levenez, F
   Galleron, N
   Gougis, S
   Rizkalla, S
   Batto, JM
   Renault, P
   Doré, J
   Zucker, JD
   Clément, K
   Ehrlich, SD
AF Cotillard, Aurelie
   Kennedy, Sean P.
   Kong, Ling Chun
   Prifti, Edi
   Pons, Nicolas
   Le Chatelier, Emmanuelle
   Almeida, Mathieu
   Quinquis, Benoit
   Levenez, Florence
   Galleron, Nathalie
   Gougis, Sophie
   Rizkalla, Salwa
   Batto, Jean-Michel
   Renault, Pierre
   Dore, Joel
   Zucker, Jean-Daniel
   Clement, Karine
   Ehrlich, Stanislav Dusko
TI Dietary intervention impact on gut microbial gene richness
SO NATURE
LA English
DT Article
ID insulin sensitivity; obese; index; inflammation; resistance; overweight; mass
AB Complex gene-environment interactions are considered important in the development of obesity(1). The composition of the gut microbiota can determine the efficacy of energy harvest from food(2-4) and changes in dietary composition have been associated with changes in the composition of gut microbial populations(5,6). The capacity to explore microbiota composition was markedly improved by the development of metagenomic approaches(7,8), which have already allowed production of the first human gut microbial gene catalogue(9) and stratifying individuals by their gut genomic profile into different enterotypes(10), but the analyses were carried out mainly in nonintervention settings. To investigate the temporal relationships between food intake, gut microbiota and metabolic and inflammatory phenotypes, we conducted diet-induced weight-loss and weight-stabilization interventions in a study sample of 38 obese and 11 overweight individuals. Here we report that individuals with reduced microbial gene richness (40%) present more pronounced dys-metabolism and low-grade inflammation, as observed concomitantly in the accompanying paper(11). Dietary intervention improves low gene richness and clinical phenotypes, but seems to be less efficient for inflammation variables in individuals with lower gene richness. Low gene richness may therefore have predictive potential for the efficacy of intervention.
C1 [Cotillard, Aurelie; Kong, Ling Chun; Prifti, Edi; Rizkalla, Salwa; Zucker, Jean-Daniel; Clement, Karine] Ctr Rech Cordeliers, Inst Natl Sante & Rech Med, U872, Equipe 7, F-75006 Paris, France.
   [Cotillard, Aurelie; Kong, Ling Chun; Prifti, Edi; Rizkalla, Salwa; Zucker, Jean-Daniel; Clement, Karine] Univ Paris 06, F-75006 Paris, France.
   [Kennedy, Sean P.; Prifti, Edi; Pons, Nicolas; Le Chatelier, Emmanuelle; Almeida, Mathieu; Quinquis, Benoit; Levenez, Florence; Galleron, Nathalie; Batto, Jean-Michel; Dore, Joel; Ehrlich, Stanislav Dusko] INRA, Metagenopolis, F-78350 Jouy En Josas, France.
   [Kong, Ling Chun; Gougis, Sophie; Rizkalla, Salwa; Clement, Karine] CRNH Ile France, AP HP, Inst Cardiometab & Nutr, F-75013 Paris, France.
   [Levenez, Florence; Batto, Jean-Michel; Renault, Pierre; Dore, Joel] INRA, UMR Micalis 1319, F-78350 Jouy En Josas, France.
   [Zucker, Jean-Daniel] France Nord, UMMISCO, IRD, UMI 209, F-93143 Bondy, France.
C3 Sorbonne Universite; Universite Paris Cite; Institut National de la Sante et de la Recherche Medicale (Inserm); Sorbonne Universite; INRAE; Universite Paris Saclay; Assistance Publique Hopitaux Paris (APHP); Sorbonne Universite; INRAE; Universite Paris Saclay; AgroParisTech; Hanoi University of Science & Technology (HUST); Hanoi Advanced School of Science & Technology; Cadi Ayyad University of Marrakech; Institut de Recherche pour le Developpement (IRD); Sorbonne Universite; University Cheikh Anta Diop Dakar; University of Yaounde I
RP Ehrlich, SD (corresponding author), INRA, F-78350 Jouy En Josas, France.
EM dusko.ehrlich@jouy.inra.fr
FU Agence Nationale de la Recherche (ANR MICRO-Obes, ANR, Nutra2sens) [ANR-10-IAHU-05]; Metagenopolis grant [ANR-11-DPBS-0001]; KOT-Ceprodi (Florence Massiera); Danone Research (Damien Paineau); association Fondacoeur; association Louis-Bonduelle; European Commission [HEALTH-F4-2007-201052]; METACARDIS
NR 29
TC 1428
Z9 1672
U1 3
U2 462
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 29
PY 2013
VL 500
IS 7464
BP 585
EP +
DI 10.1038/nature12480
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 207TD
UT WOS:000323625900036
PM 23985875
DA 2026-03-09
ER

PT J
AU Tachibana, M
   Amato, P
   Sparman, M
   Woodward, J
   Sanchis, DM
   Ma, H
   Gutierrez, NM
   Tippner-Hedges, R
   Kang, E
   Lee, HS
   Ramsey, C
   Masterson, K
   Battaglia, D
   Lee, D
   Wu, D
   Jensen, J
   Patton, P
   Gokhale, S
   Stouffer, R
   Mitalipov, S
AF Tachibana, Masahito
   Amato, Paula
   Sparman, Michelle
   Woodward, Joy
   Sanchis, Dario Melguizo
   Ma, Hong
   Gutierrez, Nuria Marti
   Tippner-Hedges, Rebecca
   Kang, Eunju
   Lee, Hyo-Sang
   Ramsey, Cathy
   Masterson, Keith
   Battaglia, David
   Lee, David
   Wu, Diana
   Jensen, Jeffrey
   Patton, Phillip
   Gokhale, Sumita
   Stouffer, Richard
   Mitalipov, Shoukhrat
TI Towards germline gene therapy of inherited mitochondrial diseases
SO NATURE
LA English
DT Article
ID oocyte vitrification; activation; common
AB Mutations in mitochondrial DNA (mtDNA) are associated with severe human diseases and are maternally inherited through the egg's cytoplasm. Here we investigated the feasibility of mtDNA replacement in human oocytes by spindle transfer (ST; also called spindle-chromosomal complex transfer). Of 106 human oocytes donated for research, 65 were subjected to reciprocal ST and 33 served as controls. Fertilization rate in ST oocytes (73%) was similar to controls (75%); however, a significant portion of ST zygotes (52%) showed abnormal fertilization as determined by an irregular number of pronuclei. Among normally fertilized ST zygotes, blastocyst development (62%) and embryonic stem cell isolation (38%) rates were comparable to controls. All embryonic stem cell lines derived from ST zygotes had normal euploid karyotypes and contained exclusively donor mtDNA. The mtDNA can be efficiently replaced in human oocytes. Although some ST oocytes displayed abnormal fertilization, remaining embryos were capable of developing to blastocysts and producing embryonic stem cells similar to controls.
C1 [Tachibana, Masahito; Sparman, Michelle; Woodward, Joy; Sanchis, Dario Melguizo; Ma, Hong; Gutierrez, Nuria Marti; Tippner-Hedges, Rebecca; Kang, Eunju; Lee, Hyo-Sang; Ramsey, Cathy; Jensen, Jeffrey; Stouffer, Richard; Mitalipov, Shoukhrat] Oregon Hlth & Sci Univ, Div Reprod & Dev Sci, Oregon Natl Primate Res Ctr, Beaverton, OR 97006 USA.
   [Amato, Paula; Masterson, Keith; Battaglia, David; Lee, David; Wu, Diana; Patton, Phillip; Stouffer, Richard; Mitalipov, Shoukhrat] Oregon Hlth & Sci Univ, Div Reprod Endocrinol, Dept Obstet & Gynecol, Portland, OR 97239 USA.
   [Jensen, Jeffrey] Oregon Hlth & Sci Univ, Ctr Womens Hlth, Portland, OR 97239 USA.
   [Gokhale, Sumita] Boston Univ, Sch Med, Univ Pathologists LLC, Providence, RI 02908 USA.
   [Gokhale, Sumita] Roger Williams Med Ctr, Providence, RI 02908 USA.
C3 Oregon Health & Science University; Oregon National Primate Research Center; Oregon Health & Science University; Oregon Health & Science University; Boston University; Roger Williams Medical Center
RP Mitalipov, S (corresponding author), Oregon Hlth & Sci Univ, Div Reprod & Dev Sci, Oregon Natl Primate Res Ctr, 505 NW 185th Ave, Beaverton, OR 97006 USA.
EM mitalipo@ohsu.edu
FU OHSU Center for Women's Health Circle of Giving; OHSU; Leducq Foundation; National Institutes of Health [HD063276, HD057121, HD059946, EY021214, 8P51OD011092]; NIH Office of the Director; National Institute on Aging [P51OD011092] Funding Source: NIH RePORTER
NR 24
TC 306
Z9 358
U1 0
U2 194
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 31
PY 2013
VL 493
IS 7434
BP 627
EP 631
DI 10.1038/nature11647
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 080CU
UT WOS:000314219600047
PM 23103867
DA 2026-03-09
ER

PT J
AU Atkinson, JD
   Murray, BJ
   Woodhouse, MT
   Whale, TF
   Baustian, KJ
   Carslaw, KS
   Dobbie, S
   O'Sullivan, D
   Malkin, TL
AF Atkinson, James D.
   Murray, Benjamin J.
   Woodhouse, Matthew T.
   Whale, Thomas F.
   Baustian, Kelly J.
   Carslaw, Kenneth S.
   Dobbie, Steven
   O'Sullivan, Daniel
   Malkin, Tamsin L.
TI The importance of feldspar for ice nucleation by mineral dust in mixed-phase clouds
SO NATURE
LA English
DT Article
ID biological particles; aerosol; climate; nuclei; model
AB The amount of ice present in mixed-phase clouds, which contain both supercooled liquid water droplets and ice particles, affects cloud extent, lifetime, particle size and radiative properties(1,2). The freezing of cloud droplets can be catalysed by the presence of aerosol particles known as ice nuclei(2). One of the most important ice nuclei is thought to be mineral dust aerosol from arid regions(2,3). It is generally assumed that clay minerals, which contribute approximately two-thirds of the dust mass, dominate ice nucleation by mineral dust, and many experimental studies have therefore focused on these materials(1,2,4-6). Here we use an established droplet-freezing technique(4,7) to show that feldspar minerals dominate ice nucleation by mineral dusts under mixed-phase cloud conditions, despite feldspar being a minor component of dust emitted from arid regions. We also find that clay minerals are relatively unimportant ice nuclei. Our results from a global aerosol model study suggest that feldspar ice nuclei are globally distributed and that feldspar particles may account for a large proportion of the ice nuclei in Earth's atmosphere that contribute to freezing at temperatures below about -15 degrees C.
C1 [Atkinson, James D.; Murray, Benjamin J.; Woodhouse, Matthew T.; Whale, Thomas F.; Baustian, Kelly J.; Carslaw, Kenneth S.; Dobbie, Steven; O'Sullivan, Daniel; Malkin, Tamsin L.] Univ Leeds, Sch Earth & Environm, Inst Climate & Atmospher Sci, Leeds LS2 9JT, W Yorkshire, England.
C3 University of Leeds
RP Murray, BJ (corresponding author), Univ Leeds, Sch Earth & Environm, Inst Climate & Atmospher Sci, Leeds LS2 9JT, W Yorkshire, England.
EM b.j.murray@leeds.ac.uk
FU European Research Council [240449 ICE]; Natural Environment Research Council [NE/I013466/1, NE/I020059/1, NE/I019057/1]; Royal Society; NERC [NE/H001050/1, NE/K004417/1, NE/I013466/1, NE/I020059/1] Funding Source: UKRI; Natural Environment Research Council [NE/I013466/1, NE/I020059/1, NE/K004417/1, 1047972, NE/H001050/1] Funding Source: researchfish
NR 30
TC 561
Z9 629
U1 13
U2 391
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 20
PY 2013
VL 498
IS 7454
BP 355
EP 358
DI 10.1038/nature12278
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 166XI
UT WOS:000320592900038
PM 23760484
DA 2026-03-09
ER

PT J
AU Caron, JB
   Morris, SC
   Cameron, CB
AF Caron, Jean-Bernard
   Morris, Simon Conway
   Cameron, Christopher B.
TI Tubicolous enteropneusts from the Cambrian period
SO NATURE
LA English
DT Article
ID deuterostome phylogeny; hemichordata; evolution; community; origins; organ
AB Hemichordates are a marine group that, apart from one mono-specific pelagic larval form, are represented by the vermiform enteropneusts and minute colonial tube-dwelling pterobranchs. Together with echinoderms, they comprise the clade Ambulacraria(1). Despite their restricted diversity, hemichordates provide important insights into early deuterostome evolution, notably because of their pharyngeal gill slits(2). Hemichordate phylogeny has long remained problematic(3,4), not least because the nature of any transitional form that might serve to link the anatomically disparate enteropneusts and pterobranchs is conjectural. Hence, inter-relationships have also remained controversial. For example, pterobranchs have sometimes been compared to ancestral echinoderms(1). Molecular data identify enteropneusts as paraphyletic, and harrimaniids(5-8) as the sister group of pterobranchs. Recent molecular phylogenies suggest that enteropneusts are probably basal within hemichordates, contrary to previous views(9), but otherwise provide little guidance as to the nature of the primitive hemichordate(7,8). In addition, the hemichordate fossil record is almost entirely restricted to peridermal skeletons of pterobranchs, notably graptolites(10,11). Owing to their low preservational potentials, fossil enteropneusts are exceedingly rare(12-15), and throw no light on either hemichordate phylogeny or the proposed harrimaniid-pterobranch transition. Here we describe an enteropneust, Spartobranchus tenuis (Walcott, 1911), from the Middle Cambrian-period (Series 3, Stage 5) Burgess Shale. It is remarkably similar to the extant harrimaniids, but differs from all known enteropneusts in that it is associated with a fibrous tube that is sometimes branched. Wesuggest that this is the precursor of the pterobranch periderm, and supports the hypothesis that pterobranchs are miniaturized and derived from an enteropneust-like worm(5,6). It also shows that the periderm was acquired before size reduction and acquisition of feeding tentacles, and that coloniality emerged through aggregation of individuals, perhaps similar to the Cambrian rhabdopleurid Fasciculitubus(11). The presence of both suggests that hemichordates originated at the onset of the Cambrian explosion.
C1 [Caron, Jean-Bernard] Royal Ontario Museum, Dept Nat Hist Palaeobiol, Toronto, ON M5S 2C6, Canada.
   [Morris, Simon Conway] Univ Cambridge, Dept Earth Sci, Cambridge CB2 3EQ, England.
   [Cameron, Christopher B.] Univ Montreal, Dept Sci Biol, Montreal, PQ H2V 2S9, Canada.
C3 Royal Ontario Museum; University of Cambridge; Universite de Montreal
RP Caron, JB (corresponding author), Royal Ontario Museum, Dept Nat Hist Palaeobiol, Toronto, ON M5S 2C6, Canada.
EM jcaron@rom.on.ca
FU Natural Sciences and Engineering Research Council; St John's College, University of Cambridge, UK; Royal Ontario Museum Burgess Shale project [41]
NR 28
TC 69
Z9 74
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 MAR 28
PY 2013
VL 495
IS 7442
BP 503
EP 506
DI 10.1038/nature12017
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 113QN
UT WOS:000316682800044
PM 23485974
DA 2026-03-09
ER

PT J
AU Zheng, XT
   O'Connor, J
   Huchzermeyer, F
   Wang, XL
   Wang, Y
   Wang, M
   Zhou, ZH
AF Zheng, Xiaoting
   O'Connor, Jingmai
   Huchzermeyer, Fritz
   Wang, Xiaoli
   Wang, Yan
   Wang, Min
   Zhou, Zhonghe
TI Preservation of ovarian follicles reveals early evolution of avian reproductive behaviour
SO NATURE
LA English
DT Article
ID alligator-mississippiensis; dinosaur; china; growth; gender; size
AB The two groups of archosaurs, crocodilians and birds, form an extant phylogenetic bracket for understanding the reproductive behaviour of dinosaurs. This behaviour is inferred from preserved nests and eggs, and even gravid individuals(1). Data indicate that many 'avian' traits were already present in Paraves-the clade that includes birds and their close relatives-and that the early evolution of the modern avian form of reproduction was already well on its way(2,3). Like living neornithine birds, non-avian maniraptorans had daily oviposition and asymmetrical eggs with complex shell microstructure, and were known to protect their clutches(4-6). However, like crocodilians, non-avian maniraptorans had two active oviducts (one present in living birds), relatively smaller eggs, and may not have turned their eggs in the way that living birds do(1,6). Here we report on the first discovery of fossilized mature or nearly mature ovarian follicles, revealing a previously undocumented stage in dinosaur reproduction: reproductively active females near ovulation. Preserved in a specimen of the long bony-tailed Jeholornis and two enantiornithine birds from the Early Cretaceous period lacustrine Jehol Biota in northeastern China, these discoveries indicate that basal birds only had one functional ovary, but retained primitive morphologies as a result of their lower metabolic rate relative to living birds. They also indicate that basal birds reached sexual maturity before skeletal maturity, as in crocodiles and paravian dinosaurs. Differences in follicular morphology between Jeholornis and the enantiornithines are interpreted as forming an evolutionary gradient from the reproductive condition in paravian dinosaurs towards neornithine birds. Furthermore, differences between the two enantiornithines indicate that this lineage might also have evolved advanced reproductive traits in parallel to the neornithine lineage.
C1 [Zheng, Xiaoting; Wang, Xiaoli; Wang, Yan] Linyi Univ, Inst Geol & Paleontol, Linyi 276000, Shandong, Peoples R China.
   [Zheng, Xiaoting] Tianyu Nat Hist Museum Shandong, Pingyi 273300, Shandong, Peoples R China.
   [O'Connor, Jingmai; Wang, Min; Zhou, Zhonghe] Chinese Acad Sci, Key Lab Vertebrate Evolut & Human Origin, Inst Vertebrate Paleontol & Paleoanthropol, Beijing 100044, Peoples R China.
   [Huchzermeyer, Fritz] Univ Pretoria, Fac Vet Sci, Dept Paraclin Sci, ZA-0110 Onderstepoort, South Africa.
C3 Linyi University; Chinese Academy of Sciences; Institute of Vertebrate Paleontology & Paleoanthropology, CAS; University of Pretoria
RP O'Connor, J (corresponding author), Linyi Univ, Inst Geol & Paleontol, Linyi 276000, Shandong, Peoples R China.
EM jingmai.oconnor@gmail.com; zhouzhonghe@ivpp.ac.cn
FU National Basic Research Program of China (973 Program) [2012CB821906]; National Natural Science Foundation of China [41172020]; Chinese Academy of Sciences
NR 29
TC 79
Z9 90
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 MAR 28
PY 2013
VL 495
IS 7442
BP 507
EP 511
DI 10.1038/nature11985
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 113QN
UT WOS:000316682800045
PM 23503663
DA 2026-03-09
ER

PT J
AU Maddocks, ODK
   Berkers, CR
   Mason, SM
   Zheng, L
   Blyth, K
   Gottlieb, E
   Vousden, KH
AF Maddocks, Oliver D. K.
   Berkers, Celia R.
   Mason, Susan M.
   Zheng, Liang
   Blyth, Karen
   Gottlieb, Eyal
   Vousden, Karen H.
TI Serine starvation induces stress and p53-dependent metabolic remodelling in cancer cells
SO NATURE
LA English
DT Article
ID pyruvate-kinase m2; p53-inducible regulator; retinoblastoma protein; cycle arrest; dna-damage; p53; apoptosis; glycine; tumors; mice
AB Cancer cells acquire distinct metabolic adaptations to survive stress associated with tumour growth and to satisfy the anabolic demands of proliferation. The tumour suppressor protein p53 (also known as TP53) influences a range of cellular metabolic processes, including glycolysis(1,2), oxidative phosphorylation(3), glutaminolysis(4,5) and anti-oxidant response(6). In contrast to its role in promoting apoptosis during DNA-damaging stress, p53 can promote cell survival during metabolic stress(7), a function that may contribute not only to tumour suppression but also to non-cancer-associated functions of p53(8). Here we show that human cancer cells rapidly use exogenous serine and that serine deprivation triggered activation of the serine synthesis pathway and rapidly suppressed aerobic glycolysis, resulting in an increased flux to the tricarboxylic acid cycle. Transient p53-p21 (also known as CDKN1A) activation and cell-cycle arrest promoted cell survival by efficiently channelling depleted serine stores to glutathione synthesis, thus preserving cellular anti-oxidant capacity. Cells lacking p53 failed to complete the response to serine depletion, resulting in oxidative stress, reduced viability and severely impaired proliferation. The role of p53 in supporting cancer cell proliferation under serine starvation was translated to an in vivo model, indicating that serine depletion has a potential role in the treatment of p53-deficient tumours.
C1 [Maddocks, Oliver D. K.; Berkers, Celia R.; Mason, Susan M.; Zheng, Liang; Blyth, Karen; Gottlieb, Eyal; Vousden, Karen H.] Beatson Inst Canc Res, Glasgow G61 1BD, Lanark, Scotland.
C3 Beatson Institute
RP Vousden, KH (corresponding author), Beatson Inst Canc Res, Switchback Rd, Glasgow G61 1BD, Lanark, Scotland.
EM k.vousden@beatson.gla.ac.uk
FU Cancer Research UK; Netherlands Organisation for Scientific Research
NR 33
TC 813
Z9 954
U1 3
U2 248
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 24
PY 2013
VL 493
IS 7433
BP 542
EP +
DI 10.1038/nature11743
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 075GF
UT WOS:000313871400040
PM 23242140
DA 2026-03-09
ER

PT J
AU Murdock, DJE
   Dong, XP
   Repetski, JE
   Marone, F
   Stampanoni, M
   Donoghue, PCJ
AF Murdock, Duncan J. E.
   Dong, Xi-Ping
   Repetski, John E.
   Marone, Federica
   Stampanoni, Marco
   Donoghue, Philip C. J.
TI The origin of conodonts and of vertebrate mineralized skeletons
SO NATURE
LA English
DT Article
ID teeth; phylogeny; anatomy; jaws
AB Conodonts are an extinct group of jawless vertebrates whose toothlike elements are the earliest instance of a mineralized skeleton in the vertebrate lineage(1,2), inspiring the 'inside-out' hypothesis that teeth evolved independently of the vertebrate dermal skeleton and before the origin of jaws(3-6). However, these propositions have been based on evidence from derived euconodonts. Here we test hypotheses of a paraconodont ancestry of euconodonts(7-11) using synchrotron radiation X-ray tomographic microscopy to characterize and compare the microstructure of morphologically similar euconodont and paraconodont elements. Paraconodonts exhibit a range of grades of structural differentiation, including tissues and a pattern of growth common to euconodont basal bodies. The different grades of structural differentiation exhibited by paraconodonts demonstrate the stepwise acquisition of euconodont characters, resolving debate over the relationship between these two groups. By implication, the putative homology of euconodont crown tissue and vertebrate enamel must be rejected as these tissues have evolved independently and convergently. Thus, the precise ontogenetic, structural and topological similarities between conodont elements and vertebrate odontodes appear to be a remarkable instance of convergence. The last common ancestor of conodonts and jawed vertebrates probably lacked mineralized skeletal tissues. The hypothesis that teeth evolved before jaws and the inside-out hypothesis of dental evolution must be rejected; teeth seem to have evolved through the extension of odontogenic competence from the external dermis to internal epithelium soon after the origin of jaws.
C1 [Murdock, Duncan J. E.; Donoghue, Philip C. J.] Univ Bristol, Sch Earth Sci, Bristol BS8 1RJ, Avon, England.
   [Dong, Xi-Ping] Peking Univ, Sch Earth & Space Sci, Beijing 100871, Peoples R China.
   [Dong, Xi-Ping] Chinese Acad Sci, Nanjing Inst Geol & Palaeontol, State Key Lab Palaeobiol & Stratig, Nanjing 210008, Jiangsu, Peoples R China.
   [Repetski, John E.] US Geol Survey, Natl Ctr, Reston, VA 20192 USA.
   [Marone, Federica; Stampanoni, Marco] Paul Scherrer Inst, Swiss Light Source, CH-5232 Villigen, Switzerland.
   [Stampanoni, Marco] Univ Zurich, Inst Biomed Engn, CH-8006 Zurich, Switzerland.
   [Stampanoni, Marco] ETH, CH-8006 Zurich, Switzerland.
C3 University of Bristol; Peking University; Chinese Academy of Sciences; United States Department of the Interior; United States Geological Survey; Swiss Federal Institutes of Technology Domain; Paul Scherrer Institute; University of Zurich; Swiss Federal Institutes of Technology Domain; ETH Zurich
RP Donoghue, PCJ (corresponding author), Univ Bristol, Sch Earth Sci, Wills Mem Bldg,Queens Rd, Bristol BS8 1RJ, Avon, England.
EM phil.donoghue@bristol.ac.uk
FU Swiss Light Source, Paul Scherrer Institut (Villigen, Switzerland); NERC [NE/G016623/1]; Paul Scherrer Institut; NSFC [41372015]; Natural Environment Research Council [NE/G016623/1] Funding Source: researchfish; NERC [NE/G016623/1] Funding Source: UKRI
NR 29
TC 76
Z9 88
U1 0
U2 127
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 24
PY 2013
VL 502
IS 7472
BP 546
EP +
DI 10.1038/nature12645
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 238YN
UT WOS:000325988400053
PM 24132236
DA 2026-03-09
ER

PT J
AU Orsi, WD
   Edgcomb, VP
   Christman, GD
   Biddle, JF
AF Orsi, William D.
   Edgcomb, Virginia P.
   Christman, Glenn D.
   Biddle, Jennifer F.
TI Gene expression in the deep biosphere
SO NATURE
LA English
DT Article
ID archaea; life; abundance; sediments; biomass
AB Scientific ocean drilling has revealed a deep biosphere of widespread microbial life in sub-seafloor sediment. Microbial metabolism in the marine subsurface probably has an important role in global biogeochemical cycles(1-3), but deep biosphere activities are not well understood(1). Here we describe and analyse the first sub-seafloor metatranscriptomes from anaerobic Peru Margin sediment up to 159 metres below the sea floor, represented by over 1 billion complementary DNA (cDNA) sequence reads. Anaerobic metabolismof amino acids, carbohydrates and lipids seem to be the dominant metabolic processes, and profiles of dissimilatory sulfite reductase (dsr) transcripts are consistent with pore-water sulphate concentration profiles(1). Moreover, transcripts involved in cell division increase as a function of microbial cell concentration, indicating that increases in sub-seafloor microbial abundance are a function of cell division across all three domains of life. These data support calculations(1) and models(4) of sub-seafloor microbial metabolism and represent the first holistic picture of deep biosphere activities.
C1 [Orsi, William D.; Edgcomb, Virginia P.] Woods Hole Oceanog Inst, Dept Geol & Geophys, Woods Hole, MA 02543 USA.
   [Christman, Glenn D.; Biddle, Jennifer F.] Univ Delaware, Coll Earth Ocean & Environm, Lewes, DE 19958 USA.
C3 Woods Hole Oceanographic Institution; University of Delaware
RP Orsi, WD (corresponding author), Woods Hole Oceanog Inst, Dept Geol & Geophys, Woods Hole, MA 02543 USA.
EM william.orsi@gmail.com
FU Center for Dark Energy Biosphere Investigations (CDEBI) [OCE-0939564]; National Science Foundation IOS [1238801]; Division Of Integrative Organismal Systems; Direct For Biological Sciences [1238801] Funding Source: National Science Foundation; Office of Integrative Activities; Office Of The Director [1301765] Funding Source: National Science Foundation
NR 30
TC 222
Z9 250
U1 1
U2 217
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 11
PY 2013
VL 499
IS 7457
BP 205
EP +
DI 10.1038/nature12230
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 179YA
UT WOS:000321557600061
PM 23760485
DA 2026-03-09
ER

PT J
AU Nishiyama, A
   Yamaguchi, L
   Sharif, J
   Johmura, Y
   Kawamura, T
   Nakanishi, K
   Shimamura, S
   Arita, K
   Kodama, T
   Ishikawa, F
   Koseki, H
   Nakanishi, M
AF Nishiyama, Atsuya
   Yamaguchi, Luna
   Sharif, Jafar
   Johmura, Yoshikazu
   Kawamura, Takeshi
   Nakanishi, Keiko
   Shimamura, Shintaro
   Arita, Kyohei
   Kodama, Tatsuhiko
   Ishikawa, Fuyuki
   Koseki, Haruhiko
   Nakanishi, Makoto
TI Uhrf1-dependent H3K23 ubiquitylation couples maintenance DNA methylation and replication
SO NATURE
LA English
DT Article
ID ubiquitin ligase activity; sra domain; epigenetic inheritance; statistical-model; mammalian-cells; gene-expression; uhrf1; protein; recognition; dnmt1
AB Faithful propagation of DNA methylation patterns during DNA replication is critical for maintaining cellular phenotypes of individual differentiated cells(1-5). Although it is well established that Uhrf1 (ubiquitin-like with PHD and ring finger domains 1; also known as Np95 and ICBP90) specifically binds to hemi-methylated DNA through its SRA (SET and RING finger associated) domain and has an essential role in maintenance of DNA methylation by recruiting Dnmt1 to hemi-methylated DNA sites(6-10), the mechanism by which Uhrf1 coordinates the maintenance of DNA methylation and DNA replication is largely unknown. Here we show that Uhrf1-dependent histone H3 ubiquitylation has a prerequisite role in the maintenance DNA methylation. Using Xenopus egg extracts, we successfully reproduce maintenance DNA methylation in vitro. Dnmt1 depletion results in a marked accumulation of Uhrf1-dependent ubiquitylation of histone H3 at lysine 23. Dnmt1 preferentially associates with ubiquitylated H3 in vitro though a region previously identified as a replication foci targeting sequence(11). The RING finger mutant of Uhrf1 fails to recruit Dnmt1 to DNA replication sites and maintain DNA methylation in mammalian cultured cells. Our findings represent the first evidence, to our knowledge, of the mechanistic link between DNA methylation and DNA replication through histone H3 ubiquitylation.
C1 [Nishiyama, Atsuya; Yamaguchi, Luna; Johmura, Yoshikazu; Nakanishi, Makoto] Nagoya City Univ, Grad Sch Med Sci, Dept Cell Biol, Mizuho Ku, Nagoya, Aichi 4678601, Japan.
   [Sharif, Jafar; Koseki, Haruhiko] RIKEN Ctr Integrat Med Sci, Tsurumi Ku, Yokohama, Kanagawa 2300045, Japan.
   [Kawamura, Takeshi; Kodama, Tatsuhiko] Univ Tokyo, RCAST, Lab Syst Biol & Med, Meguro Ku, Tokyo 1538904, Japan.
   [Nakanishi, Keiko] Aichi Human Serv Ctr, Inst Dev Res, Dept Perinatol, Kasugai, Aichi 4800392, Japan.
   [Shimamura, Shintaro] Akita Univ, Grad Sch Med, Dept Mol Med & Biochem, Akita 0108543, Japan.
   [Arita, Kyohei] Yokohama City Univ, Grad Sch Med Life Sci, Tsurumi Ku, Yokohama, Kanagawa 2300045, Japan.
   [Ishikawa, Fuyuki] Kyoto Univ, Grad Sch Biostudies, Dept Gene Mech, Sakyo Ku, Kyoto 6068501, Japan.
C3 Nagoya City University; RIKEN; University of Tokyo; Akita University; Yokohama City University; Kyoto University
RP Nakanishi, M (corresponding author), Nagoya City Univ, Grad Sch Med Sci, Dept Cell Biol, Mizuho Ku, 1 Kawasumi,Mizuho Cho, Nagoya, Aichi 4678601, Japan.
EM anishiya@med.nagoya-cu.ac.jp; mkt-naka@med.nagoya-cu.ac.jp
FU MEXT Japan; Japan Society for the Promotion of Science; Grants-in-Aid for Scientific Research [24659137, 23249015, 22118001, 24113711, 24790290] Funding Source: KAKEN
NR 35
TC 305
Z9 351
U1 1
U2 66
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 10
PY 2013
VL 502
IS 7470
BP 249
EP +
DI 10.1038/nature12488
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 231RU
UT WOS:000325436100054
PM 24013172
DA 2026-03-09
ER

PT J
AU Shingai, M
   Nishimura, Y
   Klein, F
   Mouquet, H
   Donau, OK
   Plishka, R
   Buckler-White, A
   Seaman, M
   Piatak, M
   Lifson, JD
   Dimitrov, DS
   Nussenzweig, MC
   Martin, MA
AF Shingai, Masashi
   Nishimura, Yoshiaki
   Klein, Florian
   Mouquet, Hugo
   Donau, Olivia K.
   Plishka, Ronald
   Buckler-White, Alicia
   Seaman, Michael
   Piatak, Michael, Jr.
   Lifson, Jeffrey D.
   Dimitrov, Dimiter S.
   Nussenzweig, Michel C.
   Martin, Malcolm A.
TI Antibody-mediated immunotherapy of macaques chronically infected with SHIV suppresses viraemia
SO NATURE
LA English
DT Article
ID simian/human immunodeficiency virus; neutralizing antibody; passive transfer; rhesus macaques; potent neutralization; hiv-1; broad; protection; challenge; therapy
AB Neutralizing antibodies can confer immunity to primate lentiviruses by blocking infection in macaque models of AIDS(1-4). However, earlier studies of anti-human immunodeficiency virus type 1 (HIV-1) neutralizing antibodies administered to infected individuals or humanized mice reported poor control of virus replication and the rapid emergence of resistant variants(5-7). A new generation of anti-HIV-1 monoclonal antibodies, possessing extraordinary potency and breadth of neutralizing activity, has recently been isolated from infected individuals(8). These neutralizing antibodies target different regions of the HIV-1 envelope glycoprotein including the CD4-binding site, glycans located in the V1/V2, V3 and V4 regions, and the membrane proximal external region of gp41 (refs 9-14). Here we have examined two of the new antibodies, directed to the CD4-binding site and the V3 region (3BNC117 and 10-1074, respectively), for their ability to block infection and suppress viraemia in macaques infected with the R5 tropic simian-human immunodeficiency virus (SHIV)-AD8, which emulates many of the pathogenic and immunogenic properties of HIV-1 during infections of rhesus macaques(15,16). Either antibody alone can potently block virus acquisition. When administered individually to recently infected macaques, the 10-1074 antibody caused a rapid decline in virus load to undetectable levels for 4-7 days, followed by virus rebound during which neutralization-resistant variants became detectable. When administered together, a single treatment rapidly suppressed plasma viraemia for 3-5 weeks in some long-term chronically SHIV-infected animals with low CD41 T-cell levels. A second cycle of anti-HIV-1 monoclonal antibody therapy, administered to two previously treated animals, successfully controlled virus rebound. These results indicate that immunotherapy or a combination of immunotherapy plus conventional antiretroviral drugs might be useful as a treatment for chronically HIV-1-infected individuals experiencing immune dysfunction.
C1 [Shingai, Masashi; Nishimura, Yoshiaki; Donau, Olivia K.; Plishka, Ronald; Buckler-White, Alicia; Martin, Malcolm A.] NIAID, Lab Mol Microbiol, NIH, Bethesda, MD 20892 USA.
   [Klein, Florian; Nussenzweig, Michel C.] Rockefeller Univ, Lab Mol Immunol, New York, NY 10065 USA.
   [Mouquet, Hugo] Inst Pasteur, Dept Immunol, Lab Humoral Response Pathogens, F-75015 Paris, France.
   [Seaman, Michael] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Ctr Virol & Vaccine Res, Boston, MA 02115 USA.
   [Piatak, Michael, Jr.; Lifson, Jeffrey D.] SAIC Frederick Inc, AIDS & Canc Virus Program, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
   [Dimitrov, Dimiter S.; Nussenzweig, Michel C.] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
   [Nussenzweig, Michel C.] Rockefeller Univ, Howard Hughes Med Inst, New York, NY 10065 USA.
C3 National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID); Rockefeller University; Pasteur Network; Universite Paris Cite; Institut Pasteur Paris; Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Beth Israel Deaconess Medical Center; Science Applications International Corporation (SAIC); SAIC-Frederick; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); Frederick National Laboratory for Cancer Research; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); Rockefeller University; Howard Hughes Medical Institute
RP Nussenzweig, MC (corresponding author), Rockefeller Univ, Lab Mol Immunol, New York, NY 10065 USA.
EM nussen@mail.rockefeller.edu; malm@nih.gov
FU Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH); National Cancer Institute, NIH [HHSN261200800001E]; National Institute of Allergy and Infectious Diseases [P01AI100148] Funding Source: NIH RePORTER
NR 30
TC 391
Z9 506
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 NOV 14
PY 2013
VL 503
IS 7475
BP 277
EP +
DI 10.1038/nature12746
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 250YX
UT WOS:000326894200054
PM 24172896
DA 2026-03-09
ER

PT J
AU Son, J
   Lyssiotis, CA
   Ying, H
   Wang, X
   Hua, S
   Ligorio, M
   Perera, RM
   Ferrone, CR
   Mullarky, E
   Ng, SC
   Kang, Y
   Fleming, JB
   Bardeesy, N
   Asara, JM
   Haigis, MC
   DePinho, RA
   Cantley, LC
   Kimmelman, AC
AF Son, Jaekyoung
   Lyssiotis, Costas A.
   Ying, Haoqiang
   Wang, Xiaoxu
   Hua, Sujun
   Ligorio, Matteo
   Perera, Rushika M.
   Ferrone, Cristina R.
   Mullarky, Edouard
   Ng Shyh-Chang
   Kang, Ya'an
   Fleming, Jason B.
   Bardeesy, Nabeel
   Asara, John M.
   Haigis, Marcia C.
   DePinho, Ronald A.
   Cantley, Lewis C.
   Kimmelman, Alec C.
TI Glutamine supports pancreatic cancer growth through a KRAS-regulated metabolic pathway
SO NATURE
LA English
DT Article
ID mass-spectrometry; transformed-cells; addiction; glucose
AB Cancer cells have metabolic dependencies that distinguish them from their normal counterparts(1). Among these dependencies is an increased use of the amino acid glutamine to fuel anabolic processes(2). Indeed, the spectrum of glutamine-dependent tumours and the mechanisms whereby glutamine supports cancer metabolism remain areas of active investigation. Here we report the identification of a non-canonical pathway of glutamine use in human pancreatic ductal adenocarcinoma (PDAC) cells that is required for tumour growth. Whereas most cells use glutamate dehydrogenase (GLUD1) to convert glutamine-derived glutamate into alpha-ketoglutarate in the mitochondria to fuel the tricarboxylic acid cycle, PDAC relies on a distinct pathway in which glutamine-derived aspartate is transported into the cytoplasm where it can be converted into oxaloacetate by aspartate transaminase (GOT1). Subsequently, this oxaloacetate is converted into malate and then pyruvate, ostensibly increasing the NADPH/NADP(+) ratio which can potentially maintain the cellular redox state. Importantly, PDAC cells are strongly dependent on this series of reactions, as glutamine deprivation or genetic inhibition of any enzyme in this pathway leads to an increase in reactive oxygen species and a reduction in reduced glutathione. Moreover, knockdown of any component enzyme in this series of reactions also results in a pronounced suppression of PDAC growth in vitro and in vivo. Furthermore, we establish that the reprogramming of glutamine metabolism is mediated by oncogenic KRAS, the signature genetic alteration in PDAC, through the transcriptional upregulation and repression of key metabolic enzymes in this pathway. The essentiality of this pathway in PDAC and the fact that it is dispensable in normal cells may provide novel therapeutic approaches to treat these refractory tumours.
C1 [Son, Jaekyoung; Wang, Xiaoxu; Kimmelman, Alec C.] Dana Farber Canc Inst, Dept Radiat Oncol, Div Genom Stabil & DNA Repair, Boston, MA 02215 USA.
   [Lyssiotis, Costas A.; Mullarky, Edouard; Ng Shyh-Chang; Cantley, Lewis C.] Harvard Univ, Dept Syst Biol, Sch Med, Boston, MA 02215 USA.
   [Lyssiotis, Costas A.; Mullarky, Edouard; Cantley, Lewis C.] Beth Israel Deaconess Med Ctr, Div Signal Transduct, Boston, MA 02215 USA.
   [Ying, Haoqiang; Hua, Sujun; DePinho, Ronald A.] Univ Texas MD Anderson Canc Ctr, Dept Genom Med, Houston, TX 77030 USA.
   [Ligorio, Matteo; Ferrone, Cristina R.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
   [Perera, Rushika M.; Bardeesy, Nabeel] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
   [Ng Shyh-Chang] Childrens Hosp, Div Pediat Hematol Oncol, Stem Cell Transplantat Program, Stem Cell Program, Boston, MA 02130 USA.
   [Ng Shyh-Chang] Dana Farber Canc Inst, Boston, MA 02130 USA.
   [Kang, Ya'an; Fleming, Jason B.] Univ Texas MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77030 USA.
   [Asara, John M.] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA.
   [Haigis, Marcia C.] Harvard Univ, Dept Cell Biol, Sch Med, Boston, MA 02215 USA.
C3 Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Beth Israel Deaconess Medical Center; University of Texas System; UTMD Anderson Cancer Center; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; University of Texas System; UTMD Anderson Cancer Center; Harvard University; Harvard University Medical Affiliates; Beth Israel Deaconess Medical Center; Harvard University; Harvard Medical School
RP Cantley, LC (corresponding author), Harvard Univ, Dept Syst Biol, Sch Med, Boston, MA 02215 USA.
EM lec2014@med.cornell.edu; Alec_Kimmelman@DFCI.harvard.edu
FU Dana Farber Cancer Institute; National Cancer Institute [R01 CA157490]; Kimmel Scholar Award; AACR-PanCAN Career Development Award; NIH [T32 CA009382-26, P01 CA117969, 5P01CA120964-05]; Dana-Farber/Harvard Cancer Center Support Grant [5P30CA006516-46]; National Cancer Institute [P01CA120964, P30CA006516, P01CA117969] Funding Source: NIH RePORTER
NR 25
TC 1632
Z9 1925
U1 5
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 APR 4
PY 2013
VL 496
IS 7443
BP 101
EP +
DI 10.1038/nature12040
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 117ZZ
UT WOS:000316993400033
PM 23535601
DA 2026-03-09
ER

PT J
AU Fernández-Tornero, C
   Moreno-Morcillo, M
   Rashid, UJ
   Taylor, NMI
   Ruiz, FM
   Gruene, T
   Legrand, P
   Steuerwald, U
   Müller, CW
AF Fernandez-Tornero, Carlos
   Moreno-Morcillo, Maria
   Rashid, Umar J.
   Taylor, Nicholas M. I.
   Ruiz, Federico M.
   Gruene, Tim
   Legrand, Pierre
   Steuerwald, Ulrich
   Mueller, Christoph W.
TI Crystal structure of the 14-subunit RNA polymerase I
SO NATURE
LA English
DT Article
ID conformational flexibility; transcription initiation; electron-microscopy; elongation complex; phase information; cross-linking; architecture; subunits; model; tfiif
AB Protein biosynthesis depends on the availability of ribosomes, which in turn relies on ribosomal RNA production. In eukaryotes, this process is carried out by RNA polymerase I (Pol I), a 14-subunit enzyme, the activity of which is a major determinant of cell growth. Here we present the crystal structure of Pol I from Saccharomyces cerevisiae at 3.0 angstrom resolution. The Pol I structure shows a compact core with a wide DNA-binding cleft and a tightly anchored stalk. An extended loop mimics the DNA backbone in the cleft and may be involved in regulating Pol I transcription. Subunit A12.2 extends from the A190 jaw to the active site and inserts a transcription elongation factor TFIIS-like zinc ribbon into the nucleotide triphosphate entry pore, providing insight into the role of A12.2 in RNA cleavage and Pol I insensitivity to alpha-amanitin. The A49-A34.5 heterodimer embraces subunit A135 through extended arms, thereby contacting and potentially regulating subunit A12.2.
C1 [Fernandez-Tornero, Carlos; Taylor, Nicholas M. I.; Ruiz, Federico M.] CSIC, Ctr Invest Biol, Madrid 28040, Spain.
   [Moreno-Morcillo, Maria; Rashid, Umar J.; Steuerwald, Ulrich; Mueller, Christoph W.] European Mol Biol Lab, Struct & Computat Biol Unit, D-69117 Heidelberg, Germany.
   [Gruene, Tim] Univ Gottingen, Dept Struct Chem, D-37077 Gottingen, Germany.
   [Legrand, Pierre] SOLEIL Synchrotron, F-91192 Gif Sur Yvette, France.
C3 Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Centro de Investigaciones Biologicas (CIB); European Molecular Biology Laboratory (EMBL); University of Gottingen; SOLEIL Synchrotron
RP Fernández-Tornero, C (corresponding author), CSIC, Ctr Invest Biol, Ramiro de Maeztu 9, Madrid 28040, Spain.
EM cftornero@cib.csic.es; cmueller@embl.de
FU EMBL Heidelberg Protein Expression and Purification, Proteomics Core Facilities and Crystallization Platform; 'Fermentation et culture de microorganisms' (CNRS) [IFR88]; EMBO Long-Term fellowships; Marie-Curie fellowship [FP7-PEOPLE-2011-IEF 301002]; Fundacion Futuro fellowship; ESF/CSIC; Volkswagen Stiftung; Spanish Ministry of Science [BFU2010-16336]
NR 55
TC 157
Z9 197
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 OCT 31
PY 2013
VL 502
IS 7473
BP 644
EP +
DI 10.1038/nature12636
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 243CC
UT WOS:000326293200039
PM 24153184
DA 2026-03-09
ER

PT J
AU Kaidi, A
   Jackson, SP
AF Kaidi, Abderrahmane
   Jackson, Stephen P.
TI RETRACTED: KAT5 tyrosine phosphorylation couples chromatin sensing to ATM signalling (Retracted article. See vol. 568, pg. 576, 2019)
SO NATURE
LA English
DT Article; Retracted Publication
ID dna-damage response; histone h3 methylation; double-strand breaks; c-abl; activates atm; kinase; protein; acetylation; autophosphorylation; inhibition
AB The detection of DNA lesions within chromatin represents a critical step in cellular responses to DNA damage. However, the regulatory mechanisms that couple chromatin sensing to DNA-damage signalling in mammalian cells are not well understood. Here we show that tyrosine phosphorylation of the protein acetyltransferase KAT5 (also known as TIP60) increases after DNA damage in a manner that promotes KAT5 binding to the histone mark H3K9me3. This triggers KAT5-mediated acetylation of the ATM kinase, promoting DNA-damage-checkpoint activation and cell survival. We also establish that chromatin alterations can themselves enhance KAT5 tyrosine phosphorylation and ATM-dependent signalling, and identify the proto-oncogene c-Abl as a mediator of this modification. These findings define KAT5 tyrosine phosphorylation as a key event in the sensing of genomic and chromatin perturbations, and highlight a key role for c-Abl in such processes.
C1 [Kaidi, Abderrahmane; Jackson, Stephen P.] Univ Cambridge, Gurdon Inst, Cambridge CB2 1QN, England.
   [Kaidi, Abderrahmane; Jackson, Stephen P.] Univ Cambridge, Dept Biochem, Cambridge CB2 1QN, England.
   [Jackson, Stephen P.] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England.
C3 University of Cambridge; University of Cambridge; Wellcome Trust Sanger Institute
RP Jackson, SP (corresponding author), Univ Cambridge, Gurdon Inst, Tennis Court Rd, Cambridge CB2 1QN, England.
EM s.jackson@gurdon.cam.ac.uk
FU Cancer Research UK program [C6/A11224]; European Research Council; European Community [HEALTH-F2-2010-259893 (DDR)]; CRUK [C6946/A14492]; Wellcome Trust [WT092096]; University of Cambridge, UK; Herchel Smith Fellowship from the University of Cambridge; Cancer Research UK [11224] Funding Source: researchfish
NR 35
TC 6
Z9 8
U1 1
U2 60
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 6
PY 2013
VL 498
IS 7452
BP 70
EP +
DI 10.1038/nature12201
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 158DC
UT WOS:000319947800034
DA 2026-03-09
ER

PT J
AU Yuan, CX
   Liang, Y
   Hernandez, T
   Berriochoa, A
   Houk, KN
   Siegel, D
AF Yuan, Changxia
   Liang, Yong
   Hernandez, Taylor
   Berriochoa, Adrian
   Houk, Kendall N.
   Siegel, Dionicio
TI Metal-free oxidation of aromatic carbon-hydrogen bonds through a reverse-rebound mechanism
SO NATURE
LA English
DT Article
ID cyclic diacyl peroxides; c-h oxygenation; phthaloyl peroxide; atom transfer; selectivity; photodecomposition; decomposition; reactivity; products; radicals
AB Methods for carbon-hydrogen (C-H) bond oxidation have a fundamental role in synthetic organic chemistry, providing functionality that is required in the final target molecule or facilitating subsequent chemical transformations. Several approaches to oxidizing aliphatic C-H bonds have been described, drastically simplifying the synthesis of complex molecules(1-6). However, the selective oxidation of aromatic C-H bonds under mild conditions, especially in the context of substituted arenes with diverse functional groups, remains a challenge. The direct hydroxylation of arenes was initially achieved through the use of strong Bronsted or Lewis acids to mediate electrophilic aromatic substitution reactions with super-stoichiometric equivalents of oxidants, significantly limiting the scope of the reaction(7). Because the products of these reactions are more reactive than the starting materials, over-oxidation is frequently a competitive process. Transition-metal-catalysed C-H oxidation of arenes with or without directing groups has been developed, improving on the acid-mediated process; however, precious metals are required(8-13). Here we demonstrate that phthaloyl peroxide functions as a selective oxidant for the transformation of arenes to phenols under mild conditions. Although the reaction proceeds through a radical mechanism, aromatic C-H bonds are selectively oxidized in preference to activated Csp3-H bonds. Notably, a wide array of functional groups are compatible with this reaction, and this method is therefore well suited for late-stage transformations of advanced synthetic intermediates. Quantum mechanical calculations indicate that this transformation proceeds through a novel addition-abstraction mechanism, a kind of 'reverse-rebound' mechanism as distinct from the common oxygen-rebound mechanism observed for metal-oxo oxidants. These calculations also identify the origins of the experimentally observed aryl selectivity.
C1 [Yuan, Changxia; Hernandez, Taylor; Berriochoa, Adrian; Siegel, Dionicio] Univ Texas Austin, Dept Chem & Biochem, Austin, TX 78712 USA.
   [Liang, Yong; Houk, Kendall N.] Univ Calif Los Angeles, Dept Chem & Biochem, Los Angeles, CA 90095 USA.
C3 University of Texas System; University of Texas Austin; University of California System; University of California Los Angeles
RP Siegel, D (corresponding author), Univ Texas Austin, Dept Chem & Biochem, Austin, TX 78712 USA.
EM dsiegel@cm.utexas.edu
FU University of Texas at Austin; Welch Foundation [F-1694]; US National Science Foundation [CHE-1059084, OCI-1053575]; Direct For Mathematical & Physical Scien [1059084] Funding Source: National Science Foundation; Division Of Chemistry [1059084] Funding Source: National Science Foundation; Division Of Chemistry; Direct For Mathematical & Physical Scien [1361104] Funding Source: National Science Foundation
NR 31
TC 173
Z9 195
U1 2
U2 315
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 11
PY 2013
VL 499
IS 7457
BP 192
EP 196
DI 10.1038/nature12284
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 179YA
UT WOS:000321557600058
PM 23846658
DA 2026-03-09
ER

PT J
AU Erickson, JR
   Pereira, L
   Wang, LG
   Han, GH
   Ferguson, A
   Dao, K
   Copeland, RJ
   Despa, F
   Hart, GW
   Ripplinger, CM
   Bers, DM
AF Erickson, Jeffrey R.
   Pereira, Laetitia
   Wang, Lianguo
   Han, Guanghui
   Ferguson, Amanda
   Dao, Khanha
   Copeland, Ronald J.
   Despa, Florin
   Hart, Gerald W.
   Ripplinger, Crystal M.
   Bers, Donald M.
TI Diabetic hyperglycaemia activates CaMKII and arrhythmias by O-linked glycosylation
SO NATURE
LA English
DT Article
ID ca2+/calmodulin-dependent protein-kinase; heart-failure; cardiac-hypertrophy; n-acetylglucosamine; cytosolic proteins; cardiomyocytes; myocytes; mellitus; receptor; insight
AB Ca2+/calmodulin-dependent protein kinase II (CaMKII) is an enzyme with important regulatory functions in the heart and brain, and its chronic activation can be pathological. CaMKII activation is seen in heart failure, and can directly induce pathological changes in ion channels, Ca2+ handling and gene transcription(1). Here, in human, rat and mouse, we identify a novel mechanism linking CaMKII and hyperglycaemic signalling in diabetes mellitus, which is a key risk factor for heart(2) and neurodegenerative diseases(3,4). Acute hyperglycaemia causes covalent modification of CaMKII by O-linked N-acetylglucosamine (O-GlcNAc). O-GlcNAc modification of CaMKII at Ser 279 activates CaMKII autonomously, creating molecular memory even after Ca2+ concentration declines. O-GlcNAc-modified CaMKII is increased in the heart and brain of diabetic humans and rats. In cardiomyocytes, increased glucose concentration significantly enhances CaMKII-dependent activation of spontaneous sarcoplasmic reticulum Ca2+ release events that can contribute to cardiac mechanical dysfunction and arrhythmias(1). These effects were prevented by pharmacological inhibition of O-GlcNAc signalling or genetic ablation of CaMKII delta. In intact perfused hearts, arrhythmias were aggravated by increased glucose concentration through O-GlcNAc- and CaMKII-dependent pathways. In diabetic animals, acute blockade of O-GlcNAc inhibited arrhythmogenesis. Thus, O-GlcNAc modification of CaMKII is a novel signalling event in pathways that may contribute critically to cardiac and neuronal pathophysiology in diabetes and other diseases.
C1 [Erickson, Jeffrey R.; Pereira, Laetitia; Wang, Lianguo; Ferguson, Amanda; Dao, Khanha; Despa, Florin; Ripplinger, Crystal M.; Bers, Donald M.] Univ Calif Davis, Dept Pharmacol, Davis, CA 95616 USA.
   [Erickson, Jeffrey R.] Univ Otago, Dept Physiol, Dunedin 9054, New Zealand.
   [Han, Guanghui; Copeland, Ronald J.; Hart, Gerald W.] Johns Hopkins Univ, Sch Med, Dept Biol Chem, Baltimore, MD 21205 USA.
   [Despa, Florin] Univ Kentucky, Dept Mol & Biomed Pharmacol, Lexington, KY 40536 USA.
C3 University of California System; University of California Davis; University of Otago; Johns Hopkins University; University of Kentucky
RP Bers, DM (corresponding author), Univ Calif Davis, Dept Pharmacol, 451 Hlth Sci Dr, Davis, CA 95616 USA.
EM dmbers@ucdavis.edu
FU American Heart Association [13SDG14680072]; National Institutes of Health (NIH) [T32HL86350, 1R01HL118474-01A1, R01DK61671, P01HL107153, R01HL111600, P01HL080101, R37HL30077]; NSF CBET [1133339]; ADA [1-13-IN-70]; AHA [13GRNT16470034]; Fondation Leducq Transatlantic CaMKII Alliance; Div Of Chem, Bioeng, Env, & Transp Sys; Directorate For Engineering [1133339] Funding Source: National Science Foundation; American Heart Association (AHA) [13SDG14680072, 13GRNT16470034] Funding Source: American Heart Association (AHA); National Heart Lung and Blood Institute [R01HL111600, T32HL086350] Funding Source: NIH RePORTER
NR 30
TC 501
Z9 583
U1 1
U2 162
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 17
PY 2013
VL 502
IS 7471
BP 372
EP +
DI 10.1038/nature12537
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 235GY
UT WOS:000325706300053
PM 24077098
DA 2026-03-09
ER

PT J
AU Huntingford, C
   Jones, PD
   Livina, VN
   Lenton, TM
   Cox, PM
AF Huntingford, Chris
   Jones, Philip D.
   Livina, Valerie N.
   Lenton, Timothy M.
   Cox, Peter M.
TI No increase in global temperature variability despite changing regional patterns
SO NATURE
LA English
DT Article
ID extreme events; climate; era-40; cmip5; ice
AB Evidence from Greenland ice cores shows that year-to-year temperature variability was probably higher in some past cold periods(1), but there is considerable interest in determining whether global warming is increasing climate variability at present(2-6). This interest is motivated by an understanding that increased variability and resulting extreme weather conditions may be more difficult for society to adapt to than altered mean conditions(3). So far, however, in spite of suggestions of increased variability(2), there is considerable uncertainty as to whether it is occurring(7). Here we show that although fluctuations in annual temperature have indeed shown substantial geographical variation over the past few decades(2), the time-evolving standard deviation of globally averaged temperature anomalies has been stable. A feature of the changes has been a tendency for many regions of low variability to experience increases, which might contribute to the perception of increased climate volatility. The normalization of temperature anomalies(2) creates the impression of larger relative overall increases, but our use of absolute values, which we argue is a more appropriate approach, reveals little change. Regionally, greater year-to-year changes recently occurred in much of North America and Europe. Many climate models predict that total variability will ultimately decrease under high greenhouse gas concentrations, possibly associated with reductions in sea-ice cover. Our findings contradict the view that a warming world will automatically be one of more overall climatic variation.
C1 [Huntingford, Chris] Ctr Ecol & Hydrol, Wallingford OX10 8BB, Oxon, England.
   [Jones, Philip D.] Univ E Anglia, Fac Sci, Sch Environm Sci, Climat Res Unit, Norwich NR4 7TJ, Norfolk, England.
   [Jones, Philip D.] King Abdulaziz Univ, Dept Meteorol, Ctr Excellence Climate Change Res, Jeddah 21589, Saudi Arabia.
   [Livina, Valerie N.] Univ E Anglia, Fac Sci, Sch Environm Sci, Norwich NR4 7TJ, Norfolk, England.
   [Livina, Valerie N.] Natl Phys Lab, Teddington TW11 0LW, Middx, England.
   [Lenton, Timothy M.] Univ Exeter, Coll Life & Environm Sci, Exeter EX4 4PS, Devon, England.
   [Cox, Peter M.] Univ Exeter, Coll Engn Math & Phys Sci, Exeter EX4 4QF, Devon, England.
C3 UK Centre for Ecology & Hydrology (UKCEH); University of East Anglia; King Abdulaziz University; University of East Anglia; National Physical Laboratory - UK; University of Exeter; University of Exeter
RP Huntingford, C (corresponding author), Ctr Ecol & Hydrol, Wallingford OX10 8BB, Oxon, England.
EM chg@ceh.ac.uk
FU US DOE [DE-SC0005689]; NERC [NE/F005474/1]; Natural Environment Research Council [NE/F005474/1] Funding Source: researchfish; NERC [NE/F005474/1] Funding Source: UKRI
NR 31
TC 197
Z9 227
U1 2
U2 207
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 15
PY 2013
VL 500
IS 7462
BP 327
EP +
DI 10.1038/nature12310
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 201AF
UT WOS:000323112400031
PM 23883935
DA 2026-03-09
ER

PT J
AU Safavi-Naeini, AH
   Gröblacher, S
   Hill, JT
   Chan, J
   Aspelmeyer, M
   Painter, O
AF Safavi-Naeini, Amir H.
   Groeblacher, Simon
   Hill, Jeff T.
   Chan, Jasper
   Aspelmeyer, Markus
   Painter, Oskar
TI Squeezed light from a silicon micromechanical resonator
SO NATURE
LA English
DT Article
ID quantum-noise reduction; radiation-pressure; optical cavity; ground-state; interferometer; micromirror; oscillator
AB Monitoring a mechanical object's motion, even with the gentle touch of light, fundamentally alters its dynamics. The experimental manifestation of this basic principle of quantum mechanics, its link to the quantum nature of light and the extension of quantum measurement to the macroscopic realm have all received extensive attention over the past half-century(1,2). The use of squeezed light, with quantum fluctuations below that of the vacuum field, was proposed nearly three decades ago(3) as a means of reducing the optical read-out noise in precision force measurements. Conversely, it has also been proposed that a continuous measurement of a mirror's position with light may itself give rise to squeezed light(4,5). Such squeezed-light generation has recently been demonstrated in a system of ultracold gas-phase atoms(6) whose centre-of-mass motion is analogous to the motion of a mirror. Here we describe the continuous position measurement of a solid-state, optomechanical system fabricated from a silicon microchip and comprising a micromechanical resonator coupled to a nanophotonic cavity. Laser light sent into the cavity is used to measure the fluctuations in the position of the mechanical resonator at a measurement rate comparable to its resonance frequency and greater than its thermal decoherence rate. Despite the mechanical resonator's highly excited thermal state (10(4) phonons), we observe, through homodyne detection, squeezing of the reflected light's fluctuation spectrum at a level 4.5 +/- 0.2 per cent below that of vacuum noise over a bandwidth of a few megahertz around the mechanical resonance frequency of 28 megahertz. With further device improvements, on-chip squeezing at significant levels should be possible, making such integrated microscale devices well suited for precision metrology applications.
C1 [Safavi-Naeini, Amir H.; Groeblacher, Simon; Hill, Jeff T.; Chan, Jasper; Painter, Oskar] CALTECH, Kavli Nanosci Inst, Pasadena, CA 91125 USA.
   [Safavi-Naeini, Amir H.; Groeblacher, Simon; Hill, Jeff T.; Chan, Jasper; Painter, Oskar] CALTECH, Thomas J Watson Sr Lab Appl Phys, Pasadena, CA 91125 USA.
   [Safavi-Naeini, Amir H.; Groeblacher, Simon; Hill, Jeff T.; Painter, Oskar] CALTECH, Inst Quantum Informat & Matter, Pasadena, CA 91125 USA.
   [Aspelmeyer, Markus] Univ Vienna, Fac Phys, Vienna Ctr Quantum Sci & Technol, A-1090 Vienna, Austria.
   [Painter, Oskar] Max Planck Inst Sci Light, D-91058 Erlangen, Germany.
C3 California Institute of Technology; California Institute of Technology; California Institute of Technology; University of Vienna; Max Planck Society
RP Painter, O (corresponding author), CALTECH, Kavli Nanosci Inst, Pasadena, CA 91125 USA.
EM opainter@caltech.edu
FU DARPA/MTO ORCHID from the AFOSR; Institute for Quantum Information and Matter, an NSF Physics Frontiers Center; Gordon and Betty Moore Foundation; Vienna Science and Technology Fund WWTF; European Commission through IP SIQS; European Commission through iQUOEMS; European Research Council; NSERC; European Commission through a Marie Curie Fellowship; Direct For Mathematical & Physical Scien; Division Of Physics [1125565] Funding Source: National Science Foundation
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NR 30
TC 489
Z9 561
U1 3
U2 223
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 8
PY 2013
VL 500
IS 7461
BP 185
EP 189
DI 10.1038/nature12307
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 197CH
UT WOS:000322825500030
PM 23925241
DA 2026-03-09
ER

PT J
AU Menting, JG
   Whittaker, J
   Margetts, MB
   Whittaker, LJ
   Kong, GKW
   Smith, BJ
   Watson, CJ
   Záková, L
   Kletvíková, E
   Jirácek, J
   Chan, SJ
   Steiner, DF
   Dodson, GG
   Brzozowski, AM
   Weiss, MA
   Ward, CW
   Lawrence, MC
AF Menting, John G.
   Whittaker, Jonathan
   Margetts, Mai B.
   Whittaker, Linda J.
   Kong, Geoffrey K. -W.
   Smith, Brian J.
   Watson, Christopher J.
   Zakova, Lenka
   Kletvikova, Emilia
   Jiracek, Jiri
   Chan, Shu Jin
   Steiner, Donald F.
   Dodson, Guy G.
   Brzozowski, Andrzej M.
   Weiss, Michael A.
   Ward, Colin W.
   Lawrence, Michael C.
TI How insulin engages its primary binding site on the insulin receptor
SO NATURE
LA English
DT Article
ID 1st 3 domains; diabetes-associated mutations; ligand-induced activation; molecular replacement; protein; affinity; model; refinement; peptide; element
AB Insulin receptor signalling has a central role in mammalian biology, regulating cellular metabolism, growth, division, differentiation and survival(1,2). Insulin resistance contributes to the pathogenesis of type 2 diabetes mellitus and the onset of Alzheimer's disease(3); aberrant signalling occurs in diverse cancers, exacerbated by crosstalk with the homologous type 1 insulin-like growth factor receptor (IGF1R)(4). Despite more than three decades of investigation, the three-dimensional structure of the insulin-insulin receptor complex has proved elusive, confounded by the complexity of producing the receptor protein. Here we present the first view, to our knowledge, of the interaction of insulin with its primary binding site on the insulin receptor, on the basis of four crystal structures of insulin bound to truncated insulin receptor constructs. The direct interaction of insulin with the first leucine-rich-repeat domain (L1) of insulin receptor is seen to be sparse, the hormone instead engaging the insulin receptor carboxy-terminal alpha-chain (alpha CT) segment, which is itself remodelled on the face of L1 upon insulin binding. Contact between insulin and L1 is restricted to insulin B-chain residues. The aCT segment displaces the B-chain C-terminal beta-strand away from the hormone core, revealing the mechanism of a long-proposed conformational switch in insulin upon receptor engagement. This mode of hormone-receptor recognition is novel within the broader family of receptor tyrosine kinases(5). We support these findings by photo-crosslinking data that place the suggested interactions into the context of the holoreceptor and by isothermal titration calorimetry data that dissect the hormone-insulin receptor interface. Together, our findings provide an explanation for a wealth of biochemical data from the insulin receptor and IGF1R systems relevant to the design of therapeutic insulin analogues.
C1 [Menting, John G.; Margetts, Mai B.; Kong, Geoffrey K. -W.; Smith, Brian J.; Ward, Colin W.; Lawrence, Michael C.] Walter & Eliza Hall Inst Med Res, Parkville, Vic 3052, Australia.
   [Whittaker, Jonathan; Whittaker, Linda J.; Weiss, Michael A.] Case Western Reserve Univ, Sch Med, Dept Biochem, Cleveland, OH 44106 USA.
   [Smith, Brian J.] La Trobe Univ, La Trobe Inst Mol Sci, Dept Chem, Melbourne, Vic 3086, Australia.
   [Watson, Christopher J.; Dodson, Guy G.; Brzozowski, Andrzej M.] Univ York, Dept Chem, York Struct Biol Lab, York YO10 5DD, N Yorkshire, England.
   [Zakova, Lenka; Kletvikova, Emilia; Jiracek, Jiri] Acad Sci Czech Republ, Inst Organ Chem & Biochem, Vvi, CR-16610 Prague, Czech Republic.
   [Chan, Shu Jin; Steiner, Donald F.] Univ Chicago, Dept Med, Chicago, IL 60637 USA.
   [Lawrence, Michael C.] Univ Melbourne, Dept Med Biol, Parkville, Vic 3010, Australia.
C3 Walter & Eliza Hall Institute; University System of Ohio; Case Western Reserve University; La Trobe University; University of York - UK; Czech Academy of Sciences; Institute of Organic Chemistry & Biochemistry of the Czech Academy of Sciences; University of Chicago; University of Melbourne
RP Lawrence, MC (corresponding author), Walter & Eliza Hall Inst Med Res, 1G Royal Parade, Parkville, Vic 3052, Australia.
EM michael.weiss@case.edu; lawrence@wehi.edu.au
FU Australian National Health and Medical Research Council (NHMRC) [516729, 575539, 1005896]; Hazel and Pip Appel Fund; NHMRC [361646]; Victorian State Government; NIH [DK40949, DK13914, DK20595]; American Diabetes Association [1-11INI-31]; Grant Agency of the Czech Republic [P207/11/P430]; Research Project of the Academy of Sciences of the Czech Republic [RVO: 61388963]; BBSRC; UoY Research Priming Fund; National Health and Medical Research Council (NHMRC) [575539, 516729, 1005896] Funding Source: National Health and Medical Research Council (NHMRC); National Institute of Diabetes and Digestive and Kidney Diseases [P30DK020595, R01DK040949] Funding Source: NIH RePORTER
NR 52
TC 321
Z9 394
U1 2
U2 330
PU NATURE PUBLISHING 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 10
PY 2013
VL 493
IS 7431
BP 241
EP U276
DI 10.1038/nature11781
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 066YY
UT WOS:000313259600043
PM 23302862
DA 2026-03-09
ER

PT J
AU Yan, B
   Moses, SA
   Gadway, B
   Covey, JP
   Hazzard, KRA
   Rey, AM
   Jin, DS
   Ye, J
AF Yan, Bo
   Moses, Steven A.
   Gadway, Bryce
   Covey, Jacob P.
   Hazzard, Kaden R. A.
   Rey, Ana Maria
   Jin, Deborah S.
   Ye, Jun
TI Observation of dipolar spin-exchange interactions with lattice-confined polar molecules
SO NATURE
LA English
DT Article
ID quantum; magnetism
AB With the production of polar molecules in the quantum regime(1,2), long-range dipolar interactions are expected to facilitate understanding of strongly interacting many-body quantum systems and to realize lattice spin models(3) for exploring quantum magnetism. In ordinary atomic systems, where contact interactions require wavefunction overlap, effective spin interactions on a lattice can be mediated by tunnelling, through a process referred to as superexchange; however, the coupling is relatively weak and is limited to nearest-neighbour interactions(4,5). In contrast, dipolar interactions exist even in the absence of tunnelling and extend beyond nearest neighbours. This allows coherent spin dynamics to persist even for gases with relatively high entropy and low lattice filling. Measured effects of dipolar interactions in ultracold molecular gases have been limited to the modification of inelastic collisions and chemical reactions(6,7). Here we use dipolar interactions of polar molecules pinned in a three-dimensional optical lattice to realize a lattice spin model. Spin is encoded in rotational states of molecules that are prepared and probed by microwaves. Resonant exchange of rotational angular momentum between two molecules realizes a spin-exchange interaction. The dipolar interactions are apparent in the evolution of the spin coherence, which shows oscillations in addition to an overall decay of the coherence. The frequency of these oscillations, the strong dependence of the spin coherence time on the lattice filling factor and the effect of a multipulse sequence designed to reverse dynamics due to two-body exchange interactions all provide evidence of dipolar interactions. Furthermore, we demonstrate the suppression of loss in weak lattices due to a continuous quantum Zeno mechanism(8). Measurements of these tunnelling-induced losses allow us to determine the lattice filling factor independently. Our work constitutes an initial exploration of the behaviour of many-body spin models with direct, long-range spin interactions and lays the groundwork for future studies of many-body dynamics in spin lattices.
C1 [Yan, Bo; Moses, Steven A.; Gadway, Bryce; Covey, Jacob P.; Hazzard, Kaden R. A.; Rey, Ana Maria; Jin, Deborah S.; Ye, Jun] NIST, JILA, Boulder, CO 80309 USA.
   [Yan, Bo; Moses, Steven A.; Gadway, Bryce; Covey, Jacob P.; Hazzard, Kaden R. A.; Rey, Ana Maria; Jin, Deborah S.; Ye, Jun] Univ Colorado, Boulder, CO 80309 USA.
   [Yan, Bo; Moses, Steven A.; Gadway, Bryce; Covey, Jacob P.; Hazzard, Kaden R. A.; Rey, Ana Maria; Jin, Deborah S.; 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 Jin, DS (corresponding author), NIST, JILA, Boulder, CO 80309 USA.
EM jin@jilau1.colorado.edu; ye@jila.colorado.edu
FU NIST; NSF; AFOSR-ARO (MURI); ARO; DOE; ARO-DARPA-OLE; NDSEG; Division Of Physics; Direct For Mathematical & Physical Scien [1211914] Funding Source: National Science Foundation; Division Of Physics; Direct For Mathematical & Physical Scien [1125844] Funding Source: National Science Foundation
NR 33
TC 776
Z9 876
U1 6
U2 162
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 26
PY 2013
VL 501
IS 7468
BP 521
EP +
DI 10.1038/nature12483
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 223RP
UT WOS:000324826300052
PM 24048478
DA 2026-03-09
ER

PT J
AU Hansen, BMS
   Kalirai, JS
   Anderson, J
   Dotter, A
   Richer, HB
   Rich, RM
   Shara, MM
   Fahlman, GG
   Hurley, JR
   King, IR
   Reitzel, D
   Stetson, PB
AF Hansen, B. M. S.
   Kalirai, J. S.
   Anderson, J.
   Dotter, A.
   Richer, H. B.
   Rich, R. M.
   Shara, M. M.
   Fahlman, G. G.
   Hurley, J. R.
   King, I. R.
   Reitzel, D.
   Stetson, P. B.
TI An age difference of two billion years between a metal-rich and a metal-poor globular cluster
SO NATURE
LA English
DT Article
ID dwarf cooling sequence; acs survey; galaxy; halo; disk; abundances; evolution; stars
AB Globular clusters trace the formation history of the spheroidal components of our Galaxy and other galaxies(1), which represent the bulk of star formation over the history of the Universe(2). The clusters exhibit a range of metallicities (abundances of elements heavier than helium), with metal-poor clusters dominating the stellar halo of the Galaxy, and higher-metallicity clusters found within the inner Galaxy, associated with the stellar bulge, or the thick disk(3,4). Age differences between these clusters can indicate the sequence in which the components of the Galaxy formed, and in particular which clusters were formed outside the Galaxy and were later engulfed along with their original host galaxies, and which were formed within it. Here we report an absolute age of 9.9 +/- 0.7 billion years (at 95 per cent confidence) for the metal-rich globular cluster 47 Tucanae, determined by modelling the properties of the cluster's white-dwarf cooling sequence. This is about two billion years younger than has been inferred for the metal-poor cluster NGC 6397 from the same models, and provides quantitative evidence that metal-rich clusters like 47 Tucanae formed later than metal-poor halo clusters like NGC 6397.
C1 [Hansen, B. M. S.; Rich, R. M.; Reitzel, D.] Univ Calif Los Angeles, Div Astron, Los Angeles, CA 90095 USA.
   [Kalirai, J. S.; Anderson, J.] Space Telescope Sci Inst, Baltimore, MD 21218 USA.
   [Kalirai, J. S.] Johns Hopkins Univ, Ctr Astrophys Sci, Baltimore, MD 21218 USA.
   [Dotter, A.] Australian Natl Univ, Res Sch Astron & Astrophys, Weston, ACT 2611, Australia.
   [Richer, H. B.] Univ British Columbia, Dept Phys & Astron, Vancouver, BC V6T 1Z1, Canada.
   [Shara, M. M.] Amer Museum Nat Hist, Dept Astrophys, New York, NY 10024 USA.
   [Fahlman, G. G.; Stetson, P. B.] NRC Herzberg, Victoria, BC V9E 2E7, Canada.
   [Hurley, J. R.] Swinburne Univ Technol, Ctr Astrophys & Supercomp, Hawthorn, Vic 3122, Australia.
   [King, I. R.] Univ Washington, Dept Astron, Seattle, WA 98195 USA.
C3 University of California System; University of California Los Angeles; Space Telescope Science Institute; Johns Hopkins University; Australian National University; University of British Columbia; American Museum of Natural History (AMNH); National Research Council Canada; Swinburne University of Technology; University of Washington; University of Washington Seattle
RP Hansen, BMS (corresponding author), Univ Calif Los Angeles, Div Astron, Los Angeles, CA 90095 USA.
EM hansen@astro.ucla.edu
FU NASA through Space Telescope Science Institute [GO-11677]; NASA [NAS 5-26555]; Natural Science and Engineering Research Council of Canada
NR 30
TC 109
Z9 114
U1 0
U2 17
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 1
PY 2013
VL 500
IS 7460
BP 51
EP 53
DI 10.1038/nature12334
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 192VK
UT WOS:000322514800025
PM 23903747
DA 2026-03-09
ER

PT J
AU Lam, MTY
   Cho, H
   Lesch, HP
   Gosselin, D
   Heinz, S
   Tanaka-Oishi, Y
   Benner, C
   Kaikkonen, MU
   Kim, AS
   Kosaka, M
   Lee, CY
   Watt, A
   Grossman, TR
   Rosenfeld, MG
   Evans, RM
   Glass, CK
AF Lam, Michael T. Y.
   Cho, Han
   Lesch, Hanna P.
   Gosselin, David
   Heinz, Sven
   Tanaka-Oishi, Yumiko
   Benner, Christopher
   Kaikkonen, Minna U.
   Kim, Aneeza S.
   Kosaka, Mika
   Lee, Cindy Y.
   Watt, Andy
   Grossman, Tamar R.
   Rosenfeld, Michael G.
   Evans, Ronald M.
   Glass, Christopher K.
TI Rev-Erbs repress macrophage gene expression by inhibiting enhancer-directed transcription
SO NATURE
LA English
DT Article
ID alpha; oligonucleotides; corepressor; metabolism; initiation; receptors; domains; cells
AB Rev-Erb-alpha and Rev-Erb-beta are nuclear receptors that regulate the expression of genes involved in the control of circadian rhythm(1,2), metabolism(3,4) and inflammatory responses(5). Rev-Erbs function as transcriptional repressors by recruiting nuclear receptor co-repressor (NCoR)-HDAC3 complexes to Rev-Erb response elements in enhancers and promoters of target genes(6-8), but the molecular basis for cell-specific programs of repressionis not known. Here we present evidence that in mouse macrophages Rev-Erbs regulate target gene expression by inhibiting the functions of distal enhancers that are selected by macrophage-lineage-determining factors, thereby establishing a macrophage-specific program of repression. Remarkably, the repressive functions of Rev-Erbs are associated with their ability to inhibit the transcription of enhancer-derived RNAs (eRNAs). Furthermore, targeted degradation of eRNAs at two enhancers subject to negative regulation by Rev-Erbs resulted in reduced expression of nearby messenger RNAs, suggesting a direct role of these eRNAs in enhancer function. By precisely defining eRNA start sites using a modified form of global run-on sequencing that quantifies nascent 5' ends, we show that transfer of full enhancer activity to a target promoter requires both the sequences mediating transcription-factor binding and the specific sequences encoding the eRNA transcript. These studies provide evidence for a direct role of eRNAs in contributing to enhancer functions and suggest that Rev-Erbs act to suppress gene expression at a distance by repressing eRNA transcription.
C1 [Lam, Michael T. Y.; Lesch, Hanna P.; Gosselin, David; Heinz, Sven; Tanaka-Oishi, Yumiko; Benner, Christopher; Kaikkonen, Minna U.; Kosaka, Mika; Lee, Cindy Y.; Glass, Christopher K.] Univ Calif San Diego, Dept Cellular & Mol Med, La Jolla, CA 92093 USA.
   [Cho, Han; Evans, Ronald M.] Salk Inst Biol Studies, La Jolla, CA 92037 USA.
   [Kim, Aneeza S.; Watt, Andy; Grossman, Tamar R.] Isis Pharmaceut Inc, Carlsbad, CA 92010 USA.
   [Rosenfeld, Michael G.; Glass, Christopher K.] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA.
   [Rosenfeld, Michael G.; Evans, Ronald M.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA.
C3 University of California System; University of California San Diego; Salk Institute; Ionis Pharmaceuticals, Inc.; University of California System; University of California San Diego; Howard Hughes Medical Institute
RP Glass, CK (corresponding author), Univ Calif San Diego, Dept Cellular & Mol Med, 9500 Gilman Dr, La Jolla, CA 92093 USA.
EM ckg@ucsd.edu
FU National Institutes of Health [CA17390, U19DK62434, DK091183, DK063491, CA014195, DK057978, HL088093, HL105278, CA52599]; University of California, San Diego Medical Scientist Training Program [T32 GM007198-37]; University of California, San Diego Genetics Training Program [T32 GM008666]; National Institute of General Medical Sciences; LeDucq Foundation Fellowship; Finnish Cultural Foundation; Instumentarium Foundation; Paulo Foundation; Paavo Nurmi Foundation; Finnish Foundation for Cardiovascular Research; Maud Kuistila Memorial Foundation; Fulbright Center; Leona M. and Harry B. Helmsley Charitable Trust; Samuel Waxman Cancer Research Foundation; Glenn Foundation for Medical Research; Ellison Medical Foundation; Ipsen/Biomeasure; National Cancer Institute [P30CA014195] Funding Source: NIH RePORTER; National Institute of Diabetes and Digestive and Kidney Diseases [R01DK057978, P30DK063491, R01DK018477, R01DK091183] Funding Source: NIH RePORTER; National Institute of General Medical Sciences [T32GM008666, T32GM007198] Funding Source: NIH RePORTER
NR 30
TC 470
Z9 568
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 JUN 27
PY 2013
VL 498
IS 7455
BP 511
EP +
DI 10.1038/nature12209
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 171LH
UT WOS:000320929400058
PM 23728303
DA 2026-03-09
ER

PT J
AU Schulz, TJ
   Huang, P
   Huang, TL
   Xue, RD
   McDougall, LE
   Townsend, KL
   Cypess, AM
   Mishina, Y
   Gussoni, E
   Tseng, YH
AF Schulz, Tim J.
   Huang, Ping
   Huang, Tian Lian
   Xue, Ruidan
   McDougall, Lindsay E.
   Townsend, Kristy L.
   Cypess, Aaron M.
   Mishina, Yuji
   Gussoni, Emanuela
   Tseng, Yu-Hua
TI Brown-fat paucity due to impaired BMP signalling induces compensatory browning of white fat
SO NATURE
LA English
DT Article
ID adipose-tissue; transcriptional control; adipocytes; thermogenesis; distinct; reveals; muscle; mice; identification; activation
AB Maintenance of body temperature is essential for the survival of homeotherms. Brown adipose tissue (BAT) is a specialized fat tissue that is dedicated to thermoregulation(1). Owing to its remarkable capacity to dissipate stored energy and its demonstrated presence in adult humans(2-5), BAT holds great promise for the treatment of obesity and metabolic syndrome(1). Rodent data suggest the existence of two types of brown fat cells: constitutive BAT (cBAT), which is of embryonic origin and anatomically located in the imterscapular region of mice; and recruitable BAT (rBAT), which resides within white adipose tissue (WAT)(6) and skeletal muscle(7), and has alternatively been called beige(8), brite(9) or inducible BAT(10). Bone morphogenetic proteins (BMPs) regulate the formation and thermogenic activity of BAT(10-12). Here we use mouse models to provide evidence for a systemically active regulatory mechanism that controls whole-body BAT activity for thermoregulation and energy homeostasis. Genetic ablation of the type 1A BMP receptor (Bmpr1a) in brown adipogenic progenitor cells leads to a severe paucity of cBAT. This in turn increases sympathetic input to WAT, thereby promoting the formation of rBAT within white fat depots. This previously unknown compensatory mechanism, aimed at restoring total brown-fat-mediated thermogenic capacity in the body, is sufficient to maintain normal temperature homeostasis and resistance to diet-induced obesity. These data suggest an important physiological cross-talk between constitutive and recruitable brown fat cells. This sophisticated regulatory mechanism of body temperature may participate in the control of energy balance and metabolic disease.
C1 [Schulz, Tim J.; Huang, Tian Lian; Xue, Ruidan; McDougall, Lindsay E.; Townsend, Kristy L.; Cypess, Aaron M.; Tseng, Yu-Hua] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Integrat Physiol & Metab, Boston, MA 02215 USA.
   [Huang, Ping; Gussoni, Emanuela] Harvard Univ, Sch Med, Boston Childrens Hosp, Program Genom, Boston, MA 02115 USA.
   [Huang, Ping; Gussoni, Emanuela] Harvard Univ, Sch Med, Boston Childrens Hosp, Div Genet, Boston, MA 02115 USA.
   [Xue, Ruidan] Fudan Univ, Shanghai Med Coll, Huashan Hosp, Div Endocrinol & Metab, Shanghai 200032, Peoples R China.
   [Mishina, Yuji] Univ Michigan, Sch Dent, Dept Biol & Mat Sci, Ann Arbor, MI 48109 USA.
   [Tseng, Yu-Hua] Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA.
C3 Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Joslin Diabetes Center, Inc.; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Harvard Medical School; Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Boston Children's Hospital; Fudan University; University of Michigan System; University of Michigan; Harvard University
RP Tseng, YH (corresponding author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Integrat Physiol & Metab, Boston, MA 02215 USA.
EM yu-hua.tseng@joslin.harvard.edu
FU National Institutes of Health (NIH) [R01 DK077097]; Joslin Diabetes Center's Diabetes Research Center (DRC from the NIDDK) [P30 DK036836]; Eli Lilly Research Foundation; Harvard Stem Cell Institute; Mary K. Iacocca Foundation; German Research Foundation (DFG) [SCHU2445/1-1]; American Heart Association [0730285N]; NIH [T32 DK007260, F32 DK091996]; National Natural Science Foundation of China [985III-YFX0302, NSFC81070680]; National Institute of Diabetes and Digestive and Kidney Diseases [P30DK036836, T32DK007260] Funding Source: NIH RePORTER; American Heart Association (AHA) [0730285N] Funding Source: American Heart Association (AHA)
NR 30
TC 324
Z9 372
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 MAR 21
PY 2013
VL 495
IS 7441
BP 379
EP 383
DI 10.1038/nature11943
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 113EY
UT WOS:000316650500045
PM 23485971
DA 2026-03-09
ER

PT J
AU Nussbaum, JC
   Van Dyken, SJ
   von Moltke, J
   Cheng, LE
   Mohapatra, A
   Molofsky, AB
   Thornton, EE
   Krummel, MF
   Chawla, A
   Liang, HE
   Locksley, RM
AF Nussbaum, Jesse C.
   Van Dyken, Steven J.
   von Moltke, Jakob
   Cheng, Laurence E.
   Mohapatra, Alexander
   Molofsky, Ari B.
   Thornton, Emily E.
   Krummel, Matthew F.
   Chawla, Ajay
   Liang, Hong-Erh
   Locksley, Richard M.
TI Type 2 innate lymphoid cells control eosinophil homeostasis
SO NATURE
LA English
DT Article
ID vasoactive-intestinal-peptide; vpac(2) receptor; deficient mice; immunity; lung; signals; mouse
AB Eosinophils are specialized myeloid cells associated with allergy and helminth infections. Blood eosinophils demonstrate circadian cycling, as described over 80 years ago(1), and are abundant in the healthy gastrointestinal tract. Although a cytokine, interleukin (IL)-5, and chemokines such as eotaxins mediate eosinophil development and survival(2), and tissue recruitment(3), respectively, the processes underlying the basal regulation of these signals remain unknown. Here we show that serum IL-5 levels are maintained by long-lived type 2 innate lymphoid cells (ILC2) resident in peripheral tissues. ILC2 cells secrete IL-5 constitutively and are induced to co-express IL-13 during type 2 inflammation, resulting in localized eotaxin production and eosinophil accumulation. In the small intestine where eosinophils and eotaxin are constitutive(4), ILC2 cells co-express IL-5 and IL-13; this co-expression is enhanced after caloric intake. The circadian synchronizer vasoactive intestinal peptide also stimulates ILC2 cells through the VPAC2 receptor to release IL-5, linking eosinophil levels with metabolic cycling. Tissue ILC2 cells regulate basal eosinophilopoiesis and tissue eosinophil accumulation through constitutive and stimulated cytokine expression, and this dissociated regulation can be tuned by nutrient intake and central circadian rhythms.
C1 [Nussbaum, Jesse C.; Van Dyken, Steven J.; von Moltke, Jakob; Chawla, Ajay; Liang, Hong-Erh; Locksley, Richard M.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA.
   [Cheng, Laurence E.] Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA.
   [Mohapatra, Alexander; Locksley, Richard M.] Univ Calif San Francisco, Dept Microbiol, San Francisco, CA 94143 USA.
   [Mohapatra, Alexander; Locksley, Richard M.] Univ Calif San Francisco, Dept Immunol, San Francisco, CA 94143 USA.
   [Molofsky, Ari B.] Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94143 USA.
   [Thornton, Emily E.; Krummel, Matthew F.] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94143 USA.
   [Chawla, Ajay] Univ Calif San Francisco, Dept Physiol, San Francisco, CA 94143 USA.
   [Chawla, Ajay] Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA.
   [Locksley, Richard M.] Univ Calif San Francisco, Howard Hughes Med Inst, 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; Howard Hughes Medical Institute; University of California System; University of California San Francisco
RP Locksley, RM (corresponding author), Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA.
EM locksley@medicine.ucsf.edu
FU NIH [AI026918, AI030663, AI078869, HL107202, AI007641, AI007334]; Diabetes Endocrinology Research Center [DK063720]; Howard Hughes Medical Institute; Sandler Asthma Basic Research Center at the University of California San Francisco; National Heart Lung and Blood Institute [P01HL107202] Funding Source: NIH RePORTER; National Institute of Allergy and Infectious Diseases [T32AI007334, T32AI007641, R01AI026918, U19AI077439] Funding Source: NIH RePORTER
NR 30
TC 883
Z9 1018
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 OCT 10
PY 2013
VL 502
IS 7470
BP 245
EP +
DI 10.1038/nature12526
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 231RU
UT WOS:000325436100053
PM 24037376
DA 2026-03-09
ER

PT J
AU Suweis, S
   Simini, F
   Banavar, JR
   Maritan, A
AF Suweis, Samir
   Simini, Filippo
   Banavar, Jayanth R.
   Maritan, Amos
TI Emergence of structural and dynamical properties of ecological mutualistic networks
SO NATURE
LA English
DT Article
ID nestedness analysis; stability; architecture; evolution; biodiversity; community; ecosystems; diversity; systems
AB Mutualistic networks are formed when the interactions between two classes of species are mutually beneficial. They are important examples of cooperation shaped by evolution. Mutualism between animals and plants has a key role in the organization of ecological communities(1-3). Such networks in ecology have generally evolved a nested architecture(4,5) independent of species composition and latitude(6,7); specialist species, with only few mutualistic links, tend to interact with a proper subset of the many mutualistic partners of any of the generalist species(1). Despite sustained efforts(5,8-10) to explain observed network structure on the basis of community-level stability or persistence, such correlative studies have reached minimal consensus(11-13). Here we show that nested interaction networks could emerge as a consequence of an optimization principle aimed at maximizing the species abundance in mutualistic communities. Using analytical and numerical approaches, we show that because of the mutualistic interactions, an increase in abundance of a given species results in a corresponding increase in the total number of individuals in the community, and also an increase in the nestedness of the interaction matrix. Indeed, the species abundances and the nestedness of the interaction matrix are correlated by a factor that depends on the strength of the mutualistic interactions. Nestedness and the observed spontaneous emergence of generalist and specialist species occur for several dynamical implementations of the variational principle under stationary conditions. Optimized networks, although remaining stable, tend to be less resilient than their counterparts with randomly assigned interactions. In particular, we show analytically that the abundance of the rarest species is linked directly to the resilience of the community. Our work provides a unifying framework for studying the emergent structural and dynamical properties of ecological mutualistic networks(2,5,10,14).
C1 [Suweis, Samir; Maritan, Amos] Univ Padua, Ist Nazl Fis Nucl, Dipartimento Fis & Astron G Galilei, I-35131 Padua, Italy.
   [Suweis, Samir; Maritan, Amos] Univ Padua, Ist Nazl Fis Nucl, CNISM, I-35131 Padua, Italy.
   [Simini, Filippo] Northeastern Univ, Ctr Complex Network Res, Boston, MA 02115 USA.
   [Simini, Filippo] Northeastern Univ, Dept Phys Biol & Comp Sci, Boston, MA 02115 USA.
   [Simini, Filippo] Budapest Univ Technol & Econ, Inst Phys, H-1111 Budapest, Hungary.
   [Banavar, Jayanth R.] Univ Maryland, Dept Phys, College Pk, MD 20742 USA.
C3 University of Padua; Istituto Nazionale di Fisica Nucleare (INFN); Istituto Nazionale di Fisica Nucleare (INFN); University of Padua; Northeastern University; Northeastern University; Budapest University of Technology & Economics; University System of Maryland; University of Maryland College Park
RP Suweis, S (corresponding author), Univ Padua, Ist Nazl Fis Nucl, Dipartimento Fis & Astron G Galilei, Via Marzolo 8, I-35131 Padua, Italy.
EM suweis@pd.infn.it; amos.maritan@pd.infn.it
FU Cariparo foundation
NR 30
TC 226
Z9 250
U1 5
U2 358
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 22
PY 2013
VL 500
IS 7463
BP 449
EP 452
DI 10.1038/nature12438
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 203TJ
UT WOS:000323316100033
PM 23969462
DA 2026-03-09
ER

PT J
AU Fei, HZ
   Wiedenbeck, M
   Yamazaki, D
   Katsura, T
AF Fei, Hongzhan
   Wiedenbeck, Michael
   Yamazaki, Daisuke
   Katsura, Tomoo
TI Small effect of water on upper-mantle rheology based on silicon self-diffusion coefficients
SO NATURE
LA English
DT Article
ID plastic-deformation; o diffusion; grain-size; olivine; melt; forsterite; system; phase
AB Water has been thought to affect the dynamical processes in the Earth's interior to a great extent. In particular, experimental deformation results(1-4) suggest that even only a few tens of parts per million of water by weight enhances the creep rates in olivine by orders of magnitude. However, those deformation studies have limitations, such as considering only a limited range of water concentrations and very high stresses, which might affect the results. Rock deformation can also be understood as an effect of silicon self-diffusion, because the creep rates of minerals at temperatures as high as those in the Earth's interior are limited by self-diffusion of the slowest species(5,6). Here we experimentally determine the silicon self-diffusion coefficient D-Si in forsterite at 8 GPa and 1,600 K to 1,800 K as a function of water content C-H2O from less than 1 to about 800 parts per million of water by weight, yielding the relationship, D-Si approximate to (C-H2O)(1/3). This exponent is strikingly lower than that obtained by deformation experiments (1.2; ref. 7). The high nominal creep rates in the deformation studies under wet conditions may be caused by excess grain boundary water. We conclude that the effect of water on upper-mantle rheology is very small. Hence, the smooth motion of the Earth's tectonic plates cannot be caused by mineral hydration in the asthenosphere. Also, water cannot cause the viscosity minimum zone in the upper mantle. And finally, the dominant mechanism responsible for hotspot immobility cannot be water content differences between their source and surrounding regions.
C1 [Fei, Hongzhan; Katsura, Tomoo] Univ Bayreuth, Bayer Geoinst, D-95440 Bayreuth, Germany.
   [Wiedenbeck, Michael] Helmholtz Ctr Potsdam, D-14473 Potsdam, Germany.
   [Yamazaki, Daisuke] Okayama Univ, Inst Study Earths Interior, Tottori 6820193, Japan.
C3 University of Bayreuth; Helmholtz Association; GFZ Helmholtz Centre for Geosciences; Okayama University
RP Fei, HZ (corresponding author), Univ Bayreuth, Bayer Geoinst, POB 101251, D-95440 Bayreuth, Germany.
EM hongzhan.fei@uni-bayreuth.de
FU ENB (Elite Network Bavaria) programmes; Grants-in-Aid for Scientific Research [13F03327, 21109004] Funding Source: KAKEN
NR 34
TC 136
Z9 153
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 JUN 13
PY 2013
VL 498
IS 7453
BP 213
EP +
DI 10.1038/nature12193
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 162RR
UT WOS:000320283400044
PM 23765497
DA 2026-03-09
ER

PT J
AU Chang, CY
   Pasolli, HA
   Giannopoulou, EG
   Guasch, G
   Gronostajski, RM
   Elemento, O
   Fuchs, E
AF Chang, Chiung-Ying
   Pasolli, H. Amalia
   Giannopoulou, Eugenia G.
   Guasch, Geraldine
   Gronostajski, Richard M.
   Elemento, Olivier
   Fuchs, Elaine
TI NFIB is a governor of epithelial-melanocyte stem cell behaviour in a shared niche
SO NATURE
LA English
DT Article
ID hair follicle; epidermal melanocytes; differentiation; skin; regeneration; endothelin; maintenance; activation; expression; roles
AB Adult stem cells reside in specialized niches where they receive environmental cues to maintain tissue homeostasis. In mammals, the stem cell niche within hair follicles is home to epithelial hair follicle stem cells and melanocyte stem cells, which sustain cyclical bouts of hair regeneration and pigmentation(1-4). To generate pigmented hairs, synchrony is achieved such that upon initiation of a new hair cycle, stem cells of each type activate lineage commitment(2,5). Dissecting the inter-stem-cell crosstalk governing this intricate coordination has been difficult, because mutations affecting one lineage often affect the other. Here we identify transcription factor NFIB as. an unanticipated coordinator of stem cell behaviour. Hair follicle stem-cell-specific conditional targeting of Nfib in mice uncouples stem cell synchrony. Remarkably, this happens not by perturbing hair cycle and follicle architecture, but rather by promoting melanocyte stem cell proliferation and differentiation. The early production of melanin is restricted to melanocyte stem cells at the niche base. Melanocyte stem cells more distant from the dermal papilla are unscathed, thereby preventing hair greying typical of melanocyte stem cell differentiation mutants. Furthermore, we pinpoint KIT-ligand as a dermal papilla signal promoting melanocyte stem cell differentiation. Additionally, through chromatin-immunoprecipitation with high-throughput-sequencing and transcriptional profiling, we identify endothelin 2 (Edn2) as an NFIB target aberrantly activated in NFIB-deficient hair follicle stem cells. Ectopically induced Edn2 recapitulates NFIB-deficient phenotypes in wildtype mice. Conversely, endothelin receptor antagonists and/or KIT blocking antibodies prevent precocious melanocyte stem cell differentiation in the NFIB-deficient niche. Our findings reveal how melanocyte and hair follicle stem cell behaviours maintain reliance upon cooperative factors within the niche, and how this can be uncoupled in injury, stress and disease states.
C1 [Chang, Chiung-Ying; Pasolli, H. Amalia; Fuchs, Elaine] Rockefeller Univ, Howard Hughes Med Inst, Lab Mammalian Cell Biol & Dev, New York, NY 10065 USA.
   [Giannopoulou, Eugenia G.; Elemento, Olivier] Cornell Univ, Weill Cornell Med Coll, Dept Physiol & Biophys, HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsau, New York, NY 10021 USA.
   [Guasch, Geraldine] Univ Cincinnati, Sch Med, Div Dev Biol, Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA.
   [Gronostajski, Richard M.] SUNY Buffalo, Dept Biochem, Dev Genom Grp, NYS Ctr Excellence Bioinformat & Life Sci, Buffalo, NY 14203 USA.
C3 Rockefeller University; Howard Hughes Medical Institute; Cornell University; Weill Cornell Medicine; University System of Ohio; University of Cincinnati; Cincinnati Children's Hospital Medical Center; State University of New York (SUNY) System; University at Buffalo, SUNY
RP Fuchs, E (corresponding author), Rockefeller Univ, Howard Hughes Med Inst, Lab Mammalian Cell Biol & Dev, New York, NY 10065 USA.
EM fuchslb@rockefeller.edu
FU NIH [R01-AR050452, R01-AR31737, R01-HL080624]; National Science Foundation [DB1054964]; National Institute of Arthritis and Musculoskeletal and Skin Diseases [R01AR031737, R01AR050452] Funding Source: NIH RePORTER; Direct For Biological Sciences; Div Of Biological Infrastructure [1054964] Funding Source: National Science Foundation
NR 30
TC 135
Z9 171
U1 2
U2 56
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 7
PY 2013
VL 495
IS 7439
BP 98
EP 102
DI 10.1038/nature11847
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 105BE
UT WOS:000316039800047
PM 23389444
DA 2026-03-09
ER

PT J
AU Tingley, MP
   Huybers, P
AF Tingley, Martin P.
   Huybers, Peter
TI Recent temperature extremes at high northern latitudes unprecedented in the past 600 years
SO NATURE
LA English
DT Article
ID nh mean temperature; reconstructing climate anomaly; bayesian algorithm; ice; variability; summer; trends; record; space; underestimation
AB Recently observed extreme temperatures at high northern latitudes(1-7) are rare by definition, making the longer time span afforded by climate proxies important for assessing how the frequency of such extremes may be changing. Previous reconstructions of past temperature variability have demonstrated that recent warmth is anomalous relative to preceding centuries(2,8,9) or millennia(10), but extreme events can be more thoroughly evaluated using a spatially resolved approach that provides an ensemble of possible temperature histories(11,12). Here, using a hierarchical Bayesian analysis(13,14) of instrumental, tree-ring, ice-core and lake-sediment records, we show that the magnitude and frequency of recent warm temperature extremes at high northern latitudes are unprecedented in the past 600 years. The summers of 2005, 2007, 2010 and 2011 were warmer than those of all prior years back to 1400 (probability P > 0.95), in terms of the spatial average. The summer of 2010 was the warmest in the previous 600 years in western Russia (P > 0.99) and probably the warmest in western Greenland and the Canadian Arctic as well (P > 0.90). These and other recent extremes greatly exceed those expected from a stationary climate, but can be understood as resulting from constant space-time variability about an increased mean temperature.
C1 [Tingley, Martin P.; Huybers, Peter] Harvard Univ, Dept Earth & Planetary Sci, Cambridge, MA 02138 USA.
C3 Harvard University
RP Tingley, MP (corresponding author), Harvard Univ, Dept Earth & Planetary Sci, 20 Oxford St, Cambridge, MA 02138 USA.
EM tingley@fas.harvard.edu
FU FAS Science Division Research Computing Group at Harvard University; NSF [ATM-0902374]; Directorate For Geosciences; Div Atmospheric & Geospace Sciences [0902374] Funding Source: National Science Foundation
NR 53
TC 150
Z9 176
U1 2
U2 240
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 11
PY 2013
VL 496
IS 7444
BP 201
EP +
DI 10.1038/nature11969
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 122VM
UT WOS:000317346300037
PM 23579678
DA 2026-03-09
ER

PT J
AU Hughes, KA
   Houde, AE
   Price, AC
   Rodd, FH
AF Hughes, Kimberly A.
   Houde, Anne E.
   Price, Anna C.
   Rodd, F. Helen
TI Mating advantage for rare males in wild guppy populations
SO NATURE
LA English
DT Article
ID frequency-dependent selection; sexual selection; poecilia-reticulata; color polymorphism; sperm transfer; evolution; familiarity; success; traits; choice
AB To understand the processes that maintain genetic diversity is a long-standing challenge in evolutionary biology, with implications for predicting disease resistance, response to environmental change, and population persistence(1-3). Simple population genetic models are not sufficient to explain the high levels of genetic diversity sometimes observed in ecologically important traits(2). In guppies (Poecilia reticulata), male colour pattern is both diverse and heritable, and is arguably one of the most extreme examples of morphological polymorphism known(4,5). Negative frequency-dependent selection (NFDS), a form of selection in which genotypes are favoured when they are rare(6), can potentially maintain such extensive polymorphism, but few experimental studies have confirmed its operation in nature(7,8). Here we use highly replicated experimental manipulations of natural populations to show that males with rare colour patterns have higher reproductive fitness, demonstrating NFDS mediated by sexual selection. Rare males acquired more mates and sired more offspring compared to common males and, as previously reported, had higher rates of survival(8). Orange colour, implicated in other studies of sexual selection in guppies, did predict male reproductive success, but only in one of three populations. These data support the hypothesis that NFDS maintains diversity in the colour patterns of male guppies through two selective agents, mates and predators. Similar field-based manipulations of genotype frequencies could provide a powerful approach to reveal the underlying ecological and behavioural mechanisms that maintain genetic and phenotypic diversity.
C1 [Hughes, Kimberly A.] Florida State Univ, Dept Biol Sci, Tallahassee, FL 32306 USA.
   [Houde, Anne E.] Lake Forest Coll, Dept Biol, Lake Forest, IL 60045 USA.
   [Price, Anna C.; Rodd, F. Helen] Univ Toronto, Dept Ecol & Evolutionary Biol, Toronto, ON M5S 3G5, Canada.
C3 State University System of Florida; Florida State University; University of Toronto
RP Hughes, KA (corresponding author), Florida State Univ, Dept Biol Sci, 319 Stadium Dr, Tallahassee, FL 32306 USA.
EM kahughes@bio.fsu.edu
FU National Science Foundation; Natural Sciences and Engineering Research Council (NSERC) of Canada; Direct For Biological Sciences; Division Of Integrative Organismal Systems [0934451] Funding Source: National Science Foundation; Division Of Integrative Organismal Systems; Direct For Biological Sciences [0743990] Funding Source: National Science Foundation
NR 34
TC 133
Z9 153
U1 1
U2 274
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 7
PY 2013
VL 503
IS 7474
BP 108
EP +
DI 10.1038/nature12717
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 247AS
UT WOS:000326585600041
PM 24172904
DA 2026-03-09
ER

PT J
AU Rasaiyaah, J
   Tan, CP
   Fletcher, AJ
   Price, AJ
   Blondeau, C
   Hilditch, L
   Jacques, DA
   Selwood, DL
   James, LC
   Noursadeghi, M
   Towers, GJ
AF Rasaiyaah, Jane
   Tan, Choon Ping
   Fletcher, Adam J.
   Price, Amanda J.
   Blondeau, Caroline
   Hilditch, Laura
   Jacques, David A.
   Selwood, David L.
   James, Leo C.
   Noursadeghi, Mahdad
   Towers, Greg J.
TI HIV-1 evades innate immune recognition through specific cofactor recruitment
SO NATURE
LA English
DT Article
ID gmp-amp synthase; cyclosporine-a; gene delivery; rna-binding; cleavage; cyclophilin; sensor; polyadenylation; infection; cells
AB Human immunodeficiency virus (HIV)-1 is able to replicate in primary human macrophages without stimulating innate immunity despite reverse transcription of genomic RNA into double-stranded DNA, an activity that might be expected to trigger innate pattern recognition receptors. We reasoned that if correctly orchestrated HIV-1 uncoating and nuclear entry is important for evasion of innate sensors then manipulation of specific interactions between HIV-1 capsid and host factors that putatively regulate these processes should trigger pattern recognition receptors and stimulate type 1 interferon (IFN) secretion. Here we show that HIV-1 capsid mutants N74D and P90A, which are impaired for interaction with cofactors cleavage and polyadenylation specificity factor subunit 6 (CPSF6) and cyclophilins (Nup358 and CypA), respectively(1,2), cannot replicate in primary human monocyte-derived macrophages because they trigger innate sensors leading to nuclear translocation of NF-kappa B and IRF3, the production of soluble type 1 IFN and induction of an antiviral state. Depletion of CPSF6 with short hairpin RNA expression allows wild-type virus to trigger innate sensors and IFN production. In each case, suppressed replication is rescued by IFN-receptor blockade, demonstrating a role for IFN in restriction. IFN production is dependent on viral reverse transcription but not integration, indicating that a viral reverse transcription product comprises the HIV-1 pathogen-associated molecular pattern. Finally, we show that we can pharmacologically induce wild-type HIV-1 infection to stimulate IFN secretion and an antiviral state using a non-immunosuppressive cyclosporine analogue. We conclude that HIV-1 has evolved to use CPSF6 and cyclophilins to cloak its replication, allowing evasion of innate immune sensors and induction of a cell-autonomous innate immune response in primary human macrophages.
C1 [Rasaiyaah, Jane; Tan, Choon Ping; Fletcher, Adam J.; Blondeau, Caroline; Hilditch, Laura; Noursadeghi, Mahdad; Towers, Greg J.] UCL, MRC, Ctr Med Mol Virol, Div Infect & Immun, London WC1E 6BT, England.
   [Price, Amanda J.; Jacques, David A.; James, Leo C.] MRC, Mol Biol Lab, Prot & Nucle Acid Chem Div, Cambridge CB2 0QH, England.
   [Selwood, David L.] UCL, Wolfson Inst Biomed Res, London WC1E 6BT, England.
C3 University of London; University College London; MRC Laboratory Molecular Biology; University of London; University College London
RP Towers, GJ (corresponding author), UCL, MRC, Ctr Med Mol Virol, Div Infect & Immun, 90 Gower St, London WC1E 6BT, England.
EM m.noursadeghi@ucl.ac.uk; g.towers@ucl.ac.uk
FU Wellcome Trust [090940]; Medical Research Council; MRC Confidence in Concept Award; National Institute for Health Research (NIHR) University College London Hospitals Biomedical Research Centre; MRC [G0501446, MC_PC_12024, G0801172, G0900950, G9721629, MC_U105181010] Funding Source: UKRI; Medical Research Council [G9721629B, G0900950B, G0501446, MC_PC_12024, G0900950, G0801172, MC_U105181010, G9721629] Funding Source: researchfish
NR 32
TC 376
Z9 461
U1 0
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 NOV 21
PY 2013
VL 503
IS 7476
BP 402
EP +
DI 10.1038/nature12769
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 254KG
UT WOS:000327163200042
PM 24196705
DA 2026-03-09
ER

PT J
AU Cui, GH
   Jun, SB
   Jin, X
   Pham, MD
   Vogel, SS
   Lovinger, DM
   Costa, RM
AF Cui, Guohong
   Jun, Sang Beom
   Jin, Xin
   Pham, Michael D.
   Vogel, Steven S.
   Lovinger, David M.
   Costa, Rui M.
TI Concurrent activation of striatal direct and indirect pathways during action initiation
SO NATURE
LA English
DT Article
ID basal ganglia; in-vivo; neurons; populations; circuits
AB The basal ganglia are subcortical nuclei that control voluntary actions, and they are affected by a number of debilitating neurological disorders(1-4). The prevailing model of basal ganglia function proposes that two orthogonal projection circuits originating from distinct populations of spiny projection neurons (SPNs) in the striatum(5,6)-the so-called direct and indirect pathways have opposing effects on movement: activity of direct-pathway SPNs is thought to facilitate movement, whereas activity of indirect-pathway SPNs is presumed to inhibit movement(1,2). This model has been difficult to test owing to the lack of methods to selectively measure the activity of direct- and indirect-pathway SPNs in freely moving animals: Here we develop a novel in vivo method to specifically measure direct- and indirect-pathway SPN activity, using Cre-dependent viral expression of the genetically encoded calcium indicator (GECI) GCaMP3 in the dorsal striatum of D1-Cre (direct-pathway-specific(6,7)) and A2A-Cre (indirect-pathway-specific(8,9)) mice. Using fibre optics and time-correlated single-photon counting (TCSPC) in mice performing an operant task, we observed transient-increases in neural activity in both direct- and indirect-pathway SPNs when animals initiated actions, but not when they were inactive. Concurrent activation of SPNs from both pathways in one hemisphere preceded the initiation of contraversive movements and predicted the occurrence of specific movements within 500 ms. These observations challenge the classical view of basal ganglia function and may have implications for understanding the origin of motor symptoms in basal ganglia disorders.
C1 [Cui, Guohong; Jin, Xin; Pham, Michael D.; Lovinger, David M.; Costa, Rui M.] NIAAA, Sect Vivo Neural Funct, Lab Integrat Neurosci, NIH, Bethesda, MD 20892 USA.
   [Jun, Sang Beom] Ewha Womans Univ, Dept Elect Engn, Seoul 120750, South Korea.
   [Jin, Xin] Salk Inst Biol Studies, Mol Neurobiol Lab, La Jolla, CA 92037 USA.
   [Vogel, Steven S.] NIAAA, Sect Cellular Biophoton, Lab Mol Physiol, NIH, Bethesda, MD 20892 USA.
   [Lovinger, David M.] NIAAA, Sect Synapt Pharmacol, Lab Integrat Neurosci, NIH, Bethesda, MD 20892 USA.
   [Costa, Rui M.] Inst Gulbenkian Ciencias, Champalimaud Neurosci Programme, P-1400038 Lisbon, Portugal.
   [Costa, Rui M.] Champalimaud Ctr Unknown, P-1400038 Lisbon, Portugal.
C3 National Institutes of Health (NIH) - USA; NIH National Institute on Alcohol Abuse & Alcoholism (NIAAA); Ewha Womans University; Salk Institute; National Institutes of Health (NIH) - USA; NIH National Institute on Alcohol Abuse & Alcoholism (NIAAA); National Institutes of Health (NIH) - USA; NIH National Institute on Alcohol Abuse & Alcoholism (NIAAA); Fundacao Champalimaud; Instituto Gulbenkian de Ciencia; Fundacao Champalimaud
RP Vogel, SS (corresponding author), NIAAA, Sect Cellular Biophoton, Lab Mol Physiol, NIH, 5625 Fishers Lane, Bethesda, MD 20892 USA.
EM stevevog@mail.nih.gov; lovindav@mail.nih.gov; ruicosta@fchampalimaud.org
FU Division of Intramural Clinical and Biological Research of the NIAAA; European Research Council [STG 243393]; International Early Career Scientist grant from the Howard Hughes Medical Institute; National Research Foundation of Korea [2011-0029485, 2012-0004003]; SmartIT Convergence System Research Center from the Korean government (MEST) [SIRC-2011-0031866]; Ellison Medical Foundation [AG-NS-0944-12]; National Institute on Alcohol Abuse and Alcoholism [ZIAAA000416, ZIAAA000452] Funding Source: NIH RePORTER
NR 30
TC 910
Z9 1179
U1 3
U2 192
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 14
PY 2013
VL 494
IS 7436
BP 238
EP 242
DI 10.1038/nature11846
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 092QS
UT WOS:000315137700040
PM 23354054
DA 2026-03-09
ER

PT J
AU Naik, SH
   Perié, L
   Swart, E
   Gerlach, C
   van Rooij, N
   de Boer, RJ
   Schumacher, TN
AF Naik, Shalin H.
   Perie, Leila
   Swart, Erwin
   Gerlach, Carmen
   van Rooij, Nienke
   de Boer, Rob J.
   Schumacher, Ton N.
TI Diverse and heritable lineage imprinting of early haematopoietic progenitors
SO NATURE
LA English
DT Article
ID dendritic-cell-development; stem-cells; in-vivo; t-cells; commitment; subtypes; promiscuity; compartment; subsets; system
AB Haematopoietic stem cells (HSCs) and their subsequent progenitors produce blood cells, but the precise nature and kinetics of this production is a contentious issue. In one model, lymphoid and myeloid production branch after the lymphoid-primed multipotent progenitor (LMPP)(1), with both branches subsequently producing dendritic cells(2). However, this model is based mainly on in vitro clonal assays and population-based tracking in vivo, which could miss in vivo single-cell complexity(3-7). Here we avoid these issues by using a new quantitative version of 'cellular barcoding'(8-10) to trace the in vivo fate of hundreds of LMPPs and HSCs at the single-cell level. These data demonstrate that LMPPs are highly heterogeneous in the cell types that they produce, separating into combinations of lymphoid-, myeloid-and dendritic-cell-biased producers. Conversely, although we observe a known lineage bias of some HSCs11-14, most cellular output is derived from a small number of HSCs that each generates all cell types. Crucially, in vivo analysis of the output of sibling cells derived from single LMPPs shows that they often share a similar fate, suggesting that the fate of these progenitors was imprinted. Furthermore, as this imprinting is also observed for dendritic-cell-biased LMPPs, dendritic cells may be considered a distinct lineage on the basis of separate ancestry. These data suggest a 'graded commitment' model of haematopoiesis, in which heritable and diverse lineage imprinting occurs earlier than previously thought.
C1 [Naik, Shalin H.; Perie, Leila; Swart, Erwin; Gerlach, Carmen; van Rooij, Nienke; Schumacher, Ton N.] Netherlands Canc Inst, Div Immunol, NL-1066 CX Amsterdam, Netherlands.
   [Perie, Leila; de Boer, Rob J.] Univ Utrecht, NL-3584 CH Utrecht, Netherlands.
C3 Netherlands Cancer Institute; Utrecht University
RP Naik, SH (corresponding author), Walter & Eliza Hall Inst Med Res, 1G Royal Parade, Parkville, Vic 3052, Australia.
EM naik.s@wehi.edu.au; t.schumacher@nki.nl
FU ERC grant LIFE-HIS-T and HFSP [RGP0060/2012]; National Health and Medical Research Council Australia; Marie Curie Incoming International FP6 Fellowship; Leukemia and Lymphoma Society; Marie Curie Intra European FP7 Fellowship; Bettencourt Schueller Fondation
NR 30
TC 317
Z9 373
U1 0
U2 38
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 11
PY 2013
VL 496
IS 7444
BP 229
EP +
DI 10.1038/nature12013
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 122VM
UT WOS:000317346300043
PM 23552896
DA 2026-03-09
ER

PT J
AU He, F
   Shakun, JD
   Clark, PU
   Carlson, AE
   Liu, ZY
   Otto-Bliesner, BL
   Kutzbach, JE
AF He, Feng
   Shakun, Jeremy D.
   Clark, Peter U.
   Carlson, Anders E.
   Liu, Zhengyu
   Otto-Bliesner, Bette L.
   Kutzbach, John E.
TI Northern Hemisphere forcing of Southern Hemisphere climate during the last deglaciation
SO NATURE
LA English
DT Article
ID antarctic temperature; atmospheric co2; deep; surface; cycles
AB According to the Milankovitch theory, changes in summer insolation in. the high-latitude Northern Hemisphere caused glacial cycles through their impact on ice-sheet mass balance(1). Statistical analyses of long climate records supported this theory, but they also posed a substantial challenge by showing that changes in Southern Hemisphere climate were in phase with or led those in the north(2). Although an orbitally forced Northern Hemisphere signal may have been transmitted to the Southern Hemisphere(3), insolation forcing can also directly influence local Southern Hemisphere climate, potentially intensified by sea-ice feedback(4-6), suggesting that the hemispheres may have responded independently to different aspects of orbital forcing. Signal processing of climate records cannot distinguish between these conditions, however, because the proposed insolation forcings share essentially identical variability(7). Here we use transient simulations with a coupled atmosphere-ocean general circulation model to identify the impacts of forcing from changes in orbits, atmospheric CO2 concentration, ice sheets and the Atlantic meridional overturning circulation (AMOC) on hemispheric temperatures during the first half of the last deglaciation (22-14.3 kyr BP). Although based on a single model, our transient simulation with only orbital changes supports the Milankovitch theory in showing that the last deglaciation was initiated by rising insolation during spring and summer in the mid-latitude to high-latitude Northern Hemisphere and by terrestrial snow-albedo feedback. The simulation with all forcings best reproduces the;timing and magnitude of surface temperature evolution in the Southern Hemisphere in deglacial proxy records(8,9). AMOC changes associated with an orbitally induced retreat of Northern Hemisphere ice sheets(10) is the most plausible explanation for the early Southern Hemisphere deglacial warming and its lead over Northern Hemisphere temperature; the ensuing rise in atmospheric CO2 concentration provided the critical feedback on global deglaciation(9,11).
C1 [He, Feng; Carlson, Anders E.; Liu, Zhengyu; Kutzbach, John E.] Univ Wisconsin, Nelson Inst Environm Studies, Ctr Climat Res, Madison, WI 53706 USA.
   [Shakun, Jeremy D.] Harvard Univ, Dept Earth & Planetary Sci, Cambridge, MA 02138 USA.
   [Clark, Peter U.; Carlson, Anders E.] Oregon State Univ, Coll Earth Ocean & Atmospher Sci, Corvallis, OR 97331 USA.
   [Carlson, Anders E.] Univ Wisconsin, Dept Geosci, Madison, WI 53706 USA.
   [Liu, Zhengyu] Univ Wisconsin, Dept Atmospher & Ocean Sci, Madison, WI 53706 USA.
   [Otto-Bliesner, Bette L.] Natl Ctr Atmospher Res, Climate & Global Dynam Div, Boulder, CO 80307 USA.
C3 University of Wisconsin System; University of Wisconsin Madison; Harvard University; Oregon State University; University of Wisconsin System; University of Wisconsin Madison; University of Wisconsin System; University of Wisconsin Madison; National Center Atmospheric Research (NCAR) - USA
RP He, F (corresponding author), Univ Wisconsin, Nelson Inst Environm Studies, Ctr Climat Res, Madison, WI 53706 USA.
EM fenghe@wisc.edu
FU Office of Science of the Department of Energy [DE-AC05-00OR22725]; US National Science Foundation [AGS-0902802, AGS-1203430]; Climate, People, and the Environment Program; National Science Foundation [06023950-ATM]
NR 30
TC 198
Z9 240
U1 2
U2 254
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 7
PY 2013
VL 494
IS 7435
BP 81
EP 85
DI 10.1038/nature11822
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 087DJ
UT WOS:000314741200038
PM 23389542
DA 2026-03-09
ER

PT J
AU Warr, MR
   Binnewies, M
   Flach, J
   Reynaud, D
   Garg, T
   Malhotra, R
   Debnath, J
   Passegué, E
AF Warr, Matthew R.
   Binnewies, Mikhail
   Flach, Johanna
   Reynaud, Damien
   Garg, Trit
   Malhotra, Ritu
   Debnath, Jayanta
   Passegue, Emmanuelle
TI FOXO3A directs a protective autophagy program in haematopoietic stem cells
SO NATURE
LA English
DT Article
ID gene atg5; mitochondria; maintenance; mechanisms; survival; pathways; plays; death
AB Blood production is ensured by rare, self-renewing haematopoietic stem cells (HSCs). How HSCs accommodate the diverse cellular stresses associated with their life-long activity remains elusive. Here we identify autophagy as an essential mechanism protecting HSCs from metabolic stress. We show that mouse HSCs, in contrast to their short-lived myeloid progeny, robustly induce autophagy after ex vivo cytokine withdrawal and in vivo calorie restriction. We demonstrate that FOXO3A is critical to maintain a gene expression program that poises HSCs for rapid induction of autophagy upon starvation. Notably, we find that old HSCs retain an intact FOXO3A-driven pro-autophagy gene program, and that ongoing autophagy is needed to mitigate an energy crisis and allow their survival. Our results demonstrate that autophagy is essential for the life-long maintenance of the HSC compartment and for supporting an old, failing blood system.
C1 [Warr, Matthew R.; Binnewies, Mikhail; Flach, Johanna; Reynaud, Damien; Garg, Trit; Passegue, Emmanuelle] Univ Calif San Francisco, Dept Med, Div Hematol Oncol, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, San Francisco, CA 94143 USA.
   [Malhotra, Ritu; Debnath, Jayanta] Univ Calif San Francisco, Dept Pathol, 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 Passegué, E (corresponding author), Univ Calif San Francisco, Dept Med, Div Hematol Oncol, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, San Francisco, CA 94143 USA.
EM PassegueE@stemcell.ucsf.edu
FU Culpepper Scholar Award; NIH [CA126792, HL092471]; CIRM New Faculty Award; National Cancer Institute [R01CA126792] Funding Source: NIH RePORTER
NR 33
TC 499
Z9 576
U1 1
U2 107
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 21
PY 2013
VL 494
IS 7437
BP 323
EP 327
DI 10.1038/nature11895
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 095CS
UT WOS:000315312900031
PM 23389440
DA 2026-03-09
ER

PT J
AU Nick, FM
   Vieli, A
   Andersen, ML
   Joughin, I
   Payne, A
   Edwards, TL
   Pattyn, F
   van de Wal, RSW
AF Nick, Faezeh M.
   Vieli, Andreas
   Andersen, Morten Langer
   Joughin, Ian
   Payne, Antony
   Edwards, Tamsin L.
   Pattyn, Frank
   van de Wal, Roderik S. W.
TI Future sea-level rise from Greenland's main outlet glaciers in a warming climate
SO NATURE
LA English
DT Article
ID jakobshavn isbrae; ice; stability; acceleration; dynamics
AB Over the past decade, ice loss from the Greenland Ice Sheet increased as a result of both increased surface melting and ice discharge to the ocean(1,2). The latter is controlled by the acceleration of ice flow and subsequent thinning of fast-flowing marine-terminating outlet glaciers(3). Quantifying the future dynamic contribution of such glaciers to sea-level rise (SLR) remains a major challenge because outlet glacier dynamics are poorly understood(4). Here we present a glacier flow model that includes a fully dynamic treatment of marine termini. We use this model to simulate behaviour of four major marine-terminating outlet glaciers, which collectively drain about 22 per cent of the Greenland Ice Sheet. Using atmospheric and oceanic forcing from a mid-range future warming scenario that predicts warming by 2.8 degrees Celsius by 2100, we project a contribution of 19 to 30 millimetres to SLR from these glaciers by 2200. This contribution is largely (80 per cent) dynamic in origin and is caused by several episodic retreats past overdeepenings in outlet glacier troughs. After initial increases, however, dynamic losses from these four outlets remain relatively constant and contribute to SLR individually at rates of about 0.01 to 0.06 millimetres per year. These rates correspond to ice fluxes that are less than twice those of the late 1990s, well below previous upper bounds(5). For a more extreme future warming scenario (warming by 4.5 degrees Celsius by 2100), the projected losses increase by more than 50 per cent, producing a cumulative SLR of 29 to 49 millimetres by 2200.
C1 [Nick, Faezeh M.; Pattyn, Frank] Univ Libre Bruxelles, Lab Glaciol, B-1050 Brussels, Belgium.
   [Nick, Faezeh M.; van de Wal, Roderik S. W.] Univ Utrecht, Inst Marine & Atmospher Res, NL-3508 TA Utrecht, Netherlands.
   [Nick, Faezeh M.] Univ Ctr Svalbard, Dept Geol, NO-9171 Longyearbyen, Norway.
   [Vieli, Andreas] Univ Durham, Dept Geog, Durham DH1 3LE, England.
   [Vieli, Andreas] Univ Zurich, Dept Geog, CH-8057 Zurich, Switzerland.
   [Andersen, Morten Langer] Geol Survey Denmark & Greenland, DK-1350 Copenhagen, Denmark.
   [Joughin, Ian] Univ Washington, Appl Phys Lab, Polar Sci Ctr, Seattle, WA 98108 USA.
   [Payne, Antony; Edwards, Tamsin L.] Univ Bristol, Bristol Glaciol Ctr, Bristol BS8 1SS, Avon, England.
C3 Universite Libre de Bruxelles; Utrecht University; University Centre Svalbard (UNIS); Durham University; University of Zurich; Geological Survey Of Denmark & Greenland; University of Washington; University of Washington Seattle; University of Bristol
RP Nick, FM (corresponding author), Univ Libre Bruxelles, Lab Glaciol, B-1050 Brussels, Belgium.
EM faezeh.nick@unis.no
FU ice2sea programme of the European Union 7th Framework Programme [226375]; Netherlands Polar Programme (NPP); European Union 6th Framework Programme Integrated Project ENSEMBLES [505539]; US NSF [ANT-0424589]
NR 30
TC 222
Z9 262
U1 3
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 MAY 9
PY 2013
VL 497
IS 7448
BP 235
EP 238
DI 10.1038/nature12068
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 139CD
UT WOS:000318558200035
PM 23657350
DA 2026-03-09
ER

PT J
AU Wu, LF
   Candille, SI
   Choi, Y
   Xie, D
   Jiang, LH
   Li-Pook-Than, J
   Tang, H
   Snyder, M
AF Wu, Linfeng
   Candille, Sophie I.
   Choi, Yoonha
   Xie, Dan
   Jiang, Lihua
   Li-Pook-Than, Jennifer
   Tang, Hua
   Snyder, Michael
TI Variation and genetic control of protein abundance in humans
SO NATURE
LA English
DT Article
AB Gene expression differs among individuals and populations and is thought to be a major determinant of phenotypic variation. Although variation and genetic loci responsible for RNA expression levels have been analysed extensively in human populations(1-5), our knowledge is limited regarding the differences in human protein abundance and the genetic basis for this difference. Variation in messenger RNA expression is not a perfect surrogate for protein expression because the latter is influenced by an array of post-transcriptional regulatory mechanisms, and, empirically, the correlation between protein and mRNA levels is generally modest(6,7). Here we used isobaric tag-based quantitative mass spectrometry to determine relative protein levels of 5,953 genes in lymphoblastoid cell lines from 95 diverse individuals genotyped in the HapMap Project(8,9). We found that protein levels are heritable molecular phenotypes that exhibit considerable variation between individuals, populations and sexes. Levels of specific sets of proteins involved in the same biological process covary among individuals, indicating that these processes are tightly regulated at the protein level. We identified cis-pQTLs (protein quantitative trait loci), including variants not detected by previous transcriptome studies. This study demonstrates the feasibility of high-throughput human proteome quantification that, when integrated with DNA variation and transcriptome information, adds a new dimension to the characterization of gene expression regulation.
C1 [Wu, Linfeng; Candille, Sophie I.; Choi, Yoonha; Xie, Dan; Jiang, Lihua; Li-Pook-Than, Jennifer; Tang, Hua; Snyder, Michael] Stanford Univ, Sch Med, Dept Genet, Stanford, CA 94305 USA.
C3 Stanford University
RP Snyder, M (corresponding author), Stanford Univ, Sch Med, Dept Genet, Stanford, CA 94305 USA.
EM huatang@stanford.edu; mpsnyder@stanford.edu
FU NIH
NR 24
TC 291
Z9 339
U1 0
U2 92
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 4
PY 2013
VL 499
IS 7456
BP 79
EP 82
DI 10.1038/nature12223
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 176ED
UT WOS:000321285600037
PM 23676674
DA 2026-03-09
ER

PT J
AU Choi, YJ
   Lee, SY
AF Choi, Yong Jun
   Lee, Sang Yup
TI Microbial production of short-chain alkanes
SO NATURE
LA English
DT Article
ID acyl carrier protein; fatty-acid synthesis; escherichia-coli; arabidopsis eceriferum1; synthase-iii; biosynthesis; gene; initiation; chemicals; mutants
AB Increasing concerns about limited fossil fuels and global environmental problems have focused attention on the need to develop sustainable biofuels from renewable resources. Although microbial production of diesel has been reported, production of another much in demand transport fuel, petrol (gasoline), has not yet been demonstrated. Here we report the development of platform Escherichia coli strains that are capable of producing short-chain alkanes (SCAs; petrol), free fatty acids (FFAs), fatty esters and fatty alcohols through the fatty acyl (acyl carrier protein (ACP)) to fatty acid to fatty acyl-CoA pathway. First, the beta-oxidation pathway was blocked by deleting the fadE gene to prevent the degradation of fatty acyl-CoAs generated in vivo. To increase the formation of short-chain fatty acids suitable for subsequent conversion to SCAs in vivo, the activity of 3-oxoacyl-ACP synthase (FabH)(1), which is inhibited by unsaturated fatty acyl-ACPs(2), was enhanced to promote the initiation of fatty acid biosynthesis by deleting the fadR gene; deletion of the fadR gene prevents upregulation of the fabA and fabB genes responsible for unsaturated fatty acids biosynthesis(3). A modified thioesterase(4) was used to convert short-chain fatty acyl-ACPs to the corresponding FFAs, which were then converted to SCAs by the sequential reactions of E. coli fatty acyl-CoA synthetase, Clostridium acetobutylicum fatty acyl-CoA reductase and Arabidopsis thaliana fatty aldehyde decarbonylase. The final engineered strain produced up to 580.8 mg l(-1) of SCAs consisting of nonane (327.8 mg l(-1)), dodecane (136.5 mg l(-1)), tridecane (64.8 mg l(-1)), 2-methyl-dodecane (42.8 mg l(-1)) and tetradecane (8.9 mg l(-1)), together with small amounts of other hydrocarbons. Furthermore, this platform strain could produce short-chain FFAs using a fadD-deleted strain, and short-chain fatty esters by introducing the Acinetobacter sp. ADP1 wax ester synthase (atfA)(5) and the E. coli mutant alcohol dehydrogenase (adhE(mut))(6).
C1 [Choi, Yong Jun; Lee, Sang Yup] Korea Adv Inst Sci & Technol, Metab & Biomol Engn Natl Res Lab, Dept Chem & Biomol Engn, BioProc Engn Res Ctr,Program BK21, Taejon 305701, South Korea.
   [Choi, Yong Jun; Lee, Sang Yup] Korea Adv Inst Sci & Technol, Ctr Syst & Synthet Biotechnol, Taejon 305701, South Korea.
   [Lee, Sang Yup] Korea Adv Inst Sci & Technol, Bioinformat & BioProc Engn Res Ctr, Taejon 305701, South Korea.
C3 Korea Advanced Institute of Science & Technology (KAIST); Korea Advanced Institute of Science & Technology (KAIST); Korea Advanced Institute of Science & Technology (KAIST)
RP Lee, SY (corresponding author), Korea Adv Inst Sci & Technol, Metab & Biomol Engn Natl Res Lab, Dept Chem & Biomol Engn, BioProc Engn Res Ctr,Program BK21, 291 Daehak Ro, Taejon 305701, South Korea.
EM leesy@kaist.ac.kr
FU Advanced Biomass Research and Development Center of Korea through the Global Frontier Research Program of the Ministry of Science, ICT and Future Planning (MSIP) through the National Research Foundation (NRF) [ABC-2010-0029799]; Technology Development Program to Solve Climate Changes on Systems Metabolic Engineering for Biorefineries by MSIP through NRF [NRF-2012-C1AAA001-2012M1A2A2026556]
NR 33
TC 361
Z9 440
U1 2
U2 377
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 24
PY 2013
VL 502
IS 7472
BP 571
EP +
DI 10.1038/nature12536
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 238YN
UT WOS:000325988400059
PM 24077097
DA 2026-03-09
ER

PT J
AU Park, S
   Li, XM
   Kim, HM
   Singh, CR
   Tian, G
   Hoyt, MA
   Lovell, S
   Battaile, KP
   Zolkiewski, M
   Coffino, P
   Roelofs, J
   Cheng, YF
   Finley, D
AF Park, Soyeon
   Li, Xueming
   Kim, Ho Min
   Singh, Chingakham Ranjit
   Tian, Geng
   Hoyt, Martin A.
   Lovell, Scott
   Battaile, Kevin P.
   Zolkiewski, Michal
   Coffino, Philip
   Roelofs, Jeroen
   Cheng, Yifan
   Finley, Daniel
TI Reconfiguration of the proteasome during chaperone-mediated assembly
SO NATURE
LA English
DT Article
ID yeast 26s proteasome; regulatory particle; structural basis; 20s proteasm; s proteasome; atpases; subunit; pathway; core; gate
AB The proteasomal ATPase ring, comprising Rpt1-Rpt6, associates with the heptameric alpha-ring of the proteasome core particle (CP) in the mature proteasome, with the Rpt carboxy-terminal tails inserting into pockets of the alpha-ring(1-4). Rpt ring assembly is mediated by four chaperones, each binding a distinct Rpt subunit(5-10). Here we report that the base subassembly of the Saccharomyces cerevisiae proteasome, which includes the Rpt ring, forms a high-affinity complex with the CP. This complex is subject to active dissociation by the chaperones Hsm3, Nas6 and Rpn14. Chaperone-mediated dissociation was abrogated by a non-hydrolysable ATP analogue, indicating that chaperone action is coupled to nucleotide hydrolysis by the Rpt ring. Unexpectedly, synthetic Rpt tail peptides bound alpha-pockets with poor specificity, except for Rpt6, which uniquely bound the alpha 2/alpha 3-pocket. Although the Rpt6 tail is not visualized within an alpha-pocket in mature proteasomes(2-4), it inserts into the alpha 2/alpha 3-pocket in the base-CP complex and is important for complex formation. Thus, the Rpt-CP interface is reconfigured when the lid complex joins the nascent proteasome to form the mature holoenzyme.
C1 [Park, Soyeon; Tian, Geng; Finley, Daniel] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA.
   [Park, Soyeon] Univ Colorado, MCD Biol, Boulder, CO 80309 USA.
   [Li, Xueming; Kim, Ho Min; Cheng, Yifan] Univ Calif San Francisco, Dept Biochem & Biophys, WM Keck Adv Microscopy Lab, San Francisco, CA 94158 USA.
   [Singh, Chingakham Ranjit; Roelofs, Jeroen] Kansas State Univ, Div Biol, Manhattan, KS 66506 USA.
   [Hoyt, Martin A.; Coffino, Philip] Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94143 USA.
   [Lovell, Scott] Univ Kansas, Del Shankel Struct Biol Ctr, Prot Struct Lab, Lawrence, KS 66047 USA.
   [Battaile, Kevin P.] IMCA CAT Hauptman Woodward Med Res Inst, Argonne, IL 60439 USA.
   [Zolkiewski, Michal] Kansas State Univ, Dept Biochem, Manhattan, KS 66506 USA.
C3 Harvard University; Harvard Medical School; University of Colorado System; University of Colorado Boulder; University of California System; University of California San Francisco; Kansas State University; University of California System; University of California San Francisco; University of Kansas; Hauptman Woodward Medical Research Institute; Kansas State University
RP Roelofs, J (corresponding author), Kansas State Univ, Div Biol, 338 Ackert Hall, Manhattan, KS 66506 USA.
EM jroelofs@ksu.edu; ycheng@ucsf.edu; daniel_finley@hms.harvard.edu
FU National Institutes of Health (NIH) [R01GM082893, 1S10RR026814-01]; University of California San Francisco Program for Breakthrough Biomedical Research (New Technology Award); Johnson Cancer Research Center; National Center for Research Resources [5P20RR017708, P20 RR016475]; NIH [8 P20 GM103420, P20 GM103418, R01GM045335, R37GM043601]; Charles A. King Trust Postdoctoral Research Fellowship Program of the Medical Foundation; US Department of Energy [DE-AC02-06CH11357]; National Institute of General Medical Sciences [P20GM103418] Funding Source: NIH RePORTER
NR 25
TC 61
Z9 76
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 MAY 23
PY 2013
VL 497
IS 7450
BP 512
EP 516
DI 10.1038/nature12123
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 148OG
UT WOS:000319254000053
PM 23644457
DA 2026-03-09
ER

PT J
AU Di Ruscio, A
   Ebralidze, AK
   Benoukraf, T
   Amabile, G
   Goff, LA
   Terragni, J
   Figueroa, ME
   Pontes, LLD
   Alberich-Jorda, M
   Zhang, P
   Wu, MC
   D'Alò, F
   Melnick, A
   Leone, G
   Ebralidze, KK
   Pradhan, S
   Rinn, JL
   Tenen, DG
AF Di Ruscio, Annalisa
   Ebralidze, Alexander K.
   Benoukraf, Touati
   Amabile, Giovanni
   Goff, Loyal A.
   Terragni, Jolyon
   Figueroa, Maria Eugenia
   Pontes, Lorena Lobo De Figueiredo
   Alberich-Jorda, Meritxell
   Zhang, Pu
   Wu, Mengchu
   D'Alo, Francesco
   Melnick, Ari
   Leone, Giuseppe
   Ebralidze, Konstantin K.
   Pradhan, Sriharsa
   Rinn, John L.
   Tenen, Daniel G.
TI DNMT1-interacting RNAs block gene-specific DNA methylation
SO NATURE
LA English
DT Article
ID genome-wide identification; transcription factors; expression; maintenance; polymerase; methyltransferase; chromatin; reveals; cancer; sites
AB DNA methylation was first described almost a century ago; however, the rules governing its establishment and maintenance remain elusive. Here we present data demonstrating that active transcription regulates levels of genomic methylation. We identify a novel RNA arising from the CEBPA gene locus that is critical in regulating the local DNA methylation profile. This RNA binds to DNMT1 and prevents CEBPA gene locus methylation. Deep sequencing of transcripts associated with DNMT1 combined with genome-scale methylation and expression profiling extend the generality of this finding to numerous gene loci. Collectively, these results delineate the nature of DNMT1-RNA interactions and suggest strategies for gene-selective demethylation of therapeutic targets in human diseases.
C1 [Di Ruscio, Annalisa; Ebralidze, Alexander K.; Amabile, Giovanni; Pontes, Lorena Lobo De Figueiredo; Alberich-Jorda, Meritxell; Zhang, Pu; Rinn, John L.; Tenen, Daniel G.] Harvard Univ, Sch Med, Harvard Stem Cell Inst, Boston, MA 02115 USA.
   [Di Ruscio, Annalisa; Ebralidze, Alexander K.; Amabile, Giovanni; Pontes, Lorena Lobo De Figueiredo; Alberich-Jorda, Meritxell; Ebralidze, Konstantin K.; Rinn, John L.] Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA.
   [D'Alo, Francesco; Leone, Giuseppe] Univ Cattolica Sacro Cuore, Inst Hematol, I-00168 Rome, Italy.
   [Benoukraf, Touati; Wu, Mengchu; Tenen, Daniel G.] Natl Univ Singapore, Canc Sci Inst, Singapore 117599, Singapore.
   [Goff, Loyal A.; Rinn, John L.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA.
   [Goff, Loyal A.; Rinn, John L.] Broad Inst MIT & Harvard, Cambridge Ctr 7, Cambridge, MA 02142 USA.
   [Goff, Loyal A.] MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA.
   [Terragni, Jolyon; Pradhan, Sriharsa] New England Biolabs Inc, Ipswich, MA 01938 USA.
   [Figueroa, Maria Eugenia] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA.
   [Alberich-Jorda, Meritxell] Acad Sci Czech Republ, Inst Mol Genet, CR-14220 Prague, Czech Republic.
   [Melnick, Ari] C620 Weill Cornell Med Coll, Dept Med, New York, NY 10021 USA.
C3 Harvard University; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Beth Israel Deaconess Medical Center; Catholic University of the Sacred Heart; IRCCS Policlinico Gemelli; National University of Singapore; Harvard University; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Massachusetts Institute of Technology (MIT); New England Biolabs; University of Michigan System; University of Michigan; Czech Academy of Sciences; Institute of Molecular Genetics of the Czech Academy of Sciences; Cornell University; Weill Cornell Medicine
RP Tenen, DG (corresponding author), Harvard Univ, Sch Med, Harvard Stem Cell Inst, Boston, MA 02115 USA.
EM daniel.tenen@nus.edu.sg
FU National Institutes of Health (NIH) [CA118316, CA66996, HL56745, T32 HL007917-11A1]; Italian Foundation for Cancer Research (FIRC); Societa Italiana di Ematologia Sperimentale (SIES); FAMRI CIA [103063]; Fondazione Roma; American Italian Cancer Foundation Fellowship (AICF); Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [2011/11822-6]; National Research Foundation; Singapore Ministry of Education under its Centres of Excellence initiative; MSMT Navrat grant [LK21307]; New England Biolabs; Singapore Ministry of Health's National Medical Research Council under its Singapore Translational Research (STaR) Investigator Award; Associazione Italiana per la Ricerca sul Cancro Funding Source: Custom; National Cancer Institute [P01CA066996] Funding Source: NIH RePORTER; National Heart Lung and Blood Institute [T32HL007917] Funding Source: NIH RePORTER
NR 66
TC 418
Z9 505
U1 0
U2 121
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 21
PY 2013
VL 503
IS 7476
BP 371
EP +
DI 10.1038/nature12598
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 254KG
UT WOS:000327163200035
PM 24107992
DA 2026-03-09
ER

PT J
AU Teufel, R
   Miyanaga, A
   Michaudel, Q
   Stull, F
   Louie, G
   Noel, JP
   Baran, PS
   Palfey, B
   Moore, BS
AF Teufel, Robin
   Miyanaga, Akimasa
   Michaudel, Quentin
   Stull, Frederick
   Louie, Gordon
   Noel, Joseph P.
   Baran, Phil S.
   Palfey, Bruce
   Moore, Bradley S.
TI Flavin-mediated dual oxidation controls an enzymatic Favorskii-type rearrangement
SO NATURE
LA English
DT Article
ID dependent monooxygenase; crystal-structure; swiss-model; enterocin; protein; oxygen; hydroxylation; environment; mechanism; synthase
AB Flavoproteins catalyse a diversity of fundamental redox reactions and are one of the most studied enzyme families(1,2). As monooxygenases, they are universally thought to control oxygenation by means of a peroxyflavin species that transfers a single atom of molecular oxygen to an organic substrate(1,3,4). Here we report that the bacterial flavoenzyme EncM(5,6) catalyses the peroxyflavin-independent oxygenation-dehydrogenation dual oxidation of a highly reactive poly(beta-carbonyl). The crystal structure of EncM with bound substrate mimics and isotope labelling studies reveal previously unknown flavin redox biochemistry. We show that EncM maintains an unexpected stable flavin-oxygenating species, proposed to be a flavin-N5-oxide, to promote substrate oxidation and trigger a rare Favorskii-type rearrangement that is central to the biosynthesis of the antibiotic enterocin. This work provides new insight into the fine-tuning of the flavin cofactor in offsetting the innate reactivity of a polyketide substrate to direct its efficient electrocyclization.
C1 [Teufel, Robin; Miyanaga, Akimasa; Moore, Bradley S.] Univ Calif San Diego, Scripps Inst Oceanog, Ctr Marine Biotechnol & Biomed, La Jolla, CA 92093 USA.
   [Michaudel, Quentin; Baran, Phil S.] Scripps Res Inst, Dept Chem, La Jolla, CA 92037 USA.
   [Stull, Frederick; Palfey, Bruce] Univ Michigan, Program Chem Biol, Ann Arbor, MI 48109 USA.
   [Louie, Gordon; Noel, Joseph P.] Salk Inst Biol Studies, Howard Hughes Med Inst, Jack H Skirball Ctr Chem Biol & Prote, La Jolla, CA 92037 USA.
   [Palfey, Bruce] Univ Michigan, Dept Biol Chem, Ann Arbor, MI 48109 USA.
   [Moore, Bradley S.] Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, La Jolla, CA 92093 USA.
C3 University of California System; University of California San Diego; Scripps Institution of Oceanography; Scripps Research Institute; University of Michigan System; University of Michigan; Salk Institute; Howard Hughes Medical Institute; University of Michigan System; University of Michigan; University of California System; University of California San Diego
RP Moore, BS (corresponding author), Univ Calif San Diego, Scripps Inst Oceanog, Ctr Marine Biotechnol & Biomed, La Jolla, CA 92093 USA.
EM bsmoore@ucsd.edu
FU US National Institutes of Health [R01AI47818]; National Science Foundation (NSF) [EEC-0813570, MCB-0645794, CHE-1213620]; Howard Hughes Medical Institute; Deutsche Forschungsgemeinschaft [TE 931/1-1]; Japan Society for the Promotion of Science [21-644]; National Institute of Allergy and Infectious Diseases [R01AI047818] Funding Source: NIH RePORTER
NR 40
TC 141
Z9 175
U1 1
U2 231
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 28
PY 2013
VL 503
IS 7477
BP 552
EP +
DI 10.1038/nature12643
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 258MU
UT WOS:000327464200049
PM 24162851
DA 2026-03-09
ER

PT J
AU Hansen, SG
   Piatak, M
   Ventura, AB
   Hughes, CM
   Gilbride, RM
   Ford, JC
   Oswald, K
   Shoemaker, R
   Li, Y
   Lewis, MS
   Gilliam, AN
   Xu, GW
   Whizin, N
   Burwitz, BJ
   Planer, SL
   Turner, JM
   Legasse, AW
   Axthelm, MK
   Nelson, JA
   Früh, K
   Sacha, JB
   Estes, JD
   Keele, BF
   Edlefsen, PT
   Lifson, JD
   Picker, LJ
AF Hansen, Scott G.
   Piatak, Michael, Jr.
   Ventura, Abigail B.
   Hughes, Colette M.
   Gilbride, Roxanne M.
   Ford, Julia C.
   Oswald, Kelli
   Shoemaker, Rebecca
   Li, Yuan
   Lewis, Matthew S.
   Gilliam, Awbrey N.
   Xu, Guangwu
   Whizin, Nathan
   Burwitz, Benjamin J.
   Planer, Shannon L.
   Turner, John M.
   Legasse, Alfred W.
   Axthelm, Michael K.
   Nelson, Jay A.
   Frueh, Klaus
   Sacha, Jonah B.
   Estes, Jacob D.
   Keele, Brandon F.
   Edlefsen, Paul T.
   Lifson, Jeffrey D.
   Picker, Louis J.
TI Immune clearance of highly pathogenic SIV infection
SO NATURE
LA English
DT Article
ID rhesus macaques; virus; hiv; protection; responses; model; assay; cure
AB Established infections with the human and simian immunodeficiency viruses (HIV and SIV, respectively) are thought to be permanent with even the most effective immune responses and antiretroviral therapies only able to control, but not clear, these infections(1-4). Whether the residual virus that maintains these infections is vulnerable to clearance is a question of central importance to the future management of millions of HIV-infected individuals. We recently reported that approximately 50% of rhesus macaques (RM; Macaca mulatta) vaccinated with SIV protein-expressing rhesus cytomegalovirus (RhCMV/SIV) vectors manifest durable, aviraemic control of infection with the highly pathogenic strain SIV mac239 (ref. 5). Here we show that regardless of the route of challenge, RhCMV/SIV vector-elicited immune responses control SIV mac239 after demonstrable lymphatic and haematogenous viral dissemination, and that replication-competent SIV persists in several sites for weeks to months. Over time, however, protected RM lost signs of SIV infection, showing a consistent lack of measurable plasma-or tissue-associated virus using ultrasensitive assays, and a loss of T-cell reactivity to SIV determinants not in the vaccine. Extensive ultrasensitive quantitative PCR and quantitative PCR with reverse transcription analyses of tissues from RhCMV/SIV vector-protected RM necropsied 69-172 weeks after challenge did not detect SIV RNA or DNA sequences above background levels, and replication-competent SIV was not detected in these RM by extensive co-culture analysis of tissues or by adoptive transfer of 60 million haematolymphoid cells to naive RM. These data provide compelling evidence for progressive clearance of a pathogenic lentiviral infection, and suggest that some lentiviral reservoirs may be susceptible to the continuous effector memory T-cell-mediated immune surveillance elicited and maintained by cytomegalovirus vectors.
C1 [Hansen, Scott G.; Ventura, Abigail B.; Hughes, Colette M.; Gilbride, Roxanne M.; Ford, Julia C.; Lewis, Matthew S.; Gilliam, Awbrey N.; Xu, Guangwu; Whizin, Nathan; Burwitz, Benjamin J.; Planer, Shannon L.; Turner, John M.; Legasse, Alfred W.; Axthelm, Michael K.; Nelson, Jay A.; Frueh, Klaus; Sacha, Jonah B.; Picker, Louis J.] Oregon Hlth & Sci Univ, Vaccine & Gene Therapy Inst, Beaverton, OR 97006 USA.
   [Hansen, Scott G.; Ventura, Abigail B.; Hughes, Colette M.; Gilbride, Roxanne M.; Ford, Julia C.; Lewis, Matthew S.; Gilliam, Awbrey N.; Xu, Guangwu; Whizin, Nathan; Burwitz, Benjamin J.; Planer, Shannon L.; Turner, John M.; Legasse, Alfred W.; Axthelm, Michael K.; Nelson, Jay A.; Frueh, Klaus; Sacha, Jonah B.; Picker, Louis J.] Oregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, Beaverton, OR 97006 USA.
   [Piatak, Michael, Jr.; Oswald, Kelli; Shoemaker, Rebecca; Li, Yuan; Estes, Jacob D.; Keele, Brandon F.; Lifson, Jeffrey D.] SAIC Frederick Inc, AIDS & Canc Virus Program, Frederick Natl Lab, Frederick, MD 21702 USA.
   [Edlefsen, Paul T.] Fred Hutchinson Canc Res Ctr, Stat Ctr HIV AIDS Res & Prevent, Vaccine & Infect Dis Div, Seattle, WA 98109 USA.
C3 Oregon Health & Science University; Oregon Health & Science University; Oregon National Primate Research Center; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); Frederick National Laboratory for Cancer Research; Science Applications International Corporation (SAIC); SAIC-Frederick; Fred Hutchinson Cancer Center
RP Lifson, JD (corresponding author), SAIC Frederick Inc, AIDS & Canc Virus Program, Frederick Natl Lab, Frederick, MD 21702 USA.
EM lifsonj@mail.nih.gov; pickerl@ohsu.edu
FU AIDS Vaccine Research in Nonhuman Primates Consortium of the National Institute of Allergy and Infectious Diseases (NIAID) [U19 AI095985]; NIAID [RO1 AI060392, R37 AI054292, P01 AI094417, U19 AI096109]; Bill & Melinda Gates Foundation; International AIDS Vaccine Initiative (IAVI); US Agency for International Development (USAID); National Center for Research Resources [P51OD011092]; National Cancer Institute [HHSN261200800001E]; National Institute on Aging; NIH Office of the Director [P51OD011092] Funding Source: NIH RePORTER; NIH Office of the Director [U42OD010426] Funding Source: NIH RePORTER
NR 28
TC 496
Z9 593
U1 0
U2 74
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 3
PY 2013
VL 502
IS 7469
BP 100
EP +
DI 10.1038/nature12519
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 227IM
UT WOS:000325106000039
PM 24025770
DA 2026-03-09
ER

PT J
AU Salque, M
   Bogucki, PI
   Pyzel, J
   Sobkowiak-Tabaka, I
   Grygiel, R
   Szmyt, M
   Evershed, RP
AF Salque, Melanie
   Bogucki, Peter I.
   Pyzel, Joanna
   Sobkowiak-Tabaka, Iwona
   Grygiel, Ryszard
   Szmyt, Marzena
   Evershed, Richard P.
TI Earliest evidence for cheese making in the sixth millennium BC in northern Europe
SO NATURE
LA English
DT Article
ID lipids; milk; chemistry; beeswax
AB The introduction of dairying was a critical step in early agriculture, with milk products being rapidly adopted as a major component of the diets of prehistoric farmers and pottery-using late hunter-gatherers(1-5). The processing of milk, particularly the production of cheese, would have been a critical development because it not only allowed the preservation of milk products in a non-perishable and transportable form, but also it made milk a more digestible commodity for early prehistoric farmers(6-10). The finding of abundant milk residues in pottery vessels from seventh millennium sites from north-western Anatolia provided the earliest evidence of milk processing, although the exact practice could not be explicitly defined(1). Notably, the discovery of potsherds pierced with small holes appear at early Neolithic sites in temperate Europe in the sixth millennium BC and have been interpreted typologically as 'cheese-strainers'(10), although a direct association with milk processing has not yet been demonstrated. Organic residues preserved in pottery vessels have provided direct evidence for early milk use in the Neolithic period in the Near East and south-eastern Europe, north Africa, Denmark and the British Isles, based on the delta C-13 and Delta C-13 values of the major fatty acids in milk(1-4). Here we apply the same approach to investigate the function of sieves/strainer vessels, providing direct chemical evidence for their use in milk processing. The presence of abundant milk fat in these specialized vessels, comparable in form to modern cheese strainers(11), provides compelling evidence for the vessels having being used to separate fat-rich milk curds from the lactose-containing whey. This new evidence emphasizes the importance of pottery vessels in processing dairy products, particularly in the manufacture of reduced-lactose milk products among lactose-intolerant prehistoric farming communities(6,7).
C1 [Salque, Melanie; Evershed, Richard P.] Univ Bristol, Sch Chem, Organ Geochem Unit, Bristol BS8 1TS, Avon, England.
   [Bogucki, Peter I.] Princeton Univ, Sch Engn & Appl Sci, Princeton, NJ 08544 USA.
   [Pyzel, Joanna] Univ Gdansk, Inst Archaeol, PL-80851 Gdansk, Poland.
   [Sobkowiak-Tabaka, Iwona] Polish Acad Sci, Inst Archaeol & Ethnol, Ctr Prehist & Medieval Res, PL-61612 Poznan, Poland.
   [Grygiel, Ryszard] Museum Archaeol & Ethnog Lodz, PL-91415 Lodz, Poland.
   [Szmyt, Marzena] Poznan Archaeol Museum, PL-61781 Poznan, Poland.
C3 University of Bristol; Princeton University; Fahrenheit Universities; University of Gdansk; Polish Academy of Sciences; Institute of Archaeology & Ethnology of the Polish Academy of Sciences
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
FU 7th EU framework Marie Curie Initial Training Networks [FP7-ITN-215362-2]; Biotechnology and Biological Sciences Research Council [1239307] Funding Source: researchfish; Natural Environment Research Council [lsmsf010001] Funding Source: researchfish; NERC [lsmsf010001] Funding Source: UKRI
NR 30
TC 347
Z9 407
U1 0
U2 220
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 24
PY 2013
VL 493
IS 7433
BP 522
EP 525
DI 10.1038/nature11698
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 075GF
UT WOS:000313871400036
PM 23235824
DA 2026-03-09
ER

PT J
AU Peng, T
   Tian, Y
   Boogerd, CJ
   Lu, MM
   Kadzik, RS
   Stewart, KM
   Evans, SM
   Morrisey, EE
AF Peng, Tien
   Tian, Ying
   Boogerd, Cornelis J.
   Lu, Min Min
   Kadzik, Rachel S.
   Stewart, Kathleen M.
   Evans, Sylvia M.
   Morrisey, Edward E.
TI Coordination of heart and lung co-development by a multipotent cardiopulmonary progenitor
SO NATURE
LA English
DT Article
ID sonic hedgehog; cells; expression; differentiation; proliferation; sufficient; endoderm; lineages; foregut; isl1
AB Co-development of the cardiovascular and pulmonary systems is a recent evolutionary adaption to terrestrial life that couples cardiac output with the gas exchange function of the lung(1). Here we show that the murine pulmonary vasculature develops even in the absence of lung development. We have identified a population of multipotent cardiopulmonary mesoderm progenitors (CPPs) within the posterior pole of the heart that are marked by the expression of Wnt2, Gli1 and Isl1. We show that CPPs arise from cardiac progenitors before lung development. Lineage tracing and clonal analysis demonstrates that CPPs generate the mesoderm lineages within the cardiac inflow tract and lung including cardiomyocytes, pulmonary vascular and airway smooth muscle, proximal vascular endothelium, and pericyte-like cells. CPPs are regulated by hedgehog expression from the foregut endoderm, which is required for connection of the pulmonary vasculature to the heart. Together, these studies identify a novel population of multipotent cardiopulmonary progenitors that coordinates heart and lung co-development that is required for adaptation to terrestrial existence.
C1 [Peng, Tien; Tian, Ying; Stewart, Kathleen M.; Morrisey, Edward E.] Univ Penn, Dept Med, Perelman Sch Med, Philadelphia, PA 19104 USA.
   [Peng, Tien] Univ Penn, Div Pulm & Crit Care, Philadelphia, PA 19104 USA.
   [Tian, Ying; Lu, Min Min; Stewart, Kathleen M.; Morrisey, Edward E.] Univ Penn, Cardiovasc Inst, Philadelphia, PA 19104 USA.
   [Boogerd, Cornelis J.; Evans, Sylvia M.] Univ Calif San Diego, Dept Med, Skaggs Sch Pharm, San Diego, CA 92093 USA.
   [Kadzik, Rachel S.; Morrisey, Edward E.] Univ Penn, Perelman Sch Med, Dept Cell & Dev Biol, Philadelphia, PA 19104 USA.
   [Morrisey, Edward E.] Inst Regenerat Med, Philadelphia, PA 19104 USA.
C3 University of Pennsylvania; University of Pennsylvania; University of Pennsylvania; University of California System; University of California San Diego; University of Pennsylvania
RP Morrisey, EE (corresponding author), Univ Penn, Dept Med, Perelman Sch Med, Philadelphia, PA 19104 USA.
EM emorrise@mail.med.upenn.edu
FU National Institutes of Health [HL110942, HL100405, HL087825, HL117649]; American Heart Association Jon DeHaan Myogenesis Center;  [T32 HL07586-23];  [P30 NS047101]; National Heart Lung and Blood Institute [T32HL007843, R01HL087825, T32HL007586] Funding Source: NIH RePORTER; National Institute of Neurological Disorders and Stroke [P30NS047101] Funding Source: NIH RePORTER
NR 25
TC 167
Z9 218
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 AUG 29
PY 2013
VL 500
IS 7464
BP 589
EP +
DI 10.1038/nature12358
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 207TD
UT WOS:000323625900037
PM 23873040
DA 2026-03-09
ER

PT J
AU Schloissnig, S
   Arumugam, M
   Sunagawa, S
   Mitreva, M
   Tap, J
   Zhu, A
   Waller, A
   Mende, DR
   Kultima, JR
   Martin, J
   Kota, K
   Sunyaev, SR
   Weinstock, GM
   Bork, P
AF Schloissnig, Siegfried
   Arumugam, Manimozhiyan
   Sunagawa, Shinichi
   Mitreva, Makedonka
   Tap, Julien
   Zhu, Ana
   Waller, Alison
   Mende, Daniel R.
   Kultima, Jens Roat
   Martin, John
   Kota, Karthik
   Sunyaev, Shamil R.
   Weinstock, George M.
   Bork, Peer
TI Genomic variation landscape of the human gut microbiome
SO NATURE
LA English
DT Article
ID salt hydrolase activity; iv secretion systems; escherichia-coli; helicobacter-pylori; population-genetics; human feces; diversity; bacterial; evolution; reconstruction
AB Whereas large-scale efforts have rapidly advanced the understanding and practical impact of human genomic variation, the practical impact of variation is largely unexplored in the human microbiome. We therefore developed a framework for metagenomic variation analysis and applied it to 252 faecal metagenomes of 207 individuals from Europe and North America. Using 7.4 billion reads aligned to 101 reference species, we detected 10.3 million single nucleotide polymorphisms (SNPs), 107,991 short insertions/deletions, and 1,051 structural variants. The average ratio of non-synonymous to synonymous polymorphism rates of 0.11 was more variable between gut microbial species than across human hosts. Subjects sampled at varying time intervals exhibited individuality and temporal stability of SNP variation patterns, despite considerable composition changes of their gut microbiota. This indicates that individual-specific strains are not easily replaced and that an individual might have a unique metagenomic genotype, which may be exploitable for personalized diet or drug intake.
C1 [Schloissnig, Siegfried; Arumugam, Manimozhiyan; Sunagawa, Shinichi; Tap, Julien; Zhu, Ana; Waller, Alison; Mende, Daniel R.; Kultima, Jens Roat; Bork, Peer] European Mol Biol Lab, D-69117 Heidelberg, Germany.
   [Mitreva, Makedonka; Martin, John; Kota, Karthik; Weinstock, George M.] Washington Univ, Sch Med, Genome Inst, St Louis, MO 63108 USA.
   [Sunyaev, Shamil R.] Brigham & Womens Hosp, Div Genet, Dept Med, Boston, MA 02115 USA.
   [Sunyaev, Shamil R.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
   [Bork, Peer] Max Delbruck Ctr Mol Med, D-13092 Berlin, Germany.
C3 European Molecular Biology Laboratory (EMBL); Washington University (WUSTL); Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard University; Harvard Medical School; Helmholtz Association; Max Delbruck Center for Molecular Medicine
RP Bork, P (corresponding author), European Mol Biol Lab, Meyerhofstr 1, D-69117 Heidelberg, Germany.
EM gweinsto@genome.wustl.edu; bork@embl.de
FU EMBL; European Community [HEALTH-F4-2007-201052]; IHMS [HEALTH-F4-2010-261376]; National Institutes of Health [U54HG003079, U54HG004968]
NR 48
TC 674
Z9 813
U1 1
U2 403
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 3
PY 2013
VL 493
IS 7430
BP 45
EP 50
DI 10.1038/nature11711
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 062QC
UT WOS:000312933800027
PM 23222524
DA 2026-03-09
ER

PT J
AU Knobloch, M
   Braun, SMG
   Zurkirchen, L
   von Schoultz, C
   Zamboni, N
   Araúzo-Bravo, MJ
   Kovacs, WJ
   Karalay, Ö
   Suter, U
   Machado, RAC
   Roccio, M
   Lutolf, MP
   Semenkovich, CF
   Jessberger, S
AF Knobloch, Marlen
   Braun, Simon M. G.
   Zurkirchen, Luis
   von Schoultz, Carolin
   Zamboni, Nicola
   Arauzo-Bravo, Marcos J.
   Kovacs, Werner J.
   Karalay, Oezlem
   Suter, Ueli
   Machado, Raquel A. C.
   Roccio, Marta
   Lutolf, Matthias P.
   Semenkovich, Clay F.
   Jessberger, Sebastian
TI Metabolic control of adult neural stem cell activity by Fasn-dependent lipogenesis
SO NATURE
LA English
DT Article
ID fatty-acid synthase; transgenic mice; spot 14; neurogenesis; homeostasis; glucose
AB Mechanisms controlling the proliferative activity of neural stem and progenitor cells (NSPCs) have a pivotal role to ensure life-long neurogenesis in the mammalian brain(1). How metabolic programs are coupled with NSPC activity remains unknown. Here we show that fatty acid synthase (Fasn), the key enzyme of de novo lipogenesis(2), is highly active in adult NSPCs and that conditional deletion of Fasn in mouse NSPCs impairs adult neurogenesis. The rate of de novo lipid synthesis and subsequent proliferation of NSPCs is regulated by Spot14, a gene previously implicated in lipid metabolism(3-5), that we found to be selectively expressed in low proliferating adult NSPCs. Spot14 reduces the availability of malonyl-CoA(6), which is an essential substrate for Fasn to fuel lipogenesis. Thus, we identify here a functional coupling between the regulation of lipid metabolism and adult NSPC proliferation.
C1 [Knobloch, Marlen; Braun, Simon M. G.; Machado, Raquel A. C.; Jessberger, Sebastian] Univ Zurich, Fac Med, Brain Res Inst, CH-8057 Zurich, Switzerland.
   [Knobloch, Marlen; Braun, Simon M. G.; Zurkirchen, Luis; von Schoultz, Carolin; Kovacs, Werner J.; Karalay, Oezlem; Suter, Ueli; Machado, Raquel A. C.; Jessberger, Sebastian] Swiss Fed Inst Technol, Dept Biol, Inst Mol Hlth Sci, CH-8093 Zurich, Switzerland.
   [Zamboni, Nicola] Swiss Fed Inst Technol, Dept Biol, Inst Mol Syst Biol, CH-8093 Zurich, Switzerland.
   [Arauzo-Bravo, Marcos J.] Max Planck Inst Mol Biomed, Dept Cell & Dev Biol, D-48149 Munster, Germany.
   [Roccio, Marta; Lutolf, Matthias P.] Ecole Polytech Fed Lausanne, Inst Bioengn, CH-1015 Lausanne, Switzerland.
   [Semenkovich, Clay F.] Washington Univ, Sch Med, Div Endocrinol Metab & Lipid Res, St Louis, MO 63110 USA.
C3 University of Geneva; University of Zurich; Swiss Federal Institutes of Technology Domain; ETH Zurich; Swiss Federal Institutes of Technology Domain; ETH Zurich; Max Planck Society; Swiss Federal Institutes of Technology Domain; Ecole Polytechnique Federale de Lausanne; Washington University (WUSTL)
RP Jessberger, S (corresponding author), Univ Zurich, Fac Med, Brain Res Inst, CH-8057 Zurich, Switzerland.
EM jessberger@hifo.uzh.ch
FU NCCR Neural Plasticity and Repair; Swiss National Science Foundation; TH grant [ETH-01 08-1]; Zurich Neuroscience Center (ZNZ); Novartis Foundation; Theodore Ott Foundation; EMBO Young Investigator program; Janggen-Pohn foundation; National Institute of Diabetes and Digestive and Kidney Diseases [P30DK020579] Funding Source: NIH RePORTER
NR 20
TC 396
Z9 461
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 JAN 10
PY 2013
VL 493
IS 7431
BP 226
EP 230
DI 10.1038/nature11689
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 066YY
UT WOS:000313259600040
PM 23201681
DA 2026-03-09
ER

PT J
AU Ablasser, A
   Schmid-Burgk, JL
   Hemmerling, I
   Horvath, GL
   Schmidt, T
   Latz, E
   Hornung, V
AF Ablasser, Andrea
   Schmid-Burgk, Jonathan L.
   Hemmerling, Inga
   Horvath, Gabor L.
   Schmidt, Tobias
   Latz, Eicke
   Hornung, Veit
TI Cell intrinsic immunity spreads to bystander cells via the intercellular transfer of cGAMP
SO NATURE
LA English
DT Article
ID cyclic gmp-amp; transcription factor; dna sensor; interferon; 2nd-messenger; communication; dinucleotide; responses; adapter
AB The innate immune defence of multicellular organisms against microbial pathogens requires cellular collaboration. Information exchange allowing immune cells to collaborate is generally attributed to soluble protein factors secreted by pathogen-sensing cells. Cytokines, such as type I interferons (IFNs), serve to alert noninfected cells to the possibility of pathogen challenge(1). Moreover, in conjunction with chemokines they can instruct specialized immune cells to contain and eradicate microbial infection. Several receptors and signalling pathways exist that couple pathogen sensing to the induction of cytokines, whereas cytosolic recognition of nucleic acids seems to be exquisitely important for the activation of type I IFNs, master regulators of antiviral immunity(2). Cytosolic DNA is sensed by the receptor cyclic GMP-AMP (cGAMP) synthase (cGAS), which catalyses the synthesis of the second messenger cGAMP(2'-5')(3-8). This molecule in turn activates the endoplasmic reticulum (ER)-resident receptor STING(9-11), thereby inducing an antiviral state and the secretion of type I IFNs. Here we find in murine and human cells that cGAS-synthesized cGAMP (2'-5') is transferred from producing cells to neighbouring cells through gap junctions, where it promotes STING activation and thus antiviral immunity independently of type I IFN signalling. In line with the limited cargo specificity of connexins, the proteins that assemble gap junction channels, most connexins tested were able to confer this bystander immunity, thus indicating a broad physiological relevance of this local immune collaboration. Collectively, these observations identify cGAS-triggered cGAMP(2'-5') transfer as a novel host strategy that serves to rapidly convey antiviral immunity in a transcription-independent, horizontal manner.
C1 [Ablasser, Andrea; Schmid-Burgk, Jonathan L.; Hemmerling, Inga; Schmidt, Tobias; Hornung, Veit] Univ Bonn, Univ Hosp, Inst Clin Chem & Clin Pharmacol, D-53127 Bonn, Germany.
   [Horvath, Gabor L.; Latz, Eicke] Univ Bonn, Univ Hosp, Inst Innate Immun, D-53127 Bonn, Germany.
   [Latz, Eicke] Univ Massachusetts, Sch Med, Div Infect Dis & Immunol, Dept Med, Worcester, MA 01605 USA.
C3 University of Bonn; University of Bonn; University of Massachusetts System; University of Massachusetts Worcester
RP Hornung, V (corresponding author), Univ Bonn, Univ Hosp, Inst Clin Chem & Clin Pharmacol, D-53127 Bonn, Germany.
EM veit.hornung@uni-bonn.de
FU Studienstiftung des Deutschen Volkes; BONFOR; excellence cluster ImmunoSensation; German Research Foundation [SFB670, SFB704]; European Research Council [ERC 243046]
NR 30
TC 544
Z9 655
U1 4
U2 120
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 28
PY 2013
VL 503
IS 7477
BP 530
EP +
DI 10.1038/nature12640
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 258MU
UT WOS:000327464200044
PM 24077100
DA 2026-03-09
ER

PT J
AU Crossland, EJW
   Noel, N
   Sivaram, V
   Leijtens, T
   Alexander-Webber, JA
   Snaith, HJ
AF Crossland, Edward J. W.
   Noel, Nakita
   Sivaram, Varun
   Leijtens, Tomas
   Alexander-Webber, Jack A.
   Snaith, Henry J.
TI Mesoporous TiO2 single crystals delivering enhanced mobility and optoelectronic device performance
SO NATURE
LA English
DT Article
ID metal-oxides; solar-cells; dye; efficiency; cr2o3
AB Mesoporous ceramics and semiconductors enable low-cost solar power, solar fuel, (photo)catalyst and electrical energy storage technologies(1). State-of-the-art, printable high-surface-area electrodes are fabricated from thermally sintered pre-formed nanocrystals(2-5). Mesoporosity provides the desired highly accessible surfaces but many applications also demand long-range electronic connectivity and structural coherence(6). A mesoporous single-crystal (MSC) semiconductor can meet both criteria. Here we demonstrate a general synthetic method of growing semiconductor MSCs of anatase TiO2 based on seeded nucleation and growth inside a mesoporous template immersed in a dilute reaction solution. We show that both isolated MSCs and ensembles incorporated into films have substantially higher conductivities and electron mobilities than does nanocrystalline TiO2. Conventional nanocrystals, unlike MSCs, require in-film thermal sintering to reinforce electronic contact between particles, thus increasing fabrication cost, limiting the use of flexible substrates and precluding, for instance, multijunction solar cell processing. Using MSC films processed entirely below 150 degrees C, we have fabricated all-solid-state, low-temperature sensitized solar cells that have 7.3 per cent efficiency, the highest efficiency yet reported. These high-surface-area anatase single crystals will find application in many different technologies, and this generic synthetic strategy extends the possibility of mesoporous single-crystal growth to a range of functional ceramics and semiconductors.
C1 [Crossland, Edward J. W.; Noel, Nakita; Sivaram, Varun; Leijtens, Tomas; Alexander-Webber, Jack A.; Snaith, Henry J.] Univ Oxford, Clarendon Lab, Oxford OX1 3PU, England.
C3 University of Oxford
RP Snaith, HJ (corresponding author), Univ Oxford, Clarendon Lab, Parks Rd, Oxford OX1 3PU, England.
EM h.snaith1@physics.ox.ac.uk
FU European Community [246124]; European Research Council (HYPER) [279881]; Rhodes Trust; Engineering and Physical Sciences Research Council; Government of the Republic of Trinidad and Tobago; European Research Council (ERC) [279881] Funding Source: European Research Council (ERC)
NR 30
TC 768
Z9 822
U1 5
U2 1806
PU NATURE PUBLISHING 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 14
PY 2013
VL 495
IS 7440
BP 215
EP 219
DI 10.1038/nature11936
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 113FP
UT WOS:000316652300046
PM 23467091
DA 2026-03-09
ER

PT J
AU Wickert, AD
   Mitrovica, JX
   Williams, C
   Anderson, RS
AF Wickert, Andrew D.
   Mitrovica, Jerry X.
   Williams, Carlie
   Anderson, Robert S.
TI Gradual demise of a thin southern Laurentide ice sheet recorded by Mississippi drainage
SO NATURE
LA English
DT Article
ID gulf-of-mexico; postglacial sea-level; last glacial maximum; hyperpycnal flows; transport model; lake agassiz; deglaciation; meltwater; water; sediment
AB At the Last Glacial Maximum (LGM), about 21,000 years before present, land-based ice sheets held enough water to reduce global mean sea level by 130 metres(1). Yet after decades of study, major uncertainties remain as to the distribution of that ice(2). Here we test four reconstructions of North American deglacial ice-sheet history(3-6) by quantitatively connecting them to high-resolution oxygen isotope (delta O-18) records from the Gulf of Mexico(7-11) using a water mixing model(12). For each reconstruction, we route meltwater(3-6) and seasonal runoff(13-16) through the time-evolving Mississippi drainage basin, which co-evolves with ice geometry(3-6) and changing topography as ice loads deform the solid Earth and produce spatially variable sea level in a process known as glacial isostatic adjustment(17). The delta O-18 records show that the Mississippi-drained southern Laurentide ice sheet contributed only 5.4 +/- 2.1 metres to global sea level rise, of which 0.66 +/- 0.07 metres were released during the meltwater pulse 1A event 14,650-14,310 years before present(18), far less water than previously thought(5,12,19). In contrast, the three reconstructions based on glacial isostatic adjustment(3-5) overpredict the delta O-18-based post-LGM meltwater volume by a factor of 1.6 to 3.6. The fourth reconstruction(6), which is based on ice physics, has a low enough Mississippi-routed meltwater discharge to be consistent with delta O-18 constraints, but also contains the largest LGM North American ice volume. This suggests that modelling based on ice physics may be the best way of matching isotopic records while also sequestering enough water in the North American ice sheets to match the observed LGM sea level fall(1).
C1 [Wickert, Andrew D.; Anderson, Robert S.] Univ Colorado, Inst Arctic & Alpine Res, Boulder, CO 80303 USA.
   [Wickert, Andrew D.; Anderson, Robert S.] Univ Colorado, Dept Geol Sci, Boulder, CO 80303 USA.
   [Mitrovica, Jerry X.] Harvard Univ, Dept Earth & Planetary Sci, Cambridge, MA 02138 USA.
   [Williams, Carlie] Univ S Florida, Coll Marine Sci, St Petersburg, FL 33701 USA.
C3 University of Colorado System; University of Colorado Boulder; University of Colorado System; University of Colorado Boulder; Harvard University; State University System of Florida; University of South Florida
RP Wickert, AD (corresponding author), Univ Colorado, Inst Arctic & Alpine Res, 1560 30th St, Boulder, CO 80303 USA.
EM wickert@colorado.edu
FU US Department of Defense through the National Defense Science and Engineering Graduate Fellowship Program; US National Science Foundation Graduate Research Fellowship [DGE 1144083]; Canadian Institute for Advanced Research; Harvard University
NR 58
TC 49
Z9 59
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 OCT 31
PY 2013
VL 502
IS 7473
BP 668
EP +
DI 10.1038/nature12609
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 243CC
UT WOS:000326293200044
PM 24172978
DA 2026-03-09
ER

PT J
AU Rivkin, E
   Almeida, SM
   Ceccarelli, DF
   Juang, YC
   MacLean, TA
   Srikumar, T
   Huang, H
   Dunham, WH
   Fukumura, R
   Xie, G
   Gondo, Y
   Raught, B
   Gingras, AC
   Sicheri, F
   Cordes, SP
AF Rivkin, Elena
   Almeida, Stephanie M.
   Ceccarelli, Derek F.
   Juang, Yu-Chi
   MacLean, Teresa A.
   Srikumar, Tharan
   Huang, Hao
   Dunham, Wade H.
   Fukumura, Ryutaro
   Xie, Gang
   Gondo, Yoichi
   Raught, Brian
   Gingras, Anne-Claude
   Sicheri, Frank
   Cordes, Sabine P.
TI The linear ubiquitin-specific deubiquitinase gumby regulates angiogenesis
SO NATURE
LA English
DT Article
ID kappa-b activation; du-chat-syndrome; polyubiquitin chains; signaling pathway; mouse; inflammation; dermatitis; mutations; sharpin; complex
AB A complex interaction of signalling events, including the Wnt pathway, regulates sprouting of blood vessels from pre-existing vasculature during angiogenesis. Here we show that two distinct mutations in the (uro) chordate-specific gumby (also called Fam105b) gene cause an embryonic angiogenic phenotype in gumby mice. Gumby interacts with disheveled 2 (DVL2), is expressed in canonical Wnt-responsive endothelial cells and encodes an ovarian tumour domain class of deubiquitinase that specifically cleaves linear ubiquitin linkages. A crystal structure of gumby in complex with linear diubiquitin reveals how the identified mutations adversely affect substrate binding and catalytic function in line with the severity of their angiogenic phenotypes. Gumby interacts with HOIP (also called RNF31), a key component of the linear ubiquitin assemblycomplex, and decreases linear ubiquitination and activation of NF-kappa B-dependent transcription. This work provides support for the biological importance of linear (de) ubiquitination in angiogenesis, craniofacial and neural development and in modulating Wnt signalling.
C1 [Rivkin, Elena; Almeida, Stephanie M.; Ceccarelli, Derek F.; Juang, Yu-Chi; MacLean, Teresa A.; Huang, Hao; Dunham, Wade H.; Xie, Gang; Gingras, Anne-Claude; Sicheri, Frank; Cordes, Sabine P.] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada.
   [Rivkin, Elena; Almeida, Stephanie M.; MacLean, Teresa A.; Dunham, Wade H.; Gingras, Anne-Claude; Sicheri, Frank; Cordes, Sabine P.] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A8, Canada.
   [Srikumar, Tharan; Raught, Brian] Univ Toronto, Dept Med Biophys, Toronto, ON M5G 1L7, Canada.
   [Srikumar, Tharan; Raught, Brian] Princess Margaret Canc Ctr, Ontario Canc Inst, Toronto, ON M5G 1L7, Canada.
   [Fukumura, Ryutaro; Gondo, Yoichi] RIKEN BioResource Ctr, Mutagenesis & Genom Team, Tsukuba, Ibaraki 3050074, Japan.
C3 University of Toronto; Sinai Health System Toronto; Lunenfeld Tanenbaum Research Institute; University of Toronto; University of Toronto; University of Toronto; University Health Network Toronto; Princess Margaret Cancer Centre; RIKEN
RP Sicheri, F (corresponding author), Mt Sinai Hosp, Samuel Lunenfeld Res Inst, 600 Univ Ave, Toronto, ON M5G 1X5, Canada.
EM sicheri@lunenfeld.ca; cordes@lunenfeld.ca
FU JSPS KAKENHI [15200032, 21240043]; Canadian Institutes for Health Research [MOP119289, MOP123433, MOP57795, MOP 97966, IHO 94384, MOP 111199]; Grants-in-Aid for Scientific Research [15200032, 21240043, 25241016] Funding Source: KAKEN
NR 49
TC 244
Z9 275
U1 1
U2 105
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 20
PY 2013
VL 498
IS 7454
BP 318
EP +
DI 10.1038/nature12296
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 166XI
UT WOS:000320592900031
PM 23708998
DA 2026-03-09
ER

PT J
AU Anguera, JA
   Boccanfuso, J
   Rintoul, JL
   Al-Hashimi, O
   Faraji, F
   Janowich, J
   Kong, E
   Larraburo, Y
   Rolle, C
   Johnston, E
   Gazzaley, A
AF Anguera, J. A.
   Boccanfuso, J.
   Rintoul, J. L.
   Al-Hashimi, O.
   Faraji, F.
   Janowich, J.
   Kong, E.
   Larraburo, Y.
   Rolle, C.
   Johnston, E.
   Gazzaley, A.
TI Video game training enhances cognitive control in older adults
SO NATURE
LA English
DT Article
ID down suppression deficit; working-memory; default network; brain activity; eeg dynamics; dual-task; theta; plasticity; multitasking; performance
AB Cognitive control is defined by a set of neural processes that allow us to interact with our complex environment in a goal-directed manner(1). Humans regularly challenge these control processes when attempting to simultaneously accomplish multiple goals (multitasking), generating interference as the result of fundamental information processing limitations(2). It is clear that multitasking behaviour has become ubiquitous in today's technologically dense world(3), and substantial evidence has accrued regarding multitasking difficulties and cognitive control deficits in our ageing population(4). Here we show that multitasking performance, as assessed with a custom-designed three-dimensional video game (NeuroRacer), exhibits a linear age-related decline from 20 to 79 years of age. By playing an adaptive version of NeuroRacer in multitasking training mode, older adults (60 to 85 years old) reduced multitasking costs compared to both an active control group and a no-contact control group, attaining levels beyond those achieved by untrained 20-year-old participants, with gains persisting for 6 months. Furthermore, age-related deficits in neural signatures of cognitive control, as measured with electroencephalography, were remediated by multitasking training (enhanced midline frontal theta power and frontal-posterior theta coherence). Critically, this training resulted in performance benefits that extended to untrained cognitive control abilities (enhanced sustained attention and working memory), with an increase in midline frontal theta power predicting the training-induced boost in sustained attention and preservation of multitasking improvement 6 months later. These findings highlight the robust plasticity of the prefrontal cognitive control system in the ageing brain, and provide the first evidence, to our knowledge, of how a custom-designed video game can be used to assess cognitive abilities across the lifespan, evaluate underlying neural mechanisms, and serve as a powerful tool for cognitive enhancement.
C1 [Anguera, J. A.; Boccanfuso, J.; Rintoul, J. L.; Al-Hashimi, O.; Faraji, F.; Janowich, J.; Kong, E.; Larraburo, Y.; Rolle, C.; Johnston, E.; Gazzaley, A.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94158 USA.
   [Anguera, J. A.; Al-Hashimi, O.; Gazzaley, A.] Univ Calif San Francisco, Dept Physiol, San Francisco, CA 94158 USA.
   [Anguera, J. A.; Boccanfuso, J.; Rintoul, J. L.; Al-Hashimi, O.; Faraji, F.; Janowich, J.; Kong, E.; Larraburo, Y.; Rolle, C.; Gazzaley, A.] Univ Calif San Francisco, Ctr Integrat Neurosci, San Francisco, CA 94158 USA.
   [Gazzaley, A.] Univ Calif San Francisco, Dept Psychiat, 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; University of California System; University of California San Francisco
RP Anguera, JA (corresponding author), Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94158 USA.
EM joaquin.anguera@ucsf.edu; adam.gazzaley@ucsf.edu
FU Robert Wood Johnson Foundation; National Institute of Aging; UCSF Institutional Research and Career Development Award (IRACDA)
NR 43
TC 1160
Z9 1385
U1 23
U2 1010
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 5
PY 2013
VL 501
IS 7465
BP 97
EP +
DI 10.1038/nature12486
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 211ER
UT WOS:000323888300039
PM 24005416
DA 2026-03-09
ER

PT J
AU Haider, B
   Häusser, M
   Carandini, M
AF Haider, Bilal
   Haeusser, Michael
   Carandini, Matteo
TI Inhibition dominates sensory responses in the awake cortex
SO NATURE
LA English
DT Article
ID local cortical networks; primary visual-cortex; neurons in-vivo; orientation selectivity; neocortical neurons; hz oscillation; barrel cortex; mechanisms; interneurons; sparse
AB The activity of the cerebral cortex is thought to depend on the precise relationship between synaptic excitation and inhibition(1-4). In the visual cortex, in particular, intracellular measurements have related response selectivity to coordinated increases in excitation and inhibition(5-9). These measurements, however, have all been made during anaesthesia, which strongly influences cortical state(10) and therefore sensory processing(7,11-15). The synaptic activity that is evoked by visual stimulation during wakefulness is unknown. Here we measured visually evoked responses-and the underlying synaptic conductances-in the visual cortex of anaesthetized and awake mice. Under anaesthesia, responses could be elicited from a large region of visual space(16) and were prolonged. During wakefulness, responses were more spatially selective and much briefer. Whole-cell patch-clamp recordings of synaptic conductances(5,17) showed a difference in synaptic inhibition between the two conditions. Under anaesthesia, inhibition tracked excitation in amplitude and spatial selectivity. By contrast, during wakefulness, inhibition was much stronger than excitation and had extremely broad spatial selectivity. We conclude that during wakefulness, cortical responses to visual stimulation are dominated by synaptic inhibition, restricting the spatial spread and temporal persistence of neural activity. These results provide a direct glimpse of synaptic mechanisms that control sensory responses in the awake cortex.
C1 [Haider, Bilal; Carandini, Matteo] UCL, UCL Inst Ophthalmol, London EC1V 9EL, England.
   [Haeusser, Michael] UCL, Wolfson Inst Biomed Res, London WC1E 6BT, England.
   [Haeusser, Michael] UCL, Dept Neurosci Physiol & Pharmacol, London WC1E 6BT, England.
C3 University of London; University College London; University of London; University College London; University of London; University College London
RP Haider, B (corresponding author), UCL, UCL Inst Ophthalmol, 11-43 Bath St, London EC1V 9EL, England.
EM b.haider@ucl.ac.uk
FU National Science Foundation; European Research Council; Wellcome Trust; Medical Research Council; Gatsby Charitable Foundation; MRC [G0800791] Funding Source: UKRI; Medical Research Council [G0800791] Funding Source: researchfish
NR 36
TC 401
Z9 473
U1 0
U2 99
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 3
PY 2013
VL 493
IS 7430
BP 97
EP +
DI 10.1038/nature11665
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 062QC
UT WOS:000312933800038
PM 23172139
DA 2026-03-09
ER

PT J
AU Sonati, T
   Reimann, RR
   Falsig, J
   Baral, PK
   O'Connor, T
   Hornemann, S
   Yaganoglu, S
   Li, B
   Herrmann, US
   Wieland, B
   Swayampakula, M
   Rahman, MH
   Das, D
   Kav, N
   Riek, R
   Liberski, PP
   James, MNG
   Aguzzi, A
AF Sonati, Tiziana
   Reimann, Regina R.
   Falsig, Jeppe
   Baral, Pravas Kumar
   O'Connor, Tracy
   Hornemann, Simone
   Yaganoglu, Sine
   Li, Bei
   Herrmann, Uli S.
   Wieland, Barbara
   Swayampakula, Mridula
   Rahman, Muhammad Hafizur
   Das, Dipankar
   Kav, Nat
   Riek, Roland
   Liberski, Pawel P.
   James, Michael N. G.
   Aguzzi, Adriano
TI The toxicity of antiprion antibodies is mediated by the flexible tail of the prion protein
SO NATURE
LA English
DT Article
ID prp knockout mice; macromolecular crystallography; mouse model; nmr; disease; scrapie; domain; neurodegeneration; susceptibility; infection
AB Prion infections cause lethal neurodegeneration. This process requires the cellular prion protein (PrPC; ref. 1), which contains a globular domain hinged to a long amino-proximal flexible tail(2). Here we describe rapid neurotoxicity in mice and cerebellar organotypic cultured slices exposed to ligands targeting the alpha 1 and alpha 3 helices of the PrPC globular domain. Ligands included seven distinct monoclonal antibodies(3), monovalent Fab(1) fragments and recombinant single-chain variable fragment miniantibodies. Similar to prion infections(4-6), the toxicity of globular domain ligands required neuronal PrPC, was exacerbated by PrPC overexpression, was associated with calpain activation and was antagonized by calpain inhibitors. Neurodegeneration was accompanied by a burst of reactive oxygen species, and was suppressed by antioxidants. Furthermore, genetic ablation of the superoxide-producing enzyme NOX2 (also known as CYBB) protected mice from globular domain ligand toxicity. We also found that neurotoxicity was prevented by deletions of the octapeptide repeats within the flexible tail. These deletions did not appreciably compromise globular domain antibody binding, suggesting that the flexible tail is required to transmit toxic signals that originate from the globular domain and trigger oxidative stress and calpain activation. Supporting this view, various octapeptide ligands were not only innocuous to both cerebellar organotypic cultured slices and mice, but also prevented the toxicity of globular domain ligands while not interfering with their binding. We conclude that PrPC consists of two functionally distinct modules, with the globular domain and the flexible tail exerting regulatory and executive functions, respectively. Octapeptide ligands also prolonged the life of mice expressing the toxic PrPC mutant(7), PrP(Lambda 94-134), indicating that the flexible tail mediates toxicity in two distinct PrPC-related conditions. Flexible tail-mediated toxicity may conceivably play a role in further prion pathologies, such as familial Creutzfeldt-Jakob disease in humans bearing supernumerary octapeptides.
C1 [Sonati, Tiziana; Reimann, Regina R.; Falsig, Jeppe; O'Connor, Tracy; Hornemann, Simone; Yaganoglu, Sine; Li, Bei; Herrmann, Uli S.; Aguzzi, Adriano] Univ Zurich Hosp, Inst Neuropathol, CH-8091 Zurich, Switzerland.
   [Baral, Pravas Kumar; Wieland, Barbara; Swayampakula, Mridula; James, Michael N. G.] Univ Alberta, Fac Med & Dent, Dept Biochem, Edmonton, AB T6G 2H7, Canada.
   [Rahman, Muhammad Hafizur; Das, Dipankar; Kav, Nat] Univ Alberta, Dept Agr Food & Nutr Sci, Agr Forestry Ctr 410, Edmonton, AB T6G 2P5, Canada.
   [Riek, Roland] ETH Honggerberg, ETH Zurich, CH-8093 Zurich, Switzerland.
   [Liberski, Pawel P.] Med Univ Lodz, Dept Mol Pathol & Neuropathol, Lab Electron Microscopy & Neuropathol, PL-92216 Lodz, Poland.
C3 University of Zurich; University Zurich Hospital; University of Alberta; University of Alberta; Swiss Federal Institutes of Technology Domain; ETH Zurich; Medical University Lodz
RP Aguzzi, A (corresponding author), Univ Zurich Hosp, Inst Neuropathol, Schmelzbergstr 12, CH-8091 Zurich, Switzerland.
EM Adriano.Aguzzi@usz.ch
FU European Research Council; European Union; Swiss National Foundation; Foundation Alliance BioSecure; Clinical Research Priority Program (KFSP) of the University of Zurich; Novartis Research Foundation; PrioNet Canada; Alberta Prion Research Institute (APRI); Polish Swiss Research [PSPB-062/2010]
NR 55
TC 176
Z9 192
U1 1
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 SEP 5
PY 2013
VL 501
IS 7465
BP 102
EP +
DI 10.1038/nature12402
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 211ER
UT WOS:000323888300040
PM 23903654
DA 2026-03-09
ER

PT J
AU Hashem, Y
   Georges, AD
   Fu, J
   Buss, SN
   Jossinet, F
   Jobe, A
   Zhang, Q
   Liao, HY
   Grassucci, RA
   Bajaj, C
   Westhof, E
   Madison-Antenucci, S
   Frank, J
AF Hashem, Yaser
   Georges, Amedee des
   Fu, Jie
   Buss, Sarah N.
   Jossinet, Fabrice
   Jobe, Amy
   Zhang, Qin
   Liao, Hstau Y.
   Grassucci, Robert A.
   Bajaj, Chandrajit
   Westhof, Eric
   Madison-Antenucci, Susan
   Frank, Joachim
TI High-resolution cryo-electron microscopy structure of the Trypanosoma brucei ribosome
SO NATURE
LA English
DT Article
ID eukaryotic ribosome; crystal-structure; atomic structures; 80s ribosome; small rnas; initiation; subunit; proteins; parasite; sequence
AB Ribosomes, the protein factories of living cells, translate genetic information carried by messenger RNAs into proteins, and are thus involved in virtually all aspects of cellular development and maintenance. The few available structures of the eukaryotic ribosome(1-6) reveal that it is more complex than its prokaryotic counterpart(7,8), owing mainly to the presence of eukaryote-specific ribosomal proteins and additional ribosomal RNA insertions, called expansion segments(9). The structures also differ among species, partly in the size and arrangement of these expansion segments. Such differences are extreme in kinetoplastids, unicellular eukaryotic parasites often infectious to humans. Here we present a high-resolution cryo-electron microscopy structure of the ribosome of Trypanosoma brucei, the parasite that is transmitted by the tsetse fly and that causes African sleeping sickness. The atomic model reveals the unique features of this ribosome, characterized mainly by the presence of unusually large expansion segments and ribosomal-protein extensions leading to the formation of four additional inter-subunit bridges. We also find additional rRNA insertions, including one large rRNA domain that is not found in other eukaryotes. Furthermore, the structure reveals the five cleavage sites of the kinetoplastid large ribosomal subunit (LSU) rRNA chain, which is known to be cleaved uniquely into six pieces(10-12), and suggests that the cleavage is important for the maintenance of the T. brucei ribosome in the observed structure. We discuss several possible implications of the large rRNA expansion segments for the translation-regulation process. The structure could serve as a basis for future experiments aimed at understanding the functional importance of these kinetoplastid-specific ribosomal features in protein-translation regulation, an essential step towards finding effective and safe kinetoplastid-specific drugs.
C1 [Hashem, Yaser; Georges, Amedee des; Grassucci, Robert A.; Frank, Joachim] Columbia Univ, Dept Biochem & Mol Biophys, Howard Hughes Med Inst HHMI, New York, NY 10032 USA.
   [Fu, Jie; Liao, Hstau Y.; Frank, Joachim] Columbia Univ, Dept Biochem & Mol Biophys, New York, NY 10032 USA.
   [Buss, Sarah N.; Madison-Antenucci, Susan] New York State Dept Hlth, Div Infect Dis, Wadsworth Ctr, Albany, NY 12201 USA.
   [Jossinet, Fabrice; Westhof, Eric] Univ Strasbourg, Inst Biol Mol & Cellulaire CNRS, Architecture & Reactivite ARN, F-67084 Strasbourg, France.
   [Jobe, Amy; Frank, Joachim] Columbia Univ, Dept Biol Sci, New York, NY 10027 USA.
   [Zhang, Qin; Bajaj, Chandrajit] Univ Texas Austin, Inst Computat Engn & Sci, Dept Comp Sci, Austin, TX 78712 USA.
C3 Columbia University; Howard Hughes Medical Institute; Columbia University; Wadsworth Center; State University of New York (SUNY) System; Universites de Strasbourg Etablissements Associes; Universite de Strasbourg; Columbia University; University of Texas System; University of Texas Austin
RP Frank, J (corresponding author), Columbia Univ, Dept Biochem & Mol Biophys, Howard Hughes Med Inst HHMI, 630 W 168th St, New York, NY 10032 USA.
EM jf2192@columbia.edu
FU Howard Hughes Medical Institute (HHMI); National Institutes of Health (NIH) [R01 GM29169]; L'Agence Nationale de la recherche (ANR) project AMIS ARN [ANR-09-BLAN-0160]; NIH [R01-EB004873, R01-GM074258]; Centers for Disease Control (CDC) Emerging Infectious Diseases (EID) fellowship program; Agence Nationale de la Recherche (ANR) [ANR-09-BLAN-0160] Funding Source: Agence Nationale de la Recherche (ANR)
NR 30
TC 120
Z9 139
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 FEB 21
PY 2013
VL 494
IS 7437
BP 385
EP 389
DI 10.1038/nature11872
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 095CS
UT WOS:000315312900045
PM 23395961
DA 2026-03-09
ER

PT J
AU Sampson, TR
   Saroj, SD
   Llewellyn, AC
   Tzeng, YL
   Weiss, DS
AF Sampson, Timothy R.
   Saroj, Sunil D.
   Llewellyn, Anna C.
   Tzeng, Yih-Ling
   Weiss, David S.
TI A CRISPR/Cas system mediates bacterial innate immune evasion and virulence
SO NATURE
LA English
DT Article
ID francisella-tularensis; cas systems; small rnas; dna; defense; bacteriophage; identification; lipoproteins; recognition; evolution
AB CRISPR/Cas (clustered regularly interspaced palindromic repeats/CRISPR-associated) systems are a bacterial defence against invading foreign nucleic acids derived from bacteriophages or exogenous plasmids(1-4). These systems use an array of small CRISPR RNAs (crRNAs) consisting of repetitive sequences flanking unique spacers to recognize their targets, and conserved Cas proteins to mediate target degradation(5-8). Recent studies have suggested that these systems may have broader functions in bacterial physiology, and it is unknown if they regulate expression of endogenous genes(9,10). Here we demonstrate that the Cas protein Cas9 of Francisella novicida uses a unique, small, CRISPR/Cas-associated RNA (scaRNA) to repress an endogenous transcript encoding a bacterial lipoprotein. As bacterial lipoproteins trigger a proinflammatory innate immune response aimed at combating pathogens(11,12), CRISPR/Cas-mediated repression of bacterial lipoprotein expression is critical for F. novicida to dampen this host response and promote virulence. Because Cas9 proteins are highly enriched in pathogenic and commensal bacteria, our work indicates that CRISPR/Cas-mediated gene regulation may broadly contribute to the regulation of endogenous bacterial genes, particularly during the interaction of such bacteria with eukaryotic hosts.
C1 [Sampson, Timothy R.; Llewellyn, Anna C.] Emory Univ, Dept Microbiol & Immunol, Microbiol & Mol Genet Program, Atlanta, GA 30329 USA.
   [Sampson, Timothy R.; Llewellyn, Anna C.; Weiss, David S.] Emory Univ, Emory Vaccine Ctr, Atlanta, GA 30329 USA.
   [Sampson, Timothy R.; Llewellyn, Anna C.; Weiss, David S.] Emory Univ, Yerkes Natl Primate Res Ctr, Atlanta, GA 30329 USA.
   [Saroj, Sunil D.; Tzeng, Yih-Ling; Weiss, David S.] Emory Univ, Sch Med, Dept Med, Div Infect Dis, Atlanta, GA 30329 USA.
C3 Emory University; Emory University; Emory University; Emory University
RP Weiss, DS (corresponding author), Emory Univ, Emory Vaccine Ctr, Atlanta, GA 30329 USA.
EM david.weiss@emory.edu
FU National Institutes of Health (NIH) from the Southeastern Regional Center of Excellence for Emerging Infections and Biodefense [U54-AI057157]; NSF Graduate Research Fellowship; ARCS Foundation;  [R56-AI87673];  [R56-AI061031]
NR 32
TC 331
Z9 480
U1 3
U2 267
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 9
PY 2013
VL 497
IS 7448
BP 254
EP +
DI 10.1038/nature12048
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 139CD
UT WOS:000318558200039
PM 23584588
DA 2026-03-09
ER

PT J
AU Reisz, RR
   Huang, TD
   Roberts, EM
   Peng, SR
   Sullivan, C
   Stein, K
   LeBlanc, ARH
   Shieh, D
   Chang, RS
   Chiang, CC
   Yang, CW
   Zhong, SM
AF Reisz, Robert R.
   Huang, Timothy D.
   Roberts, Eric M.
   Peng, ShinRung
   Sullivan, Corwin
   Stein, Koen
   LeBlanc, Aaron R. H.
   Shieh, DarBin
   Chang, RongSeng
   Chiang, ChengCheng
   Yang, Chuanwei
   Zhong, Shiming
TI Embryology of Early Jurassic dinosaur from China with evidence of preserved organic remains
SO NATURE
LA English
DT Article
ID soft-tissue; theropods
AB Fossil dinosaur embryos are surprisingly rare, being almost entirely restricted to Upper Cretaceous strata that record the late stages of non-avian dinosaur evolution(1,2). Notable exceptions are the oldest known embryos from the Early Jurassic South African sauropodomorph Massospondylus(3,4) and Late Jurassic embryos of a theropod from Portugal(5). The fact that dinosaur embryos are rare and typically enclosed in eggshells limits their availability for tissue and cellular level investigations of development. Consequently, little is known about growth patterns in dinosaur embryos, even though post-hatching ontogeny has been studied in several taxa(6). Here we report the discovery of an embryonic dinosaur bone bed from the Lower Jurassic of China, the oldest such occurrence in the fossil record. The embryos are similar in geological age to those of Massospondylus and are also assignable to a sauropodomorph dinosaur, probably Lufengosaurus(7). The preservation of numerous disarticulated skeletal elements and eggshells in this monotaxic bone bed, representing different stages of incubation and therefore derived from different nests, provides opportunities for new investigations of dinosaur embryology in a clade noted for gigantism. For example, comparisons among embryonic femora of different sizes and developmental stages reveal a consistently rapid rate of growth throughout development, possibly indicating that short incubation times were characteristic of sauropodomorphs. In addition, asymmetric radial growth of the femoral shaft and rapid expansion of the fourth trochanter suggest that embryonic muscle activation played an important role in the pre-hatching ontogeny of these dinosaurs. This discovery also provides the oldest evidence of in situ preservation of complex organic remains in a terrestrial vertebrate.
C1 [Reisz, Robert R.; LeBlanc, Aaron R. H.] Univ Toronto, Dept Biol, Mississauga, ON L5L 1C6, Canada.
   [Huang, Timothy D.] Natl Chung Hsing Univ, Taichung 402, Taiwan.
   [Roberts, Eric M.] James Cook Univ, Sch Earth & Environm Sci, Townsville, Qld 4811, Australia.
   [Peng, ShinRung; Shieh, DarBin] Natl Cheng Kung Univ, Coll Med, Inst Oral Med, Tainan 701, Taiwan.
   [Sullivan, Corwin] Inst Vertebrate Paleontol & Paleoanthropol, Key Lab Evolutionary Systemat Vertebrates, Beijing 100044, Peoples R China.
   [Stein, Koen] Univ Bonn, Steinmann Inst Geol Mineral & Palaontol, D-53115 Bonn, Germany.
   [Chang, RongSeng] Natl Cent Univ, Dept Opt & Photon, Chungli 32001, Taiwan.
   [Chiang, ChengCheng] Natl Synchrotron Radiat Res Ctr, Hsinchu 30076, Taiwan.
   [Yang, Chuanwei] Lufeng Cty Dinosaur Museum, Lufeng, Yunnan, Peoples R China.
   [Zhong, Shiming] Chuxiong Prefectural Museum, Chuxiong 675000, Yunnan, Peoples R China.
C3 University of Toronto; University Toronto Mississauga; National Chung Hsing University; James Cook University; National Cheng Kung University; Chinese Academy of Sciences; Institute of Vertebrate Paleontology & Paleoanthropology, CAS; University of Bonn; National Central University; National Synchrotron Radiation Research Center
RP Reisz, RR (corresponding author), Univ Toronto, Dept Biol, Mississauga, ON L5L 1C6, Canada.
EM robert.reisz@utoronto.ca
FU NSERC Discovery and SRO Grants (Canada); University of Toronto; DFG (Germany) [FOR 533]; NSC (Taiwan) [100-2116-M-008-016]; Ministry of Education (Taiwan) under the NCKU Aim for the Top University Project; Chinese Academy of Sciences and National Natural Science Foundation of China [41150110341]
NR 29
TC 67
Z9 80
U1 2
U2 120
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 11
PY 2013
VL 496
IS 7444
BP 210
EP 214
DI 10.1038/nature11978
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 122VM
UT WOS:000317346300039
PM 23579680
DA 2026-03-09
ER

PT J
AU Ashkenazy, Y
   Gildor, H
   Losch, M
   Macdonald, FA
   Schrag, DP
   Tziperman, E
AF Ashkenazy, Yosef
   Gildor, Hezi
   Losch, Martin
   Macdonald, Francis A.
   Schrag, Daniel P.
   Tziperman, Eli
TI Dynamics of a Snowball Earth ocean
SO NATURE
LA English
DT Article
ID break-up; climate; ice; deglaciation; simulation; initiation; model
AB Geological evidence suggests that marine ice extended to the Equator at least twice during the Neoproterozoic era (about 750 to 635 million years ago)(1,2), inspiring the Snowball Earth hypothesis that the Earth was globally ice-covered(3,4). In a possible Snowball Earth climate, ocean circulation and mixing processes would have set the melting and freezing rates that determine ice thickness(5,6), would have influenced the survival of photosynthetic life(4,5,7-9), and may provide important constraints for the interpretation of geochemical and sedimentological observations(4,10). Here we show that in a Snowball Earth, the ocean would have been well mixed and. characterized by a dynamic circulation(11), with vigorous equatorial meridional overturning circulation, zonal equatorial jets, a well developed eddy field, strong coastal upwelling and convective mixing. This is in contrast to the sluggish ocean often expected in a Snowball Earth scenario(3) owing to the insulation of the ocean from atmospheric forcing by the thick ice cover. As a result of vigorous convective mixing, the ocean temperature, salinity and density were either uniform in the vertical direction or weakly stratified in a few locations. Our results are based on a model that couples ice flow and ocean circulation, and is driven by a weak geothermal heat flux under a global ice cover about a kilometre thick. Compared with the modern ocean, the Snowball Earth ocean had far larger vertical mixing rates, and comparable horizontal mixing by ocean eddies. The strong circulation and coastal upwellimg resulted in melting rates near continents as much as ten times larger than previously estimated(6,7). Although we cannot resolve the debate over the existence of global ice cover(10,12,13), we discuss the implications for the nutrient supply of photosynthetic activity and for banded iron formations. Our insights and constraints on ocean dynamics may help resolve the Snowball Earth controversy when combined with future geochemical and geological observations.
C1 [Ashkenazy, Yosef] Ben Gurion Univ Negev, Blaustein Inst Desert Res, Dept Solar Energy & Environm Phys, IL-84990 Midreshet Ben Gurion, Israel.
   [Gildor, Hezi] Hebrew Univ Jerusalem, Inst Earth Sci, IL-91904 Jerusalem, Israel.
   [Losch, Martin] Alfred Wegener Inst Polar & Marine Res, D-27515 Bremerhaven, Germany.
   [Macdonald, Francis A.; Schrag, Daniel P.; Tziperman, Eli] Harvard Univ, Cambridge, MA 02138 USA.
   [Schrag, Daniel P.; Tziperman, Eli] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA.
C3 Ben-Gurion University of the Negev; Hebrew University of Jerusalem; Helmholtz Association; Alfred Wegener Institute, Helmholtz Centre for Polar & Marine Research; Harvard University; Harvard University
RP Tziperman, E (corresponding author), Harvard Univ, 20 Oxford St, Cambridge, MA 02138 USA.
EM ashkena@bgu.ac.il; eli@eps.harvard.edu
FU NSF [ATM-0902844]; Directorate For Geosciences; Div Atmospheric & Geospace Sciences [0902844] Funding Source: National Science Foundation
NR 30
TC 58
Z9 66
U1 6
U2 200
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 7
PY 2013
VL 495
IS 7439
BP 90
EP 93
DI 10.1038/nature11894
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 105BE
UT WOS:000316039800045
PM 23467167
DA 2026-03-09
ER

PT J
AU Rosenfeldt, MT
   O'Prey, J
   Morton, JP
   Nixon, C
   MacKay, G
   Mrowinska, A
   Au, A
   Rai, TS
   Zheng, L
   Ridgway, R
   Adams, PD
   Anderson, KI
   Gottlieb, E
   Sansom, OJ
   Ryan, KM
AF Rosenfeldt, Mathias T.
   O'Prey, Jim
   Morton, Jennifer P.
   Nixon, Colin
   MacKay, Gillian
   Mrowinska, Agata
   Au, Amy
   Rai, Taranjit Singh
   Zheng, Liang
   Ridgway, Rachel
   Adams, Peter D.
   Anderson, Kurt I.
   Gottlieb, Eyal
   Sansom, Owen J.
   Ryan, Kevin M.
TI p53 status determines the role of autophagy in pancreatic tumour development
SO NATURE
LA English
DT Article
ID cell; suppression; progression; principles; disease; growth; cancer; damage
AB Macroautophagy (hereafter referred to as autophagy) is a process in which organelles termed autophagosomes deliver cytoplasmic constituents to lysosomes for degradation(1). Autophagy has a major role in cellular homeostasis and has been implicated in various forms of human disease(2-4). The role of autophagy in cancer seems to be complex, with reports indicating both pro-tumorigenic and tumour-suppressive roles(3,5-12). Here we show, in a humanized genetically-modified mouse model of pancreatic ductal adenocarcinoma(PDAC), that autophagy's role in tumour development is intrinsically connected to the status of the tumour suppressor p53. Mice with pancreases containing an activated oncogenic allele of Kras (also called Ki-Ras)-the most common mutational event in PDAC(13)-develop a small number of pre-cancerous lesions that stochastically develop into PDAC over time. However, mice also lacking the essential autophagy genes Atg5 or Atg7 accumulate low-grade, pre-malignant pancreatic intraepithelial neoplasia lesions, but progression to high-grade pancreatic intraepithelial neoplasias and PDAC is blocked. In marked contrast, in mice containing oncogenic Kras and lacking p53, loss of autophagy no longer blocks tumour progression, but actually accelerates tumour onset, with metabolic analysis revealing enhanced glucose uptake and enrichment of anabolic pathways, which can fuel tumour growth. These findings provide considerable insight into the role of autophagy in cancer and have important implications for autophagy inhibition in cancer therapy. In this regard, we also show that treatment of mice with the autophagy inhibitor hydroxychloroquine, which is currently being used in several clinical trials(14), significantly accelerates tumour formation in mice containing oncogenic Kras but lacking p53.
C1 [Rosenfeldt, Mathias T.; O'Prey, Jim; Morton, Jennifer P.; Nixon, Colin; MacKay, Gillian; Mrowinska, Agata; Au, Amy; Zheng, Liang; Ridgway, Rachel; Anderson, Kurt I.; Gottlieb, Eyal; Sansom, Owen J.; Ryan, Kevin M.] Canc Res UK Beatson Inst, Glasgow G61 1BD, Lanark, Scotland.
   [Rai, Taranjit Singh; Adams, Peter D.] Univ Glasgow, Inst Canc Studies, Glasgow G61 1BD, Lanark, Scotland.
C3 Beatson Institute; University of Glasgow
RP Ryan, KM (corresponding author), Canc Res UK Beatson Inst, Garscube Estate,Switchback Rd, Glasgow G61 1BD, Lanark, Scotland.
EM k.ryan@beatson.gla.ac.uk
FU Cancer Research UK; Pancreatic Cancer Research Fund; Cancer Research UK [12481, 15816, 16566, 11650, 15565] Funding Source: researchfish
NR 33
TC 617
Z9 722
U1 2
U2 198
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 12
PY 2013
VL 504
IS 7479
BP 296
EP +
DI 10.1038/nature12865
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 267TQ
UT WOS:000328121500040
PM 24305049
DA 2026-03-09
ER

PT J
AU Kouwer, PHJ
   Koepf, M
   Le Sage, VAA
   Jaspers, M
   van Buul, AM
   Eksteen-Akeroyd, ZH
   Woltinge, T
   Schwartz, E
   Kitto, HJ
   Hoogenboom, R
   Picken, SJ
   Nolte, RJM
   Mendes, E
   Rowan, AE
AF Kouwer, Paul H. J.
   Koepf, Matthieu
   Le Sage, Vincent A. A.
   Jaspers, Maarten
   van Buul, Arend M.
   Eksteen-Akeroyd, Zaskia H.
   Woltinge, Tim
   Schwartz, Erik
   Kitto, Heather J.
   Hoogenboom, Richard
   Picken, Stephen J.
   Nolte, Roeland J. M.
   Mendes, Eduardo
   Rowan, Alan E.
TI Responsive biomimetic networks from polyisocyanopeptide hydrogels
SO NATURE
LA English
DT Article
ID elasticity; medicine; actin
AB Mechanical responsiveness is essential to all biological systems down to the level of tissues and cells(1,2). The intra- and extracellular mechanics of such systems are governed by a series of proteins, such as microtubules, actin, intermediate filaments and collagen(3,4). As a general design motif, these proteins self-assemble into helical structures and superstructures that differ in diameter and persistence length to cover the full mechanical spectrum(1). Gels of cytoskeletal proteins display particular mechanical responses (stress stiffening) that until now have been absent in synthetic polymeric and low-molar-mass gels. Here we present synthetic gels that mimic in nearly all aspects gels prepared from intermediate filaments. They are prepared from polyisocyanopeptides(5-7) grafted with oligo(ethylene glycol) side chains. These responsive polymers possess a stiff and helical architecture, and show a tunable thermal transition where the chains bundle together to generate transparent gels at extremely low concentrations. Using characterization techniques operating at different length scales (for example, macroscopic rheology, atomic force microscopy and molecular force spectroscopy) combined with an appropriate theoretical network model(8-10), we establish the hierarchical relationship between the bulk mechanical properties and the single-molecule parameters. Our results show that to develop artificial cytoskeletal or extracellular matrix mimics, the essential design parameters are not only the molecular stiffness, but also the extent of bundling. In contrast to the peptidic materials, our polyisocyanide polymers are readily modified, giving a starting point for functional biomimetic hydrogels with potentially a wide variety of applications(11-14), in particular in the biomedical field.
C1 [Kouwer, Paul H. J.; Koepf, Matthieu; Le Sage, Vincent A. A.; Jaspers, Maarten; van Buul, Arend M.; Eksteen-Akeroyd, Zaskia H.; Woltinge, Tim; Schwartz, Erik; Kitto, Heather J.; Hoogenboom, Richard; Nolte, Roeland J. M.; Rowan, Alan E.] Radboud Univ Nijmegen, Inst Mol & Mat, Dept Mol Mat, NL-6525 AJ Nijmegen, Netherlands.
   [Picken, Stephen J.; Mendes, Eduardo] Delft Univ Technol, Dept NanoStruct Mat, NL-2628 BL Delft, Netherlands.
C3 Radboud University Nijmegen; Delft University of Technology
RP Kouwer, PHJ (corresponding author), Radboud Univ Nijmegen, Inst Mol & Mat, Dept Mol Mat, Heyendaalseweg 135, NL-6525 AJ Nijmegen, Netherlands.
EM p.kouwer@science.ru.nl; a.rowan@science.ru.nl
FU Technology Foundation STW; Council for the Chemical Sciences of the Netherlands Organisation for Scientific Research [NWO-CW-7005644]; NRSCC; Royal Academy for Arts and Sciences; EU [PITN-CT-2007-215851, PITN-CT-2009-238177]
NR 28
TC 480
Z9 531
U1 9
U2 970
PU NATURE PUBLISHING 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 31
PY 2013
VL 493
IS 7434
BP 651
EP 655
DI 10.1038/nature11839
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 080CU
UT WOS:000314219600052
PM 23354048
DA 2026-03-09
ER

PT J
AU Law, JA
   Du, JM
   Hale, CJ
   Feng, SH
   Krajewski, K
   Palanca, AMS
   Strahl, BD
   Patel, DJ
   Jacobsen, SE
AF Law, Julie A.
   Du, Jiamu
   Hale, Christopher J.
   Feng, Suhua
   Krajewski, Krzysztof
   Palanca, Ana Marie S.
   Strahl, Brian D.
   Patel, Dinshaw J.
   Jacobsen, Steven E.
TI Polymerase IV occupancy at RNA-directed DNA methylation sites requires SHH1
SO NATURE
LA English
DT Article
ID arabidopsis; association; argonaute4; patterns; binding
AB DNA methylation is an epigenetic modification that has critical roles in gene silencing, development and genome integrity. In Arabidopsis, DNA methylation is established by DOMAINS REARRANGED METHYLTRANSFERASE 2 (DRM2) and targeted by 24-nucleotide small interfering RNAs (siRNAs) through a pathway termed RNA-directed DNA methylation (RdDM)(1). This pathway requires two plant-specific RNA polymerases: Pol-IV, which functions to initiate siRNA biogenesis, and Pol-V, which functions to generate scaffold transcripts that recruit downstream RdDM factors(1,2). To understand the mechanisms controlling Pol-IV targeting we investigated the function of SAWADEE HOMEODOMAIN HOMOLOG 1 (SHH1)(3,4), a Pol-IV-interacting protein(3). Here we show that SHH1 acts upstream in the RdDM pathway to enable siRNA production from a large subset of the most active RdDM targets, and that SHH1 is required for Pol-IV occupancy at these same loci. We also show that the SHH1 SAWADEE domain is a novel chromatin-binding module that adopts a unique tandem Tudor-like fold and functions as a dual lysine reader, probing for both unmethylated K4 and methylated K9 modifications on the histone 3 (H3) tail. Finally, we show that key residues within both lysine-binding pockets of SHH1 are required in vivo to maintain siRNA and DNA methylation levels as well as Pol-IV occupancy at RdDM targets, demonstrating a central role for methylated H3K9 binding in SHH1 function and providing the first insights into the mechanism of Pol-IV targeting. Given the parallels between methylation systems in plants and mammals(1,5), a further understanding of this early targeting step may aid our ability to control the expression of endogenous and newly introduced genes, which has broad implications for agriculture and gene therapy.
C1 [Law, Julie A.; Hale, Christopher J.; Feng, Suhua; Jacobsen, Steven E.] Univ Calif Los Angeles, Dept Mol Cell & Dev Biol, Los Angeles, CA 90095 USA.
   [Du, Jiamu; Patel, Dinshaw J.] Mem Sloan Kettering Canc Ctr, Struct Biol Program, New York, NY 10065 USA.
   [Feng, Suhua; Jacobsen, Steven E.] Univ Calif Los Angeles, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, Los Angeles, CA 90095 USA.
   [Feng, Suhua; Jacobsen, Steven E.] Univ Calif Los Angeles, Howard Hughes Med Inst, Los Angeles, CA 90095 USA.
   [Krajewski, Krzysztof; Strahl, Brian D.] Univ N Carolina, Dept Biochem & Biophys, Chapel Hill, NC 27599 USA.
   [Palanca, Ana Marie S.] Salk Inst Biol Studies, La Jolla, CA 92037 USA.
C3 University of California System; University of California Los Angeles; Memorial Sloan Kettering Cancer Center; University of California System; University of California Los Angeles; University of California System; University of California Los Angeles; Howard Hughes Medical Institute; University of North Carolina; University of North Carolina Chapel Hill; Salk Institute
RP Jacobsen, SE (corresponding author), Univ Calif Los Angeles, Dept Mol Cell & Dev Biol, Los Angeles, CA 90095 USA.
EM pateld@mskcc.org; jacobsen@ucla.edu
FU Abby Rockefeller Mauze Trust; Maloris Foundation; STARR Foundation; NIH [GM60398, GM85394]; Damon Runyon postdoctoral fellowship; National Cancer Institute [P30CA008748] Funding Source: NIH RePORTER
NR 36
TC 300
Z9 366
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 JUN 20
PY 2013
VL 498
IS 7454
BP 385
EP +
DI 10.1038/nature12178
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 166XI
UT WOS:000320592900045
PM 23636332
DA 2026-03-09
ER

PT J
AU Gordon, DM
AF Gordon, Deborah M.
TI The rewards of restraint in the collective regulation of foraging by harvester ant colonies
SO NATURE
LA English
DT Article
ID metabolism; ecology; size
AB Collective behaviour, arising from local interactions(1), allows groups to respond to changing conditions. Long-term studies have shown that the traits of individual mammals and birds are associated with their reproductive success(2-6), but little is known about the evolutionary ecology of collective behaviour in natural populations. An ant colony operates without central control, regulating its activity through a network of local interactions(7). This work shows that variation among harvester ant (Pogonomyrmex barbatus) colonies in collective response to changing conditions(8) is related to variation in colony lifetime reproductive success in the production of offspring colonies. Desiccation costs are high for harvester ants foraging in the desert(9,10). More successful colonies tend to forage less when conditions are dry, and show relatively stable foraging activity when conditions are more humid. Restraint from foraging does not compromise a colony's long-term survival; colonies that fail to forage at all on many days survive as long, over the colony's 20-30-year lifespan, as those that forage more regularly. Sensitivity to conditions in which to reduce foraging activity may be transmissible from parent to offspring colony. These results indicate that natural selection is shaping the collective behaviour that regulates foraging activity, and that the selection pressure, related to climate, may grow stronger if the current drought in their habitat persists.
C1 Stanford Univ, Dept Biol, Stanford, CA 94305 USA.
C3 Stanford University
RP Gordon, DM (corresponding author), Stanford Univ, Dept Biol, Stanford, CA 94305 USA.
EM dmgordon@stanford.edu
FU Stanford Office of the Dean of Research; Stanford Emergence of Cooperation Project; National Science Foundation [IOS-0718631]
NR 27
TC 116
Z9 138
U1 5
U2 142
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 6
PY 2013
VL 498
IS 7452
BP 91
EP +
DI 10.1038/nature12137
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 158DC
UT WOS:000319947800039
PM 23676676
DA 2026-03-09
ER

PT J
AU Dai, L
   Korolev, KS
   Gore, J
AF Dai, Lei
   Korolev, Kirill S.
   Gore, Jeff
TI Slower recovery in space before collapse of connected populations
SO NATURE
LA English
DT Article
ID early-warning signals; regime shifts; catastrophic shifts; tipping point; ecosystems; indicator; dynamics; forest
AB Slower recovery from perturbations near a tipping point and its indirect signatures in fluctuation patterns have been suggested to foreshadow catastrophes in a wide variety of systems(1,2). Recent studies of populations in the field and in the laboratory have used time-series data to confirm some of the theoretically predicted early warning indicators, such as an increase in recovery time or in the size and timescale of fluctuations(3-6). However, the predictive power of temporal warning signals is limited by the demand for long-term observations. Large-scale spatial data are more accessible, but the performance of warning signals in spatially extended systems(7-10) needs to be examined empirically(3,11-13). Here we use spatially extended yeast populations, an experimental system with a fold bifurcation (tipping point)(6), to evaluate early warning signals based on spatio-temporal fluctuations and to identify a novel spatial warning indicator. We found that two leading indicators based on fluctuations increased before collapse of connected populations; however, the magnitudes of the increases were smaller than those observed in isolated populations, possibly because local variation is reduced by dispersal. Furthermore, we propose a generic indicator based on deterministic spatial patterns, which we call 'recovery length'. As the spatial counterpart of recovery time(14), recovery length is the distance necessary for connected populations to recover from spatial perturbations. In our experiments, recovery length increased substantially before population collapse, suggesting that the spatial scale of recovery can provide a superior warning signal before tipping points in spatially extended systems.
C1 [Dai, Lei; Korolev, Kirill S.; Gore, Jeff] MIT, Dept Phys, Cambridge, MA 02139 USA.
C3 Massachusetts Institute of Technology (MIT)
RP Dai, L (corresponding author), MIT, Dept Phys, Cambridge, MA 02139 USA.
EM dailei@mit.edu; gore@mit.edu
FU Whitaker Health Sciences Fund Fellowship; Pappalardo Fellowship; NIH [NIH R00 GM085279-02, NIH DP2]; NSF CAREER Award; Sloan Research Fellowship; Pew Scholars Program; Allen Investigator Program
NR 33
TC 145
Z9 175
U1 2
U2 169
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 18
PY 2013
VL 496
IS 7445
BP 355
EP +
DI 10.1038/nature12071
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 126FV
UT WOS:000317599200036
PM 23575630
DA 2026-03-09
ER

PT J
AU Taruno, A
   Vingtdeux, V
   Ohmoto, M
   Ma, ZM
   Dvoryanchikov, G
   Li, A
   Adrien, L
   Zhao, HT
   Leung, S
   Abernethy, M
   Koppel, J
   Davies, P
   Civan, MM
   Chaudhari, N
   Matsumoto, I
   Hellekant, G
   Tordoff, MG
   Marambaud, P
   Foskett, JK
AF Taruno, Akiyuki
   Vingtdeux, Valerie
   Ohmoto, Makoto
   Ma, Zhongming
   Dvoryanchikov, Gennady
   Li, Ang
   Adrien, Leslie
   Zhao, Haitian
   Leung, Sze
   Abernethy, Maria
   Koppel, Jeremy
   Davies, Peter
   Civan, Mortimer M.
   Chaudhari, Nirupa
   Matsumoto, Ichiro
   Hellekant, Goeran
   Tordoff, Michael G.
   Marambaud, Philippe
   Foskett, J. Kevin
TI CALHM1 ion channel mediates purinergic neurotransmission of sweet, bitter and umami tastes
SO NATURE
LA English
DT Article
ID modulator 1 calhm1; a-beta levels; alzheimers-disease; p2x receptors; atp release; polymorphism; homeostasis; cells; communication; hemichannels
AB Recognition of sweet, bitter and umami tastes requires the non-vesicular release from taste bud cells of ATP, which acts as a neurotransmitter to activate afferent neural gustatory pathways(1). However, how ATP is released to fulfil this function is not fully understood. Here we show that calcium homeostasis modulator 1 (CALHM1), a voltage-gated ion channel(2,3), is indispensable for taste-stimuli-evoked ATP release from sweet-, bitter- and umami-sensing taste bud cells. Calhm1 knockout mice have severely impaired perceptions of sweet, bitter and umami compounds, whereas their recognition of sour and salty tastes remains mostly normal. Calhm1 deficiency affects taste perception without interfering with taste cell development or integrity. CALHM1 is expressed specifically in sweet/bitter/umami-sensing type II taste bud cells. Its heterologous expression induces a novel ATP permeability that releases ATP from cells in response to manipulations that activate the CALHM1 ion channel. Knockout of Calhm1 strongly reduces voltage-gated currents in type II cells and taste-evoked ATP release from taste buds without affecting the excitability of taste cells by taste stimuli. Thus, CALHM1 is a voltage-gated ATP-release channel required for sweet, bitter and umami taste perception.
C1 [Taruno, Akiyuki; Ma, Zhongming; Li, Ang; Civan, Mortimer M.; Foskett, J. Kevin] Univ Penn, Dept Physiol, Philadelphia, PA 19104 USA.
   [Vingtdeux, Valerie; Adrien, Leslie; Zhao, Haitian; Koppel, Jeremy; Davies, Peter; Marambaud, Philippe] Feinstein Inst Med Res, Study Alzheimers Dis, Litwin Zucker Res Ctr, Manhasset, NY 11030 USA.
   [Ohmoto, Makoto; Matsumoto, Ichiro; Tordoff, Michael G.] Monell Chem Senses Ctr, Philadelphia, PA 19104 USA.
   [Dvoryanchikov, Gennady; Chaudhari, Nirupa] Univ Miami, Miller Sch Med, Dept Physiol & Biophys, Miami, FL 33136 USA.
   [Leung, Sze; Abernethy, Maria; Hellekant, Goeran] Univ Minnesota, Sch Med, Dept Biomed Sci, Duluth, MN 55812 USA.
   [Davies, Peter] Albert Einstein Coll Med, Dept Pathol, Bronx, NY 10461 USA.
   [Civan, Mortimer M.] Univ Penn, Dept Med, Philadelphia, PA 19104 USA.
   [Chaudhari, Nirupa] Univ Miami, Miller Sch Med, Program Neurosci, Miami, FL 33136 USA.
   [Foskett, J. Kevin] Univ Penn, Dept Cell & Dev Biol, Philadelphia, PA 19104 USA.
C3 University of Pennsylvania; Northwell Health; Monell Chemical Senses Center; University of Miami; University of Minnesota System; University of Minnesota Duluth; Yeshiva University; Montefiore Medical Center; Albert Einstein College of Medicine; University of Pennsylvania; University of Miami; University of Pennsylvania
RP Marambaud, P (corresponding author), Feinstein Inst Med Res, Study Alzheimers Dis, Litwin Zucker Res Ctr, Manhasset, NY 11030 USA.
EM pmaramba@nshs.edu; foskett@mail.med.upenn.edu
FU KeySpan award; US NIH [GM56328, MH059937, NS072775, DC10393, EY13624, R03DC011143, P30 EY001583, P30DC011735]; University of Minnesota; National Eye Institute [P30EY001583] Funding Source: NIH RePORTER
NR 27
TC 401
Z9 470
U1 5
U2 249
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 14
PY 2013
VL 495
IS 7440
BP 223
EP 226
DI 10.1038/nature11906
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 113FP
UT WOS:000316652300048
PM 23467090
DA 2026-03-09
ER

PT J
AU Shao, W
   Zhang, SZ
   Tang, M
   Zhang, XH
   Zhou, Z
   Yin, YQ
   Zhou, QB
   Huang, YY
   Liu, YJ
   Wawrousek, E
   Chen, T
   Li, SB
   Xu, M
   Zhou, JN
   Hu, G
   Zhou, JW
AF Shao, Wei
   Zhang, Shu-zhen
   Tang, Mi
   Zhang, Xin-hua
   Zhou, Zheng
   Yin, Yan-qing
   Zhou, Qin-bo
   Huang, Yuan-yuan
   Liu, Ying-jun
   Wawrousek, Eric
   Chen, Teng
   Li, Sheng-bin
   Xu, Ming
   Zhou, Jiang-ning
   Hu, Gang
   Zhou, Jia-wei
TI Suppression of neuroinflammation by astrocytic dopamine D2 receptors via αB-crystallin
SO NATURE
LA English
DT Article
ID human-brain; inflammation; microglia; pathway; innate; mice
AB Chronic neuroinflammation is a common feature of the ageing brain and some neurodegenerative disorders. However, the molecular and cellular mechanisms underlying the regulation of innate immunity in the central nervous system remain elusive. Here we show that the astrocytic dopamine D2 receptor (DRD2) modulates innate immunity through alpha B-crystallin (CRYAB), which is known to suppress neuroinflammation(1,2). We demonstrate that knockout mice lacking Drd2 showed remarkable inflammatory response in multiple central nervous system regions and increased the vulnerability of nigral dopaminergic neurons to neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity(3). Astrocytes null for Drd2 became hyper-responsive to immune stimuli with a marked reduction in the level of CRYAB. Preferential ablation of Drd2 in astrocytes robustly activated astrocytes in the substantia nigra. Gain- or loss-of-function studies showed that CRYAB is critical for DRD2-mediated modulation of innate immune response in astrocytes. Furthermore, treatment of wildtype mice with the selective DRD2 agonist quinpirole increased resistance of the nigral dopaminergic neurons to MPTP through partial suppression of inflammation. Our study indicates that astrocytic DRD2 activation normally suppresses neuroinflammation in the central nervous system through a CRYAB-dependent mechanism, and provides a new strategy for targeting the astrocyte-mediated innate immune response in the central nervous system during ageing and disease.
C1 [Shao, Wei; Zhang, Shu-zhen; Tang, Mi; Zhang, Xin-hua; Zhou, Zheng; Yin, Yan-qing; Zhou, Qin-bo; Huang, Yuan-yuan; Liu, Ying-jun; Zhou, Jia-wei] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Neurosci, State Key Lab Neurosci, Shanghai 200031, Peoples R China.
   [Tang, Mi; Hu, Gang] Nanjing Med Univ, Dept Pharmacol, Jiangsu Key Lab Neurodegenerat, Nanjing 210029, Jiangsu, Peoples R China.
   [Wawrousek, Eric] NEI, NIH, Bethesda, MD 20892 USA.
   [Chen, Teng; Li, Sheng-bin] Xi An Jiao Tong Univ, Sch Med, Dept Forens Sci, Xian 710061, Shanxi, Peoples R China.
   [Xu, Ming] Univ Chicago, Dept Anesthesia & Crit Care, Chicago, IL 60637 USA.
   [Zhou, Jiang-ning] Univ Sci & Technol China, Sch Life Sci, CAS Key Lab Brain Funct & Dis, Hefei 230027, Anhui, Peoples R China.
C3 Chinese Academy of Sciences; Nanjing Medical University; National Institutes of Health (NIH) - USA; NIH National Eye Institute (NEI); Xi'an Jiaotong University; University of Chicago; Chinese Academy of Sciences; University of Science & Technology of China, CAS
RP Zhou, JW (corresponding author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Neurosci, State Key Lab Neurosci, Shanghai 200031, Peoples R China.
EM jwzhou@ion.ac.cn
FU Chinese Academy of Sciences; National Basic Research Program of China [2011CBA00408, 2011CB504102]; Natural Science Foundation of China [31021063, 31123002]; Shanghai Metropolitan Fund for Research and Development; National Eye Institute [ZICEY000458] Funding Source: NIH RePORTER
NR 22
TC 369
Z9 421
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 FEB 7
PY 2013
VL 494
IS 7435
BP 90
EP 94
DI 10.1038/nature11748
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 087DJ
UT WOS:000314741200040
PM 23242137
DA 2026-03-09
ER

PT J
AU Fukuhara, T
   Schauss, P
   Endres, M
   Hild, S
   Cheneau, M
   Bloch, I
   Gross, C
AF Fukuhara, Takeshi
   Schauss, Peter
   Endres, Manuel
   Hild, Sebastian
   Cheneau, Marc
   Bloch, Immanuel
   Gross, Christian
TI Microscopic observation of magnon bound states and their dynamics
SO NATURE
LA English
DT Article
ID atomic mott insulator; optical lattice; heisenberg ferromagnet; quantum; chain; cocl2.2h2o; solitons; bosons
AB The existence of bound states of elementary spin waves (magnons) in one-dimensional quantum magnets was predicted almost 80 years ago(1). Identifying signatures of magnon bound states has so far remained the subject of intense theoretical research(2-5), and their detection has proved challenging for experiments. Ultracold atoms offer an ideal setting in which to find such bound states by tracking the spin dynamics with single-spin and single-site resolution(6,7) following a local excitation(8). Here we use in situ correlation measurements to observe two-magnon bound states directly in a one-dimensional Heisenberg spin chain comprising ultracold bosonic atoms in an optical lattice. We observe the quantum dynamics of free and bound magnon states through time-resolved measurements of two spin impurities. The increased effective mass of the compound magnon state results in slower spin dynamics as compared to single-magnon excitations. We also determine the decay time of bound magnons, which is probably limited by scattering on thermal fluctuations in the system. Our results provide a new way of studying fundamental properties of quantum magnets and, more generally, properties of interacting impurities in quantum many-body systems.
C1 [Fukuhara, Takeshi; Schauss, Peter; Endres, Manuel; Hild, Sebastian; Cheneau, Marc; Bloch, Immanuel; Gross, Christian] Max Planck Inst Quantum Opt, D-85748 Garching, Germany.
   [Cheneau, Marc] Univ Paris Sud, CNRS, Inst Opt, Lab Charles Fabry,Grad Sch, F-91127 Palaiseau, France.
   [Bloch, Immanuel] Univ Munich, Fak Phys, D-80799 Munich, Germany.
C3 Max Planck Society; Universite Paris Saclay; Centre National de la Recherche Scientifique (CNRS); Institut Polytechnique de Paris; Ecole Polytechnique; University of Munich
RP Fukuhara, T (corresponding author), Max Planck Inst Quantum Opt, D-85748 Garching, Germany.
EM takeshi.fukuhara@mpq.mpg.de
FU MPG; DFG; EU; JSPS
NR 35
TC 381
Z9 410
U1 2
U2 136
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 3
PY 2013
VL 502
IS 7469
BP 76
EP +
DI 10.1038/nature12541
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 227IM
UT WOS:000325106000033
PM 24067608
DA 2026-03-09
ER

PT J
AU Arpaia, N
   Campbell, C
   Fan, XY
   Dikiy, S
   van der Veeken, J
   deRoos, P
   Liu, H
   Cross, JR
   Pfeffer, K
   Coffer, PJ
   Rudensky, AY
AF Arpaia, Nicholas
   Campbell, Clarissa
   Fan, Xiying
   Dikiy, Stanislav
   van der Veeken, Joris
   deRoos, Paul
   Liu, Hui
   Cross, Justin R.
   Pfeffer, Klaus
   Coffer, Paul J.
   Rudensky, Alexander Y.
TI Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation
SO NATURE
LA English
DT Article
ID chain fatty-acids; receptor; relb; induction
AB Intestinal microbes provide multicellular hosts with nutrients and confer resistance to infection. The delicate balance between pro-and anti-inflammatory mechanisms, essential for gut immune homeostasis, is affected by the composition of the commensal microbial community. Regulatory T cells (T-reg cells) expressing transcription factor Foxp3 have a key role in limiting inflammatory responses in the intestine(1). Although specific members of the commensal microbial community have been found to potentiate the generation of anti-inflammatory T-reg or pro-inflammatory T helper 17 (T(H)17) cells(2-6), the molecular cues driving this process remain elusive. Considering the vital metabolic function afforded by commensal microorganisms, we reasoned that their metabolic by-products are sensed by cells of the immune system and affect the balance between pro-and anti-inflammatory cells. We tested this hypothesis by exploring the effect of microbial metabolites on the generation of anti-inflammatory T-reg cells. We found that in mice a short-chain fatty acid (SCFA), butyrate, produced by commensal microorganisms during starch fermentation, facilitated extrathymic generation of T-reg cells. A boost in T-reg-cell numbers after provision of butyrate was due to potentiation of extrathymic differentiation of T-reg cells, as the observed phenomenon was dependent on intronic enhancer CNS1 (conserved non-coding sequence 1), essential for extrathymic but dispensable for thymic T-reg-cell differentiation(1,7). In addition to butyrate, de novo T-reg-cell generation in the periphery was potentiated by propionate, another SCFA of microbial origin capable of histone deacetylase (HDAC) inhibition, but not acetate, which lacks this HDAC-inhibitory activity. Our results suggest that bacterial metabolites mediate communication between the commensal microbiota and the immune system, affecting the balance between pro- and anti-inflammatory mechanisms.
C1 [Arpaia, Nicholas; Campbell, Clarissa; Fan, Xiying; Dikiy, Stanislav; van der Veeken, Joris; deRoos, Paul; Coffer, Paul J.; Rudensky, Alexander Y.] Mem Sloan Kettering Canc Ctr, Howard Hughes Med Inst, New York, NY 10065 USA.
   [Arpaia, Nicholas; Campbell, Clarissa; Fan, Xiying; Dikiy, Stanislav; van der Veeken, Joris; deRoos, Paul; Coffer, Paul J.; Rudensky, Alexander Y.] Mem Sloan Kettering Canc Ctr, Ludwig Ctr, New York, NY 10065 USA.
   [Arpaia, Nicholas; Campbell, Clarissa; Fan, Xiying; Dikiy, Stanislav; van der Veeken, Joris; deRoos, Paul; Coffer, Paul J.; Rudensky, Alexander Y.] Mem Sloan Kettering Canc Ctr, Program Immunol, New York, NY 10065 USA.
   [Liu, Hui; Cross, Justin R.] Mem Sloan Kettering Canc Ctr, Donald B & Catherine C Marron Canc Metab Ctr, New York, NY 10065 USA.
   [Pfeffer, Klaus] Univ Dusseldorf, Inst Med Microbiol & Hosp Hyg, D-40225 Dusseldorf, Germany.
   [Coffer, Paul J.] Univ Med Ctr Utrecht, Dept Cell Biol, NL-3584 CX Utrecht, Netherlands.
C3 Howard Hughes Medical Institute; Memorial Sloan Kettering Cancer Center; Memorial Sloan Kettering Cancer Center; Memorial Sloan Kettering Cancer Center; Memorial Sloan Kettering Cancer Center; Heinrich Heine University Dusseldorf; Utrecht University; Utrecht University Medical Center
RP Rudensky, AY (corresponding author), Mem Sloan Kettering Canc Ctr, Howard Hughes Med Inst, New York, NY 10065 USA.
EM rudenska@mskcc.org
FU Damon Runyon Cancer Research Foundation [DRG-2143-13]; Ludwig Center at Memorial Sloan Kettering Cancer Center; US National Institutes of Health (NIH) [T32 A1007621, R37 AI034206]; National Cancer Institute [P30CA008748, T32CA009149] Funding Source: NIH RePORTER; National Institute of General Medical Sciences [T32GM007739] Funding Source: NIH RePORTER
NR 25
TC 3749
Z9 4361
U1 25
U2 727
PU NATURE PUBLISHING 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 19
PY 2013
VL 504
IS 7480
BP 451
EP +
DI 10.1038/nature12726
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 273ZR
UT WOS:000328575300055
PM 24226773
DA 2026-03-09
ER

PT J
AU Bird, JC
   Dhiman, R
   Kwon, HM
   Varanasi, KK
AF Bird, James C.
   Dhiman, Rajeev
   Kwon, Hyuk-Min
   Varanasi, Kripa K.
TI Reducing the contact time of a bouncing drop
SO NATURE
LA English
DT Article
ID impact; transitions; impalement; dynamics; surfaces; liquid; wall
AB Surfaces designed so that drops do not adhere to them but instead bounce off have received substantial attention because of their ability to stay dry(1-4), self-clean(5-7) and resist icing(8-10). A drop striking a non-wetting surface of this type will spread out to a maximum diameter(11-14) and then recoil to such an extent that it completely rebounds and leaves the solid material(15-18). The amount of time that the drop is in contact with the solid-the 'contact time'-depends on the inertia and capillarity of the drop(1), internal dissipation(19) and surface-liquid interactions(20-22). And because contact time controls the extent to which mass, momentum and energy are exchanged between drop and surface(23), it is often advantageous to minimize it. The conventional approach has been to minimize surface-liquid interactions that can lead to contact line pinning(20-22); but even in the absence of any surface interactions, drop hydrodynamics imposes a minimum contact time that was conventionally assumed to be attained with axisymmetrically spreading and recoiling drops(21,24). Here we demonstrate that it is possible to reduce the contact time below this theoretical limit by using superhydrophobic surfaces with a morphology that redistributes the liquid mass and thereby alters the drop hydrodynamics. We show theoretically and experimentally that this approach allows us to reduce the overall contact time between a bouncing drop and a surface below what was previously thought possible.
C1 [Bird, James C.] Boston Univ, Dept Mech Engn, Boston, MA 02155 USA.
   [Dhiman, Rajeev; Kwon, Hyuk-Min; Varanasi, Kripa K.] MIT, Dept Mech Engn, Cambridge, MA 02139 USA.
C3 Boston University; Massachusetts Institute of Technology (MIT)
RP Varanasi, KK (corresponding author), MIT, Dept Mech Engn, Cambridge, MA 02139 USA.
EM varanasi@mit.edu
FU DARPA; MIT Energy Initiative; NSF [0952564, DMS1004678]; MIT-Deshpande Center; Directorate For Engineering; Div Of Chem, Bioeng, Env, & Transp Sys [0952564] Funding Source: National Science Foundation
NR 40
TC 990
Z9 1083
U1 23
U2 788
PU NATURE PUBLISHING 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 21
PY 2013
VL 503
IS 7476
BP 385
EP +
DI 10.1038/nature12740
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 254KG
UT WOS:000327163200038
PM 24256803
DA 2026-03-09
ER

PT J
AU Ni, XJ
   Gebo, DL
   Dagosto, M
   Meng, J
   Tafforeau, P
   Flynn, JJ
   Beard, KC
AF Ni, Xijun
   Gebo, Daniel L.
   Dagosto, Marian
   Meng, Jin
   Tafforeau, Paul
   Flynn, John J.
   Beard, K. Christopher
TI The oldest known primate skeleton and early haplorhine evolution
SO NATURE
LA English
DT Article
ID early eocene; middle eocene; locomotor adaptations; omomyidae; remains; morphology; diversity; dentition; revision; elements
AB Reconstructing the earliest phases of primate evolution has been impeded by gaps in the fossil record, so that disagreements persist regarding the palaeobiology and phylogenetic relationships of the earliest primates. Here we report the discovery of a nearly complete and partly articulated skeleton of a primitive haplorhine primate from the early Eocene of China, about 55 million years ago, the oldest fossil primate of this quality ever recovered. Coupled with detailed morphological examination using propagation phase contrast X-ray synchrotron microtomography, our phylogenetic analysis based on total available evidence indicates that this fossil is the most basal known member of the tarsiiform clade. In addition to providing further support for an early dichotomy between the strepsirrhine and haplorhine clades, this new primate further constrains the age of divergence between tarsiiforms and anthropoids. It also strengthens the hypothesis that the earliest primates were probably diurnal, arboreal and primarily insectivorous mammals the size of modern pygmy mouse lemurs.
C1 [Ni, Xijun] Chinese Acad Sci, Inst Vertebrate Paleontol & Paleoanthropol, Key Lab Vertebrate Evolut & Human Origin, Beijing 100044, Peoples R China.
   [Ni, Xijun; Meng, Jin; Flynn, John J.] Amer Museum Nat Hist, Div Paleontol, New York, NY 10024 USA.
   [Ni, Xijun; Meng, Jin; Flynn, John J.] Amer Museum Nat Hist, Richard Gilder Grad Sch, New York, NY 10024 USA.
   [Gebo, Daniel L.] No Illinois Univ, Dept Anthropol, De Kalb, IL 60115 USA.
   [Dagosto, Marian] Northwestern Univ, Feinberg Sch Med, Dept Cell & Mol Biol, Chicago, IL 60611 USA.
   [Tafforeau, Paul] European Synchrotron Radiat Facil, F-38043 Grenoble, France.
   [Beard, K. Christopher] Carnegie Museum Nat Hist, Sect Vertebrate Paleontol, Pittsburgh, PA 15213 USA.
C3 Chinese Academy of Sciences; Institute of Vertebrate Paleontology & Paleoanthropology, CAS; American Museum of Natural History (AMNH); American Museum of Natural History (AMNH); Northern Illinois University; Northwestern University; Feinberg School of Medicine; European Synchrotron Radiation Facility (ESRF)
RP Ni, XJ (corresponding author), Chinese Acad Sci, Inst Vertebrate Paleontol & Paleoanthropol, Key Lab Vertebrate Evolut & Human Origin, 142 Xi Zhi Men Wai St, Beijing 100044, Peoples R China.
EM nixijun@ivpp.ac.cn
FU Strategic Priority Research Program of Chinese Academy of Sciences (CAS) [XDB03020501]; National Basic Research Program of China [2012CB821904]; CAS 100-talent Program; National Natural Science Foundation of China [40672009, 40872032]; US National Science Foundation [BCS 0820602]; ESRF [ec347]; Postdoctoral Research Fellowship Program of the American Museum of Natural History (AMNH); Direct For Social, Behav & Economic Scie; Division Of Behavioral and Cognitive Sci [1157142] Funding Source: National Science Foundation
NR 43
TC 149
Z9 178
U1 3
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 JUN 6
PY 2013
VL 498
IS 7452
BP 60
EP 64
DI 10.1038/nature12200
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 158DC
UT WOS:000319947800032
PM 23739424
DA 2026-03-09
ER

PT J
AU Saini, N
   Ramakrishnan, S
   Elango, R
   Ayyar, S
   Zhang, Y
   Deem, A
   Ira, G
   Haber, JE
   Lobachev, KS
   Malkova, A
AF Saini, Natalie
   Ramakrishnan, Sreejith
   Elango, Rajula
   Ayyar, Sandeep
   Zhang, Yu
   Deem, Angela
   Ira, Grzegorz
   Haber, James E.
   Lobachev, Kirill S.
   Malkova, Anna
TI Migrating bubble during break-induced replication drives conservative DNA synthesis
SO NATURE
LA English
DT Article
ID double-strand breaks; saccharomyces-cerevisiae; half-crossovers; repair; recombination; yeast; bacteriophage-t4; telomerase; mutations; rad51
AB The repair of chromosomal double strand breaks (DSBs) is crucial for the maintenance of genomic integrity. However, the repair of DSBs can also destabilize the genome by causing mutations and chromosomal rearrangements, the driving forces for carcinogenesis and hereditary diseases. Break-induced replication (BIR) is one of the DSB repair pathways that is highly prone to genetic instability(1-3). BIR proceeds by invasion of one broken end into a homologous DNA sequence followed by replication that can copy hundreds of kilobases of DNA from a donor molecule all the way through its telomere(4,5). The resulting repaired chromosome comes at a great cost to the cell, as BIR promotes mutagenesis, loss of heterozygosity, translocations, and copy number variations, all hallmarks of carcinogenesis(4-9). BIR uses most known replication proteins to copy large portions of DNA, similar to S-phase replication(10,11). It has therefore been suggested that BIR proceeds by semiconservative replication; however, the model of a bona fide, stable replication fork contradicts the known instabilities associated with BIR such as a 1,000-fold increase in mutation rate compared to normal replication(9). Here we demonstrate that in budding yeast the mechanism of replication during BIR is significantly different from S-phase replication, as it proceeds via an unusual bubble-like replication fork that results in conservative inheritance of the new genetic material. We provide evidence that this atypical mode of DNA replication, dependent on Pif1 helicase, is responsible for the marked increase in BIR-associated mutations. We propose that the BIR mode of synthesis presents a powerful mechanism that can initiate bursts of genetic instability in eukaryotes, including humans.
C1 [Saini, Natalie; Zhang, Yu; Lobachev, Kirill S.] Georgia Inst Technol, Sch Biol, Atlanta, GA 30332 USA.
   [Saini, Natalie; Zhang, Yu; Lobachev, Kirill S.] Georgia Inst Technol, Inst Bioengn & Biosci, Atlanta, GA 30332 USA.
   [Ramakrishnan, Sreejith; Elango, Rajula; Ayyar, Sandeep; Deem, Angela; Malkova, Anna] IUPUI, Dept Biol, Indianapolis, IN 46202 USA.
   [Ira, Grzegorz] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA.
   [Haber, James E.] Dept Biol, Waltham, MA 02454 USA.
   [Haber, James E.] Rosenstiel Basic Med Sci Res Ctr, Waltham, MA 02454 USA.
   [Malkova, Anna] Univ Iowa, Dept Biol, Coll Liberal Arts & Sci, Iowa City, IA 52242 USA.
C3 University System of Georgia; Georgia Institute of Technology; University System of Georgia; Georgia Institute of Technology; Indiana University System; Indiana University Indianapolis; Baylor College of Medicine; University of Iowa
RP Malkova, A (corresponding author), IUPUI, Dept Biol, Indianapolis, IN 46202 USA.
EM kirill.lobachev@biology.gatech.edu; amalkova@iupui.edu
FU US National Institutes of Health; National Science Foundation; NSF [MCB-0818122]; NIH [R01GM084242, R01GM082950, R03ES016434, GM76020, GM080600]; National Institute of General Medical Sciences [R01GM080600] Funding Source: NIH RePORTER
NR 37
TC 263
Z9 329
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 OCT 17
PY 2013
VL 502
IS 7471
BP 389
EP +
DI 10.1038/nature12584
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 235GY
UT WOS:000325706300057
PM 24025772
DA 2026-03-09
ER

PT J
AU Beye, M
   Schreck, S
   Sorgenfrei, F
   Trabant, C
   Pontius, N
   Schüssler-Langeheine, C
   Wurth, W
   Föhlisch, A
AF Beye, M.
   Schreck, S.
   Sorgenfrei, F.
   Trabant, C.
   Pontius, N.
   Schuessler-Langeheine, C.
   Wurth, W.
   Foehlisch, A.
TI Stimulated X-ray emission for materials science
SO NATURE
LA English
DT Article
ID electronic-structure; scattering; operation; laser
AB Resonant inelastic X-ray scattering and X-ray emission spectroscopy can be used to probe the energy and dispersion of the elementary low-energy excitations that govern functionality in matter: vibronic, charge, spin and orbital excitations(1-7). A key drawback of resonant inelastic X-ray scattering has been the need for high photon densities to compensate for fluorescence yields of less than a per cent for soft X-rays(8). Sample damage from the dominant non-radiative decays thus limits the materials to which such techniques can be applied and the spectral resolution that can be obtained. A means of improving the yield is therefore highly desirable. Here we demonstrate stimulated X-ray emission for crystalline silicon at photon densities that are easily achievable with free-electron lasers(9). The stimulated radiative decay of core excited species at the expense of non-radiative processes reduces sample damage and permits narrow-bandwidth detection in the directed beam of stimulated radiation. We deduce how stimulated X-ray emission can be enhanced by several orders of magnitude to provide, with high yield and reduced sample damage, a superior probe for low-energy excitations and their dispersion in matter. This is the first step to bringing nonlinear X-ray physics in the condensed phase from theory(10-16) to application.
C1 [Beye, M.; Schreck, S.; Sorgenfrei, F.; Trabant, C.; Pontius, N.; Schuessler-Langeheine, C.; Foehlisch, A.] Helmholtz Zentrum Berlin Mat & Energie GmbH, Inst Methods & Instrumentat Synchrotron Radiat Re, D-12489 Berlin, Germany.
   [Schreck, S.; Trabant, C.; Foehlisch, A.] Univ Potsdam, Fak Phys & Astron, D-14476 Potsdam, Germany.
   [Sorgenfrei, F.; Wurth, W.] Univ Hamburg, Inst Expt Phys, D-22761 Hamburg, Germany.
   [Sorgenfrei, F.; Wurth, W.] Ctr Free Electron Laser Sci, D-22761 Hamburg, Germany.
   [Trabant, C.] Univ Cologne, Inst Phys 2, D-50937 Cologne, Germany.
C3 Helmholtz Association; Helmholtz-Zentrum fuer Materialien und Energie GmbH (HZB); University of Potsdam; University of Wurzburg; University of Hamburg; University of Cologne
RP Beye, M (corresponding author), Helmholtz Zentrum Berlin Mat & Energie GmbH, Inst Methods & Instrumentat Synchrotron Radiat Re, Albert Einstein Str 15, D-12489 Berlin, Germany.
EM martin.beye@helmholtz-berlin.de
FU VolkswagenStiftung; German Federal Ministry of Education and Research; Deutsche Forschungsgemeinschaft [05K10PK2]
NR 33
TC 94
Z9 102
U1 1
U2 130
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 12
PY 2013
VL 501
IS 7466
BP 191
EP +
DI 10.1038/nature12449
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 215XR
UT WOS:000324244900034
PM 23965622
DA 2026-03-09
ER

PT J
AU Humayun, M
   Nemchin, A
   Zanda, B
   Hewins, RH
   Grange, M
   Kennedy, A
   Lorand, JP
   Göpel, C
   Fieni, C
   Pont, S
   Deldicque, D
AF Humayun, M.
   Nemchin, A.
   Zanda, B.
   Hewins, R. H.
   Grange, M.
   Kennedy, A.
   Lorand, J. -P.
   Goepel, C.
   Fieni, C.
   Pont, S.
   Deldicque, D.
TI Origin and age of the earliest Martian crust from meteorite NWA 7533
SO NATURE
LA English
DT Article
ID x-ray spectrometer; siderophile elements; lunar meteorites; magma ocean; u-pb; mars; evolution; crystallization; signatures; breccias
AB The ancient cratered terrain of the southern highlands of Mars is thought to hold clues to the planet's early differentiation(1,2), but until now no meteoritic regolith breccias have been recovered from Mars. Here we show that the meteorite Northwest Africa (NWA) 7533 (paired with meteorite NWA 7034(3)) is a polymict breccia consisting of a fine-grained interclast matrix containing clasts of igneous-textured rocks and fine-grained clast-laden impact melt rocks. High abundances of meteoritic siderophiles (for example nickel and iridium) found throughout the rock reach a level in the fine-grained portions equivalent to 5 per cent CI chondritic input, which is comparable to the highest levels found in lunar breccias. Furthermore, analyses of three leucocratic monzonite clasts show a correlation between nickel, iridium and magnesium consistent with differentiation from impact melts. Compositionally, all the fine-grained material is alkalic basalt, chemically identical (except for sulphur, chlorine and zinc) to soils from Gusev crater. Thus, we propose that NWA 7533 is a Martian regolith breccia. It contains zircons for which we measured an age of 4,428 +/- 25 million years, which were later disturbed 1,712 +/- 85 million years ago. This evidence for early crustal differentiation implies that the Martian crust, and its volatile inventory(4), formed in about the first 100 million years of Martian history, coeval with earliest crust formation on the Moon(5) and the Earth(6). In addition, incompatible element abundances in clast-laden impact melt rocks and interclast matrix provide a geochemical estimate of the average thickness of the Martian crust (50 kilometres) comparable to that estimated geophysically(2,7).
C1 [Humayun, M.] Florida State Univ, Dept Earth Ocean & Atmospher Sci, Tallahassee, FL 32310 USA.
   [Humayun, M.] Florida State Univ, Natl High Magnet Field Lab, Tallahassee, FL 32310 USA.
   [Nemchin, A.; Grange, M.] Curtin Univ, Dept Appl Geol, Perth, WA 6845, Australia.
   [Zanda, B.; Hewins, R. H.; Fieni, C.; Pont, S.] CNRS, Lab Mineral & Cosmochim Museum, F-75005 Paris, France.
   [Zanda, B.; Hewins, R. H.; Fieni, C.; Pont, S.] Museum Natl Hist Nat, F-75005 Paris, France.
   [Zanda, B.; Hewins, R. H.] Rutgers State Univ, Dept Earth & Planetary Sci, Piscataway, NJ 08854 USA.
   [Kennedy, A.] Curtin Univ, Dept Appl Phys, Perth, WA 6845, Australia.
   [Lorand, J. -P.] Univ Nantes, Lab Planetol & Geodynam Nantes, CNRS, UMR 6112, F-44322 Nantes 3, France.
   [Goepel, C.] Univ Paris Diderot, Inst Phys Globe, Sorbonne Paris Cite, CNRS,UMR 7154, F-75005 Paris, France.
   [Deldicque, D.] Ecole Normale Super, UMR 8538, F-75231 Paris 5, France.
C3 State University System of Florida; Florida State University; State University System of Florida; Florida State University; Curtin University; Centre National de la Recherche Scientifique (CNRS); Museum National d'Histoire Naturelle (MNHN); Rutgers University System; Rutgers University New Brunswick; Curtin University; Nantes Universite; Centre National de la Recherche Scientifique (CNRS); Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Earth Sciences & Astronomy (INSU); Universite Paris Cite; Universite PSL; Ecole Normale Superieure (ENS); Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Earth Sciences & Astronomy (INSU)
RP Humayun, M (corresponding author), Florida State Univ, Dept Earth Ocean & Atmospher Sci, Tallahassee, FL 32310 USA.
EM humayun@magnet.fsu.edu
FU NASA [NNX10AI37G]; Programme National de Planetologie, France; ARC Centre of Excellence CCFS; NASA [132812, NNX10AI37G] Funding Source: Federal RePORTER
NR 46
TC 274
Z9 297
U1 1
U2 129
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 28
PY 2013
VL 503
IS 7477
BP 513
EP +
DI 10.1038/nature12764
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 258MU
UT WOS:000327464200040
PM 24256724
DA 2026-03-09
ER

PT J
AU Borovicka, J
   Spurny, P
   Brown, P
   Wiegert, P
   Kalenda, P
   Clark, D
   Shrbeny, L
AF Borovicka, Jiri
   Spurny, Pavel
   Brown, Peter
   Wiegert, Paul
   Kalenda, Pavel
   Clark, David
   Shrbeny, Lukas
TI The trajectory, structure and origin of the Chelyabinsk asteroidal impactor
SO NATURE
LA English
DT Article
ID near-earth objects; meteorite fall; meteoroids; dynamics; fragmentation; atmosphere; space; orbit
AB Earth is continuously colliding with fragments of asteroids and comets of various sizes. The largest encounter in historical times occurred over the Tunguska river in Siberia in 1908, producing(1,2) an airburst of energy equivalent to 5-15 megatons of trinitrotoluene (1 kiloton of trinitrotoluene represents an energy of 4.185 x 10(12) joules). Until recently, the next most energetic airburst events occurred over Indonesia(3) in 2009 and near the Marshall Islands(4) in 1994, both with energies of several tens of kilotons. Here we report an analysis of selected video records of the Chelyabinsk superbolide(5) of 15 February 2013, with energy equivalent to 500 kilotons of trinitrotoluene, and details of its atmospheric passage. We found that its orbit was similar to the orbit of the two-kilometre-diameter asteroid 86039 (1999 NC43), to a degree of statistical significance sufficient to suggest that the two were once part of the same object. The bulk strength-the ability to resist breakage-of the Chelyabinsk asteroid, of about one megapascal, was similar to that of smaller meteoroids(6) and corresponds to a heavily fractured single stone. The asteroid broke into small pieces between the altitudes of 45 and 30 kilometres, preventing more-serious damage on the ground. The total mass of surviving fragments larger than 100 grams was lower than expected(7).
C1 [Borovicka, Jiri; Spurny, Pavel; Shrbeny, Lukas] Acad Sci Czech Republ, Astron Inst, CZ-25165 Ondrejov, Czech Republic.
   [Brown, Peter; Wiegert, Paul; Clark, David] Univ Western Ontario, Dept Phys & Astron, London, ON N6A 3K7, Canada.
   [Brown, Peter; Wiegert, Paul; Clark, David] Univ Western Ontario, Ctr Planetary Sci & Explorat, London, ON N6A 5B7, Canada.
   [Kalenda, Pavel] Acad Sci Czech Republ, Inst Rock Struct & Mech, CZ-18209 Prague 8, Czech Republic.
C3 Czech Academy of Sciences; Astronomical Institute of the Czech Academy of Sciences; Western University (University of Western Ontario); Western University (University of Western Ontario); Czech Academy of Sciences; Institute of Rock Structure & Mechanics of the Czech Academy of Sciences
RP Borovicka, J (corresponding author), Acad Sci Czech Republ, Astron Inst, CZ-25165 Ondrejov, Czech Republic.
EM jiri.borovicka@asu.cas.cz
FU GACR [P209/11/1382]; Praemium Academiae; Natural Sciences and Engineering Research Council of Canada; NASA's Meteoroid Environment Office;  [67985815]
NR 29
TC 198
Z9 232
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 NOV 14
PY 2013
VL 503
IS 7475
BP 235
EP +
DI 10.1038/nature12671
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 250YX
UT WOS:000326894200045
PM 24196708
DA 2026-03-09
ER

PT J
AU Delgoffe, GM
   Woo, SR
   Turnis, ME
   Gravano, DM
   Guy, C
   Overacre, AE
   Bettini, ML
   Vogel, P
   Finkelstein, D
   Bonnevier, J
   Workman, CJ
   Vignali, DAA
AF Delgoffe, Greg M.
   Woo, Seng-Ryong
   Turnis, Meghan E.
   Gravano, David M.
   Guy, Cliff
   Overacre, Abigail E.
   Bettini, Matthew L.
   Vogel, Peter
   Finkelstein, David
   Bonnevier, Jody
   Workman, Creg J.
   Vignali, Dario A. A.
TI Stability and function of regulatory T cells is maintained by a neuropilin-1-semaphorin-4a axis
SO NATURE
LA English
DT Article
ID plasmacytoid dendritic cells; transcription factor foxp3; breast-cancer cells; in-vivo; neuropilin-1; expression; akt; differentiation; activation; marker
AB Regulatory T cells (T-reg cells) have a crucial role in the immune system by preventing autoimmunity, limiting immunopathology, and maintaining immune homeostasis(1). However, they also represent a major barrier to effective anti-tumour immunity and sterilizing immunity to chronic viral infections(1). The transcription factor Foxp3 has a major role in the development and programming of T-reg cells(2,3). The relative stability of T-reg cells at inflammatory disease sites has been a highly contentious subject(4-6). There is considerable interest in identifying pathways that control the stability of T-reg cells as many immune-mediated diseases are characterized by either exacerbated or limited T-reg-cell function. Here we show that the immune-cell-expressed ligand semaphorin-4a (Sema4a) and the T-reg-cell-expressed receptor neuropilin-1 (Nrp1) interact both in vitro, to potentiate T-reg-cell function and survival, and in vivo, at inflammatory sites. Using mice with a T-reg-cell-restricted deletion of Nrp1, we show that Nrp1 is dispensable for suppression of autoimmunity and maintenance of immune homeostasis, but is required by T-reg cells to limit anti-tumour immune responses and to cure established inflammatory colitis. Sema4a ligation of Nrp1 restrained Akt phosphorylation cellularly and at the immunologic synapse by phosphatase and tensin homologue (PTEN), which increased nuclear localization of the transcription factor Foxo3a. The Nrp1-induced transcriptome promoted T-reg-cell stability by enhancing quiescence and survival factors while inhibiting programs that promote differentiation. Importantly, this Nrp1-dependent molecular program is evident in intra-tumoral T-reg cells. Our data support a model in which T-reg-cell stability can be subverted in certain inflammatory sites, but is maintained by a Sema4a-Nrp1 axis, highlighting this pathway as a potential therapeutic target that could limit T-reg-cell-mediated tumour-induced tolerance without inducing autoimmunity.
C1 [Delgoffe, Greg M.; Woo, Seng-Ryong; Turnis, Meghan E.; Gravano, David M.; Guy, Cliff; Overacre, Abigail E.; Bettini, Matthew L.; Workman, Creg J.; Vignali, Dario A. A.] St Jude Childrens Res Hosp, Dept Immunol, Memphis, TN 38105 USA.
   [Overacre, Abigail E.] Univ Tennessee, Hlth Sci Ctr, Integrated Biomed Sci Program, Memphis, TN 38163 USA.
   [Vogel, Peter] St Jude Childrens Res Hosp, Dept Pathol, Memphis, TN 38105 USA.
   [Finkelstein, David] St Jude Childrens Res Hosp, Memphis, TN 38105 USA.
   [Bonnevier, Jody] R&D Syst Inc, Minneapolis, MN 55413 USA.
C3 St Jude Children's Research Hospital; University of Tennessee System; University of Tennessee Health Science Center; St Jude Children's Research Hospital; St Jude Children's Research Hospital; RD Systems Inc.
RP Vignali, DAA (corresponding author), St Jude Childrens Res Hosp, Dept Immunol, 332 N Lauderdale St, Memphis, TN 38105 USA.
EM vignali.lab@stjude.org
FU National Institutes of Health [R01 AI091977, AI039480, F32 AI098383]; NCI Comprehensive Cancer Center Support CORE grant [CA21765]; ALSAC; National Cancer Institute [P30CA021765] Funding Source: NIH RePORTER
NR 31
TC 474
Z9 583
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 SEP 12
PY 2013
VL 501
IS 7466
BP 252
EP +
DI 10.1038/nature12428
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 215XR
UT WOS:000324244900047
PM 23913274
DA 2026-03-09
ER

PT J
AU Nielsen, M
   Alberico, E
   Baumann, W
   Drexler, HJ
   Junge, H
   Gladiali, S
   Beller, M
AF Nielsen, Martin
   Alberico, Elisabetta
   Baumann, Wolfgang
   Drexler, Hans-Joachim
   Junge, Henrik
   Gladiali, Serafino
   Beller, Matthias
TI Low-temperature aqueous-phase methanol dehydrogenation to hydrogen and carbon dioxide
SO NATURE
LA English
DT Article
ID ruthenium complexes; ammonia-borane; catalysts; alcohols; oxidation; ligand; water; activation; osmium; esters
AB Hydrogen produced from renewable resources is a promising potential source of clean energy. With the help of low-temperature proton-exchange membrane fuel cells, Molecular hydrogen can be converted efficiently to produce electricity(1-5). The implementation of sustainable hydrogen production and subsequent hydrogen conversion to energy is called "hydrogen economy"(2). Unfortunately, its physical properties make the transport and handling of hydrogen gas difficult. To overcome this, methanol can be used as a material for the storage of hydrogen, because it is a liquid at room temperature and contains 12.6 per cent hydrogen. However, the state-of-the-art method for the production of hydrogen from methanol (methanol reforming) is conducted at high temperatures (over 200 degrees Celsius) and high pressures (25-50 bar), which limits its potential applications(6-8). Here we describe an efficient low-temperature aqueous-phase methanol dehydrogenation process, which is facilitated by ruthenium complexes. Hydrogen generation by this method proceeds at 65-95 degrees Celsius and ambient pressure with excellent catalyst turnover frequencies (4,700 per hour) and turnover numbers (exceeding 350,000). This would make the delivery of hydrogen on mobile devices-and hence the use of methanol as a practical hydrogen carrier-feasible.
C1 [Nielsen, Martin; Alberico, Elisabetta; Baumann, Wolfgang; Drexler, Hans-Joachim; Junge, Henrik; Beller, Matthias] Univ Rostock, Leibniz Inst Katalyse Eingetragener Verein, D-18059 Rostock, Germany.
   [Alberico, Elisabetta] CNR, Ist Chim Biomol, I-07040 Sassari, Italy.
   [Gladiali, Serafino] Univ Sassari, Dipartimento Chim & Farm, I-07100 Sassari, Italy.
C3 Leibniz Association; Leibniz Institut fur Katalyse e.V. an der Universitat Rostock (LIKAT); University of Rostock; Consiglio Nazionale delle Ricerche (CNR); Istituto di Chimica Biomolecolare (ICB-CNR); University of Sassari
RP Beller, M (corresponding author), Univ Rostock, Leibniz Inst Katalyse Eingetragener Verein, Albert Einstein Str 29A, D-18059 Rostock, Germany.
EM matthias.beller@catalysis.de
FU Alexander von Humboldt Foundation; BMBF; Ministry of Science and Education of Mecklenburg-Western Pommerania
NR 30
TC 729
Z9 791
U1 9
U2 1112
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 7
PY 2013
VL 495
IS 7439
BP 85
EP 89
DI 10.1038/nature11891
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 105BE
UT WOS:000316039800044
PM 23446345
DA 2026-03-09
ER

PT J
AU Werner, N
   Urban, O
   Simionescu, A
   Allen, SW
AF Werner, Norbert
   Urban, Ondrej
   Simionescu, Aurora
   Allen, Steven W.
TI A uniform metal distribution in the intergalactic medium of the Perseus cluster of galaxies
SO NATURE
LA English
DT Article
ID iron content; abundances; evolution; metallicity; enrichment; baryons; origin; gas
AB Most of the metals (elements heavier than helium) produced by stars in the member galaxies of clusters currently reside within the hot, X-ray-emitting intra-cluster gas. Observations of X-ray line emission from this intergalactic medium have suggested a relatively small cluster-to-cluster scatter outside the cluster centres(1,2) and enrichment with iron out to large radii(3-5), leading to the idea that the metal enrichment occurred early in the history of the Universe(3). Models with early enrichment predict a uniform metal distribution at large radii in clusters, whereas those with late-time enrichment(6,7) are expected to introduce significant spatial variations of the metallicity. To discriminate clearly between these competing models, it is essential to test for potential inhomogeneities by measuring the abundances out to large radii along multiple directions in clusters, which has not hitherto been done. Here we report a remarkably uniform iron abundance, as a function of radius and azimuth, that is statistically consistent with a constant value of Z(Fe) = 0.306 +/- 0.012 in solar units out to the edge of the nearby Perseus cluster. This homogeneous distribution requires that most of the metal enrichment of the intergalactic medium occurred before the cluster formed, probably more than ten billion years ago, during the period of maximal star formation and black hole activity.
C1 [Werner, Norbert; Urban, Ondrej; Simionescu, Aurora; Allen, Steven W.] Stanford Univ, Kavli Inst Particle Astrophys & Cosmol, Stanford, CA 94305 USA.
   [Werner, Norbert; Urban, Ondrej; Simionescu, Aurora; Allen, Steven W.] Stanford Univ, Dept Phys, Stanford, CA 94305 USA.
   [Urban, Ondrej; Allen, Steven W.] SLAC Natl Accelerator Lab, Menlo Pk, CA 94025 USA.
   [Simionescu, Aurora] JAXA, Inst Space & Astronaut Sci ISAS, Chuo Ku, Sagamihara, Kanagawa 2525210, Japan.
C3 Stanford University; Stanford University; Stanford University; United States Department of Energy (DOE); SLAC National Accelerator Laboratory; Japan Aerospace Exploration Agency (JAXA); Institute of Space & Astronautical Science (ISAS)
RP Werner, N (corresponding author), Stanford Univ, Kavli Inst Particle Astrophys & Cosmol, 452 Lomita Mall, Stanford, CA 94305 USA.
EM norbertw@stanford.edu
FU Suzaku grants [NNX09AV64G, NNX10AR48G]; NASA ADAP grant [NNX12AE05G]; US Department of Energy [DE-AC02-76SF00515]; NASA [53385, NNX12AE05G] Funding Source: Federal RePORTER
NR 29
TC 127
Z9 133
U1 0
U2 16
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 31
PY 2013
VL 502
IS 7473
BP 656
EP 658
DI 10.1038/nature12646
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 243CC
UT WOS:000326293200041
PM 24172976
DA 2026-03-09
ER

PT J
AU Donà, E
   Barry, JD
   Valentin, G
   Quirin, C
   Khmelinskii, A
   Kunze, A
   Durdu, S
   Newton, LR
   Fernandez-Minan, A
   Huber, W
   Knop, M
   Gilmour, D
AF Dona, Erika
   Barry, Joseph D.
   Valentin, Guillaume
   Quirin, Charlotte
   Khmelinskii, Anton
   Kunze, Andreas
   Durdu, Sevi
   Newton, Lionel R.
   Fernandez-Minan, Ana
   Huber, Wolfgang
   Knop, Michael
   Gilmour, Darren
TI Directional tissue migration through a self-generated chemokine gradient
SO NATURE
LA English
DT Article
ID collective cell-migration; lateral-line; cxcr7; receptor; guidance; target; ligand; cxcl12
AB The directed migration of cell collectives is a driving force of embryogenesis(1-3). The predominant view in the field is that cells in embryos navigate along pre-patterned chemoattractant gradients(2). One hypothetical way to free migrating collectives from the requirement of long-range gradients would be through the self-generation of local gradients that travel with them(4,5), a strategy that potentially allows self-determined directionality. However, a lack of tools for the visualization of endogenous guidance cues has prevented the demonstration of such self-generated gradients in vivo. Here we define the in vivo dynamics of one key guidance molecule, the chemokine Cxcl12a, by applying a fluorescent timer approach to measure ligand-triggered receptor turnover in living animals. Using the zebrafish lateral line primordium as a model, we show that migrating cell collectives can self-generate gradients of chemokine activity across their length via polarized receptor-mediated internalization. Finally, by engineering an external source of the atypical receptor Cxcr7 that moves with the primordium, we show that a self-generated gradient mechanism is sufficient to direct robust collective migration. This study thus provides, to our knowledge, the first in vivo proof for self-directed tissue migration through local shaping of an extracellular cue and provides a framework for investigating self-directed migration in many other contexts including cancer invasion(6).
C1 [Dona, Erika; Barry, Joseph D.; Valentin, Guillaume; Quirin, Charlotte; Kunze, Andreas; Durdu, Sevi; Newton, Lionel R.; Fernandez-Minan, Ana; Huber, Wolfgang; Gilmour, Darren] EMBL Heidelberg, D-69117 Heidelberg, Germany.
   [Khmelinskii, Anton; Knop, Michael] Heidelberg Univ, Zentrum Mol Biol, Deutsch Krebsforschungszentrum, DKFZ ZMBH Allianz, D-69120 Heidelberg, Germany.
C3 European Molecular Biology Laboratory (EMBL); Ruprecht Karls University Heidelberg; Helmholtz Association; German Cancer Research Center (DKFZ)
RP Gilmour, D (corresponding author), EMBL Heidelberg, Meyerhofstr 1, D-69117 Heidelberg, Germany.
EM gilmour@embl.de
FU European Commission's FP7 Network of Excellence 'Systems Microscopy'; Marie Curie FP6; European Molecular Biology Organization; Deutsche Forschungsgemeinschaft [SFB 488]
NR 35
TC 282
Z9 336
U1 0
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 NOV 14
PY 2013
VL 503
IS 7475
BP 285
EP +
DI 10.1038/nature12635
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 250YX
UT WOS:000326894200056
PM 24067609
DA 2026-03-09
ER

PT J
AU Liu, SH
   Zhang, Y
   Moayeri, M
   Liu, J
   Crown, D
   Fattah, RJ
   Wein, AN
   Yu, ZX
   Finkel, T
   Leppla, SH
AF Liu, Shihui
   Zhang, Yi
   Moayeri, Mahtab
   Liu, Jie
   Crown, Devorah
   Fattah, Rasem J.
   Wein, Alexander N.
   Yu, Zu-Xi
   Finkel, Toren
   Leppla, Stephen H.
TI Key tissue targets responsible for anthrax-toxin-induced lethality
SO NATURE
LA English
DT Article
ID capillary morphogenesis protein-2; bacillus-anthracis; cre-recombinase; inhalational anthrax; cellular receptor; kinase-kinase; in-vivo; cells; mouse; mice
AB Bacillus anthracis, the causative agent of anthrax disease, is lethal owing to the actions of two exotoxins: anthrax lethal toxin (LT) and oedema toxin (ET). The key tissue targets responsible for the lethal effects of these toxins are unknown. Here we generated cell-type-specific anthrax toxin receptor capillary morphogenesis protein-2 (CMG2)-null mice and cell-type-specific CMG2-expressing mice and challenged them with the toxins. Our results show that lethality induced by LT and ET occurs through damage to distinct cell types; whereas targeting cardiomyocytes and vascular smooth muscle cells is required for LT-induced mortality, ET-induced lethality occurs mainly through its action in hepatocytes. Notably, and in contradiction to what has been previously postulated, targeting of endothelial cells by either toxin does not seem to contribute significantly to lethality. Our findings demonstrate that B. anthracis has evolved to use LT and ET to induce host lethality by coordinately damaging two distinct vital systems.
C1 [Liu, Shihui; Zhang, Yi; Moayeri, Mahtab; Crown, Devorah; Fattah, Rasem J.; Wein, Alexander N.; Leppla, Stephen H.] NIAID, Microbial Pathogenesis Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
   [Liu, Jie; Finkel, Toren] NHLBI, Ctr Mol Med, NIH, Bethesda, MD 20892 USA.
   [Yu, Zu-Xi] NHLBI, Pathol Core Facil, NIH, Bethesda, MD 20892 USA.
C3 National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID); National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI); National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI)
RP Liu, SH (corresponding author), NIAID, Microbial Pathogenesis Sect, Parasit Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM shliu@niaid.nih.gov; sleppla@niaid.nih.gov
FU National Institute of Allergy and Infectious Diseases; National Heart, Lung, and Blood Institute, National Institutes of Health; National Heart Lung and Blood Institute [ZICHL005904] Funding Source: NIH RePORTER; National Institute of Allergy and Infectious Diseases [ZIAAI001032] Funding Source: NIH RePORTER; National Institute of General Medical Sciences [T32GM008169] Funding Source: NIH RePORTER
NR 44
TC 91
Z9 107
U1 3
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 SEP 5
PY 2013
VL 501
IS 7465
BP 63
EP +
DI 10.1038/nature12510
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 211ER
UT WOS:000323888300032
PM 23995686
DA 2026-03-09
ER

PT J
AU Li, S
   Zhang, L
   Yao, Q
   Li, L
   Dong, N
   Rong, J
   Gao, WQ
   Ding, XJ
   Sun, LM
   Chen, X
   Chen, S
   Shao, F
AF Li, Shan
   Zhang, Li
   Yao, Qing
   Li, Lin
   Dong, Na
   Rong, Jie
   Gao, Wenqing
   Ding, Xiaojun
   Sun, Liming
   Chen, Xing
   Chen, She
   Shao, Feng
TI Pathogen blocks host death receptor signalling by arginine GlcNAcylation of death domains
SO NATURE
LA English
DT Article
ID necrosis-factor receptor; bacterial effector; protein; tradd; superfamily; nleb; colonization; inhibition; pathways
AB The tumour necrosis factor (TNF) family is crucial for immune homeostasis, cell death and inflammation. These cytokines are recognized by members of the TNF receptor (TNFR) family of death receptors, including TNFR1 and TNFR2, and FAS and TNF-related apoptosis-inducing ligand (TRAIL) receptors(1). Death receptor signalling requires death-domain-mediated homotypic/heterotypic interactions between the receptor and its downstream adaptors, including TNFR1-associated death domain protein (TRADD) and FAS-associated death domain protein (FADD)(2). Here we discover that death domains in several proteins, including TRADD, FADD, RIPK1 and TNFR1, were directly inactivated by NleB, an entero-pathogenic Escherichia coli (EPEC) type III secretion system effector known to inhibit host nuclear factor-kappa B (NF-kappa B) signalling(3,4). NleB contained an unprecedented N-acetylglucosamine (GlcNAc) transferase activity that specifically modified a conserved arginine in these death domains (Arg 235 in the TRADD death domain). NleB GlcNAcylation (the addition of GlcNAc onto a protein side chain) of death domains blocked homotypic/heterotypic death domain interactions and assembly of the oligomeric TNFR1 complex, thereby disrupting TNF signalling in EPEC-infected cells, including NF-kappa B signalling, apoptosis and necroptosis. Type-III-delivered NleB also blocked FAS ligand and TRAIL-induced cell death by preventing formation of a FADD-mediated death-inducing signalling complex (DISC). The arginine GlcNAc transferase activity of NleB was required for bacterial colonization in the mouse model of EPEC infection. The mechanism of action of NleB represents a new model by which bacteria counteract host defences, and also a previously unappreciated post-translational modification.
C1 [Li, Shan; Yao, Qing] China Agr Univ, Coll Biol Sci, Beijing 100094, Peoples R China.
   [Li, Shan; Zhang, Li; Yao, Qing; Li, Lin; Dong, Na; Gao, Wenqing; Ding, Xiaojun; Sun, Liming; Chen, She; Shao, Feng] Natl Inst Biol Sci, Beijing 102206, Peoples R China.
   [Zhang, Li] Chinese Acad Med Sci, Grad Sch, Beijing 100730, Peoples R China.
   [Zhang, Li] Beijing Union Med Coll, Beijing 100730, Peoples R China.
   [Rong, Jie; Chen, Xing] Peking Univ, Coll Chem & Mol Engn, Dept Biol Chem, Beijing Natl Lab Mol Sci, Beijing 100871, Peoples R China.
C3 China Agricultural University; 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; Chinese Academy of Sciences; Peking University
RP Chen, S (corresponding author), Natl Inst Biol Sci, Beijing 102206, Peoples R China.
EM chenshe@nibs.ac.cn; shaofeng@nibs.ac.cn
FU Howard Hughes Medical Institute; National Basic Research Program of China 973 Programs [2010CB835400, 2012CB518700, 2010CB835204]
NR 38
TC 230
Z9 280
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 SEP 12
PY 2013
VL 501
IS 7466
BP 242
EP +
DI 10.1038/nature12436
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 215XR
UT WOS:000324244900045
PM 23955153
DA 2026-03-09
ER

PT J
AU Kanai, R
   Ogawa, H
   Vilsen, B
   Cornelius, F
   Toyoshima, C
AF Kanai, Ryuta
   Ogawa, Haruo
   Vilsen, Bente
   Cornelius, Flemming
   Toyoshima, Chikashi
TI Crystal structure of a Na+-bound Na+,K+-ATPase preceding the E1P state
SO NATURE
LA English
DT Article
ID cytoplasmic-binding sites; rat-kidney na+,k+-atpase; sodium-potassium pump; alpha-subunit; transmembrane segment; calcium-pump; k+-atpase; terminal tyrosines; cation-binding; na,k-atpase
AB Na+,K+-ATPase pumps three Na+ ions out of cells in exchange for two K+ taken up from the extracellular medium per ATP molecule hydrolysed, thereby establishing Na+ and K+ gradients across the membrane in all animal cells. These ion gradients are used in many fundamental processes, notably excitation of nerve cells. Here we describe 2.8 angstrom-resolution crystal structures of this ATPase from pig kidney with bound Na+, ADP and aluminium fluoride, a stable phosphate analogue, with and without oligomycin that promotes Na+ occlusion. These crystal structures represent a transition state preceding the phosphorylated intermediate (E1P) in which three Na+ ions are occluded. Details of the Na+-binding sites show how this ATPase functions as a Na+-specific pump, rejecting K+ and Ca2+, even though its affinity for Na+ is low (millimolar dissociation constant). A mechanism for sequential, cooperative Na+ binding can now be formulated in atomic detail.
C1 [Kanai, Ryuta; Ogawa, Haruo; Toyoshima, Chikashi] Univ Tokyo, Inst Mol & Cellular Biosci, Bunkyo Ku, Tokyo 1130032, Japan.
   [Vilsen, Bente; Cornelius, Flemming] Aarhus Univ, Dept Biomed, DK-8000 Aarhus C, Denmark.
C3 University of Tokyo; Aarhus University
RP Toyoshima, C (corresponding author), Univ Tokyo, Inst Mol & Cellular Biosci, Bunkyo Ku, Tokyo 1130032, Japan.
EM ct@iam.u-tokyo.ac.jp
FU Ministry of Education, Culture, Sports, Science and Technology of Japan [2009B0025]; Lundbeck Foundation; Novo Nordisk Foundation; Fabrikant Vilhelm Pedersen og Hustrus Legat; Danish Medical Research Council; FI/Danish-Japanese cooperation program from the Danish Agency for Science Technology and Innovation; Grants-in-Aid for Scientific Research [23000014, 25650020] Funding Source: KAKEN; Lundbeck Foundation [R48-2009-4638, R118-2012-11726] Funding Source: researchfish
NR 51
TC 260
Z9 279
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 OCT 10
PY 2013
VL 502
IS 7470
BP 201
EP +
DI 10.1038/nature12578
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 231RU
UT WOS:000325436100043
PM 24089211
DA 2026-03-09
ER

PT J
AU Schneider, C
   Rahimi-Iman, A
   Kim, NY
   Fischer, J
   Savenko, IG
   Amthor, M
   Lermer, M
   Wolf, A
   Worschech, L
   Kulakovskii, VD
   Shelykh, IA
   Kamp, M
   Reitzenstein, S
   Forchel, A
   Yamamoto, Y
   Höfling, S
AF Schneider, Christian
   Rahimi-Iman, Arash
   Kim, Na Young
   Fischer, Julian
   Savenko, Ivan G.
   Amthor, Matthias
   Lermer, Matthias
   Wolf, Adriana
   Worschech, Lukas
   Kulakovskii, Vladimir D.
   Shelykh, Ivan A.
   Kamp, Martin
   Reitzenstein, Stephan
   Forchel, Alfred
   Yamamoto, Yoshihisa
   Hoefling, Sven
TI An electrically pumped polariton laser
SO NATURE
LA English
DT Article
ID bose-einstein condensation; semiconductor microcavity; exciton-polaritons
AB Conventional semiconductor laser emission relies on stimulated emission of photons(1,2), which sets stringent requirements on the minimum amount of energy necessary for its operation(3,4). In comparison, exciton-polaritons in strongly coupled quantum well microcavities(5) can undergo stimulated scattering that promises more energy-efficient generation of coherent light by 'polariton lasers'(3,6). Polariton laser operation has been demonstrated in optically pumped semiconductor microcavities at temperatures up to room temperature(7-12), and such lasers can outperform their weak-coupling counterparts in that they have a lower threshold density(12,13). Even though polariton diodes have been realized(14-16), electrically pumped polariton laser operation, which is essential for practical applications, has not been achieved until now. Here we present an electrically pumped polariton laser based on a microcavity containing multiple quantum wells. To prove polariton laser emission unambiguously, we apply a magnetic field and probe the hybrid light-matter nature of the polaritons. Our results represent an important step towards the practical implementation of polaritonic light sources and electrically injected condensates, and can be extended to room-temperature operation using wide-bandgap materials.
C1 [Schneider, Christian; Rahimi-Iman, Arash; Fischer, Julian; Amthor, Matthias; Lermer, Matthias; Wolf, Adriana; Worschech, Lukas; Kamp, Martin; Reitzenstein, Stephan; Forchel, Alfred; Hoefling, Sven] Univ Wurzburg, Tech Phys & Wilhelm Conrad Rontgen Res Ctr Comple, Hubland, D-97074 Wurzburg, Germany.
   [Kim, Na Young; Yamamoto, Yoshihisa] Stanford Univ, EL Ginzton Lab, Stanford, CA 94305 USA.
   [Kim, Na Young] Univ Tokyo, Inst Ind Sci, Meguro Ku, Tokyo 1538505, Japan.
   [Savenko, Ivan G.; Shelykh, Ivan A.] Univ Iceland, Inst Sci, IS-107 Reykjavik, Iceland.
   [Savenko, Ivan G.; Shelykh, Ivan A.] Nanyang Technol Univ, Div Phys & Appl Phys, Singapore 637371, Singapore.
   [Kulakovskii, Vladimir D.] Russian Acad Sci, Inst Solid State Phys, Chernogolovka 142432, Russia.
   [Reitzenstein, Stephan] Tech Univ Berlin, Inst Festkorperphys, D-10623 Berlin, Germany.
   [Yamamoto, Yoshihisa] Natl Inst Informat, Chiyoda Ku, Tokyo 1018430, Japan.
C3 University of Wurzburg; Stanford University; University of Tokyo; University of Iceland; Nanyang Technological University; Russian Academy of Sciences; Osipyan Institute of Solid State Physics RAS; Technical University of Berlin; Research Organization of Information & Systems (ROIS); National Institute of Informatics (NII) - Japan
RP Höfling, S (corresponding author), Univ Wurzburg, Tech Phys & Wilhelm Conrad Rontgen Res Ctr Comple, Hubland, D-97074 Wurzburg, Germany.
EM christian.schneider@physik.uni-wuerzburg.de; sven.hoefling@physik.uni-wuerzburg.de
FU State of Bavaria; National Science Foundation; JSPS through its FIRST programme; Eimskip foundation; 'Center of excellence in polaritonics', IRSES SPINMET project; 'Center of excellence in polaritonics', POLAPHEN project; German National Academic Foundation
NR 32
TC 458
Z9 504
U1 1
U2 426
PU NATURE PUBLISHING 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 16
PY 2013
VL 497
IS 7449
BP 348
EP 352
DI 10.1038/nature12036
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 144PN
UT WOS:000318952000033
PM 23676752
DA 2026-03-09
ER

PT J
AU Ding, L
   Morrison, SJ
AF Ding, Lei
   Morrison, Sean J.
TI Haematopoietic stem cells and early lymphoid progenitors occupy distinct bone marrow niches
SO NATURE
LA English
DT Article
ID b-cell; stem/progenitor cells; cre recombinase; factor-i; mice; identification; lymphopoiesis; osteoblasts; maintenance; expression
AB Although haematopoietic stem cells (HSCs) are commonly assumed to reside within a specialized microenvironment, or niche(1), most published experimental manipulations of the HSC niche have affected the function of diverse restricted progenitors. This raises the fundamental question, of whether HSCs1 and restricted progenitors(2,3) reside within distinct, specialized niches or whether they share a common niche. Here we assess the physiological sources of the chemokine CXCL12 for HSC and restricted progenitor maintenance. Cxcl12(DsRed) knock-in mice (DsRed-Express2 recombined into the Cxcl12 locus) showed that Cxcl12 was primarily expressed by perivascular stromal cells and, at lower levels, by endothelial cells, osteoblasts and some haematopoietic cells. Conditional deletion of Cxcl12 from haematopoietic cells or nestin-cre-expressing cells had little or no effect on HSCs or restricted progenitors. Deletion of Cxcl12 from endothelial cells depleted HSCs but not myeloerythroid or lymphoid progenitors. Deletion of Cxcl12 from perivascular stromal cells depleted HSCs and certain restricted progenitors and mobilized these cells into circulation. Deletion of Cxcl12 from osteoblasts depleted certain early lymphoid progenitors but not HSCs or myeloerythroid progenitors, and did not mobilize these cells into circulation. Different stem and progenitor cells thus reside in distinct cellular niches in bone marrow: HSCs occupy a perivascular niche and early lymphoid progenitors occupy an endosteal niche.
C1 [Ding, Lei; Morrison, Sean J.] Univ Texas SW Med Ctr Dallas, Dept Pediat, Childrens Res Inst, Howard Hughes Med Inst, Dallas, TX 75390 USA.
C3 Howard Hughes Medical Institute; University of Texas System; University of Texas Southwestern Medical Center
RP Morrison, SJ (corresponding author), Univ Texas SW Med Ctr Dallas, Dept Pediat, Childrens Res Inst, Howard Hughes Med Inst, 5323 Harry Hines Blvd, Dallas, TX 75390 USA.
EM sean.morrison@utsouthwestern.edu
FU Howard Hughes Medical Institute (HHMI); US National Heart, Lung and Blood Institute [5R01-HL097760]; Helen Hay Whitney Foundation; HHMI; National Cancer Institute [P30CA142543] Funding Source: NIH RePORTER
NR 30
TC 991
Z9 1196
U1 3
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 MAR 14
PY 2013
VL 495
IS 7440
BP 231
EP 235
DI 10.1038/nature11885
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 113FP
UT WOS:000316652300050
PM 23434755
DA 2026-03-09
ER

PT J
AU Rudolph, CJ
   Upton, AL
   Stockum, A
   Nieduszynski, CA
   Lloyd, RG
AF Rudolph, Christian J.
   Upton, Amy L.
   Stockum, Anna
   Nieduszynski, Conrad A.
   Lloyd, Robert G.
TI Avoiding chromosome pathology when replication forks collide
SO NATURE
LA English
DT Article
ID escherichia-coli recg; dna-replication; rna-polymerase; genome instability; transcription; helicase; initiation; mutations; conflicts; recombination
AB Chromosome duplication normally initiates through the assembly of replication fork complexes at defined origins(1,2). DNA synthesis by any one fork is thought to cease when it meets another travelling in the opposite direction, at which stage the replication machinery may simply dissociate before the nascent strands are finally ligated. But what actually happens is not clear. Here we present evidence consistent with the idea that every fork collision has the potential to threaten genomic integrity. In Escherichia coli this threat is kept at bay by RecG DNA translocase(3) and by single-strand DNA exonucleases. Without RecG, replication initiates where forks meet through a replisome assembly mechanism normally associated with fork repair, replication restart and recombination(4,5), establishing new forks with the potential to sustain cell growth and division without an active origin. This potential is realized when roadblocks to fork progression are reduced or eliminated. It relies on the chromosome being circular, reinforcing the idea that replication initiation is triggered repeatedly by fork collision. The results reported raise the question of whether replication fork collisions have pathogenic potential for organisms that exploit several origins to replicate each chromosome.
C1 [Rudolph, Christian J.; Upton, Amy L.; Stockum, Anna; Nieduszynski, Conrad A.; Lloyd, Robert G.] Univ Nottingham, Queens Med Ctr, Ctr Genet & Genom, Nottingham NG7 2UH, England.
   [Rudolph, Christian J.; Upton, Amy L.] Brunel Univ, Div Biosci, Sch Hlth Sci & Social Care, London UB8 3PH, England.
C3 University of Nottingham; Brunel University
RP Rudolph, CJ (corresponding author), Univ Nottingham, Queens Med Ctr, Ctr Genet & Genom, Nottingham NG7 2UH, England.
EM christian.rudolph@brunel.ac.uk
FU MRC [G0800970]; Leverhulme Trust; BBSRC [BB/E023754/1]; Biotechnology and Biological Sciences Research Council [BB/E023754/1] Funding Source: researchfish; Medical Research Council [G0800970] Funding Source: researchfish; BBSRC [BB/E023754/1] Funding Source: UKRI; MRC [G0800970] Funding Source: UKRI
NR 31
TC 109
Z9 124
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 AUG 29
PY 2013
VL 500
IS 7464
BP 608
EP +
DI 10.1038/nature12312
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 207TD
UT WOS:000323625900041
PM 23892781
DA 2026-03-09
ER

PT J
AU Ibata, RA
   Lewis, GF
   Conn, AR
   Irwin, MJ
   McConnachie, AW
   Chapman, SC
   Collins, ML
   Fardal, M
   Ferguson, AMN
   Ibata, NG
   Mackey, AD
   Martin, NF
   Navarro, J
   Rich, RM
   Valls-Gabaud, D
   Widrow, LM
AF Ibata, Rodrigo A.
   Lewis, Geraint F.
   Conn, Anthony R.
   Irwin, Michael J.
   McConnachie, Alan W.
   Chapman, Scott C.
   Collins, Michelle L.
   Fardal, Mark
   Ferguson, Annette M. N.
   Ibata, Neil G.
   Mackey, A. Dougal
   Martin, Nicolas F.
   Navarro, Julio
   Rich, R. Michael
   Valls-Gabaud, David
   Widrow, Lawrence M.
TI A vast, thin plane of corotating dwarf galaxies orbiting the Andromeda galaxy
SO NATURE
LA English
DT Article
ID red giant branch; anisotropic distribution; satellite galaxy; bayesian-approach; milky-way; tip; velocity; mass
AB Dwarf satellite galaxies are thought to be the remnants of the population of primordial structures that coalesced to form giant galaxies like the Milky Way(1). It has previously been suspected(2) that dwarf galaxies may not be isotropically distributed around our Galaxy, because several are correlated with streams of H I emission, and may form coplanar groups(3). These suspicions are supported by recent analyses(4-7). It has been claimed(7) that the apparently planar distribution of satellites is not predicted within standard cosmology(8), and cannot simply represent a memory of past coherent accretion. However, other studies dispute this conclusion(9-11). Here we report the existence of a planar subgroup of satellites in the Andromeda galaxy (M 31), comprising about half of the population. The structure is at least 400 kiloparsecs in diameter, but also extremely thin, with a perpendicular scatter of less than 14.1 kiloparsecs. Radial velocity measurements(12-15) reveal that the satellites in this structure have the same sense of rotation about their host. This shows conclusively that substantial numbers of dwarf satellite galaxies share the same dynamical orbital properties and direction of angular momentum. Intriguingly, the plane we identify is approximately aligned with the pole of the Milky Way's disk and with the vector between the Milky Way and Andromeda.
C1 [Ibata, Rodrigo A.; Martin, Nicolas F.] Observ Astron, F-67000 Strasbourg, France.
   [Lewis, Geraint F.] Univ Sydney, Sch Phys, Sydney Inst Astron, Sydney, NSW 2006, Australia.
   [Conn, Anthony R.] Macquarie Univ, Dept Phys & Astron, N Ryde, NSW 2109, Australia.
   [Irwin, Michael J.] Univ Cambridge, Inst Astron, Cambridge CB3 0HA, England.
   [McConnachie, Alan W.] NRC Herzberg Inst Astrophys, Victoria, BC V9E 2E7, Canada.
   [Chapman, Scott C.] Dalhousie Univ, Dept Phys & Atmospher Sci, Halifax, NS B3H 4R2, Canada.
   [Collins, Michelle L.; Martin, Nicolas F.] Max Planck Inst Astron, D-69117 Heidelberg, Germany.
   [Fardal, Mark] Univ Massachusetts, Dept Astron, Amherst, MA 01003 USA.
   [Ferguson, Annette M. N.] Univ Edinburgh, Inst Astron, Royal Observ, Edinburgh EH9 3HJ, Midlothian, Scotland.
   [Ibata, Neil G.] Lyce Int Pontonniers, F-67000 Strasbourg, France.
   [Mackey, A. Dougal] Australian Natl Univ, Mt Stromlo Observ, Weston, ACT 2611, Australia.
   [Navarro, Julio] Univ Victoria, Dept Phys & Astron, Victoria, BC V8P 5C2, Canada.
   [Rich, R. Michael] Univ Calif Los Angeles, Dept Phys & Astron, Los Angeles, CA 90095 USA.
   [Valls-Gabaud, David] Observ Paris, LERMA, CNRS, UMR 8112, F-75014 Paris, France.
   [Widrow, Lawrence M.] Queens Univ, Dept Phys Engn Phys & Astron, Kingston, ON K7L 3N6, Canada.
C3 University of Sydney; Macquarie University; University of Cambridge; National Research Council Canada; Dalhousie University; Max Planck Society; University of Massachusetts System; University of Massachusetts Amherst; University of Edinburgh; Australian National University; University of Victoria; University of California System; University of California Los Angeles; Sorbonne Universite; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Earth Sciences & Astronomy (INSU); Universite PSL; Observatoire de Paris; Queens University - Canada
RP Ibata, RA (corresponding author), Observ Astron, 11 Rue Univ, F-67000 Strasbourg, France.
EM rodrigo.ibata@astro.unistra.fr
FU Agence Nationale de la Recherche; Australian Research Council; W.M. Keck Foundation; Science and Technology Facilities Council [ST/H004165/1, ST/J001538/1, ST/J000647/1, ST/J00541X/1, PP/C002229/1, ST/J001422/1, ST/H00243X/1, ST/H004157/1] Funding Source: researchfish; Division Of Astronomical Sciences; Direct For Mathematical & Physical Scien [1009652] Funding Source: National Science Foundation; STFC [ST/J001538/1, ST/H004157/1, ST/J001422/1, ST/H004165/1, PP/C002229/1, ST/J00541X/1, ST/J000647/1] Funding Source: UKRI
NR 26
TC 438
Z9 477
U1 0
U2 34
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 3
PY 2013
VL 493
IS 7430
BP 62
EP 65
DI 10.1038/nature11717
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 062QC
UT WOS:000312933800030
PM 23282362
DA 2026-03-09
ER

PT J
AU Fukuda, T
   Takeda, S
   Xu, R
   Ochi, H
   Sunamura, S
   Sato, T
   Shibata, S
   Yoshida, Y
   Gu, ZR
   Kimura, A
   Ma, CS
   Xu, C
   Bando, W
   Fujita, K
   Shinomiya, K
   Hirai, T
   Asou, Y
   Enomoto, M
   Okano, H
   Okawa, A
   Itoh, H
AF Fukuda, Toru
   Takeda, Shu
   Xu, Ren
   Ochi, Hiroki
   Sunamura, Satoko
   Sato, Tsuyoshi
   Shibata, Shinsuke
   Yoshida, Yutaka
   Gu, Zirong
   Kimura, Ayako
   Ma, Chengshan
   Xu, Cheng
   Bando, Waka
   Fujita, Koji
   Shinomiya, Kenichi
   Hirai, Takashi
   Asou, Yoshinori
   Enomoto, Mitsuhiro
   Okano, Hideyuki
   Okawa, Atsushi
   Itoh, Hiroshi
TI Sema3A regulates bone-mass accrual through sensory innervations
SO NATURE
LA English
DT Article
ID sympathetic innervation; immune-responses; semaphorin; cells; maintenance; expression; ablation; roles
AB Semaphorin 3A (Sema3A) is a diffusible axonal chemorepellent that has an important role in axon guidance(1-5). Previous studies have demonstrated that Sema3a(-/-) mice have multiple developmental defects due to abnormal neuronal innervations(6,7). Here we show in mice that Sema3A is abundantly expressed in bone, and cell-based assays showed that Sema3A affected osteoblast differentiation in a cell-autonomous fashion. Accordingly, Sema3a(-/-) mice had a low bone mass due to decreased bone formation. However, osteoblast-specific Sema3A-deficient mice (Sema3a(coli)(-/-) and Sema3a(osx)(-/-) mice) had normal bone mass, even though the expression of Sema3A in bone was substantially decreased. In contrast, mice lacking Sema3A in neurons (Sema3a(synapsin)(-/-) and Sema3a(nestin)(-/-) mice) had low bone mass, similar to Sema3a(-/-) mice, indicating that neuron-derived Sema3A is responsible for the observed bone abnormalities independent of the local effect of Sema3A in bone. Indeed, the number of sensory innervations of trabecular bone was significantly decreased in Sema3a(synapsin)(-/-) mice, whereas sympathetic innervations of trabecular bone were unchanged. Moreover, ablating sensory nerves decreased bone mass in wild-type mice, whereas it did not reduce the low bone mass in Sema3a(nestin)(-/-) mice further, supporting the essential role of the sensory nervous system in normal bone homeostasis. Finally, neuronal abnormalities in Sema3a(-/-) mice, such as olfactory development, were identified in Sema3a(synasin)(-/-) mice, demonstrating that neuron-derived Sema3A contributes to the abnormal neural development seen in Sema3a(-/-) mice, and indicating that Sema3A produced in neurons regulates neural development in an autocrine manner. This study demonstrates that Sema3A regulates bone remodelling indirectly by modulating sensory nerve development, but not directly by acting on osteoblasts.
C1 [Fukuda, Toru; Takeda, Shu; Ochi, Hiroki; Sunamura, Satoko] Keio Univ, Sch Med, Dept Internal Med, Shinjyuku Ku, Tokyo 1608582, Japan.
   [Xu, Ren; Kimura, Ayako; Ma, Chengshan; Xu, Cheng; Fujita, Koji; Shinomiya, Kenichi; Hirai, Takashi; Asou, Yoshinori; Enomoto, Mitsuhiro; Okawa, Atsushi] Tokyo Med & Dent Univ, Dept Orthoped Surg, Bunkyo Ku, Tokyo 1138549, Japan.
   [Xu, Ren; Ma, Chengshan; Xu, Cheng; Fujita, Koji; Okawa, Atsushi] Int Res Ctr Mol Sci Tooth & Bone Dis, Global Ctr Excellence GCOE Program, Bunkyo Ku, Tokyo 1138549, Japan.
   [Sato, Tsuyoshi] Saitama Med Univ, Dept Oral & Maxillofacial Surg, Moroyama, Saitama 3500495, Japan.
   [Shibata, Shinsuke; Okano, Hideyuki] Keio Univ, Sch Med, Dept Physiol, Shinjyuku Ku, Tokyo 1608582, Japan.
   [Yoshida, Yutaka; Gu, Zirong] Cincinnati Childrens Hosp Med Ctr, Div Dev Biol, Cincinnati, OH 45229 USA.
   [Kimura, Ayako] Tokyo Med & Dent Univ, Hard Tissue Genome Res Ctr, Bunkyo Ku, Tokyo 1138549, Japan.
   [Bando, Waka; Itoh, Hiroshi] Keio Univ, Sch Med, Dept Internal Med, Sect Nephrol Endocrinol & Metab,Shinjyuku Ku, Tokyo 1608582, Japan.
C3 Keio University; Institute of Science Tokyo; Tokyo Medical & Dental University (TMDU); Saitama Medical University; Keio University; Cincinnati Children's Hospital Medical Center; Institute of Science Tokyo; Tokyo Medical & Dental University (TMDU); Keio University
RP Takeda, S (corresponding author), Keio Univ, Sch Med, Dept Internal Med, Shinjyuku Ku, Shinanomachi 35, Tokyo 1608582, Japan.
EM shu-tky@umin.ac.jp
FU Funding Program for Next Generation World-Leading Researchers (NEXT Program); Japan Society for the Promotion of Science; National Institute of Neurological Disorders and Stroke [NS065048]; Grants-in-Aid for Scientific Research [25670637, 24791565, 24592257] Funding Source: KAKEN
NR 36
TC 340
Z9 405
U1 4
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 23
PY 2013
VL 497
IS 7450
BP 490
EP +
DI 10.1038/nature12115
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 148OG
UT WOS:000319254000048
PM 23644455
DA 2026-03-09
ER

PT J
AU Campbell, SW
   D'Orazi, V
   Yong, D
   Constantino, TN
   Lattanzio, JC
   Stancliffe, RJ
   Angelou, GC
   Wylie-de Boer, EC
   Grundahl, F
AF Campbell, Simon W.
   D'Orazi, Valentina
   Yong, David
   Constantino, Thomas N.
   Lattanzio, John C.
   Stancliffe, Richard J.
   Angelou, George C.
   Wylie-de Boer, Elizabeth C.
   Grundahl, Frank
TI Sodium content as a predictor of the advanced evolution of globular cluster stars
SO NATURE
LA English
DT Article
ID horizontal-branch stars; metal-poor stars; giant stars; light-elements; helium content; red giant; ngc-6752; abundances; scale
AB The asymptotic giant branch (AGB) phase is the final stage of nuclear burning for low-mass stars. Although Milky Way globular clusters are now known to harbour (at least) two generations of stars(1,2), they still provide relatively homogeneous samples of stars that are used to constrain stellar evolution theory(3-5). It is predicted by stellar models that the majority of cluster stars with masses around the current turn-off mass (that is, the mass of the stars that are currently leaving the main sequence phase) will evolve through the AGB phase(6,7). Here we report that all of the second-generation stars in the globular cluster NGC 6752-70 per cent of the cluster population-fail to reach the AGB phase. Through spectroscopic abundance measurements, we found that every AGB star in our sample has a low sodium abundance, indicating that they are exclusively first-generation stars. This implies that many clusters cannot reliably be used for star counts to test stellar evolution timescales if the AGB population is included. We have no clear explanation for this observation.
C1 [Campbell, Simon W.; D'Orazi, Valentina; Constantino, Thomas N.; Lattanzio, John C.; Angelou, George C.] Monash Univ, Sch Math Sci, Monash Ctr Astrophys, Melbourne, Vic 3800, Australia.
   [D'Orazi, Valentina] Macquarie Univ, Dept Phys & Astron, Sydney, NSW 2109, Australia.
   [Yong, David; Stancliffe, Richard J.; Wylie-de Boer, Elizabeth C.] Australian Natl Univ, Res Sch Astron & Astrophys, Weston, ACT 2611, Australia.
   [Stancliffe, Richard J.] Univ Bonn, Argelander Inst Astron, D-53121 Bonn, Germany.
   [Grundahl, Frank] Aarhus Univ, Dept Phys & Astron, Stellar Astrophys Ctr, DK-8000 Aarhus C, Denmark.
C3 Monash University; Macquarie University; Australian National University; University of Bonn; Aarhus University
RP Campbell, SW (corresponding author), Monash Univ, Sch Math Sci, Monash Ctr Astrophys, Melbourne, Vic 3800, Australia.
EM simon.campbell@monash.edu
FU Australian Research Council [DP1095368]; Alexander von Humboldt Foundation; Danish National Research Foundation; ASTERISK project; European Research Council [267864]; ESO telescopes at the La Silla Paranal Observatory [089.D-0038]; Australian Research Council [DP1095368] Funding Source: Australian Research Council
NR 28
TC 72
Z9 79
U1 0
U2 15
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 13
PY 2013
VL 498
IS 7453
BP 198
EP 200
DI 10.1038/nature12191
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 162RR
UT WOS:000320283400040
PM 23719375
DA 2026-03-09
ER

PT J
AU Chung, HS
   Eaton, WA
AF Chung, Hoi Sung
   Eaton, William A.
TI Single-molecule fluorescence probes dynamics of barrier crossing
SO NATURE
LA English
DT Article
ID solvent viscosity; internal-friction; folding rates; protein; dependence; kinetics; states; force; model
AB Kramers developed the theory on how chemical reaction rates are influenced by the viscosity of the medium(1,2). At the viscosity of water, the kinetics of unimolecular reactions are described by diffusion of a Brownian particle over a free-energy barrier separating reactants and products. For reactions in solution this famous theory extended Eyring's transition state theory, and is widely applied in physics, chemistry and biology, including to reactions as complex as protein folding(3,4). Because the diffusion coefficient of Kramers' theory is determined by the dynamics in the sparsely populated region of the barrier top, its properties have not been directly measured for any molecular system. Here we show that the Kramers diffusion coefficient and free-energy barrier can be characterized by measuring the temperature- and viscosity-dependence of the transition path time for protein folding. The transition path is the small fraction of an equilibrium trajectory for a single molecule when the free-energy barrier separating two states is actually crossed. Its duration, the transition path time, can now be determined from photon trajectories for single protein molecules undergoing folding/unfolding transitions(5). Our finding of a long transition path time with an unusually small solvent viscosity dependence suggests that internal friction as well as solvent friction determine the Kramers diffusion coefficient for alpha-helical proteins, as opposed to a breakdown of his theory, which occurs for many small-molecule reactions(2). It is noteworthy that the new and fundamental information concerning Kramers' theory and the dynamics of barrier crossings obtained here come from experiments on a protein rather than a much simpler chemical or physical system.
C1 [Chung, Hoi Sung; Eaton, William A.] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
C3 National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK)
RP Chung, HS (corresponding author), NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
EM chunghoi@niddk.nih.gov; eaton@helix.nih.gov
FU Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health
NR 38
TC 204
Z9 217
U1 2
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 OCT 31
PY 2013
VL 502
IS 7473
BP 685
EP +
DI 10.1038/nature12649
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 243CC
UT WOS:000326293200048
PM 24153185
DA 2026-03-09
ER

PT J
AU Dasgupta, R
   Mallik, A
   Tsuno, K
   Withers, AC
   Hirth, G
   Hirschmann, MM
AF Dasgupta, Rajdeep
   Mallik, Ananya
   Tsuno, Kyusei
   Withers, Anthony C.
   Hirth, Greg
   Hirschmann, Marc M.
TI Carbon-dioxide-rich silicate melt in the Earth's upper mantle
SO NATURE
LA English
DT Article
ID east pacific rise; midocean ridges; electrical-conductivity; peridotite; solidus; beneath; h2o; co2; asthenosphere; heterogeneity
AB The onset of melting in the Earth's upper mantle influences the thermal evolution of the planet, fluxes of key volatiles to the exo-sphere, and geochemical and geophysical properties of the mantle. Although carbonatitic melt could be stable 250 km or less beneath mid-oceanic ridges(1,2), owing to the small fraction (similar to 0.03 wt%) its effects on the mantle properties are unclear. Geophysical measurements, however, suggest that melts of greater volume may be present at similar to 200km (refs 3-5) but large melt fractions are thought to be restricted to shallower depths. Here we present experiments on carbonated peridotites over 2-5 GPa that constrain the location and the slope of the onset of silicate melting in the mantle. We find that the pressure-temperature slope of carbonated silicate melting is steeper than the solidus of volatile-free peridotite and that silicate melting of dry peridotite + CO2 beneath ridges commences at similar to 180 km. Accounting for the effect of 50-200 p.p.m. H2O on freezing point depression, the onset of silicate melting for a sub-ridge mantle with similar to 100 p.p.m. CO2 becomes as deep as similar to 220-300 km. We suggest that, on a global scale, carbonated silicate melt generation at a redox front similar to 250-200 km deep(6), with destabilization of metal and majorite in the upwelling mantle, explains the oceanic low-velocity zone and the electrical conductivity structure of the mantle. In locally oxidized domains, deeper carbonated silicate melt may contribute to the seismic X-discontinuity. Furthermore, our results, along with the electrical conductivity of molten carbonated peridotite(7) and that of the oceanic upper mantle(5), suggest that mantle at depth is CO2-rich but H2O-poor. Finally, carbonated silicate melts restrict the stability of carbonatite in the Earth's deep upper mantle, and the inventory of carbon, H2O and other highly incompatible elements at ridges becomes controlled by the flux of the former.
C1 [Dasgupta, Rajdeep; Mallik, Ananya; Tsuno, Kyusei] Rice Univ, Dept Earth Sci, Houston, TX 77005 USA.
   [Withers, Anthony C.; Hirschmann, Marc M.] Univ Minnesota, Dept Earth Sci, Minneapolis, MN 55455 USA.
   [Hirth, Greg] Brown Univ, Dept Geol Sci, Providence, RI 02912 USA.
C3 Rice University; University of Minnesota System; University of Minnesota Twin Cities; Brown University
RP Dasgupta, R (corresponding author), Rice Univ, Dept Earth Sci, 6100 Main St,MS 126, Houston, TX 77005 USA.
EM Rajdeep.Dasgupta@rice.edu
FU National Science Foundation; Packard fellowship; Directorate For Geosciences; Division Of Earth Sciences [0911442, 1019744] Funding Source: National Science Foundation
NR 34
TC 331
Z9 390
U1 8
U2 298
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 10
PY 2013
VL 493
IS 7431
BP 211
EP U222
DI 10.1038/nature11731
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 066YY
UT WOS:000313259600037
PM 23302861
DA 2026-03-09
ER

PT J
AU Ge, XY
   Li, JL
   Yang, XL
   Chmura, AA
   Zhu, GJ
   Epstein, JH
   Mazet, JK
   Hu, B
   Zhang, W
   Peng, C
   Zhang, YJ
   Luo, CM
   Tan, B
   Wang, N
   Zhu, Y
   Crameri, G
   Zhang, SY
   Wang, LF
   Daszak, P
   Shi, ZL
AF Ge, Xing-Yi
   Li, Jia-Lu
   Yang, Xing-Lou
   Chmura, Aleksei A.
   Zhu, Guangjian
   Epstein, Jonathan H.
   Mazet, Jonna K.
   Hu, Ben
   Zhang, Wei
   Peng, Cheng
   Zhang, Yu-Ji
   Luo, Chu-Ming
   Tan, Bing
   Wang, Ning
   Zhu, Yan
   Crameri, Gary
   Zhang, Shu-Yi
   Wang, Lin-Fa
   Daszak, Peter
   Shi, Zheng-Li
TI Isolation and characterization of a bat SARS-like coronavirus that uses the ACE2 receptor
SO NATURE
LA English
DT Article
ID respiratory syndrome coronavirus; functional receptor; adaptation; diversity; origin
AB The 2002-3 pandemic caused by severe acute respiratory syndrome coronavirus (SARS-CoV) was one of the most significant public health events in recent history(1). An ongoing outbreak of Middle East respiratory syndrome coronavirus(2) suggests that this group of viruses remains a key threat and that their distribution is wider than previously recognized. Although bats have been suggested to be the natural reservoirs of both viruses(3-5), attempts to isolate the progenitor virus of SARS-CoV from bats have been unsuccessful. Diverse SARS-like coronaviruses (SL-CoVs) have now been reported from bats in China, Europe and Africa(5-8), but none is considered a direct progenitor of SARS-CoV because of their phylogenetic disparity from this virus and the inability of their spike proteins to use the SARS-CoV cellular receptor molecule, the human angiotensin converting enzyme II (ACE2)(9,10). Here we report whole-genome sequences of two novel bat coronaviruses from Chinese horseshoe bats (family: Rhinolophidae) in Yunnan, China: RsSHC014 and Rs3367. These viruses are far more closely related to SARS-CoV than any previously identified bat coronaviruses, particularly in the receptor binding domain of the spike protein. Most importantly, we report the first recorded isolation of a live SL-CoV (bat SL-CoV-WIV1) from bat faecal samples in Vero E6 cells, which has typical coronavirus morphology, 99.9% sequence identity to Rs3367 and uses ACE2 from humans, civets and Chinese horseshoe bats for cell entry. Preliminary in vitro testing indicates that WIV1 also has a broad species tropism. Our results provide the strongest evidence to date that Chinese horseshoe bats are natural reservoirs of SARS-CoV, and that intermediate hosts may not be necessary for direct human infection by some bat SL-CoVs. They also highlight the importance of pathogen-discovery programs targeting high-risk wildlife groups in emerging disease hotspots as a strategy for pandemic preparedness.
C1 [Ge, Xing-Yi; Li, Jia-Lu; Yang, Xing-Lou; Hu, Ben; Zhang, Wei; Peng, Cheng; Zhang, Yu-Ji; Luo, Chu-Ming; Tan, Bing; Wang, Ning; Zhu, Yan; Shi, Zheng-Li] Chinese Acad Sci, Wuhan Inst Virol, State Key Lab Virol, Ctr Emerging Infect Dis, Wuhan 430071, Peoples R China.
   [Chmura, Aleksei A.; Zhu, Guangjian; Epstein, Jonathan H.; Daszak, Peter] EcoHlth Alliance, New York, NY 10001 USA.
   [Mazet, Jonna K.] Univ Calif Davis, Sch Vet Med, Hlth Inst 1, Davis, CA 95616 USA.
   [Crameri, Gary; Wang, Lin-Fa] CSIRO Australian Anim Hlth Lab, Geelong, Vic 3220, Australia.
   [Zhang, Shu-Yi] E China Normal Univ, Coll Life Sci, Shanghai 200062, Peoples R China.
   [Wang, Lin-Fa] Duke NUS Grad Med Sch, Emerging Infect Dis Program, Singapore 169857, Singapore.
C3 Chinese Academy of Sciences; Wuhan Institute of Virology, CAS; EcoHealth Alliance; University of California System; University of California Davis; Commonwealth Scientific & Industrial Research Organisation (CSIRO); East China Normal University; National University of Singapore
RP Daszak, P (corresponding author), EcoHlth Alliance, New York, NY 10001 USA.
EM daszak@ecohealthalliance.org; zlshi@wh.iov.cn
FU State Key Program for Basic Research [2011CB504701, 2010CB530100]; National Natural Science Foundation of China [81290341, 31321001]; Scientific and technological basis special project [2013FY113500]; CSIRO OCE Science Leaders Award; National Institute of Allergy and Infectious Diseases (NIAID) [R01AI079231]; National Institutes of Health (NIH)/National Science Foundation (NSF) 'Ecology and Evolution of Infectious Diseases' award from the NIH Fogarty International Center [R01TW005869]; NIH Fogarty International Center; Office of the Secretary of the Department of Health and Human Services [R56TW009502]; United States Agency for International Development (USAID) Emerging Pandemic Threats PREDICT; National Institute of Allergy and Infectious Diseases [R01AI110964] Funding Source: NIH RePORTER
NR 29
TC 1063
Z9 1260
U1 5
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 NOV 28
PY 2013
VL 503
IS 7477
BP 535
EP +
DI 10.1038/nature12711
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 258MU
UT WOS:000327464200045
PM 24172901
DA 2026-03-09
ER

PT J
AU Lu, GW
   Hu, YW
   Wang, QH
   Qi, JX
   Gao, F
   Li, Y
   Zhang, YF
   Zhang, W
   Yuan, Y
   Bao, JK
   Zhang, BC
   Shi, Y
   Yan, JH
   Gao, GF
AF Lu, Guangwen
   Hu, Yawei
   Wang, Qihui
   Qi, Jianxun
   Gao, Feng
   Li, Yan
   Zhang, Yanfang
   Zhang, Wei
   Yuan, Yuan
   Bao, Jinku
   Zhang, Buchang
   Shi, Yi
   Yan, Jinghua
   Gao, George F.
TI Molecular basis of binding between novel human coronavirus MERS-CoV and its receptor CD26
SO NATURE
LA English
DT Article
ID crystal-structure; spike protein; functional receptor; aminopeptidase-n; middle-east; reveals; membrane; complex; origin; virus
AB The newly emergent Middle East respiratory syndrome coronavirus (MERS-CoV) can cause severe pulmonary disease in humans(1,2), representing the second example of a highly pathogenic coronavirus, the first being SARS-CoV3. CD26 (also known as dipeptidyl peptidase 4, DPP4) was recently identified as the cellular receptor for MERS-CoV4. The engagement of the MERS-CoV spike protein with CD26 mediates viral attachment to host cells and virus-cell fusion, thereby initiating infection. Here we delineate the molecular basis of this specific interaction by presenting the first crystal structures of both the free receptor binding domain (RBD) of the MERS-CoV spike protein and its complex with CD26. Furthermore, binding between the RBD and CD26 is measured using real-time surface plasmon resonance with a dissociation constant of 16.7 nM. The viral RBD is composed of a core subdomain homologous to that of the SARS-CoV spike protein, and a unique strand-dominated external receptor binding motif that recognizes blades IV and V of the CD26 beta-propeller. The atomic details at the interface between the two binding entities reveal a surprising protein-protein contact mediated mainly by hydrophilic residues. Sequence alignment indicates, among beta-coronaviruses, a possible structural conservation for the region homologous to the MERS-CoV RBD core, but a high variation in the external receptor binding motif region for virus-specific pathogenesis such as receptor recognition.
C1 [Lu, Guangwen; Wang, Qihui; Qi, Jianxun; Li, Yan; Zhang, Yanfang; Zhang, Wei; Yuan, Yuan; Yan, Jinghua; Gao, George F.] Chinese Acad Sci, Inst Microbiol, CAS Key Lab Pathogen Microbiol & Immunol, Beijing 100101, Peoples R China.
   [Hu, Yawei; Zhang, Buchang] Anhui Univ, Sch Life Sci, Hefei 230039, Peoples R China.
   [Gao, Feng] Chinese Acad Sci, Inst Biophys, Lab Noncoding RNA, Beijing 100101, Peoples R China.
   [Gao, Feng; Bao, Jinku] Sichuan Univ, Sch Life Sci, Chengdu 610064, Sichuan, Peoples R China.
   [Zhang, Yanfang; Gao, George F.] Tianjin Inst Ind Biotechnol, Lab Prot Engn & Vaccines, Tianjin 300308, Peoples R China.
   [Yuan, Yuan; Gao, George F.] Univ Sci & Technol China, Sch Life Sci, Hefei 230026, Peoples R China.
   [Shi, Yi; Gao, George F.] Chinese Acad Sci, Beijing Inst Life Sci, RNIH, Beijing 100101, Peoples R China.
   [Gao, George F.] Chinese Ctr Dis Control & Prevent China CDC, Beijing 102206, Peoples R China.
C3 Chinese Academy of Sciences; Institute of Microbiology, CAS; Anhui University; Chinese Academy of Sciences; Institute of Biophysics, CAS; Sichuan University; Chinese Academy of Sciences; Tianjin Institute of Industrial Biotechnology, CAS; Chinese Academy of Sciences; University of Science & Technology of China, CAS; Chinese Academy of Sciences; Chinese Center for Disease Control & Prevention
RP Gao, GF (corresponding author), Chinese Acad Sci, Inst Microbiol, CAS Key Lab Pathogen Microbiol & Immunol, Beijing 100101, Peoples R China.
EM gaof@im.ac.cn
FU Ministry of Science and Technology of China (MOST) [2011CB504703]; National Natural Science Foundation of China (NSFC) [81290342]; NSFC Innovative Research Group [81021003]
NR 38
TC 571
Z9 688
U1 2
U2 273
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 8
PY 2013
VL 500
IS 7461
BP 227
EP +
DI 10.1038/nature12328
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 197CH
UT WOS:000322825500039
PM 23831647
DA 2026-03-09
ER

PT J
AU Irannejad, R
   Tomshine, JC
   Tomshine, JR
   Chevalier, M
   Mahoney, JP
   Steyaert, J
   Rasmussen, SGF
   Sunahara, RK
   El-Samad, H
   Huang, B
   von Zastrow, M
AF Irannejad, Roshanak
   Tomshine, Jin C.
   Tomshine, Jon R.
   Chevalier, Michael
   Mahoney, Jacob P.
   Steyaert, Jan
   Rasmussen, Soren G. F.
   Sunahara, Roger K.
   El-Samad, Hana
   Huang, Bo
   von Zastrow, Mark
TI Conformational biosensors reveal GPCR signalling from endosomes
SO NATURE
LA English
DT Article
ID protein-coupled receptors; adrenergic-receptor; crystal-structure; camp; endocytosis; desensitization; activation; binding; domain
AB A long-held tenet of molecular pharmacology is that canonical signal transduction mediated by G-protein-coupled receptor (GPCR) coupling to heterotrimeric G proteins is confined to the plasma membrane. Evidence supporting this traditional view is based on analytical methods that provide limited or no subcellular resolution(1). It has been subsequently proposed that signalling by internalized GPCRs is restricted to G-protein-independent mechanisms such as scaffolding by arrestins(2,3), or GPCR activation elicits a discrete formof persistent G protein signalling(4-9), or that internalized GPCRs can indeed contribute to the acute G-protein-mediated response(10). Evidence supporting these various latter hypotheses is indirect or subject to alternative interpretation, and it remains unknown if endosome-localized GPCRs are even present in an active form. Here we describe the application of conformation-specific single-domain antibodies (nanobodies) to directly probe activation of the beta(2)-adrenoceptor, a prototypical GPCR(11), and its cognate G protein, G(s) (ref. 12), in living mammalian cells. We show that the adrenergic agonist isoprenaline promotes receptor and G protein activation in the plasma membrane as expected, but also in the early endosome membrane, and that internalized receptors contribute to the overall cellular cyclic AMP response within several minutes after agonist application. These findings provide direct support for the hypothesis that canonical GPCR signalling occurs from endosomes as well as the plasma membrane, and suggest a versatile strategy for probing dynamic conformational change in vivo.
C1 [Irannejad, Roshanak; Tomshine, Jin C.; Tomshine, Jon R.; von Zastrow, Mark] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94158 USA.
   [Chevalier, Michael; El-Samad, Hana; Huang, Bo] Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94158 USA.
   [Mahoney, Jacob P.; Sunahara, Roger K.] Univ Michigan, Sch Med, Dept Pharmacol, Ann Arbor, MI 48109 USA.
   [Steyaert, Jan] Vrije Univ Brussel, Dept Mol & Cellular Interact, B-1050 Brussels, Belgium.
   [Steyaert, Jan] VIB, Struct Biol Res Ctr, B-1050 Brussels, Belgium.
   [Rasmussen, Soren G. F.] Univ Copenhagen, Panum Inst, Dept Neurosci & Pharmacol, DK-2200 Copenhagen N, Denmark.
   [Huang, Bo] Univ Calif San Francisco, Dept Pharmaceut Chem, San Francisco, CA 94158 USA.
   [von Zastrow, Mark] Univ Calif San Francisco, Dept Cellular & Mol Pharmacol, 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 Michigan System; University of Michigan; Vrije Universiteit Brussel; Flanders Institute for Biotechnology (VIB); University of Copenhagen; University of California System; University of California San Francisco; University of California System; University of California San Francisco
RP von Zastrow, M (corresponding author), Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94158 USA.
EM Mark.VonZastrow@ucsf.edu
FU National Institute on Drug Abuse of the US National Institutes of Health [DA010711, DA012864, F32 DA029993]; American Heart Association; National Institute of General Medical Sciences [GM083118, T32 GM007767]; Lundbeck Foundation; FWO-Vlaanderen grants [FWO551, FWO646]; Innoviris-Brussels [BRGEOZ132]; Packard Fellowship for Science and Engineering; National Institute of General Medical Sciences [R01GM083118] Funding Source: NIH RePORTER; National Institute on Drug Abuse [R01DA010711, R01DA012864] Funding Source: NIH RePORTER; Lundbeck Foundation [R37-2009-3457] Funding Source: researchfish
NR 41
TC 658
Z9 775
U1 2
U2 217
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 28
PY 2013
VL 495
IS 7442
BP 534
EP +
DI 10.1038/nature12000
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 113QN
UT WOS:000316682800051
PM 23515162
DA 2026-03-09
ER

PT J
AU Lavrijsen, R
   Lee, JH
   Fernández-Pacheco, A
   Petit, DCMC
   Mansell, R
   Cowburn, RP
AF Lavrijsen, Reinoud
   Lee, Ji-Hyun
   Fernandez-Pacheco, Amalio
   Petit, Dorothee C. M. C.
   Mansell, Rhodri
   Cowburn, Russell P.
TI Magnetic ratchet for three-dimensional spintronic memory and logic
SO NATURE
LA English
DT Article
ID anisotropy
AB One of the key challenges for future electronic memory and logic devices is finding viable ways of moving from today's two-dimensional structures, which hold data in an x-y mesh of cells, to three-dimensional structures in which data are stored in an x-y-z lattice of cells. This could allow a many-fold increase in performance. A suggested solution is the shift register(1,2)-a digital building block that passes data from cell to cell along a chain. In conventional digital microelectronics, two-dimensional shift registers are routinely constructed from a number of connected transistors. However, for three-dimensional devices the added process complexity and space needed for such transistors would largely cancel out the benefits of moving into the third dimension. 'Physical' shift registers, in which an intrinsic physical phenomenon is used to move data near-atomic distances, without requiring conventional transistors, are therefore much preferred. Here we demonstrate a way of implementing a spintronic unidirectional vertical shift register between perpendicularly magnetized ferromagnets of subnanometre thickness, similar to the layers used in non-volatile magnetic random-access memory(3). By carefully controlling the thickness of each magnetic layer and the exchange coupling between the layers, we form a ratchet that allows information in the form of a sharp magnetic kink soliton to be unidirectionally pumped (or 'shifted') from one magnetic layer to another. This simple and efficient shift-register concept suggests a route to the creation of three-dimensional microchips for memory and logic applications.
C1 [Lavrijsen, Reinoud; Lee, Ji-Hyun; Fernandez-Pacheco, Amalio; Petit, Dorothee C. M. C.; Mansell, Rhodri; Cowburn, Russell P.] Univ Cambridge, Cavendish Lab, Thin Film Magnetism Grp, Cambridge CB3 0HE, England.
C3 University of Cambridge
RP Cowburn, RP (corresponding author), Univ Cambridge, Cavendish Lab, Thin Film Magnetism Grp, JJ Thomson Ave, Cambridge CB3 0HE, England.
EM rpc12@cam.ac.uk
FU Netherlands Organization for Scientific Research and Marie Curie Cofund Action (NWO) [680-50-1024]; Marie Curie IEF within the Seventh European Community [251698, 3DMAG-NANOW]; European Community [247368: 3SPIN]
NR 20
TC 194
Z9 229
U1 1
U2 198
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 31
PY 2013
VL 493
IS 7434
BP 647
EP 650
DI 10.1038/nature11733
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 080CU
UT WOS:000314219600051
PM 23364743
DA 2026-03-09
ER

PT J
AU Lloyd, DJ
   St Jean, DJ
   Kurzeja, RJM
   Wahl, RC
   Michelsen, K
   Cupples, R
   Chen, M
   Wu, J
   Sivits, G
   Helmering, J
   Komorowski, R
   Ashton, KS
   Pennington, LD
   Fotsch, C
   Vazir, M
   Chen, K
   Chmait, S
   Zhang, JD
   Liu, LB
   Norman, MH
   Andrews, KL
   Bartberger, MD
   Van, G
   Galbreath, EJ
   Vonderfecht, SL
   Wang, MH
   Jordan, SR
   Véniant, MM
   Hale, C
AF Lloyd, David J.
   St Jean, David J., Jr.
   Kurzeja, Robert J. M.
   Wahl, Robert C.
   Michelsen, Klaus
   Cupples, Rod
   Chen, Michelle
   Wu, John
   Sivits, Glenn
   Helmering, Joan
   Komorowski, Renee
   Ashton, Kate S.
   Pennington, Lewis D.
   Fotsch, Christopher
   Vazir, Mukta
   Chen, Kui
   Chmait, Samer
   Zhang, Jiandong
   Liu, Longbin
   Norman, Mark H.
   Andrews, Kristin L.
   Bartberger, Michael D.
   Van, Gwyneth
   Galbreath, Elizabeth J.
   Vonderfecht, Steven L.
   Wang, Minghan
   Jordan, Steven R.
   Veniant, Murielle M.
   Hale, Clarence
TI Antidiabetic effects of glucokinase regulatory protein small-molecule disruptors
SO NATURE
LA English
DT Article
ID liver glucokinase; activator; glucose; identification; translocation; fructose; mk-0941; defect; cells
AB Glucose homeostasis is a vital and complex process, and its disruption can cause hyperglycaemia and type II diabetes mellitus(1). Glucokinase (GK), a key enzyme that regulates glucose homeostasis, converts glucose to glucose-6-phosphate(2,3) in pancreatic beta-cells, liver hepatocytes, specific hypothalamic neurons, and gut enterocytes(4). In hepatocytes, GK regulates glucose uptake and glycogen synthesis, suppresses glucose production(3,5), and is subject to the endogenous inhibitor GK regulatory protein (GKRP)(6-8). During fasting, GKRP binds, inactivates and sequesters GK in the nucleus, which removes GK from the gluconeogenic process and prevents a futile cycle of glucose phosphorylation. Compounds that directly hyperactivate GK (GK activators) lower blood glucose levels and are being evaluated clinically as potential therapeutics for the treatment of type II diabetes mellitus(1,9,10). However, initial reports indicate that an increased risk of hypoglycaemia is associated with some GK activators(11). To mitigate the risk of hypoglycaemia, we sought to increase GK activity by blocking GKRP. Here we describe the identification of two potent small-molecule GK-GKRP disruptors (AMG-1694 and AMG-3969) that normalized blood glucose levels in several rodent models of diabetes. These compounds potently reversed the inhibitory effect of GKRP on GK activity and promoted GK translocation both in vitro (isolated hepatocytes) and in vivo (liver). A co-crystal structure of full-length human GKRP in complex with AMG-1694 revealed a previously unknown binding pocket in GKRP distinct from that of the phosphofructose-binding site. Furthermore, with AMG-1694 and AMG-3969 (but not GK activators), blood glucose lowering was restricted to diabetic and not normoglycaemic animals. These findings exploit a new cellular mechanism for lowering blood glucose levels with reduced potential for hypoglycaemic risk in patients with type II diabetes mellitus.
C1 [Lloyd, David J.; Cupples, Rod; Chen, Michelle; Wu, John; Sivits, Glenn; Helmering, Joan; Komorowski, Renee; Wang, Minghan; Veniant, Murielle M.; Hale, Clarence] Amgen Inc, Dept Metab Disorders, Thousand Oaks, CA 91320 USA.
   [St Jean, David J., Jr.; Kurzeja, Robert J. M.; Wahl, Robert C.; Michelsen, Klaus; Ashton, Kate S.; Pennington, Lewis D.; Fotsch, Christopher; Vazir, Mukta; Chen, Kui; Chmait, Samer; Zhang, Jiandong; Liu, Longbin; Norman, Mark H.; Andrews, Kristin L.; Bartberger, Michael D.; Jordan, Steven R.] Amgen Inc, Dept Therapeut Discovery, Thousand Oaks, CA 91320 USA.
   [Van, Gwyneth; Galbreath, Elizabeth J.; Vonderfecht, Steven L.] Amgen Inc, Dept Comparat Biol & Safety Sci, Thousand Oaks, CA 91320 USA.
C3 Amgen; Amgen; Amgen
RP Lloyd, DJ (corresponding author), Amgen Inc, Dept Metab Disorders, 1 Amgen Ctr Dr, Thousand Oaks, CA 91320 USA.
EM dlloyd@amgen.com; chale@amgen.com
NR 28
TC 86
Z9 91
U1 0
U2 66
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 19
PY 2013
VL 504
IS 7480
BP 437
EP +
DI 10.1038/nature12724
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 273ZR
UT WOS:000328575300052
PM 24226772
DA 2026-03-09
ER

PT J
AU Kim, SY
   Adhikari, A
   Lee, SY
   Marshel, JH
   Kim, CK
   Mallory, CS
   Lo, M
   Pak, S
   Mattis, J
   Lim, BK
   Malenka, RC
   Warden, MR
   Neve, R
   Tye, KM
   Deisseroth, K
AF Kim, Sung-Yon
   Adhikari, Avishek
   Lee, Soo Yeun
   Marshel, James H.
   Kim, Christina K.
   Mallory, Caitlin S.
   Lo, Maisie
   Pak, Sally
   Mattis, Joanna
   Lim, Byung Kook
   Malenka, Robert C.
   Warden, Melissa R.
   Neve, Rachael
   Tye, Kay M.
   Deisseroth, Karl
TI Diverging neural pathways assemble a behavioural state from separable features in anxiety
SO NATURE
LA English
DT Article
ID ventral tegmental area; elevated plus-maze; stria terminalis; bed nucleus; electrical-stimulation; projections; responses; fear; amygdala; brain
AB Behavioural states in mammals, such as the anxious state, are characterized by several features that are coordinately regulated by diverse nervous system outputs, ranging from behavioural choice patterns to changes in physiology (in anxiety, exemplified respectively by risk-avoidance and respiratory rate alterations)(1,2). Here we investigate if and how defined neural projections arising from a single coordinating brain region in mice could mediate diverse features of anxiety. Integrating behavioural assays, in vivo and in vitro electrophysiology, respiratory physiology and optogenetics, we identify a surprising new role for the bed nucleus of the stria terminalis (BNST) in the coordinated modulation of diverse anxiety features. First, two BNST subregions were unexpectedly found to exert opposite effects on the anxious state: oval BNST activity promoted several independent anxious state features, whereas anterodorsal BNST-associated activity exerted anxiolytic influence for the same features. Notably, we found that three distinct anterodorsal BNST efferent projections-to the lateral hypothalamus, parabrachial nucleus and ventral tegmental area-each implemented an independent feature of anxiolysis: reduced risk-avoidance, reduced respiratory rate, and increased positive valence, respectively. Furthermore, selective inhibition of corresponding circuit elements in freely moving mice showed opposing behavioural effects compared with excitation, and in vivo recordings during free behaviour showed native spiking patterns in anterodorsal BNST neurons that differentiated safe and anxiogenic environments. These results demonstrate that distinct BNST subregions exert opposite effects in modulating anxiety, establish separable anxiolytic roles for different anterodorsal BNST projections, and illustrate circuit mechanisms underlying selection of features for the assembly of the anxious state.
C1 [Kim, Sung-Yon; Adhikari, Avishek; Lee, Soo Yeun; Marshel, James H.; Kim, Christina K.; Mallory, Caitlin S.; Lo, Maisie; Pak, Sally; Mattis, Joanna; Warden, Melissa R.; Tye, Kay M.; Deisseroth, Karl] Stanford Univ, Dept Bioengn, Stanford, CA 94305 USA.
   [Kim, Sung-Yon; Kim, Christina K.; Mallory, Caitlin S.; Mattis, Joanna; Deisseroth, Karl] Stanford Univ, Neurosci Program, Stanford, CA 94305 USA.
   [Lee, Soo Yeun; Deisseroth, Karl] Stanford Univ, CNC Program, Stanford, CA 94305 USA.
   [Lim, Byung Kook; Malenka, Robert C.; Deisseroth, Karl] Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA.
   [Neve, Rachael; Tye, Kay M.] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA.
   [Deisseroth, Karl] Stanford Univ, Howard Hughes Med Inst, Stanford, CA 94305 USA.
C3 Stanford University; Stanford University; Stanford University; Stanford University; Massachusetts Institute of Technology (MIT); Stanford University; Howard Hughes Medical Institute
RP Deisseroth, K (corresponding author), Stanford Univ, Dept Bioengn, Stanford, CA 94305 USA.
EM deissero@stanford.edu
FU Samsung Scholarship; US National Institute of Mental Health (NIMH); Berry Fellowship; NARSAD; Wiegers Family Fund; NIMH; US National Institute on Drug Abuse (NIDA); DARPA REPAIR Program; Keck Foundation; McKnight Foundation; Gatsby Charitable Foundation; Snyder Foundation; Woo Foundation; Tarlton Foundation; Albert Yu and Mary Bechman Foundation
NR 30
TC 501
Z9 653
U1 1
U2 162
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 11
PY 2013
VL 496
IS 7444
BP 219
EP 223
DI 10.1038/nature12018
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 122VM
UT WOS:000317346300041
PM 23515158
DA 2026-03-09
ER

PT J
AU Haitin, Y
   Carlson, AE
   Zagotta, WN
AF Haitin, Yoni
   Carlson, Anne E.
   Zagotta, William N.
TI The structural mechanism of KCNH-channel regulation by the eag domain
SO NATURE
LA English
DT Article
ID long-qt syndrome; herg potassium channels; amino-terminal domain; human-ether; mutations; drosophila; deactivation; physiology; binding; region
AB The KCNH voltage-dependent potassium channels (ether-a-go-go, EAG; EAG-related gene, ERG; EAG-like channels, ELK) are important regulators of cellular excitability(1-3) and have key roles in diseases such as cardiac long QT syndrome type 2 (LQT2)(4), epilepsy(5), schizophrenia(6) and cancer(7). The intracellular domains of KCNH channels are structurally distinct from other voltage-gated channels. The amino-terminal region contains an eag domain, which is composed of a Per-Arnt-Sim (PAS) domain and aPAS-cap domain(8), whereas the carboxy-terminal region contains a cyclic nucleotide-binding homology domain (CNBHD), which is connected to the pore through a C-linker domain. Many disease-causing mutations localize to these specialized intracellular domains, which underlie the unique gating and regulation of KCNH channels(9). It has been suggested that the eag domain may regulate the channel by interacting with either the S4-S5 linker or the CNBHD8,10. Here we present a 2 angstrom resolution crystal structure of the eag domain-CNBHD complex of themouse EAG1 (also known as KCNH1) channel. It displays extensive interactions between the eag domain and the CNBHD, indicating that the regulatory mechanism of the eag domain primarily involves the CNBHD. Notably, the structure reveals that a number of LQT2 mutations at homologous positions in human ERG, in addition to cancer-associated mutations in EAG channels, localize to the eag domain-CNBHD interface. Furthermore, mutations at the interface produced marked effects on channel gating, demonstrating the important physiological role of the eag domain-CNBHD interaction. Our structure of the eag domain-CNBHD complex of mouse EAG1 provides unique insights into the physiological and pathophysiological mechanisms of KCNH channels.
C1 [Haitin, Yoni; Carlson, Anne E.; Zagotta, William N.] Univ Washington, Sch Med, Dept Physiol & Biophys, Seattle, WA 98195 USA.
C3 University of Washington; University of Washington Seattle
RP Zagotta, WN (corresponding author), Univ Washington, Sch Med, Dept Physiol & Biophys, Seattle, WA 98195 USA.
EM zagotta@uw.edu
FU National Institutes of Health (NIH) [R01 EY010329]; International Human Frontier Science Program Organization (HFSPO) [LT-001025/2011]; NIH [F32 HL095241]; National Institutes of Health, National Institute of General Medical Sciences; Howard Hughes Medical Institute; Office of Science, Office of Basic Energy Sciences of the US Department of Energy [DE-AC02-05CH11231]; National Eye Institute [R01EY010329] Funding Source: NIH RePORTER
NR 38
TC 94
Z9 107
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 SEP 19
PY 2013
VL 501
IS 7467
BP 444
EP +
DI 10.1038/nature12487
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 219XT
UT WOS:000324545700051
PM 23975098
DA 2026-03-09
ER

PT J
AU Park, J
   Al-Ramahi, I
   Tan, QM
   Mollema, N
   Diaz-Garcia, JR
   Gallego-Flores, T
   Lu, HC
   Lagalwar, S
   Duvick, L
   Kang, H
   Lee, Y
   Jafar-Nejad, P
   Sayegh, LS
   Richman, R
   Liu, XY
   Gao, Y
   Shaw, CA
   Arthur, JSC
   Orr, HT
   Westbrook, TF
   Botas, J
   Zoghbi, HY
AF Park, Jeehye
   Al-Ramahi, Ismael
   Tan, Qiumin
   Mollema, Nissa
   Diaz-Garcia, Javier R.
   Gallego-Flores, Tatiana
   Lu, Hsiang-Chih
   Lagalwar, Sarita
   Duvick, Lisa
   Kang, Hyojin
   Lee, Yoontae
   Jafar-Nejad, Paymaan
   Sayegh, Layal S.
   Richman, Ronald
   Liu, Xiuyun
   Gao, Yan
   Shaw, Chad A.
   Arthur, J. Simon C.
   Orr, Harry T.
   Westbrook, Thomas F.
   Botas, Juan
   Zoghbi, Huda Y.
TI RAS-MAPK-MSK1 pathway modulates ataxin 1 protein levels and toxicity in SCA1
SO NATURE
LA English
DT Article
ID polyglutamine-induced neurodegeneration; spinocerebellar ataxia; parkinsons-disease; huntingtons-disease; alzheimers-disease; transgenic mice; kinase inhibitors; locus duplication; cag repeat; model
AB Many neurodegenerative disorders, such as Alzheimer's, Parkinson's and polyglutamine diseases, share a common pathogenic mechanism: the abnormal accumulation of disease-causing proteins, due to either the mutant protein's resistance to degradation or overexpression of the wild-type protein. We have developed a strategy to identify therapeutic entry points for such neurodegenerative disorders by screening for genetic networks that influence the levels of disease-driving proteins. We applied this approach, which integrates parallel cell-based and Drosophila genetic screens, to spinocerebellar ataxia type 1 (SCA1), a disease caused by expansion of a polyglutamine tract in ataxin 1 (ATXN1). Our approach revealed that downregulation of several components of the RAS-MAPK-MSK1 pathway decreases ATXN1 levels and suppresses neurodegeneration in Drosophila and mice. Importantly, pharmacological inhibitors of components of this pathway also decrease ATXN1 levels, suggesting that these components represent new therapeutic targets in mitigating SCA1. Collectively, these data reveal new therapeutic entry points for SCA1 and provide a proof-of-principle for tackling other classes of intractable neurodegenerative diseases.
C1 [Park, Jeehye; Al-Ramahi, Ismael; Tan, Qiumin; Diaz-Garcia, Javier R.; Gallego-Flores, Tatiana; Kang, Hyojin; Lee, Yoontae; Jafar-Nejad, Paymaan; Sayegh, Layal S.; Richman, Ronald; Liu, Xiuyun; Gao, Yan; Shaw, Chad A.; Westbrook, Thomas F.; Botas, Juan; Zoghbi, Huda Y.] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA.
   [Park, Jeehye; Al-Ramahi, Ismael; Tan, Qiumin; Diaz-Garcia, Javier R.; Gallego-Flores, Tatiana; Lu, Hsiang-Chih; Kang, Hyojin; Lee, Yoontae; Jafar-Nejad, Paymaan; Sayegh, Layal S.; Richman, Ronald; Liu, Xiuyun; Gao, Yan; Botas, Juan; Zoghbi, Huda Y.] Texas Childrens Hosp, Jan & Dan Duncan Neurol Res Inst, Houston, TX 77030 USA.
   [Park, Jeehye; Tan, Qiumin; Lee, Yoontae; Richman, Ronald; Liu, Xiuyun; Zoghbi, Huda Y.] Baylor Coll Med, Howard Hughes Med Inst, Houston, TX 77030 USA.
   [Mollema, Nissa; Lagalwar, Sarita; Duvick, Lisa; Orr, Harry T.] Univ Minnesota, Inst Translat Neurosci, Minneapolis, MN 55455 USA.
   [Mollema, Nissa; Lagalwar, Sarita; Duvick, Lisa; Orr, Harry T.] Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA.
   [Lu, Hsiang-Chih; Westbrook, Thomas F.; Zoghbi, Huda Y.] Baylor Coll Med, Program Dev Biol, Houston, TX 77030 USA.
   [Arthur, J. Simon C.] Univ Dundee, Sch Life Sci, MRC Prot Phosphorylat Unit, Dundee DD1 5EH, Scotland.
   [Westbrook, Thomas F.] Baylor Coll Med, Verna & Marrs McLean Dept Biochem & Mol Biol, Houston, TX 77030 USA.
C3 Baylor College of Medicine; Baylor College of Medicine; Baylor College Medical Hospital; Howard Hughes Medical Institute; Baylor College of Medicine; University of Minnesota System; University of Minnesota Twin Cities; University of Minnesota System; University of Minnesota Twin Cities; Baylor College of Medicine; University of Dundee; Baylor College of Medicine
RP Orr, HT (corresponding author), Univ Minnesota, Inst Translat Neurosci, Minneapolis, MN 55455 USA.
EM orrxx002@umn.edu; thomasw@bcm.edu; jbotas@bcm.edu; hzoghbi@bcm.edu
FU Howard Hughes Medical Institute Collaborative Innovation Awards grant; NIH Brain Disorders and Development training grant [NIH-NS42179]; National Institute of General Medical Sciences [T32GM007526] Funding Source: NIH RePORTER; National Institute of Neurological Disorders and Stroke [T32NS043124, R01NS027699] Funding Source: NIH RePORTER; Medical Research Council [MC_U127081014, MC_UU_12016/10] Funding Source: researchfish; MRC [MC_U127081014, MC_UU_12016/10] Funding Source: UKRI
NR 49
TC 113
Z9 128
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 JUN 20
PY 2013
VL 498
IS 7454
BP 325
EP +
DI 10.1038/nature12204
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 166XI
UT WOS:000320592900032
PM 23719381
DA 2026-03-09
ER

PT J
AU Ohouo, PY
   de Oliveira, FMB
   Liu, Y
   Ma, CJ
   Smolka, MB
AF Ohouo, Patrice Y.
   de Oliveira, Francisco M. Bastos
   Liu, Yi
   Ma, Chu Jian
   Smolka, Marcus B.
TI DNA-repair scaffolds dampen checkpoint signalling by counteracting the adaptor Rad9
SO NATURE
LA English
DT Article
ID holliday junction resolvase; damage checkpoint; protein-interaction; replication stress; phosphorylation; dpb11; slx4; activation; kinase; domain
AB In response to genotoxic stress, a transient arrest in cell-cycle progression enforced by the DNA-damage checkpoint (DDC) signalling pathway positively contributes to genome maintenance(1). Because hyperactivated DDC signalling can lead to a persistent and detrimental cell-cycle arrest(2,3), cells must tightly regulate the activity of the kinases involved in this pathway. Despite their importance, the mechanisms for monitoring and modulating DDC signalling are not fully understood. Here we show that the DNA-repair scaffolding proteins Slx4 and Rtt107 prevent the aberrant hyperactivation of DDC signalling by lesions that are generated during DNA replication in Saccharomyces cerevisiae. On replication stress, cells lacking Slx4 or Rtt107 show hyperactivation of the downstream DDC kinase Rad53, whereas activation of the upstream DDC kinase Mec1 remains normal. An Slx4-Rtt107 complex counteracts the checkpoint adaptor Rad9 by physically interacting with Dpb11 and phosphorylated histone H2A, two positive regulators of Rad9-dependent Rad53 activation. A decrease in DDC signalling results from hypomorphic mutations in RAD53 and H2A and rescues the hypersensitivity to replication stress of cells lacking Slx4 or Rtt107. We propose that the Slx4-Rtt107 complex modulates Rad53 activation by a competition-based mechanism that balances the engagement of Rad9 at replication-induced lesions. Our findings show that DDC signalling is monitored and modulated through the direct action of DNA-repair factors.
C1 [Ohouo, Patrice Y.; de Oliveira, Francisco M. Bastos; Liu, Yi; Ma, Chu Jian; Smolka, Marcus B.] Cornell Univ, Dept Mol Biol & Genet, Weill Inst Cell & Mol Biol, Ithaca, NY 14853 USA.
C3 Cornell University
RP Smolka, MB (corresponding author), Cornell Univ, Dept Mol Biol & Genet, Weill Inst Cell & Mol Biol, Ithaca, NY 14853 USA.
EM mbs266@cornell.edu
FU National Institutes of Health [RO1-GM097272, F31-GM093588]; Cornell Fleming Research Fellowship; HHMI Institutional Undergraduate Education Grant
NR 30
TC 80
Z9 93
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 JAN 3
PY 2013
VL 493
IS 7430
BP 120
EP +
DI 10.1038/nature11658
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 062QC
UT WOS:000312933800043
PM 23160493
DA 2026-03-09
ER

PT J
AU Reining, A
   Nozinovic, S
   Schlepckow, K
   Buhr, F
   Fürtig, B
   Schwalbe, H
AF Reining, Anke
   Nozinovic, Senada
   Schlepckow, Kai
   Buhr, Florian
   Fuertig, Boris
   Schwalbe, Harald
TI Three-state mechanism couples ligand and temperature sensing in riboswitches
SO NATURE
LA English
DT Article
ID base-pair resolution; adenine riboswitch; escherichia-coli; gene-expression; messenger-rnas; melting curves; nmr; binding; spectroscopy; transcription
AB Riboswitches are cis-acting gene-regulatory RNA elements that can function at the level of transcription, translation and RNA cleavage(1-3). The commonly accepted molecular mechanism for riboswitch function proposes a ligand-dependent conformational switch between two mutually exclusive states(4). According to this mechanism, ligand binding to an aptamer domain induces an allosteric conformational switch of an expression platform, leading to activation or repression of ligand-related gene expression(5). However, many riboswitch properties cannot be explained by a pure two-state mechanism. Here we show that the regulation mechanism of the adenine-sensing riboswitch, encoded by the add gene on chromosome II of the human Gram-negative pathogenic bacterium Vibrio vulnificus(6), is notably different from a two-state switch mechanism in that it involves three distinct stable conformations. We characterized the temperature and Mg2+ dependence of the population ratios of the three conformations and the kinetics of their interconversion at nucleotide resolution. The observed temperature dependence of a pre-equilibrium involving two structurally distinct ligand-free conformations of the add riboswitch conferred efficient regulation over a physiologically relevant temperature range. Such robust switching is a key requirement for gene regulation in bacteria that have to adapt to environments with varying temperatures. The translational adenine-sensing riboswitch represents the first example, to our knowledge, of a temperature-compensated regulatory RNA element.
C1 [Reining, Anke; Nozinovic, Senada; Schlepckow, Kai; Buhr, Florian; Fuertig, Boris; Schwalbe, Harald] Goethe Univ Frankfurt, Inst Organ Chem & Chem Biol, Ctr Biomol Magnet Resonance, D-60438 Frankfurt, Germany.
C3 Goethe University Frankfurt
RP Schwalbe, H (corresponding author), Goethe Univ Frankfurt, Inst Organ Chem & Chem Biol, Ctr Biomol Magnet Resonance, Max von Laue Str 7, D-60438 Frankfurt, Germany.
EM fuertig@nmr.uni-frankfurt.de; schwalbe@nmr.uni-frankfurt.de
FU German funding agency (DFG) in Collaborative Research Center 902
NR 36
TC 171
Z9 216
U1 2
U2 131
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 18
PY 2013
VL 499
IS 7458
BP 355
EP U135
DI 10.1038/nature12378
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 184RJ
UT WOS:000321910700040
PM 23842498
DA 2026-03-09
ER

PT J
AU Nystedt, B
   Street, NR
   Wetterbom, A
   Zuccolo, A
   Lin, YC
   Scofield, DG
   Vezzi, F
   Delhomme, N
   Giacomello, S
   Alexeyenko, A
   Vicedomini, R
   Sahlin, K
   Sherwood, E
   Elfstrand, M
   Gramzow, L
   Holmberg, K
   Hällman, J
   Keech, O
   Klasson, L
   Koriabine, M
   Kucukoglu, M
   Käller, M
   Luthman, J
   Lysholm, F
   Niittylä, T
   Olson, Å
   Rilakovic, N
   Ritland, C
   Rosselló, JA
   Sena, J
   Svensson, T
   Talavera-López, C
   Theissen, G
   Tuominen, H
   Vanneste, K
   Wu, ZQ
   Zhang, B
   Zerbe, P
   Arvestad, L
   Bhalerao, R
   Bohlmann, J
   Bousquet, J
   Gil, RG
   Hvidsten, TR
   de Jong, P
   MacKay, J
   Morgante, M
   Ritland, K
   Sundberg, B
   Thompson, SL
   Van de Peer, Y
   Andersson, B
   Nilsson, O
   Ingvarsson, PK
   Lundeberg, J
   Jansson, S
AF Nystedt, Bjorn
   Street, Nathaniel R.
   Wetterbom, Anna
   Zuccolo, Andrea
   Lin, Yao-Cheng
   Scofield, Douglas G.
   Vezzi, Francesco
   Delhomme, Nicolas
   Giacomello, Stefania
   Alexeyenko, Andrey
   Vicedomini, Riccardo
   Sahlin, Kristoffer
   Sherwood, Ellen
   Elfstrand, Malin
   Gramzow, Lydia
   Holmberg, Kristina
   Hallman, Jimmie
   Keech, Olivier
   Klasson, Lisa
   Koriabine, Maxim
   Kucukoglu, Melis
   Kaller, Max
   Luthman, Johannes
   Lysholm, Fredrik
   Niittyla, Totte
   Olson, Ake
   Rilakovic, Nemanja
   Ritland, Carol
   Rossello, Josep A.
   Sena, Juliana
   Svensson, Thomas
   Talavera-Lopez, Carlos
   Theissen, Guenter
   Tuominen, Hannele
   Vanneste, Kevin
   Wu, Zhi-Qiang
   Zhang, Bo
   Zerbe, Philipp
   Arvestad, Lars
   Bhalerao, Rishikesh
   Bohlmann, Joerg
   Bousquet, Jean
   Gil, Rosario Garcia
   Hvidsten, Torgeir R.
   de Jong, Pieter
   MacKay, John
   Morgante, Michele
   Ritland, Kermit
   Sundberg, Bjorn
   Thompson, Stacey Lee
   Van de Peer, Yves
   Andersson, Bjorn
   Nilsson, Ove
   Ingvarsson, Par K.
   Lundeberg, Joakim
   Jansson, Stefan
TI The Norway spruce genome sequence and conifer genome evolution
SO NATURE
LA English
DT Article
ID long noncoding rnas; transposable elements; size variation; gene family; recombination; plants; amplification; polyploidy; complexity; slow
AB Conifers have dominated forests for more than 200 million years and are of huge ecological and economic importance. Here we present the draft assembly of the 20-gigabase genome of Norway spruce (Picea abies), the first available for any gymnosperm. The number of well-supported genes (28,354) is similar to the >100 times smaller genome of Arabidopsis thaliana, and there is no evidence of a recent whole-genome duplication in the gymnosperm lineage. Instead, the large genome size seems to result from the slow and steady accumulation of a diverse set of long-terminal repeat transposable elements, possibly owing to the lack of an efficient elimination mechanism. Comparative sequencing of Pinus sylvestris, Abies sibirica, Juniperus communis, Taxus baccata and Gnetum gnemon reveals that the transposable element diversity is shared among extant conifers. Expression of 24-nucleotide small RNAs, previously implicated in transposable element silencing, is tissue-specific and much lower than in other plants. We further identify numerous long (>10,000 base pairs) introns, gene-like fragments, uncharacterized long non-coding RNAs and short RNAs. This opens up new genomic avenues for conifer forestry and breeding.
C1 [Nystedt, Bjorn; Sherwood, Ellen] Stockholm Univ, Dept Biochem & Biophys, Sci Life Lab, S-17121 Solna, Sweden.
   [Street, Nathaniel R.; Scofield, Douglas G.; Delhomme, Nicolas; Keech, Olivier; Tuominen, Hannele; Zhang, Bo; Hvidsten, Torgeir R.; Jansson, Stefan] Umea Univ, Dept Plant Physiol, Umea Plant Sci Ctr, S-90187 Umea, Sweden.
   [Wetterbom, Anna; Luthman, Johannes; Lysholm, Fredrik; Talavera-Lopez, Carlos; Andersson, Bjorn] Karolinska Inst, Sci Life Lab, Dept Cell & Mol Biol, S-17177 Stockholm, Sweden.
   [Zuccolo, Andrea; Giacomello, Stefania; Vicedomini, Riccardo; Morgante, Michele] Ist Genom Applicata, I-33100 Udine, Italy.
   [Zuccolo, Andrea] Scuola Super Sant Anna, Inst Life Sci, I-56127 Pisa, Italy.
   [Lin, Yao-Cheng; Vanneste, Kevin; Van de Peer, Yves] Univ Ghent, Dept Plant Syst Biol VIB, B-9052 Ghent, Belgium.
   [Lin, Yao-Cheng; Vanneste, Kevin; Van de Peer, Yves] Univ Ghent, Dept Plant Biotechnol & Bioinformat, B-9052 Ghent, Belgium.
   [Scofield, Douglas G.; Wu, Zhi-Qiang; Thompson, Stacey Lee; Ingvarsson, Par K.] Umea Univ, Dept Ecol & Environm Sci, Umea Plant Sci Ctr, S-90187 Umea, Sweden.
   [Vezzi, Francesco; Sahlin, Kristoffer; Arvestad, Lars] KTH Royal Inst Technol, Sch Comp Sci & Commun, Sci Life Lab, S-17121 Solna, Sweden.
   [Giacomello, Stefania; Vicedomini, Riccardo; Morgante, Michele] Univ Udine, I-33100 Udine, Italy.
   [Alexeyenko, Andrey; Holmberg, Kristina; Hallman, Jimmie; Kaller, Max; Rilakovic, Nemanja; Lundeberg, Joakim] KTH Royal Inst Technol, Sci Life Lab, Sch Biotechnol, S-17121 Solna, Sweden.
   [Elfstrand, Malin; Olson, Ake] Swedish Univ Agr Sci, Uppsala Bioctr, Dept Forest Mycol & Plant Pathol, S-75007 Uppsala, Sweden.
   [Gramzow, Lydia; Theissen, Guenter] Univ Jena, Dept Genet, D-07743 Jena, Germany.
   [Klasson, Lisa] Uppsala Univ, Dept Cell & Mol Biol, S-75237 Uppsala, Sweden.
   [Koriabine, Maxim; de Jong, Pieter] Childrens Hosp Oakland, Res Inst, BACPAC Resources, Oakland, CA 94609 USA.
   [Kucukoglu, Melis; Niittyla, Totte; Bhalerao, Rishikesh; Gil, Rosario Garcia; Sundberg, Bjorn; Nilsson, Ove] Swedish Univ Agr Sci, Dept Forest Genet & Plant Physiol, Umea Plant Sci Ctr, S-90183 Umea, Sweden.
   [Ritland, Carol; Bohlmann, Joerg; Ritland, Kermit] Univ British Columbia, Dept Forest & Conservat Sci, Vancouver, BC V6T 1Z4, Canada.
   [Rossello, Josep A.] Univ Valencia, Jardi Bot, Valencia 46008, Spain.
   [Rossello, Josep A.] Carl Faust Fdn, Marimurtra Bot Garden, Blanes 17300, Spain.
   [Sena, Juliana; Bousquet, Jean; MacKay, John] Univ Laval, Canada Res Chair Forest & Environm Genom, Ctr Forest Res, Quebec City, PQ G1V 0A6, Canada.
   [Sena, Juliana; Bousquet, Jean; MacKay, John] Univ Laval, Inst Syst & Integrat Biol, Quebec City, PQ G1V 0A6, Canada.
   [Svensson, Thomas] Karolinska Inst, Sci Life Lab, Dept Biosci & Nutr, S-17121 Solna, Sweden.
   [Zerbe, Philipp; Bohlmann, Joerg] Univ British Columbia, Michael Smith Labs, Vancouver, BC V6T 1Z4, Canada.
   [Arvestad, Lars] Stockholm Univ, Swedish E Sci Res Ctr, Dept Numer Anal & Comp Sci, S-17121 Solna, Sweden.
   [Hvidsten, Torgeir R.] Norwegian Univ Life Sci, Dept Chem Biotechnol & Food Sci, N-1432 As, Norway.
C3 Stockholm University; Umea University; Karolinska Institutet; Scuola Superiore Sant'Anna; Ghent University; Flanders Institute for Biotechnology (VIB); Ghent University; Umea University; Royal Institute of Technology; University of Udine; Royal Institute of Technology; Swedish University of Agricultural Sciences; Friedrich Schiller University of Jena; Uppsala University; University of California System; University of California San Francisco; UCSF Medical Center; UCSF Benioff Children's Hospital Oakland; Children's Hospital Oakland Research Institute; Swedish University of Agricultural Sciences; Umea University; University of British Columbia; University of Valencia; Laval University; Laval University; Karolinska Institutet; University of British Columbia; Stockholm University; Norwegian University of Life Sciences
RP Nilsson, O (corresponding author), Swedish Univ Agr Sci, Dept Forest Genet & Plant Physiol, Umea Plant Sci Ctr, S-90183 Umea, Sweden.
EM ove.nilsson@slu.se; par.ingvarsson@emg.umu.se; joakim.lundeberg@scilifelab.se; stefan.jansson@umu.se
FU Knut and Alice Wallenberg Foundation; Swedish Research Council (VR); Swedish Governmental Agency for Innovation Systems (Vinnova); Swedish Research Council for Environment, Agricultural Sciences and Spatial Planning (Formas); Swedish foundation for Strategic Research (SSF); Government of Canada through Genome Canada; Genome British Columbia; Genome Quebec; Science for Life Laboratory; National Genomics Infrastructure (NGI), Sweden
NR 50
TC 1149
Z9 1250
U1 6
U2 560
PU NATURE PUBLISHING 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 30
PY 2013
VL 497
IS 7451
BP 579
EP 584
DI 10.1038/nature12211
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 152UF
UT WOS:000319556100035
PM 23698360
DA 2026-03-09
ER

PT J
AU Hoggatt, J
   Mohammad, KS
   Singh, P
   Hoggatt, AF
   Chitteti, BR
   Speth, JM
   Hu, PR
   Poteat, BA
   Stilger, KN
   Ferraro, F
   Silberstein, L
   Wong, FK
   Farag, SS
   Czader, M
   Milne, GL
   Breyer, RM
   Serezani, CH
   Scadden, DT
   Guise, TA
   Srour, EF
   Pelus, LM
AF Hoggatt, Jonathan
   Mohammad, Khalid S.
   Singh, Pratibha
   Hoggatt, Amber F.
   Chitteti, Brahmananda R.
   Speth, Jennifer M.
   Hu, Peirong
   Poteat, Bradley A.
   Stilger, Kayla N.
   Ferraro, Francesca
   Silberstein, Lev
   Wong, Frankie K.
   Farag, Sherif S.
   Czader, Magdalena
   Milne, Ginger L.
   Breyer, Richard M.
   Serezani, Carlos H.
   Scadden, David T.
   Guise, Theresa A.
   Srour, Edward F.
   Pelus, Louis M.
TI Differential stem- and progenitor-cell trafficking by prostaglandin E2
SO NATURE
LA English
DT Article
ID bone-marrow niche; hematopoietic stem; receptor; microenvironment; osteopontin; impact; size
AB To maintain lifelong production of blood cells, haematopoietic stem cells (HSCs) are tightly regulated by inherent programs and extrinsic regulatory signals received from their microenvironmental niche. Long-term repopulating HSCs reside in several, perhaps overlapping, niches that produce regulatory molecules and signals necessary for homeostasis and for increased output after stress or injury(1-5). Despite considerable advances in the specific cellular or molecular mechanisms governing HSC-niche interactions, little is known about the regulatory function in the intact mammalian haematopoietic niche. Recently, we and others described a positive regulatory role for prostaglandin E-2 (PGE(2)) on HSC function ex vivo(6,7). Here we show that inhibition of endogenous PGE(2) by nonsteroidal anti-inflammatory drug (NSAID) treatment in mice results in modest HSC egress from the bone marrow. Surprisingly, this was independent of the SDF-1-CXCR4 axis implicated in stem-cell migration. Stem and progenitor cells were found to have differing mechanisms of egress, with HSC transit to the periphery dependent on niche attenuation and reduction in the retentive molecule osteopontin. Haematopoietic grafts mobilized with NSAIDs had superior repopulating ability and long-term engraftment. Treatment of non-human primates and healthy human volunteers confirmed NSAID-mediated egress in other species. PGE(2) receptor knockout mice demonstrated that progenitor expansion and stem/progenitor egress resulted from reduced E-prostanoid 4 (EP4) receptor signalling. These results not only uncover unique regulatory roles for EP4 signalling in HSC retention in the niche, but also define a rapidly translatable strategy to enhance transplantation therapeutically.
C1 [Hoggatt, Jonathan; Mohammad, Khalid S.; Singh, Pratibha; Hoggatt, Amber F.; Speth, Jennifer M.; Hu, Peirong; Stilger, Kayla N.; Czader, Magdalena; Serezani, Carlos H.; Guise, Theresa A.; Srour, Edward F.; Pelus, Louis M.] Indiana Univ Sch Med, Indianapolis, IN 46202 USA.
   [Hoggatt, Jonathan; Ferraro, Francesca; Silberstein, Lev; Wong, Frankie K.; Scadden, David T.] Harvard Univ, Harvard Stem Cell Inst, Harvard Med Sch, Ctr Regenerat Med,Massachusetts Gen Hosp, Boston, MA 02114 USA.
   [Hoggatt, Amber F.] Univ Illinois, Biol Resources Lab, Chicago, IL 60612 USA.
   [Chitteti, Brahmananda R.; Poteat, Bradley A.; Farag, Sherif S.; Srour, Edward F.] Indiana Univ Sch Med, Div Hematol & Oncol, Indianapolis, IN 46202 USA.
   [Milne, Ginger L.] Vanderbilt Univ, Div Clin Pharmacol, Eicosanoid Core Lab, Nashville, TN 37232 USA.
   [Breyer, Richard M.] Vanderbilt Univ, Div Nephrol & Hypertens, Nashville, TN 37232 USA.
C3 Indiana University System; Indiana University Bloomington; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard Medical School; University of Illinois System; University of Illinois Chicago; University of Illinois Chicago Hospital; Indiana University System; Indiana University Bloomington; Vanderbilt University; Vanderbilt University
RP Pelus, LM (corresponding author), Indiana Univ Sch Med, Indianapolis, IN 46202 USA.
EM lpelus@iupui.edu
FU National Institutes of Health (NIH) [HL096305, CA143057, CA069158, HL100402, DK37097]; NIH [DK07519, HL07910, HL087735]; Center of Excellence in Hematology [P01 DK090948]; National Cancer Institute [P30CA082709] Funding Source: NIH RePORTER; National Heart Lung and Blood Institute [T32HL007910] Funding Source: NIH RePORTER
NR 26
TC 125
Z9 147
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 MAR 21
PY 2013
VL 495
IS 7441
BP 365
EP 369
DI 10.1038/nature11929
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 113EY
UT WOS:000316650500042
PM 23485965
DA 2026-03-09
ER

PT J
AU Yadlapalli, S
   Yamashita, YM
AF Yadlapalli, Swathi
   Yamashita, Yukiko M.
TI Chromosome-specific nonrandom sister chromatid segregation during stem-cell division
SO NATURE
LA English
DT Article
ID drosophila oogenesis; nuclear migration; dna methylation; domain protein; germline; centrosome; gene; retrotransposon; encodes; dnmt2
AB Adult stem cells undergo asymmetric cell division to self-renew and give rise to differentiated cells that comprise mature tissue(1). Sister chromatids may be distinguished and segregated nonrandomly in asymmetrically dividing stem cells(2), although the underlying mechanism and the purpose it may serve remain elusive. Here we develop the CO-FISH(chromosome orientation fluorescence in situ hybridization) technique(3) with single-chromosome resolution and show that sister chromatids of X and Y chromosomes, but not autosomes, are segregated nonrandomly during asymmetric divisions of Drosophila male germline stem cells. This provides the first direct evidence, to our knowledge, that two sister chromatids containing identical genetic information can be distinguished and segregated nonrandomly during asymmetric stem-cell divisions. We further show that the centrosome, SUN-KASH nuclear envelope proteins and Dnmt2 (also known as Mt2) are required for nonrandom sister chromatid segregation. Our data indicate that the information on X and Y chromosomes that enables nonrandom segregation is primed during gametogenesis in the parents. Moreover, we show that sister chromatid segregation is randomized in germline stem cell overproliferation and dedifferentiated germline stem cells. We propose that nonrandom sister chromatid segregation may serve to transmit distinct information carried on two sister chromatids to the daughters of asymmetrically dividing stem cells.
C1 [Yadlapalli, Swathi; Yamashita, Yukiko M.] Univ Michigan, Inst Life Sci, Ctr Stem Cell Biol, Ann Arbor, MI 48109 USA.
   [Yadlapalli, Swathi; Yamashita, Yukiko M.] Univ Michigan, Sch Med, Dept Cell & Dev Biol, Ann Arbor, MI 48109 USA.
   [Yamashita, Yukiko M.] Univ Michigan, Cellular & Mol Biol Program, Ann Arbor, MI 48109 USA.
C3 University of Michigan System; University of Michigan; University of Michigan System; University of Michigan; University of Michigan System; University of Michigan
RP Yadlapalli, S (corresponding author), Univ Michigan, Inst Life Sci, Ctr Stem Cell Biol, Ann Arbor, MI 48109 USA.
EM swathi@umich.edu; yukikomy@umich.edu
FU University of Michigan (Life Sciences Institute and Office of the Provost and Executive Vice President for Academic Affairs); AHA [12PRE9630000]; NIH [1F31HD071727-01]; MacArthur Foundation; American Heart Association (AHA) [12PRE9630000] Funding Source: American Heart Association (AHA)
NR 30
TC 102
Z9 119
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 JUN 13
PY 2013
VL 498
IS 7453
BP 251
EP +
DI 10.1038/nature12106
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 162RR
UT WOS:000320283400053
PM 23644460
DA 2026-03-09
ER

PT J
AU Labidi, J
   Cartigny, P
   Moreira, M
AF Labidi, J.
   Cartigny, P.
   Moreira, M.
TI Non-chondritic sulphur isotope composition of the terrestrial mantle
SO NATURE
LA English
DT Article
ID mid-atlantic ridge; crust; morb; constraints; consequences; systematics; evolution; history; glasses; beneath
AB Core-mantle differentiation is the largest event experienced by a growing planet during its early history. Terrestrial core segregation imprinted the residual mantle composition by scavenging siderophile (iron-loving) elements such as tungsten, cobalt and sulphur. Cosmochemical constraints suggest that about 97% of Earth's sulphur should at present reside in the core(1), which implies that the residual silicate mantle should exhibit fractionated S-34/S-32 ratios according to the relevant metal-silicate partition coefficients(2), together with fractionated siderophile element abundances. However, Earth's mantle has long been thought to be both homogeneous and chondritic for S-34/S-32, similar to Canyon Diablo troilite(3-6), as it is for most siderophile elements. This belief was consistent with a mantle sulphur budget dominated by late-accreted chondritic components. Here we show that the mantle, as sampled bymid-ocean ridge basalts from the south Atlantic ridge, displays heterogeneous S-34/S-32 ratios, directly correlated to the strontium and neodymium isotope ratios Sr-87/Sr-86 and Nd-143/Nd-144. These isotope trends are compatible with binary mixing between a low-S-34/S-32 ambient mantle and a high-S-34/S-32 recycled component that we infer to be subducted sediments. The depleted end-member is characterized by a significantly negative delta S-34 of -1.28 +/- 0.33 parts per thousand that cannot reach a chondritic value even when surface sulphur (from continents, altered oceanic crust, sediments and oceans) is added. Such a non-chondritic S-34/S-32 ratio for the silicate Earth could be accounted for by a core-mantle differentiation record in which the core has a S-34/S-32 ratio slightly higher than that of chondrites (delta S-34=+0.07 parts per thousand). Despite evidence for late-veneer addition of siderophile elements (and therefore sulphur) after core formation, our results imply that the mantle sulphur budget retains fingerprints of core-mantle differentiation.
C1 [Labidi, J.; Cartigny, P.] Univ Paris Diderot, Inst Phys Globe Paris, Lab Geochim Isotopes Stables, Sorbonne Paris Cite,UMR 7154,CNRS, F-75005 Paris, France.
   [Moreira, M.] Univ Paris Diderot, Inst Phys Globe Paris, Lab Geochim & Cosmochim, Sorbonne Paris Cite,UMR 7154,CNRS, F-75005 Paris, France.
C3 Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Earth Sciences & Astronomy (INSU); Universite Paris Cite; Universite Paris Cite; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Earth Sciences & Astronomy (INSU)
RP Labidi, J (corresponding author), Univ Paris Diderot, Inst Phys Globe Paris, Lab Geochim Isotopes Stables, Sorbonne Paris Cite,UMR 7154,CNRS, 1 Rue Jussieu, F-75005 Paris, France.
EM labidi@ipgp.fr
FU Region Ile de France (Sesame); CNRS (INSU-Mi-lourd); CNRS (SEDIT-CNRS); IPGP (BQR)
NR 32
TC 226
Z9 253
U1 2
U2 115
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 12
PY 2013
VL 501
IS 7466
BP 208
EP +
DI 10.1038/nature12490
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 215XR
UT WOS:000324244900038
PM 24005324
DA 2026-03-09
ER

PT J
AU Yan, ZQ
   Zhang, W
   He, Y
   Gorczyca, D
   Xiang, Y
   Cheng, LE
   Meltzer, S
   Jan, LY
   Jan, YN
AF Yan, Zhiqiang
   Zhang, Wei
   He, Ye
   Gorczyca, David
   Xiang, Yang
   Cheng, Li E.
   Meltzer, Shan
   Jan, Lily Yeh
   Jan, Yuh Nung
TI Drosophila NOMPC is a mechanotransduction channel subunit for gentle-touch sensation
SO NATURE
LA English
DT Article
ID multidendritic sensory neurons; trp channel; mechanosensory transduction; ion channels; hearing; nociception; mechanisms; locomotion; larval; family
AB Touch sensation is essential for behaviours ranging from environmental exploration to social interaction; however, the underlying mechanisms are largely unknown(1). In Drosophila larvae, two types of sensory neurons, class III and class IV dendritic arborization neurons, tile the body wall. The mechanotransduction channel PIEZO in class IV neurons is essential for sensing noxious mechanical stimuli but is not involved in gentle touch(2). On the basis of electrophysiological-recording, calcium-imaging and behavioural studies, here we report that class III dendritic arborization neurons are touch sensitive and contribute to gentle-touch sensation. We further identify NOMPC (No mechanoreceptor potential C), a member of the transient receptor potential (TRP) family of ion channels, as a mechanotransduction channel for gentle touch. NOMPC is highly expressed in class III neurons and is required for their mechanotransduction. Moreover, ectopic NOMPC expression confers touch sensitivity to the normally touch-insensitive class IV neurons. In addition to the critical role of NOMPC in eliciting gentle-touch-mediated behavioural responses, expression of this protein in the Drosophila S2 cell line also gives rise to mechanosensitive channels in which ion selectivity can be altered by NOMPC mutation, indicating that NOMPC is a pore-forming subunit of a mechanotransduction channel. Our study establishes NOMPC as a bona fide mechanotransduction channel that satisfies all four criteria proposed for a channel to qualify as a transducer of mechanical stimuli(3) and mediates gentle-touch sensation. Our study also suggests that different mechanosensitive channels may be used to sense gentle touch versus noxious mechanical stimuli.
C1 [Yan, Zhiqiang; Zhang, Wei; He, Ye; Gorczyca, David; Xiang, Yang; Cheng, Li E.; Meltzer, Shan; Jan, Lily Yeh; Jan, Yuh Nung] Univ Calif San Francisco, Dept Physiol, Howard Hughes Med Inst, San Francisco, CA 94158 USA.
   [Yan, Zhiqiang; Zhang, Wei; He, Ye; Gorczyca, David; Xiang, Yang; Cheng, Li E.; Meltzer, Shan; Jan, Lily Yeh; Jan, Yuh Nung] Univ Calif San Francisco, Dept Biochem, Howard Hughes Med Inst, San Francisco, CA 94158 USA.
   [Yan, Zhiqiang; Zhang, Wei; He, Ye; Gorczyca, David; Xiang, Yang; Cheng, Li E.; Meltzer, Shan; Jan, Lily Yeh; Jan, Yuh Nung] Univ Calif San Francisco, Dept Biophys, Howard Hughes Med Inst, 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; Howard Hughes Medical Institute; University of California System; University of California San Francisco; Howard Hughes Medical Institute
RP Jan, YN (corresponding author), Univ Calif San Francisco, Dept Physiol, Howard Hughes Med Inst, San Francisco, CA 94158 USA.
EM yuhnung.jan@ucsf.edu
FU Long-Term Fellowship from the Human Frontier Science Program; National Institutes of Health [R37NS040929, 5R01MH084234]
NR 30
TC 219
Z9 237
U1 1
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 JAN 10
PY 2013
VL 493
IS 7431
BP 221
EP 225
DI 10.1038/nature11685
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 066YY
UT WOS:000313259600039
DA 2026-03-09
ER

PT J
AU Findley, K
   Oh, J
   Yang, J
   Conlan, S
   Deming, C
   Meyer, JA
   Schoenfeld, D
   Nomicos, E
   Park, M
   Kong, HH
   Segre, JA
AF Findley, Keisha
   Oh, Julia
   Yang, Joy
   Conlan, Sean
   Deming, Clayton
   Meyer, Jennifer A.
   Schoenfeld, Deborah
   Nomicos, Effie
   Park, Morgan
   Kong, Heidi H.
   Segre, Julia A.
TI Topographic diversity of fungal and bacterial communities in human skin
SO NATURE
LA English
DT Article
ID human microbiome; risk-factors; tinea-pedis; sequences; prevalence; alignment; accuracy; project; silva
AB Traditional culture-based methods have incompletely defined the microbial landscape of common recalcitrant human fungal skin diseases, including athlete's foot and toenail infections. Skin protects humans from invasion by pathogenic microorganisms and provides a home for diverse commensal microbiota(1). Bacterial genomic sequence data have generated novel hypotheses about species and community structures underlying human disorders(2-4). However, microbial diversity is not limited to bacteria; microorganisms such as fungi also have major roles in microbial community stability, human health and disease(5). Genomic methodologies to identify fungal species and communities have been limited compared with those that are available for bacteria(6). Fungal evolution can be reconstructed with phylogenetic markers, including ribosomal RNA gene regions and other highly conserved genes(7). Here we sequenced and analysed fungal communities of 14 skin sites in 10 healthy adults. Eleven core-body and arm sites were dominated by fungi of the genus Malassezia, with only species-level classifications revealing fungal-community composition differences between sites. By contrast, three foot sites-plantar heel, toenail and toe web-showed high fungal diversity. Concurrent analysis of bacterial and fungal communities demonstrated that physiologic attributes and topography of skin differentially shape these two microbial communities. These results provide a framework for future investigation of the contribution of interactions between pathogenic and commensal fungal and bacterial communities to the maintainenace of human health and to disease pathogenesis.
C1 [Findley, Keisha; Oh, Julia; Yang, Joy; Conlan, Sean; Deming, Clayton; Meyer, Jennifer A.; Segre, Julia A.] NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA.
   [Schoenfeld, Deborah; Nomicos, Effie; Kong, Heidi H.] NCI, Dermatol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
   [Park, Morgan] NHGRI, NIH Intramural Sequencing Ctr, NIH, Rockville, MD 20852 USA.
C3 National Institutes of Health (NIH) - USA; NIH National Human Genome Research Institute (NHGRI); National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); National Institutes of Health (NIH) - USA; NIH National Human Genome Research Institute (NHGRI)
RP Kong, HH (corresponding author), NCI, Dermatol Branch, Ctr Canc Res, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM konghe@mail.nih.gov; jsegre@nhgri.nih.gov
FU US National Institutes of Health (NIH) NHGRI and NCI Intramural Research Programs; NIH [1K99AR059222, 1UH2AR057504-01, 4UH3AR057504-02]; National Cancer Institute [ZIABC010938] Funding Source: NIH RePORTER; National Human Genome Research Institute [ZIBHG000196, ZIAHG000180] Funding Source: NIH RePORTER
NR 41
TC 893
Z9 1076
U1 5
U2 438
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 20
PY 2013
VL 498
IS 7454
BP 367
EP +
DI 10.1038/nature12171
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 166XI
UT WOS:000320592900041
PM 23698366
DA 2026-03-09
ER

PT J
AU Tobias, SM
   Cattaneo, F
AF Tobias, S. M.
   Cattaneo, F.
TI Shear-driven dynamo waves at high magnetic Reynolds number
SO NATURE
LA English
DT Article
ID flows
AB Astrophysical magnetic fields often display remarkable organization, despite being generated by dynamo action driven by turbulent flows at high conductivity(1,2). An example is the eleven-year solar cycle, which shows spatial coherence over the entire solar surface(3-5). The difficulty in understanding the emergence of this large-scale organization is that whereas at low conductivity (measured by the magnetic Reynolds number, Rm) dynamo fields are well organized, at high Rm their structure is dominated by rapidly varying small-scale fluctuations. This arises because the smallest scales have the highest rate of strain, and can amplify magnetic field most efficiently. Therefore most of the effort to find flows whose large-scale dynamo properties persist at high Rm has been frustrated. Here we report high-resolution simulations of a dynamo that can generate organized fields at high Rm; indeed, the generation mechanism, which involves the interaction between helical flows and shear, only becomes effective at large Rm. The shear does not enhance generation at large scales, as is commonly thought; instead it reduces generation at small scales. The solution consists of propagating dynamo waves, whose existence was postulated more than 60 years ago(6) and which have since been used to model the solar cycle(7).
C1 [Tobias, S. M.] Univ Leeds, Dept Appl Math, Leeds LS2 9JT, W Yorkshire, England.
   [Cattaneo, F.] Univ Chicago, Computat Inst, Chicago, IL 60637 USA.
   [Cattaneo, F.] Univ Chicago, Dept Astron & Astrophys, Chicago, IL 60637 USA.
C3 University of Leeds; University of Chicago; University of Chicago
RP Tobias, SM (corresponding author), Univ Leeds, Dept Appl Math, Leeds LS2 9JT, W Yorkshire, England.
EM smt@maths.leeds.ac.uk
FU Science and Technology Facilities Council (STFC); Center for Magnetic Self-Organisation (National Science Foundation) at the University of Chicago; STFC [ST/K000853/1, ST/H008802/1] Funding Source: UKRI; Science and Technology Facilities Council [ST/H008802/1, ST/K000853/1] Funding Source: researchfish; Direct For Mathematical & Physical Scien; Division Of Physics [0821899] Funding Source: National Science Foundation
NR 18
TC 65
Z9 72
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 MAY 23
PY 2013
VL 497
IS 7450
BP 463
EP 465
DI 10.1038/nature12177
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 148OG
UT WOS:000319254000041
PM 23698444
DA 2026-03-09
ER

PT J
AU Hepworth, MR
   Monticelli, LA
   Fung, TC
   Ziegler, CGK
   Grunberg, S
   Sinha, R
   Mantegazza, AR
   Ma, HL
   Crawford, A
   Angelosanto, JM
   Wherry, EJ
   Koni, PA
   Bushman, FD
   Elson, CO
   Eberl, G
   Artis, D
   Sonnenberg, GF
AF Hepworth, Matthew R.
   Monticelli, Laurel A.
   Fung, Thomas C.
   Ziegler, Carly G. K.
   Grunberg, Stephanie
   Sinha, Rohini
   Mantegazza, Adriana R.
   Ma, Hak-Ling
   Crawford, Alison
   Angelosanto, Jill M.
   Wherry, E. John
   Koni, Pandelakis A.
   Bushman, Frederic D.
   Elson, Charles O.
   Eberl, Gerard
   Artis, David
   Sonnenberg, Gregory F.
TI Innate lymphoid cells regulate CD4+ T-cell responses to intestinal commensal bacteria
SO NATURE
LA English
DT Article
ID tissue homeostasis; activation; identity; fate
AB Innate lymphoid cells (ILCs) are a recently characterized family of immune cells that have critical roles in cytokine-mediated regulation of intestinal epithelial cell barrier integrity(1-10). Alterations in ILC responses are associated with multiple chronic human diseases, including inflammatory bowel disease, implicating a role for ILCs in disease pathogenesis(3,8,11-13). Owing to an inability to target ILCs selectively, experimental studies assessing ILC function have predominantly used mice lacking adaptive immune cells(1-10). However, in lymphocyte-sufficient hosts ILCs are vastly outnumbered by CD4(+) T cells, which express similar profiles of effector cytokines. Therefore, the function of ILCs in the presence of adaptive immunity and their potential to influence adaptive immune cell responses remain unknown. To test this, we used genetic or antibody-mediated depletion strategies to target murine ILCs in the presence of an adaptive immune system. We show that loss of retinoic-acid-receptor-related orphan receptor-gamma t-positive (ROR gamma t(+)) ILCs was associated with dysregulated adaptive immune cell responses against commensal bacteria and low-grade systemic inflammation. Remarkably, ILC-mediated regulation of adaptive immune cells occurred independently of interleukin (IL)-17A, IL-22 or IL-23. Genome-wide transcriptional profiling and functional analyses revealed that ROR gamma t(+) ILCs express major histocompatibility complex class II (MHCII) and can process and present antigen. However, rather than inducing T-cell proliferation, ILCs acted to limit commensal bacteria-specific CD4(+) T-cell responses. Consistent with this, selective deletion of MHCII in murine ROR gamma t(+) ILCs resulted in dysregulated commensal bacteria-dependent CD4(+) T-cell responses that promoted spontaneous intestinal inflammation. These data identify that ILCs maintain intestinal homeostasis through MHCII-dependent interactions with CD4(+) T cells that limit pathological adaptive immune cell responses to commensal bacteria.
C1 [Hepworth, Matthew R.; Fung, Thomas C.; Sonnenberg, Gregory F.] Univ Penn, Dept Med, Perelman Sch Med, Div Gastroenterol, Philadelphia, PA 19104 USA.
   [Hepworth, Matthew R.; Monticelli, Laurel A.; Fung, Thomas C.; Crawford, Alison; Angelosanto, Jill M.; Wherry, E. John; Artis, David; Sonnenberg, Gregory F.] Univ Penn, Perelman Sch Med, Inst Immunol, Philadelphia, PA 19104 USA.
   [Monticelli, Laurel A.; Fung, Thomas C.; Grunberg, Stephanie; Sinha, Rohini; Crawford, Alison; Angelosanto, Jill M.; Wherry, E. John; Bushman, Frederic D.; Artis, David] Univ Penn, Perelman Sch Med, Dept Microbiol, Philadelphia, PA 19104 USA.
   [Ziegler, Carly G. K.] Mem Sloan Kettering Canc Ctr, ImmunoDynam Grp, Program Computat Biol, New York, NY 10065 USA.
   [Ziegler, Carly G. K.] Mem Sloan Kettering Canc Ctr, ImmunoDynam Grp, Program Immunol, New York, NY 10065 USA.
   [Mantegazza, Adriana R.] Univ Penn, Perelman Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA.
   [Mantegazza, Adriana R.] Univ Penn, Perelman Sch Med, Dept Physiol, Philadelphia, PA 19104 USA.
   [Ma, Hak-Ling] Pfizer Worldwide R&D, Biotherapeut Res & Dev, Inflammat & Immunol Res Unit, Cambridge, MA 02140 USA.
   [Koni, Pandelakis A.] Georgia Hlth Sci Univ, Ctr Canc, Canc Immunol Inflammat & Tolerance Program, Augusta, GA 30912 USA.
   [Elson, Charles O.] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA.
   [Eberl, Gerard] Inst Pasteur, Lymphoid Tissue Dev Unit, F-75724 Paris, France.
   [Eberl, Gerard] CNRS, URA 1961, F-75724 Paris, France.
   [Artis, David] Univ Penn, Sch Vet Med, Dept Pathobiol, Philadelphia, PA 19104 USA.
C3 University of Pennsylvania; University of Pennsylvania; University of Pennsylvania; Memorial Sloan Kettering Cancer Center; Memorial Sloan Kettering Cancer Center; University of Pennsylvania; University of Pennsylvania; Pfizer; Pfizer USA; University System of Georgia; Augusta University; University of Alabama System; University of Alabama Birmingham; Pasteur Network; Universite Paris Cite; Institut Pasteur Paris; Centre National de la Recherche Scientifique (CNRS); University of Pennsylvania
RP Sonnenberg, GF (corresponding author), Univ Penn, Dept Med, Perelman Sch Med, Div Gastroenterol, Philadelphia, PA 19104 USA.
EM gfield@mail.med.upenn.edu
FU National Institutes of Health [AI061570, AI087990, AI074878, AI095776, AI102942, AI095466, AI095608, AI097333, T32-AI055428, DK071176, DP5OD012116]; Crohn's and Colitis Foundation of America; Burroughs Wellcome Fund; NCI Comprehensive Cancer Center [2-P30 CA016520]; National Cancer Institute; National Cancer Institute [P30CA016520] Funding Source: NIH RePORTER; National Institute of Allergy and Infectious Diseases [T32AI007532, R01AI095466, U01AI095608, T32AI055428] Funding Source: NIH RePORTER; National Institute of Diabetes and Digestive and Kidney Diseases [P30DK050306] Funding Source: NIH RePORTER
NR 32
TC 628
Z9 756
U1 4
U2 148
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 6
PY 2013
VL 498
IS 7452
BP 113
EP +
DI 10.1038/nature12240
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 158DC
UT WOS:000319947800044
PM 23698371
DA 2026-03-09
ER

PT J
AU Gaffney, LP
   Butler, PA
   Scheck, M
   Hayes, AB
   Wenander, F
   Albers, M
   Bastin, B
   Bauer, C
   Blazhev, A
   Bönig, S
   Bree, N
   Cederkäll, J
   Chupp, T
   Cline, D
   Cocolios, TE
   Davinson, T
   DeWitte, H
   Diriken, J
   Grahn, T
   Herzan, A
   Huyse, M
   Jenkins, DG
   Joss, DT
   Kesteloot, N
   Konki, J
   Kowalczyk, M
   Kröll, T
   Kwan, E
   Lutter, R
   Moschner, K
   Napiorkowski, P
   Pakarinen, J
   Pfeiffer, M
   Radeck, D
   Reiter, P
   Reynders, K
   Rigby, SV
   Robledo, LM
   Rudigier, M
   Sambi, S
   Seidlitz, M
   Siebeck, B
   Stora, T
   Thoele, P
   Van Duppen, P
   Vermeulen, MJ
   von Schmid, M
   Voulot, D
   Warr, N
   Wimmer, K
   Wrzosek-Lipska, K
   Wu, CY
   Zielinska, M
AF Gaffney, L. P.
   Butler, P. A.
   Scheck, M.
   Hayes, A. B.
   Wenander, F.
   Albers, M.
   Bastin, B.
   Bauer, C.
   Blazhev, A.
   Boenig, S.
   Bree, N.
   Cederkall, J.
   Chupp, T.
   Cline, D.
   Cocolios, T. E.
   Davinson, T.
   DeWitte, H.
   Diriken, J.
   Grahn, T.
   Herzan, A.
   Huyse, M.
   Jenkins, D. G.
   Joss, D. T.
   Kesteloot, N.
   Konki, J.
   Kowalczyk, M.
   Kroell, Th.
   Kwan, E.
   Lutter, R.
   Moschner, K.
   Napiorkowski, P.
   Pakarinen, J.
   Pfeiffer, M.
   Radeck, D.
   Reiter, P.
   Reynders, K.
   Rigby, S. V.
   Robledo, L. M.
   Rudigier, M.
   Sambi, S.
   Seidlitz, M.
   Siebeck, B.
   Stora, T.
   Thoele, P.
   Van Duppen, P.
   Vermeulen, M. J.
   von Schmid, M.
   Voulot, D.
   Warr, N.
   Wimmer, K.
   Wrzosek-Lipska, K.
   Wu, C. Y.
   Zielinska, M.
TI Studies of pear-shaped nuclei using accelerated radioactive beams
SO NATURE
LA English
DT Article
ID e4 transition moments; coulomb-excitation; reflection asymmetry; dipole-moments; data sheets; states; quadrupole; isotopes; detector; model
AB There is strong circumstantial evidence that certain heavy, unstable atomic nuclei are 'octupole deformed', that is, distorted into a pear shape. This contrasts with the more prevalent rugby-ball shape of nuclei with reflection-symmetric, quadrupole deformations. The elusive octupole deformed nuclei are of importance for nuclear structure theory, and also in searches for physics beyond the standard model; any measurable electric-dipole moment (a signature of the latter) is expected to be amplified in such nuclei. Here we determine electric octupole transition strengths (a direct measure of octupole correlations) for short-lived isotopes of radon and radium. Coulomb excitation experiments were performed using accelerated beams of heavy, radioactive ions. Our data on Rn-220 and Ra-224 show clear evidence for stronger octupole deformation in the latter. The results enable discrimination between differing theoretical approaches to octupole correlations, and help to constrain suitable candidates for experimental studies of atomic electric-dipole moments that might reveal extensions to the standard model.
C1 [Gaffney, L. P.; Butler, P. A.; Scheck, M.; Joss, D. T.; Rigby, S. V.] Univ Liverpool, Oliver Lodge Lab, Liverpool L69 7ZE, Merseyside, England.
   [Scheck, M.; Bauer, C.; Boenig, S.; Kroell, Th.; von Schmid, M.] Tech Univ Darmstadt, Inst Kernphys, D-64289 Darmstadt, Germany.
   [Hayes, A. B.; Cline, D.] Univ Rochester, Dept Phys & Astron, Rochester, NY 14627 USA.
   [Wenander, F.; Cocolios, T. E.; Pakarinen, J.; Stora, T.; Voulot, D.] CERN Org Europeenne Rech Nucl, ISOLDE, CH-1211 Geneva, Switzerland.
   [Albers, M.; Blazhev, A.; Moschner, K.; Pfeiffer, M.; Radeck, D.; Reiter, P.; Rudigier, M.; Seidlitz, M.; Siebeck, B.; Thoele, P.; Warr, N.] Univ Cologne, Inst Kernphys, D-50937 Cologne, Germany.
   [Bastin, B.] GANIL, F-14076 Caen, France.
   [Bree, N.; DeWitte, H.; Diriken, J.; Huyse, M.; Kesteloot, N.; Reynders, K.; Sambi, S.; Van Duppen, P.; Wrzosek-Lipska, K.] Katholieke Univ Leuven, Inst Kern & Stralingsfys, B-3001 Louvain, Belgium.
   [Cederkall, J.] Lund Univ, Dept Nucl Phys, S-22100 Lund, Sweden.
   [Chupp, T.] Univ Michigan, Dept Phys, Ann Arbor, MI 48104 USA.
   [Davinson, T.] Univ Edinburgh, Sch Phys & Astron, Edinburgh EH9 3JZ, Midlothian, Scotland.
   [Diriken, J.; Kesteloot, N.] Ctr Etud Energie Nucl, SCK CEN Studiectr Kernenergie, B-2400 Mol, Belgium.
   [Grahn, T.; Herzan, A.; Konki, J.; Pakarinen, J.] Univ Jyvaskyla, Dept Phys, FI-40014 Jyvaskyla, Finland.
   [Grahn, T.; Herzan, A.; Konki, J.; Pakarinen, J.] Helsinki Inst Phys, FI-00014 Helsinki, Finland.
   [Jenkins, D. G.; Vermeulen, M. J.] Univ York, Dept Phys, York YO10 5DD, N Yorkshire, England.
   [Kowalczyk, M.; Napiorkowski, P.; Wrzosek-Lipska, K.; Zielinska, M.] Univ Warsaw, Heavy Ion Lab, PL-02093 Warsaw, Poland.
   [Kwan, E.; Wu, C. Y.] Lawrence Livermore Natl Lab, Div Phys, Livermore, CA 94551 USA.
   [Lutter, R.] Univ Munich, Maier Leibnitz Lab, D-85748 Garching, Germany.
   [Lutter, R.] Tech Univ Munich, D-85748 Garching, Germany.
   [Robledo, L. M.] Univ Autonoma Madrid, Dept Fis Teor, E-28049 Madrid, Spain.
   [Wimmer, K.] Tech Univ Munich, Phys Dept E12, D-85748 Garching, Germany.
   [Zielinska, M.] CEA Saclay, DSM IRFU SPhN, F-91191 Gif Sur Yvette, France.
C3 University of Liverpool; Technical University of Darmstadt; University of Rochester; University of Cologne; CEA; KU Leuven; Lund University; University of Michigan System; University of Michigan; University of Edinburgh; Belgian Nuclear Research Centre (SCK CEN); University of Jyvaskyla; Helsinki Institute of Physics; University of York - UK; University of Warsaw; United States Department of Energy (DOE); Lawrence Livermore National Laboratory; University of Munich; Technical University of Munich; Autonomous University of Madrid; Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - UAM - Institut de Fisica Teorica (IFT); Technical University of Munich; CEA; Universite Paris Saclay
RP Butler, PA (corresponding author), Univ Liverpool, Oliver Lodge Lab, Liverpool L69 7ZE, Merseyside, England.
EM peter.butler@liverpool.ac.uk
FU ISOLDE; STFC (UK); BMBF(Germany) [05P12RDCIA, 06DA9036I, 06KY9136I, 06KY205I]; HIC for FAIR (Germany); FWO-Vlaanderen (Belgium); Belgian Science Policy Office (IAP-BriX network) [P7/12]; Academy of Finland [131665]; DOE (US) [DE-AC52-07NA27344, DE-FG02-04ER41331]; NSF (US); MICINN (Spain) [FPA2009-08958, FIS2009-07277]; Consolider-Ingenio Programmes (Spain) [CPAN CSD2007-00042, MULTIDARK CSD2009-00064]; Polish Ministry for Science and Higher Education [589/N-G-POOL/2009/0]; EC via I3-EURONS (FP6) [RII3-CT-2004-506065]; MC Fellowship scheme (FP7) [PIEF-GA-2008-219175]; IA-ENSAR (FP7) [262010]; U.S. Department of Energy (DOE) [DE-FG02-04ER41331] Funding Source: U.S. Department of Energy (DOE); Division Of Physics; Direct For Mathematical & Physical Scien [0969079] Funding Source: National Science Foundation; Science and Technology Facilities Council [ST/J000094/1, ST/J00006X/1] Funding Source: researchfish; STFC [ST/J000094/1, ST/J00006X/1] Funding Source: UKRI
NR 50
TC 306
Z9 337
U1 1
U2 107
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 9
PY 2013
VL 497
IS 7448
BP 199
EP 204
DI 10.1038/nature12073
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 139CD
UT WOS:000318558200028
PM 23657348
DA 2026-03-09
ER

PT J
AU Kucsko, G
   Maurer, PC
   Yao, NY
   Kubo, M
   Noh, HJ
   Lo, PK
   Park, H
   Lukin, MD
AF Kucsko, G.
   Maurer, P. C.
   Yao, N. Y.
   Kubo, M.
   Noh, H. J.
   Lo, P. K.
   Park, H.
   Lukin, M. D.
TI Nanometre-scale thermometry in a living cell
SO NATURE
LA English
DT Article
ID temperature; cancer; thermogenesis; fluorescence; tissue; space; spins; time
AB Sensitive probing of temperature variations on nanometre scales is an outstanding challenge in many areas of modern science and technology(1). In particular, a thermometer capable of subdegree temperature resolution over a large range of temperatures as well as integration within a living system could provide a powerful new tool in many areas of biological, physical and chemical research. Possibilities range from the temperature-induced control of gene expression(2-5) and tumour metabolism(6) to the cell-selective treatment of disease(7,8) and the study of heat dissipation in integrated circuits(1). By combining local light-induced heat sources with sensitive nanoscale thermometry, it may also be possible to engineer biological processes at the subcellular level(2-5). Here we demonstrate a new approach to nanoscale thermometry that uses coherent manipulation of the electronic spin associated with nitrogen-vacancy colour centres in diamond. Our technique makes it possible to detect temperature variations as small as 1.8 mK (a sensitivity of 9 mK Hz(-1/2)) in an ultrapure bulk diamond sample. Using nitrogen-vacancy centres in diamond nanocrystals (nanodiamonds), we directly measure the local thermal environment on length scales as short as 200 nanometres. Finally, by introducing both nanodiamonds and gold nanoparticles into a single human embryonic fibroblast, we demonstrate temperature-gradient control and mapping at the subcellular level, enabling unique potential applications in life sciences.
C1 [Kucsko, G.; Maurer, P. C.; Yao, N. Y.; Park, H.; Lukin, M. D.] Harvard Univ, Dept Phys, Cambridge, MA 02138 USA.
   [Kubo, M.; Park, H.] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA.
   [Noh, H. J.; Park, H.] MIT, Broad Inst, Cambridge, MA 02142 USA.
   [Noh, H. J.; Park, H.] Harvard Univ, Cambridge, MA 02142 USA.
   [Lo, P. K.] City Univ Hong Kong, Dept Biol & Chem, Kowloon, Hong Kong, Peoples R China.
C3 Harvard University; Harvard University; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Harvard University; City University of Hong Kong
RP Park, H (corresponding author), Harvard Univ, Dept Phys, Cambridge, MA 02138 USA.
EM hongkun_park@harvard.edu; lukin@physics.harvard.edu
FU NSF; Center for Ultracold Atoms; Defense Advanced Research Projects Agency (QUASAR programme); Army Research Office (MURI programme); Packard Foundation; NIH [5DP1OD003893-03]; NHGRI [1P50HG006193-01]; Swiss National Science Foundation [PBSKP2_143918]; Swiss National Science Foundation (SNF) [PBSKP2_143918] Funding Source: Swiss National Science Foundation (SNF); Direct For Mathematical & Physical Scien; Division Of Physics [1125846] Funding Source: National Science Foundation; Direct For Mathematical & Physical Scien; Division Of Physics [0969816] Funding Source: National Science Foundation
NR 30
TC 1625
Z9 1861
U1 16
U2 973
PU NATURE PUBLISHING 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 1
PY 2013
VL 500
IS 7460
BP 54
EP U71
DI 10.1038/nature12373
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 192VK
UT WOS:000322514800026
PM 23903748
DA 2026-03-09
ER

PT J
AU Manzanillo, PS
   Ayres, JS
   Watson, RO
   Collins, AC
   Souza, G
   Rae, CS
   Schneider, DS
   Nakamura, K
   Shiloh, MU
   Cox, JS
AF Manzanillo, Paolo S.
   Ayres, Janelle S.
   Watson, Robert O.
   Collins, Angela C.
   Souza, Gianne
   Rae, Chris S.
   Schneider, David S.
   Nakamura, Ken
   Shiloh, Michael U.
   Cox, Jeffery S.
TI The ubiquitin ligase parkin mediates resistance to intracellular pathogens
SO NATURE
LA English
DT Article
ID mycobacterium-tuberculosis; deficient mice; body formation; autophagy; drosophila; p62/sqstm1; mitophagy; disease; susceptibility; associations
AB Ubiquitin-mediated targeting of intracellular bacteria to the autophagy pathway is a key innate defence mechanism against invading microbes, including the important human pathogen Mycobacterium tuberculosis. However, the ubiquitin ligases responsible for catalysing ubiquitin chains that surround intracellular bacteria are poorly understood. The parkin protein is a ubiquitin ligase with a well-established role in mitophagy, and mutations in the parkin gene (PARK2) lead to increased susceptibility to Parkinson's disease. Surprisingly, genetic polymorphisms in the PARK2 regulatory region are also associated with increased susceptibility to intracellular bacterial pathogens in humans, including Mycobacterium leprae and Salmonella enterica serovar Typhi, but the function of parkin in immunity has remained unexplored. Here we show that parkin has a role in ubiquitin-mediated autophagy of M. tuberculosis. Both parkin-deficient mice and flies are sensitive to various intracellular bacterial infections, indicating parkin has a conserved role in metazoan innate defence. Moreover, our work reveals an unexpected functional link between mitophagy and infectious disease.
C1 [Manzanillo, Paolo S.; Watson, Robert O.; Souza, Gianne; Cox, Jeffery S.] Univ Calif San Francisco, Dept Microbiol & Immunol, Program Microbial Pathogenesis & Host Def, San Francisco, CA 94158 USA.
   [Ayres, Janelle S.] Salk Inst Biol Studies, Immunobiol & Microbial Pathogenesis Lab, La Jolla, CA 92037 USA.
   [Collins, Angela C.; Shiloh, Michael U.] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Dallas, TX 75390 USA.
   [Rae, Chris S.] Univ Calif Berkeley, Dept Mol & Cellular Biol, Div Immunol & Pathogenesis, Berkeley, CA 94720 USA.
   [Schneider, David S.] Stanford Univ, Dept Microbiol & Immunol, Stanford, CA 94305 USA.
   [Nakamura, Ken] Univ Calif San Francisco, Gladstone Inst Neurol Dis, San Francisco, CA 94158 USA.
   [Nakamura, Ken] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94158 USA.
   [Nakamura, Ken] Univ Calif San Francisco, Grad Program Neurosci, San Francisco, CA 94158 USA.
   [Nakamura, Ken] Univ Calif San Francisco, Grad Program Biomed Sci, San Francisco, CA 94158 USA.
C3 University of California System; University of California San Francisco; Salk Institute; University of Texas System; University of Texas Southwestern Medical Center; University of California System; University of California Berkeley; Stanford University; 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
RP Cox, JS (corresponding author), Univ Calif San Francisco, Dept Microbiol & Immunol, Program Microbial Pathogenesis & Host Def, San Francisco, CA 94158 USA.
EM jeffery.cox@ucsf.edu
FU National Institutes of Health [R01 AI081727, P01 AI063302, R01 AI099439]; NINDS [P30NS069496]; National Institute of Allergy and Infectious Diseases [P01AI063302, T32AI060537] Funding Source: NIH RePORTER
NR 39
TC 454
Z9 518
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 SEP 26
PY 2013
VL 501
IS 7468
BP 512
EP +
DI 10.1038/nature12566
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 223RP
UT WOS:000324826300050
PM 24005326
DA 2026-03-09
ER

PT J
AU Floyd, SR
   Pacold, ME
   Huang, QY
   Clarke, SM
   Lam, FC
   Cannell, IG
   Bryson, BD
   Rameseder, J
   Lee, MJ
   Blake, EJ
   Fydrych, A
   Ho, R
   Greenberger, BA
   Chen, GC
   Maffa, A
   Del Rosario, AM
   Root, DE
   Carpenter, AE
   Hahn, WC
   Sabatini, DM
   Chen, CC
   White, FM
   Bradner, JE
   Yaffe, MB
AF Floyd, Scott R.
   Pacold, Michael E.
   Huang, Qiuying
   Clarke, Scott M.
   Lam, Fred C.
   Cannell, Ian G.
   Bryson, Bryan D.
   Rameseder, Jonathan
   Lee, Michael J.
   Blake, Emily J.
   Fydrych, Anna
   Ho, Richard
   Greenberger, Benjamin A.
   Chen, Grace C.
   Maffa, Amanda
   Del Rosario, Amanda M.
   Root, David E.
   Carpenter, Anne E.
   Hahn, William C.
   Sabatini, David M.
   Chen, Clark C.
   White, Forest M.
   Bradner, James E.
   Yaffe, Michael B.
TI The bromodomain protein Brd4 insulates chromatin from DNA damage signalling
SO NATURE
LA English
DT Article
ID p-tefb; gamma-h2ax; activation; transcription; repair; breaks
AB DNA damage activates a signalling network that blocks cell-cycle progression, recruits DNA repair factors and/or triggers senescence or programmed cell death(1). Alterations in chromatin structure are implicated in the initiation and propagation of the DNA damage response(2). Here we further investigate the role of chromatin structure in the DNA damage response by monitoring ionizing-radiation-induced signalling and response events with a high-content multiplex RNA-mediated interference screen of chromatin-modifying and -interacting genes. We discover that an isoform of Brd4, a bromodomain and extra-terminal (BET) family member, functions as an endogenous inhibitor of DNA damage response signalling by recruiting the condensin II chromatin remodelling complex to acetylated histones through bromodomain interactions. Loss of this isoform results in relaxed chromatin structure, rapid cell-cycle checkpoint recovery and enhanced survival after irradiation, whereas functional gain of this isoform compacted chromatin, attenuated DNA damage response signalling and enhanced radiation-induced lethality. These data implicate Brd4, previously known for its role in transcriptional control, as an insulator of chromatin that can modulate the signalling response to DNA damage.
C1 [Floyd, Scott R.; Pacold, Michael E.; Huang, Qiuying; Clarke, Scott M.; Lam, Fred C.; Cannell, Ian G.; Bryson, Bryan D.; Rameseder, Jonathan; Lee, Michael J.; Blake, Emily J.; Fydrych, Anna; Ho, Richard; Greenberger, Benjamin A.; Chen, Grace C.; Maffa, Amanda; Del Rosario, Amanda M.; White, Forest M.; Yaffe, Michael B.] MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA.
   [Floyd, Scott R.] Beth Israel Deaconess Med Ctr, Dept Radiat Oncol, Boston, MA 02215 USA.
   [Pacold, Michael E.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02215 USA.
   [Pacold, Michael E.; Sabatini, David M.] Whitehead Inst, Cambridge, MA 02139 USA.
   [Root, David E.; Carpenter, Anne E.; Hahn, William C.; Sabatini, David M.; Bradner, James E.; Yaffe, Michael B.] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA.
   [Hahn, William C.; Chen, Clark C.; Bradner, James E.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA.
   [Chen, Clark C.; Yaffe, Michael B.] Beth Israel Deaconess Med Ctr, Dept Surg, Boston, MA 02215 USA.
   [White, Forest M.; Yaffe, Michael B.] MIT, Dept Biol Engn, Cambridge, MA 02139 USA.
   [Yaffe, Michael B.] MIT, Dept Biol, Cambridge, MA 02139 USA.
C3 Massachusetts Institute of Technology (MIT); Harvard University; Harvard University Medical Affiliates; Beth Israel Deaconess Medical Center; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Massachusetts Institute of Technology (MIT); Whitehead Institute; 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; Beth Israel Deaconess Medical Center; Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT)
RP Yaffe, MB (corresponding author), MIT, Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
EM myaffe@mit.edu
FU Koch Institute; Center for Environmental Health Sciences National Institutes of Health [P30-CA14051, ES-002109]; SPARC; Holman Pathway Research Resident Seed Grant; American Society for Radiation Oncology Junior Faculty Career Research Training Award; Burroughs Wellcome Career Award for Medical Scientists;  [R01-ES15339];  [1-U54-CA112967-04];  [R21-NS063917]; National Cancer Institute [P30CA014051] Funding Source: NIH RePORTER
NR 22
TC 268
Z9 341
U1 2
U2 84
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 13
PY 2013
VL 498
IS 7453
BP 246
EP +
DI 10.1038/nature12147
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 162RR
UT WOS:000320283400052
PM 23728299
DA 2026-03-09
ER

PT J
AU Palomaki, TA
   Harlow, JW
   Teufel, JD
   Simmonds, RW
   Lehnert, KW
AF Palomaki, T. A.
   Harlow, J. W.
   Teufel, J. D.
   Simmonds, R. W.
   Lehnert, K. W.
TI Coherent state transfer between itinerant microwave fields and a mechanical oscillator
SO NATURE
LA English
DT Article
ID quantum ground-state; nanomechanical motion; resonator; circuit
AB Macroscopic mechanical oscillators have been coaxed into a regime of quantum behaviour by direct refrigeration(1) or a combination of refrigeration and laser-like cooling(2,3). This result supports the idea that mechanical oscillators may perform useful functions in the processing of quantum information with superconducting circuits(4-7), either by serving as a quantum memory for the ephemeral state of a microwave field or by providing a quantum interface between otherwise incompatible systems(8-14). As yet, the transfer of an itinerant state or a propagating mode of a microwave field to and from a storage medium has not been demonstrated, owing to the inability to turn on and off the interaction between the microwave field and the medium sufficiently quickly. Here we demonstrate that the state of an itinerant microwave field can be coherently transferred into, stored in and retrieved from a mechanical oscillator with amplitudes at the single-quantum level. Crucially, the time to capture and to retrieve the microwave state is shorter than the quantum state lifetime of the mechanical oscillator. In this quantum regime, the mechanical oscillator can both store quantum information and enable its transfer between otherwise incompatible systems.
C1 [Palomaki, T. A.; Harlow, J. W.; Lehnert, K. W.] NIST, JILA, Boulder, CO 80309 USA.
   [Palomaki, T. A.; Harlow, J. W.; Lehnert, K. W.] Univ Colorado, Boulder, CO 80309 USA.
   [Palomaki, T. A.; Harlow, J. W.; Lehnert, K. W.] Univ Colorado, Dept Phys, Boulder, CO USA.
   [Teufel, J. D.; Simmonds, R. W.] NIST, Boulder, CO 80305 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; National Institute of Standards & Technology (NIST) - USA
RP Lehnert, KW (corresponding author), NIST, JILA, Boulder, CO 80309 USA.
EM konrad.lehnert@jila.colorado.edu
FU DARPA QuASAR programme; US NSF Physics Frontier Center; NIST
NR 30
TC 376
Z9 428
U1 5
U2 140
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 14
PY 2013
VL 495
IS 7440
BP 210
EP 214
DI 10.1038/nature11915
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 113FP
UT WOS:000316652300045
PM 23486060
DA 2026-03-09
ER

PT J
AU Goujon, C
   Moncorgé, O
   Bauby, H
   Doyle, T
   Ward, CC
   Schaller, T
   Hué, S
   Barclay, WS
   Schulz, R
   Malim, MH
AF Goujon, Caroline
   Moncorge, Olivier
   Bauby, Helene
   Doyle, Tomas
   Ward, Christopher C.
   Schaller, Torsten
   Hue, Stephane
   Barclay, Wendy S.
   Schulz, Reiner
   Malim, Michael H.
TI Human MX2 is an interferon-induced post-entry inhibitor of HIV-1 infection
SO NATURE
LA English
DT Article
ID immunodeficiency-virus type-1; primary human macrophages; influenza-virus; nuclear import; human-cells; in-vivo; antiviral function; nondividing cells; protein; expression
AB Animal cells harbour multiple innate effector mechanisms that inhibit virus replication. For the pathogenic retrovirus human immunodeficiency virus type 1 (HIV-1), these include widely expressed restriction factors(1), such as APOBEC3 proteins(2), TRIM5-alpha(3), BST2 (refs 4, 5) and SAMHD1 (refs 6, 7), as well as additional factors that are stimulated by type 1 interferon (IFN)(8-14). Here we use both ectopic expression and gene-silencing experiments to define the human dynamin-like, IFN-induced myxovirus resistance 2 (MX2, also known as MXB) protein as a potent inhibitor of HIV-1 infection and as a key effector of IFN-alpha-mediated resistance to HIV-1 infection. MX2 suppresses infection by all HIV-1 strains tested, has equivalent or reduced effects on divergent simian immunodeficiency viruses, and does not inhibit other retroviruses such as murine leukaemia virus. The Capsid region of the viral Gag protein dictates susceptibility to MX2, and the block to infection occurs at a late post-entry step, with both the nuclear accumulation and chromosomal integration of nascent viral complementary DNA suppressed. Finally, human MX1 (also known as MXA), a closely related protein that has long been recognized as a broadly acting inhibitor of RNA and DNA viruses, including the orthomyxovirus influenza A virus(15,16), does not affect HIV-1, whereas MX2 is ineffective against influenza virus. MX2 is therefore a cell-autonomous, anti-HIV-1 resistance factor whose purposeful mobilization may represent a new therapeutic approach for the treatment of HIV/AIDS.
C1 [Goujon, Caroline; Bauby, Helene; Doyle, Tomas; Ward, Christopher C.; Schaller, Torsten; Malim, Michael H.] Kings Coll London, Dept Infect Dis, London SE1 9RT, England.
   [Moncorge, Olivier; Barclay, Wendy S.] Univ London Imperial Coll Sci Technol & Med, Div Infect Dis, Virol Sect, London W2 1PG, England.
   [Hue, Stephane] UCL, Div Infect & Immun, Ctr Med Mol Virol, London WC1 6RT, England.
   [Schulz, Reiner] Kings Coll London, Dept Med & Mol Genet, London SE1 9RT, England.
C3 University of London; King's College London; Imperial College London; University of London; University College London; University of London; King's College London
RP Malim, MH (corresponding author), Kings Coll London, Dept Infect Dis, London SE1 9RT, England.
EM michael.malim@kcl.ac.uk
FU UK Medical Research Council; National Institutes of Health [DA033773]; European Commission [PIEF-GA-2009-237501]; Wellcome Trust; Department of Health via a National Institute for Health Research comprehensive Biomedical Research Centre; King's College London; King's College Hospital NHS Foundation Trust; MRC [G1001081, G1000196] Funding Source: UKRI; Engineering and Physical Sciences Research Council [836374] Funding Source: researchfish; Medical Research Council [G1001081, G1000196] Funding Source: researchfish; National Institute for Health Research [ACF-2011-17-013] Funding Source: researchfish
NR 61
TC 476
Z9 577
U1 0
U2 96
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 24
PY 2013
VL 502
IS 7472
BP 559
EP +
DI 10.1038/nature12542
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 238YN
UT WOS:000325988400056
PM 24048477
DA 2026-03-09
ER

PT J
AU van Geen, A
   Bostick, BC
   Trang, PTK
   Lan, VM
   Mai, NN
   Manh, PD
   Viet, PH
   Radloff, K
   Aziz, Z
   Mey, JL
   Stahl, MO
   Harvey, CF
   Oates, P
   Weinman, B
   Stengel, C
   Frei, F
   Kipfer, R
   Berg, M
AF van Geen, Alexander
   Bostick, Benjamin C.
   Pham Thi Kim Trang
   Vi Mai Lan
   Nguyen-Ngoc Mai
   Phu Dao Manh
   Pham Hung Viet
   Radloff, Kathleen
   Aziz, Zahid
   Mey, Jacob L.
   Stahl, Mason O.
   Harvey, Charles F.
   Oates, Peter
   Weinman, Beth
   Stengel, Caroline
   Frei, Felix
   Kipfer, Rolf
   Berg, Michael
TI Retardation of arsenic transport through a Pleistocene aquifer
SO NATURE
LA English
DT Article
ID river flood-plain; geochemical processes; drinking-water; noble-gases; groundwater; bangladesh; vietnam; release; delta; migration
AB Groundwater drawn daily from shallow alluvial sands by millions of wells over large areas of south and southeast Asia exposes an estimated population of over a hundred million people to toxic levels of arsenic(1). Holocene aquifers are the source of widespread arsenic poisoning across the region(2,3). In contrast, Pleistocene sands deposited in this region more than 12,000 years ago mostly do not host groundwater with high levels of arsenic. Pleistocene aquifers are increasingly used as a safe source of drinking water(4) and it is therefore important to understand under what conditions low levels of arsenic can be maintained. Here we reconstruct the initial phase of contamination of a Pleistocene aquifer near Hanoi, Vietnam. We demonstrate that changes in groundwater flow conditions and the redox state of the aquifer sands induced by groundwater pumping caused the lateral intrusion of arsenic contamination more than 120 metres from a Holocene aquifer into a previously uncontaminated Pleistocene aquifer. We also find that arsenic adsorbs onto the aquifer sands and that there is a 16-20-fold retardation in the extent of the contamination relative to the reconstructed lateral movement of groundwater over the same period. Our findings suggest that arsenic contamination of Pleistocene aquifers in south and southeast Asia as a consequence of increasing levels of groundwater pumping may have been delayed by the retardation of arsenic transport.
C1 [van Geen, Alexander; Bostick, Benjamin C.; Radloff, Kathleen; Aziz, Zahid; Mey, Jacob L.] Columbia Univ, Lamont Doherty Earth Observ, Palisades, NY 10964 USA.
   [Pham Thi Kim Trang; Vi Mai Lan; Nguyen-Ngoc Mai; Phu Dao Manh; Pham Hung Viet] Vietnam Natl Univ, Hanoi Univ Sci, Res Ctr Environm Technol & Sustainable Dev CETASD, Hanoi, Vietnam.
   [Mey, Jacob L.] Kingsborough Community Coll, Dept Phys Sci, Brooklyn, NY 11235 USA.
   [Stahl, Mason O.; Harvey, Charles F.] MIT, Cambridge, MA 02139 USA.
   [Oates, Peter] Anchor QEA, Montvale, NJ 07645 USA.
   [Weinman, Beth] Vanderbilt Univ, Nashville, TN 37235 USA.
   [Stengel, Caroline; Frei, Felix; Kipfer, Rolf; Berg, Michael] Eawag, Swiss Fed Inst Aquat Sci & Technol, CH-8600 Dubendorf, Switzerland.
   [Kipfer, Rolf] Zurich ETHZ, Swiss Fed Inst Technol, Inst Geochem & Petrol, CH-8092 Zurich, Switzerland.
C3 Columbia University; Vietnam National University Hanoi (VNU Hanoi) System; City University of New York (CUNY) System; Massachusetts Institute of Technology (MIT); Vanderbilt University; Swiss Federal Institutes of Technology Domain; Swiss Federal Institute of Aquatic Science & Technology (EAWAG); Swiss Federal Institutes of Technology Domain; ETH Zurich
RP van Geen, A (corresponding author), Columbia Univ, Lamont Doherty Earth Observ, Palisades, NY 10964 USA.
EM avangeen@ldeo.columbia.edu
FU NSF [EAR 09-11557]; Swiss Agency for Development and Cooperation [NAFOSTED 105-09-59-09]; NIEHS [P42 ES010349, P42 ES016454]; Directorate For Geosciences; Division Of Earth Sciences [0911557] Funding Source: National Science Foundation
NR 38
TC 141
Z9 154
U1 4
U2 278
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 12
PY 2013
VL 501
IS 7466
BP 204
EP +
DI 10.1038/nature12444
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 215XR
UT WOS:000324244900037
PM 24025840
DA 2026-03-09
ER

PT J
AU Liu, MZ
   Johnston, MB
   Snaith, HJ
AF Liu, Mingzhen
   Johnston, Michael B.
   Snaith, Henry J.
TI Efficient planar heterojunction perovskite solar cells by vapour deposition
SO NATURE
LA English
DT Article
ID low-cost
AB Many different photovoltaic technologies are being developed for large-scale solar energy conversion(1-4). The wafer-based first-generation photovoltaic devices(1) have been followed by thin-film solid semiconductor absorber layers sandwiched between two charge-selective contacts(3) and nanostructured (or mesostructured) solar cells that rely on a distributed heterojunction to generate charge and to transport positive and negative charges in spatially separated phases(4-6). Although many materials have been used in nanostructured devices, the goal of attaining high-efficiency thin-film solar cells in such a way has yet to be achieved(7). Organometal halide perovskites have recently emerged as a promising material for high-efficiency nanostructured devices(8-11). Here we show that nanostructuring is not necessary to achieve high efficiencies with this material: a simple planar heterojunction solar cell incorporating vapour-deposited perovskite as the absorbing layer can have solar-to-electrical power conversion efficiencies of over 15 per cent (as measured under simulated full sunlight). This demonstrates that perovskite absorbers can function at the highest efficiencies in simplified device architectures, without the need for complex nanostructures.
C1 [Liu, Mingzhen; Johnston, Michael B.; Snaith, Henry J.] Univ Oxford, Dept Phys, Clarendon Lab, Oxford OX1 3PU, England.
C3 University of Oxford
RP Snaith, HJ (corresponding author), Univ Oxford, Dept Phys, Clarendon Lab, Parks Rd, Oxford OX1 3PU, England.
EM h.snaith1@physics.ox.ac.uk
FU EPSRC; European Research Council (ERC) 'Hyper Project' [279881]; European Research Council (ERC) [279881] Funding Source: European Research Council (ERC)
NR 25
TC 7211
Z9 7954
U1 62
U2 8247
PU NATURE PUBLISHING 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 19
PY 2013
VL 501
IS 7467
BP 395
EP +
DI 10.1038/nature12509
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 219XT
UT WOS:000324545700040
PM 24025775
DA 2026-03-09
ER

PT J
AU Burns, MB
   Lackey, L
   Carpenter, MA
   Rathore, A
   Land, AM
   Leonard, B
   Refsland, EW
   Kotandeniya, D
   Tretyakova, N
   Nikas, JB
   Yee, D
   Temiz, NIA
   Donohue, DE
   McDougle, RM
   Brown, WL
   Law, EK
   Harris, RS
AF Burns, Michael B.
   Lackey, Lela
   Carpenter, Michael A.
   Rathore, Anurag
   Land, Allison M.
   Leonard, Brandon
   Refsland, Eric W.
   Kotandeniya, Delshanee
   Tretyakova, Natalia
   Nikas, Jason B.
   Yee, Douglas
   Temiz, Nuri I. A.
   Donohue, Duncan E.
   McDougle, Rebecca M.
   Brown, William L.
   Law, Emily K.
   Harris, Reuben S.
TI APOBEC3B is an enzymatic source of mutation in breast cancer
SO NATURE
LA English
DT Article
ID foreign dna; landscape; aid
AB Several mutations are required for cancer development, and genome sequencing has revealed that many cancers, including breast cancer, have somatic mutation spectra dominated by C-to-T transitions(1-9). Most of these mutations occur at hydrolytically disfavoured(10) non-methylated cytosines throughout the genome, and are sometimes clustered(8). Here we show that the DNA cytosine deaminase APOBEC3B is a probable source of these mutations. APOBEC3B messenger RNA is upregulated in most primary breast tumours and breast cancer cell lines. Tumours that express high levels of APOBEC3B have twice as many mutations as those that express low levels and are more likely to have mutations in TP53. Endogenous APOBEC3B protein is predominantly nuclear and the only detectable source of DNA C-to-U editing activity in breast cancer cell-line extracts. Knockdown experiments show that endogenous APOBEC3B correlates with increased levels of genomic uracil, increased mutation frequencies, and C-to-T transitions. Furthermore, induced APOBEC3B overexpression causes cell cycle deviations, cell death, DNA fragmentation, gamma-H2AX accumulation and C-to-T mutations. Our data suggest a model in which APOBEC3B-catalysed deamination provides a chronic source of DNA damage in breast cancers that could select TP53 inactivation and explain how some tumours evolve rapidly and manifest heterogeneity.
C1 [Burns, Michael B.; Lackey, Lela; Carpenter, Michael A.; Rathore, Anurag; Land, Allison M.; Refsland, Eric W.; McDougle, Rebecca M.; Brown, William L.; Law, Emily K.; Harris, Reuben S.] Univ Minnesota, Biochem Mol Biol & Biophys Dept, Minneapolis, MN 55455 USA.
   [Burns, Michael B.; Lackey, Lela; Carpenter, Michael A.; Rathore, Anurag; Land, Allison M.; Leonard, Brandon; Refsland, Eric W.; Kotandeniya, Delshanee; Tretyakova, Natalia; Nikas, Jason B.; Yee, Douglas; McDougle, Rebecca M.; Brown, William L.; Law, Emily K.; Harris, Reuben S.] Univ Minnesota, Masonic Canc Ctr, Minneapolis, MN 55455 USA.
   [Burns, Michael B.; Lackey, Lela; Carpenter, Michael A.; Rathore, Anurag; Land, Allison M.; Leonard, Brandon; Refsland, Eric W.; McDougle, Rebecca M.; Brown, William L.; Law, Emily K.; Harris, Reuben S.] Univ Minnesota, Inst Mol Virol, Minneapolis, MN 55455 USA.
   [Burns, Michael B.; Lackey, Lela; Carpenter, Michael A.; Rathore, Anurag; Land, Allison M.; Leonard, Brandon; Refsland, Eric W.; McDougle, Rebecca M.; Brown, William L.; Law, Emily K.; Harris, Reuben S.] Univ Minnesota, Ctr Genome Engn, Minneapolis, MN 55455 USA.
   [Leonard, Brandon; Harris, Reuben S.] Univ Minnesota, Microbiol Canc Biol & Immunol Grad Program, Minneapolis, MN 55455 USA.
   [Kotandeniya, Delshanee; Tretyakova, Natalia] Univ Minnesota, Dept Med Chem, Minneapolis, MN 55455 USA.
   [Temiz, Nuri I. A.; Donohue, Duncan E.] SAIC Frederick Inc, In Silico Res Ctr Excellence, Adv Biomed Comp Ctr, Informat Syst Program,Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
C3 University of Minnesota System; University of Minnesota Twin Cities; University of Minnesota System; University of Minnesota Twin Cities; University of Minnesota System; University of Minnesota Twin Cities; University of Minnesota System; University of Minnesota Twin Cities; University of Minnesota System; University of Minnesota Twin Cities; University of Minnesota System; University of Minnesota Twin Cities; Science Applications International Corporation (SAIC); SAIC-Frederick; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); Frederick National Laboratory for Cancer Research
RP Harris, RS (corresponding author), Univ Minnesota, Biochem Mol Biol & Biophys Dept, Minneapolis, MN 55455 USA.
EM rsh@umn.edu
FU Academic Health Center; National Institutes of Health (NIH) [P30 CA77598, P50 CA101955, KL2 RR033182]; Cancer Biology Training Grant [NIH NCI T32 CA009138]; Department of Defense Breast Cancer Research Program Predoctoral Fellowship [BC101124]; National Science Foundation Predoctoral Fellowship; Institute for Molecular Virology Training Grant NIH [T32 AI083196]; NIH [F32 GM095219, F31 DA033186, R01 AI064046, NIH P01 GM091743, 1UL1RR033183]; CIHR; National Cancer Institute, NIH, CBIIT/caBIG ISRCE [09-260]; Children's Cancer Research Fund; National Cancer Institute [P30CA077598, T32CA009138] Funding Source: NIH RePORTER; National Institute of Allergy and Infectious Diseases [T32AI083196] Funding Source: NIH RePORTER
NR 27
TC 689
Z9 817
U1 1
U2 114
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 21
PY 2013
VL 494
IS 7437
BP 366
EP 370
DI 10.1038/nature11881
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 095CS
UT WOS:000315312900041
PM 23389445
DA 2026-03-09
ER

PT J
AU Sistla, SA
   Moore, JC
   Simpson, RT
   Gough, L
   Shaver, GR
   Schimel, JP
AF Sistla, Seeta A.
   Moore, John C.
   Simpson, Rodney T.
   Gough, Laura
   Shaver, Gaius R.
   Schimel, Joshua P.
TI Long-term warming restructures Arctic tundra without changing net soil carbon storage
SO NATURE
LA English
DT Article
ID microbial biomass; organic-matter; fungal abundance; alaskan tundra; ecosystems; nitrogen; bacterial; fertilization; respiration; community
AB High latitudes contain nearly half of global soil carbon, prompting interest in understanding how the Arctic terrestrial carbon balance will respond to rising temperatures(1,2). Low temperatures suppress the activity of soil biota, retarding decomposition and nitrogen release, which limits plant and microbial growth(3). Warming initially accelerates decomposition(4-6), increasing nitrogen availability, productivity and woody-plant dominance(3,7). However, these responses may be transitory, because coupled abiotic-biotic feedback loops that alter soil-temperature dynamics and change the structure and activity of soil communities, can develop(8,9). Here we report the results of a two-decade summer warming experiment in an Alaskan tundra ecosystem. Warming increased plant biomass and woody dominance, indirectly increased winter soil temperature, homogenized the soil trophic structure across horizons and suppressed surface-soil-decomposer activity, but did not change total soil carbon or nitrogen stocks, thereby increasing net ecosystem carbon storage. Notably, the strongest effects were in the mineral horizon, where warming increased decomposer activity and carbon stock: a 'biotic awakening' at depth.
C1 [Sistla, Seeta A.; Schimel, Joshua P.] Univ Calif Santa Barbara, Dept Ecol Evolut & Marine Biol, Santa Barbara, CA 93108 USA.
   [Moore, John C.; Simpson, Rodney T.] Colorado State Univ, Nat Resource Ecol Lab, Ft Collins, CO 80523 USA.
   [Moore, John C.] Colorado State Univ, Dept Ecosyst Sci & Sustainabil, Ft Collins, CO 80523 USA.
   [Gough, Laura] Univ Texas Arlington, Dept Biol, Arlington, TX 76019 USA.
   [Shaver, Gaius R.] Marine Biol Lab, Ctr Ecosyst, Woods Hole, MA 02543 USA.
C3 University of California System; University of California Santa Barbara; Colorado State University System; Colorado State University Fort Collins; Colorado State University System; Colorado State University Fort Collins; University of Texas System; University of Texas Arlington; Marine Biological Laboratory - Woods Hole
RP Sistla, SA (corresponding author), Univ Calif Santa Barbara, Dept Ecol Evolut & Marine Biol, Santa Barbara, CA 93108 USA.
EM sistla@lifesci.ucsb.edu
FU DOE; Leal Anne Kerry Mertes scholarship; Explorer's Club grant; NSF [OPP-1023524, OPP-0425606, OPP-0909441, OPP-0425827, OPP-0909507]; Arctic LTER program NSF-DEB [1026843]; Division Of Environmental Biology; Direct For Biological Sciences [1026843] Funding Source: National Science Foundation; Emerging Frontiers; Direct For Biological Sciences [1065587] Funding Source: National Science Foundation; Office of Polar Programs (OPP); Directorate For Geosciences [0909441, 0902038, 1107707, 0807639] Funding Source: National Science Foundation; Office of Polar Programs (OPP); Directorate For Geosciences [0856853, 0909507] Funding Source: National Science Foundation
NR 38
TC 375
Z9 443
U1 16
U2 799
PU NATURE PUBLISHING 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 30
PY 2013
VL 497
IS 7451
BP 615
EP +
DI 10.1038/nature12129
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 152UF
UT WOS:000319556100043
PM 23676669
DA 2026-03-09
ER

PT J
AU Chen, CC
   Zhu, C
   White, ER
   Chiu, CY
   Scott, MC
   Regan, BC
   Marks, LD
   Huang, Y
   Miao, JW
AF Chen, Chien-Chun
   Zhu, Chun
   White, Edward R.
   Chiu, Chin-Yi
   Scott, M. C.
   Regan, B. C.
   Marks, Laurence D.
   Huang, Yu
   Miao, Jianwei
TI Three-dimensional imaging of dislocations in a nanoparticle at atomic resolution
SO NATURE
LA English
DT Article
ID electron-microscopy; phase-contrast; tomography; enhancement; defects; gold
AB Dislocations and their interactions strongly influence many material properties, ranging from the strength of metals and alloys to the efficiency of light-emitting diodes and laser diodes(1-4). Several experimental methods can be used to visualize dislocations. Transmission electron microscopy (TEM) has long been used to image dislocations in materials(5-9), and high-resolution electron microscopy can reveal dislocation core structures in high detail(10), particularly in annular dark-field mode(11). A TEM image, however, represents a two-dimensional projection of a three-dimensional (3D) object (although stereo TEM provides limited information about 3D dislocations(4)). X-ray topography can image dislocations in three dimensions, but with reduced resolution(12). Using weak-beam dark-field TEM13 and scanning TEM14, electron tomography has been used to image 3D dislocations at a resolution of about five nanometres (refs 15, 16). Atom probe tomography can offer higher-resolution 3D characterization of dislocations, but requires needle-shaped samples and can detect only about 60 per cent of the atoms in a sample(17). Here we report 3D imaging of dislocations in materials at atomic resolution by electron tomography. By applying 3D Fourier filtering together with equal-slope tomographic reconstruction, we observe nearly all the atoms in a multiply twinned platinum nanoparticle. We observed atomic steps at 3D twin boundaries and imaged the 3D core structure of edge and screw dislocations at atomic resolution. These dislocations and the atomic steps at the twin boundaries, which appear to be stress-relief mechanisms, are not visible in conventional two-dimensional projections. The ability to image 3D disordered structures such as dislocations at atomic resolution is expected to find applications in materials science, nanoscience, solid-state physics and chemistry.
C1 [Chen, Chien-Chun; Zhu, Chun; White, Edward R.; Scott, M. C.; Regan, B. C.; Miao, Jianwei] Univ Calif Los Angeles, Dept Phys & Astron, Los Angeles, CA 90095 USA.
   [Chen, Chien-Chun; Zhu, Chun; White, Edward R.; Chiu, Chin-Yi; Scott, M. C.; Regan, B. C.; Huang, Yu; Miao, Jianwei] Univ Calif Los Angeles, Calif NanoSyst Inst, Los Angeles, CA 90095 USA.
   [Chiu, Chin-Yi; Huang, Yu] Univ Calif Los Angeles, Dept Mat Sci & Engn, Los Angeles, CA 90095 USA.
   [Marks, Laurence D.] Northwestern Univ, Dept Mat Sci & Engn, Evanston, IL 60201 USA.
C3 University of California System; University of California Los Angeles; University of California System; University of California Los Angeles; University of California System; University of California Los Angeles; Northwestern University
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]; NSF MRSEC at the Materials Research Center of Northwestern University [DMR-1121262]; Direct For Mathematical & Physical Scien; Division Of Materials Research [1121262] Funding Source: National Science Foundation
NR 38
TC 331
Z9 400
U1 9
U2 883
PU NATURE PUBLISHING 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 4
PY 2013
VL 496
IS 7443
BP 74
EP +
DI 10.1038/nature12009
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 117ZZ
UT WOS:000316993400027
PM 23535594
DA 2026-03-09
ER

PT J
AU Trigo, MD
   Miller-Jones, JCA
   Migliari, S
   Broderick, JW
   Tzioumis, T
AF Trigo, Maria Diaz
   Miller-Jones, James C. A.
   Migliari, Simone
   Broderick, Jess W.
   Tzioumis, Tasso
TI Baryons in the relativistic jets of the stellar-mass black-hole candidate 4U 1630-47
SO NATURE
LA English
DT Article
ID gamma-ray emission; accretion disks; tev neutrinos; xmm-newton; radio; line; telescope; model; state; power
AB Accreting black holes are known to power relativistic jets, both in stellar-mass binary systems and at the centres of galaxies. The power carried away by the jets, and, hence, the feedback they provide to their surroundings, depends strongly on their composition. Jets containing a baryonic component should carry significantly more energy than electron-positron jets. Energetic considerations(1,2) and circular-polarization measurements(3) have provided conflicting circumstantial evidence for the presence or absence of baryons in jets, and the only system in which they have been unequivocally detected is the peculiar X-ray binary SS 433 (refs 4, 5). Here we report the detection of Doppler-shifted X-ray emission lines from a more typical black-hole candidate X-ray binary, 4U 1630-47, coincident with the reappearance of radio emission from the jets of the source. We argue that these lines arise from baryonic matter in a jet travelling at approximately two-thirds the speed of light, thereby establishing the presence of baryons in the jet. Such baryonic jets are more likely to be powered by the accretion disk(6) than by the spin of the black hole(7), and if the baryons can be accelerated to relativistic speeds, the jets should be strong sources of gamma-rays and neutrino emission.
C1 [Trigo, Maria Diaz] European So Observ, D-85748 Garching, Germany.
   [Miller-Jones, James C. A.] Curtin Univ, Int Ctr Radio Astron Res, Perth, WA 6845, Australia.
   [Migliari, Simone] Univ Barcelona, Dept Astron & Meteorol, E-08028 Barcelona, Spain.
   [Broderick, Jess W.] Univ Southampton, Sch Phys & Astron, Southampton SO17 1BJ, Hants, England.
   [Tzioumis, Tasso] CSIRO, Australia Telescope Natl Facil, Epping, NSW 1710, Australia.
C3 European Southern Observatory; University of Western Australia; Curtin University; University of Barcelona; University of Southampton; Commonwealth Scientific & Industrial Research Organisation (CSIRO); Australia Telescope National Facility
RP Trigo, MD (corresponding author), European So Observ, Karl Schwarzschild Str 2, D-85748 Garching, Germany.
EM mdiaztri@eso.org
FU Commonwealth of Australia; Australian Research Council [DP120102393]; Spanish Ministerio de Economia y Competitividad; European Social Funds through a Ramon y Cajal Fellowship; Spanish Ministerio de Ciencia e Innovacion [AYA2010-21782-C03-01]; ESA member states; USA (NASA)
NR 39
TC 64
Z9 65
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 DEC 12
PY 2013
VL 504
IS 7479
BP 260
EP +
DI 10.1038/nature12672
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 267TQ
UT WOS:000328121500032
PM 24226774
DA 2026-03-09
ER

PT J
AU Stieglitz, B
   Rana, RR
   Koliopoulos, MG
   Morris-Davies, AC
   Schaeffer, V
   Christodoulou, E
   Howell, S
   Brown, NR
   Dikic, I
   Rittinger, K
AF Stieglitz, Benjamin
   Rana, Rohini R.
   Koliopoulos, Marios G.
   Morris-Davies, Aylin C.
   Schaeffer, Veronique
   Christodoulou, Evangelos
   Howell, Steven
   Brown, Nicholas R.
   Dikic, Ivan
   Rittinger, Katrin
TI Structural basis for ligase-specific conjugation of linear ubiquitin chains by HOIP
SO NATURE
LA English
DT Article
ID ring domain; e3 ligase; reveals; parkin; mechanism; protein; insights; sharpin; family; hhari
AB Linear ubiquitin chains are important regulators of cellular signalling pathways that control innate immunity and inflammation through nuclear factor (NF)-kappa B activation and protection against tumour necrosis factor-alpha-induced apoptosis(1-5). They are synthesized by HOIP, which belongs to the RBR (RING-between-RING) family of E3 ligases and is the catalytic component of LUBAC (linear ubiquitin chain assembly complex), a multisubunit E3 ligase(6). RBR family members act as RING/HECT hybrids, employing RING1 to recognize ubiquitin-loaded E2 while a conserved cysteine in RING2 subsequently forms a thioester intermediate with the transferred or 'donor' ubiquitin(7). Here we report the crystal structure of the catalytic core of HOIP in its apo form and in complex with ubiquitin. The carboxy-terminal portion of HOIP adopts a novel fold that, together with a zinc-finger, forms a ubiquitin-binding platform that orients the acceptor ubiquitin and positions its alpha-amino group for nucleophilic attack on the E3 similar to ubiquitin thioester. The C-terminal tail of a second ubiquitin molecule is located in close proximity to the catalytic cysteine, providing a unique snapshot of the ubiquitin transfer complex containing both donor and acceptor ubiquitin. These interactions are required for activation of the NF-kappa B pathway in vivo, and they explain the determinants of linear ubiquitin chain specificity by LUBAC.
C1 [Stieglitz, Benjamin; Rana, Rohini R.; Koliopoulos, Marios G.; Morris-Davies, Aylin C.; Christodoulou, Evangelos; Howell, Steven; Brown, Nicholas R.; Rittinger, Katrin] Natl Inst Med Res, MRC, Div Mol Struct, London NW7 1AA, England.
   [Schaeffer, Veronique; Dikic, Ivan] Goethe Univ Frankfurt, Sch Med, Inst Biochem 2, D-60590 Frankfurt, Main, Germany.
C3 MRC National Institute for Medical Research; Goethe University Frankfurt
RP Rittinger, K (corresponding author), Natl Inst Med Res, MRC, Div Mol Struct, London NW7 1AA, England.
EM katrin.rittinger@nimr.mrc.ac.uk
FU Medical Research Council [U117565398]; Wellcome Foundation [094112/Z/10/Z]; European Research Council (ERC) under the European Union; ERC [250241-LineUb]; Wellcome Trust [094112/Z/10/Z] Funding Source: Wellcome Trust; MRC [MC_U117565398] Funding Source: UKRI; Medical Research Council [MC_U117565398] Funding Source: researchfish
NR 37
TC 181
Z9 201
U1 0
U2 57
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 21
PY 2013
VL 503
IS 7476
BP 422
EP +
DI 10.1038/nature12638
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 254KG
UT WOS:000327163200047
PM 24141947
DA 2026-03-09
ER

PT J
AU Ponomarenko, LA
   Gorbachev, RV
   Yu, GL
   Elias, DC
   Jalil, R
   Patel, AA
   Mishchenko, A
   Mayorov, AS
   Woods, CR
   Wallbank, JR
   Mucha-Kruczynski, M
   Piot, BA
   Potemski, M
   Grigorieva, IV
   Novoselov, KS
   Guinea, F
   Fal'ko, VI
   Geim, AK
AF Ponomarenko, L. A.
   Gorbachev, R. V.
   Yu, G. L.
   Elias, D. C.
   Jalil, R.
   Patel, A. A.
   Mishchenko, A.
   Mayorov, A. S.
   Woods, C. R.
   Wallbank, J. R.
   Mucha-Kruczynski, M.
   Piot, B. A.
   Potemski, M.
   Grigorieva, I. V.
   Novoselov, K. S.
   Guinea, F.
   Fal'ko, V. I.
   Geim, A. K.
TI Cloning of Dirac fermions in graphene superlattices
SO NATURE
LA English
DT Article
ID scanning-tunneling-microscopy; hexagonal boron-nitride; magnetotransport
AB Superlattices have attracted great interest because their use may make it possible to modify the spectra of two-dimensional electron systems and, ultimately, create materials with tailored electronic properties(1-8). In previous studies (see, for example, refs 1-8), it proved difficult to realize superlattices with short periodicities and weak disorder, and most of their observed features could be explained in terms of cyclotron orbits commensurate with the superlattice(1-4). Evidence for the formation of superlattice mini-bands (forming a fractal spectrum known as Hofstadter's butterfly(9)) has been limited to the observation of new low-field oscillations(5) and an internal structure within Landau levels(6-8). Here we report transport properties of graphene placed on a boron nitride substrate and accurately aligned along its crystallographic directions. The substrate's moire potential(10-12) acts as a superlattice and leads to profound changes in the graphene's electronic spectrum. Second-generation Dirac points(13-22) appear as pronounced peaks in resistivity, accompanied by reversal of the Hall effect. The latter indicates that the effective sign of the charge carriers changes within graphene's conduction and valence bands. Strong magnetic fields lead to Zak-type cloning(23) of the third generation of Dirac points, which are observed as numerous neutrality points in fields where a unit fraction of the flux quantum pierces the superlattice unit cell. Graphene superlattices such as this one provide a way of studying the rich physics expected in incommensurable quantum systems(7-9,22-24) and illustrate the possibility of controllably modifying the electronic spectra of two-dimensional atomic crystals by varying their crystallographic alignment within van der Waals heterostuctures(25).
C1 [Ponomarenko, L. A.; Yu, G. L.; Elias, D. C.; Mishchenko, A.; Mayorov, A. S.; Woods, C. R.; Grigorieva, I. V.; Novoselov, K. S.; Geim, A. K.] Univ Manchester, Sch Phys & Astron, Manchester M13 9PL, Lancs, England.
   [Gorbachev, R. V.; Jalil, R.; Geim, A. K.] Univ Manchester, Ctr Mesosci & Nanotechnol, Manchester M13 9PL, Lancs, England.
   [Patel, A. A.; Wallbank, J. R.; Mucha-Kruczynski, M.; Fal'ko, V. I.] Univ Lancaster, Dept Phys, Lancaster LA1 4YB, England.
   [Piot, B. A.; Potemski, M.] CNRS UJF UPS INSA, Lab Natl Champs Magnet Intenses, F-38042 Grenoble, France.
   [Guinea, F.] Inst Ciencia Mat Madrid, Madrid 28049, Spain.
C3 University of Manchester; University of Manchester; Lancaster University; Communaute Universite Grenoble Alpes; Universite Grenoble Alpes (UGA); Centre National de la Recherche Scientifique (CNRS); Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Instituto de Ciencia de Materiales de Madrid (ICMM)
RP Gorbachev, RV (corresponding author), Univ Manchester, Ctr Mesosci & Nanotechnol, Manchester M13 9PL, Lancs, England.
EM blizza@gmail.com
FU European Research Council; Korber Foundation; Office of Naval Research; Air Force Office of Scientific Research; Royal Society; EPSRC [EP/K005014/1, EP/G02491X/1] Funding Source: UKRI; Engineering and Physical Sciences Research Council [EP/G02491X/1, EP/K005014/1, 1240086] Funding Source: researchfish
NR 30
TC 1125
Z9 1333
U1 6
U2 873
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 30
PY 2013
VL 497
IS 7451
BP 594
EP 597
DI 10.1038/nature12187
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 152UF
UT WOS:000319556100038
PM 23676678
DA 2026-03-09
ER

PT J
AU Nicoletti, O
   de la Peña, F
   Leary, RK
   Holland, DJ
   Ducati, C
   Midgley, PA
AF Nicoletti, Olivia
   de la Pena, Francisco
   Leary, Rowan K.
   Holland, Daniel J.
   Ducati, Caterina
   Midgley, Paul A.
TI Three-dimensional imaging of localized surface plasmon resonances of metal nanoparticles
SO NATURE
LA English
DT Article
ID reconstruction; energy; tomography; substrate; modes; gold; eels
AB The remarkable optical properties of metal nanoparticles are governed by the excitation of localized surface plasmon resonances (LSPRs). The sensitivity of each LSPR mode, whose spatial distribution and resonant energy depend on the nanoparticle structure, composition and environment, has given rise to many potential photonic, optoelectronic, catalytic, photovoltaic, and gas-and bio-sensing applications(1-3). However, the precise interplay between the three-dimensional (3D) nanoparticle structure and the LSPRs is not always fully understood and a spectrally sensitive 3D imaging technique is needed to visualize the excitation on the nanometre scale. Here we show that 3D images related to LSPRs of an individual silver nanocube can be reconstructed through the application of electron energy-loss spectrum imaging(4), mapping the excitation across a range of orientations, with a novel combination of non-negative matrix factorization(5,6), compressed sensing(7,8) and electron tomography(9). Our results extend the idea of substrate-mediated hybridization of dipolar and quadrupolar modes predicted by theory, simulations, and electron and optical spectroscopy(10-12), and provide experimental evidence of higher-energy mode hybridization. This work represents an advance both in the understanding of the optical response of noble-metal nanoparticles and in the probing, analysis and visualization of LSPRs.
C1 [Nicoletti, Olivia; de la Pena, Francisco; Leary, Rowan K.; Ducati, Caterina; Midgley, Paul A.] Univ Cambridge, Dept Mat Sci & Met, Cambridge CB2 3QZ, England.
   [Holland, Daniel J.] Univ Cambridge, Dept Chem Engn & Biotechnol, Cambridge CB2 3RA, England.
C3 University of Cambridge; University of Cambridge
RP Midgley, PA (corresponding author), Univ Cambridge, Dept Mat Sci & Met, Pembroke St, Cambridge CB2 3QZ, England.
EM pam33@cam.ac.uk
FU US National Science Foundation under NSF [ECS-0335765]; ERC [259619 PHOTO EM]; Royal Society; European Union under European Research Council ERC [291522-3DIMAGE, 312483-ESTEEM2]; Microsoft Research Connections; EPSRC [EP/K008218/1, EP/K039318/1]; Engineering and Physical Sciences Research Council [EP/K008218/1] Funding Source: researchfish; EPSRC [EP/K008218/1] Funding Source: UKRI
NR 43
TC 458
Z9 501
U1 2
U2 801
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 3
PY 2013
VL 502
IS 7469
BP 80
EP +
DI 10.1038/nature12469
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 227IM
UT WOS:000325106000034
PM 24091976
DA 2026-03-09
ER

PT J
AU Smith, SL
   Smith, IT
   Branco, T
   Häusser, M
AF Smith, Spencer L.
   Smith, Ikuko T.
   Branco, Tiago
   Haeusser, Michael
TI Dendritic spikes enhance stimulus selectivity in cortical neurons in vivo
SO NATURE
LA English
DT Article
ID mouse visual-cortex; pyramidal neurons; barrel cortex; synaptic integration; receptive-fields; basal dendrites; striate cortex; input; organization; potentials
AB Neuronal dendrites are electrically excitable: they can generate regenerative events such as dendritic spikes in response to sufficiently strong synaptic input(1-3). Although such events have been observed in many neuronal types(4-9), it is not well understood how active dendrites contribute to the tuning of neuronal output in vivo. Here we show that dendritic spikes increase the selectivity of neuronal responses to the orientation of a visual stimulus (orientation tuning). We performed direct patch-clamp recordings from the dendrites of pyramidal neurons in the primary visual cortex of lightly anaesthetized and awake mice, during sensory processing. Visual stimulation triggered regenerative local dendritic spikes that were distinct from back-propagating action potentials. These events were orientation tuned and were suppressed by either hyperpolarization of membrane potential or intracellular blockade of NMDA(N-methyl-D-aspartate) receptors. Both of these manipulations also decreased the selectivity of subthreshold orientation tuning measured at the soma, thus linking dendritic regenerative events to somatic orientation tuning. Together, our results suggest that dendritic spikes that are triggered by visual input contribute to a fundamental cortical computation: enhancing orientation selectivity in the visual cortex. Thus, dendritic excitability is an essential component of behaviourally relevant computations in neurons.
C1 [Smith, Spencer L.; Smith, Ikuko T.; Branco, Tiago; Haeusser, Michael] UCL, Wolfson Inst Biomed Res, London WC1E 6BT, England.
   [Smith, Spencer L.; Smith, Ikuko T.; Branco, Tiago; Haeusser, Michael] UCL, Dept Neurosci Physiol & Pharmacol, London WC1E 6BT, England.
   [Smith, Spencer L.; Smith, Ikuko T.] Univ N Carolina, Sch Med, Dept Cell Biol & Physiol, Chapel Hill, NC 27599 USA.
   [Smith, Spencer L.; Smith, Ikuko T.] Univ N Carolina, Sch Med, Ctr Neurosci, Chapel Hill, NC 27599 USA.
   [Branco, Tiago] MRC, Mol Biol Lab, Cambridge CB2 0QH, England.
C3 University of London; University College London; University of London; University College London; 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; MRC Laboratory Molecular Biology
RP Smith, SL (corresponding author), UCL, Wolfson Inst Biomed Res, Gower St, London WC1E 6BT, England.
EM slab@unc.edu; m.hausser@ucl.ac.uk
FU Long-Term Fellowship; Career Development Award from the Human Frontier Science Program; Klingenstein Fellowship; Helen Lyng White Fellowship; Wellcome Trust; Royal Society; MRC; ERC; Gatsby Charitable Foundation; Medical Research Council [MC_UP_1201/1] Funding Source: researchfish; MRC [MC_UP_1201/1] Funding Source: UKRI
NR 38
TC 292
Z9 341
U1 0
U2 70
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 7
PY 2013
VL 503
IS 7474
BP 115
EP +
DI 10.1038/nature12600
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 247AS
UT WOS:000326585600043
PM 24162850
DA 2026-03-09
ER

PT J
AU O'Malley, J
   Skylaki, S
   Iwabuchi, KA
   Chantzoura, E
   Ruetz, T
   Johnsson, A
   Tomlinson, SR
   Linnarsson, S
   Kaji, K
AF O'Malley, James
   Skylaki, Stavroula
   Iwabuchi, Kumiko A.
   Chantzoura, Eleni
   Ruetz, Tyson
   Johnsson, Anna
   Tomlinson, Simon R.
   Linnarsson, Sten
   Kaji, Keisuke
TI High-resolution analysis with novel cell-surface markers identifies routes to iPS cells
SO NATURE
LA English
DT Article
ID differential expression analysis; somatic-cells; reprogramming factors; pluripotency; bioinformatics; transposition; bioconductor; induction; piggybac; murine
AB The generation of induced pluripotent stem (iPS) cells presents a challenge to normal developmental processes. The low efficiency and heterogeneity of most methods have hindered understanding of the precise molecular mechanisms promoting, and roadblocks preventing, efficient reprogramming. Although several intermediate populations have been described(1-7), it has proved difficult to characterize the rare, asynchronous transition from these intermediate stages to iPS cells. The rapid expansion of minor reprogrammed cells in the heterogeneous population can also obscure investigation of relevant transition processes. Understanding the biological mechanisms essential for successful iPS cell generation requires both accurate capture of cells undergoing the reprogramming process and identification of the associated global gene expression changes. Here we demonstrate that in mouse embryonic fibroblasts, reprogramming follows an orderly sequence of stage transitions, marked by changes in the cell-surface markers CD44 and ICAM1, and a Nanog-enhanced green fluorescent protein (Nanog-eGFP) reporter. RNA-sequencing analysis of these populations demonstrates two waves of pluripotency gene upregulation, and unexpectedly, transient upregulation of several epidermis-related genes, demonstrating that reprogramming is not simply the reversal of the normal developmental processes. This novel high-resolution analysis enables the construction of a detailed reprogramming route map, and the improved understanding of the reprogramming process will lead to new reprogramming strategies.
C1 [O'Malley, James; Iwabuchi, Kumiko A.; Chantzoura, Eleni; Ruetz, Tyson; Tomlinson, Simon R.; Kaji, Keisuke] Univ Edinburgh, MRC Ctr Regenerat Med, Edinburgh BioQuarter, Edinburgh EH16 4UU, Midlothian, Scotland.
   [Skylaki, Stavroula] Helmholtz Ctr Munich, Stem Cell Dynam Res Unit, D-85764 Neuherberg, Germany.
   [Johnsson, Anna; Linnarsson, Sten] Karolinska Inst, Dept Med Biochem & Biophys, Lab Mol Neurobiol, SE-17177 Stockholm, Sweden.
C3 University of Edinburgh; Helmholtz Association; Helmholtz-Center Munich - German Research Center for Environmental Health; Karolinska Institutet
RP Kaji, K (corresponding author), Univ Edinburgh, MRC Ctr Regenerat Med, Edinburgh BioQuarter, 5 Little France Dr, Edinburgh EH16 4UU, Midlothian, Scotland.
EM keisuke.kaji@ed.ac.uk
FU ERC grant ROADTOIPS [261075]; ERC grant BRAINCELL [261063]; Anne Rowling Regenerative Neurology Clinic; MRC PhD Studentship; Darwin Trust of Edinburgh Scholarship; European Research Council (ERC) [261063, 261075] Funding Source: European Research Council (ERC); Medical Research Council [G0700711B] Funding Source: researchfish
NR 38
TC 121
Z9 143
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 JUL 4
PY 2013
VL 499
IS 7456
BP 88
EP +
DI 10.1038/nature12243
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 176ED
UT WOS:000321285600039
PM 23728301
DA 2026-03-09
ER

PT J
AU Raina, JB
   Tapiolas, DM
   Forêt, S
   Lutz, A
   Abrego, D
   Ceh, J
   Seneca, FO
   Clode, PL
   Bourne, DG
   Willis, BL
   Motti, CA
AF Raina, Jean-Baptiste
   Tapiolas, Dianne M.
   Foret, Sylvain
   Lutz, Adrian
   Abrego, David
   Ceh, Janja
   Seneca, Francois O.
   Clode, Peta L.
   Bourne, David G.
   Willis, Bette L.
   Motti, Cherie A.
TI DMSP biosynthesis by an animal and its role in coral thermal stress response
SO NATURE
LA English
DT Article
ID particulate dimethylsulfoniopropionate dmsp; great-barrier-reef; dimethyl sulfide; sulfur-compounds; solar-radiation; acropora; bacteria; primers; climate; quantification
AB Globally, reef-building corals are the most prolific producers of dimethylsulphoniopropionate (DMSP)(1,2), a central molecule in the marine sulphur cycle and precursor of the climate-active gas dimethylsulphide(3,4). At present, DMSP production by corals is attributed entirely to their algal endosymbiont, Symbiodinium(2). Combining chemical, genomic and molecular approaches, we show that coral juveniles produce DMSP in the absence of algal symbionts. DMSP levels increased up to 54% over time in newly settled coral juveniles lacking algal endosymbionts, and further increases, up to 76%, were recorded when juveniles were subjected to thermal stress. We uncovered coral orthologues of two algal genes recently identified in DMSP biosynthesis, strongly indicating that corals possess the enzymatic machinery necessary for DMSP production. Our results overturn the paradigm that photosynthetic organisms are the sole biological source of DMSP, and highlight the double jeopardy represented by worldwide declining coral cover, as the potential to alleviate thermal stress through coral-produced DMSP declines correspondingly.
C1 [Raina, Jean-Baptiste; Lutz, Adrian; Seneca, Francois O.; Willis, Bette L.] James Cook Univ, AIMS JCU, Townsville, Qld 4811, Australia.
   [Raina, Jean-Baptiste; Seneca, Francois O.; Willis, Bette L.] James Cook Univ, Sch Marine & Trop Biol, Townsville, Qld 4811, Australia.
   [Raina, Jean-Baptiste; Tapiolas, Dianne M.; Lutz, Adrian; Abrego, David; Seneca, Francois O.; Bourne, David G.; Motti, Cherie A.] Australian Inst Marine Sci, Townsville, Qld 4810, Australia.
   [Raina, Jean-Baptiste; Foret, Sylvain; Lutz, Adrian; Willis, Bette L.] James Cook Univ, Sch Marine & Trop Biol, ARC Ctr Excellence Coral Reef Studies, Townsville, Qld 4811, Australia.
   [Foret, Sylvain] Australian Natl Univ, Canberra, ACT 2601, Australia.
   [Lutz, Adrian] James Cook Univ, Sch Pharm & Mol Sci, Townsville, Qld 4811, Australia.
   [Ceh, Janja] Murdoch Univ, Sch Biol Sci & Biotechnol, Perth, WA 6050, Australia.
   [Clode, Peta L.] Univ Western Australia, Ctr Microscopy Characterisat & Anal, Crawley, WA 6009, Australia.
   [Clode, Peta L.] Univ Western Australia, Oceans Inst, Crawley, WA 6009, Australia.
C3 James Cook University; James Cook University; Australian Institute of Marine Science; James Cook University; ARC Centre of Excellence for Coral Reef Studies; Australian National University; James Cook University; Murdoch University; University of Western Australia; University of Western Australia
RP Raina, JB (corresponding author), James Cook Univ, AIMS JCU, Townsville, Qld 4811, Australia.
EM j.raina@aims.gov.au
FU AMMRF Centre for Microscopy, Characterisation and Analysis (UWA); ARC Centre of Excellence for Coral Reef Studies; AIMS
NR 51
TC 247
Z9 277
U1 6
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 OCT 31
PY 2013
VL 502
IS 7473
BP 677
EP +
DI 10.1038/nature12677
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 243CC
UT WOS:000326293200046
PM 24153189
DA 2026-03-09
ER

PT J
AU Pampliega, O
   Orhon, I
   Patel, B
   Sridhar, S
   Díaz-Carretero, A
   Beau, I
   Codogno, P
   Satir, BH
   Satir, P
   Cuervo, AM
AF Pampliega, Olatz
   Orhon, Idil
   Patel, Bindi
   Sridhar, Sunandini
   Diaz-Carretero, Antonio
   Beau, Isabelle
   Codogno, Patrice
   Satir, Birgit H.
   Satir, Peter
   Cuervo, Ana Maria
TI Functional interaction between autophagy and ciliogenesis
SO NATURE
LA English
DT Article
ID hedgehog promotes autophagy; primary cilium; complex; level
AB Nutrient deprivation is a stimulus shared by both autophagy and the formation of primary cilia. The recently discovered role of primary cilia in nutrient sensing and signalling motivated us to explore the possible functional interactions between this signalling hub and autophagy. Here we show that part of the molecular machinery involved in ciliogenesis also participates in the early steps of the autophagic process. Signalling from the cilia, such as that from the Hedgehog pathway, induces autophagy by acting directly on essential autophagy-related proteins strategically located in the base of the cilium by ciliary trafficking proteins. Whereas abrogation of ciliogenesis partially inhibits autophagy, blockage of autophagy enhances primary cilia growth and cilia-associated signalling during normal nutritional conditions. We propose that basal autophagy regulates ciliary growth through the degradation of proteins required for intraflagellar transport. Compromised ability to activate the autophagic response may underlie some common ciliopathies.
C1 [Pampliega, Olatz; Patel, Bindi; Sridhar, Sunandini; Diaz-Carretero, Antonio; Cuervo, Ana Maria] Albert Einstein Coll Med, Dept Dev & Mol Biol, Bronx, NY 10461 USA.
   [Orhon, Idil; Codogno, Patrice] INSERM, U845, F-75014 Paris, France.
   [Orhon, Idil; Codogno, Patrice] Paris Descartes Univ, F-75014 Paris, France.
   [Orhon, Idil; Beau, Isabelle; Codogno, Patrice] INSERM, U984, F-92296 Chatenay Malabry, France.
   [Orhon, Idil; Beau, Isabelle; Codogno, Patrice] Univ Paris Sud, F-92296 Chatenay Malabry, France.
   [Satir, Birgit H.; Satir, Peter; Cuervo, Ana Maria] Albert Einstein Coll Med, Dept Anat & Struct Biol, Bronx, NY 10461 USA.
   [Cuervo, Ana Maria] Albert Einstein Coll Med, Inst Aging Studies, Bronx, NY 10461 USA.
C3 Yeshiva University; Montefiore Medical Center; Albert Einstein College of Medicine; Institut National de la Sante et de la Recherche Medicale (Inserm); Universite Paris Cite; Universite Paris Cite; Institut National de la Sante et de la Recherche Medicale (Inserm); Universite Paris Saclay; Montefiore Medical Center; Albert Einstein College of Medicine; Yeshiva University; Yeshiva University; Montefiore Medical Center; Albert Einstein College of Medicine
RP Cuervo, AM (corresponding author), Albert Einstein Coll Med, Dept Dev & Mol Biol, Bronx, NY 10461 USA.
EM peter.satir@einstein.yu.edu; ana-maria.cuervo@einstein.yu.edu
FU National Institute of Health National Institute on Aging [AG031782, AG038072]; National Institute of Diabetes and Digestive and Kidney Diseases [DK098408]; Institut National de la Sante et de la Recherche Medicale; Institut National du Cancer and L'Agence Nationale de la Recherche; Basque Government; National Institute of Diabetes and Digestive and Kidney Diseases [R01DK098408] Funding Source: NIH RePORTER; National Institute on Aging [R37AG021904, P30AG038072, P01AG031782] Funding Source: NIH RePORTER
NR 30
TC 363
Z9 428
U1 0
U2 89
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 10
PY 2013
VL 502
IS 7470
BP 194
EP +
DI 10.1038/nature12639
PG 20
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 231RU
UT WOS:000325436100042
PM 24089209
DA 2026-03-09
ER

PT J
AU Loh, E
   Kugelberg, E
   Tracy, A
   Zhang, Q
   Gollan, B
   Ewles, H
   Chalmers, R
   Pelicic, V
   Tang, CM
AF Loh, Edmund
   Kugelberg, Elisabeth
   Tracy, Alexander
   Zhang, Qian
   Gollan, Bridget
   Ewles, Helen
   Chalmers, Ronald
   Pelicic, Vladimir
   Tang, Christoph M.
TI Temperature triggers immune evasion by Neisseria meningitidis
SO NATURE
LA English
DT Article
ID polysialic acid capsule; upper respiratory-tract; influenza-a; virus-infection; biosynthesis; genes; complement; mechanisms; expression; resistance
AB Neisseria meningitidis has several strategies to evade complement-mediated killing, and these contribute to its ability to cause septicaemic disease and meningitis. However, the meningococcus is primarily an obligate commensal of the human nasopharynx, and it is unclear why the bacterium has evolved exquisite mechanisms to avoid host immunity. Here we demonstrate that mechanisms of meningococcal immune evasion and resistance against complement increase in response to an increase in ambient temperature. We have identified three independent RNA thermosensors located in the 5' untranslated regions of genes necessary for capsule biosynthesis, the expression of factor H binding protein, and sialylation of lipopolysaccharide, which are essential for meningococcal resistance against immune killing(1,2). Therefore increased temperature (which occurs during inflammation) acts as a 'danger signal' for the meningococcus, enhancing its defence against human immune killing. Infection with viral pathogens, such as influenza, leads to inflammation in the nasopharynx with an increased temperature and recruitment of immune effectors(3,4). Thermoregulation of immune defence could offer an adaptive advantage to the meningococcus during co-infection with other pathogens, and promote the emergence of virulence in an otherwise commensal bacterium.
C1 [Loh, Edmund; Tracy, Alexander; Tang, Christoph M.] Univ Oxford, Sir William Dunn Sch Pathol, Oxford OX1 3RE, England.
   [Kugelberg, Elisabeth; Zhang, Qian; Gollan, Bridget; Ewles, Helen; Pelicic, Vladimir; Tang, Christoph M.] Univ London Imperial Coll Sci Technol & Med, Ctr Mol Microbiol & Infect, London SW7 2AZ, England.
   [Chalmers, Ronald] Univ Nottingham, Sch Biomed Sci, Nottingham NG7 2NR, England.
C3 University of Oxford; Imperial College London; University of Nottingham
RP Tang, CM (corresponding author), Univ Oxford, Sir William Dunn Sch Pathol, Sir Parks Rd, Oxford OX1 3RE, England.
EM christoph.tang@path.ox.ac.uk
FU Wellcome Trust; Medical Research Council; Oxford Martin School; Swedish Research Council [524-2010-6726]; EMBO; Medical Research Council [MR/J006874/1, G0900888] Funding Source: researchfish; MRC [G0900888, MR/J006874/1] Funding Source: UKRI
NR 25
TC 111
Z9 139
U1 1
U2 54
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 10
PY 2013
VL 502
IS 7470
BP 237
EP +
DI 10.1038/nature12616
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 231RU
UT WOS:000325436100051
PM 24067614
DA 2026-03-09
ER

PT J
AU Schmitz, RJ
   Schultz, MD
   Urich, MA
   Nery, JR
   Pelizzola, M
   Libiger, O
   Alix, A
   McCosh, RB
   Chen, HM
   Schork, NJ
   Ecker, JR
AF Schmitz, Robert J.
   Schultz, Matthew D.
   Urich, Mark A.
   Nery, Joseph R.
   Pelizzola, Mattia
   Libiger, Ondrej
   Alix, Andrew
   McCosh, Richard B.
   Chen, Huaming
   Schork, Nicholas J.
   Ecker, Joseph R.
TI Patterns of population epigenomic diversity
SO NATURE
LA English
DT Article
ID genome-wide association; dna methylation; arabidopsis-thaliana; epigenetic mutation; natural variation; gene; elements; model; demethylation; plants
AB Natural epigenetic variation provides a source for the generation of phenotypic diversity, but to understand its contribution to such diversity, its interaction with genetic variation requires further investigation. Here we report population-wide DNA sequencing of genomes, transcriptomes and methylomes of wild Arabidopsis thaliana accessions. Single cytosine methylation polymorphisms are not linked to genotype. However, the rate of linkage disequilibrium decay amongst differentially methylated regions targeted by RNA-directed DNA methylation is similar to the rate for single nucleotide polymorphisms. Association analyses of these RNA-directed DNA methylation regions with genetic variants identified thousands of methylation quantitative trait loci, which revealed the population estimate of genetically dependent methylation variation. Analysis of invariably methylated transposons and genes across this population indicates that loci targeted by RNA-directed DNA methylation are epigenetically activated in pollen and seeds, which facilitates proper development of these structures.
C1 [Schmitz, Robert J.; Urich, Mark A.; Alix, Andrew; McCosh, Richard B.; Ecker, Joseph R.] Salk Inst Biol Studies, Plant Biol Lab, La Jolla, CA 92037 USA.
   [Schmitz, Robert J.; Schultz, Matthew D.; Urich, Mark A.; Nery, Joseph R.; Pelizzola, Mattia; Chen, Huaming; Ecker, Joseph R.] Salk Inst Biol Studies, Genom Anal Lab, La Jolla, CA 92037 USA.
   [Schultz, Matthew D.] Univ Calif San Diego, Bioinformat Program, La Jolla, CA 92093 USA.
   [Libiger, Ondrej; Schork, Nicholas J.] Scripps Res Inst, Scripps Translat Sci Inst, La Jolla, CA 92037 USA.
   [Libiger, Ondrej; Schork, Nicholas J.] Scripps Res Inst, Dept Mol & Expt Med, La Jolla, CA 92037 USA.
   [Ecker, Joseph R.] 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; Scripps Research Institute; Scripps Research Institute; Salk Institute; Howard Hughes Medical Institute
RP Ecker, JR (corresponding author), Salk Inst Biol Studies, Plant Biol Lab, La Jolla, CA 92037 USA.
EM ecker@salk.edu
FU NIH [F32HG004830, K99GM100000]; NSF IGERT [DGE-0504645]; NIH/NCRR [UL1 RR025774]; NSF [MCB-0929402, MCB-1122246]; Howard Hughes Medical Institute; Gordon and Betty Moore Foundation [GBMF3034]; Div Of Molecular and Cellular Bioscience; Direct For Biological Sciences [1122246] Funding Source: National Science Foundation
CR Ahmed I, 2011, NUCLEIC ACIDS RES, V39, P6919, DOI 10.1093/nar/gkr324
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NR 37
TC 433
Z9 507
U1 2
U2 237
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 14
PY 2013
VL 495
IS 7440
BP 193
EP 198
DI 10.1038/nature11968
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 113FP
UT WOS:000316652300042
PM 23467092
DA 2026-03-09
ER

PT J
AU Simon, MD
   Pinter, SF
   Fang, R
   Sarma, K
   Rutenberg-Schoenberg, M
   Bowman, SK
   Kesner, BA
   Maier, VK
   Kingston, RE
   Lee, JT
AF Simon, Matthew D.
   Pinter, Stefan F.
   Fang, Rui
   Sarma, Kavitha
   Rutenberg-Schoenberg, Michael
   Bowman, Sarah K.
   Kesner, Barry A.
   Maier, Verena K.
   Kingston, Robert E.
   Lee, Jeannie T.
TI High-resolution Xist binding maps reveal two-step spreading during X-chromosome inactivation
SO NATURE
LA English
DT Article
ID facultative heterochromatin; rna; gene; chromatin; localization; annotation; domains; design
AB TheXist long noncodingRNA(lncRNA) is essential for X-chromosome inactivation (XCI), the process by which mammals compensate for unequal numbers of sex chromosomes(1-3). During XCI, Xist coats the future inactiveXchromosome(Xi)(4) and recruitsPolycomb repressive complex 2 (PRC2) to the X-inactivation centre (Xic)(5). How Xist spreads silencing on a 150-megabases scale is unclear. Here we generate high-resolution maps of Xist binding on the X chromosome across a developmental time course using CHART-seq. In female cells undergoing XCI de novo, Xist follows a two-step mechanism, initially targeting gene-rich islands before spreading to intervening gene-poor domains. Xist is depleted from genes that escape XCI but may concentrate near escapee boundaries. Xist binding is linearly proportional to PRC2 density and H3 lysine 27 trimethylation (H3K27me3), indicating co-migration of Xist and PRC2. Interestingly, when Xist is acutely stripped off from the Xi in post-XCI cells, Xist recovers quickly within both gene-rich and gene-poor domains on a timescale of hours instead of days, indicating a previously primed Xi chromatin state. We conclude that Xist spreading takes distinct stage-specific forms. During initial establishment, Xist follows a two-step mechanism, but during maintenance, Xist spreads rapidly to both gene-rich and gene-poor regions.
C1 [Simon, Matthew D.; Pinter, Stefan F.; Sarma, Kavitha; Bowman, Sarah K.; Kesner, Barry A.; Maier, Verena K.; Kingston, Robert E.; Lee, Jeannie T.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
   [Simon, Matthew D.; Pinter, Stefan F.; Sarma, Kavitha; Bowman, Sarah K.; Kesner, Barry A.; Maier, Verena K.; Kingston, Robert E.; Lee, Jeannie T.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA.
   [Simon, Matthew D.; Fang, Rui; Rutenberg-Schoenberg, Michael] Yale Univ, Dept Mol Biophys & Biochem, West Haven, CT 06516 USA.
   [Simon, Matthew D.; Fang, Rui; Rutenberg-Schoenberg, Michael] Yale Univ, Inst Chem Biol, West Haven, CT 06516 USA.
   [Pinter, Stefan F.; Sarma, Kavitha; Kesner, Barry A.; Maier, Verena K.; Lee, Jeannie T.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA.
C3 Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard Medical School; Yale University; Yale University; Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Massachusetts General Hospital; Howard Hughes Medical Institute
RP Simon, MD (corresponding author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
EM matthew.simon@yale.edu; kingston@molbio.mgh.harvard.edu; lee@molbio.mgh.harvard.edu
FU Yale University; Deutsche Forschungsgemeinschaft; MGH Fund for Medical Discovery; National Institutes of Health [F32-GM090765, RO1-GM043901, RO1-GM090278]
NR 43
TC 306
Z9 391
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 DEC 19
PY 2013
VL 504
IS 7480
BP 465
EP +
DI 10.1038/nature12719
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 273ZR
UT WOS:000328575300058
PM 24162848
DA 2026-03-09
ER

PT J
AU Pollier, J
   Moses, T
   González-Guzmán, M
   De Geyter, N
   Lippens, S
   Vanden Bossche, R
   Marhavy, P
   Kremer, A
   Morreel, K
   Guérin, CJ
   Tava, A
   Oleszek, W
   Thevelein, JM
   Campos, N
   Goormachtig, S
   Goossens, A
AF Pollier, Jacob
   Moses, Tessa
   Gonzalez-Guzman, Miguel
   De Geyter, Nathan
   Lippens, Saskia
   Vanden Bossche, Robin
   Marhavy, Peter
   Kremer, Anna
   Morreel, Kris
   Guerin, Christopher J.
   Tava, Aldo
   Oleszek, Wieslaw
   Thevelein, Johan M.
   Campos, Narciso
   Goormachtig, Sofie
   Goossens, Alain
TI The protein quality control system manages plant defence compound synthesis
SO NATURE
LA English
DT Article
ID 3-hydroxy-3-methylglutaryl-coa reductase; triterpenoid glycosides; medicago; biosynthesis; degradation; saponins; gene; identification; evolution; software
AB Jasmonates are ubiquitous oxylipin-derived phytohormones that are essential in the regulation of many development, growth and defence processes. Across the plant kingdom, jasmonates act as elicitors of the production of bioactive secondary metabolites that serve in defence against attackers(1-3). Knowledge of the conserved jasmonate perception and early signalling machineries is increasing(3-6), but the downstream mechanisms that regulate defence metabolism remain largely unknown. Here we show that, in the legume Medicago truncatula, jasmonate recruits the endoplasmic-reticulum-associated degradation (ERAD) quality control system to manage the production of triterpene saponins, widespread bioactive compounds that share a biogenic origin with sterols(7-9). An ERAD-type RING membrane-anchor E3 ubiquitin ligase is co-expressed with saponin synthesis enzymes to control the activity of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR), the rate-limiting enzyme in the supply of the ubiquitous terpene precursor isopentenyl diphosphate. Thus, unrestrained bioactive saponin accumulation is prevented and plant development and integrity secured. This control apparatus is equivalent to the ERAD system that regulates sterol synthesis in yeasts and mammals but that uses distinct E3 ubiquitin ligases, of the HMGR degradation 1 (HRD1) type, to direct destruction of HMGR(10-13). Hence, the general principles for the management of sterol and triterpene saponin biosynthesis are conserved across eukaryotes but can be controlled by divergent regulatory cues.
C1 [Pollier, Jacob; Moses, Tessa; Gonzalez-Guzman, Miguel; De Geyter, Nathan; Vanden Bossche, Robin; Marhavy, Peter; Morreel, Kris; Goormachtig, Sofie; Goossens, Alain] VIB, Dept Plant Syst Biol, B-9052 Ghent, Belgium.
   [Pollier, Jacob; Moses, Tessa; Gonzalez-Guzman, Miguel; De Geyter, Nathan; Vanden Bossche, Robin; Marhavy, Peter; Morreel, Kris; Goormachtig, Sofie; Goossens, Alain] Univ Ghent, Dept Plant Biotechnol & Bioinformat, B-9052 Ghent, Belgium.
   [Moses, Tessa; Thevelein, Johan M.] Katholieke Univ Leuven, Inst Bot & Microbiol, Mol Cell Biol Lab, B-3001 Louvain, Belgium.
   [Moses, Tessa; Thevelein, Johan M.] VIB, Dept Mol Microbiol, B-3001 Louvain, Belgium.
   [Lippens, Saskia; Kremer, Anna; Guerin, Christopher J.] VIB, VIB Bio Imaging Core Gent, B-9052 Ghent, Belgium.
   [Lippens, Saskia; Kremer, Anna; Guerin, Christopher J.] VIB, Inflammat Res Ctr, B-9052 Ghent, Belgium.
   [Tava, Aldo] Ctr Ric Prod Foraggere & Lattiero Casearie, Consiglio Ric & Sperimentaz Agr, I-26900 Lodi, Italy.
   [Oleszek, Wieslaw] State Res Inst, Inst Soil Sci & Plant Cultivat, Dept Biochem, PL-24100 Pulawy, Poland.
   [Campos, Narciso] Univ Barcelona, Fac Biol, Dept Bioquim & Biol Mol, E-08028 Barcelona, Spain.
   [Campos, Narciso] Consorci CSIC IRTA UAB UB, Ctr Recerca Agrigen, Dept Mol Genet, Barcelona 08193, Spain.
C3 Flanders Institute for Biotechnology (VIB); Ghent University; KU Leuven; Flanders Institute for Biotechnology (VIB); Flanders Institute for Biotechnology (VIB); Flanders Institute for Biotechnology (VIB); Consiglio per la Ricerca in Agricoltura e L'analisi Dell'economia Agraria (CREA); Institute of Soil Science & Plant Cultivation; University of Barcelona; Autonomous University of Barcelona; Consejo Superior de Investigaciones Cientificas (CSIC); Centre de Recerca en Agrigenomica (CRAG); IRTA
RP Goossens, A (corresponding author), VIB, Dept Plant Syst Biol, Technol Pk 927, B-9052 Ghent, Belgium.
EM alain.goossens@psb.vib-ugent.be
FU Agency for Innovation by Science and Technology in Flanders [SBO040093]; European Union [222716]; Spanish Ministerio de Economia y Competitividad [BFU2011-24208]; VIB International PhD Fellowship Program; Agency for Innovation by Science and Technology
NR 50
TC 102
Z9 113
U1 2
U2 187
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 5
PY 2013
VL 504
IS 7478
BP 148
EP +
DI 10.1038/nature12685
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 264BK
UT WOS:000327851700049
PM 24213631
DA 2026-03-09
ER

PT J
AU Rogelj, J
   McCollum, DL
   Reisinger, A
   Meinshausen, M
   Riahi, K
AF Rogelj, Joeri
   McCollum, David L.
   Reisinger, Andy
   Meinshausen, Malte
   Riahi, Keywan
TI Probabilistic cost estimates for climate change mitigation
SO NATURE
LA English
DT Article
ID carbon-cycle models; atmosphere-ocean; simpler model; scenarios; targets
AB For more than a decade, the target of keeping global warming below 2 degrees C has been a key focus of the international climate debate(1). In response, the scientific community has published a number of scenario studies that estimate the costs of achieving such a target(2-5). Producing these estimates remains a challenge, particularly because of relatively well known, but poorly quantified, uncertainties, and owing to limited integration of scientific knowledge across disciplines(6). The integrated assessment community, on the one hand, has extensively assessed the influence of technological and socio-economic uncertainties on low-carbon scenarios and associated costs(2-4,7). The climate modelling community, on the other hand, has spent years improving its understanding of the geophysical response of the Earth system to emissions of greenhouse gases(8-12). This geophysical response remains a key uncertainty in the cost of mitigation scenarios but has been integrated with assessments of other uncertainties in only a rudimentary manner, that is, for equilibrium conditions(6,13). Here we bridge this gap between the two research communities by generating distributions of the costs associated with limiting transient global temperature increase to below specific values, taking into account uncertainties in four factors: geophysical, technological, social and political. Wefind that political choices that delay mitigation have the largest effect on the cost-risk distribution, followed by geophysical uncertainties, social factors influencing future energy demand and, lastly, technological uncertainties surrounding the availability of greenhouse gas mitigation options. Our information on temperature risk and mitigation costs provides crucial information for policy-making, because it clarifies the relative importance of mitigation costs, energy demand and the timing of global action in reducing the risk of exceeding a global temperature increase of 2 degrees C, or other limits such as 3 degrees C or 1.5 degrees C, across a wide range of scenarios.
C1 [Rogelj, Joeri] ETH, Inst Atmospher & Climate Sci, CH-8092 Zurich, Switzerland.
   [Rogelj, Joeri; McCollum, David L.; Riahi, Keywan] Int Inst Appl Syst Anal, A-2361 Laxenburg, Austria.
   [Reisinger, Andy] New Zealand Agr Greenhouse Gas Res Ctr, Palmerston North 4442, New Zealand.
   [Meinshausen, Malte] Univ Melbourne, Sch Earth Sci, Melbourne, Vic 3010, Australia.
   [Meinshausen, Malte] Potsdam Inst Climate Impact Res, PRIMAP Grp, D-14412 Potsdam, Germany.
   [Riahi, Keywan] Graz Univ Technol, A-8010 Graz, Austria.
C3 Swiss Federal Institutes of Technology Domain; ETH Zurich; International Institute for Applied Systems Analysis (IIASA); University of Melbourne; Potsdam Institut fur Klimafolgenforschung; Graz University of Technology
RP Rogelj, J (corresponding author), ETH, Inst Atmospher & Climate Sci, Univ Str 16, CH-8092 Zurich, Switzerland.
EM joeri.rogelj@env.ethz.ch
FU Swiss National Science Foundation [200021-135067]; IIASA Peccei Award Grant; Swiss National Science Foundation (SNF) [200021_135067] Funding Source: Swiss National Science Foundation (SNF)
NR 28
TC 253
Z9 281
U1 1
U2 222
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 3
PY 2013
VL 493
IS 7430
BP 79
EP 83
DI 10.1038/nature11787
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 062QC
UT WOS:000312933800034
PM 23282364
DA 2026-03-09
ER

PT J
AU Adelman, CA
   Lolo, RL
   Birkbak, NJ
   Murina, O
   Matsuzaki, K
   Horejsi, Z
   Parmar, K
   Borel, V
   Skehel, JM
   Stamp, G
   D'Andrea, A
   Sartori, AA
   Swanton, C
   Boulton, SJ
AF Adelman, Carrie A.
   Lolo, Rafal L.
   Birkbak, Nicolai J.
   Murina, Olga
   Matsuzaki, Kenichiro
   Horejsi, Zuzana
   Parmar, Kalindi
   Borel, Valerie
   Skehel, J. Mark
   Stamp, Gordon
   D'Andrea, Alan
   Sartori, Alessandro A.
   Swanton, Charles
   Boulton, Simon J.
TI HELQ promotes RAD51 paralogue-dependent repair to avert germ cell loss and tumorigenesis
SO NATURE
LA English
DT Article
ID cross-link repair; fanconi-anemia; hematopoietic stem; dna-repair; confer susceptibility; ovarian; mutations; gene; deficiency; drosophila
AB Repair of interstrand crosslinks (ICLs) requires the coordinated action of the intra-S-phase checkpoint and the Fanconi anaemia pathway, which promote ICL incision, translesion synthesis and homologous recombination (reviewed in refs 1, 2). Previous studies have implicated the 3'-5' superfamily 2 helicase HELQ in ICL repair in Drosophila melanogaster (MUS301 (ref. 3)) and Caenorhabditis elegans (HELQ-1 (ref. 4)). Although in vitro analysis suggests that HELQ preferentially unwinds synthetic replication fork substrates with 3' single-stranded DNA overhangs and also disrupts protein DNA interactions while translocating along DNA(5,6), little is known regarding its functions in mammalian organisms. Here we report that HELQ helicase-deficient mice exhibit subfertility, germ cell attrition, ICL sensitivity and tumour predisposition, with Helq heterozygous mice exhibiting a similar, albeit less severe, phenotype than the null, indicative of haploinsufficiency. We establish that HELQ interacts directly with the RAD51 paralogue complex BCDX2 and functions in parallel to the Fanconi anaemia pathway to promote efficient homologous recombination at damaged replication forks. Thus, our results reveal a critical role for HELQ in replication-coupled DNA repair, germ cell maintenance and tumour suppression in mammals.
C1 [Adelman, Carrie A.; Lolo, Rafal L.; Matsuzaki, Kenichiro; Horejsi, Zuzana; Borel, Valerie; Boulton, Simon J.] Canc Res UK, London Res Inst, DNA Damage Response Lab, S Mimms EN6 3LD, Herts, England.
   [Birkbak, Nicolai J.] Tech Univ Denmark, Ctr Biol Sequence Anal, DK-2800 Lyngby, Denmark.
   [Murina, Olga; Sartori, Alessandro A.] Univ Zurich, Inst Mol Canc Res, CH-8057 Zurich, Switzerland.
   [Parmar, Kalindi; D'Andrea, Alan] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02215 USA.
   [Skehel, J. Mark] Canc Res UK, London Res Inst, Prot Anal & Prote Lab, S Mimms EN6 3LD, Herts, England.
   [Stamp, Gordon] Canc Res UK, London Res Inst, Expt Histopathol Lab, London WC2A 3LY, England.
   [Swanton, Charles] Canc Res UK, London Res Inst, Translat Canc Therapeut Lab, London WC2A 3LY, England.
   [Swanton, Charles] UCL Canc Inst, London WC1E 6DD, England.
C3 Cancer Research UK; Technical University of Denmark; University of Zurich; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Cancer Research UK; Cancer Research UK; Cancer Research UK; University of London; University College London
RP Boulton, SJ (corresponding author), Canc Res UK, London Res Inst, DNA Damage Response Lab, Clare Hall, S Mimms EN6 3LD, Herts, England.
EM simon.boulton@cancer.org.uk
FU Swiss National Science Foundation [PDFMP3_127523]; Vontobel Foundation; National Institutes of Health [R01-DK43889]; Cancer Research UK; European Research Council; Royal Society; MRC [G0701935] Funding Source: UKRI; Swiss National Science Foundation (SNF) [PDFMP3_127523] Funding Source: Swiss National Science Foundation (SNF); Cancer Research UK [11581] Funding Source: researchfish; Medical Research Council [G0701935] Funding Source: researchfish
NR 35
TC 85
Z9 104
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 OCT 17
PY 2013
VL 502
IS 7471
BP 381
EP +
DI 10.1038/nature12565
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 235GY
UT WOS:000325706300055
PM 24005329
DA 2026-03-09
ER

PT J
AU Watson, AJ
   Ledwell, JR
   Messias, MJ
   King, BA
   Mackay, N
   Meredith, MP
   Mills, B
   Garabato, ACN
AF Watson, Andrew J.
   Ledwell, James R.
   Messias, Marie-Jose
   King, Brian A.
   Mackay, Neill
   Meredith, Michael P.
   Mills, Benjamin
   Garabato, Alberto C. Naveira
TI Rapid cross-density ocean mixing at mid-depths in the Drake Passage measured by tracer release
SO NATURE
LA English
DT Article
ID southern-ocean; sulfur-hexafluoride; spatial variability; circulation; dissipation; topography
AB Diapycnal mixing (across density surfaces) is an important process in the global ocean overturning circulation(1-3). Mixing in the interior of most of the ocean, however, is thought to have a magnitude just one-tenth of that required to close the global circulation by the downward mixing of less dense waters(4). Some of this deficit is made up by intense near-bottom mixing occurring in restricted 'hot-spots' associated with rough ocean-floor topography(5,6), but it is not clear whether the waters at mid-depth, 1,000 to 3,000 metres, are returned to the surface by cross-densitymixing or by along-density flows(7). Here we show that diapycnal mixing of mid-depth (similar to 1,500 metres) waters undergoes a sustained 20-fold increase as the Antarctic Circumpolar Current flows through the Drake Passage, between the southern tip of South America and Antarctica. Our results are based on an open-ocean tracer release of trifluoromethyl sulphur pentafluoride. We ascribe the increased mixing to turbulence generated by the deep-reaching Antarctic Circumpolar Current as it flows over rough bottom topography in the Drake Passage. Scaled to the entire circumpolar current, the mixing we observe is compatible with there being a southern component to the global overturning in which about 20 sverdrups (1 Sv = 10(6) m(3) s(-1)) upwell in the Southern Ocean, with cross-density mixing contributing a significant fraction (20 to 30 per cent) of this total, and the remainder upwelling along constant-density surfaces. The great majority of the diapycnal flux is the result of interaction with restricted regions of rough ocean-floor topography.
C1 [Watson, Andrew J.; Messias, Marie-Jose; Mackay, Neill; Mills, Benjamin] Univ E Anglia, Sch Environm Sci, Norwich NR4 7TJ, Norfolk, England.
   [Ledwell, James R.] Woods Hole Oceanog Inst, Woods Hole, MA 02543 USA.
   [King, Brian A.; Garabato, Alberto C. Naveira] Natl Oceanog Ctr, Southampton SO14 3ZH, Hants, England.
   [Meredith, Michael P.] British Antarctic Survey, Cambridge CB3 0ET, England.
   [Meredith, Michael P.] Scottish Assoc Marine Sci, Oban PA37 1QA, Argyll, Scotland.
   [Garabato, Alberto C. Naveira] Univ Southampton, Natl Oceanog Ctr, Southampton SO14 3ZH, Hants, England.
C3 University of East Anglia; Woods Hole Oceanographic Institution; NERC National Oceanography Centre; UK Research & Innovation (UKRI); Natural Environment Research Council (NERC); NERC British Antarctic Survey; University of the Highlands & Islands; University of Southampton; NERC National Oceanography Centre
RP Watson, AJ (corresponding author), Univ Exeter, Coll Life & Environm Sci, Laver Bldg, Exeter EX4 4QE, Devon, England.
EM andrew.watson@exeter.ac.uk
FU UK Natural Environment Research Council; US National Science Foundation; Royal Society; NERC [NE/E005985/1, NE/E005985/2, bas0100028, NE/E007058/1] Funding Source: UKRI; Natural Environment Research Council [noc010012, NE/E007058/1, NE/E005985/2, NE/E005985/1, bas0100028] Funding Source: researchfish; Directorate For Geosciences; Division Of Ocean Sciences [1232962] Funding Source: National Science Foundation
NR 34
TC 63
Z9 66
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 SEP 19
PY 2013
VL 501
IS 7467
BP 408
EP +
DI 10.1038/nature12432
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 219XT
UT WOS:000324545700043
PM 24048070
DA 2026-03-09
ER

PT J
AU Hawkins, M
   Malla, S
   Blythe, MJ
   Nieduszynski, CA
   Allers, T
AF Hawkins, Michelle
   Malla, Sunir
   Blythe, Martin J.
   Nieduszynski, Conrad A.
   Allers, Thorsten
TI Accelerated growth in the absence of DNA replication origins
SO NATURE
LA English
DT Article
ID archaeon haloferax-volcanii; sequence; initiation; recombination; polyploidy; proteins; dynamics; elements; binding
AB DNA replication initiates at defined sites called origins, which serve as binding sites for initiator proteins that recruit the replicative machinery. Origins differ in number and structure across the three domains of life(1) and their properties determine the dynamics of chromosome replication. Bacteria and some archaea replicate from single origins, whereas most archaea and all eukaryotes replicate using multiple origins. Initiation mechanisms that rely on homologous recombination operate in some viruses. Here we show that such mechanisms also operate in archaea. We use deep sequencing to study replication in Haloferax volcanii and identify four chromosomal origins of differing activity. Deletion of individual origins results in perturbed replication dynamics and reduced growth. However, a strain lacking all origins has no apparent defects and grows significantly faster than wild type. Origin-less cells initiate replication at dispersed sites rather than at discrete origins and have an absolute requirement for the recombinase RadA, unlike strains lacking individual origins. Our results demonstrate that homologous recombination alone can efficiently initiate the replication of an entire cellular genome. This raises the question of what purpose replication origins serve and why they have evolved.
C1 [Hawkins, Michelle; Nieduszynski, Conrad A.; Allers, Thorsten] Univ Nottingham, Queens Med Ctr, Sch Biol, Nottingham NG7 2UH, England.
   [Malla, Sunir; Blythe, Martin J.] Univ Nottingham, Queens Med Ctr, Deep Seq, Nottingham NG7 2UH, England.
C3 University of Nottingham; University of Nottingham
RP Allers, T (corresponding author), Univ Nottingham, Queens Med Ctr, Sch Biol, Nottingham NG7 2UH, England.
EM conrad.nieduszynski@nottingham.ac.uk; thorsten.allers@nottingham.ac.uk
FU Biotechnology and Biological Sciences Research Council (BBSRC) [BB/E023754/1, BB/G001596/1]; Royal Society; BBSRC [BB/G001596/1, BB/E023754/1] Funding Source: UKRI; Biotechnology and Biological Sciences Research Council [BB/G001596/1, BB/E023754/1, BB/C501641/1] Funding Source: researchfish
NR 38
TC 115
Z9 146
U1 2
U2 65
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 28
PY 2013
VL 503
IS 7477
BP 544
EP +
DI 10.1038/nature12650
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 258MU
UT WOS:000327464200047
PM 24185008
DA 2026-03-09
ER

PT J
AU Zhang, RL
   Han, PD
   Yang, HB
   Ouyang, KF
   Lee, D
   Lin, YF
   Ocorr, K
   Kang, GS
   Chen, J
   Stainier, DYR
   Yelon, D
   Chi, NC
AF Zhang, Ruilin
   Han, Peidong
   Yang, Hongbo
   Ouyang, Kunfu
   Lee, Derek
   Lin, Yi-Fan
   Ocorr, Karen
   Kang, Guson
   Chen, Ju
   Stainier, Didier Y. R.
   Yelon, Deborah
   Chi, Neil C.
TI In vivo cardiac reprogramming contributes to zebrafish heart regeneration
SO NATURE
LA English
DT Article
ID cardiomyocyte; renewal; differentiation; transient; ablation; myocytes; field; tube
AB Despite current treatment regimens, heart failure remains the leading cause of morbidity and mortality in the developed world due to the limited capacity of adult mammalian ventricular cardiomyocytes to divide and replace ventricular myocardium lost from ischaemia-induced infarct(1,2). Hence there is great interest to identify potential cellular sources and strategies to generate new ventricular myocardium(3). Past studies have shown that fish and amphibians and early postnatal mammalian ventricular cardiomyocytes can proliferate to help regenerate injured ventricles(4-6); however, recent studies have suggested that additional endogenous cellular sources may contribute to this overall ventricular regeneration(3). Here we have developed, in the zebrafish (Danio rerio), a combination of fluorescent reporter transgenes, genetic fate-mapping strategies and a ventricle-specific genetic ablation system to discover that differentiated atrial cardiomyocytes can transdifferentiate into ventricular cardiomyocytes to contribute to zebrafish cardiac ventricular regeneration. Using in vivo time-lapse and confocal imaging, we monitored the dynamic cellular events during atrial-to-ventricular cardiomyocyte transdifferentiation to define intermediate cardiac reprogramming stages. We observed that Notch signalling becomes activated in the atrial endocardium following ventricular ablation, and discovered that inhibiting Notch signalling blocked the atrial-to-ventricular transdifferentiation and cardiac regeneration. Overall, these studies not only provide evidence for the plasticity of cardiac lineages during myocardial injury, but more importantly reveal an abundant new potential cardiac resident cellular source for cardiac ventricular regeneration.
C1 [Zhang, Ruilin; Han, Peidong; Yang, Hongbo; Ouyang, Kunfu; Lee, Derek; Chen, Ju; Chi, Neil C.] Univ Calif San Diego, Dept Med, Div Cardiol, La Jolla, CA 92093 USA.
   [Lin, Yi-Fan; Yelon, Deborah] Univ Calif San Diego, Div Biol Sci, La Jolla, CA 92093 USA.
   [Ocorr, Karen] Sanford Burnham Inst Med Res, Dev & Aging Program, La Jolla, CA 92037 USA.
   [Kang, Guson; Stainier, Didier Y. R.] Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94158 USA.
   [Chi, Neil C.] Univ Calif San Diego, Inst Genom Med, La Jolla, CA 92093 USA.
C3 University of California System; University of California San Diego; University of California System; University of California San Diego; Sanford Burnham Prebys Medical Discovery Institute; University of California System; University of California San Francisco; University of California System; University of California San Diego
RP Chi, NC (corresponding author), Univ Calif San Diego, Dept Med, Div Cardiol, La Jolla, CA 92093 USA.
EM nchi@ucsd.edu
FU American Heart Association [0940041N, 11POST7090024, 12POST12050080]; Packard Foundation; National Institutes of Health (NIH) [HL54737]; NIH/NHLBI (NIH Heart, Lung, and Blood Institute); NIH [OD007464, HL104239]; American Heart Association (AHA) [0940041N, 11POST7090024, 12POST12050080] Funding Source: American Heart Association (AHA)
NR 41
TC 211
Z9 249
U1 0
U2 127
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 27
PY 2013
VL 498
IS 7455
BP 497
EP +
DI 10.1038/nature12322
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 171LH
UT WOS:000320929400055
PM 23783515
DA 2026-03-09
ER

PT J
AU Yoshimoto, S
   Loo, TM
   Atarashi, K
   Kanda, H
   Sato, S
   Oyadomari, S
   Iwakura, Y
   Oshima, K
   Morita, H
   Hattori, M
   Honda, K
   Ishikawa, Y
   Hara, E
   Ohtani, N
AF Yoshimoto, Shin
   Loo, Tze Mun
   Atarashi, Koji
   Kanda, Hiroaki
   Sato, Seidai
   Oyadomari, Seiichi
   Iwakura, Yoichiro
   Oshima, Kenshiro
   Morita, Hidetoshi
   Hattori, Masahisa
   Honda, Kenya
   Ishikawa, Yuichi
   Hara, Eiji
   Ohtani, Naoko
TI Obesity-induced gut microbial metabolite promotes liver cancer through senescence secretome
SO NATURE
LA English
DT Article
ID hepatic stellate cells; hepatocellular-carcinoma; mechanisms; clostridium; expression; acid; inflammation; phenotype; bacterium; stress
AB Obesity has become more prevalent in most developed countries over the past few decades, and is increasingly recognized as a major risk factor for several common types of cancer(1). As the worldwide obesity epidemic has shown no signs of abating(2), better understanding of the mechanisms underlying obesity-associated cancer is urgently needed. Although several events were proposed to be involved in obesity-associated cancer1,3, the exact molecular mechanisms that integrate these events have remained largely unclear. Here we show that senescence-associated secretory phenotype (SASP)(4,5) has crucial roles in promoting obesity-associated hepatocellular carcinoma (HCC) development in mice. Dietary or genetic obesity induces alterations of gut microbiota, thereby increasing the levels of deoxycholic acid (DCA), a gut bacterial metabolite known to cause DNA damage(6). The enterohepatic circulation of DCA provokes SASP phenotype in hepatic stellate cells (HSCs)(7), which in turn secretes various inflammatory and tumour-promoting factors in the liver, thus facilitating HCC development in mice after exposure to chemical carcinogen. Notably, blocking DCA production or reducing gut bacteria efficiently prevents HCC development in obese mice. Similar results were also observed in mice lacking an SASP inducer(8) or depleted of senescent HSCs, indicating that the DCA-SASP axis in HSCs has key roles in obesity-associated HCC development. Moreover, signs of SASP were also observed in the HSCs in the area of HCC arising in patients with non-alcoholic steatohepatitis(3), indicating that a similar pathway may contribute to at least certain aspects of obesity-associated HCC development in humans as well. These findings provide valuable new insights into the development of obesity-associated cancer and open up new possibilities for its control.
C1 [Yoshimoto, Shin; Loo, Tze Mun; Sato, Seidai; Hara, Eiji; Ohtani, Naoko] Japanese Fdn Canc Res, Inst Canc, Div Canc Biol, Koto Ku, Tokyo 1358550, Japan.
   [Yoshimoto, Shin; Loo, Tze Mun; Sato, Seidai; Honda, Kenya; Hara, Eiji] Japan Sci & Technol Agcy, CREST, Kawaguchi, Saitama 3320012, Japan.
   [Loo, Tze Mun] Tokyo Univ Sci, Dept Appl Biol Sci, Noda, Chiba 2788510, Japan.
   [Atarashi, Koji; Honda, Kenya] RIKEN, Res Ctr Allergy & Immunol, Yokohama, Kanagawa 2300045, Japan.
   [Atarashi, Koji; Ohtani, Naoko] Japan Sci & Technol Agcy, PRESTO, Kawaguchi, Saitama 3320012, Japan.
   [Kanda, Hiroaki; Ishikawa, Yuichi] Japanese Fdn Canc Res, Inst Canc, Div Pathol, Koto Ku, Tokyo 1358550, Japan.
   [Oyadomari, Seiichi] Univ Tokushima, Inst Genome Res, Tokushima 7708503, Japan.
   [Iwakura, Yoichiro] Tokyo Univ Sci, Res Inst Biol Sci, Noda, Chiba 2788510, Japan.
   [Oshima, Kenshiro; Hattori, Masahisa] Univ Tokyo, Grad Sch Frontier Sci, Kashiwa, Chiba 2778561, Japan.
   [Morita, Hidetoshi] Azabu Univ, Sch Vet Med, Sagamihara, Kanagawa 2298501, Japan.
C3 Japanese Foundation for Cancer Research; Japan Science & Technology Agency (JST); Tokyo University of Science; RIKEN; Japan Science & Technology Agency (JST); Japanese Foundation for Cancer Research; Tokushima University; Tokyo University of Science; University of Tokyo; Azabu University
RP Hara, E (corresponding author), Japanese Fdn Canc Res, Inst Canc, Div Canc Biol, Koto Ku, Tokyo 1358550, Japan.
EM eiji.hara@jfcr.or.jp
FU Japan Science and Technology Agency (JST); Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT); Ministry of Health, Labour and Welfare of Japan (MHLW); Uehara Memorial Foundation; Takeda Science Foundation; Japan Society for Promotion of Science (JSPS); Ajinomoto Scholarship Foundation; Grants-in-Aid for Scientific Research [25293080, 23300343, 24650625, 221S0001, 23300352] Funding Source: KAKEN
NR 39
TC 1788
Z9 2053
U1 7
U2 514
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 4
PY 2013
VL 499
IS 7456
BP 97
EP +
DI 10.1038/nature12347
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 176ED
UT WOS:000321285600041
PM 23803760
DA 2026-03-09
ER

PT J
AU Pfeiffer, BE
   Foster, DJ
AF Pfeiffer, Brad E.
   Foster, David J.
TI Hippocampal place-cell sequences depict future paths to remembered goals
SO NATURE
LA English
DT Article
ID phase precession; memory; replay; navigation; ca3; information; experience; striatum; dynamics; predicts
AB Effective navigation requires planning extended routes to remembered goal locations. Hippocampal place cells have been proposed to have a role in navigational planning, but direct evidence has been lacking. Here we show that before goal-directed navigation in an open arena, the rat hippocampus generates brief sequences encoding spatial trajectories strongly biased to progress from the subject's current location to a known goal location. These sequences predict immediate future behaviour, even in cases in which the specific combination of start and goal locations is novel. These results indicate that hippocampal sequence events characterized previously in linearly constrained environments as 'replay' are also capable of supporting a goal-directed, trajectory-finding mechanism, which identifies important places and relevant behavioural paths, at specific times when memory retrieval is required, and in a manner that could be used to control subsequent navigational behaviour.
C1 [Pfeiffer, Brad E.; Foster, David J.] Johns Hopkins Univ, Sch Med, Solomon H Snyder Dept Neurosci, Baltimore, MD 21205 USA.
C3 Johns Hopkins University
RP Foster, DJ (corresponding author), Johns Hopkins Univ, Sch Med, Solomon H Snyder Dept Neurosci, Baltimore, MD 21205 USA.
EM david.foster@jhu.edu
FU Alfred P. Sloan Foundation; Brain and Behavior Research Foundation (NARSAD); National Institutes of Health [MH085823]
NR 50
TC 815
Z9 1015
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 MAY 2
PY 2013
VL 497
IS 7447
BP 74
EP +
DI 10.1038/nature12112
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 134OK
UT WOS:000318221500036
PM 23594744
DA 2026-03-09
ER

PT J
AU Huch, M
   Dorrell, C
   Boj, SF
   van Es, JH
   Li, VSW
   van de Wetering, M
   Sato, T
   Hamer, K
   Sasaki, N
   Finegold, MJ
   Haft, A
   Vries, RG
   Grompe, M
   Clevers, H
AF Huch, Meritxell
   Dorrell, Craig
   Boj, Sylvia F.
   van Es, Johan H.
   Li, Vivian S. W.
   van de Wetering, Marc
   Sato, Toshiro
   Hamer, Karien
   Sasaki, Nobuo
   Finegold, Milton J.
   Haft, Annelise
   Vries, Robert G.
   Grompe, Markus
   Clevers, Hans
TI In vitro expansion of single Lgr5+ liver stem cells induced by Wnt-driven regeneration
SO NATURE
LA English
DT Article
ID progenitor cells; mouse-liver; differentiation; expression; mice; hepatocytes; epithelium; receptors; colon; gene
AB The Wnt target gene Lgr5 (leucine-rich-repeat-containing G-protein-coupled receptor 5) marks actively dividing stem cells in Wnt-driven, self-renewing tissues such as small intestine and colon(1), stomach(2) and hair follicles(3). A three-dimensional culture system allows long-term clonal expansion of single Lgr5(+) stem cells into transplantable organoids (budding cysts) that retain many characteristics of the original epithelial architecture(2,4,5). A crucial component of the culture medium is the Wnt agonist RSPO1(6), the recently discovered ligand of LGR5(7,8). Here we show that Lgr5-lacZ is not expressed in healthy adult liver, however, small Lgr5-LacZ(+) cells appear near bile ducts upon damage, coinciding with robust activation of Wnt signalling. As shown by mouse lineage tracing using a new Lgr5-IRES-creERT2 knock-in allele, damage-induced Lgr5(+) cells generate hepatocytes and bile ducts in vivo. Single Lgr5(+) cells from damaged mouse liver can be clonally expanded as organoids in Rspo1-based culture medium over several months. Such clonal organoids can be induced to differentiate in vitro and to generate functional hepatocytes upon transplantation into Fah(-/-) mice. These findings indicate that previous observations concerning Lgr5(+) stem cells in actively self-renewing tissues can also be extended to damage-induced stem cells in a tissue with a low rate of spontaneous proliferation.
C1 [Huch, Meritxell; Boj, Sylvia F.; van Es, Johan H.; Li, Vivian S. W.; van de Wetering, Marc; Sato, Toshiro; Hamer, Karien; Sasaki, Nobuo; Vries, Robert G.; Clevers, Hans] Hubrecht Inst Dev Biol & Stem Cell Res, NL-3584 CT Utrecht, Netherlands.
   [Huch, Meritxell; Boj, Sylvia F.; van Es, Johan H.; Li, Vivian S. W.; van de Wetering, Marc; Sato, Toshiro; Hamer, Karien; Sasaki, Nobuo; Vries, Robert G.; Clevers, Hans] Univ Med Ctr Utrecht, Utrecht, Netherlands.
   [Dorrell, Craig; Haft, Annelise; Grompe, Markus] Oregon Hlth & Sci Univ, Oregon Stem Cell Ctr, Pape Family Pediat Res Inst, Portland, OR 97239 USA.
   [Finegold, Milton J.] Texas Childrens Hosp, Dept Pathol, Houston, TX 77030 USA.
C3 Royal Netherlands Academy of Arts & Sciences; Hubrecht Institute (KNAW); Utrecht University; Utrecht University Medical Center; Oregon Health & Science University; Baylor College of Medicine; Baylor College Medical Hospital
RP Clevers, H (corresponding author), Hubrecht Inst Dev Biol & Stem Cell Res, Uppsalalaan 8, NL-3584 CT Utrecht, Netherlands.
EM h.clevers@hubrecht.eu
FU [EU/236954];  [EU/232814];  [Ti Pharma/T3-106]; National Institute of Diabetes and Digestive and Kidney Diseases [P30DK056338] Funding Source: NIH RePORTER; Grants-in-Aid for Scientific Research [24112523] Funding Source: KAKEN
NR 30
TC 1259
Z9 1519
U1 16
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 14
PY 2013
VL 494
IS 7436
BP 247
EP 250
DI 10.1038/nature11826
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 092QS
UT WOS:000315137700042
PM 23354049
DA 2026-03-09
ER

PT J
AU Tsai, IJ
   Zarowiecki, M
   Holroyd, N
   Garciarrubio, A
   Sanchez-Flores, A
   Brooks, KL
   Tracey, A
   Bobes, RJ
   Fragoso, G
   Sciutto, E
   Aslett, M
   Beasley, H
   Bennett, HM
   Cai, JP
   Camicia, F
   Clark, R
   Cucher, M
   De Silva, N
   Day, TA
   Deplazes, P
   Estrada, K
   Fernandez, C
   Holland, PWH
   Hou, JL
   Hu, SN
   Huckvale, T
   Hung, SS
   Kamenetzky, L
   Keane, JA
   Kiss, F
   Koziol, U
   Lambert, O
   Liu, K
   Luo, XN
   Luo, YF
   Macchiaroli, N
   Nichol, S
   Paps, J
   Parkinson, J
   Pouchkina-Stantcheva, N
   Riddiford, N
   Rosenzvit, M
   Salinas, G
   Wasmuth, JD
   Zamanian, M
   Zheng, YD
   Cai, XP
   Soberón, X
   Olson, PD
   Laclette, JP
   Brehm, K
   Berriman, M
AF Tsai, Isheng J.
   Zarowiecki, Magdalena
   Holroyd, Nancy
   Garciarrubio, Alejandro
   Sanchez-Flores, Alejandro
   Brooks, Karen L.
   Tracey, Alan
   Bobes, Raul J.
   Fragoso, Gladis
   Sciutto, Edda
   Aslett, Martin
   Beasley, Helen
   Bennett, Hayley M.
   Cai, Jianping
   Camicia, Federico
   Clark, Richard
   Cucher, Marcela
   De Silva, Nishadi
   Day, Tim A.
   Deplazes, Peter
   Estrada, Karel
   Fernandez, Cecilia
   Holland, Peter W. H.
   Hou, Junling
   Hu, Songnian
   Huckvale, Thomas
   Hung, Stacy S.
   Kamenetzky, Laura
   Keane, Jacqueline A.
   Kiss, Ferenc
   Koziol, Uriel
   Lambert, Olivia
   Liu, Kan
   Luo, Xuenong
   Luo, Yingfeng
   Macchiaroli, Natalia
   Nichol, Sarah
   Paps, Jordi
   Parkinson, John
   Pouchkina-Stantcheva, Natasha
   Riddiford, Nick
   Rosenzvit, Mara
   Salinas, Gustavo
   Wasmuth, James D.
   Zamanian, Mostafa
   Zheng, Yadong
   Cai, Xuepeng
   Soberon, Xavier
   Olson, Peter D.
   Laclette, Juan P.
   Brehm, Klaus
   Berriman, Matthew
TI The genomes of four tapeworm species reveal adaptations to parasitism
SO NATURE
LA English
DT Article
ID echinococcus-multilocularis; taenia-solium; granulosus; identification; cultivation; infections; biology; target; hox
AB Tapeworms (Cestoda) cause neglected diseases that can be fatal and are difficult to treat, owing to inefficient drugs. Here we present an analysis of tapeworm genome sequences using the human-infective species Echinococcus multilocularis, E. granulosus, Taenia solium and the laboratory model Hymenolepis microstoma as examples. The 115- to 141-megabase genomes offer insights into the evolution of parasitism. Synteny is maintained with distantly related blood flukes but we find extreme losses of genes and pathways that are ubiquitous in other animals, including 34 homeobox families and several determinants of stem cell fate. Tapeworms have specialized detoxification pathways, metabolism that is finely tuned to rely on nutrients scavenged from their hosts, and species-specific expansions of non-canonical heat shock proteins and families of known antigens. We identify new potential drug targets, including some on which existing pharmaceuticals may act. The genomes provide a rich resource to underpin the development of urgently needed treatments and control.
C1 [Tsai, Isheng J.; Zarowiecki, Magdalena; Holroyd, Nancy; Sanchez-Flores, Alejandro; Brooks, Karen L.; Tracey, Alan; Aslett, Martin; Beasley, Helen; Bennett, Hayley M.; Clark, Richard; De Silva, Nishadi; Huckvale, Thomas; Keane, Jacqueline A.; Lambert, Olivia; Berriman, Matthew] Wellcome Trust Genome Campus, Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England.
   [Tsai, Isheng J.] Miyazaki Univ, Div Parasitol, Dept Infect Dis, Fac Med, Miyazaki 8891692, Japan.
   [Garciarrubio, Alejandro; Sanchez-Flores, Alejandro] Univ Nacl Autonoma Mexico, Inst Biotechnol, Cuernavaca 62210, Morelos, Mexico.
   [Bobes, Raul J.; Fragoso, Gladis] Univ Nacl Autonoma Mexico, Inst Biomed Res, Mexico City 04510, DF, Mexico.
   [Cai, Jianping] Chinese Acad Agr Sci, State Key Lab Vet Etiol Biol, Key Lab Vet Parasitol Gansu Prov, Lanzhou Vet Res Inst, Lanzhou 730046, Gansu, Peoples R China.
   [Cucher, Marcela] Univ Buenos Aires, Inst Microbiol & Parasitol Med, Fac Med, Consejo Nacl Invest Cient Tecnol IMPAM, Buenos Aires, DF, Argentina.
   [Day, Tim A.] Iowa State Univ, Dept Biomed Sci, Ames, IA 50011 USA.
   [Deplazes, Peter] Univ Zurich, Inst Parasitol, Vet Fac, CH-8057 Zurich, Switzerland.
   [Fernandez, Cecilia] Univ Republica, Fac Quam, Montevideo 11600, Uruguay.
   [Holland, Peter W. H.] Univ Oxford, Dept Zool, Oxford OX1 3PS, England.
   [Hu, Songnian] Chinese Acad Sci, Beijing Inst Genom, Beijing 100029, Peoples R China.
   [Parkinson, John] Univ Toronto, Dept Biochem & Mol & Med Genet, Program Mol Struct & Funct, Hosp Sick Children, Toronto, ON M5G 1X8, Canada.
   [Parkinson, John] Univ Wurzburg, Inst Hyg & Microbiol, D-97080 Wurzburg, Germany.
   [Riddiford, Nick] Nat Hist Museum, Dept Life Sci, London SW7 5BD, England.
   [Riddiford, Nick] Natl Univ Ireland Galway, Dept Zool, Sch Nat Sci, Galway, Ireland.
   [Zamanian, Mostafa] McGill Univ, Inst Parasitol, Ste Anne De Bellevue, PQ H9X 3V9, Canada.
   [Soberon, Xavier] Inst Nacl Medicina Genom, Mexico City 14610, DF, Mexico.
C3 Wellcome Trust Sanger Institute; University of Miyazaki; Universidad Nacional Autonoma de Mexico; Universidad Nacional Autonoma de Mexico; Chinese Academy of Agricultural Sciences; Lanzhou Veterinary Research Institute, CAAS; University of Buenos Aires; Iowa State University; University of Zurich; Universidad de la Republica, Uruguay; University of Oxford; Chinese Academy of Sciences; Beijing Institute of Genomics, CAS; University of Toronto; Hospital for Sick Children (SickKids); University of Wurzburg; Natural History Museum London; Ollscoil na Gaillimhe-University of Galway; McGill University; Instituto Nacional de Medicina Genomica
RP Berriman, M (corresponding author), Wellcome Trust Genome Campus, Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England.
EM laclette@biomedicas.unam.mx; kbrehm@hygiene.uni-wuerzburg.de; mb4@sanger.ac.uk
FU BBSRC [BBG0038151]; SynTax joint UK Research Council; European Research Council; Canadian Institute for Health Research (CIHR MOP) [84556]; FIRCA-NIH [TW008588]; Universidad de la Republica, CSIC [CSIC 625]; Wellcome Trust through Wellcome Trust Sanger Institute [098051]; Deutsche Forschungsgemeinschaft (DFG) [BR2045/4-1]; Universidad Nacional Autonoma de Mexico; Biotechnology and Biological Sciences Research Council [BB/G003815/1] Funding Source: researchfish; BBSRC [BB/G003815/1] Funding Source: UKRI
NR 47
TC 568
Z9 636
U1 6
U2 270
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 4
PY 2013
VL 496
IS 7443
BP 57
EP 63
DI 10.1038/nature12031
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 117ZZ
UT WOS:000316993400024
PM 23485966
DA 2026-03-09
ER

PT J
AU Kruse, AC
   Ring, AM
   Manglik, A
   Hu, JX
   Hu, K
   Eitel, K
   Hübner, H
   Pardon, E
   Valant, C
   Sexton, PM
   Christopoulos, A
   Felder, CC
   Gmeiner, P
   Steyaert, J
   Weis, WI
   Garcia, KC
   Wess, J
   Kobilka, BK
AF Kruse, Andrew C.
   Ring, Aaron M.
   Manglik, Aashish
   Hu, Jianxin
   Hu, Kelly
   Eitel, Katrin
   Huebner, Harald
   Pardon, Els
   Valant, Celine
   Sexton, Patrick M.
   Christopoulos, Arthur
   Felder, Christian C.
   Gmeiner, Peter
   Steyaert, Jan
   Weis, William I.
   Garcia, K. Christopher
   Wess, Juergen
   Kobilka, Brian K.
TI Activation and allosteric modulation of a muscarinic acetylcholine receptor
SO NATURE
LA English
DT Article
ID protein-coupled receptor; site-directed mutagenesis; binding-site; beta(2)-adrenergic receptor; crystal-structure; structural basis; amino-acids; identification; nanobody; ligands
AB Despite recent advances in crystallography and the availability of G-protein-coupled receptor (GPCR) structures, little is known about the mechanism of their activation process, as only the beta(2) adrenergic receptor (beta(2)AR) and rhodopsin have been crystallized in fully active conformations. Here we report the structure of an agonist-bound, active state of the human M2 muscarinic acetylcholine receptor stabilized by a G-protein mimetic camelid antibody fragment isolated by conformational selection using yeast surface display. In addition to the expected changes in the intracellular surface, the structure reveals larger conformational changes in the extracellular region and orthosteric binding site than observed in the active states of the beta(2)AR and rhodopsin. We also report the structure of the M2 receptor simultaneously bound to the orthosteric agonist iperoxo and the positive allosteric modulator LY2119620. This structure reveals that LY2119620 recognizes a largely pre-formed binding site in the extracellular vestibule of the iperoxo-bound receptor, inducing a slight contraction of this outer binding pocket. These structures offer important insights into the activation mechanism and allosteric modulation of muscarinic receptors.
C1 [Kruse, Andrew C.; Ring, Aaron M.; Manglik, Aashish; Weis, William I.; Garcia, K. Christopher; Kobilka, Brian K.] Stanford Univ, Sch Med, Dept Mol & Cellular Physiol, Stanford, CA 94305 USA.
   [Ring, Aaron M.; Weis, William I.; Garcia, K. Christopher] Stanford Univ, Sch Med, Dept Biol Struct, Stanford, CA 94305 USA.
   [Hu, Jianxin; Hu, Kelly; Wess, Juergen] NIDDKD, Mol Signaling Sect, Bioorgan Chem Lab, Bethesda, MD 20892 USA.
   [Eitel, Katrin; Huebner, Harald; Gmeiner, Peter] Univ Erlangen Nurnberg, Dept Chem & Pharm, D-91052 Erlangen, Germany.
   [Pardon, Els; Steyaert, Jan] Vrije Univ Brussel, Struct Biol Brussels, B-1050 Brussels, Belgium.
   [Pardon, Els; Steyaert, Jan] VIB, Struct Biol Res Ctr, B-1050 Brussels, Belgium.
   [Valant, Celine; Sexton, Patrick M.; Christopoulos, Arthur] Monash Inst Pharmaceut Sci, Parkville, Vic 3052, Australia.
   [Valant, Celine; Sexton, Patrick M.; Christopoulos, Arthur] Monash Univ, Dept Pharmacol, Parkville, Vic 3052, Australia.
   [Felder, Christian C.] Eli Lilly & Co, Neurosci, Indianapolis, IN 46285 USA.
C3 Stanford University; Stanford University; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK); University of Erlangen Nuremberg; Vrije Universiteit Brussel; Flanders Institute for Biotechnology (VIB); Monash University; Eli Lilly
RP Kobilka, BK (corresponding author), Stanford Univ, Sch Med, Dept Mol & Cellular Physiol, 279 Campus Dr, Stanford, CA 94305 USA.
EM kobilka@stanford.edu
FU National Science Foundation [1223785]; Stanford Medical Scientist Training Program; American Heart Association; Ruth L. Kirschstein National Research Service Award; National Institutes of Health [NS02847123, GM08311806]; Mathers Foundation; Deutsche Forschungsgemeinschaft [GM 13/10-1]; National Health and Medical Research Council (NHMRC) of Australia [519461]; NHMRC; Howard Hughes Medical Institute; Intramural Research Program, NIDDK; NIH; US Department of Health and Human Services; National Institute of Diabetes and Digestive and Kidney Diseases [ZIADK031129] Funding Source: NIH RePORTER; Division Of Chemistry; Direct For Mathematical & Physical Scien [1223785] Funding Source: National Science Foundation
NR 48
TC 768
Z9 871
U1 1
U2 270
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 5
PY 2013
VL 504
IS 7478
BP 101
EP +
DI 10.1038/nature12735
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 264BK
UT WOS:000327851700039
PM 24256733
DA 2026-03-09
ER

PT J
AU Tanvir, NR
   Levan, AJ
   Fruchter, AS
   Hjorth, J
   Hounsell, RA
   Wiersema, K
   Tunnicliffe, RL
AF Tanvir, N. R.
   Levan, A. J.
   Fruchter, A. S.
   Hjorth, J.
   Hounsell, R. A.
   Wiersema, K.
   Tunnicliffe, R. L.
TI A 'kilonova' associated with the short-duration γ-ray burst GRB130603B
SO NATURE
LA English
DT Article
ID neutron-star; r-process; nucleosynthesis; mergers
AB Short-duration gamma-ray bursts are intense flashes of cosmic gamma-rays, lasting less than about two seconds, whose origin is unclear(1,2). The favoured hypothesis is that they are produced by a relativistic jet created by the merger of two compact stellar objects (specifically two neutron stars or a neutron star and a black hole). This is supported by indirect evidence such as the properties of their host galaxies(3), but unambiguous confirmation of the model is still lacking. Mergers of this kind are also expected to create significant quantities of neutron-rich radioactive species(4,5), whose decay should result in a faint transient, known as a 'kilonova', in the days following the burst(6-8). Indeed, it is speculated that this mechanism may be the predominant source of stable r-process elements in the Universe(5,9). Recent calculations suggest that much of the kilonova energy should appear in the near-infrared spectral range, because of the high optical opacity created by these heavy r-process elements(10-13). Here we report optical and near-infrared observations that provide strong evidence for such an event accompanying the short-duration gamma-ray burst GRB130603B. If this, the simplest interpretation of the data, is correct, then it confirms that compact-object mergers are the progenitors of short-duration gamma-ray bursts and the sites of significant production of r-process elements. It also suggests that kilonovae offer an alternative, unbeamed electromagnetic signature of the most promising sources for direct detection of gravitational waves.
C1 [Tanvir, N. R.; Wiersema, K.] Univ Leicester, Dept Phys & Astron, Leicester LE1 7RH, Leics, England.
   [Levan, A. J.; Tunnicliffe, R. L.] Univ Warwick, Dept Phys, Coventry CV4 7AL, W Midlands, England.
   [Fruchter, A. S.; Hounsell, R. A.] Space Telescope Sci Inst, Baltimore, MD 21218 USA.
   [Hjorth, J.] Univ Copenhagen, Niels Bohr Inst, Dark Cosmol Ctr, DK-2100 Copenhagen, Denmark.
C3 University of Leicester; University of Warwick; Space Telescope Science Institute; University of Copenhagen; Niels Bohr Institute
RP Tanvir, NR (corresponding author), Univ Leicester, Dept Phys & Astron, Univ Rd, Leicester LE1 7RH, Leics, England.
EM nrt3@le.ac.uk
FU Danish National Research Foundation;  [GO/DD 13497]; Science and Technology Facilities Council [ST/K001000/1, ST/L001306/1, ST/F007159/1, PP/E002064/1, ST/I001719/1] Funding Source: researchfish; STFC [ST/I001719/1, ST/L001306/1, PP/E002064/1, ST/K001000/1, ST/F007159/1] Funding Source: UKRI
NR 29
TC 639
Z9 712
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 AUG 29
PY 2013
VL 500
IS 7464
BP 547
EP 549
DI 10.1038/nature12505
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 207TD
UT WOS:000323625900027
PM 23912055
DA 2026-03-09
ER

PT J
AU Herzog, BH
   Fu, JX
   Wilson, SJ
   Hess, PR
   Sen, A
   McDaniel, JM
   Pan, YF
   Sheng, MJ
   Yago, T
   Silasi-Mansat, R
   McGee, S
   May, F
   Nieswandt, B
   Morris, AJ
   Lupu, F
   Coughlin, SR
   McEver, RP
   Chen, H
   Kahn, ML
   Xia, LJ
AF Herzog, Brett H.
   Fu, Jianxin
   Wilson, Stephen J.
   Hess, Paul R.
   Sen, Aslihan
   McDaniel, J. Michael
   Pan, Yanfang
   Sheng, Minjia
   Yago, Tadayuki
   Silasi-Mansat, Robert
   McGee, Samuel
   May, Frauke
   Nieswandt, Bernhard
   Morris, Andrew J.
   Lupu, Florea
   Coughlin, Shaun R.
   McEver, Rodger P.
   Chen, Hong
   Kahn, Mark L.
   Xia, Lijun
TI Podoplanin maintains high endothelial venule integrity by interacting with platelet CLEC-2
SO NATURE
LA English
DT Article
ID vascular integrity; stromal cells; ve-cadherin; lymph-nodes; mice; sphingosine-1-phosphate; lymphocytes; selectin; mouse; blood
AB Circulating lymphocytes continuously enter lymph nodes for immune surveillance through specialized blood vessels named high endothelial venules(1-5), a process that increases markedly during immune responses. How high endothelial venules (HEVs) permit lymphocyte transmigration while maintaining vascular integrity is unknown. Here we report a role for the transmembrane O-glycoprotein podoplanin (PDPN, also known as gp38 and T1 alpha)(6-8) in maintaining HEV barrier function. Mice with postnatal deletion of Pdpn lost HEV integrity and exhibited spontaneous bleeding in mucosal lymph nodes, and bleeding in the draining peripheral lymph nodes after immunization. Blocking lymphocyte homing rescued bleeding, indicating that PDPN is required to protect the barrier function of HEVs during lymphocyte trafficking. Further analyses demonstrated that PDPN expressed on fibroblastic reticular cells(7), which surround HEVs, functions as an activating ligand for platelet C-type lectin-like receptor 2 (CLEC-2, also known as CLEC1B)(9,10). Mice lacking fibroblastic reticular cell PDPN or platelet CLEC-2 exhibited significantly reduced levels of VE-cadherin (also known as CDH5), which is essential for overall vascular integrity(11,12), on HEVs. Infusion of wild-type platelets restored HEV integrity in Clec-2-deficient mice. Activation of CLEC-2 induced release of sphingosine-1-phosphate(13,14) from platelets, which promoted expression of VE-cadherin on HEVs ex vivo. Furthermore, draining peripheral lymph nodes of immunized mice lacking sphingosine-1-phosphate had impaired HEV integrity similar to Pdpn- and Clec-2-deficient mice. These data demonstrate that local sphingosine-1-phosphate release after PDPN-CLEC-2-mediated platelet activation is critical for HEV integrity during immune responses.
C1 [Herzog, Brett H.; Fu, Jianxin; McDaniel, J. Michael; Pan, Yanfang; Sheng, Minjia; Yago, Tadayuki; Silasi-Mansat, Robert; McGee, Samuel; Lupu, Florea; McEver, Rodger P.; Chen, Hong; Xia, Lijun] Oklahoma Med Res Fdn, Cardiovasc Biol Res Program, Oklahoma City, OK 73104 USA.
   [Herzog, Brett H.; Pan, Yanfang; McEver, Rodger P.; Chen, Hong; Xia, Lijun] Univ Oklahoma, Hlth Sci Ctr, Dept Biochem & Mol Biol, Oklahoma City, OK 73104 USA.
   [Fu, Jianxin; Xia, Lijun] Soochow Univ, Affiliated Hosp 1, Jiangsu Inst Hematol, Suzhou 215006, Jiangsu, Peoples R China.
   [Fu, Jianxin; Xia, Lijun] Soochow Univ, Affiliated Hosp 1, Minist Hlth, Key Lab Thrombosis & Hemostasis, Suzhou 215006, Jiangsu, Peoples R China.
   [Wilson, Stephen J.; Coughlin, Shaun R.] Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94158 USA.
   [Hess, Paul R.; Sen, Aslihan; Kahn, Mark L.] Univ Penn, Dept Med, Philadelphia, PA 19104 USA.
   [Hess, Paul R.; Sen, Aslihan; Kahn, Mark L.] Univ Penn, Div Cardiol, Philadelphia, PA 19104 USA.
   [May, Frauke; Nieswandt, Bernhard] Univ Hosp Wurzburg, D-97080 Wurzburg, Germany.
   [May, Frauke; Nieswandt, Bernhard] DFG Res Ctr Expt Biomed, Rudolf Virchow Ctr, D-97080 Wurzburg, Germany.
   [Morris, Andrew J.] Univ Kentucky, Div Cardiovasc Med, Lexington, KY 40502 USA.
   [Morris, Andrew J.] Lexington Vet Affairs Med Ctr, Lexington, KY 40502 USA.
C3 Oklahoma Medical Research Foundation; University of Oklahoma System; University of Oklahoma Health Sciences Center; Soochow University - China; Soochow University - China; University of California System; University of California San Francisco; University of Pennsylvania; University of Pennsylvania; University of Wurzburg; German Research Foundation (DFG); University of Wurzburg; University of Kentucky; US Department of Veterans Affairs; Veterans Health Administration (VHA); Lexington VA Medical Center
RP Xia, LJ (corresponding author), Oklahoma Med Res Fdn, Cardiovasc Biol Res Program, Oklahoma City, OK 73104 USA.
EM Lijun-Xia@omrf.org
FU National Institutes of Health [GM103441, GM097747, HL085607, HL093242, HL103432, HL065590, HL112788]; VA Merit Award [BX001984]; American Heart Association [SDG7410022]; Deutsche Forschungsgemeinschaft [SFB688]; National Natural Science Foundation of China [30928010]; Jiangsu Provincial Special Program of Medical Science [BL2012005]; Jiangsu Province's Key Medical Center [ZX201102]; National Heart Lung and Blood Institute [R01HL093242] Funding Source: NIH RePORTER
NR 38
TC 258
Z9 302
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 OCT 3
PY 2013
VL 502
IS 7469
BP 105
EP +
DI 10.1038/nature12501
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 227IM
UT WOS:000325106000040
PM 23995678
DA 2026-03-09
ER

PT J
AU Power, S
   Delage, F
   Chung, C
   Kociuba, G
   Keay, K
AF Power, Scott
   Delage, Francois
   Chung, Christine
   Kociuba, Greg
   Keay, Kevin
TI Robust twenty-first-century projections of El Nino and related precipitation variability
SO NATURE
LA English
DT Article
ID climate; ocean; enso
AB The El Nino-Southern Oscillation (ENSO) drives substantial variability in rainfall(1-3), severe weather(4,5), agricultural production(3,6), ecosystems(7) and disease(8) in many parts of the world. Given that further human-forced changes in the Earth's climate system seem inevitable(9,10), the possibility exists that the character of ENSO and its impacts might change over the coming century. Although this issue has been investigated many times during the past 20 years, there is very little consensus on future changes in ENSO, apart from an expectation that ENSO will continue to be a dominant source of year-to-year variability(9,11,12). Here we show that there are in fact robust projected changes in the spatial patterns of year-to-year ENSO-driven variability in both surface temperature and precipitation. These changes are evident in the two most recent generations of climate models(13,14), using four different scenarios for CO2 and other radiatively active gases(14-17). By the mid- to late twenty-first century, the projections include an intensification of both El-Nino-driven drying in the western Pacific Ocean and rainfall increases in the central and eastern equatorial Pacific. Experiments with an Atmospheric General Circulation Model reveal that robust projected changes in precipitation anomalies during El Nino years are primarily determined by a nonlinear response to surface global warming. Uncertain projected changes in the amplitude of ENSO-driven surface temperature variability have only a secondary role. Projected changes in key characteristics of ENSO are consequently much clearer than previously realized.
C1 [Power, Scott; Delage, Francois; Chung, Christine; Kociuba, Greg; Keay, Kevin] Bur Meteorol, Ctr Australian Weather & Climate Res, Melbourne, Vic 3008, Australia.
C3 Bureau of Meteorology - Australia; Commonwealth Scientific & Industrial Research Organisation (CSIRO)
RP Power, S (corresponding author), Bur Meteorol, Ctr Australian Weather & Climate Res, Melbourne, Vic 3008, Australia.
EM s.power@bom.gov.au
FU Australian Climate Change Science Program (ACCSP); Pacific-Australia Climate Change Science and Adaptation planning Program (PACCSAP); AusAID; Department of Industry, Innovation, Climate Change, Science, Research and Tertiary Education
NR 30
TC 390
Z9 423
U1 2
U2 215
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 24
PY 2013
VL 502
IS 7472
BP 541
EP +
DI 10.1038/nature12580
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 238YN
UT WOS:000325988400052
PM 24121439
DA 2026-03-09
ER

PT J
AU Marchetto, MCN
   Narvaiza, I
   Denli, AM
   Benner, C
   Lazzarini, TA
   Nathanson, JL
   Paquola, ACM
   Desai, KN
   Herai, RH
   Weitzman, MD
   Yeo, GW
   Muotri, AR
   Gage, FH
AF Marchetto, Maria C. N.
   Narvaiza, Inigo
   Denli, Ahmet M.
   Benner, Christopher
   Lazzarini, Thomas A.
   Nathanson, Jason L.
   Paquola, Apua C. M.
   Desai, Keval N.
   Herai, Roberto H.
   Weitzman, Matthew D.
   Yeo, Gene W.
   Muotri, Alysson R.
   Gage, Fred H.
TI Differential L1 regulation in pluripotent stem cells of humans and apes
SO NATURE
LA English
DT Article
ID line-1 retrotransposition; mobile elements; chimpanzee; amplification; apobec3a; database; update; mili
AB Identifying cellular and molecular differences between human and non-human primates (NHPs) is essential to the basic understanding of the evolution and diversity of our own species. Until now, preserved tissues have been the main source for most comparative studies between humans, chimpanzees (Pan troglodytes) and bonobos (Pan paniscus)(1,2). However, these tissue samples do not fairly represent the distinctive traits of live cell behaviour and are not amenable to genetic manipulation. We propose that induced pluripotent stem (iPS) cells could be a unique biological resource to determine relevant phenotypical differences between human and NHPs, and that those differences could have potential adaptation and speciation value. Here we describe the generation and initial characterization of iPS cells from chimpanzees and bonobos as new tools to explore factors that may have contributed to great ape evolution. Comparative gene expression analysis of human and NHP iPS cells revealed differences in the regulation of long interspersed element-1 (L1, also known as LINE-1) transposons. A force of change in mammalian evolution, L1 elements are retrotransposons that have remained active during primate evolution(3-5). Decreased levels of L1-restricting factors APOBEC3B (also known as A3B)(6) and PIWIL2 (ref. 7) in NHP iPS cells correlated with increased L1 mobility and endogenous L1 messenger RNA levels. Moreover, results from the manipulation of A3B and PIWIL2 levels in iPS cells supported a causal inverse relationship between levels of these proteins and L1 retrotransposition. Finally, we found increased copy numbers of species-specific L1 elements in the genome of chimpanzees compared to humans, supporting the idea that increased L1 mobility in NHPs is not limited to iPS cells in culture and may have also occurred in the germ line or embryonic cells developmentally upstream to germline specification during primate evolution. We propose that differences in L1 mobility may have differentially shaped the genomes of humans and NHPs and could have continuing adaptive significance.
C1 [Marchetto, Maria C. N.; Narvaiza, Inigo; Denli, Ahmet M.; Benner, Christopher; Lazzarini, Thomas A.; Paquola, Apua C. M.; Gage, Fred H.] Salk Inst Biol Studies, Genet Lab, La Jolla, CA 92037 USA.
   [Nathanson, Jason L.; Yeo, Gene W.] Univ Calif San Diego, Dept Cellular & Mol Med, Stem Cell Program, Inst Genom Med,Sanford Consortium Regenerat Med, La Jolla, CA 92037 USA.
   [Desai, Keval N.] Univ Calif San Diego, Div Biol Sci, La Jolla, CA 92093 USA.
   [Herai, Roberto H.; Muotri, Alysson R.] Univ Calif San Diego, Rady Childrens Hosp San Diego, Dept Cellular & Mol Med,Dept Pediat, Stem Cell Program,Sanford Consortium,Sch Med, La Jolla, CA 92093 USA.
   [Weitzman, Matthew D.] Univ Penn, Perelman Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA.
   [Weitzman, Matthew D.] Childrens Hosp Philadelphia, Ctr Cellular & Mol Therapeut, Philadelphia, PA 19104 USA.
   [Muotri, Alysson R.; Gage, Fred H.] CARTA, La Jolla, CA 92093 USA.
C3 Salk Institute; University of California System; University of California San Diego; University of California System; University of California San Diego; Rady Childrens Hospital San Diego; University of California System; University of California San Diego; University of Pennsylvania; University of Pennsylvania; Pennsylvania Medicine; Childrens Hospital of Philadelphia
RP Gage, FH (corresponding author), Salk Inst Biol Studies, Genet Lab, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA.
EM gage@salk.edu
FU National Institutes of Health (NIH) [TR01: MH095741, Eureka: MH08848, MH094753, AI074967, NS075449, HG004659, GM084317]; Mathers Foundation; Helmsley Foundation; Alfred P. Sloan Research Fellowship; National Cancer Institute [P30CA014195] Funding Source: NIH RePORTER; National Human Genome Research Institute [R01HG004659] Funding Source: NIH RePORTER
NR 51
TC 179
Z9 220
U1 0
U2 47
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 28
PY 2013
VL 503
IS 7477
BP 525
EP +
DI 10.1038/nature12686
PG 20
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 258MU
UT WOS:000327464200043
PM 24153179
DA 2026-03-09
ER

PT J
AU Inokuma, Y
   Yoshioka, S
   Ariyoshi, J
   Arai, T
   Hitora, Y
   Takada, K
   Matsunaga, S
   Rissanen, K
   Fujita, M
AF Inokuma, Yasuhide
   Yoshioka, Shota
   Ariyoshi, Junko
   Arai, Tatsuhiko
   Hitora, Yuki
   Takada, Kentaro
   Matsunaga, Shigeki
   Rissanen, Kari
   Fujita, Makoto
TI X-ray analysis on the nanogram to microgram scale using porous complexes
SO NATURE
LA English
DT Article
ID absolute-configuration; guest exchange; crystal; molecules; network; inclusion; framework; santonin; citrus
AB X-ray single-crystal diffraction (SCD) analysis has the intrinsic limitation that the target molecules must be obtained as single crystals. Here we report a protocol for SCD analysis that does not require the crystallization of the sample. In our method, tiny crystals of porous complexes are soaked in a solution of the target, such that the complexes can absorb the target molecules. Crystallographic analysis clearly determines the absorbed guest structures along with the host frameworks. Because the SCD analysis is carried out on only one tiny crystal of the complex, the required sample mass is of the nanogram-microgram order. We demonstrate that as little as about 80 nanograms of a sample is enough for the SCD analysis. In combination with high-performance liquid chromatography, our protocol allows the direct characterization of multiple fractions, establishing a prototypical means of liquid chromatography SCD analysis. Furthermore, we unambiguously determined the structure of a scarce marine natural product using only 5 micrograms of the compound.
C1 [Inokuma, Yasuhide; Yoshioka, Shota; Ariyoshi, Junko; Arai, Tatsuhiko; Fujita, Makoto] Univ Tokyo, Dept Appl Chem, Grad Sch Engn, Bunkyo Ku, Tokyo 1138656, Japan.
   [Hitora, Yuki; Takada, Kentaro; Matsunaga, Shigeki] Univ Tokyo, Lab Aquat Nat Prod Chem, Grad Sch Agr & Life Sci, Bunkyo Ku, Tokyo 1138657, Japan.
   [Rissanen, Kari] Univ Jyvaskyla, Dept Chem, NanoSci Ctr, Jyvaskyla 40014, Finland.
C3 University of Tokyo; University of Tokyo; University of Jyvaskyla
RP Fujita, M (corresponding author), Univ Tokyo, Dept Appl Chem, Grad Sch Engn, Bunkyo Ku, Tokyo 1138656, Japan.
EM mfujita@appchem.t.u-tokyo.ac.jp
FU CREST project of the Japan Science and Technology Agency;  [24000009];  [23750146]; Grants-in-Aid for Scientific Research [12J07872, 23750146] Funding Source: KAKEN
NR 40
TC 754
Z9 850
U1 9
U2 742
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 28
PY 2013
VL 495
IS 7442
BP 461
EP +
DI 10.1038/nature11990
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 113QN
UT WOS:000316682800036
PM 23538828
DA 2026-03-09
ER

PT J
AU Füllgrabe, J
   Lynch-Day, MA
   Heldring, N
   Li, WB
   Struijk, RB
   Ma, Q
   Hermanson, O
   Rosenfeld, MG
   Klionsky, DJ
   Joseph, B
AF Fullgrabe, Jens
   Lynch-Day, Melinda A.
   Heldring, Nina
   Li, Wenbo
   Struijk, Robert B.
   Ma, Qi
   Hermanson, Ola
   Rosenfeld, Michael G.
   Klionsky, Daniel J.
   Joseph, Bertrand
TI The histone H4 lysine 16 acetyltransferase hMOF regulates the outcome of autophagy
SO NATURE
LA English
DT Article
ID h4k16 acetylation; in-vivo; protein; activation; death; sirt1; mof
AB Autophagy is an evolutionarily conserved catabolic process involved in several physiological and pathological processes(1,2). Although primarily cytoprotective, autophagy can also contribute to cell death; it is thus important to understand what distinguishes the life or death decision in autophagic cells(3). Here we report that induction of autophagy is coupled to reduction of histone H4 lysine 16 acetylation (H4K16ac) through downregulation of the histone acetyltransferase hMOF (also called KAT8 or MYST1), and demonstrate that this histone modification regulates the outcome of autophagy. At a genome-wide level, we find that H4K16 deacetylation is associated predominantly with the downregulation of autophagy-related genes. Antagonizing H4K16ac downregulation upon autophagy induction results in the promotion of cell death. Our findings establish that alteration in a specific histone post-translational modification during autophagy affects the transcriptional regulation of autophagy-related genes and initiates a regulatory feedback loop, which serves as a key determinant of survival versus death responses upon autophagy induction.
C1 [Fullgrabe, Jens; Struijk, Robert B.; Joseph, Bertrand] Karolinska Inst, Dept Oncol Pathol, Canc Ctr Karolinska, S-17176 Stockholm, Sweden.
   [Lynch-Day, Melinda A.; Klionsky, Daniel J.] Univ Michigan, Inst Life Sci, Ann Arbor, MI 48109 USA.
   [Lynch-Day, Melinda A.; Klionsky, Daniel J.] Univ Michigan, Dept Mol Cellular & Dev Biol, Ann Arbor, MI 48109 USA.
   [Lynch-Day, Melinda A.; Klionsky, Daniel J.] Univ Michigan, Dept Biol Chem, Ann Arbor, MI 48109 USA.
   [Heldring, Nina; Hermanson, Ola] Karolinska Inst, Dept Neurosci, S-17177 Stockholm, Sweden.
   [Li, Wenbo; Ma, Qi; Rosenfeld, Michael G.] Univ Calif San Diego, Sch Med, Howard Hughes Med Inst, Dept Med, La Jolla, CA 92093 USA.
   [Ma, Qi] Univ Calif San Diego, Grad Program Bioinformat & Syst Biol, La Jolla, CA 92093 USA.
C3 Karolinska Institutet; University of Michigan System; University of Michigan; University of Michigan System; University of Michigan; University of Michigan System; University of Michigan; Karolinska Institutet; University of California System; University of California San Diego; Howard Hughes Medical Institute; University of California System; University of California San Diego
RP Joseph, B (corresponding author), Karolinska Inst, Dept Oncol Pathol, Canc Ctr Karolinska, S-17176 Stockholm, Sweden.
EM bertrand.joseph@ki.se
FU Karolinska Institutet Foundations; Rackham Predoctoral Fellowship; US Department of Defense [BC110381]; National Institutes of Health [GM53396]; National Institutes of Health/National Cancer Institute; Department of Defense; Swedish Cancer Society; Swedish Childhood Cancer Foundation; Swedish Research Council
NR 36
TC 280
Z9 298
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 AUG 22
PY 2013
VL 500
IS 7463
BP 468
EP +
DI 10.1038/nature12313
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 203TJ
UT WOS:000323316100037
PM 23863932
DA 2026-03-09
ER

PT J
AU Parker, J
   Tsagkogeorga, G
   Cotton, JA
   Liu, Y
   Provero, P
   Stupka, E
   Rossiter, SJ
AF Parker, Joe
   Tsagkogeorga, Georgia
   Cotton, James A.
   Liu, Yuan
   Provero, Paolo
   Stupka, Elia
   Rossiter, Stephen J.
TI Genome-wide signatures of convergent evolution in echolocating mammals
SO NATURE
LA English
DT Article
ID parallel evolution; sequence evolution; genes; adaptation; thousands; selection; alignment; accuracy; flight; space
AB Evolution is typically thought to proceed through divergence of genes, proteins and ultimately phenotypes(1-3). However, similar traits might also evolve convergently in unrelated taxa owing to similar selection pressures(4,5). Adaptive phenotypic convergence is widespread in nature, and recent results from several genes have suggested that this phenomenon is powerful enough to also drive recurrent evolution at the sequence level(6-9). Where homoplasious substitutions do occur these have long been considered the result of neutral processes. However, recent studies have demonstrated that adaptive convergent sequence evolution can be detected in vertebrates using statistical methods that model parallel evolution(9,10), although the extent to which sequence convergence between genera occurs across genomes is unknown. Here we analyse genomic sequence data in mammals that have independently evolved echolocation and show that convergence is not a rare process restricted to several loci but is instead widespread, continuously distributed and commonly driven by natural selection acting on a small number of sites per locus. Systematic analyses of convergent sequence evolution in 805,053 amino acids within 2,326 orthologous coding gene sequences compared across 22 mammals (including four newly sequenced bat genomes) revealed signatures consistent with convergence in nearly 200 loci. Strong and significant support for convergence among bats and the bottlenose dolphin was seen in numerous genes linked to hearing or deafness, consistent with an involvement in echolocation. Unexpectedly, we also found convergence in many genes linked to vision: the convergent signal of many sensory genes was robustly correlated with the strength of natural selection. This first attempt to detect genome-wide convergent sequence evolution across divergent taxa reveals the phenomenon to be much more pervasive than previously recognized.
C1 [Parker, Joe; Tsagkogeorga, Georgia; Cotton, James A.; Rossiter, Stephen J.] Univ London, Sch Biol & Chem Sci, London E1 4NS, England.
   [Liu, Yuan] BGI Europe, DK-2200 Copenhagen N, Denmark.
   [Provero, Paolo; Stupka, Elia] Ist Sci San Raffaele, Ctr Translat Genom & Bioinformat, I-20132 Milan, Italy.
   [Provero, Paolo] Univ Turin, Dept Mol Biotechnol & Hlth Sci, I-10126 Turin, Italy.
C3 University of London; Vita-Salute San Raffaele University; IRCCS Ospedale San Raffaele; University of Turin
RP Parker, J (corresponding author), Univ London, Sch Biol & Chem Sci, London E1 4NS, England.
EM j.d.parker@qmul.ac.uk; s.j.rossiter@qmul.ac.uk
FU Biotechnology and Biological Sciences Research [BB/H017178/1]; BBSRC [BB/H017178/1] Funding Source: UKRI; Biotechnology and Biological Sciences Research Council [BB/H017178/1] Funding Source: researchfish
NR 59
TC 282
Z9 345
U1 9
U2 318
PU NATURE PUBLISHING 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 10
PY 2013
VL 502
IS 7470
BP 228
EP +
DI 10.1038/nature12511
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 231RU
UT WOS:000325436100049
PM 24005325
DA 2026-03-09
ER

PT J
AU Jutzi, M
   Asphaug, E
   Gillet, P
   Barrat, JA
   Benz, W
AF Jutzi, M.
   Asphaug, E.
   Gillet, P.
   Barrat, J. -A.
   Benz, W.
TI The structure of the asteroid 4 Vesta as revealed by models of planet-scale collisions
SO NATURE
LA English
DT Article
ID parent body; simulations; dawn; geochemistry; diogenites; howardite; core
AB Asteroid 4 Vesta seems to be a major intact protoplanet, with a surface composition similar to that of the HED (howardite-eucrite-diogenite) meteorites(1-4). The southern hemisphere is dominated by a giant impact scar(5), but previous impact models(6-8) have failed to reproduce the observed topography. The recent discovery that Vesta's southern hemisphere is dominated by two overlapping basins' provides an opportunity to model Vesta's topography more accurately. Here we report three-dimensional simulations of Vesta's global evolution under two overlapping planet-scale collisions. We closely reproduce its observed shape, and provide maps of impact excavation and ejecta deposition. Spiral patterns observed in the younger basin Rheasilvia(9), about one billion years old(10), are attributed to Coriolis forces during crater collapse. Surface materials exposed in the north come from a depth of about 20 kilometres, according to our models, whereas materials exposed inside the southern double-excavation come from depths of about 60-100 kilometres. If Vesta began as a layered, completely differentiated protoplanet, then our model predicts large areas of pure diogenites and olivine-rich rocks. These are not seen(11-13), possibly implying that the outer 100 kilometres or so of Vesta is composed mainly of a basaltic crust (eucrites) with ultramafic intrusions (diogenites).
C1 [Jutzi, M.; Benz, W.] Univ Bern, Inst Phys, Ctr Space & Habitabil, CH-3012 Bern, Switzerland.
   [Asphaug, E.] Arizona State Univ, Sch Earth & Space Explorat, Tempe, AZ 85287 USA.
   [Gillet, P.] Ecole Polytech Fed Lausanne, Inst Condensed Matter Phys, CH-1015 Lausanne, Switzerland.
   [Barrat, J. -A.] Univ Bretagne Occidentale, Inst Univ Europeen Mer, CNRS, UMR 6538, F-29280 Plouzane, France.
C3 University of Bern; Arizona State University; Arizona State University-Tempe; Swiss Federal Institutes of Technology Domain; Ecole Polytechnique Federale de Lausanne; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Earth Sciences & Astronomy (INSU); Universite de Bretagne Occidentale; Institut Universitaire Europeen de la Mer (IUEM)
RP Jutzi, M (corresponding author), Univ Bern, Inst Phys, Ctr Space & Habitabil, Sidlerstr 5, CH-3012 Bern, Switzerland.
EM martin.jutzi@space.unibe.ch
FU Ambizione programme of the Swiss National Science Foundation; NASA's Planetary Geology and Geophysics Program; Programme National de Planetologie de l'JNSU; Swiss National Science Foundation
NR 29
TC 79
Z9 89
U1 1
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 FEB 14
PY 2013
VL 494
IS 7436
BP 207
EP 210
DI 10.1038/nature11892
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 092QS
UT WOS:000315137700033
PM 23407535
DA 2026-03-09
ER

PT J
AU Ferreon, ACM
   Ferreon, JC
   Wright, PE
   Deniz, AA
AF Ferreon, Allan Chris M.
   Ferreon, Josephine C.
   Wright, Peter E.
   Deniz, Ashok A.
TI Modulation of allostery by protein intrinsic disorder
SO NATURE
LA English
DT Article
ID adenovirus e1a; structural basis; phase-diagrams; p300; biology; binding; domain
AB Allostery is an intrinsic property of many globular proteins and enzymes that is indispensable for cellular regulatory and feedback mechanisms. Recent theoretical(1) and empirical(2) observations indicate that allostery is also manifest in intrinsically disordered proteins, which account for a substantial proportion of the proteome(3,4). Many intrinsically disordered proteins are promiscuous binders that interact with multiple partners and frequently function as molecular hubs in protein interaction networks. The adenovirus early region 1A (E1A) oncoprotein is a prime example of a molecular hub intrinsically disordered protein(5). E1A can induce marked epigenetic reprogramming of the cell within hours after infection, through interactions with a diverse set of partners that include key host regulators such as the general transcriptional coactivator CREB binding protein (CBP), its paralogue p300, and the retinoblastoma protein (pRb; also called RB1)(6,7). Little is known about the allosteric effects at play in E1A-CBP-pRb interactions, or more generally in hub intrinsically disordered protein interaction networks. Here we used single-molecule fluorescence resonance energy transfer (smFRET) to study coupled binding and folding processes in the ternary E1A system. The low concentrations used in these high-sensitivity experiments proved to be essential for these studies, which are challenging owing to a combination of E1A aggregation propensity and high-affinity binding interactions. Our data revealed that E1A-CBP-pRb interactions have either positive or negative cooperativity, depending on the available E1A interaction sites. This striking cooperativity switch enables fine-tuning of the thermodynamic accessibility of the ternary versus binary E1A complexes, and may permit a context-specific tuning of associated downstream signalling outputs. Such a modulation of allosteric interactions is probably a common mechanism in molecular hub intrinsically disordered protein function.
C1 [Ferreon, Allan Chris M.; Ferreon, Josephine C.; Wright, Peter E.; Deniz, Ashok A.] Scripps Res Inst, Dept Integrat Struct & Computat Biol, La Jolla, CA 92037 USA.
   [Wright, Peter E.] Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA.
C3 Scripps Research Institute; Scripps Research Institute
RP Deniz, AA (corresponding author), Scripps Res Inst, Dept Integrat Struct & Computat Biol, 10550 North Torrey Pines Rd, La Jolla, CA 92037 USA.
EM wright@scripps.edu; deniz@scripps.edu
FU National Institutes of Health [GM066833, CA96865]; Skaggs Institute for Chemical Biology
NR 31
TC 270
Z9 318
U1 0
U2 179
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 20
PY 2013
VL 498
IS 7454
BP 390
EP +
DI 10.1038/nature12294
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 166XI
UT WOS:000320592900046
PM 23783631
DA 2026-03-09
ER

PT J
AU Sidorenkov, LA
   Tey, MK
   Grimm, R
   Hou, YH
   Pitaevskii, L
   Stringari, S
AF Sidorenkov, Leonid A.
   Tey, Meng Khoon
   Grimm, Rudolf
   Hou, Yan-Hua
   Pitaevskii, Lev
   Stringari, Sandro
TI Second sound and the superfluid fraction in a Fermi gas with resonant interactions
SO NATURE
LA English
DT Article
ID bose-einstein condensate; helium ii; liquid-helium; lambda-point; thermodynamics; viscosity; transport; flow
AB Superfluidity is a macroscopic quantum phenomenon occurring in systems as diverse as liquid helium and neutron stars. It occurs below a critical temperature(1,2) and leads to peculiar behaviour such as frictionless flow, the formation of quantized vortices and quenching of the moment of inertia. Ultracold atomic gases offer control of interactions and external confinement, providing unique opportunities to explore superfluid phenomena. Many such (finite-temperature) phenomena can be explained in terms of a two-fluid mixture(3,4) comprising a normal component, which behaves like an ordinary fluid, and a superfluid component with zero viscosity and zero entropy. The two-component nature of a superfluid is manifest in 'second sound', an entropy wave in which the superfluid and the non-superfluid components oscillate with opposite phases (as opposed to ordinary 'first sound', where they oscillate in phase). Here we report the observation of second sound in an ultracold Fermi gas with resonant interactions. The speed of second sound depends explicitly on the value of the superfluid fraction(5), a quantity that is sensitive to the spectrum of elementary excitations(6). Our measurements allow us to extract the temperature dependence of the superfluid fraction, a previously inaccessible quantity that will provide a benchmark for theories of strongly interacting quantum gases.
C1 [Sidorenkov, Leonid A.; Tey, Meng Khoon; Grimm, Rudolf] Austrian Acad Sci, Inst Quantenopt & Quanteninformat, A-6020 Innsbruck, Austria.
   [Sidorenkov, Leonid A.; Tey, Meng Khoon; Grimm, Rudolf] Univ Innsbruck, Inst Expt Phys, A-6020 Innsbruck, Austria.
   [Sidorenkov, Leonid A.; Tey, Meng Khoon; Grimm, Rudolf] Univ Innsbruck, Zentrum Quantenphys, A-6020 Innsbruck, Austria.
   [Hou, Yan-Hua; Pitaevskii, Lev; Stringari, Sandro] Univ Trent, Dipartimento Fis, I-38123 Povo, Italy.
   [Hou, Yan-Hua; Pitaevskii, Lev; Stringari, Sandro] INO CNR BEC Ctr, I-38123 Povo, Italy.
   [Pitaevskii, Lev] Russian Acad Sci, Kapitza Inst Phys Problems, Moscow 119334, Russia.
C3 Austrian Academy of Sciences; University of Innsbruck; University of Innsbruck; University of Trento; Consiglio Nazionale delle Ricerche (CNR); Istituto Nazionale di Ottica (INO-CNR); PL Kapitza Institute for Physical Problems of Russian Academy of Sciences; Russian Academy of Sciences
RP Tey, MK (corresponding author), Austrian Acad Sci, Inst Quantenopt & Quanteninformat, A-6020 Innsbruck, Austria.
EM mengkhoon.tey@ultracold.at
FU Austrian Science Fund (FWF) within SFB FoQuS [F4004-N16]; European Research Council; Provincia Autonoma di Trento
NR 31
TC 156
Z9 170
U1 1
U2 57
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 6
PY 2013
VL 498
IS 7452
BP 78
EP +
DI 10.1038/nature12136
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 158DC
UT WOS:000319947800036
PM 23676679
DA 2026-03-09
ER

PT J
AU de Wit, E
   Bouwman, BAM
   Zhu, Y
   Klous, P
   Splinter, E
   Verstegen, MJAM
   Krijger, PHL
   Festuccia, N
   Nora, EP
   Welling, M
   Heard, E
   Geijsen, N
   Poot, RA
   Chambers, I
   de Laat, W
AF de Wit, Elzo
   Bouwman, Britta A. M.
   Zhu, Yun
   Klous, Petra
   Splinter, Erik
   Verstegen, Marjon J. A. M.
   Krijger, Peter H. L.
   Festuccia, Nicola
   Nora, Elphege P.
   Welling, Maaike
   Heard, Edith
   Geijsen, Niels
   Poot, Raymond A.
   Chambers, Ian
   de Laat, Wouter
TI The pluripotent genome in three dimensions is shaped around pluripotency factors
SO NATURE
LA English
DT Article
ID chromosome conformation capture; chromatin interactions; regulatory landscape; gene-expression; self-renewal; domains; maps; differentiation; proteins; cells
AB It is becoming increasingly clear that the shape of the genome importantly influences transcription regulation. Pluripotent stem cells such as embryonic stem cells were recently shown to organize their chromosomes into topological domains that are largely invariant between cell types(1,2). Here we combine chromatin conformation capture technologies with chromatin factor binding data to demonstrate that inactive chromatin is unusually disorganized in pluripotent stem-cell nuclei. We show that gene promoters engage in contacts between topological domains in a largely tissue-independent manner, whereas enhancers have a more tissue-restricted interaction profile. Notably, genomic clusters of pluripotency factor binding sites find each other very efficiently, in a manner that is strictly pluripotent-stem-cell-specific, dependent on the presence of Oct4 and Nanog protein and inducible after artificial recruitment of Nanog to a selected chromosomal site. We conclude that pluripotent stem cells have a unique higher-order genome structure shaped by pluripotency factors. We speculate that this interactome enhances the robustness of the pluripotent state.
C1 [de Wit, Elzo; Bouwman, Britta A. M.; Zhu, Yun; Klous, Petra; Splinter, Erik; Verstegen, Marjon J. A. M.; Krijger, Peter H. L.; Welling, Maaike; Geijsen, Niels; de Laat, Wouter] Hubrecht Inst KNAW, NL-3584 CT Utrecht, Netherlands.
   [de Wit, Elzo; Bouwman, Britta A. M.; Zhu, Yun; Klous, Petra; Splinter, Erik; Verstegen, Marjon J. A. M.; Krijger, Peter H. L.; Welling, Maaike; Geijsen, Niels; de Laat, Wouter] Univ Med Ctr Utrecht, NL-3584 CT Utrecht, Netherlands.
   [Festuccia, Nicola; Chambers, Ian] Univ Edinburgh, Inst Stem Cell Res, Sch Biol Sci, MRC Ctr Regenerat Med, Edinburgh EH16 4UU, Midlothian, Scotland.
   [Nora, Elphege P.; Heard, Edith] Inst Curie, CNRS, Mammalian Dev Epigenet Grp, INSERM,UMR3215,U934, F-75231 Paris, France.
   [Geijsen, Niels] Univ Utrecht, Sch Vet Med, NL-3584 CL Utrecht, Netherlands.
   [Poot, Raymond A.] Erasmus MC, Dept Cell Biol, NL-3015 GE Rotterdam, Netherlands.
C3 Royal Netherlands Academy of Arts & Sciences; Hubrecht Institute (KNAW); Utrecht University; Utrecht University Medical Center; University of Edinburgh; Universite PSL; UNICANCER; Institut Curie; Centre National de la Recherche Scientifique (CNRS); Institut National de la Sante et de la Recherche Medicale (Inserm); CNRS - National Institute for Biology (INSB); Utrecht University; Erasmus University Rotterdam; Erasmus MC
RP de Laat, W (corresponding author), Hubrecht Inst KNAW, Uppsalalaan 8, NL-3584 CT Utrecht, Netherlands.
EM w.delaat@hubrecht.eu
FU Netherlands Institute for Regenerative Medicine (NIRM) network; Medical Research Council UK; Dutch Scientific Organization (NWO) [700.10.402, 91204082, 935170621]; InteGeR FP7 Marie Curie ITN [PITN-GA-2007-214902]; European Research Council Starting Grant [209700]; European Research Council (ERC) [209700] Funding Source: European Research Council (ERC); MRC [G0901533] Funding Source: UKRI
NR 40
TC 216
Z9 237
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 SEP 12
PY 2013
VL 501
IS 7466
BP 227
EP +
DI 10.1038/nature12420
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 215XR
UT WOS:000324244900042
PM 23883933
DA 2026-03-09
ER

PT J
AU Norman, TM
   Lord, ND
   Paulsson, J
   Losick, R
AF Norman, Thomas M.
   Lord, Nathan D.
   Paulsson, Johan
   Losick, Richard
TI Memory and modularity in cell-fate decision making
SO NATURE
LA English
DT Article
ID stochastic gene-expression; bacillus-subtilis; single-cell; master regulator; population heterogeneity; epigenetic inheritance; biofilm formation; noise; switch; protein
AB Genetically identical cells sharing an environment can display markedly different phenotypes. It is often unclear how much of this variation derives from chance, external signals, or attempts by individual cells to exert autonomous phenotypic programs. By observing thousands of cells for hundreds of consecutive generations under constant conditions, we dissect the stochastic decision between a solitary, motile state and a chained, sessile state in Bacillus subtilis. We show that the motile state is 'memoryless', exhibiting no autonomous control over the time spent in the state. In contrast, the time spent as connected chains of cells is tightly controlled, enforcing coordination among related cells in the multicellular state. We show that the three-protein regulatory circuit governing the decision is modular, as initiation and maintenance of chaining are genetically separable functions. As stimulation of the same initiating pathway triggers biofilm formation, we argue that autonomous timing allows a trial commitment to multicellularity that external signals could extend.
C1 [Norman, Thomas M.; Lord, Nathan D.; Paulsson, Johan] Harvard Univ, Sch Med, Dept Systemat Bot, Boston, MA 02115 USA.
   [Losick, Richard] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA.
C3 Harvard University; Harvard Medical School; Harvard University
RP Paulsson, J (corresponding author), Harvard Univ, Sch Med, Dept Systemat Bot, Boston, MA 02115 USA.
EM Johan_Paulsson@hms.harvard.edu; losick@mcb.harvard.edu
FU National Science Foundation [ECS-0335765]; NIH [GM18568, GM081563]; National Institute of General Medical Sciences [R01GM081563] Funding Source: NIH RePORTER
NR 51
TC 202
Z9 252
U1 0
U2 106
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 28
PY 2013
VL 503
IS 7477
BP 481
EP +
DI 10.1038/nature12804
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 258MU
UT WOS:000327464200034
PM 24256735
DA 2026-03-09
ER

PT J
AU Lauschke, VM
   Tsiairis, CD
   François, P
   Aulehla, A
AF Lauschke, Volker M.
   Tsiairis, Charisios D.
   Francois, Paul
   Aulehla, Alexander
TI Scaling of embryonic patterning based on phase-gradient encoding
SO NATURE
LA English
DT Article
ID segmentation clock; mouse embryo; vertebrate; dynamics; somitogenesis; oscillation; initiation; number; model
AB A fundamental feature of embryonic patterning is the ability to scale and maintain stable proportions despite changes in overall size, for instance during growth(1-6). A notable example occurs during vertebrate segment formation: after experimental reduction of embryo size, segments form proportionally smaller, and consequently, a normal number of segments is formed(1,7,8). Despite decades of experimental(1,7) and theoretical work(9-11), the underlying mechanism remains unknown. More recently, ultradian oscillations in gene activity have been linked to the temporal control of segmentation(12); however, their implication in scaling remains elusive. Here we show that scaling of gene oscillation dynamics underlies segment scaling. To this end, we develop a new experimental model, an ex vivo primary cell culture assay that recapitulates mouse mesoderm patterning and segment scaling, in a quasi-monolayer of presomitic mesoderm cells (hereafter termed monolayer PSM or mPSM). Combined with real-time imaging of gene activity, this enabled us to quantify the gradual shift in the oscillation phase and thus determine the resulting phase gradient across the mPSM. Crucially, we show that this phase gradient scales by maintaining a fixed amplitude across mPSM of different lengths. We identify the slope of this phase gradient as a single predictive parameter for segment size, which functions in a size-and temperature-independent manner, revealing a hitherto unrecognized mechanism for scaling. Notably, in contrast to molecular gradients, a phase gradient describes the distribution of a dynamical cellular state. Thus, our phase-gradient scaling findings reveal a new level of dynamic information-processing, and provide evidence for the concept of phase-gradient encoding during embryonic patterning and scaling.
C1 [Lauschke, Volker M.; Tsiairis, Charisios D.; Aulehla, Alexander] European Mol Biol Lab, Dev Biol Unit, D-69117 Heidelberg, Germany.
   [Francois, Paul] McGill Univ, Dept Phys, Montreal, PQ H3A 2T8, Canada.
C3 European Molecular Biology Laboratory (EMBL); McGill University
RP Aulehla, A (corresponding author), European Mol Biol Lab, Dev Biol Unit, D-69117 Heidelberg, Germany.
EM aulehla@embl.de
FU Natural Science and Engineering Research Council of Canada (NSERC) [RGPIN 401950-11]; Regroupement Quebecois pour les materiaux de pointe (RQMP); McGill University
CR Aulehla A, 2003, DEV CELL, V4, P395, DOI 10.1016/S1534-5807(03)00055-8
   Aulehla A, 2008, NAT CELL BIOL, V10, P186, DOI 10.1038/ncb1679
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   Morimoto M, 2006, DEV BIOL, V300, P687, DOI 10.1016/j.ydbio.2006.08.043
   Niwa Y, 2007, DEV CELL, V13, P298, DOI 10.1016/j.devcel.2007.07.013
   Palmeirim I, 1997, CELL, V91, P639, DOI 10.1016/S0092-8674(00)80451-1
   Pikovsky A, 2001, SYNCHRONIZATION UNIV, V0, P0
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   Riedel-Kruse IH, 2007, SCIENCE, V317, P1911, DOI 10.1126/science.1142538
   Roeling D, 2011, CELL, V145, P800, DOI 10.1016/j.cell.2011.05.007
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NR 34
TC 149
Z9 166
U1 0
U2 73
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 3
PY 2013
VL 493
IS 7430
BP 101
EP +
DI 10.1038/nature11804
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 062QC
UT WOS:000312933800039
PM 23254931
DA 2026-03-09
ER

PT J
AU Jasechko, S
   Sharp, ZD
   Gibson, JJ
   Birks, SJ
   Yi, Y
   Fawcett, PJ
AF Jasechko, Scott
   Sharp, Zachary D.
   Gibson, John J.
   Birks, S. Jean
   Yi, Yi
   Fawcett, Peter J.
TI Terrestrial water fluxes dominated by transpiration
SO NATURE
LA English
DT Article
ID evapotranspiration; carbon; isotope; climate; vapor; evaporation; vegetation; balance; size
AB Renewable fresh water over continents has input from precipitation and losses to the atmosphere through evaporation and transpiration. Global-scale estimates of transpiration from climate models are poorly constrained owing to large uncertainties in stomatal conductance and the lack of catchment-scale measurements required for model calibration, resulting in a range of predictions spanning 20 to 65 per cent of total terrestrial evapotranspiration (14,000 to 41,000 km(3) per year) (refs 1-5). Here we use the distinct isotope effects of transpiration and evaporation to show that transpiration is by far the largest water flux from Earth's continents, representing 80 to 90 per cent of terrestrial evapotranspiration. On the basis of our analysis of a global data set of large lakes and rivers, we conclude that transpiration recycles 62,000 +/- 8,000 km(3) of water per year to the atmosphere, using half of all solar energy absorbed by land surfaces in the process. We also calculate CO2 uptake by terrestrial vegetation by connecting transpiration losses to carbon assimilation using water-use efficiency ratios of plants, and show the global gross primary productivity to be 129 +/- 32 gigatonnes of carbon per year, which agrees, within the uncertainty, with previous estimates(6). The dominance of transpiration water fluxes in continental evapotranspiration suggests that, from the point of view of water resource forecasting, climate model development should prioritize improvements in simulations of biological fluxes rather than physical (evaporation) fluxes.
C1 [Jasechko, Scott; Sharp, Zachary D.; Fawcett, Peter J.] Univ New Mexico, Dept Earth & Planetary Sci, Albuquerque, NM 87131 USA.
   [Gibson, John J.; Birks, S. Jean; Yi, Yi] Alberta Innovates Technol Futures, Victoria, BC V8Z 7X8, Canada.
   [Gibson, John J.; Yi, Yi] Univ Victoria, Dept Geog, Victoria, BC V8W 3R4, Canada.
   [Birks, S. Jean] Univ Waterloo, Dept Earth & Environm Sci, Waterloo, ON N2L 3G1, Canada.
C3 University of New Mexico; Alberta Innovates; University of Victoria; University of Waterloo
RP Jasechko, S (corresponding author), Univ New Mexico, Dept Earth & Planetary Sci, Albuquerque, NM 87131 USA.
EM jasechko@unm.edu
FU Caswell Silver Foundation through the University of New Mexico
NR 30
TC 1071
Z9 1234
U1 18
U2 958
PU NATURE PUBLISHING 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 18
PY 2013
VL 496
IS 7445
BP 347
EP +
DI 10.1038/nature11983
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 126FV
UT WOS:000317599200034
PM 23552893
DA 2026-03-09
ER

PT J
AU Hunt, KA
   Mistry, V
   Bockett, NA
   Ahmad, T
   Ban, M
   Barker, JN
   Barrett, JC
   Blackburn, H
   Brand, O
   Burren, O
   Capon, F
   Compston, A
   Gough, SCL
   Jostins, L
   Kong, Y
   Lee, JC
   Lek, M
   MacArthur, DG
   Mansfield, JC
   Mathew, CG
   Mein, CA
   Mirza, M
   Nutland, S
   Onengut-Gumuscu, S
   Papouli, E
   Parkes, M
   Rich, SS
   Sawcer, S
   Satsangi, J
   Simmonds, MJ
   Trembath, RC
   Walker, NM
   Wozniak, E
   Todd, JA
   Simpson, MA
   Plagnol, V
   van Heel, DA
AF Hunt, Karen A.
   Mistry, Vanisha
   Bockett, Nicholas A.
   Ahmad, Tariq
   Ban, Maria
   Barker, Jonathan N.
   Barrett, Jeffrey C.
   Blackburn, Hannah
   Brand, Oliver
   Burren, Oliver
   Capon, Francesca
   Compston, Alastair
   Gough, Stephen C. L.
   Jostins, Luke
   Kong, Yong
   Lee, James C.
   Lek, Monkol
   MacArthur, Daniel G.
   Mansfield, John C.
   Mathew, Christopher G.
   Mein, Charles A.
   Mirza, Muddassar
   Nutland, Sarah
   Onengut-Gumuscu, Suna
   Papouli, Efterpi
   Parkes, Miles
   Rich, Stephen S.
   Sawcer, Steven
   Satsangi, Jack
   Simmonds, Matthew J.
   Trembath, Richard C.
   Walker, Neil M.
   Wozniak, Eva
   Todd, John A.
   Simpson, Michael A.
   Plagnol, Vincent
   van Heel, David A.
TI Negligible impact of rare autoimmune-locus coding-region variants on missing heritability
SO NATURE
LA English
DT Article
ID inflammatory-bowel-disease; genome-wide association; psoriasis susceptibility loci; rheumatoid-arthritis; common variants; low-frequency; genes; risk; architecture; reveals
AB Genome-wide association studies(GWAS) have identified common variants of modest-effect size at hundreds of loci for common autoimmune diseases; however, a substantial fraction of heritability remains unexplained, to which rare variants may contribute(1,2). To discover rare variants and test them for association with a phenotype, most studies re-sequence a small initial sample size and then genotype the discovered variants in a larger sample set(3-5). This approach fails to analyse a large fraction of the rare variants present in the entire sample set. Here we perform simultaneous amplicon-sequencing-based variant discovery and genotyping for coding exons of 25 GWAS risk genes in 41,911 UK residents of white European origin, comprising 24,892 subjects with six autoimmune disease phenotypes and 17,019 controls, and show that rare coding-region variants at known loci have a negligible role in common autoimmune disease susceptibility. These results do not support the rare-variant synthetic genome-wide-association hypothesis(6) (in which unobserved rare causal variants lead to association detected at common tag variants). Many known autoimmune disease risk loci contain multiple, independently associated, common and low-frequency variants, and so genes at these loci are a priori stronger candidates for harbouring rare coding-region variants than other genes. Our data indicate that the missing heritability for common autoimmune diseases may not be attributable to the rare coding-region variant portion of the allelic spectrum, but perhaps, as others have proposed, may be a result of many common-variant loci of weak effect(7-10).
C1 [Hunt, Karen A.; Mistry, Vanisha; Bockett, Nicholas A.; van Heel, David A.] Queen Mary Univ London, Barts & London Sch Med & Dent, Blizard Inst, London E1 2AT, England.
   [Ahmad, Tariq] Peninsula Coll Med & Dent, Exeter EX2 5DW, Devon, England.
   [Ban, Maria; Compston, Alastair; Sawcer, Steven] Univ Cambridge, Addenbrookes Hosp, Dept Clin Neurosci, Cambridge CB2 0QQ, England.
   [Barker, Jonathan N.; Capon, Francesca; Mathew, Christopher G.; Mirza, Muddassar; Papouli, Efterpi; Simpson, Michael A.] Kings Coll London, Sch Med, Div Genet & Mol Med, Guys Hosp, London SE1 9RT, England.
   [Barrett, Jeffrey C.; Blackburn, Hannah] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England.
   [Brand, Oliver; Gough, Stephen C. L.; Simmonds, Matthew J.] Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford OX3 7LJ, England.
   [Burren, Oliver; Nutland, Sarah; Walker, Neil M.; Todd, John A.] Univ Cambridge, Cambridge Inst Med Res, Dept Med Genet, Juvenile Diabet Res Fdn,Wellcome Trust Diabet & I, Cambridge CB2 0XY, England.
   [Jostins, Luke] Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.
   [Kong, Yong] Yale Univ, WM Keck Fdn Biotechnol Resource Lab, Dept Mol Biophys & Biochem, New Haven, CT 06510 USA.
   [Lee, James C.; Parkes, Miles] Univ Cambridge, Addenbrookes Hosp, Sch Clin Med, Dept Med, Cambridge CB2 0QQ, England.
   [Lek, Monkol; MacArthur, Daniel G.] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA.
   [Mansfield, John C.] Newcastle Univ, Inst Med Genet, Newcastle Upon Tyne NE1 3BZ, Tyne & Wear, England.
   [Mein, Charles A.; Wozniak, Eva] Queen Mary Univ London, Barts & London Sch Med & Dent, John Vane Sci Ctr, Genome Ctr, London EC1M 6BQ, England.
   [Onengut-Gumuscu, Suna; Rich, Stephen S.] Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA 22908 USA.
   [Satsangi, Jack] Univ Edinburgh, Western Gen Hosp, Mol Med Ctr, Gastrointestinal Unit, Edinburgh EH4 2XU, Midlothian, Scotland.
   [Trembath, Richard C.] Queen Mary Univ London, Barts & London Sch Med & Dent, London E1 2AT, England.
   [Plagnol, Vincent] UCL, Genet Inst, London WC1E 6BT, England.
C3 University of London; Queen Mary University London; University of Exeter; University of Plymouth; Cambridge University Hospitals NHS Foundation Trust; Addenbrooke's Hospital; University of Cambridge; University of London; King's College London; Guy's & St Thomas' NHS Foundation Trust; Wellcome Trust Sanger Institute; University of Oxford; University of Cambridge; University of Oxford; Wellcome Centre for Human Genetics; Yale University; University of Cambridge; Cambridge University Hospitals NHS Foundation Trust; Addenbrooke's Hospital; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Newcastle University - UK; University of London; Queen Mary University London; University of Virginia; University of Edinburgh; University of London; Queen Mary University London; University of London; University College London
RP van Heel, DA (corresponding author), Queen Mary Univ London, Barts & London Sch Med & Dent, Blizard Inst, London E1 2AT, England.
EM v.plagnol@ucl.ac.uk; d.vanheel@qmul.ac.uk
FU Medical Research Council [MRC G1001158]; Coeliac UK; MRC [G0601387]; National Institutes for Health Research (NIHR) Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust; King's College London; Cambridge NIHR Biomedical Research Centre; Wellcome Trust [076113/C/04/Z, 068545/Z/02, 068181, JDRF 4-2001-1008, WT061858]; NIHR [RP-PG-0310-1002]; UK MRC [G0000934]; British Society for Paediatric Endocrinology and Diabetes; Academy of Medical Sciences (AMS) [AMS-SGCL9-Lee] Funding Source: researchfish; Chief Scientist Office [ETM/137, CZB/4/540, ETM/75] Funding Source: researchfish; Medical Research Council [G0800759, G0601387, G0000934, G0800675, G1001158, G0600329] Funding Source: researchfish; National Institute for Health Research [NF-SI-0508-10335, NF-SI-0508-10275, NF-SI-0507-10379] Funding Source: researchfish; MRC [G0601387, G0800675, G0600329, G1001158, G0800759, G0000934] Funding Source: UKRI
NR 30
TC 151
Z9 186
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 JUN 13
PY 2013
VL 498
IS 7453
BP 232
EP +
DI 10.1038/nature12170
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 162RR
UT WOS:000320283400049
PM 23698362
DA 2026-03-09
ER

PT J
AU Chang, HM
   Triboulet, R
   Thornton, JE
   Gregory, RI
AF Chang, Hao-Ming
   Triboulet, Robinson
   Thornton, James E.
   Gregory, Richard I.
TI A role for the Perlman syndrome exonuclease Dis3l2 in the Lin28-let-7 pathway
SO NATURE
LA English
DT Article
ID microrna biogenesis; rna degradation; 3' uridylation; messenger-rna; let-7; exosome; expression; maturation; recruits; zcchc11
AB The pluripotency factor Lin28 blocks the expression of let-7 microRNAs in undifferentiated cells during development, and functions as an oncogene in a subset of cancers(1). Lin28 binds to let-7 precursor (pre-let-7) RNAs and recruits 39 terminal uridylyl transferases to selectively inhibit let-7 biogenesis(2-4). Uridylated pre-let-7 is refractory to processing by Dicer, and is rapidly degraded by an unknown RNase(5). Here we identify Dis3l2 as the 3'-5' exonuclease responsible for the decay of uridylated pre-let-7 in mouse embryonic stem cells. Biochemical reconstitution assays show that 3' oligouridylation stimulates Dis3l2 activity in vitro, and knockdown of Dis3l2 in mouse embryonic stem cells leads to the stabilization of pre-let-7. Our study establishes 3' oligouridylation as an RNA decay signal for Dis3l2, and identifies the first physiological RNA substrate of this new exonuclease, which is mutated in the Perlman syndrome of fetal overgrowth and causes a predisposition to Wilms' tumour development(6).
C1 [Chang, Hao-Ming; Triboulet, Robinson; Thornton, James E.; Gregory, Richard I.] Boston Childrens Hosp, Stem Cell Program, Boston, MA 02115 USA.
   [Chang, Hao-Ming; Triboulet, Robinson; Thornton, James E.; Gregory, Richard I.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
   [Chang, Hao-Ming; Triboulet, Robinson; Thornton, James E.; Gregory, Richard I.] Harvard Stem Cell Inst, Boston, MA 02115 USA.
C3 Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Harvard University; Harvard Medical School; Harvard University
RP Gregory, RI (corresponding author), Boston Childrens Hosp, Stem Cell Program, Boston, MA 02115 USA.
EM rgregory@enders.tch.harvard.edu
FU US National Institute of General Medical Sciences (NIGMS) [R01GM086386]; American Cancer Society [121635-RSG-11-175-01-RMC]; National Science Foundation; Boston Children's Hospital
NR 30
TC 274
Z9 318
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 MAY 9
PY 2013
VL 497
IS 7448
BP 244
EP +
DI 10.1038/nature12119
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 139CD
UT WOS:000318558200037
PM 23594738
DA 2026-03-09
ER

PT J
AU Fradet-Turcotte, A
   Canny, MD
   Escribano-Díaz, C
   Orthwein, A
   Leung, CCY
   Huang, H
   Landry, MC
   Kitevski-LeBlanc, J
   Noordermeer, SM
   Sicheri, F
   Durocher, D
AF Fradet-Turcotte, Amelie
   Canny, Marella D.
   Escribano-Diaz, Cristina
   Orthwein, Alexandre
   Leung, Charles C. Y.
   Huang, Hao
   Landry, Marie-Claude
   Kitevski-LeBlanc, Julianne
   Noordermeer, Sylvie M.
   Sicheri, Frank
   Durocher, Daniel
TI 53BP1 is a reader of the DNA-damage-induced H2A Lys 15 ubiquitin mark (Publication with Expression of Concern. See JAN, 2025)
SO NATURE
LA English
DT Article; Publication with Expression of Concern
ID dependent response; recruitment; methylation; crb2; recognition; nucleosome; resection; sites; ubiquitylation; recombination
AB 53BP1 (also called TP53BP1) is a chromatin-associated factor that promotes immunoglobulin class switching and DNA double-strand-break (DSB) repair by non-homologous end joining. To accomplish its function in DNA repair, 53BP1 accumulates at DSB sites downstream of the RNF168 ubiquitin ligase. How ubiquitin recruits 53BP1 to break sites remains unknown as its relocalization involves recognition of histone H4 Lys 20 (H4K20) methylation by its Tudor domain. Here we elucidate how vertebrate 53BP1 is recruited to the chromatin that flanks DSB sites. We show that 53BP1 recognizes mononucleosomes containing dimethylated H4K20 (H4K20me2) and H2A ubiquitinated on Lys 15 (H2AK15ub), the latter being a product of RNF168 action on chromatin. 53BP1 binds to nucleosomes minimally as a dimer using its previously characterized methyl-lysine-binding Tudor domain and a carboxy-terminal extension, termed the ubiquitination-dependent recruitment (UDR) motif, which interacts with the epitope formed by H2AK15ub and its surrounding residues on the H2A tail. 53BP1 is therefore a bivalent histone modification reader that recognizes a histone 'code' produced by DSB signalling.
C1 [Fradet-Turcotte, Amelie; Canny, Marella D.; Escribano-Diaz, Cristina; Orthwein, Alexandre; Leung, Charles C. Y.; Huang, Hao; Landry, Marie-Claude; Noordermeer, Sylvie M.; Sicheri, Frank; Durocher, Daniel] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada.
   [Kitevski-LeBlanc, Julianne; Sicheri, Frank; Durocher, Daniel] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 3E1, Canada.
   [Kitevski-LeBlanc, Julianne; Sicheri, Frank] Univ Toronto, Dept Biochem, Toronto, ON M5S 3E1, Canada.
   [Kitevski-LeBlanc, Julianne] Univ Toronto, Dept Chem, Toronto, ON M5S 3E1, Canada.
C3 University of Toronto; Sinai Health System Toronto; Lunenfeld Tanenbaum Research Institute; University of Toronto; University of Toronto; University of Toronto
RP Durocher, D (corresponding author), Mt Sinai Hosp, Samuel Lunenfeld Res Inst, 600 Univ Ave, Toronto, ON M5G 1X5, Canada.
EM durocher@lunenfeld.ca
FU CIHR; Leukemia and Lymphoma Society; CIHR [MOP84297]; Ontario Research Fund [GL2-01-010]
NR 40
TC 566
Z9 694
U1 1
U2 110
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 4
PY 2013
VL 499
IS 7456
BP 50
EP +
DI 10.1038/nature12318
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 176ED
UT WOS:000321285600030
PM 23760478
DA 2026-03-09
ER

PT J
AU Belser, JA
   Gustin, KM
   Pearce, MB
   Maines, TR
   Zeng, H
   Pappas, C
   Sun, XJ
   Carney, PJ
   Villanueva, JM
   Stevens, J
   Katz, JM
   Tumpey, TM
AF Belser, Jessica A.
   Gustin, Kortney M.
   Pearce, Melissa B.
   Maines, Taronna R.
   Zeng, Hui
   Pappas, Claudia
   Sun, Xiangjie
   Carney, Paul J.
   Villanueva, Julie M.
   Stevens, James
   Katz, Jacqueline M.
   Tumpey, Terrence M.
TI Pathogenesis and transmission of avian influenza A (H7N9) virus in ferrets and mice
SO NATURE
LA English
DT Article
ID h5n1 virus; increased virulence; receptor-binding; human infection; interferon; tropism
AB On 29 March 2013, the Chinese Center for Disease Control and Prevention confirmed the first reported case of human infection with an avian influenza A (H7N9) virus(1). The recent human infections with H7N9 virus, totalling over 130 cases with 39 fatalities to date, have been characterized by severe pulmonary disease and acute respiratory distress syndrome (ARDS)(2). This is concerning because H7 viruses have typically been associated with ocular disease in humans, rather than severe respiratory disease(3). This recent outbreak underscores the need to better understand the pathogenesis and transmission of these viruses in mammals. Here we assess the ability of A/Anhui/1/2013 and A/Shanghai/1/2013 (H7N9) viruses, isolated from fatal human cases, to cause disease in mice and ferrets and to transmit to naive animals. Both H7N9 viruses replicated to higher titre in human airway epithelial cells and in the respiratory tract of ferrets compared to a seasonal H3N2 virus. Moreover, the H7N9 viruses showed greater infectivity and lethality in mice compared to genetically related H7N9 and H9N2 viruses. The H7N9 viruses were readily transmitted to naive ferrets through direct contact but, unlike the seasonal H3N2 virus, did not transmit readily by respiratory droplets. The lack of efficient respiratory droplet transmission was corroborated by low receptor-binding specificity for human-like alpha 2,6-linked sialosides. Our results indicate that H7N9 viruses have the capacity for efficient replication in mammals and human airway cells and highlight the need for continued public health surveillance of this emerging virus.
C1 [Belser, Jessica A.; Gustin, Kortney M.; Pearce, Melissa B.; Maines, Taronna R.; Zeng, Hui; Pappas, Claudia; Sun, Xiangjie; Carney, Paul J.; Villanueva, Julie M.; Stevens, James; Katz, Jacqueline M.; Tumpey, Terrence M.] Ctr Dis Control & Prevent, Influenza Div, Natl Ctr Immunizat & Resp Dis, Atlanta, GA 30333 USA.
C3 Centers for Disease Control & Prevention - USA; CDC National Center for Immunization & Respiratory Diseases (NCIRD)
RP Tumpey, TM (corresponding author), Ctr Dis Control & Prevent, Influenza Div, Natl Ctr Immunizat & Resp Dis, Atlanta, GA 30333 USA.
EM tft9@cdc.gov
FU National Institute of General Medical Sciences [GM62116]
NR 28
TC 273
Z9 306
U1 0
U2 106
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 26
PY 2013
VL 501
IS 7468
BP 556
EP +
DI 10.1038/nature12391
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 223RP
UT WOS:000324826300060
PM 23842497
DA 2026-03-09
ER

PT J
AU Lee, AM
   Kanter, BR
   Wang, D
   Lim, JP
   Zou, ME
   Qiu, CC
   McMahon, T
   Dadgar, J
   Fischbach-Weiss, SC
   Messing, RO
AF Lee, Anna M.
   Kanter, Benjamin R.
   Wang, Dan
   Lim, Jana P.
   Zou, Mimi E.
   Qiu, Chichen
   McMahon, Thomas
   Dadgar, Jahan
   Fischbach-Weiss, Sarah C.
   Messing, Robert O.
TI Prkcz null mice show normal learning and memory
SO NATURE
LA English
DT Article
ID kinase m-zeta; anxiety-like behavior; pkm-zeta; drug reward; c-zeta; mechanism; inhibition; preference; 3-kinase
AB Protein kinase M-zeta (PKM-zeta) is a constitutively active form of atypical protein kinase C that is exclusively expressed in the brain and implicated in the maintenance of long-term memory(1-9). Most studies that support a role for PKM-zeta in memory maintenance have used pharmacological PKM-zeta inhibitors such as the myristoylated zeta inhibitory peptide (ZIP) or chelerythrine. Here we use a genetic approach and target exon 9 of the Prkcz gene to generate mice that lack both protein kinase C-zeta (PKC-zeta) and PKM-zeta (Prkcz(-/-) mice). Prkcz(-/-) mice showed normal behaviour in a cage environment and in baseline tests of motor function and sensory perception, but displayed reduced anxiety-like behaviour. Notably, Prkcz(-/-) mice did not show deficits in learning or memory in tests of cued fear conditioning, novel object recognition, object location recognition, conditioned place preference for cocaine, or motor learning, when compared with wild-type littermates. ZIP injection into the nucleus accumbens reduced expression of cocaine-conditioned place preference in Prkcz(-/-) mice. In vitro, ZIP and scrambled ZIP inhibited PKM-zeta, PKC-iota and PKC-zeta with similar inhibition constant (K-i) values. Chelerythrine was a weak inhibitor of PKM-zeta (K-i = 76 mu M). Our findings show that absence of PKM-zeta does not impair learning and memory in mice, and that ZIP can erase reward memory even when PKM-zeta is not present.
C1 [Lee, Anna M.; Kanter, Benjamin R.; Wang, Dan; Lim, Jana P.; Zou, Mimi E.; Qiu, Chichen; McMahon, Thomas; Dadgar, Jahan; Fischbach-Weiss, Sarah C.; Messing, Robert O.] Univ Calif San Francisco, Dept Neurol, Ernest Gallo Clin & Res Ctr, Emeryville, CA 94608 USA.
C3 University of California System; University of California San Francisco; Ernest Gallo Clinic & Research Center
RP Messing, RO (corresponding author), Univ Calif San Francisco, Dept Neurol, Ernest Gallo Clin & Res Ctr, 5858 Horton St,Suite 200, Emeryville, CA 94608 USA.
EM romes@gallo.ucsf.edu
FU National Institutes of Health [AA017072]; Canadian Institute of Health Research; State of California for medical research on alcohol and drug abuse
NR 24
TC 194
Z9 229
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 17
PY 2013
VL 493
IS 7432
BP 416
EP U163
DI 10.1038/nature11803
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 071TA
UT WOS:000313615900054
PM 23283171
DA 2026-03-09
ER

PT J
AU Das Thakur, M
   Salangsang, F
   Landman, AS
   Sellers, WR
   Pryer, NK
   Levesque, MP
   Dummer, R
   McMahon, M
   Stuart, DD
AF Das Thakur, Meghna
   Salangsang, Fernando
   Landman, Allison S.
   Sellers, William R.
   Pryer, Nancy K.
   Levesque, Mitchell P.
   Dummer, Reinhard
   McMahon, Martin
   Stuart, Darrin D.
TI Modelling vemurafenib resistance in melanoma reveals a strategy to forestall drug resistance
SO NATURE
LA English
DT Article
ID raf inhibitor resistance; braf; braf(v600e); senescence; pathway; cancer
AB Mutational activation of BRAF is the most prevalent genetic alteration in human melanoma, with >= 50% of tumours expressing the BRAF(V600E) oncoprotein(1,2). Moreover, the marked tumour regression and improved survival of late-stage BRAF-mutated melanoma patients in response to treatment with vemurafenib demonstrates the essential role of oncogenic BRAF in melanoma maintenance(3,4). However, as most patients relapse with lethal drug-resistant disease, understanding and preventing mechanism(s) of resistance is critical to providing improved therapy(5). Here we investigate the cause and consequences of vemurafenib resistance using two independently derived primary human melanoma xenograft models in which drug resistance is selected by continuous vemurafenib administration. In one of these models, resistant tumours show continued dependency on BRAF(V600E)-> MEK -> ERK signalling owing to elevated BRAF(V600E) expression. Most importantly, we demonstrate that vemurafenib-resistant melanomas become drug dependent for their continued proliferation, such that cessation of drug administration leads to regression of established drug-resistant tumours. We further demonstrate that a discontinuous dosing strategy, which exploits the fitness disadvantage displayed by drug-resistant cells in the absence of the drug, forestalls the onset of lethal drug-resistant disease. These data highlight the concept that drug-resistant cells may also display drug dependency, such that altered dosing may prevent the emergence of lethal drug resistance. Such observations may contribute to sustaining the durability of the vemurafenib response with the ultimate goal of curative therapy for the subset of melanoma patients with BRAF mutations.
C1 [Das Thakur, Meghna; Salangsang, Fernando; Pryer, Nancy K.; Stuart, Darrin D.] Novartis Inst Biomed Res, Emeryville, CA 94608 USA.
   [Landman, Allison S.; McMahon, Martin] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA.
   [Landman, Allison S.; McMahon, Martin] Univ Calif San Francisco, Dept Cellular & Mol Pharmacol, San Francisco, CA 94143 USA.
   [Sellers, William R.] Novartis Inst Biomed Res, Cambridge, MA 02139 USA.
   [Levesque, Mitchell P.; Dummer, Reinhard] Univ Zurich Hosp, Dept Dermatol, CH-8091 Zurich, Switzerland.
C3 Novartis; Novartis USA; 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; Novartis; Novartis USA; University of Zurich; University Zurich Hospital
RP Stuart, DD (corresponding author), Novartis Inst Biomed Res, Emeryville, CA 94608 USA.
EM mcmahon@cc.ucsf.edu; darrin.stuart@novartis.com
FU NIBR Presidential Postdoctoral Fellowship; Melanoma Research Alliance; National Cancer Institute [R01-CA176839]; National Research Service Award T32 training grant [HL007185]; National Heart Lung and Blood Institute [T32HL007185] Funding Source: NIH RePORTER
NR 22
TC 602
Z9 703
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 FEB 14
PY 2013
VL 494
IS 7436
BP 251
EP 255
DI 10.1038/nature11814
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 092QS
UT WOS:000315137700043
PM 23302800
DA 2026-03-09
ER

PT J
AU Maddaluno, L
   Rudini, N
   Cuttano, R
   Bravi, L
   Giampietro, C
   Corada, M
   Ferrarini, L
   Orsenigo, F
   Papa, E
   Boulday, G
   Tournier-Lasserve, E
   Chapon, F
   Richichi, C
   Retta, SF
   Lampugnani, MG
   Dejana, E
AF Maddaluno, Luigi
   Rudini, Noemi
   Cuttano, Roberto
   Bravi, Luca
   Giampietro, Costanza
   Corada, Monica
   Ferrarini, Luca
   Orsenigo, Fabrizio
   Papa, Eleanna
   Boulday, Gwenola
   Tournier-Lasserve, Elisabeth
   Chapon, Francoise
   Richichi, Cristina
   Retta, Saverio Francesco
   Lampugnani, Maria Grazia
   Dejana, Elisabetta
TI EndMT contributes to the onset and progression of cerebral cavernous malformations
SO NATURE
LA English
DT Article
ID epithelial-mesenchymal transition; blood-brain-barrier; growth-factor; vascular integrity; signaling pathway; beta-catenin; ve-cadherin; cancer; cells; expression
AB Cerebral cavernous malformation (CCM) is a vascular dysplasia, mainly localized within the brain and affecting up to 0.5% of the human population. CCM lesions are formed by enlarged and irregular blood vessels that often result in cerebral haemorrhages. CCM is caused by loss-of-function mutations in one of three genes, namely CCM1 (also known as KRIT1), CCM2 (OSM) and CCM3 (PDCD10), and occurs in both sporadic and familial forms(1). Recent studies(2-7) have investigated the cause of vascular dysplasia and fragility in CCM, but the in vivo functions of this ternary complex remain unclear(8). Postnatal deletion of any of the three Ccm genes in mouse endothelium results in a severe phenotype, characterized by multiple brain vascular malformations that are markedly similar to human CCM lesions(9). Endothelial-to-mesenchymal transition (EndMT) has been described in different pathologies, and it is defined as the acquisition of mesenchymal- and stem-cell-like characteristics by the endothelium(10-12). Here we show that endothelial-specific disruption of the Ccm1 gene in mice induces EndMT, which contributes to the development of vascular malformations. EndMT in CCM1-ablated endothelial cells is mediated by the upregulation of endogenous BMP6 that, in turn, activates the transforming growth factor-beta (TGF-beta) and bone morphogenetic protein (BMP) signalling pathway. Inhibitors of the TGF-beta and BMP pathway prevent EndMT both in vitro and in vivo and reduce the number and size of vascular lesions in CCM1-deficient mice. Thus, increased TGF-beta and BMP signalling, and the consequent EndMT of CCM1-null endothelial cells, are crucial events in the onset and progression of CCM disease. These studies offer novel therapeutic opportunities for this severe, and so far incurable, pathology.
C1 [Maddaluno, Luigi; Rudini, Noemi; Cuttano, Roberto; Bravi, Luca; Giampietro, Costanza; Corada, Monica; Ferrarini, Luca; Orsenigo, Fabrizio; Papa, Eleanna; Lampugnani, Maria Grazia; Dejana, Elisabetta] IFOM Fdn, FIRC Inst Mol Oncol, I-20139 Milan, Italy.
   [Boulday, Gwenola; Tournier-Lasserve, Elisabeth] INSERM, UMR S740, F-75010 Paris, France.
   [Boulday, Gwenola; Tournier-Lasserve, Elisabeth] Univ Paris Diderot, Sorbonne Paris Cite, Genet Malad Vasc UMR S740, F-75010 Paris, France.
   [Tournier-Lasserve, Elisabeth] Grp Hosp St Louis Lariboisiere Fernand Widal, AP HP, F-75010 Paris, France.
   [Chapon, Francoise] CHU Caen, Dept Pathol, F-14032 Caen, France.
   [Richichi, Cristina] IEO European Inst Oncol, I-20139 Milan, Italy.
   [Retta, Saverio Francesco] Univ Turin, CCM Italia Dept Clin & Biol Sci, I-10043 Turin, Italy.
   [Lampugnani, Maria Grazia] Mario Negri Inst Pharmacol Res, I-20156 Milan, Italy.
   [Dejana, Elisabetta] Univ Milan, Dept Biosci, I-20133 Milan, Italy.
C3 IFOM - FIRC Institute of Molecular Oncology; Institut National de la Sante et de la Recherche Medicale (Inserm); Universite Paris Cite; Assistance Publique Hopitaux Paris (APHP); Universite Paris Cite; Hopital Universitaire Saint-Louis - APHP; Hopital Universitaire Lariboisiere-Fernand-Widal - APHP; Universite de Caen Normandie; CHU de Caen NORMANDIE; IRCCS European Institute of Oncology (IEO); University of Turin; Istituto di Ricerche Farmacologiche Mario Negri IRCCS; University of Milan
RP Dejana, E (corresponding author), IFOM Fdn, FIRC Inst Mol Oncol, I-20139 Milan, Italy.
EM luigi.maddaluno@ifom.eu; elisabetta.dejana@ifom.eu
FU Fondation Leducq Transatlantic Network of Excellence; Associazione Italiana per la Ricerca sul Cancro (AIRC); 'Special Program Molecular Clinical Oncology 5x1000' to AIRC-Gruppo Italiano Malattie Mieloproliferative (AGIMM); European Community: European Research Council (ERC) [268870, ERC-2010-SdG]; EU [202213, 223098, ENDOSTEM-HEALTH-2009-241440, JUSTBRAIN-HEALTH-2009-241861]; CARIPLO Foundation; European Research Council (ERC) [268870] Funding Source: European Research Council (ERC)
CR Ao A, 2012, PLOS ONE, V7, P0, DOI 10.1371/journal.pone.0041627
   Bergametti F, 2005, AM J HUM GENET, V76, P42, DOI 10.1086/426952
   Boulday G, 2011, J EXP MED, V208, P1835, DOI 10.1084/jem.20110571
   BUSSOLINO F, 1991, J IMMUNOL, V147, P2122
   Chan AC, 2011, J CLIN INVEST, V121, P1871, DOI 10.1172/JCI44393
   Corada M, 2010, DEV CELL, V18, P938, DOI 10.1016/j.devcel.2010.05.006
   Faurobert E, 2010, FEBS J, V277, P1084, DOI 10.1111/j.1742-4658.2009.07537.x
   Felici A, 2003, EMBO J, V22, P4465, DOI 10.1093/emboj/cdg428
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   Glading AJ, 2010, DIS MODEL MECH, V3, P73, DOI 10.1242/dmm.003293
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   Lampugnani MG, 2010, J CELL SCI, V123, P1073, DOI 10.1242/jcs.059329
   Li YJ, 2007, J AM SOC NEPHROL, V18, P449, DOI 10.1681/ASN.2006030236
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   Liebner S, 2008, J CELL BIOL, V183, P409, DOI 10.1083/jcb.200806024
   Liebner S, 2011, INT J DEV BIOL, V55, P467, DOI 10.1387/ijdb.103224sl
   Lopez D, 2009, ARCH BIOCHEM BIOPHYS, V482, P77, DOI 10.1016/j.abb.2008.11.016
   Louvi A, 2011, P NATL ACAD SCI USA, V108, P3737, DOI 10.1073/pnas.1012617108
   Mariotti A, 2007, EXPERT OPIN INV DRUG, V16, P451, DOI 10.1517/13543784.16.4.451
   McLean K, 2011, J CLIN INVEST, V121, P3206, DOI 10.1172/JCI45273
   Medici D, 2010, NAT MED, V16, P1400, DOI 10.1038/nm.2252
   Melisi D, 2008, MOL CANCER THER, V7, P829, DOI 10.1158/1535-7163.MCT-07-0337
   Murtaugh LC, 2003, P NATL ACAD SCI USA, V100, P14920, DOI 10.1073/pnas.2436557100
   Soriano P, 1999, NAT GENET, V21, P70, DOI 10.1038/5007
   Spagnuolo R, 2004, BLOOD, V103, P3005, DOI 10.1182/blood-2003-07-2459
   Stockton RA, 2010, J EXP MED, V207, P881, DOI 10.1084/jem.20091258
   Tanaka H, 2010, ONCOL REP, V24, P1637, DOI 10.3892/or_00001028
   Thiery JP, 2009, CELL, V139, P871, DOI 10.1016/j.cell.2009.11.007
   Vivien C, 2012, J BIOL CHEM, V287, P7427, DOI 10.1074/jbc.M111.324368
   Whitehead KJ, 2009, NAT MED, V15, P177, DOI 10.1038/nm.1911
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   Zeisberg EM, 2007, NAT MED, V13, P952, DOI 10.1038/nm1613
NR 37
TC 408
Z9 465
U1 1
U2 67
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 27
PY 2013
VL 498
IS 7455
BP 492
EP +
DI 10.1038/nature12207
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 171LH
UT WOS:000320929400054
PM 23748444
DA 2026-03-09
ER

PT J
AU Naif, S
   Key, K
   Constable, S
   Evans, RL
AF Naif, S.
   Key, K.
   Constable, S.
   Evans, R. L.
TI Melt-rich channel observed at the lithosphere-asthenosphere boundary
SO NATURE
LA English
DT Article
ID water; dynamics; origin
AB The lithosphere-asthenosphere boundary (LAB) separates rigid oceanic plates from the underlying warm ductile asthenosphere. Although a viscosity decrease beneath this boundary is essential for plate tectonics, a consensus on its origin remains elusive. Seismic studies identify a prominent velocity discontinuity at depths thought to coincide with the LAB but disagree on its cause(1-5), generally invoking either partial melting(6) or a mantle dehydration boundary(7) as explanations. Here we use sea-floor magnetotelluric data to image the electrical conductivity of the LAB beneath the edge of the Cocos plate at the Middle America trench offshore of Nicaragua. Underneath the resistive oceanic lithosphere, the magnetotelluric data reveal a high-conductivity layer confined to depths of 45 to 70 kilometres. Because partial melts are stable at these depths in a warm damp mantle(8), we interpret the conductor to be a partially molten layer capped by an impermeable frozen lid that is the base of the lithosphere. A conductivity anisotropy parallel to plate motion indicates that this melt has been sheared into flow-aligned tube-like structures(9). We infer that the LAB beneath young plates consists of a thin, partially molten, channel of low viscosity that acts to decouple the overlying brittle lithosphere from the deeper convecting mantle. Because this boundary layer has the potential to behave as a lubricant to plate motion, its proximity to the trench may have implications for subduction dynamics.
C1 [Naif, S.; Key, K.; Constable, S.] Univ Calif San Diego, Scripps Inst Oceanog, Inst Geophys & Planetary Phys, La Jolla, CA 92093 USA.
   [Evans, R. L.] Woods Hole Oceanog Inst, Dept Geol & Geophys, Woods Hole, MA 02543 USA.
C3 University of California System; University of California San Diego; Scripps Institution of Oceanography; Woods Hole Oceanographic Institution
RP Naif, S (corresponding author), Univ Calif San Diego, Scripps Inst Oceanog, Inst Geophys & Planetary Phys, La Jolla, CA 92093 USA.
EM snaif@ucsd.edu
FU National Science Foundation [OCE-08411141, OCE-0840894]; Seafloor Electromagnetic Methods Consortium at Scripps Institution of Oceanography; Directorate For Geosciences; Division Of Ocean Sciences [0840894] Funding Source: National Science Foundation
NR 30
TC 223
Z9 272
U1 1
U2 161
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 21
PY 2013
VL 495
IS 7441
BP 356
EP 359
DI 10.1038/nature11939
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 113EY
UT WOS:000316650500040
PM 23518564
DA 2026-03-09
ER

PT J
AU Corbett-Detig, RB
   Zhou, J
   Clark, AG
   Hartl, DL
   Ayroles, JF
AF Corbett-Detig, Russell B.
   Zhou, Jun
   Clark, Andrew G.
   Hartl, Daniel L.
   Ayroles, Julien F.
TI Genetic incompatibilities are widespread within species
SO NATURE
LA English
DT Article
ID hybrid male-sterility; dobzhansky-muller incompatibility; synthetic population resource; drosophila-melanogaster; complex trait; epistasis; evolution; genome; dissection; discovery
AB The importance of epistasis-non-additive interactions between alleles-in shaping population fitness has long been a controversial topic, hampered in part by lack of empirical evidence(1-4). Traditionally, epistasis is inferred on the basis of non-independence of genotypic values between loci for a given trait. However, epistasis for fitness should also have a genomic footprint(5-7). To capture this signal, we have developed a simple approach that relies on detecting genotype ratio distortion as a sign of epistasis, and we apply this method to a large panel of Drosophila melanogaster recombinant inbred lines(8,9). Here we confirm experimentally that instances of genotype ratio distortion represent loci with epistatic fitness effects; we conservatively estimate that any two haploid genomes in this study are expected to harbour 1.15 pairs of epistatically interacting alleles. This observation has important implications for speciation genetics, as it indicates that the raw material to drive reproductive isolation is segregating contemporaneously within species and does not necessarily require, as proposed by the Dobzhansky-Muller model, the emergence of incompatible mutations independently derived and fixed in allopatry. The relevance of our result extends beyond speciation, as it demonstrates that epistasis is widespread but that it may often go undetected owing to lack of statistical power or lack of genome-wide scope of the experiments.
C1 [Corbett-Detig, Russell B.; Zhou, Jun; Hartl, Daniel L.; Ayroles, Julien F.] Harvard Univ, Dept Organism & Evolutionary Biol, Cambridge, MA 02138 USA.
   [Clark, Andrew G.; Ayroles, Julien F.] Cornell Univ, Dept Biol Stat & Computat Biol, Ithaca, NY 14853 USA.
   [Clark, Andrew G.] Cornell Univ, Dept Mol Biol & Genet, Ithaca, NY 14853 USA.
   [Ayroles, Julien F.] Harvard Univ, Harvard Soc Fellows, Cambridge, MA 02138 USA.
C3 Harvard University; Cornell University; Cornell University; Harvard University
RP Ayroles, JF (corresponding author), Harvard Univ, Dept Organism & Evolutionary Biol, Cambridge, MA 02138 USA.
EM ayroles@fas.harvard.edu
FU NIH [GM065169, GM084236, HD059060]; Harvard Society; Harvard Milton Funds; Harvard Prize Fellowship; Eunice Kennedy Shriver National Institute of Child Health and Human Development [R01HD059060] Funding Source: NIH RePORTER
NR 37
TC 151
Z9 178
U1 0
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 DEC 5
PY 2013
VL 504
IS 7478
BP 135
EP +
DI 10.1038/nature12678
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 264BK
UT WOS:000327851700046
PM 24196712
DA 2026-03-09
ER

PT J
AU Salichos, L
   Rokas, A
AF Salichos, Leonidas
   Rokas, Antonis
TI Inferring ancient divergences requires genes with strong phylogenetic signals
SO NATURE
LA English
DT Article
ID evolution; sequence; phylogenomics; incongruence; inference; networks; model; power; taxa; tree
AB To tackle incongruence, the topological conflict between different gene trees, phylogenomic studies couple concatenation with practices such as rogue taxon removal or the use of slowly evolving genes. Phylogenomic analysis of 1,070 orthologues from 23 yeast genomes identified 1,070 distinct gene trees, which were all incongruent with the phylogeny inferred from concatenation. Incongruence severity increased for shorter internodes located deeper in the phylogeny. Notably, whereas most practices had little or negative impact on the yeast phylogeny, the use of genes or internodes with high average internode support significantly improved the robustness of inference. We obtained similar results in analyses of vertebrate and metazoan phylogenomic data sets. These results question the exclusive reliance on concatenation and associated practices, and argue that selecting genes with strong phylogenetic signals and demonstrating the absence of significant incongruence are essential for accurately reconstructing ancient divergences.
C1 [Salichos, Leonidas; Rokas, Antonis] Vanderbilt Univ, Dept Biol Sci, Nashville, TN 37235 USA.
C3 Vanderbilt University
RP Rokas, A (corresponding author), Vanderbilt Univ, Dept Biol Sci, Nashville, TN 37235 USA.
EM antonis.rokas@vanderbilt.edu
FU National Science Foundation [DEB-0844968]; Division Of Environmental Biology; Direct For Biological Sciences [0844968] Funding Source: National Science Foundation
NR 63
TC 513
Z9 586
U1 2
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 MAY 16
PY 2013
VL 497
IS 7449
BP 327
EP +
DI 10.1038/nature12130
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 144PN
UT WOS:000318952000029
PM 23657258
DA 2026-03-09
ER

PT J
AU Adey, A
   Burton, JN
   Kitzman, JO
   Hiatt, JB
   Lewis, AP
   Martin, BK
   Qiu, RL
   Lee, C
   Shendure, J
AF Adey, Andrew
   Burton, Joshua N.
   Kitzman, Jacob O.
   Hiatt, Joseph B.
   Lewis, Alexandra P.
   Martin, Beth K.
   Qiu, Ruolan
   Lee, Choli
   Shendure, Jay
TI The haplotype-resolved genome and epigenome of the aneuploid HeLa cancer cell line
SO NATURE
LA English
DT Article
ID sequence; dna; contamination; integration; framework; breast
AB The HeLa cell line was established in 1951 from cervical cancer cells taken from a patient, Henrietta Lacks. This was the first successful attempt to immortalize human-derived cells in vitro(1). The robust growth and unrestricted distribution of HeLa cells resulted in its broad adoption-both intentionally and through widespread cross-contamination(2)-and for the past 60 years it has served a role analogous to that of a model organism(3). The cumulative impact of the HeLa cell line on research is demonstrated by its occurrence in more than 74,000 PubMed abstracts (approximately 0.3%). The genomic architecture of HeLa remains largely unexplored beyond its karyotype(4), partly because like many cancers, its extensive aneuploidy renders such analyses challenging. We carried out haplotype-resolved whole-genome sequencing(5) of the HeLa CCL-2 strain, examined point-and indel-mutation variations, mapped copy-number variations and loss of heterozygosity regions, and phased variants across full chromosome arms. We also investigated variation and copy-number profiles for HeLa S3 and eight additional strains. We find that HeLa is relatively stable in terms of point variation, with few new mutations accumulating after early passaging. Haplotype resolution facilitated reconstruction of an amplified, highly rearranged region of chromosome 8q24.21 at which integration of the human papilloma virus type 18 (HPV-18) genome occurred and that is likely to be the event that initiated tumorigenesis. We combined these maps with RNA-seq(6) and ENCODE Project(7) data sets to phase the HeLa epigenome. This revealed strong, haplotype-specific activation of the proto-oncogene MYC by the integrated HPV-18 genome approximately 500 kilobases upstream, and enabled global analyses of the relationship between gene dosage and expression. These data provide an extensively phased, high-quality reference genome for past and future experiments relying on HeLa, and demonstrate the value of haplotype resolution for characterizing cancer genomes and epigenomes.
C1 [Adey, Andrew; Burton, Joshua N.; Kitzman, Jacob O.; Hiatt, Joseph B.; Lewis, Alexandra P.; Martin, Beth K.; Qiu, Ruolan; Lee, Choli; Shendure, Jay] Univ Washington, Dept Genome Sci, Seattle, WA 98115 USA.
C3 University of Washington; University of Washington Seattle
RP Shendure, J (corresponding author), Univ Washington, Dept Genome Sci, Seattle, WA 98115 USA.
EM acadey@uw.edu; shendure@uw.edu
FU National Genome Research Institute (NHGRI) [HG006283]; National Cancer Institute [CA160080]; National Science Foundation [DGE-0718124]; NHGRI [T32HG000035]; National Institute of Aging [AG039173]; National Human Genome Research Institute [T32HG000035] Funding Source: NIH RePORTER; National Institute of General Medical Sciences [T32GM007266] Funding Source: NIH RePORTER
NR 42
TC 279
Z9 337
U1 1
U2 125
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 8
PY 2013
VL 500
IS 7461
BP 207
EP +
DI 10.1038/nature12064
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 197CH
UT WOS:000322825500035
PM 23925245
DA 2026-03-09
ER

PT J
AU Ohno, H
   Shinoda, K
   Ohyama, K
   Sharp, LZ
   Kajimura, S
AF Ohno, Haruya
   Shinoda, Kosaku
   Ohyama, Kana
   Sharp, Louis Z.
   Kajimura, Shingo
TI EHMT1 controls brown adipose cell fate and thermogenesis through the PRDM16 complex
SO NATURE
LA English
DT Article
ID transcriptional control; nonshivering thermogenesis; histone methyltransferases; tissue; methylation; deletion; obesity; ucp1; 9q34
AB Brown adipose tissue (BAT) dissipates chemical energy in the form of heat as a defence against hypothermia and obesity. Current evidence indicates that brown adipocytes arise from Myf5(+) dermotomal precursors through the action of PR domain containing protein 16 (PRDM16) transcriptional complex(1,2). However, the enzymatic component of the molecular switch that determines lineage specification of brown adipocytes remains unknown. Here we show that euchromatic histone-lysine N-methyltransferase 1 (EHMT1) is an essential BAT-enriched lysine methyltransferase in the PRDM16 transcriptional complex and controls brown adipose cell fate. Loss of EHMT1 in brown adipocytes causes a severe loss of brown fat characteristics and induces muscle differentiation in vivo through demethylation of histone 3 lysine 9 (H3K9me2 and 3) of the muscle-selective gene promoters. Conversely, EHMT1 expression positively regulates the BAT-selective thermogenic program by stabilizing the PRDM16 protein. Notably, adipose-specific deletion of EHMT1 leads to a marked reduction of BAT-mediated adaptive thermogenesis, obesity and systemic insulin resistance. These data indicate that EHMT1 is an essential enzymatic switch that controls brown adipose cell fate and energy homeostasis.
C1 [Ohno, Haruya; Shinoda, Kosaku; Ohyama, Kana; Sharp, Louis Z.; Kajimura, Shingo] Univ Calif San Francisco, Dept Cell & Tissue Biol, UCSF Diabet Ctr, San Francisco, CA 94143 USA.
C3 University of California System; University of California San Francisco
RP Kajimura, S (corresponding author), Univ Calif San Francisco, Dept Cell & Tissue Biol, UCSF Diabet Ctr, 35 Med Ctr Way, San Francisco, CA 94143 USA.
EM skajimura@diabetes.ucsf.edu
FU National Institutes of Health [DK087853, DK97441]; DERC center [DK63720]; University of California, San Francisco Program for Breakthrough Biomedical Research program; Pew Charitable Trust; PRESTO from the Japan Science and Technology Agency; Manpei Suzuki Diabetes Foundation; Japan Society for the Promotion of Science; National Institute of Diabetes and Digestive and Kidney Diseases [R01DK097441] Funding Source: NIH RePORTER
NR 36
TC 278
Z9 318
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 DEC 5
PY 2013
VL 504
IS 7478
BP 163
EP +
DI 10.1038/nature12652
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 264BK
UT WOS:000327851700052
PM 24196706
DA 2026-03-09
ER

PT J
AU Li, WB
   Notani, D
   Ma, Q
   Tanasa, B
   Nunez, E
   Chen, AY
   Merkurjev, D
   Zhang, J
   Ohgi, K
   Song, XY
   Oh, S
   Kim, HS
   Glass, CK
   Rosenfeld, MG
AF Li, Wenbo
   Notani, Dimple
   Ma, Qi
   Tanasa, Bogdan
   Nunez, Esperanza
   Chen, Aaron Yun
   Merkurjev, Daria
   Zhang, Jie
   Ohgi, Kenneth
   Song, Xiaoyuan
   Oh, Soohwan
   Kim, Hong-Sook
   Glass, Christopher K.
   Rosenfeld, Michael G.
TI Functional roles of enhancer RNAs for oestrogen-dependent transcriptional activation
SO NATURE
LA English
DT Article
ID long noncoding rna; genome-wide analysis; gene-expression; chromatin; principles; alpha; insights; mediator
AB The functional importance of gene enhancers in regulated gene expression is well established(1-3). In addition to widespread transcription of long non-coding RNAs (lncRNAs) in mammalian cells(4-6), bidirectional ncRNAs are transcribed on enhancers, and are thus referred to as enhancer RNAs (eRNAs)(7-9). However, it has remained unclear whether these eRNAs are functional or merely a reflection of enhancer activation. Here we report that in human breast cancer cells 17 beta-oestradiol (E2)-bound oestrogen receptor alpha (ER-alpha) causes a global increase in eRNA transcription on enhancers adjacent to E2-upregulated coding genes. These induced eRNAs, as functional transcripts, seem to exert important roles for the observed ligand-dependent induction of target coding genes, increasing the strength of specific enhancer-promoter looping initiated by ER-alpha binding. Cohesin, present on many ER-alpha-regulated enhancers even before ligand treatment, apparently contributes to E2-dependent gene activation, at least in part by stabilizing E2/ER-alpha/eRNA-induced enhancer-promoter looping. Our data indicate that eRNAs are likely to have important functions in many regulated programs of gene transcription.
C1 [Li, Wenbo; Notani, Dimple; Ma, Qi; Tanasa, Bogdan; Nunez, Esperanza; Chen, Aaron Yun; Merkurjev, Daria; Zhang, Jie; Ohgi, Kenneth; Song, Xiaoyuan; Oh, Soohwan; Kim, Hong-Sook; Rosenfeld, Michael G.] Univ Calif San Diego, Sch Med, Dept Med, Howard Hughes Med Inst, La Jolla, CA 92093 USA.
   [Ma, Qi; Merkurjev, Daria] Univ Calif San Diego, Grad Program Bioinformat, La Jolla, CA 92093 USA.
   [Tanasa, Bogdan] Scripps Res Inst, Kellogg Sch Sci & Technol, Grad Program, La Jolla, CA 92037 USA.
   [Oh, Soohwan] Univ Calif San Diego, Grad Program Biol Sci, La Jolla, CA 92093 USA.
   [Glass, Christopher K.] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA.
C3 Howard Hughes Medical Institute; University of California System; University of California San Diego; University of California System; University of California San Diego; Scripps Research Institute; University of California System; University of California San Diego; University of California System; University of California San Diego
RP Rosenfeld, MG (corresponding author), Univ Calif San Diego, Sch Med, Dept Med, Howard Hughes Med Inst, La Jolla, CA 92093 USA.
EM mrosenfeld@ucsd.edu
FU UCSD Cancer Center [P30 CA23100]; Department of Defense (DoD) [BC110381, BC103858]; DoD;  [DK 039949];  [DK018477];  [NS034934];  [HL065445];  [CA173903]; National Cancer Institute [T32CA009523, P30CA023100] Funding Source: NIH RePORTER; National Institute of Diabetes and Digestive and Kidney Diseases [R01DK018477, R01DK039949] Funding Source: NIH RePORTER
NR 40
TC 805
Z9 1000
U1 0
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 JUN 27
PY 2013
VL 498
IS 7455
BP 516
EP +
DI 10.1038/nature12210
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 171LH
UT WOS:000320929400059
PM 23728302
DA 2026-03-09
ER

PT J
AU Talpalar, AE
   Bouvier, J
   Borgius, L
   Fortin, G
   Pierani, A
   Kiehn, O
AF Talpalar, Adolfo E.
   Bouvier, Julien
   Borgius, Lotta
   Fortin, Gilles
   Pierani, Alessandra
   Kiehn, Ole
TI Dual-mode operation of neuronal networks involved in left-right alternation
SO NATURE
LA English
DT Article
ID green fluorescent protein; spinal-cord; commissural interneurons; locomotor-activity; mice; identification; coordination; expression; zebrafish; circuits
AB All forms of locomotion are repetitive motor activities that require coordinated bilateral activation of muscles. The executive elements of locomotor control are networks of spinal neurons that determine gait pattern through the sequential activation of motor-neuron pools on either side of the body axis(1-4). However, little is known about the constraints that link left-right coordination to locomotor speed. Recent advances have indicated that both excitatory and inhibitory commissural neurons may be involved in left-right coordination(5-7). But the neural underpinnings of this, and a possible causal link between these different groups of commissural neurons and left-right alternation, are lacking. Here we show, using intersectional mouse genetics, that ablation of a group of transcriptionally defined commissural neurons-the V0 population-leads to a quadrupedal hopping at all frequencies of locomotion. The selective ablation of inhibitory V0 neurons leads to a lack of left-right pattern at low frequencies, mixed coordination at medium frequencies, and alternation at high locomotor frequencies. When ablation is targeted to excitatory V0 neurons, left-right alternation is present at low frequencies, and hopping is restricted to medium and high locomotor frequencies. Therefore, the intrinsic logic of the central control of locomotion incorporates a modular organization, with two subgroups of V0 neurons required for the existence of left-right alternating modes at different speeds of locomotion. The two molecularly distinct sets of commissural neurons may constrain species-related naturally occurring frequency-dependent coordination and be involved in the evolution of different gaits.
C1 [Talpalar, Adolfo E.; Bouvier, Julien; Borgius, Lotta; Kiehn, Ole] Karolinska Inst, Dept Neurosci, Mammalian Locomotor Lab, S-17177 Stockholm, Sweden.
   [Fortin, Gilles] CNRS, F-91198 Gif Sur Yvette, France.
   [Pierani, Alessandra] Univ Paris Diderot, Sorbonne Paris Cite, Inst Jacques Monod, CNRS,UMR 7592, F-75205 Paris, France.
C3 Karolinska Institutet; Centre National de la Recherche Scientifique (CNRS); Universite Paris Saclay; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB); Universite Paris Cite
RP Kiehn, O (corresponding author), Karolinska Inst, Dept Neurosci, Mammalian Locomotor Lab, S-17177 Stockholm, Sweden.
EM ole.kiehn@ki.se
FU Soderberg Foundation; Swedish Research Council; European Research Council
NR 39
TC 254
Z9 305
U1 2
U2 49
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 1
PY 2013
VL 500
IS 7460
BP 85
EP U108
DI 10.1038/nature12286
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 192VK
UT WOS:000322514800033
PM 23812590
DA 2026-03-09
ER

PT J
AU Mashaghi, A
   Kramer, G
   Bechtluft, P
   Zachmann-Brand, B
   Driessen, AJM
   Bukau, B
   Tans, SJ
AF Mashaghi, Alireza
   Kramer, Guenter
   Bechtluft, Philipp
   Zachmann-Brand, Beate
   Driessen, Arnold J. M.
   Bukau, Bernd
   Tans, Sander J.
TI Reshaping of the conformational search of a protein by the chaperone trigger factor
SO NATURE
LA English
DT Article
ID single-molecule; ribosome; spectroscopy; domain
AB Protein folding is often described as a search process, in which polypeptides explore different conformations to find their native structure. Molecular chaperones are known to improve folding yields by suppressing aggregation between polypeptides before this conformational search starts(1,2), as well as by rescuing misfolds after it ends(1,3). Although chaperones have long been speculated to also affect the conformational search itself-by reshaping the underlying folding landscape along the folding trajectory(4,5)-direct experimental evidence has been scarce so far. In Escherichia coli, the general chaperone trigger factor(6-8) (TF) could play such a role. TF has been shown to interact with nascent chains at the ribosome(9,10), with polypeptides released from the ribosome into the cytosol(11), and with fully folded proteins before their assembly into larger complexes(12). To investigate the effect of TF from E. coli on the conformational search of polypeptides to their native state, we investigated individual maltose binding protein (MBP) molecules using optical tweezers. Here we show that TF binds folded structures smaller than one domain, which are then stable for seconds and ultimately convert to the native state. Moreover, TF stimulates native folding in constructs of repeated MBP domains. The results indicate that TF promotes correct folding by protecting partially folded states from distant interactions that produce stable misfolded states. As TF interacts with most newly synthesized proteins in E. coli, we expect these findings to be of general importance in understanding protein folding pathways.
C1 [Mashaghi, Alireza; Bechtluft, Philipp; Tans, Sander J.] FOM Inst AMOLF, NL-1098 XG Amsterdam, Netherlands.
   [Kramer, Guenter; Zachmann-Brand, Beate; Bukau, Bernd] Univ Heidelberg ZMBH, Zentrum Mol Biol, DKFZ ZMBH Allianz, D-69120 Heidelberg, Germany.
   [Driessen, Arnold J. M.] Univ Groningen, Dept Mol Microbiol, Groningen Biomol Sci & Biotechnol Inst, NL-9749 AG Groningen, Netherlands.
   [Driessen, Arnold J. M.] Univ Groningen, Zernike Inst Adv Mat, NL-9749 AG Groningen, Netherlands.
C3 AMOLF; Helmholtz Association; German Cancer Research Center (DKFZ); Ruprecht Karls University Heidelberg; University of Groningen; University of Groningen
RP Tans, SJ (corresponding author), FOM Inst AMOLF, Sci Pk 104, NL-1098 XG Amsterdam, Netherlands.
EM tans@amolf.nl
FU Nederlandse Organisatie voor Wetenschappelijke Onderzoek (NWO); Deutsche Forschungsgemeinschaft [SFB 638, FOR967]
NR 30
TC 110
Z9 130
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 AUG 1
PY 2013
VL 500
IS 7460
BP 98
EP U125
DI 10.1038/nature12293
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 192VK
UT WOS:000322514800036
PM 23831649
DA 2026-03-09
ER

PT J
AU Carslaw, KS
   Lee, LA
   Reddington, CL
   Pringle, KJ
   Rap, A
   Forster, PM
   Mann, GW
   Spracklen, DV
   Woodhouse, MT
   Regayre, LA
   Pierce, JR
AF Carslaw, K. S.
   Lee, L. A.
   Reddington, C. L.
   Pringle, K. J.
   Rap, A.
   Forster, P. M.
   Mann, G. W.
   Spracklen, D. V.
   Woodhouse, M. T.
   Regayre, L. A.
   Pierce, J. R.
TI Large contribution of natural aerosols to uncertainty in indirect forcing
SO NATURE
LA English
DT Article
ID cloud condensation nuclei; sulfate aerosol; number concentrations; global-model; glomap-mode; climate; sensitivity; impact; emissions; microphysics
AB The effect of anthropogenic aerosols on cloud droplet concentrations and radiative properties is the source of one of the largest uncertainties in the radiative forcing of climate over the industrial period. This uncertainty affects our ability to estimate how sensitive the climate is to greenhouse gas emissions. Here we perform a sensitivity analysis on a global model to quantify the uncertainty in cloud radiative forcing over the industrial period caused by uncertainties in aerosol emissions and processes. Our results show that 45 per cent of the variance of aerosol forcing since about 1750 arises from uncertainties in natural emissions of volcanic sulphur dioxide, marine dimethylsulphide, biogenic volatile organic carbon, biomass burning and sea spray. Only 34 per cent of the variance is associated with anthropogenic emissions. The results point to the importance of understanding pristine pre-industrial-like environments, with natural aerosols only, and suggest that improved measurements and evaluation of simulated aerosols in polluted present-day conditions will not necessarily result in commensurate reductions in the uncertainty of forcing estimates.
C1 [Carslaw, K. S.; Lee, L. A.; Reddington, C. L.; Pringle, K. J.; Rap, A.; Forster, P. M.; Mann, G. W.; Spracklen, D. V.; Woodhouse, M. T.; Regayre, L. A.] Univ Leeds, Sch Earth & Environm, Leeds LS2 9JT, W Yorkshire, England.
   [Mann, G. W.] Univ Leeds, Natl Ctr Atmospher Sci, Leeds LS2 9JT, W Yorkshire, England.
   [Pierce, J. R.] Colorado State Univ, Dept Atmospher Sci, Ft Collins, CO 80523 USA.
C3 University of Leeds; University of Leeds; UK Research & Innovation (UKRI); Natural Environment Research Council (NERC); NERC National Centre for Atmospheric Science; Colorado State University System; Colorado State University Fort Collins
RP Carslaw, KS (corresponding author), Univ Leeds, Sch Earth & Environm, Leeds LS2 9JT, W Yorkshire, England.
EM k.s.carslaw@leeds.ac.uk
FU Natural Environment Research Council [NE/G006172/1, NE/J024252/1]; EC [FP7-ENV-2010-265148]; National Centre for Atmospheric Science; Royal Society; Natural Environment Research Council [NE/J024252/1, 1230782, NE/G015015/1, NE/G006172/1] Funding Source: researchfish; EPSRC [EP/I014721/1] Funding Source: UKRI; NERC [NE/G015015/1, NE/J024252/1, NE/G006172/1] Funding Source: UKRI
NR 66
TC 823
Z9 923
U1 8
U2 594
PU NATURE PUBLISHING 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 7
PY 2013
VL 503
IS 7474
BP 67
EP +
DI 10.1038/nature12674
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 247AS
UT WOS:000326585600033
PM 24201280
DA 2026-03-09
ER

PT J
AU Alenghat, T
   Osborne, LC
   Saenz, SA
   Kobuley, D
   Ziegler, CGK
   Mullican, SE
   Choi, I
   Grunberg, S
   Sinha, R
   Wynosky-Dolfi, M
   Snyder, A
   Giacomin, PR
   Joyce, KL
   Hoang, TB
   Bewtra, M
   Brodsky, IE
   Sonnenberg, GF
   Bushman, FD
   Won, KJ
   Lazar, MA
   Artis, D
AF Alenghat, Theresa
   Osborne, Lisa C.
   Saenz, Steven A.
   Kobuley, Dmytro
   Ziegler, Carly G. K.
   Mullican, Shannon E.
   Choi, Inchan
   Grunberg, Stephanie
   Sinha, Rohini
   Wynosky-Dolfi, Meghan
   Snyder, Annelise
   Giacomin, Paul R.
   Joyce, Karen L.
   Hoang, Tram B.
   Bewtra, Meenakshi
   Brodsky, Igor E.
   Sonnenberg, Gregory F.
   Bushman, Frederic D.
   Won, Kyoung-Jae
   Lazar, Mitchell A.
   Artis, David
TI Histone deacetylase 3 coordinates commensal-bacteria-dependent intestinal homeostasis
SO NATURE
LA English
DT Article
ID expression; cells; hdac3; maintenance; metabolism; microbiota; disease; unifrac; energy
AB The development and severity of inflammatory bowel diseases and other chronic inflammatory conditions can be influenced by host genetic and environmental factors, including signals derived from commensal bacteria(1-6). However, the mechanisms that integrate these diverse cues remain undefined. Here we demonstrate that mice with an intestinal epithelial cell (IEC)-specific deletion of the epigenome-modifying enzyme histone deacetylase 3 (HDAC3(Delta IEC) mice) exhibited extensive dysregulation of IEC-intrinsic gene expression, including decreased basal expression of genes associated with antimicrobial defence. Critically, conventionally housed HDAC3(Delta IEC) mice demonstrated loss of Paneth cells, impaired IEC function and alterations in the composition of intestinal commensal bacteria. In addition, HDAC3(Delta IEC) mice showed significantly increased susceptibility to intestinal damage and inflammation, indicating that epithelial expression of HDAC3 has a central role in maintaining intestinal homeostasis. Re-derivation of HDAC3(Delta IEC) mice into germ-free conditions revealed that dysregulated IEC gene expression, Paneth cell homeostasis and intestinal barrier function were largely restored in the absence of commensal bacteria. Although the specific mechanisms through which IEC-intrinsic HDAC3 expression regulates these complex phenotypes remain to be determined, these data indicate that HDAC3 is a critical factor that integrates commensal-bacteria-derived signals to calibrate epithelial cell responses required to establish normal host-commensal relationships and maintain intestinal homeostasis.
C1 [Alenghat, Theresa; Osborne, Lisa C.; Saenz, Steven A.; Kobuley, Dmytro; Ziegler, Carly G. K.; Grunberg, Stephanie; Sinha, Rohini; Giacomin, Paul R.; Joyce, Karen L.; Bushman, Frederic D.; Artis, David] Univ Penn, Perelman Sch Med, Dept Microbiol, Philadelphia, PA 19104 USA.
   [Alenghat, Theresa; Osborne, Lisa C.; Saenz, Steven A.; Kobuley, Dmytro; Wynosky-Dolfi, Meghan; Giacomin, Paul R.; Joyce, Karen L.; Brodsky, Igor E.; Sonnenberg, Gregory F.; Artis, David] Univ Penn, Perelman Sch Med, Inst Immunol, Philadelphia, PA 19104 USA.
   [Alenghat, Theresa; Wynosky-Dolfi, Meghan; Snyder, Annelise; Brodsky, Igor E.; Artis, David] Univ Penn, Sch Vet Med, Dept Pathobiol, Philadelphia, PA 19104 USA.
   [Mullican, Shannon E.; Lazar, Mitchell A.] Univ Penn, Dept Med, Div Endocrinol Diabet & Metab, Philadelphia, PA 19104 USA.
   [Mullican, Shannon E.; Choi, Inchan; Won, Kyoung-Jae; Lazar, Mitchell A.] Univ Penn, Perelman Sch Med, Inst Diabet Obes & Metab, Philadelphia, PA 19104 USA.
   [Choi, Inchan; Won, Kyoung-Jae; Lazar, Mitchell A.] Univ Penn, Perelman Sch Med, Dept Genet, Philadelphia, PA 19104 USA.
   [Hoang, Tram B.; Bewtra, Meenakshi; Sonnenberg, Gregory F.] Univ Penn, Perelman Sch Med, Dept Med, Div Gastroenterol, Philadelphia, PA 19104 USA.
   [Bewtra, Meenakshi] Univ Penn, Perelman Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA.
C3 University of Pennsylvania; University of Pennsylvania; University of Pennsylvania; University of Pennsylvania; University of Pennsylvania; University of Pennsylvania; University of Pennsylvania; University of Pennsylvania
RP Artis, D (corresponding author), Univ Penn, Perelman Sch Med, Dept Microbiol, Philadelphia, PA 19104 USA.
EM dartis@mail.med.upenn.edu
FU National Institutes of Health [AI061570, AI095608, AI087990, AI074878, AI095466, AI106697, AI102942, AI097333, DK043806, T32-RR007063, K08-DK093784, DP5OD012116, F31-GM082187, K08-DK084347, R21-AI105346]; Crohns and Colitis Foundation of America; Burroughs Wellcome Fund Investigator in Pathogenesis of Infectious Disease Award; Irvington Institute Postdoctoral Fellowship of the Cancer Research Institute; Abramson Cancer Center Flow Cytometry and Cell Sorting Resource Laboratory; NCI Comprehensive Cancer Center Support Grant [2-P30 CA016520]; National Cancer Institute; National Cancer Institute [P30CA016520] Funding Source: NIH RePORTER; National Institute of Allergy and Infectious Diseases [R01AI095466, P01AI106697, U01AI095608] Funding Source: NIH RePORTER; National Institute of Diabetes and Digestive and Kidney Diseases [R01DK043806, P30DK019525, P30DK050306] Funding Source: NIH RePORTER
NR 39
TC 199
Z9 236
U1 0
U2 63
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 5
PY 2013
VL 504
IS 7478
BP 153
EP +
DI 10.1038/nature12687
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 264BK
UT WOS:000327851700050
PM 24185009
DA 2026-03-09
ER

PT J
AU Niu, DW
   Willoughby, PH
   Woods, BP
   Baire, B
   Hoye, TR
AF Niu, Dawen
   Willoughby, Patrick H.
   Woods, Brian P.
   Baire, Beeraiah
   Hoye, Thomas R.
TI Alkane desaturation by concerted double hydrogen atom transfer to benzyne
SO NATURE
LA English
DT Article
ID diels-alder reaction; cycloaromatization; intermediate; generation; arynes
AB The removal of two vicinal hydrogen atoms from an alkane to produce an alkene is a challenge for synthetic chemists(1,2). In nature, desaturases and acetylenases are adept at achieving this essential oxidative functionalization reaction, for example during the biosynthesis of unsaturated fatty acids(3), eicosanoids, gibberellins(4) and carotenoids(5). Alkane-to-alkene conversion almost always involves one or more chemical intermediates in a multistep reaction pathway; these may be either isolable species (such as alcohols or alkyl halides) or reactive intermediates (such as carbocations, alkyl radicals, or sigma-alkyl-metal species). Here we report a desaturation reaction of simple, unactivated alkanes that is mechanistically unique. We show that benzynes are capable of the concerted removal of two vicinal hydrogen atoms from a hydrocarbon. The discovery of this exothermic, net redox process was enabled by the simple thermal generation of reactive benzyne intermediates through the hexadehydro-Diels-Alder cycloisomerization reaction of triyne substrates(6). We are not aware of any single-step, bimolecular reaction in which two hydrogen atoms are simultaneously transferred from a saturated alkane. Computational studies indicate a preferred geometry with eclipsed vicinal C-H bonds in the alkane donor.
C1 [Niu, Dawen; Willoughby, Patrick H.; Woods, Brian P.; Baire, Beeraiah; Hoye, Thomas R.] 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 University of Minnesota Graduate School Doctoral Dissertation Fellowship; National Science Foundation Graduate Research Fellowship program; National Institute of General Medical Sciences [GM65597]; National Cancer Institute of the US Department of Health and Human Services [CA76497]
NR 27
TC 128
Z9 156
U1 1
U2 190
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 26
PY 2013
VL 501
IS 7468
BP 531
EP 534
DI 10.1038/nature12492
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 223RP
UT WOS:000324826300054
PM 24067712
DA 2026-03-09
ER

PT J
AU Adorno, M
   Sikandar, S
   Mitra, SS
   Kuo, A
   Di Robilant, BN
   Haro-Acosta, V
   Ouadah, Y
   Quarta, M
   Rodriguez, J
   Qian, DL
   Reddy, VM
   Cheshier, S
   Garner, CC
   Clarke, MF
AF Adorno, Maddalena
   Sikandar, Shaheen
   Mitra, Siddhartha S.
   Kuo, Angera
   Di Robilant, Benedetta Nicolis
   Haro-Acosta, Veronica
   Ouadah, Youcef
   Quarta, Marco
   Rodriguez, Jacqueline
   Qian, Dalong
   Reddy, Vadiyala M.
   Cheshier, Samuel
   Garner, Craig C.
   Clarke, Michael F.
TI Usp16 contributes to somatic stem-cell defects in Down's syndrome
SO NATURE
LA English
DT Article
ID mouse model; hematopoietic stem; alzheimers-disease; self-renewal; proliferation; purification; expression; bmi-1; dissection; biomarker
AB Down's syndrome results from full or partial trisomy of chromosome 21. However, the consequences of the underlying gene-dosage imbalance on adult tissues remain poorly understood. Here we show that in Ts65Dn mice, which are trisomic for 132 genes homologous to genes on human chromosome 21, triplication of Usp16 reduces the self-renewal of haematopoietic stem cells and the expansion of mammary epithelial cells, neural progenitors and fibroblasts. In addition, Usp16 is associated with decreased ubiquitination of Cdkn2a and accelerated senescence in Ts65Dn fibroblasts. Usp16 can remove ubiquitin from histone H2A on lysine 119, a critical mark for the maintenance of multiple somatic tissues. Downregulation of Usp16, either by mutation of a single normal Usp16 allele or by short interfering RNAs, largely rescues all of these defects. Furthermore, in human tissues overexpression of USP16 reduces the expansion of normal fibroblasts and postnatal neural progenitors, whereas downregulation of USP16 partially rescues the proliferation defects of Down's syndrome fibroblasts. Taken together, these results suggest that USP16 has an important role in antagonizing the self-renewal and/or senescence pathways in Down's syndrome and could serve as an attractive target to ameliorate some of the associated pathologies.
C1 [Adorno, Maddalena; Sikandar, Shaheen; Mitra, Siddhartha S.; Kuo, Angera; Di Robilant, Benedetta Nicolis; Haro-Acosta, Veronica; Ouadah, Youcef; Qian, Dalong; Cheshier, Samuel; Clarke, Michael F.] Stanford Univ, Sch Med, Inst Stem Cell Biol & Regenerat Med, Stanford, CA 94305 USA.
   [Di Robilant, Benedetta Nicolis] San Raffaele Univ, Int PhD Sch Mol Med, Milan, Italy.
   [Ouadah, Youcef] Stanford Univ, Sch Med, Program Canc Biol, Stanford, CA 94305 USA.
   [Quarta, Marco] Stanford Univ, Sch Med, Dept Neurol, Stanford, CA 94305 USA.
   [Rodriguez, Jacqueline; Garner, Craig C.] Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA.
   [Reddy, Vadiyala M.] Stanford Univ, Sch Med, Dept Pediat, Div Pediat Cardiol, Stanford, CA 94305 USA.
   [Cheshier, Samuel] Stanford Univ, Sch Med, Dept Neurosurg, Div Pediat Neurosurg, Stanford, CA 94305 USA.
C3 Stanford University; Vita-Salute San Raffaele University; Stanford University; Stanford University; Stanford University; Stanford University; Stanford University
RP Clarke, MF (corresponding author), Stanford Univ, Sch Med, Inst Stem Cell Biol & Regenerat Med, Stanford, CA 94305 USA.
EM mfclarke@stanford.edu
FU California Institute for Regenerative Medicine (CIRM) basic biology award III; National Institutes of Health [CA100225, CA154209]; CIRM bridges fellowship; Fondazione Umberto Veronesi; Breast Cancer Research Program; Department of Defense; The Breast Cancer Research Foundation (BCRF); Stanford Graduate Fellowship; Down Syndrome Research and Treatment Foundation; Fidelity Foundation; National Cancer Institute [T32CA009302] Funding Source: NIH RePORTER
NR 39
TC 107
Z9 127
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 SEP 19
PY 2013
VL 501
IS 7467
BP 380
EP +
DI 10.1038/nature12530
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 219XT
UT WOS:000324545700037
PM 24025767
DA 2026-03-09
ER

PT J
AU Chen, Q
   Chen, YB
   Bian, CJ
   Fujiki, R
   Yu, XC
AF Chen, Qiang
   Chen, Yibin
   Bian, Chunjing
   Fujiki, Ryoji
   Yu, Xiaochun
TI TET2 promotes histone O-GlcNAcylation during gene transcription
SO NATURE
LA English
DT Article
ID embryonic stem-cells; glcnac transferase; tetratricopeptide repeats; 5-hydroxymethylcytosine; genome; 5-methylcytosine; proteins; nuclear; dna; differentiation
AB Ten eleven translocation (TET) enzymes, including TET1, TET2 and TET3, convert 5-methylcytosine to 5-hydroxymethylcytosine(1) and regulate gene transcription(2-5). However, the molecular mechanism by which TET family enzymes regulate gene transcription remains elusive(5,6). Using protein affinity purification, here we search for functional partners of TET proteins, and find that TET2 and TET3 associate with O-linked beta-N-acetylglucosamine (O-GlcNAc) transferase (OGT), an enzyme that by itself catalyses the addition of O-GlcNAc onto serine and threonine residues (O-GlcNAcylation) in vivo(7,8). TET2 directly interacts with OGT, which is important for the chromatin association of OGT in vivo. Although this specific interaction does not regulate the enzymatic activity of TET2, it facilitates OGT-dependent histone O-GlcNAcylation. Moreover, OGT associates with TET2 at transcription start sites. Downregulation of TET2 reduces the amount of histone 2B Ser 112 GlcNAc marks in vivo, which are associated with gene transcription regulation. Taken together, these results reveal a TET2-dependent O-GlcNAcylation of chromatin. The double epigenetic modifications on both DNA and histones by TET2 and OGT coordinate together for the regulation of gene transcription.
C1 [Chen, Qiang; Chen, Yibin; Bian, Chunjing; Yu, Xiaochun] Univ Michigan, Sch Med, Dept Internal Med, Div Mol Med & Genet, Ann Arbor, MI 48109 USA.
   [Fujiki, Ryoji] Univ Tokyo, Inst Mol & Cellular Biosci, Bunkyo Ku, Tokyo 1130032, Japan.
   [Fujiki, Ryoji] JST, PRESTO, Kawaguchi, Saitama 3320012, Japan.
C3 University of Michigan System; University of Michigan; University of Tokyo; Japan Science & Technology Agency (JST)
RP Yu, XC (corresponding author), Univ Michigan, Sch Med, Dept Internal Med, Div Mol Med & Genet, 1150 W Med Ctr Dr,5560A MSRBII, Ann Arbor, MI 48109 USA.
EM xiayu@med.umich.edu
FU National Institutes of Health [CA132755, CA130899]; University of Michigan Cancer Center; GI Peptide Research Center; Department of Defense; National Cancer Institute [R01CA130899] Funding Source: NIH RePORTER
NR 35
TC 429
Z9 526
U1 1
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 JAN 24
PY 2013
VL 493
IS 7433
BP 561
EP +
DI 10.1038/nature11742
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 075GF
UT WOS:000313871400044
PM 23222540
DA 2026-03-09
ER

PT J
AU Papitto, A
   Ferrigno, C
   Bozzo, E
   Rea, N
   Pavan, L
   Burderi, L
   Burgay, M
   Campana, S
   Di Salvo, T
   Falanga, M
   Filipovic, MD
   Freire, PCC
   Hessels, JWT
   Possenti, A
   Ransom, SM
   Riggio, A
   Romano, P
   Sarkissian, JM
   Stairs, IH
   Stella, L
   Torres, DF
   Wieringa, MH
   Wong, GF
AF Papitto, A.
   Ferrigno, C.
   Bozzo, E.
   Rea, N.
   Pavan, L.
   Burderi, L.
   Burgay, M.
   Campana, S.
   Di Salvo, T.
   Falanga, M.
   Filipovic, M. D.
   Freire, P. C. C.
   Hessels, J. W. T.
   Possenti, A.
   Ransom, S. M.
   Riggio, A.
   Romano, P.
   Sarkissian, J. M.
   Stairs, I. H.
   Stella, L.
   Torres, D. F.
   Wieringa, M. H.
   Wong, G. F.
TI Swings between rotation and accretion power in a binary millisecond pulsar
SO NATURE
LA English
DT Article
ID x-ray transients; neutron-stars; evolution; emission; spin; orbit
AB It is thought that neutron stars in low-mass binary systems can accrete matter and angular momentum from the companion star and be spun-up to millisecond rotational periods(1-3). During the accretion stage, the system is called a low-mass X-ray binary, and bright X-ray emission is observed. When the rate of mass transfer decreases in the later evolutionary stages, these binaries host a radio millisecond pulsar(4,5) whose emission is powered by the neutron star's rotating magnetic field(6). This evolutionary model is supported by the detection of millisecond X-ray pulsations from several accreting neutron stars(7,8) and also by the evidence for a past accretion disc in a rotation-powered millisecond pulsar(9). It has been proposed that a rotation-powered pulsar may temporarily switch on(10-12) during periods of low mass inflow(13) in some such systems. Only indirect evidence for this transition has hitherto been observed(14-18). Here we report observations of accretion-powered, millisecond X-ray pulsations from a neutron star previously seen as a rotation-powered radio pulsar. Within a few days after a month-long X-ray outburst, radio pulses were again detected. This not only shows the evolutionary link between accretion and rotation-powered millisecond pulsars, but also that some systems can swing between the two states on very short timescales.
C1 [Papitto, A.; Rea, N.; Torres, D. F.] Fac Sci, Inst Space Sci ICE IEEC CSIC, E-08193 Barcelona, Spain.
   [Ferrigno, C.; Bozzo, E.; Pavan, L.] Univ Geneva, Dept Astron, ISDC, CH-1290 Versoix, Switzerland.
   [Burderi, L.; Riggio, A.] Univ Cagliari, Dipartimento Fis, SP Monserrato Sestu, I-09042 Monserrato, Italy.
   [Burgay, M.; Possenti, A.] INAF Osservatorio Astron Cagliari, I-09012 Capoterra, Italy.
   [Campana, S.] INAF Osservatorio Astron Brera, I-23807 Merate, Lecco, Italy.
   [Di Salvo, T.] Univ Palermo, Dipartimento Fis & Chim, I-90123 Palermo, Italy.
   [Falanga, M.] Int Space Sci Inst, CH-3012 Bern, Switzerland.
   [Filipovic, M. D.; Wong, G. F.] Univ Western Sydney, Penrith, NSW 1797, Australia.
   [Freire, P. C. C.] Max Planck Inst Radioastron, D-53121 Bonn, Germany.
   [Hessels, J. W. T.] ASTRON, NL-7990 AA Dwingeloo, Netherlands.
   [Hessels, J. W. T.] Univ Amsterdam, Astron Inst Anton Pannekoek, NL-1098 XH Amsterdam, Netherlands.
   [Ransom, S. M.] NRAO, Charlottesville, VA 22901 USA.
   [Romano, P.] INAF Ist Astrofis Spaziale & Fis Cosm, I-90146 Palermo, Italy.
   [Sarkissian, J. M.; Wong, G. F.] CSIRO Astron & Space Sci, Epping, NSW 1710, Australia.
   [Stairs, I. H.] Univ British Columbia, Dept Phys & Astron, Vancouver, BC V6T 1Z1, Canada.
   [Stella, L.] INAF Osservatorio Astron Roma, I-00040 Monte Porzio Catone, Roma, Italy.
   [Torres, D. F.] ICREA, Barcelona 08010, Spain.
   [Wieringa, M. H.] CSIRO Astron & Space Sci, Narrabri, NSW 2390, Australia.
C3 Institut d'Estudis Espacials de Catalunya (IEEC); Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Instituto de Ciencias del Espacio (ICE); University of Geneva; University of Cagliari; Istituto Nazionale Astrofisica (INAF); Istituto Nazionale Astrofisica (INAF); University of Palermo; Western Sydney University; Max Planck Society; University of Amsterdam; National Radio Astronomy Observatory (NRAO); Istituto Nazionale Astrofisica (INAF); Commonwealth Scientific & Industrial Research Organisation (CSIRO); CSIRO Astronomy & Space; University of British Columbia; Istituto Nazionale Astrofisica (INAF); ICREA; Commonwealth Scientific & Industrial Research Organisation (CSIRO); CSIRO Astronomy & Space
RP Papitto, A (corresponding author), Fac Sci, Inst Space Sci ICE IEEC CSIC, Campus UAB,Torre C5,2A Planta, E-08193 Barcelona, Spain.
EM papitto@ice.csic.es
FU CEA/Irfu (France); IN2P3/CNRS (France); CNES (France); INAF (Italy); NWO (The Netherlands); NSERC (Canada); Juan de la Cierva Research Fellowship; Sardinia Regional Government [ESF 2007-13]; Friedrich Wilhelm Bessel Award of the Alexander von Humboldt Foundation;  [AYA2012-39303];  [SGR2009-811];  [iLINK2011-0303]; ICREA Funding Source: Custom
NR 30
TC 382
Z9 414
U1 0
U2 27
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 26
PY 2013
VL 501
IS 7468
BP 517
EP 520
DI 10.1038/nature12470
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 223RP
UT WOS:000324826300051
PM 24067710
DA 2026-03-09
ER

PT J
AU Chung, WS
   Clarke, LE
   Wang, GX
   Stafford, BK
   Sher, A
   Chakraborty, C
   Joung, J
   Foo, LC
   Thompson, A
   Chen, CF
   Smith, SJ
   Barres, BA
AF Chung, Won-Suk
   Clarke, Laura E.
   Wang, Gordon X.
   Stafford, Benjamin K.
   Sher, Alexander
   Chakraborty, Chandrani
   Joung, Julia
   Foo, Lynette C.
   Thompson, Andrew
   Chen, Chinfei
   Smith, Stephen J.
   Barres, Ben A.
TI Astrocytes mediate synapse elimination through MEGF10 and MERTK pathways
SO NATURE
LA English
DT Article
ID cell corpse engulfment; retinal waves; receptor; phagocytosis; kinase; segregation; refinement; clearance; microglia; roles
AB To achieve its precise neural connectivity, the developing mammalian nervous system undergoes extensive activity-dependent synapse remodelling. Recently, microglial cells have been shown to be responsible for a portion of synaptic pruning, but the remaining mechanisms remain unknown. Here we report a new role for astrocytes in actively engulfing central nervous system synapses. This process helps to mediate synapse elimination, requires the MEGF10 and MERTK phagocytic pathways, and is strongly dependent on neuronal activity. Developing mice deficient in both astrocyte pathways fail to refine their retinogeniculate connections normally and retain excess functional synapses. Finally, we show that in the adult mouse brain, astrocytes continuously engulf both excitatory and inhibitory synapses. These studies reveal a novel role for astrocytes in mediating synapse elimination in the developing and adult brain, identify MEGF10 and MERTK as critical proteins in the synapse remodelling underlying neural circuit refinement, and have important implications for understanding learning and memory as well as neurological disease processes.
C1 [Chung, Won-Suk; Clarke, Laura E.; Chakraborty, Chandrani; Joung, Julia; 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.
   [Stafford, Benjamin K.] Univ Michigan, Dept Ophthalmol & Visual Sci, Ann Arbor, MI 48105 USA.
   [Sher, Alexander] Univ Calif Santa Cruz, Santa Cruz Inst Particle Phys, Santa Cruz, CA 95064 USA.
   [Sher, Alexander] Univ Calif Santa Cruz, Dept Phys, Santa Cruz, CA 95064 USA.
   [Foo, Lynette C.] ASTAR, Inst Mol & Cell Biol, Singapore 138673, Singapore.
   [Thompson, Andrew; Chen, Chinfei] Harvard Univ, Sch Med, Childrens Hosp, Boston, MA 02115 USA.
C3 Stanford University; Stanford University; University of Michigan System; University of Michigan; University of California System; University of California Santa Cruz; University of California System; University of California Santa Cruz; Agency for Science Technology & Research (A*STAR); A*STAR - Institute of Molecular & Cell Biology (IMCB); Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Harvard Medical School
RP Chung, WS (corresponding author), Stanford Univ, Sch Med, Dept Neurobiol, Stanford, CA 94305 USA.
EM wschung@stanford.edu
FU NIH [NS069375, 5 R21NS072556]; Damon Runyon Cancer Research Foundation [DRG 2020-09]; EMBO ALTF fellowship; Mcknight Foundation; National Institute on Aging; National Institute of Mental Health; National Institute of General Medical Sciences [T32MH020016] Funding Source: NIH RePORTER
NR 39
TC 1051
Z9 1278
U1 2
U2 147
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 19
PY 2013
VL 504
IS 7480
BP 394
EP +
DI 10.1038/nature12776
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 273ZR
UT WOS:000328575300043
PM 24270812
DA 2026-03-09
ER

PT J
AU Straub, M
   Sigman, DM
   Ren, HJ
   Martínez-García, A
   Meckler, AN
   Hain, MP
   Haug, GH
AF Straub, Marietta
   Sigman, Daniel M.
   Ren, Haojia
   Martinez-Garcia, Alfredo
   Meckler, A. Nele
   Hain, Mathis P.
   Haug, Gerald H.
TI Changes in North Atlantic nitrogen fixation controlled by ocean circulation
SO NATURE
LA English
DT Article
ID african humid period; isotopic composition; arabian sea; climate; nitrate; denitrification; termination; phosphorus; responses; latitude
AB In the ocean, the chemical forms of nitrogen that are readily available for biological use (known collectively as 'fixed' nitrogen) fuel the global phytoplankton productivity that exports carbon to the deep ocean(1-3). Accordingly, variation in the oceanic fixed nitrogen reservoir has been proposed as a cause of glacial-interglacial changes in atmospheric carbon dioxide concentration(2,3). Marine nitrogen fixation, which produces most of the ocean's fixed nitrogen, is thought to be affected by multiple factors, including ocean temperature(4) and the availability of iron(2,3,5) and phosphorus(6). Here we reconstruct changes in North Atlantic nitrogen fixation over the past 160,000 years from the shell-bound nitrogen isotope ratio (N-15/N-14) of planktonic foraminifera in Caribbean Sea sediments. The observed changes cannot be explained by reconstructed changes in temperature, the supply of (iron-bearing) dust or water column denitrification. We identify a strong, roughly 23,000-year cycle in nitrogen fixation and suggest that it is a response to orbitally driven changes in equatorial Atlantic upwelling(7), which imports 'excess' phosphorus (phosphorus in stoichiometric excess of fixed nitrogen) into the tropical North Atlantic surface(5,6). In addition, we find that nitrogen fixation was reduced during glacial stages 6 and 4, when North Atlantic Deep Water had shoaled to become glacial North Atlantic intermediate water(8), which isolated the Atlantic thermocline from excess phosphorus-rich mid-depth waters that today enter from the Southern Ocean. Although modern studies have yielded diverse views of the controls on nitrogen fixation(1,2,4,5), our palaeobiogeochemical data suggest that excess phosphorus is the master variable in the North Atlantic Ocean and indicate that the variations in its supply over the most recent glacial cycle were dominated by the response of regional ocean circulation to the orbital cycles.
C1 [Straub, Marietta; Martinez-Garcia, Alfredo; Meckler, A. Nele; Haug, Gerald H.] ETH, Inst Geol, Dept Earth Sci, CH-8092 Zurich, Switzerland.
   [Sigman, Daniel M.; Hain, Mathis P.] Princeton Univ, Dept Geosci, Princeton, NJ 08544 USA.
   [Ren, Haojia] Columbia Univ, Lamont Doherty Earth Observ, New York, NY 10964 USA.
C3 Swiss Federal Institutes of Technology Domain; ETH Zurich; Princeton University; Columbia University
RP Straub, M (corresponding author), ETH, Inst Geol, Dept Earth Sci, CH-8092 Zurich, Switzerland.
EM marietta.straub@alumni.ethz.ch
FU SNF [200021-131886/1]; US NSF [OCE-1060947]; Grand Challenges Program of Princeton University; NSF; DFG-Leibniz Center for Surface Process and Climate Studies at the University of Potsdam; Directorate For Geosciences; Division Of Ocean Sciences [1060947] Funding Source: National Science Foundation
NR 45
TC 78
Z9 91
U1 0
U2 240
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 12
PY 2013
VL 501
IS 7466
BP 200
EP +
DI 10.1038/nature12397
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 215XR
UT WOS:000324244900036
PM 23965620
DA 2026-03-09
ER

PT J
AU Fu, G
   Casas, J
   Rigaud, S
   Rybakin, V
   Lambolez, F
   Brzostek, J
   Hoerter, JAH
   Paster, W
   Acuto, O
   Cheroutre, H
   Sauer, K
   Gascoigne, NRJ
AF Fu, Guo
   Casas, Javier
   Rigaud, Stephanie
   Rybakin, Vasily
   Lambolez, Florence
   Brzostek, Joanna
   Hoerter, John A. H.
   Paster, Wolfgang
   Acuto, Oreste
   Cheroutre, Hilde
   Sauer, Karsten
   Gascoigne, Nicholas R. J.
TI Themis sets the signal threshold for positive and negative selection in T-cell development
SO NATURE
LA English
DT Article
ID tyrosine phosphatase shp-1; thymocyte selection; multiple common; self-peptides; receptor; tcr; activation; protein; identification; strength
AB Development of a self-tolerant T-cell receptor (TCR) repertoire with the potential to recognize the universe of infectious agents depends on proper regulation of TCR signalling. The repertoire is whittled down during T-cell development in the thymus by the ability of quasi-randomly generated TCRs to interact with selfpeptides presented by major histocompatibility complex (MHC) proteins. Low-affinity TCR interactions with self-MHC proteins generate weak signals that initiate 'positive selection', causing maturation of CD4- or CD8ab-expressing 'single-positive' thymocytes from CD4(+)CD8 alpha beta(+) 'double-positive' precursors(1). These develop into mature naive T cells of the secondary lymphoid organs. TCR interaction with high-affinity agonist self-ligands results in 'negative selection' by activation-induced apoptosis or 'agonist selection' of functionally differentiated self-antigen-experienced T cells(2,3). Here we show that positive selection is enabled by the ability of the T-cell-specific protein Themis(4-9) to specifically attenuate TCR signal strength via SHP1 recruitment and activation in response to low-but not high-affinity TCR engagement. Themis acts as an analog-to-digital converter translating graded TCR affinity into clear-cut selection outcome. By dampening mild TCR signals Themis increases the affinity threshold for activation, enabling positive selection of T cells with a naive phenotype in response to low-affinity self-antigens.
C1 [Fu, Guo; Casas, Javier; Rigaud, Stephanie; Rybakin, Vasily; Brzostek, Joanna; Hoerter, John A. H.; Sauer, Karsten; Gascoigne, Nicholas R. J.] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA.
   [Casas, Javier; Rybakin, Vasily; Brzostek, Joanna; Gascoigne, Nicholas R. J.] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Microbiol, Singapore 117545, Singapore.
   [Casas, Javier; Rybakin, Vasily; Brzostek, Joanna; Gascoigne, Nicholas R. J.] Natl Univ Singapore, Immunol Programme, Singapore 117545, Singapore.
   [Lambolez, Florence; Cheroutre, Hilde] La Jolla Inst Allergy & Immunol, La Jolla, CA 92037 USA.
   [Paster, Wolfgang; Acuto, Oreste] Univ Oxford, Sir William Dunn Sch Pathol, Oxford OX1 3RE, England.
   [Sauer, Karsten] Scripps Res Inst, Dept Cell & Mol Biol, La Jolla, CA 92037 USA.
C3 Scripps Research Institute; National University of Singapore; National University of Singapore; La Jolla Institute for Immunology; University of Oxford; Scripps Research Institute
RP Gascoigne, NRJ (corresponding author), Scripps Res Inst, Dept Immunol & Microbial Sci, 10550 North Torrey Pines Rd, La Jolla, CA 92037 USA.
EM micnrjg@nus.edu.sg
FU NIH [AI073870, DK094173, GM065230, DP1OD006433, GM100785, AI070845, T32AI07244]; Wellcome Trust [GR076558MA]; National University of Singapore; Spanish Ministerio de Ciencia e Innovacion (MICIIN); American Chemical Society; The Leukemia & Lymphoma Society Scholar Award [1440-11]; National Institute of Allergy and Infectious Diseases, the NIH; National Institute of Allergy and Infectious Diseases [T32AI007244] Funding Source: NIH RePORTER
NR 44
TC 103
Z9 127
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 DEC 19
PY 2013
VL 504
IS 7480
BP 441
EP +
DI 10.1038/nature12718
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 273ZR
UT WOS:000328575300053
PM 24226767
DA 2026-03-09
ER

PT J
AU Shekhter, A
   Ramshaw, BJ
   Liang, RX
   Hardy, WN
   Bonn, DA
   Balakirev, FF
   McDonald, RD
   Betts, JB
   Riggs, SC
   Migliori, A
AF Shekhter, Arkady
   Ramshaw, B. J.
   Liang, Ruixing
   Hardy, W. N.
   Bonn, D. A.
   Balakirev, Fedor F.
   McDonald, Ross D.
   Betts, Jon B.
   Riggs, Scott C.
   Migliori, Albert
TI Bounding the pseudogap with a line of phase transitions in YBa2Cu3O6+δ
SO NATURE
LA English
DT Article
ID temperature; state; anomaly; symmetry; order
AB Close to optimal doping, the copper oxide superconductors show 'strange metal' behaviour(1,2), suggestive of strong fluctuations associated with a quantum critical point(3-6). Such a critical point requires a line of classical phase transitions terminating at zero temperature near optimal doping inside the superconducting 'dome'. The underdoped region of the temperature-doping phase diagram from which superconductivity emerges is referred to as the 'pseudogap'(7-13) because evidence exists for partial gapping of the conduction electrons, but so far there is no compelling thermodynamic evidence as to whether the pseudogap is a distinct phase or a continuous evolution of physical properties on cooling. Here we report that the pseudogap in YBa2Cu3O6+delta is a distinct phase, bounded by a line of phase transitions. The doping dependence of this line is such that it terminates at zero temperature inside the superconducting dome. From this we conclude that quantum criticality drives the strange metallic behaviour and therefore superconductivity in the copper oxide superconductors.
C1 [Shekhter, Arkady; Ramshaw, B. J.; Balakirev, Fedor F.; McDonald, Ross D.; Betts, Jon B.; Migliori, Albert] Los Alamos Natl Lab, Natl High Magnet Field Lab, Pulsed Field Facil, Los Alamos, NM 87545 USA.
   [Liang, Ruixing; Hardy, W. N.; Bonn, D. A.] Univ British Columbia, Dept Phys & Astron, Vancouver, BC V6T 1Z1, Canada.
   [Liang, Ruixing; Hardy, W. N.; Bonn, D. A.] Canadian Inst Adv Res, Toronto, ON M5G 1Z8, Canada.
   [Riggs, Scott C.] Stanford Univ, Stanford Inst Mat & Energy Sci, Stanford, CA 94305 USA.
   [Riggs, Scott C.] Stanford Univ, Dept Phys, Stanford, CA 94305 USA.
   [Riggs, Scott C.] Stanford Univ, Dept Appl Phys, Stanford, CA 94305 USA.
   [Riggs, Scott C.] Stanford Univ, Geballe Lab Adv Mat, Stanford, CA 94305 USA.
C3 United States Department of Energy (DOE); Los Alamos National Laboratory; University of British Columbia; Canadian Institute for Advanced Research (CIFAR); Stanford University; Stanford University; Stanford University; Stanford University
RP Shekhter, A (corresponding author), Los Alamos Natl Lab, Natl High Magnet Field Lab, Pulsed Field Facil, POB 1663, Los Alamos, NM 87545 USA.
EM arkady.shekhter@gmail.com
FU National Science Foundation [DMR-0654118]; US Department of Energy; State of Florida; Canadian Institute for Advanced Research; Natural Science and Engineering Research Council
NR 30
TC 155
Z9 173
U1 1
U2 149
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 6
PY 2013
VL 498
IS 7452
BP 75
EP 77
DI 10.1038/nature12165
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 158DC
UT WOS:000319947800035
PM 23739425
DA 2026-03-09
ER

PT J
AU Konermann, S
   Brigham, MD
   Trevino, AE
   Hsu, PD
   Heidenreich, M
   Cong, L
   Platt, RJ
   Scott, DA
   Church, GM
   Zhang, F
AF Konermann, Silvana
   Brigham, Mark D.
   Trevino, Alexandro E.
   Hsu, Patrick D.
   Heidenreich, Matthias
   Cong, Le
   Platt, Randall J.
   Scott, David A.
   Church, George M.
   Zhang, Feng
TI Optical control of mammalian endogenous transcription and epigenetic states
SO NATURE
LA English
DT Article
ID spatiotemporal control; protein interactions; interrogation; activation; expression; induction; promoter
AB The dynamic nature of gene expression enables cellular programming, homeostasis and environmental adaptation in living systems. Dissection of causal gene functions in cellular and organismal processes therefore necessitates approaches that enable spatially and temporally precise modulation of gene expression. Recently, a variety of microbial and plant-derived light-sensitive proteins have been engineered as optogenetic actuators, enabling high-precision spatiotemporal control of many cellular functions(1-11). However, versatile and robust technologies that enable optical modulation of transcription in the mammalian endogenous genome remain elusive. Here we describe the development of light-inducible transcriptional effectors (LITEs), an optogenetic two-hybrid system integrating the customizable TALE DNA-binding domain(12-14) with the light-sensitive cryptochrome 2 protein and its interacting partner CIB1 from Arabidopsis thaliana. LITEs do not require additional exogenous chemical cofactors, are easily customized to target many endogenous genomic loci, and can be activated within minutes with reversibility(6,15). LITEs can be packaged into viral vectors and genetically targeted to probe specific cell populations. We have applied this system in primary mouse neurons, as well as in the brain of freely behaving mice in vivo to mediate reversible modulation of mammalian endogenous gene expression as well as targeted epigenetic chromatin modifications. The LITE system establishes a novel mode of optogenetic control of endogenous cellular processes and enables direct testing of the causal roles of genetic and epigenetic regulation in normal biological processes and disease states.
C1 [Konermann, Silvana; Brigham, Mark D.; Trevino, Alexandro E.; Hsu, Patrick D.; Heidenreich, Matthias; Cong, Le; Platt, Randall J.; Scott, David A.; Church, George M.; Zhang, Feng] Broad Inst MIT & Harvard, Cambridge Ctr 7, Cambridge, MA 02142 USA.
   [Konermann, Silvana; Brigham, Mark D.; Trevino, Alexandro E.; Hsu, Patrick D.; Heidenreich, Matthias; Cong, Le; Platt, Randall J.; Scott, David A.; Zhang, Feng] MIT, Dept Biol Engn, Dept Brain & Cognit Sci, McGovern Inst Brain Res, Cambridge, MA 02139 USA.
   [Brigham, Mark D.] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA.
   [Hsu, Patrick D.] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA.
   [Cong, Le] Harvard Univ, Sch Med, Program Biol & Biomed Sci, Boston, MA 02115 USA.
   [Church, George M.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
C3 Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Massachusetts Institute of Technology (MIT); Harvard University; Harvard University; Harvard University; Harvard Medical School; Harvard University; Harvard Medical School
RP Zhang, F (corresponding author), Broad Inst MIT & Harvard, Cambridge Ctr 7, Cambridge, MA 02142 USA.
EM zhang@broadinstitute.org
FU McGovern Institute for Brain Research at MIT; Human Frontiers Science Program; NIH NHGRI CEGS [P50-HG005550]; NIH [R01-NS073124, DP1-MH100706]; Keck Foundation; McKnight Foundation; Vallee Foundation; Damon Runyon Foundation; Searle Scholars Foundation; Klingenstein Foundation; Simons Foundation
NR 34
TC 565
Z9 741
U1 0
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 AUG 22
PY 2013
VL 500
IS 7463
BP 472
EP +
DI 10.1038/nature12466
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 203TJ
UT WOS:000323316100038
DA 2026-03-09
ER

PT J
AU Pronin, SV
   Reiher, CA
   Shenvi, RA
AF Pronin, Sergey V.
   Reiher, Christopher A.
   Shenvi, Ryan A.
TI Stereoinversion of tertiary alcohols to tertiary-alkyl isonitriles and amines
SO NATURE
LA English
DT Article
ID derivatives; solvolysis; catalysts; exchange; carbon
AB The S(N)2 reaction (bimolecular nucleophilic substitution) is a well-known chemical transformation that can be used to join two smaller molecules together into a larger molecule or to exchange one functional group for another. The S(N)2 reaction proceeds in a very predictable manner: substitution occurs with inversion of stereochemistry, resulting from the 'backside attack' of the electrophilic carbon by the nucleophile. A significant limitation of the S(N)2 reaction is its intolerance for tertiary carbon atoms: whereas primary and secondary alcohols are viable precursor substrates, tertiary alcohols and their derivatives usually either fail to react or produce stereochemical mixtures of products(1-3). Here we report the stereochemical inversion of chiral tertiary alcohols with a nitrogenous nucleophile facilitated by a Lewis-acid-catalysed solvolysis. The method is chemoselective against secondary and primary alcohols, thereby complementing the selectivity of the S(N)2 reaction. Furthermore, this method for carbon-nitrogen bond formation mimics a putative biosynthetic step in the synthesis of marine terpenoids(4) and enables their preparation from the corresponding terrestrial terpenes. We expect that the general attributes of the methodology will allow chiral tertiary alcohols to be considered viable substrates for stereoinversion reactions.
C1 [Pronin, Sergey V.; Reiher, Christopher A.; Shenvi, Ryan A.] Scripps Res Inst, Dept Chem, La Jolla, CA 92037 USA.
C3 Scripps Research Institute
RP Shenvi, RA (corresponding author), Scripps Res Inst, Dept Chem, 10550 North Torrey Pines Rd, La Jolla, CA 92037 USA.
EM rshenvi@scripps.edu
FU Eli Lilly; Boehringer Ingelheim; Scripps Research Institute
CR BUNTON CA, 1950, NATURE, V166, P680, DOI 10.1038/166680a0
   Castellanos L, 2007, TETRAHEDRON, V63, P1544, DOI 10.1016/j.tet.2006.12.019
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   SASAKI T, 1981, J ORG CHEM, V46, P5445, DOI 10.1021/jo00339a050
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NR 30
TC 144
Z9 164
U1 2
U2 128
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 12
PY 2013
VL 501
IS 7466
BP 195
EP 199
DI 10.1038/nature12472
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 215XR
UT WOS:000324244900035
PM 24025839
DA 2026-03-09
ER

PT J
AU He, Y
   Fang, J
   Taatjes, DJ
   Nogales, E
AF He, Yuan
   Fang, Jie
   Taatjes, Dylan J.
   Nogales, Eva
TI Structural visualization of key steps in human transcription initiation
SO NATURE
LA English
DT Article
ID rna-polymerase-ii; dna-binding domain; preinitiation complex; electron-microscopy; conformational flexibility; subunit architecture; angstrom resolution; accurate initiation; promoter clearance; elongation complex
AB Eukaryotic transcription initiation requires the assembly of general transcription factors into a pre-initiation complex that ensures the accurate loading of RNA polymerase II (Pol II) at the transcription start site. The molecular mechanism and function of this assembly have remained elusive due to lack of structural information. Here we have used an in vitro reconstituted system to study the stepwise assembly of human TBP, TFIIA, TFIIB, Pol II, TFIIF, TFIIE and TFIIH onto promoter DNA using cryo-electron microscopy. Our structural analyses provide pseudo-atomic models at various stages of transcription initiation that illuminate critical molecular interactions, including how TFIIF engages Pol II and promoter DNA to stabilize both the closed pre-initiation complex and the open-promoter complex, and to regulate start-site selection. Comparison of open versus closed pre-initiation complexes, combined with the localization of the TFIIH helicases XPD and XPB, support a DNA translocation model of XPB and explain its essential role in promoter opening.
C1 [He, Yuan; Nogales, Eva] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Life Sci Div, Berkeley, CA 94720 USA.
   [Fang, Jie; Nogales, Eva] Univ Calif Berkeley, Howard Hughes Med Inst, Berkeley, CA 94720 USA.
   [Taatjes, Dylan J.] Univ Colorado, Dept Chem & Biochem, Boulder, CO 80303 USA.
   [Nogales, Eva] Univ Calif Berkeley, QB3 Inst, Berkeley, CA 94720 USA.
   [Nogales, Eva] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA.
C3 University of California System; University of California Berkeley; United States Department of Energy (DOE); Lawrence Berkeley National Laboratory; Howard Hughes Medical Institute; University of California System; University of California Berkeley; University of Colorado System; University of Colorado Boulder; University of California System; University of California Berkeley; University of California System; University of California Berkeley
RP Nogales, E (corresponding author), Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Life Sci Div, Berkeley, CA 94720 USA.
EM ENogales@lbl.gov
FU NIGMS [GM63072]; NCI [CA127364]
NR 63
TC 218
Z9 290
U1 0
U2 82
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 28
PY 2013
VL 495
IS 7442
BP 481
EP +
DI 10.1038/nature11991
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 113QN
UT WOS:000316682800039
PM 23446344
DA 2026-03-09
ER

PT J
AU Getz, G
   Gabriel, SB
   Cibulskis, K
   Lander, E
   Sivachenko, A
   Sougnez, C
   Lawrence, M
   Kandoth, C
   Dooling, D
   Fulton, R
   Fulton, L
   Kalicki-Veizer, J
   McLellan, MD
   O'Laughlin, M
   Schmidt, H
   Wilson, RK
   Ye, K
   Ding, L
   Mardis, ER
   Ally, A
   Balasundaram, M
   Birol, I
   Butterfield, YSN
   Carlsen, R
   Carter, C
   Chu, A
   Chuah, E
   Chun, HJE
   Dhalla, N
   Guin, R
   Hirst, C
   Holt, RA
   Jones, SJM
   Lee, D
   Li, HI
   Marra, MA
   Mayo, M
   Moore, RA
   Mungall, AJ
   Plettner, P
   Schein, JE
   Sipahimalani, P
   Tam, A
   Varhol, RJ
   Robertson, AG
   Pashtan, I
   Saksena, G
   Onofrio, RC
   Schumacher, SE
   Tabak, B
   Carter, SL
   Hernandez, B
   Gentry, J
   Salvesen, HB
   Ardlie, K
   Getz, G
   Winckler, W
   Beroukhim, R
   Gabriel, SB
   Meyerson, M
   Hadjipanayis, A
   Lee, S
   Mahadeshwar, HS
   Park, P
   Protopopov, A
   Ren, XJ
   Seth, S
   Song, XZ
   Tang, JB
   Xi, RB
   Yang, LX
   Zeng, D
   Kucherlapati, R
   Chin, L
   Zhang, JH
   Auman, JT
   Balu, S
   Bodenheimer, T
   Buda, E
   Hayes, DN
   Hoyle, AP
   Jefferys, SR
   Jones, CD
   Meng, SW
   Mieczkowski, PA
   Mose, LE
   Parker, JS
   Perou, CM
   Roach, J
   Shi, Y
   Simons, JV
   Soloway, MG
   Tan, DH
   Topal, MD
   Waring, S
   Wu, JY
   Hoadley, KA
   Baylin, SB
   Bootwalla, MS
   Lai, PH
   Triche, TJ
   Van Den Berg, D
   Weisenberger, DJ
   Laird, PW
   Shen, H
   Chin, L
   Zhang, JH
   Getz, G
   Cho, J
   DiCara, D
   Frazer, S
   Heiman, D
   Jing, R
   Lin, P
   Mallard, W
   Stojanov, P
   Voet, D
   Zhang, HL
   Zou, LH
   Noble, M
   Lawrence, M
   Reynolds, SM
   Shmulevich, I
   Aksoy, BA
   Antipin, Y
   Ciriello, G
   Dresdner, G
   Gao, JJ
   Gross, B
   Jacobsen, A
   Ladanyi, M
   Reva, B
   Sander, C
   Sinha, R
   Sumer, SO
   Taylor, BS
   Cerami, E
   Weinhold, N
   Schultz, N
   Shen, RL
   Benz, S
   Goldstein, T
   Haussler, D
   Sam, N
   Szeto, C
   Stuart, J
   Benz, CC
   Yau, C
   Zhang, W
   Annala, M
   Broom, BM
   Casasent, TD
   Ju, ZL
   Liang, H
   Liu, GY
   Lu, YL
   Unruh, AK
   Wakefield, C
   Weinstein, JN
   Zhang, NX
   Liu, YX
   Broaddus, R
   Akbani, R
   Mills, GB
   Adams, C
   Barr, T
   Black, AD
   Bowen, J
   Deardurff, J
   Frick, J
   Gastier-Foster, JM
   Grossman, T
   Harper, HA
   Hart-Kothari, M
   Helsel, C
   Hobensack, A
   Kuck, H
   Kneile, K
   Leraas, K
   Lichtenberg, TM
   McAllister, C
   Pyatt, RE
   Ramirez, NC
   Tabler, TR
   Vanhoose, N
   White, P
   Wise, L
   Zmuda, E
   Barnabas, N
   Berry-Green, C
   Blanc, V
   Boice, L
   Button, M
   Farkas, A
   Green, A
   MacKenzie, J
   Nicholson, D
   Kalloger, SE
   Gilks, CB
   Karlan, BY
   Lester, J
   Orsulic, S
   Borowsky, M
   Cadungog, M
   Czerwinski, C
   Huelsenbeck-Dill, L
   Iacocca, M
   Petrelli, N
   Petrelli, N
   Witkin, G
   Nemirovich-Danchenko, E
   Potapova, O
   Rotin, D
   Berchuck, A
   Birrer, M
   DiSaia, P
   Monovich, L
   Curley, E
   Gardner, J
   Mallery, D
   Penny, R
   Dowdy, SC
   Winterhoff, B
   Dao, L
   Gostout, B
   Meuter, A
   Teoman, A
   Dao, F
   Olvera, N
   Bogomolniy, F
   Garg, K
   Soslow, RA
   Levine, DA
   Abramov, M
   Bartlett, JMS
   Kodeeswaran, S
   Parfitt, J
   Moiseenko, F
   Clarke, BA
   Goodman, MT
   Carney, ME
   Matsuno, RK
   Fisher, J
   Huang, M
   Rathmell, WK
   Thorne, L
   Van Le, L
   Dhir, R
   Edwards, R
   Elishaev, E
   Zorn, K
   Broaddus, R
   Goodfellow, PJ
   Mutch, D
   Schultz, N
   Liu, YX
   Akbani, R
   Cherniack, AD
   Cerami, E
   Weinhold, N
   Shen, H
   Hoadley, KA
   Kahn, AB
   Bell, DW
   Pollock, PM
   Wang, C
   Wheeler, DA
   Shinbrot, E
   Karlan, BY
   Berchuck, A
   Dowdy, SC
   Winterhoff, B
   Goodman, MT
   Robertson, AG
   Beroukhim, R
   Pashtan, I
   Salvesen, HB
   Laird, PW
   Noble, M
   Stuart, J
   Ding, L
   Kandoth, C
   Gilks, CB
   Soslow, RA
   Goodfellow, PJ
   Mutch, D
   Broaddus, R
   Zhang, W
   Mills, GB
   Kucherlapati, R
   Mardis, ER
   Levine, DA
   Ayala, B
   Chu, AL
   Jensen, MA
   Kothiyal, P
   Pihl, TD
   Pontius, J
   Pot, DA
   Snyder, EE
   Srinivasan, D
   Kahn, AB
   Shaw, KRM
   Sheth, M
   Davidsen, T
   Eley, G
   Ferguson, ML
   Demchok, JA
   Yang, LM
   Guyer, MS
   Ozenberger, BA
   Sofia, HJ
   Kandoth, C
   Schultz, N
   Cherniack, AD
   Akbani, R
   Liu, YX
   Shen, H
   Robertson, AG
   Pashtan, I
   Shen, R
   Benz, CC
   Yau, C
   Laird, PW
   Ding, L
   Zhang, W
   Mills, GB
   Kucherlapati, R
   Mardis, ER
   Levine, DA
AF Getz, Gad
   Gabriel, Stacey B.
   Cibulskis, Kristian
   Lander, Eric
   Sivachenko, Andrey
   Sougnez, Carrie
   Lawrence, Mike
   Kandoth, Cyriac
   Dooling, David
   Fulton, Robert
   Fulton, Lucinda
   Kalicki-Veizer, Joelle
   McLellan, Michael D.
   O'Laughlin, Michelle
   Schmidt, Heather
   Wilson, Richard K.
   Ye, Kai
   Ding, Li
   Mardis, Elaine R.
   Ally, Adrian
   Balasundaram, Miruna
   Birol, Inanc
   Butterfield, Yaron S. N.
   Carlsen, Rebecca
   Carter, Candace
   Chu, Andy
   Chuah, Eric
   Chun, Hye-Jung E.
   Dhalla, Noreen
   Guin, Ranabir
   Hirst, Carrie
   Holt, Robert A.
   Jones, Steven J. M.
   Lee, Darlene
   Li, Haiyan I.
   Marra, Marco A.
   Mayo, Michael
   Moore, Richard A.
   Mungall, Andrew J.
   Plettner, Patrick
   Schein, Jacqueline E.
   Sipahimalani, Payal
   Tam, Angela
   Varhol, Richard J.
   Robertson, A. Gordon
   Pashtan, Itai
   Saksena, Gordon
   Onofrio, Robert C.
   Schumacher, Steven E.
   Tabak, Barbara
   Carter, Scott L.
   Hernandez, Bryan
   Gentry, Jeff
   Salvesen, Helga B.
   Ardlie, Kristin
   Getz, Gad
   Winckler, Wendy
   Beroukhim, Rameen
   Gabriel, Stacey B.
   Meyerson, Matthew
   Hadjipanayis, Angela
   Lee, Semin
   Mahadeshwar, Harshad S.
   Park, Peter
   Protopopov, Alexei
   Ren, Xiaojia
   Seth, Sahil
   Song, Xingzhi
   Tang, Jiabin
   Xi, Ruibin
   Yang, Lixing
   Zeng, Dong
   Kucherlapati, Raju
   Chin, Lynda
   Zhang, Jianhua
   Auman, J. Todd
   Balu, Saianand
   Bodenheimer, Tom
   Buda, Elizabeth
   Hayes, D. Neil
   Hoyle, Alan P.
   Jefferys, Stuart R.
   Jones, Corbin D.
   Meng, Shaowu
   Mieczkowski, Piotr A.
   Mose, Lisle E.
   Parker, Joel S.
   Perou, Charles M.
   Roach, Jeff
   Shi, Yan
   Simons, Janae V.
   Soloway, Mathew G.
   Tan, Donghui
   Topal, Michael D.
   Waring, Scot
   Wu, Junyuan
   Hoadley, Katherine A.
   Baylin, Stephen B.
   Bootwalla, Moiz S.
   Lai, Phillip H.
   Triche, Timothy J., Jr.
   Van Den Berg, DavidJ.
   Weisenberger, Daniel J.
   Laird, Peter W.
   Shen, Hui
   Chin, Lynda
   Zhang, Jianhua
   Getz, Gad
   Cho, Juok
   DiCara, Daniel
   Frazer, Scott
   Heiman, David
   Jing, Rui
   Lin, Pei
   Mallard, Will
   Stojanov, Petar
   Voet, Doug
   Zhang, Hailei
   Zou, Lihua
   Noble, Michael
   Lawrence, Mike
   Reynolds, Sheila M.
   Shmulevich, Ilya
   Aksoy, B. Arman
   Antipin, Yevgeniy
   Ciriello, Giovanni
   Dresdner, Gideon
   Gao, Jianjiong
   Gross, Benjamin
   Jacobsen, Anders
   Ladanyi, Marc
   Reva, Boris
   Sander, Chris
   Sinha, Rileen
   Sumer, S. Onur
   Taylor, Barry S.
   Cerami, Ethan
   Weinhold, Nils
   Schultz, Nikolaus
   Shen, Ronglai
   Benz, Stephen
   Goldstein, Ted
   Haussler, David
   Sam, Ng
   Szeto, Christopher
   Stuart, Joshua
   Benz, Christopher C.
   Yau, Christina
   Zhang, Wei
   Annala, Matti
   Broom, Bradley M.
   Casasent, Tod D.
   Ju, Zhenlin
   Liang, Han
   Liu, Guoyan
   Lu, Yiling
   Unruh, Anna K.
   Wakefield, Chris
   Weinstein, John N.
   Zhang, Nianxiang
   Liu, Yuexin
   Broaddus, Russell
   Akbani, Rehan
   Mills, Gordon B.
   Adams, Christopher
   Barr, Thomas
   Black, Aaron D.
   Bowen, Jay
   Deardurff, John
   Frick, Jessica
   Gastier-Foster, Julie M.
   Grossman, Thomas
   Harper, Hollie A.
   Hart-Kothari, Melissa
   Helsel, Carmen
   Hobensack, Aaron
   Kuck, Harkness
   Kneile, Kelley
   Leraas, KristenM.
   Lichtenberg, Tara M.
   McAllister, Cynthia
   Pyatt, Robert E.
   Ramirez, Nilsa C.
   Tabler, Teresa R.
   Vanhoose, Nathan
   White, Peter
   Wise, Lisa
   Zmuda, Erik
   Barnabas, Nandita
   Berry-Green, Charlenia
   Blanc, Victoria
   Boice, Lori
   Button, Michael
   Farkas, Adam
   Green, Alex
   MacKenzie, Jean
   Nicholson, Dana
   Kalloger, Steve E.
   Gilks, C. Blake
   Karlan, Beth Y.
   Lester, Jenny
   Orsulic, Sandra
   Borowsky, Mark
   Cadungog, Mark
   Czerwinski, Christine
   Huelsenbeck-Dill, Lori
   Iacocca, Mary
   Petrelli, Nicholas
   Petrelli, Nicholas
   Witkin, Gary
   Nemirovich-Danchenko, Elena
   Potapova, Olga
   Rotin, Daniil
   Berchuck, Andrew
   Birrer, Michael
   DiSaia, Phillip
   Monovich, Laura
   Curley, Erin
   Gardner, Johanna
   Mallery, David
   Penny, Robert
   Dowdy, Sean C.
   Winterhoff, Boris
   Dao, Linda
   Gostout, Bobbie
   Meuter, Alexandra
   Teoman, Attila
   Dao, Fanny
   Olvera, Narciso
   Bogomolniy, Faina
   Garg, Karuna
   Soslow, Robert A.
   Levine, Douglas A.
   Abramov, Mikhail
   Bartlett, John M. S.
   Kodeeswaran, Sugy
   Parfitt, Jeremy
   Moiseenko, Fedor
   Clarke, Blaise A.
   Goodman, Marc T.
   Carney, Michael E.
   Matsuno, Rayna K.
   Fisher, Jennifer
   Huang, Mei
   Rathmell, W. Kimryn
   Thorne, Leigh
   Van Le, Linda
   Dhir, Rajiv
   Edwards, Robert
   Elishaev, Esther
   Zorn, Kristin
   Broaddus, Russell
   Goodfellow, Paul J.
   Mutch, David
   Schultz, Nikolaus
   Liu, Yuexin
   Akbani, Rehan
   Cherniack, Andrew D.
   Cerami, Ethan
   Weinhold, Nils
   Shen, Hui
   Hoadley, Katherine A.
   Kahn, Ari B.
   Bell, Daphne W.
   Pollock, Pamela M.
   Wang, Chen
   Wheeler, David A.
   Shinbrot, Eve
   Karlan, Beth Y.
   Berchuck, Andrew
   Dowdy, Sean C.
   Winterhoff, Boris
   Goodman, Marc T.
   Robertson, A. Gordon
   Beroukhim, Rameen
   Pashtan, Itai
   Salvesen, Helga B.
   Laird, Peter W.
   Noble, Michael
   Stuart, Joshua
   Ding, Li
   Kandoth, Cyriac
   Gilks, C. Blake
   Soslow, Robert A.
   Goodfellow, Paul J.
   Mutch, David
   Broaddus, Russell
   Zhang, Wei
   Mills, Gordon B.
   Kucherlapati, Raju
   Mardis, Elaine R.
   Levine, Douglas A.
   Ayala, Brenda
   Chu, Anna L.
   Jensen, Mark A.
   Kothiyal, Prachi
   Pihl, Todd D.
   Pontius, Joan
   Pot, David A.
   Snyder, Eric E.
   Srinivasan, Deepak
   Kahn, Ari B.
   Shaw, Kenna R. Mills
   Sheth, Margi
   Davidsen, Tanja
   Eley, Greg
   Ferguson, Martin L.
   Demchok, John A.
   Yang, Liming
   Guyer, Mark S.
   Ozenberger, Bradley A.
   Sofia, Heidi J.
   Kandoth, Cyriac
   Schultz, Nikolaus
   Cherniack, Andrew D.
   Akbani, Rehan
   Liu, Yuexin
   Shen, Hui
   Robertson, A. Gordon
   Pashtan, Itai
   Shen, Ronglai
   Benz, Christopher C.
   Yau, Christina
   Laird, Peter W.
   Ding, Li
   Zhang, Wei
   Mills, Gordon B.
   Kucherlapati, Raju
   Mardis, Elaine R.
   Levine, Douglas A.
TI Integrated genomic characterization of endometrial carcinoma
SO NATURE
LA English
DT Article
ID microsatellite instability; somatic mutations; high-frequency; lung-cancer; protein; pik3r1; tumors; grade; model
AB We performed an integrated genomic, transcriptomic and proteomic characterization of 373 endometrial carcinomas using array- and sequencing-based technologies. Uterine seroustumours and similar to 25% of high-grade endometrioid tumours had extensive copy number alterations, few DNA methylation changes, low oestrogen receptor/progesterone receptor levels, and frequent TP53 mutations. Most endometrioid tumours had few copy number alterations or TP53 mutations, but frequent mutations in PTEN, CTNNB1, PIK3CA, ARID1A and KRAS and novel mutations in the SWI/SNF chromatin remodelling complex gene ARID5B. A subset of endometrioid tumours that we identified had a markedly increased transversion mutation frequency and newly identified hotspot mutations in POLE. Our results classified endometrial cancers into four categories: POLE ultramutated, microsatellite instability hypermutated, copy-number low, and copy-number high. Uterine serous carcinomas share genomic features with ovarian serous and basal-like breast carcinomas. We demonstrated that the genomic features of endometrial carcinomas permit a reclassification that may affect post-surgical adjuvant treatment for women with aggressive tumours.
C1 [Getz, Gad; Gabriel, Stacey B.; Cibulskis, Kristian; Lander, Eric; Sivachenko, Andrey; Sougnez, Carrie; Lawrence, Mike; Pashtan, Itai; Saksena, Gordon; Onofrio, Robert C.; Schumacher, Steven E.; Tabak, Barbara; Carter, Scott L.; Hernandez, Bryan; Gentry, Jeff; Salvesen, Helga B.; Ardlie, Kristin; Winckler, Wendy; Beroukhim, Rameen; Meyerson, Matthew; Chin, Lynda; Cho, Juok; DiCara, Daniel; Frazer, Scott; Heiman, David; Jing, Rui; Lin, Pei; Mallard, Will; Stojanov, Petar; Voet, Doug; Zhang, Hailei; Zou, Lihua; Noble, Michael; Cherniack, Andrew D.] MIT, Eli & Edythe L Broad Inst, Cambridge, MA 02139 USA.
   [Kandoth, Cyriac; Dooling, David; Fulton, Robert; Fulton, Lucinda; Kalicki-Veizer, Joelle; McLellan, Michael D.; O'Laughlin, Michelle; Schmidt, Heather; Wilson, Richard K.; Ye, Kai; Ding, Li; Mardis, Elaine R.] Washington Univ, Genome Inst, St Louis, MO 63108 USA.
   [Mardis, Elaine R.; Ally, Adrian; Balasundaram, Miruna; Birol, Inanc; Butterfield, Yaron S. N.; Carlsen, Rebecca; Carter, Candace; Chu, Andy; Chuah, Eric; Chun, Hye-Jung E.; Dhalla, Noreen; Guin, Ranabir; Hirst, Carrie; Holt, Robert A.; Jones, Steven J. M.; Lee, Darlene; Li, Haiyan I.; Marra, Marco A.; Mayo, Michael; Moore, Richard A.; Mungall, Andrew J.; Plettner, Patrick; Schein, Jacqueline E.; Sipahimalani, Payal; Tam, Angela; Varhol, Richard J.; Robertson, A. Gordon] BC Canc Agcy, Canadas Michael Smith Genome Sci Ctr, Vancouver, BC, Canada.
   Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA.
   Brigham & Womens Hosp, Boston, MA 02115 USA.
   Dana Farber Canc Inst, Boston, MA 02215 USA.
   Haukeland Hosp, Dept Obstet & Gynecol, N-5021 Bergen, Norway.
   Univ Bergen, Dept Clin Med, N-5020 Bergen, Norway.
   [Meyerson, Matthew] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA.
   [Hadjipanayis, Angela; Ren, Xiaojia; Kucherlapati, Raju] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
   [Lee, Semin; Park, Peter; Xi, Ruibin; Yang, Lixing] Harvard Univ, Sch Med, Ctr Biomed Informat, Boston, MA 02115 USA.
   [Mahadeshwar, Harshad S.; Protopopov, Alexei; Seth, Sahil; Song, Xingzhi; Tang, Jiabin; Zeng, Dong; Zhang, Jianhua] Univ Texas MD Anderson Canc Ctr, Dept Genom Med, Inst Appl Canc Sci, Houston, TX 77054 USA.
   [Park, Peter] Boston Childrens Hosp, Informat Program, Boston, MA 02115 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.
   [Balu, Saianand; Bodenheimer, Tom; Buda, Elizabeth; Hayes, D. Neil; Hoyle, Alan P.; Jefferys, Stuart R.; Meng, Shaowu; Mose, Lisle E.; Parker, Joel S.; Perou, Charles M.; Shi, Yan; Simons, Janae V.; Soloway, Mathew G.; Tan, Donghui; Topal, Michael D.; Waring, Scot; Wu, Junyuan; Rathmell, W. Kimryn] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA.
   [Hayes, D. Neil] Univ N Carolina, Div Med Oncol, Dept Internal Med, Chapel Hill, NC 27599 USA.
   [Jones, Corbin D.] Univ N Carolina, Dept Biol, Chapel Hill, NC 27599 USA.
   [Mieczkowski, Piotr A.; Perou, Charles M.] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA.
   [Perou, Charles M.; Topal, Michael D.] Univ N Carolina, Dept Pathol & Lab Med, Chapel Hill, NC 27599 USA.
   [Roach, Jeff] Univ N Carolina, Res Comp Ctr, Chapel Hill, NC 27599 USA.
   [Baylin, Stephen B.] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Canc Biol Div, Baltimore, MD 21231 USA.
   [Bootwalla, Moiz S.; Lai, Phillip H.; Triche, Timothy J., Jr.; Van Den Berg, DavidJ.; Weisenberger, Daniel J.; Laird, Peter W.; Shen, Hui] Univ So Calif, Epigenome Ctr, Los Angeles, CA 90089 USA.
   [Reynolds, Sheila M.; Shmulevich, Ilya] Inst Syst Biol, Seattle, WA 98109 USA.
   [Aksoy, B. Arman; Antipin, Yevgeniy; Ciriello, Giovanni; Dresdner, Gideon; Gao, Jianjiong; Gross, Benjamin; Jacobsen, Anders; Reva, Boris; Sander, Chris; Sinha, Rileen; Sumer, S. Onur; Cerami, Ethan; Weinhold, Nils; Schultz, Nikolaus] Mem Sloan Kettering Canc Ctr, Computat Biol Ctr, New York, NY 10065 USA.
   [Ladanyi, Marc] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10065 USA.
   [Taylor, Barry S.] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94158 USA.
   [Shen, Ronglai] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10065 USA.
   [Benz, Stephen; Goldstein, Ted; Haussler, David; Sam, Ng; Szeto, Christopher; Stuart, Joshua] Univ Calif Santa Cruz, Dept Biomol Engn, Santa Cruz, CA 95064 USA.
   [Benz, Stephen; Goldstein, Ted; Sam, Ng; Szeto, Christopher; Stuart, Joshua] Univ Calif Santa Cruz, Ctr Biomol Sci & Engn, Santa Cruz, CA 95064 USA.
   [Benz, Christopher C.; Yau, Christina] Buck Inst Age Res, Novato, CA 94945 USA.
   [Zhang, Wei; Annala, Matti; Liu, Guoyan; Liu, Yuexin] Univ Texas MD Anderson Canc Ctr, Canc Genom Core Lab, Houston, TX 77054 USA.
   [Liu, Guoyan; Liu, Yuexin; Broaddus, Russell] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA.
   Tampere Univ Technol, FI-33720 Tampere, Finland.
   [Bootwalla, Moiz S.; Van Den Berg, DavidJ.; Weisenberger, Daniel J.; Broom, Bradley M.; Ju, Zhenlin; Liang, Han; Unruh, Anna K.; Wakefield, Chris; Akbani, Rehan] Univ Texas MD Anderson Canc Ctr, Dept Bioinformat & Computat Biol, Houston, TX 77030 USA.
   [Lu, Yiling; Mills, Gordon B.] Univ Texas MD Anderson Canc Ctr, Dept Syst Biol, Houston, TX 77030 USA.
   [Adams, Christopher; Barr, Thomas; Black, Aaron D.; Bowen, Jay; Deardurff, John; Frick, Jessica; Gastier-Foster, Julie M.; Grossman, Thomas; Harper, Hollie A.; Hart-Kothari, Melissa; Helsel, Carmen; Hobensack, Aaron; Kuck, Harkness; Kneile, Kelley; Leraas, KristenM.; Lichtenberg, Tara M.; McAllister, Cynthia; Pyatt, Robert E.; Ramirez, Nilsa C.; Tabler, Teresa R.; Vanhoose, Nathan; White, Peter; Wise, Lisa; Zmuda, Erik] Nationwide Childrens Hosp, Res Inst, Columbus, OH 43205 USA.
   [Gastier-Foster, Julie M.; Ramirez, Nilsa C.; Goodfellow, Paul J.] Ohio State Univ, Columbus, OH 43210 USA.
   [Barnabas, Nandita; Berry-Green, Charlenia; Blanc, Victoria; Button, Michael; Farkas, Adam; Green, Alex; MacKenzie, Jean; Nicholson, Dana] Asterand, Detroit, MI 48202 USA.
   [Boice, Lori; Fisher, Jennifer; Huang, Mei; Thorne, Leigh; Van Le, Linda] Univ N Carolina, Chapel Hill, NC 27599 USA.
   [Kalloger, Steve E.; Gilks, C. Blake] British Columbia Canc Agcy, OvCaRe British Columbia, Vancouver, BC V5Z 4E6, Canada.
   [Kalloger, Steve E.; Gilks, C. Blake] Univ British Columbia, Dept Pathol & Lab Med, Vancouver, BC V6T 2B5, Canada.
   [Karlan, Beth Y.; Lester, Jenny; Orsulic, Sandra] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Womens Canc Program, Los Angeles, CA 90048 USA.
   [Borowsky, Mark; Cadungog, Mark; Czerwinski, Christine; Huelsenbeck-Dill, Lori; Iacocca, Mary; Petrelli, Nicholas; Witkin, Gary] Helen F Graham Canc Ctr Christiana Care, Newark, DC 19713 USA.
   [Nemirovich-Danchenko, Elena; Potapova, Olga; Rotin, Daniil] Cureline Inc, San Francisco, CA 94080 USA.
   [Berchuck, Andrew] Duke Univ, Med Ctr, Duke Canc Inst, Durham, NC 27710 USA.
   [Birrer, Michael] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
   [DiSaia, Phillip] Univ Calif Irvine, Med Ctr, Orange, CA 92868 USA.
   [Monovich, Laura] Nationwide Childrens Hosp, Res Inst, GOG Tissue Bank, Columbus, OH 43205 USA.
   [Curley, Erin; Gardner, Johanna; Mallery, David; Penny, Robert] Int Genom Consortium, Phoenix, AZ 85004 USA.
   [Dowdy, Sean C.; Winterhoff, Boris; Gostout, Bobbie; Meuter, Alexandra; Teoman, Attila] Mayo Clin, Div Gynecol Oncol, Dept OB Gyn, Rochester, MN 55905 USA.
   [Dao, Linda] Mayo Clin, Dept Pathol, Rochester, MN 55905 USA.
   [Dao, Fanny; Olvera, Narciso; Bogomolniy, Faina; Levine, Douglas A.] Mem Sloan Kettering Canc Ctr, Dept Surg, Gynecol Serv, New York, NY 10065 USA.
   [Garg, Karuna; Soslow, Robert A.] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10065 USA.
   [Abramov, Mikhail] NN Blokhin Russian Canc Res Ctr RAMS, Moscow 115478, Russia.
   [Bartlett, John M. S.; Kodeeswaran, Sugy] Ontario Inst Canc Res, Ontario Tumour Bank, Toronto, ON M5G 0A3, Canada.
   [Parfitt, Jeremy] London Hlth Sci Ctr, Ontario Tumour Bank, London, ON N6A 5A5, Canada.
   [Moiseenko, Fedor] St Petersburg Acad Univ, St Petersburg 199034, Russia.
   [Clarke, Blaise A.; Demchok, John A.; Yang, Liming] Univ Hlth Network, Dept Pathol, Toronto, ON M5G 2C4, Canada.
   [Goodman, Marc T.; Carney, Michael E.; Matsuno, Rayna K.; Eley, Greg] Univ Hawaii, Honolulu, HI 96813 USA.
   [Goodman, Marc T.] Cedars Sinai Med Ctr, Los Angeles, CA 90024 USA.
   [Dhir, Rajiv; Edwards, Robert; Elishaev, Esther; Zorn, Kristin] Univ Pittsburgh, Pittsburgh, PA 15213 USA.
   [Goodfellow, Paul J.; Mutch, David] Washington Univ, Sch Med, St Louis, MO 63110 USA.
   [Kahn, Ari B.; Ayala, Brenda; Chu, Anna L.; Jensen, Mark A.; Kothiyal, Prachi; Pihl, Todd D.; Pontius, Joan; Pot, David A.; Snyder, Eric E.; Srinivasan, Deepak] SRA Int, Fairfax, VA 22033 USA.
   [Bell, Daphne W.] NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA.
   [Pollock, Pamela M.] Queensland Univ Technol, Inst Hlth & Biomed Innovat, Brisbane, Qld 4059, Australia.
   [Wang, Chen] Mayo Clin, Dept Biomed Stat & Informat, Rochester, MN 55905 USA.
   [Wheeler, David A.; Shinbrot, Eve] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA.
   [Shaw, Kenna R. Mills; Sheth, Margi; Davidsen, Tanja] NCI, Canc Genome Atlas Program Off, NIH, Bethesda, MD 20892 USA.
   Scimentis LLC, Atlanta, GA 30666 USA.
   [Ferguson, Martin L.] MLF Consulting, Arlington, MD 02474 USA.
   [Guyer, Mark S.; Ozenberger, Bradley A.; Sofia, Heidi J.] NHGRI, NIH, Bethesda, MD 20892 USA.
C3 Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Washington University (WUSTL); British Columbia Cancer Agency; 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; Dana-Farber Cancer Institute; University of Bergen; Haukeland University Hospital; University of Bergen; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard Medical School; Harvard University; Harvard Medical School; University of Texas System; UTMD Anderson Cancer Center; Harvard University; Harvard University Medical Affiliates; Boston Children'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 North Carolina; University of North Carolina Chapel Hill; University of North Carolina; University of North Carolina Chapel Hill; University of North Carolina; University of North Carolina Chapel Hill; Johns Hopkins University; Johns Hopkins Medicine; University of Southern California; Institute for Systems Biology (ISB); Memorial Sloan Kettering Cancer Center; Memorial Sloan Kettering Cancer Center; University of California System; University of California San Francisco; UCSF Medical Center; UCSF Helen Diller Family Comprehensive Cancer Center; Memorial Sloan Kettering Cancer Center; University of California System; University of California Santa Cruz; University of California System; University of California Santa Cruz; Buck Institute for Research on Aging; University of Texas System; UTMD Anderson Cancer Center; University of Texas System; UTMD Anderson Cancer Center; Tampere University; University of Texas System; UTMD Anderson Cancer Center; University of Texas System; UTMD Anderson Cancer Center; University System of Ohio; Ohio State University; Nationwide Childrens Hospital; Research Institute at Nationwide Children's Hospital; University System of Ohio; Ohio State University; University of North Carolina; University of North Carolina Chapel Hill; British Columbia Cancer Agency; University of British Columbia; Cedars Sinai Medical Center; Helen F. Graham Cancer Center & Research Institute; Christiana Care Health System; Duke University; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard Medical School; University of California System; University of California Irvine; University System of Ohio; Ohio State University; Nationwide Childrens Hospital; Research Institute at Nationwide Children's Hospital; International Genomics Consortium; Mayo Clinic; Mayo Clinic; Memorial Sloan Kettering Cancer Center; Memorial Sloan Kettering Cancer Center; N.N. Blokhin Russian Cancer Research Center; Russian Academy of Medical Sciences; Ontario Institute for Cancer Research; University of Toronto; London Health Sciences Centre; Russian Academy of Sciences; St. Petersburg Scientific Centre of the Russian Academy of Sciences; St Petersburg Academic University; University of Toronto; University Health Network Toronto; University of Hawaii System; Cedars Sinai Medical Center; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh; Washington University (WUSTL); SRA International; National Institutes of Health (NIH) - USA; NIH National Human Genome Research Institute (NHGRI); Queensland University of Technology (QUT); Mayo Clinic; Baylor College of Medicine; 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 Human Genome Research Institute (NHGRI)
RP Levine, DA (corresponding author), Mem Sloan Kettering Canc Ctr, Dept Surg, Gynecol Serv, New York, NY 10065 USA.
EM levine2@mskcc.org
FU US National Institutes of Health [5U24CA143799-04, 5U24CA143835-04, 5U24CA143840-04, 5U24CA143843-04, 5U24CA143845-04, 5U24CA143848-04, 5U24CA143858-04, 5U24CA143866-04, 5U24CA143867-04, 5U24CA143882-04, 5U24CA143883-04, 5U24CA144025-04, U54HG003067-11, U54HG003079-10, U54HG003273-10]; National Cancer Institute [P30CA016086, P30CA016056, P30CA008748, P30CA016672] Funding Source: NIH RePORTER; National Human Genome Research Institute [ZIAHG200338] Funding Source: NIH RePORTER; Direct For Biological Sciences [0845783] Funding Source: National Science Foundation; Div Of Biological Infrastructure [0845783] Funding Source: National Science Foundation
NR 39
TC 4423
Z9 4929
U1 13
U2 449
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 2
PY 2013
VL 497
IS 7447
BP 67
EP 73
DI 10.1038/nature12113
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 134OK
UT WOS:000318221500035
PM 23636398
DA 2026-03-09
ER

PT J
AU Yin, QZ
AF Yin, Qiuzhen
TI Insolation-induced mid-Brunhes transition in Southern Ocean ventilation and deep-ocean temperature
SO NATURE
LA English
DT Article
ID midpleistocene transition; carbon-dioxide; climate; record; hemisphere; atlantic; front
AB Glacial-interglacial cycles characterized by long cold periods interrupted by short periods of warmth are the dominant feature of Pleistocene climate, with the relative intensity and duration of past and future interglacials being of particular interest for civilization. The interglacials after 430,000 years ago were characterized by warmer climates(1,2) and higher atmospheric concentrations of carbon dioxide(3) than the interglacials before, but the cause of this climatic transition (the so-called mid-Brunhes event (MBE)) is unknown. Here I show, on the basis of model simulations, that in response to insolation changes only, feedbacks between sea ice, temperature, evaporation and salinity caused vigorous pre-MBE Antarctic bottom water formation and Southern Ocean ventilation. My results also show that strong westerlies increased the pre-MBE overturning in the Southern Ocean via an increased latitudinal insolation gradient created by changes in eccentricity during austral winter and by changes in obliquity during austral summer. The stronger bottom water formation led to a cooler deep ocean during the older interglacials. These insolation-induced differences in the deep-sea temperature and in the Southern Ocean ventilation between the more recent interglacials and the older ones were not expected, because there is no straightforward systematic difference in the astronomical parameters between the Interglacials before and after 430,000 years ago(4). Rather than being a real 'event', the apparent MBE seems to have resulted from a series of individual interglacial responses including notable exceptions to the general pattern to various combinations of insolation conditions. Consequently, assuming no anthropogenic interference, future interglacials may have pre- or post-MBE characteristics without there being a systematic change in forcings. These findings are a first step towards understanding the magnitude change of the interglacial carbon dioxide concentration around 430,000 years ago.
C1 Catholic Univ Louvain, Earth & Life Inst, Georges Lemaitre Ctr Earth & Climate Res, B-1348 Louvain, Belgium.
C3 Universite Catholique Louvain
RP Yin, QZ (corresponding author), Catholic Univ Louvain, Earth & Life Inst, Georges Lemaitre Ctr Earth & Climate Res, Chemin Cyclotron 2, B-1348 Louvain, Belgium.
EM qiuzhen.yin@uclouvain.be
FU European Research Council [227348]; Belgian National Fund for Scientific Research (FRS-FNRS); S. A. Electrabel, Belgium; European Research Council (ERC) [227348] Funding Source: European Research Council (ERC)
NR 22
TC 80
Z9 92
U1 1
U2 78
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 14
PY 2013
VL 494
IS 7436
BP 222
EP 225
DI 10.1038/nature11790
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 092QS
UT WOS:000315137700036
PM 23407538
DA 2026-03-09
ER

PT J
AU Ostrem, JM
   Peters, U
   Sos, ML
   Wells, JA
   Shokat, KM
AF Ostrem, Jonathan M.
   Peters, Ulf
   Sos, Martin L.
   Wells, James A.
   Shokat, Kevan M.
TI K-Ras(G12C) inhibitors allosterically control GTP affinity and effector interactions
SO NATURE
LA English
DT Article
ID oncogene product p21; h-ras p21; protein; kras; site; mutagenesis; discovery; mutation; reveals; domain
AB Somatic mutations in the small GTPase K-Ras are the most common activating lesions found in human cancer, and are generally associated with poor response to standard therapies(1-3). Efforts to target this oncogene directly have faced difficulties owing to its picomolar affinity for GTP/GDP(4) and the absence of known allosteric regulatory sites. Oncogenic mutations result in functional activation of Ras family proteins by impairing GTP hydrolysis(5,6). With diminished regulation by GTPase activity, the nucleotide state of Ras becomes more dependent on relative nucleotide affinity and concentration. This gives GTP an advantage over GDP(7) and increases the proportion of active GTP-bound Ras. Here we report the development of small molecules that irreversibly bind to a common oncogenic mutant, K-Ras(G12C). These compounds rely on the mutant cysteine for binding and therefore do not affect the wild-type protein. Crystallographic studies reveal the formation of a new pocket that is not apparent in previous structures of Ras, beneath the effector binding switch-II region. Binding of these inhibitors to K-Ras(G12C) disrupts both switch-I and switch-II, subverting the native nucleotide preference to favour GDP over GTP and impairing binding to Raf. Our data provide structure-based validation of a new allosteric regulatory site on Ras that is targetable in a mutant-specific manner.
C1 [Ostrem, Jonathan M.; Peters, Ulf; Sos, Martin L.; Shokat, Kevan M.] Univ Calif San Francisco, Howard Hughes Med Inst, Dept Cellular & Mol Pharmacol, San Francisco, CA 94158 USA.
   [Wells, James A.] Univ Calif San Francisco, Dept Pharmaceut Chem, San Francisco, CA 94158 USA.
   [Wells, James A.] Univ Calif San Francisco, Dept Cellular & Mol Pharmacol, San Francisco, CA 94158 USA.
C3 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 Shokat, KM (corresponding author), Univ Calif San Francisco, Howard Hughes Med Inst, Dept Cellular & Mol Pharmacol, San Francisco, CA 94158 USA.
EM kevan.shokat@ucsf.edu
FU postdoctoral fellowship of the Tobacco-related Disease Research Program [19FT-0069]; Office of Science, Office of Basic Energy Sciences, of the US Department of Energy [DE-AC02-05CH11231]; Prostate Cancer Foundation (PCF); National Institute of General Medical Sciences [T32GM064337] Funding Source: NIH RePORTER
NR 30
TC 1977
Z9 2535
U1 24
U2 480
PU NATURE PUBLISHING 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 28
PY 2013
VL 503
IS 7477
BP 548
EP +
DI 10.1038/nature12796
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 258MU
UT WOS:000327464200048
PM 24256730
DA 2026-03-09
ER

PT J
AU Gafni, O
   Weinberger, L
   Mansour, AA
   Manor, YS
   Chomsky, E
   Ben-Yosef, D
   Kalma, Y
   Viukov, S
   Maza, I
   Zviran, A
   Rais, Y
   Shipony, Z
   Mukamel, Z
   Krupalnik, V
   Zerbib, M
   Geula, S
   Caspi, I
   Schneir, D
   Shwartz, T
   Gilad, S
   Amann-Zalcenstein, D
   Benjamin, S
   Amit, I
   Tanay, A
   Massarwa, R
   Novershtern, N
   Hanna, JH
AF Gafni, Ohad
   Weinberger, Leehee
   Mansour, Abed AlFatah
   Manor, Yair S.
   Chomsky, Elad
   Ben-Yosef, Dalit
   Kalma, Yael
   Viukov, Sergey
   Maza, Itay
   Zviran, Asaf
   Rais, Yoach
   Shipony, Zohar
   Mukamel, Zohar
   Krupalnik, Vladislav
   Zerbib, Mirie
   Geula, Shay
   Caspi, Inbal
   Schneir, Dan
   Shwartz, Tamar
   Gilad, Shlomit
   Amann-Zalcenstein, Daniela
   Benjamin, Sima
   Amit, Ido
   Tanay, Amos
   Massarwa, Rada
   Novershtern, Noa
   Hanna, Jacob H.
TI Derivation of novel human ground state naive pluripotent stem cells
SO NATURE
LA English
DT Article
ID demethylation; inactivation; inhibition
AB Mouse embryonic stem (ES) cells are isolated from the inner cell mass of blastocysts, and can be preserved in vitro in a naive inner-cell-mass-like configuration by providing exogenous stimulation with leukaemia inhibitory factor (LIF) and small molecule inhibition of ERK1/ERK2 and GSK3 beta signalling (termed 2i/LIF conditions)(1,2). Hallmarks of naive pluripotency include driving Oct4 (also known as Pou5f1) transcription by its distal enhancer, retaining a pre-inactivation Xchromosome state, and global reduction in DNA methylation and in H3K27me3 repressive chromatin mark deposition on developmental regulatory gene promoters(3). Upon withdrawal of 2i/LIF, naive mouse ES cells can drift towards a primed pluripotent state resembling that of the post-implantation epiblast(4). Although human ES cells share several molecular features with naive mouse ES cells(5), they also share a variety of epigenetic properties with primed murine epiblast stemcells (EpiSCs)(6,7). These include predominant use of the proximal enhancer element to maintain OCT4 expression, pronounced tendency for X chromosome inactivation in most female human ES cells, increase in DNA methylation and prominent deposition of H3K27me3 and bivalent domain acquisition on lineage regulatory genes(7). The feasibility of establishing human ground state naive pluripotency in vitro with equivalent molecular and functional features to those characterized in mouse ES cells remains to be defined(1). Here we establish defined conditions that facilitate the derivation of genetically unmodified human naive pluripotent stem cells from already established primed human ES cells, from somatic cells through induced pluripotent stem(iPS) cell reprogramming or directly from blastocysts. The novel naive pluripotent cells validated herein retain molecular characteristics and functional properties that are highly similar to mouse naive ES cells, and distinct from conventional primed human pluripotent cells. This includes competence in the generation of cross-species chimaeric mouse embryos that underwent organogenesis following microinjection of human naive iPS cells into mouse morulas. Collectively, our findings establish new avenues for regenerative medicine, patient-specific iPS cell disease modelling and the study of early human development in vitro and in vivo.
C1 [Gafni, Ohad; Weinberger, Leehee; Mansour, Abed AlFatah; Manor, Yair S.; Chomsky, Elad; Viukov, Sergey; Maza, Itay; Zviran, Asaf; Rais, Yoach; Krupalnik, Vladislav; Zerbib, Mirie; Geula, Shay; Caspi, Inbal; Schneir, Dan; Massarwa, Rada; Novershtern, Noa; Hanna, Jacob H.] Weizmann Inst Sci, Dept Mol Genet, IL-76100 Rehovot, Israel.
   [Chomsky, Elad; Shipony, Zohar; Mukamel, Zohar; Tanay, Amos] Weizmann Inst Sci, Dept Regulat Biol, IL-76100 Rehovot, Israel.
   [Chomsky, Elad; Shipony, Zohar; Mukamel, Zohar; Tanay, Amos] Weizmann Inst Sci, Dept Comp Sci & Appl Math, IL-76100 Rehovot, Israel.
   [Ben-Yosef, Dalit; Kalma, Yael; Shwartz, Tamar] Tel Aviv Univ, Tel Aviv Sourasky Med Ctr, Lis Matern Hosp, Wolfe PGD Stem Cell Lab,Racine IVF Unit, IL-69978 Tel Aviv, Israel.
   [Ben-Yosef, Dalit] Tel Aviv Univ, Sackler Sch Med, Dept Cell & Dev Biol, IL-69978 Tel Aviv, Israel.
   [Gilad, Shlomit; Amann-Zalcenstein, Daniela; Benjamin, Sima] Weizmann Inst Sci, INCPM, IL-76100 Rehovot, Israel.
   [Amit, Ido] Weizmann Inst Sci, Dept Immunol, IL-76100 Rehovot, Israel.
C3 Weizmann Institute of Science; Weizmann Institute of Science; Weizmann Institute of Science; Tel Aviv University; Sackler Faculty of Medicine; Tel Aviv Sourasky Medical Center; Tel Aviv University; Sackler Faculty of Medicine; Weizmann Institute of Science; Weizmann Institute of Science
RP Hanna, JH (corresponding author), Weizmann Inst Sci, Dept Mol Genet, IL-76100 Rehovot, Israel.
EM rada.massarwa@weizmann.ac.il; noa.novershtern@weizmann.ac.il; jacob.hanna@weizmann.ac.il
FU Ilana and Pascal Mantoux; European Research Council [StG-2011-281906]; Leona M. and Harry B. Helmsley Charitable Trust; BIRAX (Britain Israel Research and Academic Exchange Partnership); Sir Charles Clore Research Prize; Israel Science Foundation (Bikura, ICORE (Israeli Centre of Research Excellence) and Regular research program); Israel Cancer Research Foundation; ERANET E-Rare disease program; Benoziyo Endowment fund; Fritz Thyssen Stiftung; EMBO; Alon Foundation scholar award; ICRF; Weizmann Dean fellowship award
NR 29
TC 860
Z9 1054
U1 1
U2 270
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 12
PY 2013
VL 504
IS 7479
BP 282
EP +
DI 10.1038/nature12745
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 267TQ
UT WOS:000328121500037
PM 24172903
DA 2026-03-09
ER

PT J
AU Allen, V
   Bates, KT
   Li, ZH
   Hutchinson, JR
AF Allen, Vivian
   Bates, Karl T.
   Li, Zhiheng
   Hutchinson, John R.
TI Linking the evolution of body shape and locomotor biomechanics in bird-line archosaurs
SO NATURE
LA English
DT Article
ID electromyographic analysis; limb function; performance; theropods; mechanics; walking; flight
AB Locomotion in living birds (Neornithes) has two remarkable features: feather-assisted flight, and the use of unusually crouched hindlimbs for bipedal support and movement. When and how these defining functional traits evolved remains controversial(1-8). However, the advent of computer modelling approaches and the discoveries of exceptionally preserved key specimens now make it possible to use quantitative data on whole-body morphology to address the biomechanics underlying this issue. Here we use digital body reconstructions to quantify evolutionary trends in locomotor biomechanics (whole-body proportions and centre-of-mass position) across the clade Archosauria. We use three-dimensional digital reconstruction to estimate body shape from skeletal dimensions for 17 archosaurs along the ancestral bird line, including the exceptionally preserved, feathered taxa Microraptor, Archaeopteryx, Pengornis and Yixia-nornis, which represent key stages in the evolution of the avian body plan. Rather than a discrete transition from more-upright postures in the basal-most birds (Avialae) and their immediate outgroup deinonychosauria(5,6), our results support hypotheses of a gradual, stepwise acquisition of more-crouched limb postures across much of theropod evolution(1-4), although we find evidence of an accelerated change within the clade Maniraptora (birds and their closest relatives, such as deinonychosaurs). In addition, whereas reduction of the tail is widely accepted to be the primary morphological factor correlated with centre-of-mass position and, hence, evolution of hindlimb posture(1-8), we instead find that enlargement of the pectoral limb and several associated trends have a much stronger influence. Intriguingly, our support for the onset of accelerated morpho-functional trends within Maniraptora is closely correlated with the evolution of flight. Because we find that the evolution of enlarged forelimbs is strongly linked, via whole-body centre of mass, to hindlimb function during terrestrial locomotion, we suggest that the evolution of avian flight is linked to anatomical novelties in the pelvic limb as well as the pectoral.
C1 [Allen, Vivian] Univ Jena, Inst Spezielle Zool & Evolut Biol, D-07743 Jena, Germany.
   [Allen, Vivian; Hutchinson, John R.] Univ London Royal Vet Coll, Struct & Mot Lab, Hatfield AL9 7TA, Herts, England.
   [Bates, Karl T.] Univ Liverpool, Inst Ageing & Chron Dis, Dept Musculoskeletal Biol 2, Liverpool L69 3GA, Merseyside, England.
   [Li, Zhiheng] Chinese Acad Sci, Inst Vertebrate Paleontol & Paleoanthropol, Key Lab Evolutionary Systemat Vertebrates, Beijing 100034, Peoples R China.
   [Li, Zhiheng] Univ Texas Austin, Dept Geol Sci, Austin, TX 78712 USA.
C3 Friedrich Schiller University of Jena; University of London; University of London Royal Veterinary College; University of Liverpool; Chinese Academy of Sciences; Institute of Vertebrate Paleontology & Paleoanthropology, CAS; University of Texas System; University of Texas Austin
RP Hutchinson, JR (corresponding author), Univ London Royal Vet Coll, Struct & Mot Lab, Hatfield AL9 7TA, Herts, England.
EM jrhutch@rvc.ac.uk
FU NERC [NE/G005877/1]; Royal Society International Joint Project; Sam and Doris Welles Fund (University of California); Natural Environment Research Council [NE/G005877/1] Funding Source: researchfish; NERC [NE/G005877/1] Funding Source: UKRI
CR Allen V, 2009, ANAT REC, V292, P1442, DOI 10.1002/ar.20973
   Bates KT, 2009, PLOS ONE, V4, P0, DOI 10.1371/journal.pone.0004532
   Biewener AA, 2004, J APPL PHYSIOL, V97, P2266, DOI 10.1152/japplphysiol.00003.2004
   Carrano MT, 1999, J MORPHOL, V240, P237, DOI 10.1002/(SICI)1097-4687(199906)240:3<237::AID-JMOR3>3.0.CO;2-N
   Chatterjee S, 2007, P NATL ACAD SCI USA, V104, P1576, DOI 10.1073/pnas.0609975104
   Christiansen P, 2002, J ORNITHOL, V143, P356
   CLARK J, 1975, J ZOOL, V176, P87
   Farlow JO, 2000, AM ZOOL, V40, P640, DOI 10.1668/0003-1569(2000)040[0640:TL]2.0.CO;2
   Gatesy SM, 1999, J MORPHOL, V240, P127, DOI 10.1002/(SICI)1097-4687(199905)240:2<127::AID-JMOR4>3.0.CO;2-Q
   GATESY SM, 1990, PALEOBIOLOGY, V16, P170, DOI 10.1017/S0094837300009866
   GATESY SM, 1991, J MORPHOL, V209, P83, DOI 10.1002/jmor.1052090107
   Gatesy SM, 1996, EVOLUTION, V50, P331, DOI 10.1111/j.1558-5646.1996.tb04496.x
   Gatesy SM, 1997, J VERTEBR PALEONTOL, V17, P308, DOI 10.1080/02724634.1997.10010977
   Gatesy SM, 1997, J MORPHOL, V234, P197, DOI 10.1002/(SICI)1097-4687(199711)234:2<197::AID-JMOR6>3.0.CO;2-9
   GATESY SM, 1995, FUNCTIONAL MORPHOLOGY IN VERTEBRATE PALEONTOLOGY, V0, P219
   Hancock JA, 2007, IBIS, V149, P605, DOI 10.1111/j.1474-919X.2007.00688.x
   Herr H, 2008, J EXP BIOL, V211, P467, DOI 10.1242/jeb.008573
   Hutchinson JR, 2001, COMP BIOCH PHYSL A, V131, P169
   Hutchinson JR, 2007, J THEOR BIOL, V246, P660, DOI 10.1016/j.jtbi.2007.01.023
   Hutchinson JR, 2011, PLOS ONE, V6, P0, DOI 10.1371/journal.pone.0026037
   Hutchinson JR, 2009, NATURWISSENSCHAFTEN, V96, P423, DOI 10.1007/s00114-008-0488-3
   Hutchinson JR, 2004, J MORPHOL, V262, P421, DOI 10.1002/jmor.10241
   Hutchinson JR, 2000, PALEOBIOLOGY, V26, P734, DOI 10.1666/0094-8373(2000)026<0734:AAATEO>2.0.CO;2
   Jones TD, 2000, NATURE, V406, P716, DOI 10.1038/35021041
   Marsh RL, 2006, J EXP BIOL, V209, P2050, DOI 10.1242/jeb.02226
   Persons WS, 2011, ANAT REC, V294, P119, DOI 10.1002/ar.21290
   Roberts TJ, 2002, J EXP BIOL, V205, P1485
   Roberts TJ, 1998, J EXP BIOL, V201, P2753
   TARSITANO S, 1983, ACTA PALAEONTOLOGICA POLONICA, V28, P251
   Turner AH, 2007, SCIENCE, V317, P1721, DOI 10.1126/science.1145076
NR 30
TC 112
Z9 126
U1 1
U2 187
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 2
PY 2013
VL 497
IS 7447
BP 104
EP 107
DI 10.1038/nature12059
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 134OK
UT WOS:000318221500042
PM 23615616
DA 2026-03-09
ER

PT J
AU Voloch-Bloch, N
   Lereah, Y
   Lilach, Y
   Gover, A
   Arie, A
AF Voloch-Bloch, Noa
   Lereah, Yossi
   Lilach, Yigal
   Gover, Avraham
   Arie, Ady
TI Generation of electron Airy beams
SO NATURE
LA English
DT Article
ID orbital angular-momentum; vortex beams; wave; laser
AB Within the framework of quantum mechanics, a unique particle wave packet exists(1) in the form of the Airy function(2,3). Its counter-intuitive properties are revealed as it propagates in time or space; the quantum probability wave packet preserves its shape despite dispersion or diffraction and propagates along a parabolic caustic trajectory, even though no force is applied. This does not contradict Newton's laws of motion, because the wave packet centroid propagates along a straight line. Nearly 30 years later, this wave packet, known as an accelerating Airy beam, was realized(4) in the optical domain; later it was generalized to an orthogonal and complete family of beams(5) that propagate along parabolic trajectories, as well as to beams that propagate along arbitrary convex trajectories(6). Here we report the experimental generation and observation of the Airy beams of free electrons. These electron Airy beams were generated by diffraction of electrons through a nanoscale hologram(7-9), which imprinted on the electrons' wavefunction a cubic phase modulation in the transverse plane. The highest-intensity lobes of the generated beams indeed followed parabolic trajectories. We directly observed a non-spreading electron wavefunction that self-heals(10), restoring its original shape after passing an obstacle. This holographic generation of electron Airy beams opens up. new avenues for steering electronic wave packets like their photonic counterparts, because the wave packets can be imprinted with arbitrary shapes(5) or trajectories(6).
C1 [Voloch-Bloch, Noa; Lereah, Yossi; Lilach, Yigal; Gover, Avraham; Arie, Ady] Tel Aviv Univ, Dept Phys Elect, Sch Elect Engn, Fleischman Fac Engn, IL-69978 Tel Aviv, Israel.
C3 Tel Aviv University
RP Voloch-Bloch, N (corresponding author), Tel Aviv Univ, Dept Phys Elect, Sch Elect Engn, Fleischman Fac Engn, IL-69978 Tel Aviv, Israel.
EM noavoloch@gmail.com
FU Israel Science Foundation; Israeli Ministry of Science
NR 27
TC 403
Z9 429
U1 2
U2 273
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 21
PY 2013
VL 494
IS 7437
BP 331
EP 335
DI 10.1038/nature11840
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 095CS
UT WOS:000315312900033
PM 23426323
DA 2026-03-09
ER

PT J
AU Atwood, SX
   Li, MC
   Lee, A
   Tang, JY
   Oro, AE
AF Atwood, Scott X.
   Li, Mischa
   Lee, Alex
   Tang, Jean Y.
   Oro, Anthony E.
TI GLI activation by atypical protein kinase C ι/λ regulates the growth of basal cell carcinomas
SO NATURE
LA English
DT Article
ID hedgehog pathway; gene; resistance
AB Growth of basal cell carcinomas (BCCs) requires high levels of hedgehog (HH) signalling through the transcription factor GLI(1). Although inhibitors of membrane protein smoothened (SMO) effectively suppress HH signalling, early tumour resistance illustrates the need for additional downstream targets for therapy(1-6). Here we identify atypical protein kinase C (aPKC-iota/lambda) as a novel GLI regulator in mammals. aPKC-iota/lambda and its polarity signalling partners' co-localize at the centrosome and form a complex with missing-in-metastasis (MIM), a scaffolding protein that potentiates HH signalling(8,9). Genetic or pharmacological loss of aPKC-iota/lambda function blocks HH signalling and proliferation of BCC cells. Prkci is a HH target gene that forms a positive feedback loop with GLI and exists at increased levels in BCCs. Genome-wide transcriptional profiling shows that aPKC-iota/lambda? and SMO control the expression of similar genes in tumour cells. aPKC-iota/lambda functions downstream of SMO to phosphorylate and activate GLI1, resulting in maximal DNA binding and transcriptional activation. Activated aPKC-iota/lambda. is upregulated in SMO-inhibitor-resistant tumours and targeting aPKC-iota/lambda suppresses signalling and growth of resistant BCC cell lines. These results demonstrate that aPKC-iota/lambda is critical for HH-dependent processes and implicates aPKC-iota/lambda as a new, tumour-selective therapeutic target for the treatment of SMO-inhibitor-resistant cancers. [GRAPHICS] .
C1 [Atwood, Scott X.; Li, Mischa; Lee, Alex; Tang, Jean Y.; Oro, Anthony E.] Stanford Univ, Sch Med, Program Epithelial Biol, Stanford, CA 94305 USA.
C3 Stanford University
RP Oro, AE (corresponding author), Stanford Univ, Sch Med, Program Epithelial Biol, Stanford, CA 94305 USA.
EM satwood@stanford.edu; oro@stanford.edu
FU NIH NRSA [1F32CA14208701]; NIH [AR052785, AR046786]; National Cancer Institute [T32CA009302] Funding Source: NIH RePORTER; National Institute of Arthritis and Musculoskeletal and Skin Diseases [R01AR046786] Funding Source: NIH RePORTER
NR 21
TC 210
Z9 250
U1 0
U2 43
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 28
PY 2013
VL 494
IS 7438
BP 484
EP 488
DI 10.1038/nature11889
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 099YI
UT WOS:000315661500040
PM 23446420
DA 2026-03-09
ER

PT J
AU Briggs, F
   Mangun, GR
   Usrey, WM
AF Briggs, Farran
   Mangun, George R.
   Usrey, W. Martin
TI Attention enhances synaptic efficacy and the signal-to-noise ratio in neural circuits
SO NATURE
LA English
DT Article
ID primary visual-cortex; lateral geniculate-nucleus; macaque area v4; selective attention; spatial attention; neuronal responses; simple cells; monkey; v1; performance
AB Attention is a critical component of perception(1). However, the mechanisms by which attention modulates neuronal communication to guide behaviour are poorly understood. To elucidate the synaptic mechanisms of attention, we developed a sensitive assay of attentional modulation of neuronal communication. In alert monkeys performing a visual spatial attention task, we probed thalamocortical communication by electrically stimulating neurons in the lateral geniculate nucleus of the thalamus while simultaneously recording shock-evoked responses from monosynaptically connected neurons in primary visual cortex. We found that attention enhances neuronal communication by increasing the efficacy of presynaptic input in driving postsynaptic responses, by increasing synchronous responses among ensembles of postsynaptic neurons receiving independent input, and by decreasing redundant signals between postsynaptic neurons receiving common input. The results demonstrate that attention finely tunes neuronal communication at the synaptic level by selectively altering synaptic weights, enabling enhanced detection of salient events in the noisy sensory environment.
C1 [Briggs, Farran; Usrey, W. Martin] Univ Calif Davis, Ctr Neurosci, Davis, CA 95618 USA.
   [Briggs, Farran] Geisel Sch Med Dartmouth, Dept Physiol & Neurobiol, Lebanon, NH 03756 USA.
   [Mangun, George R.] Univ Calif Davis, Ctr Mind & Brain, Davis, CA 95618 USA.
   [Mangun, George R.] Univ Calif Davis, Dept Psychol, Davis, CA 95616 USA.
   [Mangun, George R.; Usrey, W. Martin] Univ Calif Davis, Dept Neurol, Sacramento, CA 95817 USA.
   [Usrey, W. Martin] Univ Calif Davis, Dept Neurobiol Physiol & Behav, Davis, CA 95616 USA.
C3 University of California System; University of California Davis; Dartmouth College; University of California System; University of California Davis; University of California System; University of California Davis; University of California System; University of California Davis; University of California System; University of California Davis
RP Usrey, WM (corresponding author), Univ Calif Davis, Ctr Neurosci, 1544 Newton Court, Davis, CA 95618 USA.
EM wmusrey@ucdavis.edu
FU National Institutes of Health [EY18683, EY013588, MH055714]; NSF [BCS-0727115, 1228535]; National Eye Institute [R01EY013588] Funding Source: NIH RePORTER; Direct For Social, Behav & Economic Scie [1228535] Funding Source: National Science Foundation; Division Of Behavioral and Cognitive Sci [1228535] Funding Source: National Science Foundation
NR 34
TC 151
Z9 194
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 JUL 25
PY 2013
VL 499
IS 7459
BP 476
EP +
DI 10.1038/nature12276
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 187YP
UT WOS:000322157900040
PM 23803766
DA 2026-03-09
ER

PT J
AU Xiong, XL
   Coombs, PJ
   Martin, SR
   Liu, JF
   Xiao, HX
   McCauley, JW
   Locher, K
   Walker, PA
   Collins, PJ
   Kawaoka, Y
   Skehel, JJ
   Gamblin, SJ
AF Xiong, Xiaoli
   Coombs, Peter J.
   Martin, Stephen R.
   Liu, Junfeng
   Xiao, Haixia
   McCauley, John W.
   Locher, Kathrin
   Walker, Philip A.
   Collins, Patrick J.
   Kawaoka, Yoshihiro
   Skehel, John J.
   Gamblin, Steven J.
TI Receptor binding by a ferret-transmissible H5 avian influenza virus
SO NATURE
LA English
DT Article
ID a virus; hemagglutinin; specificity; evolution; selection; variants; mammals; fusion; cell; h2
AB Cell-surface-receptor binding by influenza viruses is a key determinant of their transmissibility, both from avian and animal species to humans as well as from human to human. Highly pathogenic avian H5N1 viruses that are a threat to public health have been observed to acquire affinity for human receptors, and transmissible-mutant-selection experiments have identified a virus that is transmissible in ferrets(1-3), the generally accepted experimental model for influenza in humans. Here, our quantitative biophysical measurements of the receptor-binding properties of haemagglutinin (HA) from the transmissible mutant indicate a small increase in affinity for human receptor and a marked decrease in affinity for avian receptor. From analysis of virus and HA binding data we have derived an algorithm that predicts virus avidity from the affinity of individual HA-receptor interactions. It reveals that the transmissible-mutant virus has a 200-fold preference for binding human over avian receptors. The crystal structure of the transmissible-mutant HA in complex with receptor analogues shows that it has acquired the ability to bind human receptor in the same folded-back conformation as seen for HA from the 1918, 1957 (ref. 4), 1968 (ref. 5) and 2009 (ref. 6) pandemic viruses. This binding mode is substantially different from that by which non-transmissible wild-type H5 virus HA binds human receptor. The structure of the complex also explains how the change in preference from avian to human receptors arises from the Gln226Leu substitution, which facilitates binding to human receptor but restricts binding to avian receptor. Both features probably contribute to the acquisition of transmissibility by this mutant virus.
C1 [Xiong, Xiaoli; Coombs, Peter J.; Martin, Stephen R.; Xiao, Haixia; McCauley, John W.; Walker, Philip A.; Collins, Patrick J.; Skehel, John J.; Gamblin, Steven J.] Natl Inst Med Res, MRC, London NW7 1AA, England.
   [Liu, Junfeng] China Agr Univ, Minist Agr, Key Lab Plant Pathol, Beijing 100193, Peoples R China.
   [Locher, Kathrin] Novartis Inst BioMed Res, CH-4057 Basel, Switzerland.
   [Kawaoka, Yoshihiro] Univ Wisconsin Madison, Dept Pathobiol Sci, Madison, WI 53711 USA.
C3 MRC National Institute for Medical Research; China Agricultural University; Novartis; University of Wisconsin System; University of Wisconsin Madison
RP Gamblin, SJ (corresponding author), Natl Inst Med Res, MRC, Mill Hill, London NW7 1AA, England.
EM skeheljj@nimr.mrc.ac.uk; sgambli@nimr.mrc.ac.uk
FU BBSRC [BB/E010806]; Medical Research Council [U117584222, U117512723, U117570592]; Medical Research Council [MC_U117512723, MC_U117584222] Funding Source: researchfish; MRC [MC_U117512723, MC_U117584222] Funding Source: UKRI
NR 30
TC 193
Z9 215
U1 0
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 MAY 16
PY 2013
VL 497
IS 7449
BP 392
EP +
DI 10.1038/nature12144
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 144PN
UT WOS:000318952000043
PM 23615615
DA 2026-03-09
ER

PT J
AU Barry, ER
   Morikawa, T
   Butler, BL
   Shrestha, K
   de la Rosa, R
   Yan, KS
   Fuchs, CS
   Magness, ST
   Smits, R
   Ogino, S
   Kuo, CJ
   Camargo, FD
AF Barry, Evan R.
   Morikawa, Teppei
   Butler, Brian L.
   Shrestha, Kriti
   de la Rosa, Rosemarie
   Yan, Kelley S.
   Fuchs, Charles S.
   Magness, Scott T.
   Smits, Ron
   Ogino, Shuji
   Kuo, Calvin J.
   Camargo, Fernando D.
TI Restriction of intestinal stem cell expansion and the regenerative response by YAP
SO NATURE
LA English
DT Article
ID hippo signaling pathway; wnt/beta-catenin; colorectal-cancer; in-vitro; mouse model; expression; homeostasis; epithelium; crypt; lgr5
AB A remarkable feature of regenerative processes is their ability to halt proliferation once an organ's structure has been restored. The Wnt signalling pathway is the major driving force for homeostatic self-renewal and regeneration in the mammalian intestine. However, the mechanisms that counterbalance Wnt-driven proliferation are poorly understood. Here we demonstrate in mice and humans that yes-associated protein 1 (YAP; also known as YAP1)-a protein known for its powerful growth-inducing and oncogenic properties(1,2)-has an unexpected growth-suppressive function, restricting Wnt signals during intestinal regeneration. Transgenic expression of YAP reduces Wnt target gene expression and results in the rapid loss of intestinal crypts. In addition, loss of YAP results in Wnt hypersensitivity during regeneration, leading to hyperplasia, expansion of intestinal stem cells and niche cells, and formation of ectopic crypts and microadenomas. We find that cytoplasmic YAP restricts elevated Wnt signalling independently of the AXIN-APC-GSK-3 beta complex partly by limiting the activity of dishevelled (DVL). DVL signals in the nucleus of intestinal stem cells, and its forced expression leads to enhanced Wnt signalling in crypts. YAP dampens Wnt signals by restricting DVL nuclear translocation during regenerative growth. Finally, we provide evidence that YAP is silenced in a subset of highly aggressive and undifferentiated human colorectal carcinomas, and that its expression can restrict the growth of colorectal carcinoma xenografts. Collectively, our work describes a novel mechanistic paradigm for how proliferative signals are counterbalanced in regenerating tissues. Additionally, our findings have important implications for the targeting of YAP in human malignancies.
C1 [Barry, Evan R.; Butler, Brian L.; Shrestha, Kriti; de la Rosa, Rosemarie; Camargo, Fernando D.] Childrens Hosp, Stem Cell Program, Boston, MA 02115 USA.
   [Barry, Evan R.; Butler, Brian L.; Shrestha, Kriti; de la Rosa, Rosemarie; Camargo, Fernando D.] Childrens Hosp, Dept Hematol Oncol, Boston, MA 02115 USA.
   [Barry, Evan R.; Butler, Brian L.; Camargo, Fernando D.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA.
   [Barry, Evan R.; Camargo, Fernando D.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA.
   [Morikawa, Teppei; Fuchs, Charles S.; Ogino, Shuji] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA.
   [Morikawa, Teppei; Fuchs, Charles S.; Ogino, Shuji] Harvard Univ, Sch Med, Boston, MA 02215 USA.
   [Yan, Kelley S.; Kuo, Calvin J.] Stanford Univ, Dept Med, Div Hematol, Stanford, CA 94305 USA.
   [Fuchs, Charles S.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA.
   [Fuchs, Charles S.; Ogino, Shuji] Harvard Univ, Sch Med, Boston, MA 02115 USA.
   [Magness, Scott T.] Univ N Carolina, Dept Med, Chapel Hill, NC 27599 USA.
   [Magness, Scott T.] Univ N Carolina, Dept Biomed Engn, Chapel Hill, NC 27599 USA.
   [Smits, Ron] Erasmus MC, Dept Gastroenterol & Hepatol, NL-3000 CA Rotterdam, Netherlands.
   [Ogino, Shuji] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
C3 Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Harvard University; Harvard University; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard Medical School; Stanford University; Harvard University; Harvard University Medical Affiliates; Brigham & Women'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; Erasmus University Rotterdam; Erasmus MC; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital
RP Camargo, FD (corresponding author), Childrens Hosp, Stem Cell Program, 300 Longwood Ave, Boston, MA 02115 USA.
EM Fernando.camargo@childrens.harvard.edu
FU Stand Up to Cancer-AACR initiative; National Institutes of Health [R01 CA131426, AR064036]; Harvard Stem Cell Institute; American Cancer Society Illinois Division [PF-12-245-01-CCG]; CIRM [1K08DK096048];  [1U01DK085527];  [R01 CA151993];  [R01 DK091427];  [P01CA87969];  [P50CA127003]; National Cancer Institute [P50CA127003] Funding Source: NIH RePORTER; National Institute of Diabetes and Digestive and Kidney Diseases [U01DK085527] Funding Source: NIH RePORTER
NR 39
TC 465
Z9 560
U1 0
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 JAN 3
PY 2013
VL 493
IS 7430
BP 106
EP +
DI 10.1038/nature11693
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 062QC
UT WOS:000312933800040
PM 23178811
DA 2026-03-09
ER

PT J
AU Chen, BT
   Yau, HJ
   Hatch, C
   Kusumoto-Yoshida, I
   Cho, SL
   Hopf, FW
   Bonci, A
AF Chen, Billy T.
   Yau, Hau-Jie
   Hatch, Christina
   Kusumoto-Yoshida, Ikue
   Cho, Saemi L.
   Hopf, F. Woodward
   Bonci, Antonello
TI Rescuing cocaine-induced prefrontal cortex hypoactivity prevents compulsive cocaine seeking
SO NATURE
LA English
DT Article
ID pyramidal cells; drug seeking; rat; addiction; interneurons; dysfunction; extinction; channels; behavior
AB Loss of control over harmful drug seeking is one of the most intractable aspects of addiction, as human substance abusers continue to pursue drugs despite incurring significant negative consequences(1). Human studies have suggested that deficits in prefrontal cortical function and consequential loss of inhibitory control(2-4) could be crucial in promoting compulsive drug use. However, it remains unknown whether chronic drug use compromises cortical activity and, equally important, whether this deficit promotes compulsive cocaine seeking. Here we use a rat model of compulsive drug seeking(5-8) in which cocaine seeking persists in a subgroup of rats despite delivery of noxious foot shocks. We show that prolonged cocaine self-administration decreases ex vivo intrinsic excitability of deep-layer pyramidal neurons in the prelimbic cortex, which was significantly more pronounced in compulsive drug-seeking animals. Furthermore, compensating for hypoactive prelimbic cortex neurons with in vivo optogenetic prelimbic cortex stimulation significantly prevented compulsive cocaine seeking, whereas optogenetic prelimbic cortex inhibition significantly increased compulsive cocaine seeking. Our results show a marked reduction in prelimbic cortex excitability in compulsive cocaine-seeking rats, and that in vivo optogenetic prelimbic cortex stimulation decreased compulsive drug-seeking behaviours. Thus, targeted stimulation of the prefrontal cortex could serve as a promising therapy for treating compulsive drug use.
C1 [Chen, Billy T.; Yau, Hau-Jie; Hatch, Christina; Kusumoto-Yoshida, Ikue; Bonci, Antonello] NIDA, Intramural Res Program, Baltimore, MD 21224 USA.
   [Cho, Saemi L.; Hopf, F. Woodward] Univ Calif San Francisco, Dept Neurol, Ernest Gallo Clin & Res Ctr, San Francisco, CA 94608 USA.
   [Hopf, F. Woodward; Bonci, Antonello] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94110 USA.
   [Bonci, Antonello] Johns Hopkins Sch Med, Solomon H Snyder Neurosci Inst, Baltimore, MD 21205 USA.
C3 National Institutes of Health (NIH) - USA; NIH National Institute on Drug Abuse (NIDA); University of California System; University of California San Francisco; Ernest Gallo Clinic & Research Center; University of California System; University of California San Francisco; Johns Hopkins University; Johns Hopkins Medicine
RP Chen, BT (corresponding author), NIDA, Intramural Res Program, Baltimore, MD 21224 USA.
EM billy.chen@nih.gov; antonello.bonci@nih.gov
FU NIDA/IRP; State of California through the University of California at San Francisco
NR 30
TC 403
Z9 496
U1 0
U2 123
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 18
PY 2013
VL 496
IS 7445
BP 359
EP +
DI 10.1038/nature12024
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 126FV
UT WOS:000317599200037
PM 23552889
DA 2026-03-09
ER

PT J
AU Uzureau, P
   Uzureau, S
   Lecordier, L
   Fontaine, F
   Tebabi, P
   Homblé, F
   Grélard, A
   Zhendre, V
   Nolan, DP
   Lins, L
   Crowet, JM
   Pays, A
   Felu, C
   Poelvoorde, P
   Vanhollebeke, B
   Moestrup, SK
   Lyngso, J
   Pedersen, JS
   Mottram, JC
   Dufourc, EJ
   Pérez-Morga, D
   Pays, E
AF Uzureau, Pierrick
   Uzureau, Sophie
   Lecordier, Laurence
   Fontaine, Frederic
   Tebabi, Patricia
   Homble, Fabrice
   Grelard, Axelle
   Zhendre, Vanessa
   Nolan, Derek P.
   Lins, Laurence
   Crowet, Jean-Marc
   Pays, Annette
   Felu, Cecile
   Poelvoorde, Philippe
   Vanhollebeke, Benoit
   Moestrup, Soren K.
   Lyngso, Jeppe
   Pedersen, Jan Skov
   Mottram, Jeremy C.
   Dufourc, Erick J.
   Perez-Morga, David
   Pays, Etienne
TI Mechanism of Trypanosoma brucei gambiense resistance to human serum
SO NATURE
LA English
DT Article
ID blood-stream forms; haptoglobin-hemoglobin receptor; lytic factor; trypanolytic factor; expression; gene; differentiation; glycoprotein; aggregation; membranes
AB The African parasite Trypanosoma brucei gambiense accounts for 97% of human sleeping sickness cases(1). T. b. gambiense resists the specific human innate immunity acting against several other tsetsefly-transmitted trypanosome species such as T. b. brucei, the causative agent of nagana disease in cattle. Human immunity to some African trypanosomes is due to two serum complexes designated trypanolytic factors (TLF-1 and -2), which both contain haptoglobin-related protein (HPR) and apolipoprotein LI (APOL1)(2-4). Whereas HPR association with haemoglobin (Hb) allows TLF-1 binding and uptake via the trypanosome receptor TbHpHbR (ref. 5), TLF-2 enters trypanosomes independently of TbHpHbR (refs 4, 5). APOL1 kills trypanosomes after insertion into endosomal/lysosomal membranes(2,6,7). Here we report that T. b. gambiense resists TLFs via a hydrophobic beta-sheet of the T. b. gambiense-specific glycoprotein (TgsGP)(8), which prevents APOL1 toxicity and induces stiffening of membranes upon interaction with lipids. Two additional features contribute to resistance to TLFs: reduction of sensitivity to APOL1 requiring cysteine protease activity, and TbHpHbR inactivation due to a L210S substitution. According to such a multifactorial defence mechanism, transgenic expression of T. b. brucei TbHpHbR in T. b. gambiense did not cause parasite lysis in normal human serum. However, these transgenic parasites were killed in hypohaptoglobinaemic serum, after high TLF-1 uptake in the absence of haptoglobin (Hp) that competes for Hb and receptor binding. TbHpHbR inactivation preventing high APOL1 loading in hypohaptoglobinaemic serum may have evolved because of the overlapping endemic area of T. b. gambiense infection and malaria, the main cause of haemolysis-induced hypohaptoglobinaemia in western and central Africa(9).
C1 [Uzureau, Pierrick; Uzureau, Sophie; Lecordier, Laurence; Fontaine, Frederic; Tebabi, Patricia; Pays, Annette; Felu, Cecile; Poelvoorde, Philippe; Vanhollebeke, Benoit] Univ Libre Bruxelles ULB, IBMM, Lab Mol Parasitol, B-6041 Gosselies, Belgium.
   [Homble, Fabrice] Univ Libre Bruxelles, B-1050 Brussels, Belgium.
   [Grelard, Axelle; Zhendre, Vanessa; Dufourc, Erick J.] Univ Bordeaux, Inst Polytech Bordeaux, Inst Chem & Biol Membranes & Nanoobjects, CNRS,UMR 5248, F-33600 Pessac, France.
   [Nolan, Derek P.] Trinity Coll Dublin, Sch Biochem & Immunol, Mol Parasitol Grp, Dublin 2, Ireland.
   [Lins, Laurence; Crowet, Jean-Marc] Univ Liege, Ctr Numer Mol Biophys, B-5030 Gembloux, Belgium.
   [Moestrup, Soren K.] Univ Aarhus, Dept Biomed, DK-8000 Aarhus, Denmark.
   [Lyngso, Jeppe; Pedersen, Jan Skov] Univ Aarhus, Interdisciplinary Nanosci Ctr INANO, DK-8000 Aarhus, Denmark.
   [Lyngso, Jeppe; Pedersen, Jan Skov] Univ Aarhus, Dept Chem, DK-8000 Aarhus, Denmark.
   [Mottram, Jeremy C.] Univ Glasgow, Wellcome Trust Ctr Mol Parasitol, Glasgow G12 8TA, Lanark, Scotland.
   [Perez-Morga, David] Univ Libre Bruxelles, Ctr Microscopy & Mol Imaging CMMI, B-6041 Gosselies, Belgium.
   [Perez-Morga, David; Pays, Etienne] Univ Libre Bruxelles, Mol Parasitol Lab, IBMM, B-6041 Gosselies, Belgium.
   [Pays, Etienne] Univ Libre Bruxelles, Walloon Excellence Life Sci & Biotechnol WELBIO, B-6041 Gosselies, Belgium.
C3 Universite Libre de Bruxelles; Universite Libre de Bruxelles; Universite de Bordeaux; Centre National de la Recherche Scientifique (CNRS); CNRS - Institute of Chemistry (INC); Trinity College Dublin; University of Liege; Aarhus University; Aarhus University; Aarhus University; University of Glasgow; Universite Libre de Bruxelles; Universite Libre de Bruxelles; Universite Libre de Bruxelles; WELBIO
RP Pays, E (corresponding author), Univ Libre Bruxelles, Walloon Excellence Life Sci & Biotechnol WELBIO, B-6041 Gosselies, Belgium.
EM epays@ulb.ac.be
FU Belgian Fund for Scientific Research; Walloon WELBIO excellence programme; Interuniversity Attraction Poles Programme-Belgian Science Policy; ERC [233312 TROJA]; European Regional Development Fund; Walloon Region; TGIR-RMN-THC Fr3050 (French high-field NMR network); Welcome Trust; Lundbeck Foundation [R54-2010-5637] Funding Source: researchfish
NR 47
TC 128
Z9 151
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 SEP 19
PY 2013
VL 501
IS 7467
BP 430
EP +
DI 10.1038/nature12516
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 219XT
UT WOS:000324545700048
PM 23965626
DA 2026-03-09
ER

PT J
AU Ling, HQ
   Zhao, SC
   Liu, DC
   Wang, JY
   Sun, H
   Zhang, C
   Fan, HJ
   Li, D
   Dong, LL
   Tao, Y
   Gao, C
   Wu, HL
   Li, YW
   Cui, Y
   Guo, XS
   Zheng, SS
   Wang, B
   Yu, K
   Liang, QS
   Yang, WL
   Lou, XY
   Chen, J
   Feng, MJ
   Jian, JB
   Zhang, XF
   Luo, GB
   Jiang, Y
   Liu, JJ
   Wang, ZB
   Sha, YH
   Zhang, BR
   Wu, HJ
   Tang, DZ
   Shen, QH
   Xue, PY
   Zou, SH
   Wang, XJ
   Liu, X
   Wang, FM
   Yang, YP
   An, XL
   Dong, ZY
   Zhang, KP
   Zhang, XQ
   Luo, MC
   Dvorak, J
   Tong, YP
   Wang, J
   Yang, HM
   Li, ZS
   Wang, DW
   Zhang, AM
   Wang, J
AF Ling, Hong-Qing
   Zhao, Shancen
   Liu, Dongcheng
   Wang, Junyi
   Sun, Hua
   Zhang, Chi
   Fan, Huajie
   Li, Dong
   Dong, Lingli
   Tao, Yong
   Gao, Chuan
   Wu, Huilan
   Li, Yiwen
   Cui, Yan
   Guo, Xiaosen
   Zheng, Shusong
   Wang, Biao
   Yu, Kang
   Liang, Qinsi
   Yang, Wenlong
   Lou, Xueyuan
   Chen, Jie
   Feng, Mingji
   Jian, Jianbo
   Zhang, Xiaofei
   Luo, Guangbin
   Jiang, Ying
   Liu, Junjie
   Wang, Zhaobao
   Sha, Yuhui
   Zhang, Bairu
   Wu, Huajun
   Tang, Dingzhong
   Shen, Qianhua
   Xue, Pengya
   Zou, Shenhao
   Wang, Xiujie
   Liu, Xin
   Wang, Famin
   Yang, Yanping
   An, Xueli
   Dong, Zhenying
   Zhang, Kunpu
   Zhang, Xiangqi
   Luo, Ming-Cheng
   Dvorak, Jan
   Tong, Yiping
   Wang, Jian
   Yang, Huanming
   Li, Zhensheng
   Wang, Daowen
   Zhang, Aimin
   Wang, Jun
TI Draft genome of the wheat A-genome progenitor Triticum urartu
SO NATURE
LA English
DT Article
ID evolution; gene; identification; loci; map
AB Bread wheat (Triticum aestivum, AABBDD) is one of the most widely cultivated and consumed food crops in the world. However, the complex polyploid nature of its genome makes genetic and functional analyses extremely challenging. The A genome, as a basic genome of bread wheat and other polyploid wheats, for example, T. turgidum (AABB), T. timopheevii (AAGG) and T. zhukovskyi (AAGGA(m)A(m)), is central to wheat evolution, domestication and genetic improvement(1). The progenitor species of the A genome is the diploid wild einkorn wheat T. urartu(2), which resembles cultivated wheat more extensively than do Aegilops speltoides (the ancestor of the B genome(3)) and Ae. tauschii (the donor of the D genome(4)), especially in the morphology and development of spike and seed. Here we present the generation, assembly and analysis of a whole-genome shotgun draft sequence of the T. urartu genome. We identified protein-coding gene models, performed genome structure analyses and assessed its utility for analysing agronomically important genes and for developing molecular markers. Our T. urartu genome assembly provides a diploid reference for analysis of polyploid wheat genomes and is a valuable resource for the genetic improvement of wheat.
C1 [Ling, Hong-Qing; Liu, Dongcheng; Wang, Junyi; Sun, Hua; Fan, Huajie; Dong, Lingli; Wu, Huilan; Li, Yiwen; Cui, Yan; Zheng, Shusong; Wang, Biao; Yu, Kang; Yang, Wenlong; Lou, Xueyuan; Zhang, Xiaofei; Luo, Guangbin; Zhang, Bairu; Tang, Dingzhong; Shen, Qianhua; Xue, Pengya; Zou, Shenhao; Liu, Xin; Wang, Famin; Yang, Yanping; An, Xueli; Dong, Zhenying; Zhang, Kunpu; Zhang, Xiangqi; Tong, Yiping; Li, Zhensheng; Wang, Daowen; Zhang, Aimin] Chinese Acad Sci, Inst Genet & Dev Biol, State Key Lab Plant Cell & Chromosome Engn, Beijing 100101, Peoples R China.
   [Zhao, Shancen; Wang, Junyi; Zhang, Chi; Li, Dong; Tao, Yong; Gao, Chuan; Guo, Xiaosen; Liang, Qinsi; Chen, Jie; Feng, Mingji; Jian, Jianbo; Jiang, Ying; Liu, Junjie; Wang, Zhaobao; Sha, Yuhui; Wang, Jian; Yang, Huanming; Wang, Jun] BGI Shenzhen, Shenzhen 518038, Peoples R China.
   [Zhao, Shancen] Chinese Univ Hong Kong, State Key Lab Agrobiotechnol, Hong Kong, Hong Kong, Peoples R China.
   [Zhao, Shancen] Chinese Univ Hong Kong, Sch Life Sci, Hong Kong, Hong Kong, Peoples R China.
   [Wu, Huajun; Wang, Xiujie] Chinese Acad Sci, Inst Genet & Dev Biol, State Key Lab Plant Genom, Beijing 100101, Peoples R China.
   [Luo, Ming-Cheng; Dvorak, Jan] Univ Calif Davis, Dept Plant Sci, Davis, CA 95616 USA.
   [Wang, Jun] Univ Copenhagen, Dept Biol, DK-2200 Copenhagen, Denmark.
   [Wang, Jun] King Abdulaziz Univ, Jeddah 21589, Saudi Arabia.
C3 Chinese Academy of Sciences; Institute of Genetics & Developmental Biology, CAS; Beijing Genomics Institute (BGI); Chinese University of Hong Kong; Chinese University of Hong Kong; Chinese Academy of Sciences; Institute of Genetics & Developmental Biology, CAS; University of California System; University of California Davis; University of Copenhagen; King Abdulaziz University
RP Wang, J (corresponding author), BGI Shenzhen, Shenzhen 518038, Peoples R China.
EM hqling@genetics.ac.cn; zsli@genetics.ac.cn; dwwang@genetics.ac.cn; amzhang@genetics.ac.cn; wangj@genomics.cn
FU Ministry of Science and Technology of China [2010DFB33540, 2011CB100304, 2011AA100104, 2009CB118300]; Ministry of Science and Technology of China [2010DFB33540, 2011CB100304, 2011AA100104, 2009CB118300]
NR 26
TC 584
Z9 720
U1 3
U2 382
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 4
PY 2013
VL 496
IS 7443
BP 87
EP 90
DI 10.1038/nature11997
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 117ZZ
UT WOS:000316993400030
PM 23535596
DA 2026-03-09
ER

PT J
AU Helbing, D
AF Helbing, Dirk
TI Globally networked risks and how to respond
SO NATURE
LA English
DT Article
ID complex networks; systemic risk; innovation; cascades; failures; dynamics; spread
AB Today's strongly connected, global networks have produced highly interdependent systems that we do not understand and cannot control well. These systems are vulnerable to failure at all scales, posing serious threats to society, even when external shocks are absent. As the complexity and interaction strengths in our networked world increase, man-made systems can become unstable, creating uncontrollable situations even when decision-makers are well-skilled, have all data and technology at their disposal, and do their best. To make these systems manageable, a fundamental redesign is needed. A 'Global Systems Science' might create the required knowledge and paradigm shift in thinking.
C1 [Helbing, Dirk] ETH, CH-8092 Zurich, Switzerland.
   [Helbing, Dirk] ETH, Swiss Fed Inst Technol, Risk Ctr, CH-8092 Zurich, Switzerland.
C3 Swiss Federal Institutes of Technology Domain; ETH Zurich; Swiss Federal Institutes of Technology Domain; ETH Zurich
RP Helbing, D (corresponding author), ETH, Clausiusstr 50, CH-8092 Zurich, Switzerland.
EM dhelbing@ethz.ch
FU FET Flagship Pilot Project FuturICT [284709]; ETH project "Systemic Risks-Systemic Solutions'' (CHIRP II project) [ETH 48 12-1]
NR 89
TC 791
Z9 939
U1 22
U2 516
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 2
PY 2013
VL 497
IS 7447
BP 51
EP 59
DI 10.1038/nature12047
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 134OK
UT WOS:000318221500033
PM 23636396
DA 2026-03-09
ER

PT J
AU Venters, BJ
   Pugh, BF
AF Venters, Bryan J.
   Pugh, B. Franklin
TI RETRACTED: Genomic organization of human transcription initiation complexes (Retracted Article)
SO NATURE
LA English
DT Article; Retracted Publication
ID rna-polymerase-ii; core promoter element; tata box; binding; sequences; visualization; cpg
AB The human genome is pervasively transcribed, yet only a small fraction is coding. Here we address whether this non-coding transcription arises at promoters, and detail the interactions of initiation factors TATA box binding protein (TBP), transcription factor IIB (TFIIB) and RNA polymerase (Pol) II. Using ChIP-exo (chromatin immunoprecipitation with lambda exonuclease digestion followed by high-throughput sequencing), we identify approximately 160,000 transcription initiation complexes across the human K562 genome, and more in other cancer genomes. Only about 5% associate with messenger RNA genes. The remainder associates with non-polyadenylated non-coding transcription. Regardless, Pol II moves into a transcriptionally paused state, and TBP and TFIIB remain at the promoter. Remarkably, the vast majority of locations contain the four core promoter elements-upstream TFIIB recognition element (BREu), TATA, downstream TFIIB recognition element (BREd), and initiator element (INR)-in constrained positions. All but the INR also reside at Pol III promoters, where TBP makes similar contacts. This comprehensive and high-resolution genome-wide detection of the initiation machinery produces a consolidated view of transcription initiation events from yeast to humans at Pol II/III TATA-containing/TATA-less coding and non-coding genes.
C1 [Venters, Bryan J.; 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]
NR 42
TC 53
Z9 75
U1 0
U2 79
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 3
PY 2013
VL 502
IS 7469
BP 53
EP +
DI 10.1038/nature12535
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 227IM
UT WOS:000325106000029
PM 24048476
DA 2026-03-09
ER

PT J
AU Johnson, PTJ
   Preston, DL
   Hoverman, JT
   Richgels, KLD
AF Johnson, Pieter T. J.
   Preston, Daniel L.
   Hoverman, Jason T.
   Richgels, Katherine L. D.
TI Biodiversity decreases disease through predictable changes in host community competence
SO NATURE
LA English
DT Article
ID west-nile-virus; species-diversity; infectious-disease; parasite diversity; risk; extinction; ecosystem; invasion; dilution
AB Accelerating rates of species extinctions and disease emergence underscore the importance of understanding how changes in bio-diversity affect disease outcomes(1-3). Over the past decade, a growing number of studies have reported negative correlations between host biodiversity and disease risk(4-8), prompting suggestions that biodiversity conservation could promote human and wildlife health(9,10). Yet the generality of the diversity-disease linkage remains conjectural(11-13), in part because empirical evidence of a relationship between host competence (the ability to maintain and transmit infections) and the order in which communities assemble has proven elusive. Here we integrate high-resolution field data with multi-scale experiments to show that host diversity inhibits transmission of the virulent pathogen Ribeiroia ondatrae and reduces amphibian disease as a result of consistent linkages among species richness, host composition and community competence. Surveys of 345 wetlands indicated that community composition changed nonrandomly with species richness, such that highly competent hosts dominated in species-poor assemblages whereas more resistant species became progressively more common in diverse assemblages. As a result, amphibian species richness strongly moderated pathogen transmission and disease pathology among 24,215 examined hosts, with a 78.4% decline in realized transmission in richer assemblages. Laboratory and mesocosm manipulations revealed an approximately 50% decrease in pathogen transmission and host pathology across a realistic diversity gradient while controlling for host density, helping to establish mechanisms underlying the diversity-disease relationship and their consequences for host fitness. By revealing a consistent link between species richness and community competence, these findings highlight the influence of biodiversity on infection risk and emphasize the benefit of a community-based approach to understanding infectious diseases.
C1 [Johnson, Pieter T. J.; Preston, Daniel L.; Richgels, Katherine L. D.] Univ Colorado, Boulder, CO 80309 USA.
   [Hoverman, Jason T.] Purdue Univ, Dept Forestry & Nat Resources, W Lafayette, IN 47907 USA.
C3 University of Colorado System; University of Colorado Boulder; Purdue University System; Purdue University
RP Johnson, PTJ (corresponding author), Univ Colorado, Boulder, CO 80309 USA.
EM pieter.johnson@colorado.edu
FU US National Science Foundation [DEB-0841758, DEB-1149308]; National Geographic Society; David and Lucile Packard Foundation; Division Of Environmental Biology; Direct For Biological Sciences [1149308, 1311467] Funding Source: National Science Foundation
CR Allan BF, 2009, OECOLOGIA, V158, P699, DOI 10.1007/s00442-008-1169-9
   Bracken MES, 2008, P NATL ACAD SCI USA, V105, P924, DOI 10.1073/pnas.0704103105
   Cardinale BJ, 2012, NATURE, V486, P59, DOI 10.1038/nature11148
   Clay CA, 2009, PLOS ONE, V4, P0, DOI 10.1371/journal.pone.0006467
   Ezenwa VO, 2006, P ROY SOC B-BIOL SCI, V273, P109, DOI 10.1098/rspb.2005.3284
   Graham SP, 2009, PLOS ONE, V4, P0, DOI 10.1371/journal.pone.0007873
   Haas SE, 2011, ECOL LETT, V14, P1108, DOI 10.1111/j.1461-0248.2011.01679.x
   Hamer GL, 2011, PLOS ONE, V6, P0, DOI 10.1371/journal.pone.0023767
   Hechinger RF, 2005, P ROY SOC B-BIOL SCI, V272, P1059, DOI 10.1098/rspb.2005.3070
   Johnson PTJ, 2012, P NATL ACAD SCI USA, V109, P9006, DOI 10.1073/pnas.1201790109
   Johnson PTJ, 2012, ECOLOGY, V93, P56, DOI 10.1890/11-0636.1
   Johnson PTJ, 2012, ECOL LETT, V15, P235, DOI 10.1111/j.1461-0248.2011.01730.x
   Jones KE, 2008, NATURE, V451, P990, DOI 10.1038/nature06536
   Keesing F, 2006, ECOL LETT, V9, P485, DOI 10.1111/j.1461-0248.2006.00885.x
   Keesing F, 2010, NATURE, V468, P647, DOI 10.1038/nature09575
   Kilpatrick AM, 2011, SCIENCE, V334, P323, DOI 10.1126/science.1201010
   Lee KA, 2008, J ANIM ECOL, V77, P356, DOI 10.1111/j.1365-2656.2007.01347.x
   LoGiudice K, 2003, P NATL ACAD SCI USA, V100, P567, DOI 10.1073/pnas.0233733100
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NR 29
TC 309
Z9 379
U1 1
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 FEB 14
PY 2013
VL 494
IS 7436
BP 230
EP 233
DI 10.1038/nature11883
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 092QS
UT WOS:000315137700038
PM 23407539
DA 2026-03-09
ER

PT J
AU Grinberg, I
   West, DV
   Torres, M
   Gou, GY
   Stein, DM
   Wu, LY
   Chen, GN
   Gallo, EM
   Akbashev, AR
   Davies, PK
   Spanier, JE
   Rappe, AM
AF Grinberg, Ilya
   West, D. Vincent
   Torres, Maria
   Gou, Gaoyang
   Stein, David M.
   Wu, Liyan
   Chen, Guannan
   Gallo, Eric M.
   Akbashev, Andrew R.
   Davies, Peter K.
   Spanier, Jonathan E.
   Rappe, Andrew M.
TI Perovskite oxides for visible-light-absorbing ferroelectric and photovoltaic materials
SO NATURE
LA English
DT Article
ID substitution; photocurrent
AB Ferroelectrics have recently attracted attention as a candidate class of materials for use in photovoltaic devices, and for the coupling of light absorption with other functional properties(1-7). In these materials, the strong inversion symmetry breaking that is due to spontaneous electric polarization promotes the desirable separation of photo-excited carriers and allows voltages higher than the bandgap, which may enable efficiencies beyond the maximum possible in a conventional p-n junction solar cell(2,6,8-10). Ferroelectric oxides are also stable in a wide range of mechanical, chemical and thermal conditions and can be fabricated using low-cost methods such as sol-gel thin-film deposition and sputtering(3,5). Recent work(3,5,11) has shown how a decrease in ferroelectric layer thickness and judicious engineering of domain structures and ferroelectric-electrode interfaces can greatly increase the current harvested from ferroelectric absorber materials, increasing the power conversion efficiency from about 10(-4) to about 0.5 per cent. Further improvements in photovoltaic efficiency have been inhibited by the wide bandgaps (2.7-4 electronvolts) of ferroelectric oxides, which allow the use of only 8-20 per cent of the solar spectrum. Here we describe a family of single-phase solid oxide solutions made from low-cost and non-toxic elements using conventional solid-state methods: [KNbO3](1-x)[BaNi1/2Nb1/2O3-delta](x) (KBNNO). These oxides exhibit both ferroelectricity and a wide variation of direct bandgaps in the range 1.1-3.8 electronvolts. In particular, the x = 0.1 composition is polar at room temperature, has a direct bandgap of 1.39 electronvolts and has a photocurrent density approximately 50 times larger than that of the classic ferroelectric (Pb,La)(Zr,Ti)O-3 material. The ability of KBNNO to absorb three to six times more solar energy than the current ferroelectric materials suggests a route to viable ferroelectric semiconductor-based cells for solar energy conversion and other applications.
C1 [Grinberg, Ilya; Gou, Gaoyang; Rappe, Andrew M.] Univ Penn, Dept Chem, Makineni Theoret Labs, Philadelphia, PA 19104 USA.
   [West, D. Vincent; Stein, David M.; Wu, Liyan; Davies, Peter K.] Univ Penn, Dept Mat Sci & Engn, Philadelphia, PA 19104 USA.
   [Torres, Maria; Chen, Guannan; Gallo, Eric M.; Akbashev, Andrew R.; Spanier, Jonathan E.] Drexel Univ, Dept Mat Sci & Engn, Philadelphia, PA 19104 USA.
C3 University of Pennsylvania; University of Pennsylvania; Drexel University
RP Rappe, AM (corresponding author), Univ Penn, Dept Chem, Makineni Theoret Labs, Philadelphia, PA 19104 USA.
EM rappe@sas.upenn.edu
FU Energy Commercialization Institute of BFTP; US Department of Energy, Office of Basic Sciences [DE-AC02-06CH11357]; Army Research Office [W911NF-08-1-0067]; NSF [DMR 0907381, DMR 1124696, DMR 0722845]; ASEE Postdoctoral Fellowship; Department of Energy, Office of Basic Energy Sciences [DE-FG02-07ER46431]; Energy Commercialization Institute; Office of Naval Research [N00014-12-1-1033]; High Performance Computing Modernization Office of the US Department of Defense; National Energy Research Scientific Computing Center of the US Department of Energy; Division Of Materials Research; Direct For Mathematical & Physical Scien [1124696] Funding Source: National Science Foundation
CR Alexe M, 2011, NAT COMMUN, V2, P0, DOI 10.1038/ncomms1261
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NR 32
TC 1235
Z9 1328
U1 12
U2 2517
PU NATURE PUBLISHING 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 28
PY 2013
VL 503
IS 7477
BP 509
EP +
DI 10.1038/nature12622
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 258MU
UT WOS:000327464200039
PM 24213630
DA 2026-03-09
ER

PT J
AU Fattal, D
   Peng, Z
   Tran, T
   Vo, S
   Fiorentino, M
   Brug, J
   Beausoleil, RG
AF Fattal, David
   Peng, Zhen
   Tho Tran
   Vo, Sonny
   Fiorentino, Marco
   Brug, Jim
   Beausoleil, Raymond G.
TI A multi-directional backlight for a wide-angle, glasses-free three-dimensional display
SO NATURE
LA English
DT Article
AB Multiview three-dimensional (3D) displays can project the correct perspectives of a 3D image in many spatial directions simultaneously(1-4). They provide a 3D stereoscopic experience to many viewers at the same time with full motion parallax and do not require special glasses or eye tracking. None of the leading multiview 3D solutions is particularly well suited to mobile devices (watches, mobile phones or tablets), which require the combination of a thin, portable form factor, a high spatial resolution and a wide full-parallax view zone (for short viewing distance from potentially steep angles). Here we introduce a multi-directional diffractive backlight technology that permits the rendering of high-resolution, full-parallax 3D images in a very wide view zone (up to 180 degrees in principle) at an observation distance of up to a metre. The key to our design is a guided-wave illumination technique based on light-emitting diodes that produces wide-angle multiview images in colour from a thin planar transparent light-guide. Pixels associated with different views or colours are spatially multiplexed and can be independently addressed and modulated at video rate using an external shutter plane. To illustrate the capabilities of this technology, we use simple ink masks or a high-resolution commercial liquid-crystal display unit to demonstrate passive and active (30 frames per second) modulation of a 64-view backlight, producing 3D images with a spatial resolution of 88 pixels per inch and full-motion parallax in an unprecedented view zone of 90 degrees. We also present several transparent hand-held prototypes showing animated sequences of up to six different 200-view images at a resolution of 127 pixels per inch.
C1 [Fattal, David; Peng, Zhen; Tho Tran; Vo, Sonny; Fiorentino, Marco; Brug, Jim; Beausoleil, Raymond G.] Hewlett Packard Labs, Palo Alto, CA 94304 USA.
C3 Hewlett-Packard
RP Fattal, D (corresponding author), Hewlett Packard Labs, 1501 Page Mill Rd, Palo Alto, CA 94304 USA.
EM david.fattal@hp.com
NR 17
TC 285
Z9 541
U1 8
U2 241
PU NATURE PUBLISHING 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 21
PY 2013
VL 495
IS 7441
BP 348
EP 351
DI 10.1038/nature11972
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 113EY
UT WOS:000316650500038
PM 23518562
DA 2026-03-09
ER

PT J
AU Chang, WC
   Dey, M
   Liu, PH
   Mansoorabadi, SO
   Moon, SJ
   Zhao, ZBK
   Drennan, CL
   Liu, HW
AF Chang, Wei-chen
   Dey, Mishtu
   Liu, Pinghua
   Mansoorabadi, Steven O.
   Moon, Sung-Ju
   Zhao, Zongbao K.
   Drennan, Catherine L.
   Liu, Hung-wen
TI Mechanistic studies of an unprecedented enzyme-catalysed 1,2-phosphono-migration reaction
SO NATURE
LA English
DT Article
ID (s)-2-hydroxypropylphosphonic acid epoxidase; antibiotic fosfomycin biosynthesis; mononuclear iron enzyme; escherichia-coli; identification; activation; resistant; insight; oxygen; site
AB (S)-2-hydroxypropylphosphonate ((S)-2-HPP) epoxidase (HppE) is a mononuclear non-haem-iron-dependent enzyme(1-3) responsible for the final step in the biosynthesis of the clinically useful antibiotic fosfomycin(4). Enzymes of this class typically catalyse oxygenation reactions that proceed via the formation of substrate radical intermediates. By contrast, HppE catalyses an unusual dehydrogenation reaction while converting the secondary alcohol of (S)-2-HPP to the epoxide ring of fosfomycin(1,5). Here we show that HppE also catalyses a biologically unprecedented 1,2-phosphono migration with the alternative substrate (R)-1-HPP. This transformation probably involves an intermediary carbocation, based on observations with additional substrate analogues, such as (1R)-1-hydroxyl-2-aminopropylphosphonate, and model reactions for both radical- and carbocation-mediated migration. The ability of HppE to catalyse distinct reactions depending on the regio- and stereochemical properties of the substrate is given a structural basis using X-ray crystallography. These results provide compelling evidence for the formation of a substrate-derived cation intermediate in the catalytic cycle of a mononuclear non-haem-iron-dependent enzyme. The underlying chemistry of this unusual phosphono migration may represent a new paradigm for the in vivo construction of phosphonate-containing natural products that can be exploited for the preparation of new phosphonate derivatives.
C1 [Chang, Wei-chen; Liu, Pinghua; Mansoorabadi, Steven O.; Moon, Sung-Ju; Zhao, Zongbao K.; Liu, Hung-wen] Univ Texas Austin, Coll Pharm, Div Med Chem, Austin, TX 78712 USA.
   [Chang, Wei-chen; Liu, Pinghua; Mansoorabadi, Steven O.; Moon, Sung-Ju; Zhao, Zongbao K.; Liu, Hung-wen] Univ Texas Austin, Dept Chem & Biochem, Austin, TX 78712 USA.
   [Dey, Mishtu; Drennan, Catherine L.] MIT, Howard Hughes Med Inst, Cambridge, MA 02139 USA.
   [Dey, Mishtu; Drennan, Catherine L.] MIT, Dept Chem, Cambridge, MA 02139 USA.
   [Dey, Mishtu; Drennan, Catherine L.] MIT, Dept Biol, Cambridge, MA 02139 USA.
C3 University of Texas System; University of Texas Austin; University of Texas System; University of Texas Austin; Howard Hughes Medical Institute; Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT)
RP Liu, HW (corresponding author), Univ Texas Austin, Coll Pharm, Div Med Chem, Austin, TX 78712 USA.
EM h.w.liu@mail.utexas.edu
FU National Institutes of Health [GM040541]; Welch Foundation [F-1511]; Advanced Light Source, a Department of Energy (DOE) national user facility [DE-AC02-05CH11231]; DOE; National Institutes of Health/National Institute of General Medical Sciences; National Institute of General Medical Sciences [R01GM040541] Funding Source: NIH RePORTER
NR 29
TC 51
Z9 59
U1 2
U2 170
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 4
PY 2013
VL 496
IS 7443
BP 114
EP 118
DI 10.1038/nature11998
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 117ZZ
UT WOS:000316993400036
PM 23552950
DA 2026-03-09
ER

PT J
AU Fu, WQ
   O'Connor, TD
   Jun, G
   Kang, HM
   Abecasis, G
   Leal, SM
   Gabriel, S
   Altshuler, D
   Shendure, J
   Nickerson, DA
   Bamshad, MJ
   Akey, JM
AF Fu, Wenqing
   O'Connor, Timothy D.
   Jun, Goo
   Kang, Hyun Min
   Abecasis, Goncalo
   Leal, Suzanne M.
   Gabriel, Stacey
   Altshuler, David
   Shendure, Jay
   Nickerson, Deborah A.
   Bamshad, Michael J.
   Akey, Joshua M.
TI Analysis of 6,515 exomes reveals the recent origin of most human protein-coding variants
SO NATURE
LA English
DT Article
ID population-growth; rare; mutations; disease; gene; evolution; history; excess; age
AB Establishing the age of each mutation segregating in contemporary human populations is important to fully understand our evolutionary history(1,2) and will help to facilitate the development of new approaches for disease-gene discovery(3). Large-scale surveys of human genetic variation have reported signatures of recent explosive population growth(4-6), notable for an excess of rare genetic variants, suggesting that many mutations arose recently. To more quantitatively assess the distribution of mutation ages, we resequenced 15,336 genes in 6,515 individuals of European American and African American ancestry and inferred the age of 1,146,401 autosomal single nucleotide variants (SNVs). We estimate that approximately 73% of all protein-coding SNVs and approximately 86% of SNVs predicted to be deleterious arose in the past 5,000-10,000 years. The average age of deleterious SNVs varied significantly across molecular pathways, and disease genes contained a significantly higher proportion of recently arisen deleterious SNVs than other genes. Furthermore, European Americans had an excess of deleterious variants in essential and Mendelian disease genes compared to African Americans, consistent with weaker purifying selection due to the Out-of-Africa dispersal. Our results better delimit the historical details of human protein-coding variation, show the profound effect of recent human history on the burden of deleterious SNVs segregating in contemporary populations, and provide important practical information that can be used to prioritize variants in disease-gene discovery.
C1 [Fu, Wenqing; O'Connor, Timothy D.; Shendure, Jay; Nickerson, Deborah A.; Bamshad, Michael J.; Akey, Joshua M.] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA.
   [Jun, Goo; Kang, Hyun Min; Abecasis, Goncalo] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.
   [Leal, Suzanne M.] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA.
   [Gabriel, Stacey; Altshuler, David] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.
   [Bamshad, Michael J.] Univ Washington, Dept Pediat, Seattle, WA 98195 USA.
C3 University of Washington; University of Washington Seattle; University of Michigan System; University of Michigan; Baylor College of Medicine; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; University of Washington; University of Washington Seattle
RP Fu, WQ (corresponding author), Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA.
EM wqfu@u.washington.edu; akeyj@u.washington.edu
FU National Heart, Lung and Blood Institute (NHLBI); NHLBI [RC2 HL-103010, RC2 HL-102923, RC2 HL-102924, RC2 HL-102925, RC2 HL-102926]
NR 27
TC 727
Z9 863
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 JAN 10
PY 2013
VL 493
IS 7431
BP 216
EP 220
DI 10.1038/nature11690
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 066YY
UT WOS:000313259600038
PM 23201682
DA 2026-03-09
ER

PT J
AU Donato, F
   Rompani, SB
   Caroni, P
AF Donato, Flavio
   Rompani, Santiago Belluco
   Caroni, Pico
TI Parvalbumin-expressing basket-cell network plasticity induced by experience regulates adult learning
SO NATURE
LA English
DT Article
ID critical-period; visual-cortex; interneurons; inhibition; circuits; mouse; connectivity; innervation; activation; synapses
AB Learning and memory processes can be influenced by recent experience, but the mechanisms involved are poorly understood. Enhanced plasticity during critical periods of early life is linked to differentiating parvalbumin (PV)-interneuron networks(1-7), suggesting that recent experience may modulate learning by targeting the differentiation state of PV neurons(8-11) in the adult. Here we show that environmental enrichment and Pavlovian contextual fear conditioning induce opposite, sustained and reversible hippocampal PV-network configurations in adult mice. Specifically, enrichment promotes the emergence of large fractions of low-differentiation (low PV and GAD67 expression) basket cells with low excitatory-to-inhibitory synaptic-density ratios, whereas fear conditioning leads to large fractions of high-differentiation (high PV and GAD67 expression) basket cells with high excitatory-to-inhibitory synaptic-density ratios. Pharmacogenetic inhibition or activation of PV neurons was sufficient to induce such opposite low-PV-network or high-PV-network configurations, respectively. The low-PV-network configuration enhanced structural synaptic plasticity(12,13), and memory consolidation and retrieval, whereas these were reduced by the high-PV-network configuration. We then show that maze navigation learning(14) induces a hippocampal low-PV-network configuration paralleled by enhanced memory and structural synaptic plasticity throughout training, followed by a shift to a high-PV-network configuration after learning completion. The shift to a low-PV-network configuration specifically involved increased vasoactive intestinal polypeptide (VIP)-positive GABAergic boutons and synaptic transmission onto PV neurons(15,16). Closely comparable low-and high-PV-network configurations involving VIP boutons were specifically induced in primary motor cortex upon rotarod motor learning(17,18). These results uncover a network plasticity mechanism induced after learning through VIP-PV microcircuit modulation(19), and involving large, sustained and reversible shifts in the configuration of PV basket-cell networks in the adult. This novel form of experience-related plasticity in the adult modulates memory consolidation, retrieval and learning, and might be harnessed for therapeutic strategies to promote cognitive enhancement and neuroprotection.
C1 [Donato, Flavio; Rompani, Santiago Belluco; Caroni, Pico] Friedrich Miescher Inst, CH-4058 Basel, Switzerland.
C3 Friedrich Miescher Institute for Biomedical Research
RP Caroni, P (corresponding author), Friedrich Miescher Inst, Maulbeerstr 66, CH-4058 Basel, Switzerland.
EM caroni@fmi.ch
FU Novartis Research Foundation; NCCR Synapsy
NR 31
TC 563
Z9 670
U1 3
U2 104
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 12
PY 2013
VL 504
IS 7479
BP 272
EP +
DI 10.1038/nature12866
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 267TQ
UT WOS:000328121500035
PM 24336286
DA 2026-03-09
ER

PT J
AU Demirörs, AF
   Pillai, PP
   Kowalczyk, B
   Grzybowski, BA
AF Demiroers, Ahmet F.
   Pillai, Pramod P.
   Kowalczyk, Bartlomiej
   Grzybowski, Bartosz A.
TI Colloidal assembly directed by virtual magnetic moulds
SO NATURE
LA English
DT Article
ID crystals; arrays; molecules; symmetry; forces; growth; field
AB Interest in assemblies of colloidal particles(1-4) has long been motivated by their applications in photonics(5,6), electronics(7,8), sensors(8) and microlenses(9). Existing assembly schemes(10-15) can position colloids of one type relatively flexibly into a range of desired structures, but it remains challenging to produce multicomponent lattices, clusters with precisely controlled symmetries and three-dimensional assemblies(16). A few schemes can efficiently produce complex colloidal structures(2,17,18), but they require system-specific procedures. Here we show that magnetic field microgradients established in a paramagnetic fluid(19,20) can serve as 'virtual moulds' to act as templates for the assembly of large numbers (similar to 10(8)) of both non-magnetic and magnetic colloidal particles with micrometre precision and typical yields of 80 to 90 per cent. We illustrate the versatility of this approach by producing single-component and multicomponent colloidal arrays, complex three-dimensional structures and a variety of colloidal molecules from polymeric particles, silica particles and live bacteria and by showing that all of these structures can be made permanent. In addition, although our magnetic moulds currently resemble optical traps in that they are limited to the manipulation of micrometre-sized objects, they are massively parallel and can manipulate non-magnetic and magnetic objects simultaneously in two and three dimensions.
C1 [Demiroers, Ahmet F.; Pillai, Pramod P.; Kowalczyk, Bartlomiej; Grzybowski, Bartosz A.] Northwestern Univ, Dept Chem, Evanston, IL 60208 USA.
   [Demiroers, Ahmet F.; Pillai, Pramod P.; Kowalczyk, Bartlomiej; Grzybowski, Bartosz A.] Northwestern Univ, Dept Chem & Biol Engn, Evanston, IL 60208 USA.
C3 Northwestern University; Northwestern University
RP Grzybowski, BA (corresponding author), Northwestern Univ, Dept Chem, 2145 Sheridan Rd, Evanston, IL 60208 USA.
EM grzybor@northwestern.edu
FU US Department of Energy, Office of Science, Office of Basic Energy Sciences [DE-SC0000989]; Non-equilibrium Energy Research Center, Energy Frontier Research Center
NR 27
TC 179
Z9 209
U1 3
U2 325
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 7
PY 2013
VL 503
IS 7474
BP 99
EP 103
DI 10.1038/nature12591
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 247AS
UT WOS:000326585600039
PM 24141949
DA 2026-03-09
ER

PT J
AU Kasuga, H
   Fukuyama, M
   Kitazawa, A
   Kontani, K
   Katada, T
AF Kasuga, Hidefumi
   Fukuyama, Masamitsu
   Kitazawa, Aya
   Kontani, Kenji
   Katada, Toshiaki
TI The microRNA miR-235 couples blast-cell quiescence to the nutritional state
SO NATURE
LA English
DT Article
ID caenorhabditis-elegans; c-elegans; stem-cell; nuclear factor; arrest; lin-4; expression; germline; lineages; behavior
AB The coordination of stem-and blast-cell behaviours, such as self-renewal, differentiation and quiescence, with physiological changes underlies growth, regeneration and tissue homeostasis(1-3). Germline stem and somatic blast cells in newly hatched Caenorhabditis elegans larvae can suspend postembryonic development, which consists of diverse cellular events such as migration, proliferation and differentiation, until the nutritional state becomes favourable (termed L1 diapause(4-6)). Although previous studies showed that the insulin/insulin-like growth factor (IGF) signalling (IIS) pathway regulates this developmental quiescence(5-8), the detailed mechanism by which the IIS pathway enables these multipotent cells to respond to nutrient availability is unknown. Here we show in C. elegans that the microRNA (miRNA) miR-235, a sole orthologue of mammalian miR-92 from the oncogenicmiR-17-92 cluster(9,10), acts in the hypodermis and glial cells to arrest postembryonic developmental events in both neuroblasts and mesoblasts. Expression of mir-235 persists during L1 diapause, and decreases upon feeding in a manner dependent on the IIS pathway. Upregulation of one of the miR-235 targets, nhr-91, which encodes an orthologue of mammalian germ cell nuclear factor, is responsible for defects caused by loss of the miRNA. Our findings establish a novel role of a miR-92 orthologue in coupling blast-cell behaviours to the nutritional state.
C1 [Kasuga, Hidefumi; Fukuyama, Masamitsu; Kitazawa, Aya; Kontani, Kenji; Katada, Toshiaki] Univ Tokyo, Grad Sch Pharmaceut Sci, Physiol Chem Lab, Bunkyo Ku, Tokyo 1130033, Japan.
C3 University of Tokyo
RP Fukuyama, M (corresponding author), Univ Tokyo, Grad Sch Pharmaceut Sci, Physiol Chem Lab, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1130033, Japan.
EM mfukuyam@mol.f.u-tokyo.ac.jp
FU National Institutes of Health National Center for Research Resources; MITANI Lab through the National Bio-Resource Project of the Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan; Japan Society for the Promotion of Science KAKENHI [23229001, 23370083]; MEXT KAKENHI [24657081, 23116703]; Grants-in-Aid for Scientific Research [24657081, 23370083, 23229001] Funding Source: KAKEN
NR 29
TC 46
Z9 56
U1 0
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 23
PY 2013
VL 497
IS 7450
BP 503
EP +
DI 10.1038/nature12117
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 148OG
UT WOS:000319254000051
PM 23644454
DA 2026-03-09
ER

PT J
AU Murch, KW
   Weber, SJ
   Macklin, C
   Siddiqi, I
AF Murch, K. W.
   Weber, S. J.
   Macklin, C.
   Siddiqi, I.
TI Observing single quantum trajectories of a superconducting quantum bit
SO NATURE
LA English
DT Article
ID current situation; noise; amplification; mechanics; feedback; collapse; qubit; spin
AB The length of time that a quantum system can exist in a superposition state is determined by how strongly it interacts with its environment. This interaction entangles the quantum state with the inherent fluctuations of the environment. If these fluctuations are not measured, the environment can be viewed as a source of noise, causing random evolution of the quantum system from an initially pure state into a statistical mixture-a process known as decoherence. However, by accurately measuring the environment in real time, the quantum system can be maintained in a pure state and its time evolution described by a 'quantum trajectory'(1,2) determined by the measurement outcome. Here we use weak measurements to monitor a microwave cavity containing a superconducting quantum bit (qubit), and track the individual quantum trajectories(3) of the system. In this setup, the environment is dominated by the fluctuations of a single electromagnetic mode of the cavity. Using a near-quantum-limited parametric amplifier(4,5), we selectively measure either the phase or the amplitude of the cavity field, and thereby confine trajectories to either the equator or a meridian of the Bloch sphere. We perform quantum state tomography at discrete times along the trajectory to verify that we have faithfully tracked the state of the quantum system as it diffuses on the surface of the Bloch sphere. Our results demonstrate that decoherence can be mitigated by environmental monitoring, and validate the foundation of quantum feedback approaches based on Bayesian statistics(6-8). Moreover, our experiments suggest a new means of implementing 'quantum steering'(9)-the harnessing of action at a distance to manipulate quantum states through measurement.
C1 [Murch, K. W.; Weber, S. J.; Macklin, C.; Siddiqi, I.] Univ Calif Berkeley, Dept Phys, Quantum Nanoelect Lab, Berkeley, CA 94720 USA.
   [Murch, K. W.] Washington Univ, Dept Phys, St Louis, MO 63130 USA.
C3 University of California System; University of California Berkeley; Washington University (WUSTL)
RP Murch, KW (corresponding author), Univ Calif Berkeley, Dept Phys, Quantum Nanoelect Lab, Berkeley, CA 94720 USA.
EM katerm@berkeley.edu
FU Army Research Office, Office of Naval Research and the Office of the Director of National Intelligence (ODNI), Intelligence Advanced Research Projects Activity (IARPA) through the Army Research Office
NR 32
TC 319
Z9 381
U1 0
U2 107
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 10
PY 2013
VL 502
IS 7470
BP 211
EP 214
DI 10.1038/nature12539
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 231RU
UT WOS:000325436100045
PM 24108052
DA 2026-03-09
ER

PT J
AU Yelenik, SG
   D'Antonio, CM
AF Yelenik, Stephanie G.
   D'Antonio, Carla M.
TI Self-reinforcing impacts of plant invasions change over time
SO NATURE
LA English
DT Article
ID dry hawaiian woodlands; biological invasions; restoration ecology; nitrogen dynamics; exotic grasses; soil feedbacks; c-4 grasses; fire; states; succession
AB Returning native species to habitats degraded by biological invasions is a critical conservation goal(1). A leading hypothesis poses that exotic plant dominance is self-reinforced by impacts on ecosystem processes, leading to persistent stable states(2-6). Invaders have been documented to modify fire regimes, alter soil nutrients or shift microbial communities in ways that feed back to benefit themselves over competitors(2,5-7). However, few studies have followed invasions through time to ask whether ecosystem impacts and feedbacks persist(8,9). Here we return to woodland sites in Hawai'i Volcanoes National Park that were invaded by exotic C-4 grasses in the 1960s, the ecosystem impacts of which were studied intensively in the 1990s(10-12). We show that positive feedbacks between exotic grasses and soil nitrogen cycling have broken down, but rather than facilitating native vegetation, the weakening feedbacks facilitate new exotic species. Data from the 1990s showed that exotic grasses increased nitrogen-mineralization rates by two-to fourfold, but were nitrogen-limited(10,12,13). Thus, the impacts of the invader created a positive feedback early in the invasion. We now show that annual net soil nitrogen mineralization has since dropped to pre-invasion levels. In addition, a seedling outplanting experiment that varied soil nitrogen and grass competition demonstrates that the changing impacts of grasses do not favour native species re-establishment. Instead, decreased nitrogen availability most benefits another aggressive invader, the nitrogen-fixing tree Morella faya. Long-term studies of invasions may reveal that ecosystem impacts and feedbacks shift over time, but that this may not benefit native species recovery.
C1 [Yelenik, Stephanie G.; D'Antonio, Carla M.] Univ Calif Santa Barbara, Dept Ecol Evolut & Marine Biol, Santa Barbara, CA 93106 USA.
C3 University of California System; University of California Santa Barbara
RP Yelenik, SG (corresponding author), US Geol Survey, Pacific Isl Ecosyst Res Ctr, Hawaii Natl Pk, HI 96718 USA.
EM syelenik@usgs.gov
FU National Science Foundation [DEB 1029168]
NR 30
TC 137
Z9 156
U1 7
U2 335
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 28
PY 2013
VL 503
IS 7477
BP 517
EP +
DI 10.1038/nature12798
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 258MU
UT WOS:000327464200041
PM 24256723
DA 2026-03-09
ER

PT J
AU Gerhart-Hines, Z
   Feng, D
   Emmett, MJ
   Everett, LJ
   Loro, E
   Briggs, ER
   Bugge, A
   Hou, C
   Ferrara, C
   Seale, P
   Pryma, DA
   Khurana, TS
   Lazar, MA
AF Gerhart-Hines, Zachary
   Feng, Dan
   Emmett, Matthew J.
   Everett, Logan J.
   Loro, Emanuele
   Briggs, Erika R.
   Bugge, Anne
   Hou, Catherine
   Ferrara, Christine
   Seale, Patrick
   Pryma, Daniel A.
   Khurana, Tejvir S.
   Lazar, Mitchell A.
TI The nuclear receptor Rev-erbα controls circadian thermogenic plasticity
SO NATURE
LA English
DT Article
ID brown adipose-tissue; nonshivering thermogenesis; metabolism; cold; behavior; rhythm; ucp1
AB Circadian oscillation of body temperature is a basic, evolutionarily conserved feature of mammalian biology(1). In addition, homeostatic pathways allow organisms to protect their core temperatures in response to cold exposure(2). However, the mechanism responsible for coordinating daily body temperature rhythm and adaptability to environmental challenges is unknown. Here we show that the nuclear receptor Rev-erb alpha (also known as Nr1d1), a powerful transcriptional repressor, links circadian and thermogenic networks through the regulation of brown adipose tissue (BAT) function. Mice exposed to cold fare considerably better at 05:00 (Zeitgeber time 22) when Rev-erb alpha is barely expressed than at 17:00 (Zeitgeber time 10) when Rev-erb alpha is abundant. Deletion of Rev-erb alpha markedly improves cold tolerance at 17: 00, indicating that overcoming Rev-erb alpha-dependent repression is a fundamental feature of the thermogenic response to cold. Physiological induction of uncoupling protein 1 (Ucp1) by cold temperatures is preceded by rapid downregulation of Rev-erb alpha in BAT. Rev-erb alpha represses Ucp1 in a brown-adipose-cell-autonomous manner and BAT Ucp1 levels are high in Rev-erb alpha-null mice, even at thermoneutrality. Genetic loss of Rev-erb alpha also abolishes normal rhythms of body temperature and BAT activity. Thus, Rev-erb alpha acts as a thermogenic focal point required for establishing and maintaining body temperature rhythm in a manner that is adaptable to environmental demands.
C1 [Gerhart-Hines, Zachary; Feng, Dan; Emmett, Matthew J.; Everett, Logan J.; Briggs, Erika R.; Bugge, Anne; Lazar, Mitchell A.] Univ Penn, Perelman Sch Med, Div Endocrinol Diabet & Metab, Dept Med,Dept Genet, Philadelphia, PA 19104 USA.
   [Gerhart-Hines, Zachary; Feng, Dan; Emmett, Matthew J.; Everett, Logan J.; Briggs, Erika R.; Bugge, Anne; Seale, Patrick; Lazar, Mitchell A.] Univ Penn, Perelman Sch Med, Inst Diabet Obes & Metab, Philadelphia, PA 19104 USA.
   [Loro, Emanuele; Khurana, Tejvir S.] Univ Penn, Perelman Sch Med, Dept Physiol, Philadelphia, PA 19104 USA.
   [Loro, Emanuele; Khurana, Tejvir S.] Univ Penn, Perelman Sch Med, Penn Muscle Inst, Philadelphia, PA 19104 USA.
   [Hou, Catherine; Pryma, Daniel A.] Univ Penn, Perelman Sch Med, Dept Radiol, Philadelphia, PA 19104 USA.
   [Ferrara, Christine] Childrens Hosp Philadelphia, Dept Pediat, Philadelphia, PA 19104 USA.
   [Seale, Patrick] Univ Penn, Perelman Sch Med, Dept Cell & Dev Biol, Philadelphia, PA 19104 USA.
C3 University of Pennsylvania; University of Pennsylvania; University of Pennsylvania; University of Pennsylvania; University of Pennsylvania; University of Pennsylvania; Pennsylvania Medicine; Childrens Hospital of Philadelphia; University of Pennsylvania
RP Lazar, MA (corresponding author), Univ Penn, Perelman Sch Med, Div Endocrinol Diabet & Metab, Dept Med,Dept Genet, Philadelphia, PA 19104 USA.
EM lazar@mail.med.upenn.edu
FU NIH [R01 DK45586, F-32 DK095563]; JPB Foundation; Novo Nordisk STAR postdoctoral program; National Institute of Diabetes and Digestive and Kidney Diseases [R01DK045586, P30DK019525] Funding Source: NIH RePORTER
NR 30
TC 221
Z9 254
U1 1
U2 52
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 21
PY 2013
VL 503
IS 7476
BP 410
EP +
DI 10.1038/nature12642
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 254KG
UT WOS:000327163200044
PM 24162845
DA 2026-03-09
ER

PT J
AU Buczacki, SJA
   Zecchini, HI
   Nicholson, AM
   Russell, R
   Vermeulen, L
   Kemp, R
   Winton, DJ
AF Buczacki, Simon J. A.
   Zecchini, Heather Ireland
   Nicholson, Anna M.
   Russell, Roslin
   Vermeulen, Louis
   Kemp, Richard
   Winton, Douglas J.
TI Intestinal label-retaining cells are secretory precursors expressing Lgr5
SO NATURE
LA English
DT Article
ID stem-cells; marker; segregation; homeostasis; polyposis; quiescent; renewal; lrig1; gene; dna
AB The rapid cell turnover of the intestinal epithelium is achieved from small numbers of stem cells located in the base of glandular crypts. These stem cells have been variously described as rapidly cycling or. quiescent. A functional arrangement of stem cells that reconciles both of these behaviours has so far been difficult to obtain. Alternative explanations for quiescent cells have been that they act as a parallel or reserve population that replace rapidly cycling stem cells periodically or after injury; their exact nature remains unknown. Here we show mouse intestinal quiescent cells to be precursors that are committed to mature into differentiated secretory cells of the Paneth and enteroendocrine lineage. However, crucially we find that after intestinal injury they are capable of extensive proliferation and can give rise to clones comprising the main epithelial cell types. Thus, quiescent cells can be recalled to the-stem-cell state. These findings establish quiescent cells as an effective clonogenic reserve and provide a motivation for investigating their role in pathologies such as colorectal cancers and intestinal inflammation.
C1 [Winton, Douglas J.] Canc Res UK Cambridge Res Inst, Li Ka Shing Ctr, Cambridge CB2 0RE, England.
   [Buczacki, Simon J. A.; Zecchini, Heather Ireland; Nicholson, Anna M.; Russell, Roslin; Vermeulen, Louis; Kemp, Richard; Winton, Douglas J.] Canc Res UK Cambridge Res Inst, Li Ka Shing Ctr, Cambridge CB2 0RE, England.
C3 Cancer Research UK; CRUK Cambridge Institute; Cancer Research UK; CRUK Cambridge Institute
RP Winton, DJ (corresponding author), Canc Res UK Cambridge Res Inst, Li Ka Shing Ctr, Robinson Way, Cambridge CB2 0RE, England.
EM doug.winton@cruk.cam.ac.uk
FU Cancer Research UK; KWF fellowship; Cancer Research UK [22310, 17044] Funding Source: researchfish
NR 25
TC 627
Z9 744
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 MAR 7
PY 2013
VL 495
IS 7439
BP 65
EP 69
DI 10.1038/nature11965
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 105BE
UT WOS:000316039800040
PM 23446353
DA 2026-03-09
ER

PT J
AU Takebe, T
   Sekine, K
   Enomura, M
   Koike, H
   Kimura, M
   Ogaeri, T
   Zhang, RR
   Ueno, Y
   Zheng, YW
   Koike, N
   Aoyama, S
   Adachi, Y
   Taniguchi, H
AF Takebe, Takanori
   Sekine, Keisuke
   Enomura, Masahiro
   Koike, Hiroyuki
   Kimura, Masaki
   Ogaeri, Takunori
   Zhang, Ran-Ran
   Ueno, Yasuharu
   Zheng, Yun-Wen
   Koike, Naoto
   Aoyama, Shinsuke
   Adachi, Yasuhisa
   Taniguchi, Hideki
TI Vascularized and functional human liver from an iPSC-derived organ bud transplant
SO NATURE
LA English
DT Article
ID chimeric mice; stem-cell; organogenesis; generation; endoderm; growth; mouse; model
AB A critical shortage of donor organs for treating end-stage organ failure highlights the urgent need for generating organs from human induced pluripotent stem cells (iPSCs)(1). Despite many reports describing functional cell differentiation(2-4), no studies have succeeded in generating a three-dimensional vascularized organ such as liver. Here we show the generation of vascularized and functional human liver from human iPSCs by transplantation of liver buds created in vitro (iPSC-LBs). Specified hepatic cells (immature endodermal cells destined to track the hepatic cell fate) self-organized into three-dimensional iPSC-LBs by recapitulating organogenetic interactions between endothelial and mesenchymal cells(5). Immunostaining and gene-expression analyses revealed a resemblance between in vitro grown iPSC-LBs and in vivo liver buds. Human vasculatures in iPSC-LB transplants became functional by connecting to the host vessels within 48 hours. The formation of functional vasculatures stimulated the maturation of iPSC-LBs into tissue resembling the adult liver. Highly metabolic iPSC-derived tissue performed liver-specific functions such as protein production and human-specific drug metabolism without recipient liver replacement(6). Furthermore, mesenteric transplantation of iPSC-LBs rescued the drug-induced lethal liver failure model. To our knowledge, this is the first report demonstrating the generation of a functional human organ from pluripotent stem cells. Although efforts must ensue to translate these techniques to treatments for patients, this proof-of-concept demonstration of organ-bud transplantation provides a promising new approach to study regenerative medicine.
C1 [Takebe, Takanori; Sekine, Keisuke; Enomura, Masahiro; Koike, Hiroyuki; Kimura, Masaki; Ogaeri, Takunori; Zhang, Ran-Ran; Ueno, Yasuharu; Zheng, Yun-Wen; Koike, Naoto; Taniguchi, Hideki] Yokohama City Univ, Grad Sch Med, Dept Regenerat Med, Kanazawa Ku, Yokohama, Kanagawa 2360004, Japan.
   [Takebe, Takanori; Taniguchi, Hideki] Yokohama City Univ, Adv Med Res Ctr, Yokohama, Kanagawa 2360004, Japan.
   [Koike, Naoto] Seirei Sakura Citizen Hosp, Dept Surg, Sakura, Chiba 2858765, Japan.
   [Aoyama, Shinsuke; Adachi, Yasuhisa] Sekisui Med Co Ltd, ADME & Tox Res Inst, Tokai, Ibaraki 3191182, Japan.
C3 Yokohama City University; Yokohama City University; Sekisui Chemical Co Ltd
RP Takebe, T (corresponding author), Yokohama City Univ, Grad Sch Med, Dept Regenerat Med, Kanazawa Ku, 3-9 Fukuura, Yokohama, Kanagawa 2360004, Japan.
EM ttakebe@yokohama-cu.ac.jp; rtanigu@yokohama-cu.ac.jp
FU Strategic Promotion of Innovative Research and Development (S-innovation) of the Japan Science and Technology Agency (JST) [62890004]; Ministry of Education, Culture, Sports, Science, and Technology of Japan [24106510, 24689052, 22390260, 21249071, 25253079]; Takeda Science Foundation; Japan IDDM network; Yokohama Foundation for Advanced Medical Science; Grants-in-Aid for Scientific Research [62890004, 24689052, 21249071, 24106510, 25461956, 24659593, 22390260, 24659785, 25253079] Funding Source: KAKEN
NR 23
TC 1657
Z9 2026
U1 18
U2 683
PU NATURE PUBLISHING 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 25
PY 2013
VL 499
IS 7459
BP 481
EP +
DI 10.1038/nature12271
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 187YP
UT WOS:000322157900041
PM 23823721
DA 2026-03-09
ER

PT J
AU Gerber, EE
   Gallo, EM
   Fontana, SC
   Davis, EC
   Wigley, FM
   Huso, DL
   Dietz, HC
AF Gerber, Elizabeth E.
   Gallo, Elena M.
   Fontana, Stefani C.
   Davis, Elaine C.
   Wigley, Fredrick M.
   Huso, David L.
   Dietz, Harry C.
TI Integrin-modulating therapy prevents fibrosis and autoimmunity in mouse models of scleroderma
SO NATURE
LA English
DT Article
ID plasmacytoid dendritic cells; tgf-beta; expression; pathogenesis; disease; skin; beta-1-integrin; contributes; mechanisms; proteins
AB In systemic sclerosis (SSc), a common and aetiologically mysterious form of scleroderma (defined as pathological fibrosis of the skin), previously healthy adults acquire fibrosis of the skin and viscera in association with autoantibodies(1). Familial recurrence is extremely rare and causal genes have not been identified. Although the onset of fibrosis in SSc typically correlates with the production of autoantibodies, whether they contribute to disease pathogenesis or simply serve as a marker of disease remains controversial and the mechanism for their induction is largely unknown(2). The study of SSc is hindered by a lack of animal models that recapitulate the aetiology of this complex disease. To gain a foothold in the pathogenesis of pathological skin fibrosis, we studied stiff skin syndrome (SSS), a rare but tractable Mendelian disorder leading to childhood onset of diffuse skin fibrosis with autosomal dominant inheritance and complete penetrance. We showed previously that SSS is caused by heterozygous missense mutations in the gene (FBN1) encoding fibrillin-1, the main constituent of extracellular microfibrils(3). SSS mutations all localize to the only domain in fibrillin-1 that harbours an Arg-Gly-Asp (RGD) motif needed to mediate cell-matrix interactions by binding to cell-surface integrins(3). Here we show that mouse lines harbouring analogous amino acid substitutions in fibrillin-1 recapitulate aggressive skin fibrosis that is prevented by integrin-modulating therapies and reversed by antagonism of the pro-fibrotic cytokine transforming growth factor beta (TGF-beta). Mutant mice show skin infiltration of pro-inflammatory immune cells including plasmacytoid dendritic cells, T helper cells and plasma cells, and also autoantibody production; these findings are normalized by integrin-modulating therapies or TGF-beta antagonism. These results show that alterations in cell-matrix interactions are sufficient to initiate and sustain inflammatory and pro-fibrotic programmes and highlight new therapeutic strategies.
C1 [Gerber, Elizabeth E.; Gallo, Elena M.; Fontana, Stefani C.; Dietz, Harry C.] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD 21205 USA.
   [Davis, Elaine C.] McGill Univ, Montreal, PQ H3A 2K6, Canada.
   [Wigley, Fredrick M.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA.
   [Huso, David L.] Johns Hopkins Univ, Sch Med, Dept Mol & Comparat Pathobiol, Baltimore, MD 21205 USA.
   [Dietz, Harry C.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA.
C3 Johns Hopkins University; McGill University; Johns Hopkins University; Johns Hopkins University; Howard Hughes Medical Institute
RP Dietz, HC (corresponding author), Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD 21205 USA.
EM hdietz@jhmi.edu
FU Scleroderma Research Foundation; National Institutes of Health [RO1-AR41135, PO1-AR049698]; National Marfan Foundation; Smilow Center for Marfan Syndrome Research; Howard Hughes Medical Institute; National Institute of General Medical Sciences [T32GM007814] Funding Source: NIH RePORTER
NR 39
TC 155
Z9 183
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 NOV 7
PY 2013
VL 503
IS 7474
BP 126
EP +
DI 10.1038/nature12614
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 247AS
UT WOS:000326585600045
PM 24107997
DA 2026-03-09
ER

PT J
AU Zhou, WJ
   Geng, ZH
   Spence, JR
   Geng, JG
AF Zhou, Wei-Jie
   Geng, Zhen H.
   Spence, Jason R.
   Geng, Jian-Guo
TI Induction of intestinal stem cells by R-spondin 1 and Slit2 augments chemoradioprotection
SO NATURE
LA English
DT Article
ID in-vitro; r-spondin1; cancer; growth; colon; mice
AB Cancer research has been rightly and successfully focused on prevention, early detection, and identification of specific molecular targets that distinguish the malignant cells from the neighbouring benign cells(1). However, reducing lethal tissue injury caused by intensive chemoradiotherapy during treatment of late-stage metastatic cancers remains a key clinical challenge. Here we tested whether the induction of adult stem cells could repair chemoradiation-induced tissue injury and prolong overall survival in mice. We found that intestinal stem cells (ISCs)(2) expressed Slit2 and its single-span transmembrane cell-surface receptor roundabout 1 (Robo1)(3,4). Partial genetic deletion of Robo1 decreased ISC numbers and caused villus hypotrophy, whereas a Slit2 transgene increased ISC numbers and triggered villus hypertrophy. During lethal dosages of chemoradiation, administering a short pulse of R-spondin 1 (Rspo1; a Wnt agonist)(5-14) plus Slit2 reduced ISC loss, mitigated gut impairment and protected animals from death, without concomitantly decreasing tumour sensitivity to chemotherapy. Therefore Rspo1 and Slit2 may act as therapeutic adjuvants to enhance host tolerance to aggressive chemoradiotherapy for eradicating metastatic cancers.
C1 [Zhou, Wei-Jie; Geng, Zhen H.; Geng, Jian-Guo] Univ Michigan, Sch Dent, Dept Biol & Mat Sci, Ann Arbor, MI 48109 USA.
   [Spence, Jason R.] Univ Michigan, Sch Med, Dept Cell & Dev Biol, Div Gastroenterol, Ann Arbor, MI 48109 USA.
   [Spence, Jason R.] Univ Michigan, Sch Med, Dept Internal Med, Div Gastroenterol, Ann Arbor, MI 48109 USA.
C3 University of Michigan System; University of Michigan; University of Michigan System; University of Michigan; University of Michigan System; University of Michigan
RP Geng, JG (corresponding author), Univ Michigan, Sch Dent, Dept Biol & Mat Sci, Ann Arbor, MI 48109 USA.
EM jgeng@umich.edu
FU National Institutes of Health [CA126897]
NR 30
TC 121
Z9 139
U1 1
U2 56
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 5
PY 2013
VL 501
IS 7465
BP 107
EP +
DI 10.1038/nature12416
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 211ER
UT WOS:000323888300041
PM 23903657
DA 2026-03-09
ER

PT J
AU Wang, J
   Wurm, Y
   Nipitwattanaphon, M
   Riba-Grognuz, O
   Huang, YC
   Shoemaker, D
   Keller, L
AF Wang, John
   Wurm, Yannick
   Nipitwattanaphon, Mingkwan
   Riba-Grognuz, Oksana
   Huang, Yu-Ching
   Shoemaker, DeWayne
   Keller, Laurent
TI A Y-like social chromosome causes alternative colony organization in fire ants
SO NATURE
LA English
DT Article
ID gene; gp-9; fitness; genome; life; red
AB Intraspecific variability in social organization is common, yet the underlying causes are rarely known(1-3). In the fire ant Solenopsis invicta, the existence of two divergent forms of social organization is under the control of a single Mendelian genomic element marked by two variants of an odorant-binding protein gene(4-8). Here we characterize the genomic region responsible for this important social polymorphism, and show that it is part of a pair of heteromorphic chromosomes that have many of the key properties of sex chromosomes. The two variants, hereafter referred to as the social B and social b (SB and Sb) chromosomes, are characterized by a large region of approximately 13 megabases (55% of the chromosome) in which recombination is completely suppressed between SB and Sb. Recombination seems to occur normally between the SB chromosomes but not between Sb chromosomes because Sb/Sb individuals are non-viable. Genomic comparisons revealed limited differentiation between SB and Sb, and the vast majority of the 616 genes identified in the non-recombining region are present in the two variants. The lack of recombination over more than half of the two heteromorphic social chromosomes can be explained by at least one large inversion of around 9 megabases, and this absence of recombination has led to the accumulation of deleterious mutations, including repetitive elements in the non-recombining region of Sb compared with the homologous region of SB. Importantly, most of the genes with demonstrated expression differences between individuals of the two social forms reside in the non-recombining region. These findings highlight how genomic rearrangements can maintain divergent adaptive social phenotypes involving many genes acting together by locally limiting recombination.
C1 [Wang, John; Wurm, Yannick; Nipitwattanaphon, Mingkwan; Riba-Grognuz, Oksana; Keller, Laurent] Univ Lausanne, Dept Ecol & Evolut, CH-1015 Lausanne, Switzerland.
   [Wang, John; Huang, Yu-Ching] Acad Sinica, Biodivers Res Ctr, Taipei 115, Taiwan.
   [Wurm, Yannick] Queen Mary Univ London, Sch Biol & Chem Sci, London E1 4NS, England.
   [Wurm, Yannick; Riba-Grognuz, Oksana] Swiss Inst Bioinformat, CH-1015 Lausanne, Switzerland.
   [Shoemaker, DeWayne] USDA ARS, Ctr Med Agr & Vet Entomol, Gainesville, FL 32608 USA.
C3 University of Lausanne; Academia Sinica - Taiwan; University of London; Queen Mary University London; Swiss Institute of Bioinformatics; United States Department of Agriculture (USDA)
RP Wang, J (corresponding author), Univ Lausanne, Dept Ecol & Evolut, CH-1015 Lausanne, Switzerland.
EM johnwang@gate.sinica.edu.tw; y.wurm@qmul.ac.uk; laurent.keller@unil.ch
FU Biodiversity Research Center (Academia Sinica, Taiwan), Taiwan NSC [100-2311-B-001-015-MY3]; NERC; BBSRC [BB/K004204/1]; USDA; Swiss NSF; ERC; BBSRC [BB/K004204/1] Funding Source: UKRI; Biotechnology and Biological Sciences Research Council [BB/K004204/1] Funding Source: researchfish
NR 30
TC 314
Z9 351
U1 3
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 JAN 31
PY 2013
VL 493
IS 7434
BP 664
EP 668
DI 10.1038/nature11832
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 080CU
UT WOS:000314219600055
PM 23334415
DA 2026-03-09
ER

PT J
AU Chiu, IM
   Heesters, BA
   Ghasemlou, N
   Von Hehn, CA
   Zhao, F
   Tran, J
   Wainger, B
   Strominger, A
   Muralidharan, S
   Horswill, AR
   Wardenburg, JB
   Hwang, SW
   Carroll, MC
   Woolf, CJ
AF Chiu, Isaac M.
   Heesters, Balthasar A.
   Ghasemlou, Nader
   Von Hehn, Christian A.
   Zhao, Fan
   Tran, Johnathan
   Wainger, Brian
   Strominger, Amanda
   Muralidharan, Sriya
   Horswill, Alexander R.
   Wardenburg, Juliane Bubeck
   Hwang, Sun Wook
   Carroll, Michael C.
   Woolf, Clifford J.
TI Bacteria activate sensory neurons that modulate pain and inflammation
SO NATURE
LA English
DT Article
ID formyl-peptide receptors; staphylococcus-aureus; alpha-hemolysin; t-cells; immunity; usa300; mice; identification; pathogenesis; nociceptors
AB Nociceptor sensory neurons are specialized to detect potentially damaging stimuli, protecting the organism by initiating the sensation of pain and eliciting defensive behaviours. Bacterial infections produce pain by unknown molecular mechanisms, although they are presumed to be secondary to immune activation. Here we demonstrate that bacteria directly activate nociceptors, and that the immune response mediated through TLR2, MyD88, T cells, B cells, and neutrophils and monocytes is not necessary for Staphylococcus aureus-induced pain in mice. Mechanical and thermal hyperalgesia in mice is correlated with live bacterial load rather than tissue swelling or immune activation. Bacteria induce calcium flux and action potentials in nociceptor neurons, in part via bacterial N-formylated peptides and the pore-forming toxin alpha-haemolysin, through distinct mechanisms. Specific ablation of Nav1.8-lineage neurons, which include nociceptors, abrogated pain during bacterial infection, but concurrently increased local immune infiltration and lymphadenopathy of the draining lymph node. Thus, bacterial pathogens produce pain by directly activating sensory neurons that modulate inflammation, an unsuspected role for the nervous systemin host-pathogen interactions.
C1 [Chiu, Isaac M.; Ghasemlou, Nader; Von Hehn, Christian A.; Tran, Johnathan; Wainger, Brian; Strominger, Amanda; Muralidharan, Sriya; Hwang, Sun Wook; Woolf, Clifford J.] Boston Childrens Hosp, Kirby Neurobiol Ctr, Boston, MA 02115 USA.
   [Chiu, Isaac M.; Ghasemlou, Nader; Von Hehn, Christian A.; Tran, Johnathan; Wainger, Brian; Strominger, Amanda; Muralidharan, Sriya; Hwang, Sun Wook; Woolf, Clifford J.] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA.
   [Heesters, Balthasar A.; Carroll, Michael C.] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA.
   [Heesters, Balthasar A.; Carroll, Michael C.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
   [Heesters, Balthasar A.] Univ Med Ctr, NL-3584 CX Utrecht, Netherlands.
   [Zhao, Fan] Brandeis Univ, Dept Chem, Quantitat Biol Program, Waltham, MA 02454 USA.
   [Horswill, Alexander R.] Univ Iowa, Dept Microbiol, Roy J & Lucille A Carver Coll Med, Iowa City, IA 52242 USA.
   [Wardenburg, Juliane Bubeck] Univ Chicago, Dept Pediat, Chicago, IL 60637 USA.
   [Wardenburg, Juliane Bubeck] Univ Chicago, Dept Microbiol, Chicago, IL 60637 USA.
   [Hwang, Sun Wook] Korea Univ, Grad Sch Med, Seoul 136705, South Korea.
C3 Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Harvard University; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Program in Cellular & Molecular Medicine (PCMM); Harvard University; Harvard Medical School; Utrecht University; Utrecht University Medical Center; Brandeis University; University of Iowa; University of Chicago; University of Chicago; Korea University; Korea University Medicine (KU Medicine)
RP Woolf, CJ (corresponding author), Boston Childrens Hosp, Kirby Neurobiol Ctr, Boston, MA 02115 USA.
EM clifford.woolf@childrens.harvard.edu
FU NIH [PO1AI078897, 5RO1AI039246, R37NS039518, 5P01NS072040, 5F32NS076297]; FACS
NR 53
TC 718
Z9 829
U1 6
U2 217
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 5
PY 2013
VL 501
IS 7465
BP 52
EP +
DI 10.1038/nature12479
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 211ER
UT WOS:000323888300030
PM 23965627
DA 2026-03-09
ER

PT J
AU Moore, WB
   Webb, AAG
AF Moore, William B.
   Webb, A. Alexander G.
TI Heat-pipe Earth
SO NATURE
LA English
DT Article
ID barberton greenstone-belt; southern west greenland; itsaq gneiss complex; isotope evidence; plate-tectonics; jack hills; crust; ga; zircons; origin
AB The heat transport and lithospheric dynamics of early Earth are currently explained by plate tectonic and vertical tectonic models, but these do not offer a global synthesis consistent with the geologic record. Here we use numerical simulations and comparison with the geologic record to explore a heat-pipe model in which volcanism dominates surface heat transport. These simulations indicate that a cold and thick lithosphere developed as a result of frequent volcanic eruptions that advected surface materials downwards. Declining heat sources over time led to an abrupt transition to plate tectonics. Consistent with model predictions, the geologic record shows rapid volcanic resurfacing, contractional deformation, a low geothermal gradient across the bulk of the lithosphere and a rapid decrease in heat-pipe volcanism after initiation of plate tectonics. The heat-pipe Earth model therefore offers a coherent geodynamic framework in which to explore the evolution of our planet before the onset of plate tectonics.
C1 [Moore, William B.] Hampton Univ, Dept Atmospher & Planetary Sci, Hampton, VA 23668 USA.
   [Moore, William B.] Natl Inst Aerosp, Hampton, VA 23666 USA.
   [Webb, A. Alexander G.] Louisiana State Univ, Dept Geol & Geophys, Baton Rouge, LA 70803 USA.
C3 Hampton University; National Institute for Aerospace; Louisiana State University System; Louisiana State University
RP Moore, WB (corresponding author), Hampton Univ, Dept Atmospher & Planetary Sci, Hampton, VA 23668 USA.
EM william.moore@hamptonu.edu
FU NSF Geophysics; NASA PGG; NASA Astrobiology Institute; Louisiana State University; Division Of Earth Sciences; Directorate For Geosciences [1246983] Funding Source: National Science Foundation
NR 42
TC 268
Z9 306
U1 1
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 SEP 26
PY 2013
VL 501
IS 7468
BP 501
EP 505
DI 10.1038/nature12473
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 223RP
UT WOS:000324826300048
PM 24067709
DA 2026-03-09
ER

PT J
AU Lee, W
   Kim, K
   Jeong, W
   Zotti, LA
   Pauly, F
   Cuevas, JC
   Reddy, P
AF Lee, Woochul
   Kim, Kyeongtae
   Jeong, Wonho
   Angela Zotti, Linda
   Pauly, Fabian
   Carlos Cuevas, Juan
   Reddy, Pramod
TI Heat dissipation in atomic-scale junctions
SO NATURE
LA English
DT Article
ID single-molecule junctions; conductance; thermopower; thermoelectricity; dependence; contact; flow
AB Atomic and single-molecule junctions represent the ultimate limit to the miniaturization of electrical circuits(1). They are also ideal platforms for testing quantum transport theories that are required to describe charge and energy transfer in novel functional nano-metre-scale devices. Recent work has successfully probed electric and thermoelectric phenomena(2-8) in atomic-scale junctions. However, heat dissipation and transport in atomic-scale devices remain poorly characterized owing to experimental challenges. Here we use custom-fabricated scanning probes with integrated nanoscale thermocouples to investigate heat dissipation in the electrodes of single-molecule ('molecular') junctions. We find that if the junctions have transmission characteristics that are strongly energy dependent, this heat dissipation is asymmetric-that is, unequal between the electrodes-and also dependent on both the bias polarity and the identity of the majority charge carriers (electrons versus holes). In contrast, junctions consisting of only a few gold atoms ('atomic junctions') whose transmission characteristics show weak energy dependence do not exhibit appreciable asymmetry. Our results unambiguously relate the electronic transmission characteristics of atomic-scale junctions to their heat dissipation properties, establishing a framework for understanding heat dissipation in a range of mesoscopic systems where transport is elastic-that is, without exchange of energy in the contact region. We anticipate that the techniques established here will enable the study of Peltier effects at the atomic scale, a field that has been barely explored experimentally despite interesting theoretical predictions(9-11). Furthermore, the experimental advances described here are also expected to enable the study of heat transport in atomic and molecular junctions-an important and challenging scientific and technological goal that has remained elusive(12,13).
C1 [Lee, Woochul; Kim, Kyeongtae; Jeong, Wonho; Reddy, Pramod] Univ Michigan, Dept Mech Engn, Ann Arbor, MI 48109 USA.
   [Angela Zotti, Linda; Carlos Cuevas, Juan] Univ Autonoma Madrid, Dept Fis Teor Mat Condensada, E-28049 Madrid, Spain.
   [Angela Zotti, Linda; Carlos Cuevas, Juan] Univ Autonoma Madrid, Condensed Matter Phys Ctr IFIMAC, E-28049 Madrid, Spain.
   [Pauly, Fabian] Univ Konstanz, Dept Phys, D-78457 Constance, Germany.
   [Reddy, Pramod] Univ Michigan, Dept Mat Sci & Engn, Ann Arbor, MI 48109 USA.
C3 University of Michigan System; University of Michigan; Autonomous University of Madrid; Autonomous University of Madrid; University of Konstanz; University of Michigan System; University of Michigan
RP Reddy, P (corresponding author), Univ Michigan, Dept Mech Engn, Ann Arbor, MI 48109 USA.
EM juancarlos.cuevas@uam.es; pramodr@umich.edu
FU US Department of Energy, Office of Basic Energy Sciences, Division of Materials Sciences and Engineering [DE-SC0004871]; National Science Foundation [CBET 0844902]; Center for Solar and Thermal Energy conversion, an Energy Frontier Research Center; US Department of Energy, Office of Science, Basic Energy Sciences [DE-SC0000957]; Spanish MICINN [FIS2010-21883]; Carl Zeiss Stiftung; DFG [SFB 767]; Baden-Wurttemberg Stiftung; Directorate For Engineering [0844902] Funding Source: National Science Foundation; Div Of Chem, Bioeng, Env, & Transp Sys [0844902] Funding Source: National Science Foundation
NR 30
TC 240
Z9 267
U1 5
U2 381
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 13
PY 2013
VL 498
IS 7453
BP 209
EP +
DI 10.1038/nature12183
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 162RR
UT WOS:000320283400043
PM 23765496
DA 2026-03-09
ER

PT J
AU Mizuno, K
   Miyabe, I
   Schalbetter, SA
   Carr, AM
   Murray, JM
AF Mizuno, Ken'Ichi
   Miyabe, Izumi
   Schalbetter, Stephanie A.
   Carr, Antony M.
   Murray, Johanne M.
TI Recombination-restarted replication makes inverted chromosome fusions at inverted repeats
SO NATURE
LA English
DT Article
ID break-induced replication; genomic rearrangements; template exchange; ribosomal dna; fragile site; mechanisms; disorders; repair
AB Impediments to DNA replication are known to induce gross chromosomal rearrangements (GCRs) and copy-number variations (CNVs). GCRs and CNVs underlie human genomic disorders(1) and are a feature of cancer(2). During cancer development, environmental factors and oncogene-driven proliferation promote replication stress. Resulting GCRs and CNVs are proposed to contribute to cancer development and therapy resistance(3). When stress arrests replication, the replisome remains associated with the fork DNA(stalled fork) and is protected by the inter-S-phase checkpoint. Stalled forks efficiently resume when the stress is relieved. However, if the polymerases dissociate from the fork (fork collapse) or the fork structure breaks (broken fork), replication restart can proceed either by homologous recombination or microhomology-primed re-initiation(4,5). Here we ascertain the consequences of replication with a fork restarted by homologous recombination in fission yeast. We identify a new mechanism of chromosomal rearrangement through the observation that recombination-restarted forks have a considerably high propensity to execute a U-turn at small inverted repeats (up to 1 in 40 replication events). We propose that the error-prone nature of restarted forks contributes to the generation of GCRs and gene amplification in cancer, and to non-recurrent CNVs in genomic disorders.
C1 [Mizuno, Ken'Ichi; Miyabe, Izumi; Schalbetter, Stephanie A.; Carr, Antony M.; Murray, Johanne M.] Univ Sussex, Genome Damage & Stabil Ctr, Brighton BN1 9RQ, E Sussex, England.
C3 University of Sussex
RP Carr, AM (corresponding author), Univ Sussex, Genome Damage & Stabil Ctr, Brighton BN1 9RQ, E Sussex, England.
EM a.m.carr@sussex.ac.uk
FU Cancer Research UK (CRUK) [C9601/A9484]; Medical Research Council (MRC) [G0600233]; MRC [G0600233, G1100074, G0500308] Funding Source: UKRI; Biotechnology and Biological Sciences Research Council [BB/C510291/1] Funding Source: researchfish; Medical Research Council [G1100074, G0600233, G0500308] Funding Source: researchfish
NR 30
TC 122
Z9 132
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 JAN 10
PY 2013
VL 493
IS 7431
BP 246
EP 249
DI 10.1038/nature11676
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 066YY
UT WOS:000313259600044
PM 23178809
DA 2026-03-09
ER

PT J
AU Miller, RA
   Chu, QW
   Xie, JX
   Foretz, M
   Viollet, B
   Birnbaum, MJ
AF Miller, Russell A.
   Chu, Qingwei
   Xie, Jianxin
   Foretz, Marc
   Viollet, Benoit
   Birnbaum, Morris J.
TI Biguanides suppress hepatic glucagon signalling by decreasing production of cyclic AMP
SO NATURE
LA English
DT Article
ID adenylate-cyclase activity; diabetes-mellitus; respiratory-chain; protein-kinase; energy-state; metformin; adenosine; liver; inhibition; glucose
AB Glucose production by the liver is essential for providing a substrate for the brain during fasting. The inability of insulin to suppress hepatic glucose output is a major aetiological factor in the hyperglycaemia of type-2 diabetes mellitus and other diseases of insulin resistance(1,2). For fifty years, one of the few classes of therapeutics effective in reducing glucose production has been the biguanides, which include phenformim and metformin, the latter the most frequently prescribed drug for type-2 diabetes(3). Nonetheless, the mechanism of action of biguanides remains imperfectly understood. The suggestion a decade ago that metformin reduces glucose synthesis through activation of the enzyme AMP-activated protein kinase (AMPK) has recently been challenged by genetic loss-of-function experiments(4). Here we provide a novel mechanism by which metformin antagonizes the action of glucagon, thus reducing fasting glucose levels. In mouse hepatocytes, metformin leads to the accumulation of AMP and related nucleotides, which inhibit adenylate cyclase, reduce levels of cyclic AMP and protein kinase A (PICA) activity, abrogate phosphorylation of critical protein targets of PICA, and block glucagon-dependent glucose output from hepatocytes. These data support a mechanism of action for metformin involving antagonism of glucagon, and suggest an approach for the development of antidiabetic drugs.
C1 [Miller, Russell A.; Chu, Qingwei; Birnbaum, Morris J.] Univ Penn, Perelman Sch Med, Inst Diabet Obes & Metab, Philadelphia, PA 19104 USA.
   [Xie, Jianxin] Cell Signaling Technol Inc, Danvers, MA 01923 USA.
   [Foretz, Marc; Viollet, Benoit] Inst Cochin Genet Mol, INSERM, U1016, F-75014 Paris, France.
   [Foretz, Marc; Viollet, Benoit] CNRS, UMR8104, F-75014 Paris, France.
   [Foretz, Marc; Viollet, Benoit] Univ Paris 05, F-75006 Paris, France.
C3 University of Pennsylvania; Cell Signaling Technology; Universite Paris Cite; Institut National de la Sante et de la Recherche Medicale (Inserm); Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB); Universite Paris Cite; Universite Paris Cite
RP Birnbaum, MJ (corresponding author), Univ Penn, Perelman Sch Med, Inst Diabet Obes & Metab, Philadelphia, PA 19104 USA.
EM birnbaum@mail.med.upenn.edu
FU National Institutes of Health (NIH) [RO1 DK56886, PO1 DK49210, F32 DK079572]; Association pour l'Etude des Diabetes et des Maladies Metaboliques (ALFEDIAM); Programme National de Recherche sur le Diabete (PNRD); Institut Benjamin Delessert; National Institute of Diabetes and Digestive and Kidney Diseases [P30DK019525] Funding Source: NIH RePORTER
NR 30
TC 694
Z9 811
U1 1
U2 190
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 14
PY 2013
VL 494
IS 7436
BP 256
EP 260
DI 10.1038/nature11808
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 092QS
UT WOS:000315137700044
PM 23292513
DA 2026-03-09
ER

PT J
AU Derex, M
   Beugin, MP
   Godelle, B
   Raymond, M
AF Derex, Maxime
   Beugin, Marie-Pauline
   Godelle, Bernard
   Raymond, Michel
TI Experimental evidence for the influence of group size on cultural complexity
SO NATURE
LA English
DT Article
ID demography; evolution
AB The remarkable ecological and demographic success of humanity is largely attributed to our capacity for cumulative culture(1-3). The accumulation of beneficial cultural innovations across generations is puzzling because transmission events are generally imperfect, although there is large variance in fidelity. Events of perfect cultural transmission and innovations should be more frequent in a large population(4). As a consequence, a large population size may be a prerequisite for the evolution of cultural complexity(4,5), although anthropological studies have produced mixed results(6-9) and empirical evidence is lacking(10). Here we use a dual-task computer game to show that cultural evolution strongly depends on population size, as players in larger groups maintained higher cultural complexity. We found that when group size increases, cultural knowledge is less deteriorated, improvements to existing cultural traits are more frequent, and cultural trait diversity is maintained more often. Our results demonstrate how changes in group size can generate both adaptive cultural evolution and maladaptive losses of culturally acquired skills. As humans live in habitats for which they are ill-suited without specific cultural adaptations(11,12), it suggests that, in our evolutionary past, group-size reduction may have exposed human societies to significant risks, including societal collapse(13).
C1 [Derex, Maxime; Beugin, Marie-Pauline; Godelle, Bernard; Raymond, Michel] Univ Montpellier 2, F-34095 Montpellier 5, France.
   [Raymond, Michel] CNRS, Inst Evolutionary Sci, Montpellier, France.
C3 Universite de Montpellier; Centre National de la Recherche Scientifique (CNRS); Universite de Montpellier
RP Derex, M (corresponding author), Univ Montpellier 2, Pl Eugene Bataillon, F-34095 Montpellier 5, France.
EM maxime.derex@gmail.com
NR 28
TC 209
Z9 238
U1 0
U2 94
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 21
PY 2013
VL 503
IS 7476
BP 389
EP +
DI 10.1038/nature12774
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 254KG
UT WOS:000327163200039
PM 24226775
DA 2026-03-09
ER

PT J
AU Hasson, SA
   Kane, LA
   Yamano, K
   Huang, CH
   Sliter, DA
   Buehler, E
   Wang, CX
   Heman-Ackah, SM
   Hessa, T
   Guha, R
   Martin, SE
   Youle, RJ
AF Hasson, Samuel A.
   Kane, Lesley A.
   Yamano, Koji
   Huang, Chiu-Hui
   Sliter, Danielle A.
   Buehler, Eugen
   Wang, Chunxin
   Heman-Ackah, Sabrina M.
   Hessa, Tara
   Guha, Rajarshi
   Martin, Scott E.
   Youle, Richard J.
TI High-content genome-wide RNAi screens identify regulators of parkin upstream of mitophagy
SO NATURE
LA English
DT Article
ID mitochondria; recruitment; sensitivity; activation; mutations; promotes; complex
AB An increasing body of evidence points to mitochondrial dysfunction as a contributor to the molecular pathogenesis of neurodegenerative diseases such as Parkinson's disease(1). Recent studies of the Parkinson's disease associated genes PINK1 (ref. 2) and parkin (PARK2, ref. 3) indicate that they may act in a quality control pathway preventing the accumulation of dysfunctional mitochondria(4-8). Here we elucidate regulators that have an impact on parkin translocation to damaged mitochondria with genome-wide small interfering RNA (siRNA) screens coupled to high-content microscopy. Screening yielded gene candidates involved in diverse cellular processes that were subsequently validated in low-throughput assays. This led to characterization of TOMM7 as essential for stabilizing PINK1 on the outer mitochondrial membrane following mitochondrial damage. We also discovered that HSPA1L (HSP70 family member) and BAG4 have mutually opposing roles in the regulation of parkin translocation. The screens revealed that SIAH3, found to localize to mitochondria, inhibits PINK1 accumulation after mitochondrial insult, reducing parkin translocation. Overall, our screens provide a rich resource to understand mitochondrial quality control.
C1 [Hasson, Samuel A.; Kane, Lesley A.; Yamano, Koji; Huang, Chiu-Hui; Sliter, Danielle A.; Wang, Chunxin; Hessa, Tara; Youle, Richard J.] NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA.
   [Hasson, Samuel A.; Buehler, Eugen; Guha, Rajarshi; Martin, Scott E.] NIH, Div Preclin Innovat, Natl Ctr Adv Translat Sci, Rockville, MD 20850 USA.
   [Heman-Ackah, Sabrina M.] NIH, Ctr Regenerat Med, 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 Center for Advancing Translational Sciences (NCATS); National Institutes of Health (NIH) - USA
RP Youle, RJ (corresponding author), NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA.
EM youler@ninds.nih.gov
FU Japan Society for Promotion of Science; NIGMS Research Associate Program; NIH, NINDS; Trans-NIH RNAi initiative; National Institute of Neurological Disorders and Stroke [ZIANS003123] Funding Source: NIH RePORTER
NR 30
TC 306
Z9 367
U1 1
U2 89
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 12
PY 2013
VL 504
IS 7479
BP 291
EP +
DI 10.1038/nature12748
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 267TQ
UT WOS:000328121500039
PM 24270810
DA 2026-03-09
ER

PT J
AU Lancaster, MA
   Renner, M
   Martin, CA
   Wenzel, D
   Bicknell, LS
   Hurles, ME
   Homfray, T
   Penninger, JM
   Jackson, AP
   Knoblich, JA
AF Lancaster, Madeline A.
   Renner, Magdalena
   Martin, Carol-Anne
   Wenzel, Daniel
   Bicknell, Louise S.
   Hurles, Matthew E.
   Homfray, Tessa
   Penninger, Josef M.
   Jackson, Andrew P.
   Knoblich, Juergen A.
TI Cerebral organoids model human brain development and microcephaly
SO NATURE
LA English
DT Article
ID embryonic stem-cells; outer subventricular zone; spindle orientation; human neocortex; in-vitro; mammalian neurogenesis; 3-dimensional culture; extrinsic signals; mouse neocortex; self-formation
AB The complexity of the human brain has made it difficult to study many brain disorders in model organisms, highlighting the need for an in vitro model of human brain development. Here we have developed a human pluripotent stem cell-derived three-dimensional organoid culture system, termed cerebral organoids, that develop various discrete, although interdependent, brain regions. These include a cerebral cortex containing progenitor populations that organize and produce mature cortical neuron subtypes. Furthermore, cerebral organoids are shown to recapitulate features of human cortical development, namely characteristic progenitor zone organization with abundant outer radial glial stem cells. Finally, we use RNA interference and patient-specific induced pluripotent stem cells to model microcephaly, a disorder that has been difficult to recapitulate in mice. We demonstrate premature neuronal differentiation in patient organoids, a defect that could help to explain the disease phenotype. Together, these data show that three-dimensional organoids can recapitulate development and disease even in this most complex human tissue.
C1 [Lancaster, Madeline A.; Renner, Magdalena; Wenzel, Daniel; Penninger, Josef M.; Knoblich, Juergen A.] Austrian Acad Sci IMBA, Inst Mol Biotechnol, A-1030 Vienna, Austria.
   [Martin, Carol-Anne; Bicknell, Louise S.; Jackson, Andrew P.] Univ Edinburgh, Inst Genet & Mol Med, MRC Human Genet Unit, Edinburgh EH4 2XU, Midlothian, Scotland.
   [Hurles, Matthew E.] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England.
   [Homfray, Tessa] St Georges Univ, Dept Clin Genet, London SW17 0RE, England.
C3 Austrian Academy of Sciences; Vienna Biocenter (VBC); Institute of Molecular Biotechnology (IMBA); University of Edinburgh; Wellcome Trust Sanger Institute; City St Georges, University of London
RP Knoblich, JA (corresponding author), Austrian Acad Sci IMBA, Inst Mol Biotechnol, A-1030 Vienna, Austria.
EM juergen.knoblich@imba.oeaw.ac.at
FU Wellcome Trust [WT098051]; Austrian Academy of Sciences; Austrian Science Fund (FWF) [Z153-B09, I552-B19]; ERC; EMBO; Helen Hay Whitney; Medical Research Council; European Research Council (ERC); Lister Institute for Preventative Medicine; Austrian Science Fund (FWF) [Z 153] Funding Source: researchfish; Medical Research Council [MC_PC_U127580972] Funding Source: researchfish; Austrian Science Fund (FWF) [Z153] Funding Source: Austrian Science Fund (FWF); MRC [MC_PC_U127580972] Funding Source: UKRI
NR 53
TC 3864
Z9 4679
U1 47
U2 1201
PU NATURE PUBLISHING 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 19
PY 2013
VL 501
IS 7467
BP 373
EP +
DI 10.1038/nature12517
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 219XT
UT WOS:000324545700036
PM 23995685
DA 2026-03-09
ER

PT J
AU Mangravite, LM
   Engelhardt, BE
   Medina, MW
   Smith, JD
   Brown, CD
   Chasman, DI
   Mecham, BH
   Howie, B
   Shim, H
   Naidoo, D
   Feng, QP
   Rieder, MJ
   Chen, YDI
   Rotter, JI
   Ridker, PM
   Hopewell, JC
   Parish, S
   Armitage, J
   Collins, R
   Wilke, RA
   Nickerson, DA
   Stephens, M
   Krauss, RM
AF Mangravite, Lara M.
   Engelhardt, Barbara E.
   Medina, Marisa W.
   Smith, Joshua D.
   Brown, Christopher D.
   Chasman, Daniel I.
   Mecham, Brigham H.
   Howie, Bryan
   Shim, Heejung
   Naidoo, Devesh
   Feng, QiPing
   Rieder, Mark J.
   Chen, Yii-Der I.
   Rotter, Jerome I.
   Ridker, Paul M.
   Hopewell, Jemma C.
   Parish, Sarah
   Armitage, Jane
   Collins, Rory
   Wilke, Russell A.
   Nickerson, Deborah A.
   Stephens, Matthew
   Krauss, Ronald M.
TI A statin-dependent QTL for GATM expression is associated with statin-induced myopathy
SO NATURE
LA English
DT Article
ID lipid-lowering response; simvastatin therapy; gene-expression; cholesterol; transformation; discovery; risk; loci
AB Statins are prescribed widely to lower plasma low-density lipoprotein (LDL) concentrations and cardiovascular disease risk(1) and have been shown to have beneficial effects in a broad range of patients(2,3). However, statins are associated with an increased risk, albeit small, of clinical myopathy(4) and type 2 diabetes(5). Despite evidence for substantial genetic influence on LDL concentrations(6), pharmacogenomic trials have failed to identify genetic variations with large effects on either statin efficacy(7-9) or toxicity(10), and have produced little information regarding mechanisms that modulate statin response. Here we identify a downstream target of statin treatment by screening for the effects of in vitro statin exposure on genetic associations with gene expression levels in lymphoblastoid cell lines derived from 480 participants of a clinical trial of simvastatin treatment(7). This analysis identified six expression quantitative trait loci (eQTLs) that interacted with simvastatin exposure, including rs9806699, a cis-eQTL for the gene glycine amidinotransferase (GATM) that encodes the rate-limiting enzyme in creatine synthesis. We found this locus to be associated with incidence of statin-induced myotoxicity in two separate populations (meta-analysis odds ratio = 0.60). Furthermore, we found that GATM knockdown in hepatocyte-derived cell lines attenuated transcriptional response to sterol depletion, demonstrating that GATM may act as a functional link between statin-mediated lowering of cholesterol and susceptibility to statin-induced myopathy.
C1 [Mangravite, Lara M.; Mecham, Brigham H.] Sage Bionetworks, Seattle, WA 98109 USA.
   [Engelhardt, Barbara E.; Howie, Bryan; Shim, Heejung; Stephens, Matthew] Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA.
   [Medina, Marisa W.; Naidoo, Devesh; Krauss, Ronald M.] Childrens Hosp Oakland, Res Inst, Oakland, CA 94609 USA.
   [Smith, Joshua D.; Rieder, Mark J.; Nickerson, Deborah A.] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA.
   [Brown, Christopher D.] Univ Penn, Dept Genet, Philadelphia, PA 19103 USA.
   [Chasman, Daniel I.; Ridker, Paul M.] Brigham & Womens Hosp, Div Preventat Med, Ctr Cardiovasc Dis Prevent, Boston, MA 02115 USA.
   [Feng, QiPing; Wilke, Russell A.] Vanderbilt Univ, Med Ctr, Div Clin Pharmacol, Dept Med, Nashville, TN 37232 USA.
   [Chen, Yii-Der I.; Rotter, Jerome I.] Harbor UCLA Med Ctr, Los Angeles BioMed Res Inst, Inst Translat Genom & Populat Sci, Torrance, CA 90502 USA.
   [Hopewell, Jemma C.; Parish, Sarah; Armitage, Jane; Collins, Rory] Univ Oxford, Clin Trial Serv Unit, Oxford OX3 7LF, England.
   [Hopewell, Jemma C.; Parish, Sarah; Armitage, Jane; Collins, Rory] Univ Oxford, Epidemiol Studies Unit, Oxford OX3 7LF, England.
   [Stephens, Matthew] Univ Chicago, Dept Stat, Chicago, IL 60637 USA.
C3 University of Chicago; Children's Hospital Oakland Research Institute; University of California System; University of California San Francisco; UCSF Medical Center; UCSF Benioff Children's Hospital Oakland; University of Washington; University of Washington Seattle; University of Pennsylvania; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Vanderbilt University; University of California System; University of California Los Angeles; University of California Los Angeles Medical Center; Lundquist Institute; University of Oxford; University of Oxford; University of Chicago
RP Mangravite, LM (corresponding author), Sage Bionetworks, 1100 Fairview Ave North, Seattle, WA 98109 USA.
EM lara.mangravite@sagebase.org; mstephens@uchicago.edu; rkrauss@chori.org
FU US National Institutes of Health (NIH) [U01 HL69757]; Bioinformatics Research Development Fund; NIH [K99/R00HG006265, HG002585]; Medical Research Council; British Heart Foundation; National Health Service Genetic Knowledge Park; Centre National de Genotypage; Merck; Roche Vitamins; BHF Centre of Research Excellence, Oxford, UK; AstraZeneca; National Human Genome Research Institute [R01HG002585] Funding Source: NIH RePORTER; National Institute of Diabetes and Digestive and Kidney Diseases [P30DK063491] Funding Source: NIH RePORTER; Medical Research Council [MC_U137686853] Funding Source: researchfish; MRC [MC_U137686853] Funding Source: UKRI
NR 40
TC 176
Z9 204
U1 0
U2 47
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 17
PY 2013
VL 502
IS 7471
BP 377
EP +
DI 10.1038/nature12508
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 235GY
UT WOS:000325706300054
PM 23995691
DA 2026-03-09
ER

PT J
AU Chung, K
   Wallace, J
   Kim, SY
   Kalyanasundaram, S
   Andalman, AS
   Davidson, TJ
   Mirzabekov, JJ
   Zalocusky, KA
   Mattis, J
   Denisin, AK
   Pak, S
   Bernstein, H
   Ramakrishnan, C
   Grosenick, L
   Gradinaru, V
   Deisseroth, K
AF Chung, Kwanghun
   Wallace, Jenelle
   Kim, Sung-Yon
   Kalyanasundaram, Sandhiya
   Andalman, Aaron S.
   Davidson, Thomas J.
   Mirzabekov, Julie J.
   Zalocusky, Kelly A.
   Mattis, Joanna
   Denisin, Aleksandra K.
   Pak, Sally
   Bernstein, Hannah
   Ramakrishnan, Charu
   Grosenick, Logan
   Gradinaru, Viviana
   Deisseroth, Karl
TI Structural and molecular interrogation of intact biological systems
SO NATURE
LA English
DT Article
ID mouse-brain; fluorescent proteins; nervous-system; self-avoidance; tomography; microscopy; localization; organization; architecture; connectome
AB Obtaining high-resolution information from a complex system, while maintaining the global perspective needed to understand system function, represents a key challenge in biology. Here we address this challenge with a method (termed CLARITY) for the transformation of intact tissue into a nanoporous hydrogel-hybridized form (crosslinked to a three-dimensional network of hydrophilic polymers) that is fully assembled but optically transparent and macromolecule-permeable. Using mouse brains, we show intact-tissue imaging of long-range projections, local circuit wiring, cellular relationships, subcellular structures, protein complexes, nucleic acids and neurotransmitters. CLARITY also enables intact-tissue in situ hybridization, immunohistochemistry with multiple rounds of staining and de-staining in non-sectioned tissue, and antibody labelling throughout the intact adult mouse brain. Finally, we show that CLARITY enables fine structural analysis of clinical samples, including non-sectioned human tissue from a neuropsychiatric-disease setting, establishing a path for the transmutation of human tissue into a stable, intact and accessible form suitable for probing structural and molecular underpinnings of physiological function and disease.
C1 [Chung, Kwanghun; Wallace, Jenelle; Kim, Sung-Yon; Andalman, Aaron S.; Davidson, Thomas J.; Mirzabekov, Julie J.; Zalocusky, Kelly A.; Mattis, Joanna; Denisin, Aleksandra K.; Pak, Sally; Bernstein, Hannah; Ramakrishnan, Charu; Grosenick, Logan; Deisseroth, Karl] Stanford Univ, Dept Bioengn, Stanford, CA 94305 USA.
   [Chung, Kwanghun; Kalyanasundaram, Sandhiya; Andalman, Aaron S.; Davidson, Thomas J.; Zalocusky, Kelly A.; Gradinaru, Viviana; Deisseroth, Karl] Stanford Univ, CNC Program, Stanford, CA 94305 USA.
   [Deisseroth, Karl] Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA.
   [Deisseroth, Karl] Stanford Univ, Howard Hughes Med Inst, Stanford, CA 94305 USA.
C3 Stanford University; Stanford University; Stanford University; Howard Hughes Medical Institute; Stanford University
RP Deisseroth, K (corresponding author), Stanford Univ, Dept Bioengn, Stanford, CA 94305 USA.
EM deissero@stanford.edu
FU National Institutes of Health (NIH) from NIMH [TR01]; NSF; Simons Foundation; Stanford University; NIDA; DARPA REPAIR program; Wiegers Foundation; Snyder Foundation; Reeves Foundation; Gatsby Foundation; Yu Foundation; Burroughs Wellcome Fund Career Award at the Scientific Interface; Samsung Scholarship; Helen Hay Whitney Foundation; NSF Graduate Research Fellowship; NIH MSTP; Deisseroth laboratory; Division Of Integrative Organismal Systems; Direct For Biological Sciences [1247950] Funding Source: National Science Foundation; National Institute on Drug Abuse [R37DA035377] Funding Source: NIH RePORTER
NR 46
TC 1538
Z9 2016
U1 7
U2 886
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 16
PY 2013
VL 497
IS 7449
BP 332
EP +
DI 10.1038/nature12107
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 144PN
UT WOS:000318952000030
PM 23575631
DA 2026-03-09
ER

PT J
AU Bommert, P
   Il Je, B
   Goldshmidt, A
   Jackson, D
AF Bommert, Peter
   Il Je, Byoung
   Goldshmidt, Alexander
   Jackson, David
TI The maize Gα gene COMPACT PLANT2 functions in CLAVATA signalling to control shoot meristem size
SO NATURE
LA English
DT Article
ID heterotrimeric g-protein; receptor-like protein; arabidopsis; encodes; identification; proliferation; subunit; kinase; flower
AB Shoot growth depends on meristems, pools of stem cells that are maintained by a negative feedback loop between the CLAVATA pathway and the WUSCHEL homeobox gene(1). CLAVATA signalling involves a secreted peptide, CLAVATA3 (CLV3)(2), and its perception by cell surface leucine-rich repeat (LRR) receptors, including the CLV1 receptor kinase(3) and a LRR receptor-like protein, CLV2 (ref. 4). However, the signalling mechanisms downstream of these receptors are poorly understood, especially for LRR receptor-like proteins, which lack a signalling domain(5). Here we show that maize COMPACT PLANT2 (CT2) encodes the predicted alpha-subunit (G alpha) of a heterotrimeric GTP binding protein. Maize ct2 phenotypes resemble Arabidopsis thaliana clavata mutants, and genetic, biochemical and functional assays indicate that CT2/G alpha transmits a stem-cell-restrictive signal from a CLAVATA LRR receptor, suggesting a new function for G alpha signalling in plants. Heterotrimeric GTP-binding proteins are membrane-associated molecular switches that are commonly activated by ligand binding to an associated seven-pass transmembrane (7TM) G-protein-coupled receptor (GPCR)(6). Recent studies have questioned the idea that plant heterotrimeric G proteins interact with canonical GPCRs(7), and our findings suggest that single pass transmembrane receptors act as GPCRs in plants, challenging the dogma that GPCRs are exclusively 7TM proteins.
C1 [Bommert, Peter; Il Je, Byoung; Goldshmidt, Alexander; Jackson, David] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA.
C3 Cold Spring Harbor Laboratory
RP Jackson, D (corresponding author), Cold Spring Harbor Lab, POB 100, Cold Spring Harbor, NY 11724 USA.
EM jacksond@cshl.edu
FU DFG [Bo 3012/1-1]; BARD [FI-431-2008]; Dupont-Pioneer; National Science Foundation [DBI-0604923]; Division Of Integrative Organismal Systems; Direct For Biological Sciences [1238202] Funding Source: National Science Foundation
NR 34
TC 249
Z9 289
U1 3
U2 169
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 24
PY 2013
VL 502
IS 7472
BP 555
EP +
DI 10.1038/nature12583
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 238YN
UT WOS:000325988400055
PM 24025774
DA 2026-03-09
ER

PT J
AU Dai, W
   Fu, C
   Raytcheva, D
   Flanagan, J
   Khant, HA
   Liu, XG
   Rochat, RH
   Haase-Pettingell, C
   Piret, J
   Ludtke, SJ
   Nagayama, K
   Schmid, MF
   King, JA
   Chiu, W
AF Dai, Wei
   Fu, Caroline
   Raytcheva, Desislava
   Flanagan, John
   Khant, Htet A.
   Liu, Xiangan
   Rochat, Ryan H.
   Haase-Pettingell, Cameron
   Piret, Jacqueline
   Ludtke, Steve J.
   Nagayama, Kuniaki
   Schmid, Michael F.
   King, Jonathan A.
   Chiu, Wah
TI Visualizing virus assembly intermediates inside marine cyanobacteria
SO NATURE
LA English
DT Article
ID electron cryotomography; cryoelectron microscopy; bacteriophage epsilon15; resolution; prochlorococcus; carboxysm; organization; architecture; tomography; reveal
AB Cyanobacteria are photosynthetic organisms responsible for similar to 25% of organic carbon fixation on the Earth. These bacteria began to convert solar energy and carbon dioxide into bioenergy and oxygen more than two billion years ago. Cyanophages, which infect these bacteria, have an important role in regulating the marine ecosystem by controlling cyanobacteria community organization and mediating lateral gene transfer. Here we visualize the maturation process of cyanophage Syn5 inside its host cell, Synechococcus, using Zernike phase contrast electron cryo-tomography (cryoET)(1,2). This imaging modality yields dramatic enhancement of image contrast over conventional cryoET and thus facilitates the direct identification of subcellular components, including thylakoid membranes, carboxysomes and polyribosomes, as well as phages, inside the congested cytosol of the infected cell. By correlating the structural features and relative abundance of viral progeny within cells at different stages of infection, we identify distinct Syn5 assembly intermediates. Our results indicate that the procapsid releases scaffolding proteins and expands its volume at an early stage of genome packaging. Later in the assembly process, we detected full particles with a tail either with or without an additional horn. The morphogenetic pathway we describe here is highly conserved and was probably established long before that of double-stranded DNA viruses infecting more complex organisms.
C1 [Dai, Wei; Fu, Caroline; Flanagan, John; Khant, Htet A.; Liu, Xiangan; Rochat, Ryan H.; Ludtke, Steve J.; Schmid, Michael F.; Chiu, Wah] Baylor Coll Med, Verna & Marrs Mclean Dept Biochem & Mol Biol, Natl Ctr Macromol Imaging, Houston, TX 77030 USA.
   [Raytcheva, Desislava; Haase-Pettingell, Cameron; King, Jonathan A.] MIT, Dept Biol, Cambridge, MA 02139 USA.
   [Raytcheva, Desislava; Piret, Jacqueline] Northeastern Univ, Dept Biol, Boston, MA 02115 USA.
   [Rochat, Ryan H.; Ludtke, Steve J.; Schmid, Michael F.; Chiu, Wah] Baylor Coll Med, Program Struct & Computat Biol & Mol Biophys, Houston, TX 77030 USA.
   [Nagayama, Kuniaki] Natl Inst Nat Sci, Natl Inst Physiol Sci, Okazaki, Aichi 4448787, Japan.
C3 Baylor College of Medicine; Massachusetts Institute of Technology (MIT); Northeastern University; Baylor College of Medicine; Baylor College Medical Hospital; National Institutes of Natural Sciences (NINS) - Japan; National Institute for Physiological Sciences (NIPS)
RP Chiu, W (corresponding author), Baylor Coll Med, Verna & Marrs Mclean Dept Biochem & Mol Biol, Natl Ctr Macromol Imaging, Houston, TX 77030 USA.
EM wah@bcm.edu
FU Robert Welch Foundation [Q1242]; National Institutes of Health [P41GM123832, AI0175208, PN2EY016525, GM080139]; National Institutes of Health through the Gulf Coast Consortia [T15LM007093]; National Institutes of Health through the MSTP [T32GM007330]; National Institute of General Medical Sciences [R01GM080139] Funding Source: NIH RePORTER
NR 33
TC 96
Z9 117
U1 0
U2 127
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 31
PY 2013
VL 502
IS 7473
BP 707
EP +
DI 10.1038/nature12604
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 243CC
UT WOS:000326293200053
PM 24107993
DA 2026-03-09
ER

PT J
AU Xu, Y
   Ma, PJ
   Shah, P
   Rokas, A
   Liu, Y
   Johnson, CH
AF Xu, Yao
   Ma, Peijun
   Shah, Premal
   Rokas, Antonis
   Liu, Yi
   Johnson, Carl Hirschie
TI Non-optimal codon usage is a mechanism to achieve circadian clock conditionality
SO NATURE
LA English
DT Article
ID gene-expression; escherichia-coli; cyanobacteria; selection; bias; temperature; prokaryotes; adaptation; efficiency; drosophila
AB Circadian rhythms are oscillations in biological processes that function as a key adaptation to the daily rhythms of most environments. In the model cyanobacterial circadian clock system, the core oscillator proteins are encoded by the gene cluster kaiABC(1). Genes with high expression and functional importance, such as the kai genes, are usually encoded by optimal codons, yet the codon-usage bias of the kaiBC genes is not optimized for translational efficiency. We discovered a relationship between codon usage and a general property of circadian rhythms called conditionality; namely, that endogenous rhythmicity is robustly expressed under some environmental conditions but not others(2). Despite the generality of circadian conditionality, however, its molecular basis is unknown for any system. Here we show that in the cyanobacterium Synechococcus elongate, non-optimal codon usage was selected as a post-transcriptional. mechanism to switch between circadian and non-circadian regulation of gene expression as an adaptive response to environmental conditions. When the kaiBC sequence was experimentally optimized to enhance expression of the KaiB and KaiC proteins, intrinsic rhythmicity was enhanced at cool temperatures that are experienced by this organism in. its natural habitat. However, fitness at those temperatures was highest in cells hi which the endogenous rhythms were suppressed at cool temperatures as compared with cells exhibiting high-amplitude rhythmicity. These results indicate natural selection against circadian systems in cyanobacteria that are intrinsically robust at cool temperatures. Modulation of circadian amplitude is therefore crucial to its adaptive significance(3). Moreover, these results show the direct effects of codon usage on a complex phenotype and organismal fitness. Our work also challenges the long-standing view of directional selection towards optimal codons(4-7), and provides a key example of natural selection against optimal codons to achieve adaptive responses to environmental changes.
C1 [Xu, Yao; Ma, Peijun; Rokas, Antonis; Johnson, Carl Hirschie] Vanderbilt Univ, Dept Biol Sci, Nashville, TN 37235 USA.
   [Shah, Premal] Univ Penn, Dept Biol, Philadelphia, PA 19104 USA.
   [Liu, Yi] Univ Texas SW Med Ctr Dallas, Dept Physiol, Dallas, TX 75390 USA.
C3 Vanderbilt University; University of Pennsylvania; University of Texas System; University of Texas Southwestern Medical Center
RP Johnson, CH (corresponding author), Vanderbilt Univ, Dept Biol Sci, Nashville, TN 37235 USA.
EM carl.h.johnson@vanderbilt.edu
FU National Institute of General Medical Science [R01 GM067152, R01 GM088595, GM068496, GM062591]; Welch Foundation [I-1560]; National Science Foundation [DEB-0844968]; Searle Scholars Program; Burroughs Wellcome Fund Career Award; David & Lucille Packard Foundation; National Institute of General Medical Sciences [R01GM107434, R37GM067152, R35GM118118] Funding Source: NIH RePORTER; Direct For Biological Sciences; Division Of Environmental Biology [0844968] Funding Source: National Science Foundation
NR 30
TC 141
Z9 168
U1 0
U2 60
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 7
PY 2013
VL 495
IS 7439
BP 116
EP 120
DI 10.1038/nature11942
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 105BE
UT WOS:000316039800051
PM 23417065
DA 2026-03-09
ER

PT J
AU Bieniossek, C
   Papai, G
   Schaffitzel, C
   Garzoni, F
   Chaillet, M
   Scheer, E
   Papadopoulos, P
   Tora, L
   Schultz, P
   Berger, I
AF Bieniossek, Christoph
   Papai, Gabor
   Schaffitzel, Christiane
   Garzoni, Frederic
   Chaillet, Maxime
   Scheer, Elisabeth
   Papadopoulos, Petros
   Tora, Laszlo
   Schultz, Patrick
   Berger, Imre
TI The architecture of human general transcription factor TFIID core complex
SO NATURE
LA English
DT Article
ID crystal-structure; terminal domain; yeast; identification; subcomplex; subunit; octamer; tafs
AB The initiation of gene transcription by RNA polymerase II is regulated by a plethora of proteins in human cells. The first general transcription factor to bind gene promoters is transcription factor IID (TFIID). TFIID triggers pre-initiation complex formation, functions as a coactivator by interacting with transcriptional activators and reads epigenetic marks(1-3). TFIID is a megadalton-sized multiprotein complex composed of TATA-box-binding protein (TBP) and 13 TBP-associated factors (TAFs)(3). Despite its crucial role, the detailed architecture and assembly mechanism of TFIID remain elusive. Histone fold domains are prevalent in TAFs, and histone-like tetramer and octamer structures have been proposed in TFIID4-6. A functional core-TFIID subcomplex was revealed in Drosophila nuclei, consisting of a subset of TAFs (TAF4, TAF5, TAF6, TAF9 and TAF12)(7). These core subunits are thought to be present in two copies in holo-TFIID, in contrast to TBP and other TAFs that are present in a single copy(8), conveying a transition from symmetry to asymmetry in the TFIID assembly pathway. Here we present the structure of human core-TFIID determined by cryoelectron microscopy at 11.6 angstrom resolution. Our structure reveals a two-fold symmetric, interlaced architecture, with pronounced protrusions, that accommodates all conserved structural features of the TAFs including the histone folds. We further demonstrate that binding of one TAF8-TAF10 complex breaks the original symmetry of core-TFIID. We propose that the resulting asymmetric structure serves as a functional scaffold to nucleate holo-TFIID assembly, by accreting one copy each of the remaining TAFs and TBP.
C1 [Bieniossek, Christoph; Schaffitzel, Christiane; Garzoni, Frederic; Chaillet, Maxime; Berger, Imre] UJF CNRS EMBL, Unite Mixte Int UMI 3265, European Mol Biol Lab EMBL Grenoble Outstn, F-38042 Grenoble 9, France.
   [Bieniossek, Christoph; Schaffitzel, Christiane; Garzoni, Frederic; Chaillet, Maxime; Berger, Imre] UJF CNRS EMBL, Unite Mixte Int UMI 3265, Unit Virus Host Cell Interact UVHCI, F-38042 Grenoble 9, France.
   [Papai, Gabor; Schultz, Patrick] IGBMC, Dept Integrated Struct Biol, F-67404 Illkirch Graffenstaden, France.
   [Papai, Gabor; Scheer, Elisabeth; Tora, Laszlo; Schultz, Patrick] INSERM, U964, F-67400 Paris, France.
   [Papai, Gabor; Scheer, Elisabeth; Tora, Laszlo; Schultz, Patrick] CNRS Illkirch, UMR7104, F-67000 Strasbourg, France.
   [Papai, Gabor; Scheer, Elisabeth; Tora, Laszlo; Schultz, Patrick] Univ Strasbourg, F-67000 Strasbourg, France.
   [Scheer, Elisabeth; Tora, Laszlo] IGBMC, Dept Funct Genom & Canc, F-67404 Illkirch Graffenstaden, France.
   [Papadopoulos, Petros] Erasmus MC, Dept Cell Biol, NL-3015 GE Rotterdam, Netherlands.
C3 European Molecular Biology Laboratory (EMBL); Communaute Universite Grenoble Alpes; Universite Grenoble Alpes (UGA); Communaute Universite Grenoble Alpes; Universite Grenoble Alpes (UGA); European Molecular Biology Laboratory (EMBL); Institut National de la Sante et de la Recherche Medicale (Inserm); Institut National de la Sante et de la Recherche Medicale (Inserm); Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB); Universites de Strasbourg Etablissements Associes; Universite de Strasbourg; Institut National de la Sante et de la Recherche Medicale (Inserm); Erasmus University Rotterdam; Erasmus MC
RP Schultz, P (corresponding author), IGBMC, Dept Integrated Struct Biol, 1 Rue Laurent Fries,BP10142, F-67404 Illkirch Graffenstaden, France.
EM patrick.schultz@igbmc.fr; iberger@embl.fr
FU European Research Council (ERC); Agence Nationale de la Recherche (ANR); EC Marie Curie Action; EC; Institut National de la Sante et de la Recherche Medicale (INSERM); Centre National pour la Recherche Scientifique (CNRS); Association pour la Recherche sur le Cancer (ARC); Fondation pour la Recherche Medicale (FRM); ANR; ChromAct; TFIID-Complexes
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   Timmers HTM, 2005, TRENDS BIOCHEM SCI, V30, P7, DOI 10.1016/j.tibs.2004.11.007
   Wang XP, 2007, P NATL ACAD SCI USA, V104, P7839, DOI 10.1073/pnas.0608570104
   Werten S, 2002, J BIOL CHEM, V277, P45502, DOI 10.1074/jbc.M206587200
   Wright KJ, 2006, P NATL ACAD SCI USA, V103, P12347, DOI 10.1073/pnas.0605499103
   Xie XL, 1996, NATURE, V380, P316, DOI 10.1038/380316a0
NR 30
TC 123
Z9 153
U1 0
U2 57
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 31
PY 2013
VL 493
IS 7434
BP 699
EP 702
DI 10.1038/nature11791
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 080CU
UT WOS:000314219600062
PM 23292512
DA 2026-03-09
ER

PT J
AU Hoffmann, SS
   McManus, JF
   Curry, WB
   Brown-Leger, LS
AF Hoffmann, Sharon S.
   McManus, Jerry F.
   Curry, William B.
   Brown-Leger, L. Susan
TI Persistent export of 231Pa from the deep central Arctic Ocean over the past 35,000 years
SO NATURE
LA English
DT Article
ID thermohaline circulation; rapid-determination; late quaternary; particle-flux; glacial ocean; sea-ice; th-230; profiles; basin; rates
AB The Arctic Ocean has an important role in Earth's climate, both through surface processes(1) such as sea-ice formation and transport, and through the production and export of waters at depth that contribute to the global thermohaline circulation(2,3). Deciphering the deep Arctic Ocean's palaeo-oceanographic history is a crucial part of understanding its role in climatic change. Here we show that sedimentary ratios of the radionuclides thorium-230 (Th-230) and protactinium-231 (Pa-231), which are produced in sea water and removed by particle scavenging on timescales of decades to centuries, respectively(4), record consistent evidence for the export of 231Pa from the deep Arctic and may indicate continuous deep-water exchange between the Arctic and Atlantic oceans throughout the past 35,000 years. Seven well-dated box-core records provide a comprehensive overview of Pa-231 and Th-230 burial in Arctic sediments during glacial, deglacial and interglacial conditions. Sedimentary Pa-231/Th-230 ratios decrease nearly linearly with increasing water depth above the core sites, indicating efficient particle scavenging in the upper water column and greater influence of removal by lateral transport at depth. Although the measured Th-230 burial is in balance with its production in Arctic sea water, integrated depth profiles for all time intervals reveal a deficit in Pa-231 burial that can be balanced only by lateral export in the water column. Because no enhanced sink for Pa-231 has yet been found in the Arctic, our records suggest that deep-water exchange through the Fram strait may export Pa-231. Such export may have continued for the past 35,000 years, suggesting a century-scale replacement time for deep waters in the Arctic Ocean since the most recent glaciation and a persistent contribution of Arctic waters to the global ocean circulation.
C1 [Hoffmann, Sharon S.; McManus, Jerry F.] Columbia Univ, Lamont Doherty Earth Observ, Palisades, NY 10964 USA.
   [Curry, William B.; Brown-Leger, L. Susan] Woods Hole Oceanog Inst, Woods Hole, MA 02543 USA.
   [Curry, William B.] Bermuda Inst Ocean Sci, GE-01 St Georges, Bermuda.
C3 Columbia University; Woods Hole Oceanographic Institution; Bermuda Institute of Ocean Sciences
RP Hoffmann, SS (corresponding author), Columbia Univ, Lamont Doherty Earth Observ, Palisades, NY 10964 USA.
EM ssh13@columbia.edu
FU Comer Science and Education Fund; US NSF [OCE-0402565, OCE-0550637, OCE-0902985, AGS-0936496, ARC-0520073]; Directorate For Geosciences; Division Of Ocean Sciences [0902985] Funding Source: National Science Foundation
NR 41
TC 39
Z9 40
U1 2
U2 57
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 30
PY 2013
VL 497
IS 7451
BP 603
EP +
DI 10.1038/nature12145
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 152UF
UT WOS:000319556100040
PM 23719461
DA 2026-03-09
ER

PT J
AU Strugatsky, D
   McNulty, R
   Munson, K
   Chen, CK
   Soltis, SM
   Sachs, G
   Luecke, H
AF Strugatsky, David
   McNulty, Reginald
   Munson, Keith
   Chen, Chiung-Kuang
   Soltis, S. Michael
   Sachs, George
   Luecke, Hartmut
TI Structure of the proton-gated urea channel from the gastric pathogen Helicobacter pylori
SO NATURE
LA English
DT Article
ID ph; protein; complex
AB Half the world's population is chronically infected with Helico-bacter pylori(1), causing gastritis, gastric ulcers and an increased incidence of gastric adenocarcinoma(2). Its proton-gated inner-membrane urea channel, HpUreI, is essential for survival in the acidic environment of the stomach(3). The channel is closed at neutral pH and opens at acidic pH to allow the rapid access of urea to cytoplasmic urease(4). Urease produces NH3 and CO2, neutralizing entering protons and thus buffering the periplasm to a pH of roughly 6.1 even in gastric juice at a pH below 2.0. Here we report the structure of HpUreI, revealing six protomers assembled in a hexameric ring surrounding a central bilayer plug of ordered lipids. Each protomer encloses a channel formed by a twisted bundle of six transmembrane helices. The bundle defines a previously unobserved fold comprising a two-helix hairpin motif repeated three times around the central axis of the channel, without the inverted repeat of mammalian-type urea transporters. Both the channel and the protomer interface contain residues conserved in the AmiS/UreI superfamily, suggesting the preservation of channel architecture and oligomeric state in this superfamily. Predominantly aromatic or aliphatic side chains line the entire channel and define two consecutive constriction sites in the middle of the channel. Mutation of Trp 153 in the cytoplasmic constriction site to Ala or Phe decreases the selectivity for urea in comparison with thiourea, suggesting that solute interaction with Trp 153 contributes specificity. The previously unobserved hexameric channel structure described here provides a new model for the permeation of urea and other small amide solutes in prokaryotes and archaea.
C1 [Strugatsky, David; Munson, Keith; Sachs, George] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90073 USA.
   [Strugatsky, David; Munson, Keith; Sachs, George] Greater W Angeles Hlth Care Syst, Los Angeles, CA 90073 USA.
   [McNulty, Reginald; Chen, Chiung-Kuang; Luecke, Hartmut] Univ Calif Irvine, Dept Mol Biol & Biochem, Irvine, CA 92697 USA.
   [Soltis, S. Michael] Stanford Synchrotron Radiat Lightsource, Menlo Pk, CA 94025 USA.
   [Luecke, Hartmut] Univ Calif Irvine, Ctr Biomembrane Syst, Irvine, CA 92697 USA.
   [Luecke, Hartmut] Univ Calif Irvine, Dept Physiol & Biophys, Irvine, CA 92697 USA.
   [Luecke, Hartmut] Univ Calif Irvine, Dept Comp Sci, Irvine, CA 92697 USA.
C3 University of California System; University of California Los Angeles; University of California Los Angeles Medical Center; David Geffen School of Medicine at UCLA; University of California System; University of California Irvine; University of California System; University of California Irvine; University of California System; University of California Irvine; University of California System; University of California Irvine
RP Sachs, G (corresponding author), Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90073 USA.
EM gsachs@ucla.edu; hudel@uci.edu
FU National Institutes of Health (NIH) [R01AI78000, P30CA062203]; National Cancer Institute institutional training grant [5T32CA9054-34]; University of California Irvine Center for Biomembrane Systems; NIH [R01DK53462, R01DK58333]; US Veterans Administration; DOE Office of Biological and Environmental Research; HIN, National Center for Research Resources, Biomedical Technology Program [P41RR001209]; National Institute of General Medical Sciences; National Cancer Institute [T32CA009054, P30CA062203] Funding Source: NIH RePORTER
NR 33
TC 77
Z9 96
U1 3
U2 75
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 10
PY 2013
VL 493
IS 7431
BP 255
EP U144
DI 10.1038/nature11684
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 066YY
UT WOS:000313259600046
PM 23222544
DA 2026-03-09
ER

PT J
AU Shen, B
   Zhao, XJ
   O'Brien, KA
   Stojanovic-Terpo, A
   Delaney, MK
   Kim, K
   Cho, J
   Lam, SCT
   Du, XP
AF Shen, Bo
   Zhao, Xiaojuan
   O'Brien, Kelly A.
   Stojanovic-Terpo, Aleksandra
   Delaney, M. Keegan
   Kim, Kyungho
   Cho, Jaehyung
   Lam, Stephen C. -T.
   Du, Xiaoping
TI A directional switch of integrin signalling and a new anti-thrombotic strategy
SO NATURE
LA English
DT Article
ID outside-in; inside-out; structural basis; talin-binding; activation; fibrinogen; adhesion; domain; roles
AB Integrins have a critical role in thrombosis and haemostasis(1). Antagonists of the platelet integrin alpha(IIb)beta(3) are potent anti-thrombotic drugs, but also have the life-threatening adverse effect of causing bleeding(2,3). It is therefore desirable to develop new antagonists that do not cause bleeding. Integrins transmit signals bidirectionally(4,5). Inside-out signalling activates integrins through a talin-dependent mechanism(6,7). Integrin ligation mediates thrombus formation and outside-in signalling(8,9), which requires G alpha(13) and greatly expands thrombi. Here we show that G alpha(13) and talin bind to mutually exclusive but distinct sites within the integrin beta(3) cytoplasmic domain in opposing waves. The first talin-binding wave mediates inside-out signalling and also ligand-induced integrin activation, but is not required for outside-in signalling. Integrin ligation induces transient talin dissociation and G alpha(13) binding to an EXE motif (in which X denotes any residue), which selectively mediates outside-in signalling and platelet spreading. The second talin-binding wave is associated with clot retraction. An EXE-motif-based inhibitor of G alpha(13)-integrin interaction selectively abolishes outside-in signalling without affecting integrin ligation, and suppresses occlusive arterial thrombosis without affecting bleeding time. Thus, we have discovered a new mechanism for the directional switch of integrin signalling and, on the basis of this mechanism, designed a potent new anti-thrombotic drug that does not cause bleeding.
C1 [Shen, Bo; Zhao, Xiaojuan; O'Brien, Kelly A.; Stojanovic-Terpo, Aleksandra; Delaney, M. Keegan; Kim, Kyungho; Cho, Jaehyung; Lam, Stephen C. -T.; Du, Xiaoping] Univ Illinois, Dept Pharmacol, Chicago, IL 60612 USA.
C3 University of Illinois System; University of Illinois Chicago; University of Illinois Chicago Hospital
RP Du, XP (corresponding author), Univ Illinois, Dept Pharmacol, 835 South Wolcott Ave, Chicago, IL 60612 USA.
EM xdu@uic.edu
FU National Heart, Lung, and Blood Institute [HL080264, HL062350, HL109439]; National Heart Lung and Blood Institute [T32HL007829] Funding Source: NIH RePORTER
CR Arias-Salgado EG, 2005, J BIOL CHEM, V280, P29699, DOI 10.1074/jbc.M503508200
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   Delaney MK, 2012, ARTERIOSCL THROM VAS, V32, P2761, DOI 10.1161/ATVBAHA.112.254920
   DU XP, 1991, CELL, V65, P409, DOI 10.1016/0092-8674(91)90458-B
   Flevaris P, 2007, J CELL BIOL, V179, P553, DOI 10.1083/jcb.200703185
   Goksoy E, 2008, MOL CELL, V31, P124, DOI 10.1016/j.molcel.2008.06.011
   Gong HX, 2010, SCIENCE, V327, P340, DOI 10.1126/science.1174779
   Haling JR, 2011, BLOOD, V117, P1719, DOI 10.1182/blood-2010-09-305433
   Hynes RO, 2002, CELL, V110, P673, DOI 10.1016/S0092-8674(02)00971-6
   Krishnadas A, 2003, PHARMACEUT RES, V20, P297, DOI 10.1023/A:1022243709003
   Ma YQ, 2008, J CELL BIOL, V181, P439, DOI 10.1083/jcb.200710196
   Marjanovic JA, 2005, J BIOL CHEM, V280, P37430, DOI 10.1074/jbc.M506518200
   Moissoglu K, 2006, BIOL CELL, V98, P547, DOI 10.1042/BC20060025
   Moser M, 2008, NAT MED, V14, P325, DOI 10.1038/nm1722
   NIMURA N, 1988, ANAL CHEM, V60, P2067, DOI 10.1021/ac00170a017
   OBrien KA, 2012, ARTERIOSCL THROM VAS, V32, P2232, DOI 10.1161/ATVBAHA.112.254680
   OBrien KA, 2011, BLOOD, V118, P4215, DOI 10.1182/blood-2010-12-323204
   Obergfell A, 2002, J CELL BIOL, V157, P265, DOI 10.1083/jcb.200112113
   Patil S, 1999, J BIOL CHEM, V274, P28575, DOI 10.1074/jbc.274.40.28575
   Petrich BG, 2007, J EXP MED, V204, P3103, DOI 10.1084/jem.20071800
   Serebruany VL, 2004, AM J HEMATOL, V75, P40, DOI 10.1002/ajh.10451
   Shattil SJ, 2004, BLOOD, V104, P1606, DOI 10.1182/blood-2004-04-1257
   Shen B, 2012, CURR OPIN CELL BIOL, V24, P600, DOI 10.1016/j.ceb.2012.08.011
   Tadokoro S, 2003, SCIENCE, V302, P103, DOI 10.1126/science.1086652
   UGAROVA TP, 1993, J BIOL CHEM, V268, P21080
   Wegener KL, 2007, CELL, V128, P171, DOI 10.1016/j.cell.2006.10.048
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   Ye F, 2011, J THROMB HAEMOST, V9, P20, DOI 10.1111/j.1538-7836.2011.04355.x
NR 30
TC 161
Z9 192
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 7
PY 2013
VL 503
IS 7474
BP 131
EP +
DI 10.1038/nature12613
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 247AS
UT WOS:000326585600046
PM 24162846
DA 2026-03-09
ER

PT J
AU Stuart-Smith, RD
   Bates, AE
   Lefcheck, JS
   Duffy, JE
   Baker, SC
   Thomson, RJ
   Stuart-Smith, JF
   Hill, NA
   Kininmonth, SJ
   Airoldi, L
   Becerro, MA
   Campbell, SJ
   Dawson, TP
   Navarrete, SA
   Soler, GA
   Strain, EMA
   Willis, TJ
   Edgar, GJ
AF Stuart-Smith, Rick D.
   Bates, Amanda E.
   Lefcheck, Jonathan S.
   Duffy, J. Emmett
   Baker, Susan C.
   Thomson, Russell J.
   Stuart-Smith, Jemina F.
   Hill, Nicole A.
   Kininmonth, Stuart J.
   Airoldi, Laura
   Becerro, Mikel A.
   Campbell, Stuart J.
   Dawson, Terence P.
   Navarrete, Sergio A.
   Soler, German A.
   Strain, Elisabeth M. A.
   Willis, Trevor J.
   Edgar, Graham J.
TI Integrating abundance and functional traits reveals new global hotspots of fish diversity
SO NATURE
LA English
DT Article
ID marine biodiversity; patterns; biogeography; community; consumers; evenness; gradient; entropy; forests
AB Species richness has dominated our view of global biodiversity patterns for centuries(1,2). The dominance of this paradigm is reflected in the focus by ecologists and conservation managers on richness and associated occurrence-based measures for understanding drivers of broad-scale diversity patterns and as a biological basis for management(3,4). However, this is changing rapidly, as it is now recognized that not only the number of species but the species present, their phenotypes and the number of individuals of each species are critical in determining the nature and strength of the relationships between species diversity and a range of ecological functions (such as biomass production and nutrient cycling)(5). Integrating these measures should provide a more relevant representation of global biodiversity patterns in terms of ecological functions than that provided by simple species counts. Here we provide comparisons of a traditional global biodiversity distribution measure based on richness with metrics that incorporate species abundances and functional traits. We use data from standardized quantitative surveys of 2,473 marine reef fish species at 1,844 sites, spanning 133 degrees of latitude from all ocean basins, to identify new diversity hotspots in some temperate regions and the tropical eastern Pacific Ocean. These relate to high diversity of functional traits amongst individuals in the community (calculated using Rao's Q(6)), and differ from previously reported patterns in functional diversity and richness for terrestrial animals, which emphasize species-rich tropical regions only(7,8). There is a global trend for greater evenness in the number of individuals of each species, across the reef fish species observed at sites ('community evenness'), at higher latitudes. This contributes to the distribution of functional diversity hotspots and contrasts with well-known latitudinal gradients in richness(2,4). Our findings suggest that the contribution of species diversity to a range of ecosystem functions varies over large scales, and imply that in tropical regions, which have higher numbers of species, each species contributes proportionally less to community-level ecological processes on average than species in temperate regions. Metrics of ecological function usefully complement metrics of species diversity in conservation management, including when identifying planning priorities and when tracking changes to biodiversity values.
C1 [Stuart-Smith, Rick D.; Bates, Amanda E.; Thomson, Russell J.; Stuart-Smith, Jemina F.; Hill, Nicole A.; Soler, German A.; Edgar, Graham J.] Univ Tasmania, Inst Marine & Antarctic Studies, Hobart, Tas 7001, Australia.
   [Lefcheck, Jonathan S.; Duffy, J. Emmett] Virginia Inst Marine Sci, Dept Biol Sci, Gloucester Point, VA 23062 USA.
   [Baker, Susan C.] Univ Tasmania, Sch Plant Sci, Hobart, Tas 7001, Australia.
   [Kininmonth, Stuart J.] Stockholm Univ, Stockholm Resilience Ctr, SE-11419 Stockholm, Sweden.
   [Airoldi, Laura; Strain, Elisabeth M. A.] Univ Bologna, Dipartimento Sci Biol Geol & Ambientali, I-48123 Ravenna, Italy.
   [Airoldi, Laura] Stanford Univ, Hopkins Marine Stn, Pacific Grove, CA 93950 USA.
   [Becerro, Mikel A.] IPNA CSIC, Nat Prod & Agrobiol Inst, Tenerife 38206, Spain.
   [Campbell, Stuart J.] Wildlife Conservat Soc, Indonesia Marine Program, Bogor 16151, Jawa Barat, Indonesia.
   [Dawson, Terence P.] Univ Dundee, Sch Environm, Dundee DD1 4HN, Scotland.
   [Navarrete, Sergio A.] Pontificia Univ Catolica Chile, Estn Costera Invest Marinas, Santiago, Chile.
   [Navarrete, Sergio A.] Pontificia Univ Catolica Chile, Ctr Marine Conservat, Santiago, Chile.
   [Willis, Trevor J.] Univ Portsmouth, Inst Marine Sci, Sch Biol Sci, Portsmouth PO4 9LY, Hants, England.
C3 University of Tasmania; William & Mary; Virginia Institute of Marine Science; University of Tasmania; Stockholm University; University of Bologna; Stanford University; Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Instituto de Productos Naturales y Agrobiologia (IPNA); Wildlife Conservation Society - Indonesia; University of Dundee; Pontificia Universidad Catolica de Chile; Pontificia Universidad Catolica de Chile; University of Portsmouth
RP Stuart-Smith, RD (corresponding author), Univ Tasmania, Inst Marine & Antarctic Studies, Private Bag 49, Hobart, Tas 7001, Australia.
EM rstuarts@utas.edu.au
FU Australian Government's National Environmental Research Program; National Geographic Society; Conservation International; Wildlife Conservation Society Indonesia; Winston Churchill Memorial Trust; ASSEMBLE Marine
NR 42
TC 486
Z9 537
U1 7
U2 579
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 26
PY 2013
VL 501
IS 7468
BP 539
EP +
DI 10.1038/nature12529
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 223RP
UT WOS:000324826300056
PM 24067714
DA 2026-03-09
ER

PT J
AU Bauer, F
   Heyder, J
   Schubert, E
   Borowsky, D
   Taubert, D
   Bruognolo, B
   Schuh, D
   Wegscheider, W
   von Delft, J
   Ludwig, S
AF Bauer, Florian
   Heyder, Jan
   Schubert, Enrico
   Borowsky, David
   Taubert, Daniela
   Bruognolo, Benedikt
   Schuh, Dieter
   Wegscheider, Werner
   von Delft, Jan
   Ludwig, Stefan
TI Microscopic origin of the '0.7-anomaly' in quantum point contacts
SO NATURE
LA English
DT Article
ID dimensional electron-gas; kondo; conductance; signatures; devices
AB Quantum point contacts are narrow, one-dimensional constrictions usually patterned in a two-dimensional electron system, for example by applying voltages to local gates. The linear conductance of a point contact, when measured as function of its channel width, is quantized(1-3) in units of G(Q) = 2e(2)/h, where e is the electron charge and h is Planck's constant. However, the conductance also has an unexpected shoulder at similar to 0.7 G(Q), known as the '0.7-anomaly'(4-12), whose origin is still subject to debate(11-21). Proposed theoretical explanations have invoked spontaneous spin polarization(4,17), ferromagnetic spin coupling(19), the formation of a quasi-bound state leading to the Kondo effect(13,14), Wigner crystallization(16,20) and various treatments of inelastic scattering(18,21). However, explicit calculations that fully reproduce the various experimental observations in the regime of the 0.7-anomaly, including the zero-bias peak that typically accompanies it(6,9-11), are still lacking. Here we offer a detailed microscopic explanation for both the 0.7-anomaly and the zero-bias peak: their common origin is a smeared van Hove singularity in the local density of states at the bottom of the lowest one-dimensional subband of the point contact, which causes an anomalous enhancement in the Hartree potential barrier, the magnetic spin susceptibility and the inelastic scattering rate. We find good qualitative agreement between theoretical calculations and experimental results on the dependence of the conductance on gate voltage, magnetic field, temperature, source-drain voltage (including the zero-bias peak) and interaction strength. We also clarify how the low-energy scale governing the 0.7-anomaly depends on gate voltage and interactions. For low energies, we predict and observe Fermi-liquid behaviour similar to that associated with the Kondo effect in quantum dots(22). At high energies, however, the similarities between the 0.7-anomaly and the Kondo effect end.
C1 [Bauer, Florian; Heyder, Jan; Schubert, Enrico; Borowsky, David; Taubert, Daniela; Bruognolo, Benedikt; von Delft, Jan; Ludwig, Stefan] Univ Munich, Ctr NanoSci, D-80539 Munich, Germany.
   [Bauer, Florian; Heyder, Jan; Schubert, Enrico; Borowsky, David; Taubert, Daniela; Bruognolo, Benedikt; von Delft, Jan; Ludwig, Stefan] Univ Munich, Fak Phys, D-80539 Munich, Germany.
   [Bauer, Florian; Heyder, Jan; Bruognolo, Benedikt; von Delft, Jan] Univ Munich, Arnold Sommerfeld Ctr Theoret Phys, D-80333 Munich, Germany.
   [Schuh, Dieter] Univ Regensburg, Inst Angew Phys, D-93040 Regensburg, Germany.
   [Wegscheider, Werner] ETH, Solid State Phys Lab, CH-8093 Zurich, Switzerland.
C3 University of Munich; University of Munich; University of Munich; University of Regensburg; Swiss Federal Institutes of Technology Domain; ETH Zurich
RP von Delft, J (corresponding author), Univ Munich, Ctr NanoSci, Geschwister Scholl Pl 1, D-80539 Munich, Germany.
EM vondelft@lmu.de; ludwig@lmu.de
FU DFG [SFB-631, SFB-TR12, De730/3-2, De730/4-1, De730/4-2, De730/4-3, HO 4687/1-3, LU819/4-1]; Cluster of Excellence Nanosystems Initiative Munich; Center for NanoScience; US National Science Foundation [NSF PHY05-51164]; DFG
NR 30
TC 91
Z9 100
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 SEP 5
PY 2013
VL 501
IS 7465
BP 73
EP 78
DI 10.1038/nature12421
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 211ER
UT WOS:000323888300034
PM 23995681
DA 2026-03-09
ER

PT J
AU de Bakker, MAG
   Fowler, DA
   den Oude, K
   Dondorp, EM
   Navas, MCG
   Horbanczuk, JO
   Sire, JY
   Szczerbinska, D
   Richardson, MK
AF de Bakker, Merijn A. G.
   Fowler, Donald A.
   den Oude, Kelly
   Dondorp, Esther M.
   Navas, M. Carmen Garrido
   Horbanczuk, Jaroslaw O.
   Sire, Jean-Yves
   Szczerbinska, Danuta
   Richardson, Michael K.
TI Digit loss in archosaur evolution and the interplay between selection and constraints
SO NATURE
LA English
DT Article
ID sonic hedgehog; dromaius-novaehollandiae; developmental basis; limb bud; birds; reduction; pattern; locomotion; genes; size
AB Evolution involves interplay between natural selection and developmental constraints(1-3). This is seen, for example, when digits are lost from the limbs during evolution(1,3,4). Extant archosaurs (crocodiles and birds) show several instances of digit loss(3,5,6) under different selective regimes, and show limbs with one, two, three, four or the ancestral number of five digits. The 'lost' digits sometimes persist for millions of years as developmental vestiges(7-10). Here we examine digit loss in the Nile crocodile and five birds, using markers of three successive stages of digit development. In two independent lineages under different selection, wing digit I and all its markers disappear. In contrast, hindlimb digit V persists in all species sampled, both as cartilage, and as Sox9-expressing precartilage domains, 250 million years after the adult digit disappeared. There is therefore a mismatch between evolution of the embryonic and adult phenotypes. All limbs, regardless of digit number, showed similar expression of sonic hedgehog (Shh). Even in the one-fingered emu wing, expression of posterior genes Hoxd11 and Hoxd12 was conserved, whereas expression of anterior genes Gli3 and Alx4 was not. We suggest that the persistence of digit V in the embryo may reflect constraints, particularly the conserved posterior gene networks associated with the zone of polarizing activity (ZPA(11)). The more rapid and complete disappearance of digit I may reflect its ZPA-independent specification, and hence, weaker developmental constraints. Interacting with these constraints are selection pressures for limb functions such as flying and perching. This model may help to explain the diverse patterns of digit loss in tetrapods. Our study may also help to understand how selection on adults leads to changes in development.
C1 [de Bakker, Merijn A. G.; Fowler, Donald A.; den Oude, Kelly; Dondorp, Esther M.; Navas, M. Carmen Garrido; Richardson, Michael K.] Leiden Univ, Inst Biol, Dept Integrat Zool, Sylvius Lab, NL-2333 BE Leiden, Netherlands.
   [Horbanczuk, Jaroslaw O.] Polish Acad Sci, Inst Genet & Anim Breeding, PL-05552 Jastrzebiec, Poland.
   [Sire, Jean-Yves] Univ Paris 06, UMR 7138, F-75005 Paris, France.
   [Szczerbinska, Danuta] Western Pomeranian Univ Technol, Dept Poultry & Ornamental Bird Breeding, PL-71466 Szczecin, Poland.
C3 Leiden University - Excl LUMC; Leiden University; Polish Academy of Sciences; Institute of Genetics & Animal Biotechnology, Polish Academy of Sciences; Museum National d'Histoire Naturelle (MNHN); Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB); Sorbonne Universite; West Pomeranian University of Technology
RP Richardson, MK (corresponding author), Leiden Univ, Inst Biol, Dept Integrat Zool, Sylvius Lab, Sylviusweg 72, NL-2333 BE Leiden, Netherlands.
EM m.k.richardson@biology.leidenuniv.nl
NR 30
TC 70
Z9 76
U1 1
U2 74
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 22
PY 2013
VL 500
IS 7463
BP 445
EP +
DI 10.1038/nature12336
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 203TJ
UT WOS:000323316100032
PM 23831646
DA 2026-03-09
ER

PT J
AU Wang, C
   Wu, HX
   Katritch, V
   Han, GW
   Huang, XP
   Liu, W
   Siu, FY
   Roth, BL
   Cherezov, V
   Stevens, RC
AF Wang, Chong
   Wu, Huixian
   Katritch, Vsevolod
   Han, Gye Won
   Huang, Xi-Ping
   Liu, Wei
   Siu, Fai Yiu
   Roth, Bryan L.
   Cherezov, Vadim
   Stevens, Raymond C.
TI Structure of the human smoothened receptor bound to an antitumour agent
SO NATURE
LA English
DT Article
ID resolution crystal-structure; protein-coupled receptor; opioid receptor; international union; lipidic mesophases; frizzled receptors; membrane-proteins; hedgehog; activation; pathway
AB The smoothened (SMO) receptor, a key signal transducer in the hedgehog signalling pathway, is responsible for the maintenance of normal embryonic development and is implicated in carcinogenesis. It is classified as a class frizzled (class F) G-protein-coupled receptor (GPCR), although the canonical hedgehog signalling pathway involves the GLI transcription factors and the sequence similarity with class A GPCRs is less than 10%. Here we report the crystal structure of the transmembrane domain of the human SMO receptor bound to the small-molecule antagonist LY2940680 at 2.5 angstrom resolution. Although the SMO receptor shares the seven-transmembrane helical fold, most of the conserved motifs for class A GPCRs are absent, and the structure reveals an unusually complex arrangement of long extracellular loops stabilized by four disulphide bonds. The ligand binds at the extracellular end of the seven-transmembrane-helix bundle and forms extensive contacts with the loops.
C1 [Wang, Chong; Wu, Huixian; Katritch, Vsevolod; Han, Gye Won; Liu, Wei; Siu, Fai Yiu; Cherezov, Vadim; Stevens, Raymond C.] Scripps Res Inst, Dept Integrat Struct & Computat Biol, La Jolla, CA 92037 USA.
   [Huang, Xi-Ping; Roth, Bryan L.] Univ N Carolina Chapel Hill, Natl Inst Mental Hlth Psychoact Drug Screening Pr, Dept Pharmacol, Sch Med, Chapel Hill, NC 27514 USA.
   [Huang, Xi-Ping; Roth, Bryan L.] Univ N Carolina Chapel Hill, Sch Med, Div Chem Biol & Med Chem, Chapel Hill, NC 27514 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
RP Stevens, RC (corresponding author), Scripps Res Inst, Dept Integrat Struct & Computat Biol, 10550 North Torrey Pines Rd, La Jolla, CA 92037 USA.
EM stevens@scripps.edu
FU National Institutes of Health [P50 GM073197, U54 GM094618]; NIMH Psychoactive Drug Screening Program; Michael Hooker Chair of Pharmacology; National Cancer Institute [Y1-CO-1020]; National Institute of General Medical Sciences [Y1-GM-1104];  [F32 DK088392];  [R01 MH61887];  [U19 MH82441];  [R01 DA27170]
NR 49
TC 397
Z9 480
U1 2
U2 111
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 16
PY 2013
VL 497
IS 7449
BP 338
EP +
DI 10.1038/nature12167
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 144PN
UT WOS:000318952000031
PM 23636324
DA 2026-03-09
ER

PT J
AU Llordés, A
   Garcia, G
   Gazquez, J
   Milliron, DJ
AF Llordes, Anna
   Garcia, Guillermo
   Gazquez, Jaume
   Milliron, Delia J.
TI Tunable near-infrared and visible-light transmittance in nanocrystal-in-glass composites
SO NATURE
LA English
DT Article
ID optical-property; amorphous oxide; raman-spectra; nanocomposite; chemistry; ion
AB Amorphous metal oxides are useful in optical(1,2), electronic(3-5) and electrochemical devices(6,7). The bonding arrangement within these glasses largely determines their properties, yet it remains a challenge to manipulate their structures in a controlled manner. Recently, we developed synthetic protocols for incorporating nanocrystals that are covalently bonded into amorphous materials(8,9). This 'nanocrystal-in-glass' approach not only combines two functional components in one material, but also the covalent link enables us to manipulate the glass structure to change its properties. Here we illustrate the power of this approach by introducing tin-doped indium oxide nanocrystals into niobium oxide glass (NbOx), and realize a new amorphous structure as a consequence of linking it to the nanocrystals. The resulting material demonstrates a previously unrealized optical switching behaviour that will enable the dynamic control of solar radiation transmittance through windows. These transparent films can block near-infrared and visible light selectively and independently by varying the applied electrochemical voltage over a range of 2.5 volts. We also show that the reconstructed NbOx glass has superior properties-its optical contrast is enhanced fivefold and it has excellent electrochemical stability, with 96 per cent of charge capacity retained after 2,000 cycles.
C1 [Llordes, Anna; Garcia, Guillermo; Milliron, Delia J.] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Mol Foundry, Berkeley, CA 94720 USA.
   [Gazquez, Jaume] ICMAB CSIC, Inst Ciencia Mat Barcelona, Bellaterra 08193, Catalonia, Spain.
C3 United States Department of Energy (DOE); Lawrence Berkeley National Laboratory; University of California System; University of California Berkeley; Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Instituto de Ciencia de Materiales de Barcelona (ICMAB)
RP Milliron, DJ (corresponding author), Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Mol Foundry, 1 Cyclotron Rd, Berkeley, CA 94720 USA.
EM dmilliron@lbl.gov
FU Office of Science, Office of Basic Energy Sciences, of the US Department of Energy (DOE) [DE-AC02-05CH11231]; DOE Early Career Research Program; Consejo Superior de Investigaciones Cientificas, CSIC, JAE; DOE-BES, Materials Sciences and Engineering Division; ORNL's Shared Research Equipment (ShaRE) User Program; DOE-BES
NR 32
TC 796
Z9 913
U1 8
U2 826
PU NATURE PUBLISHING 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 15
PY 2013
VL 500
IS 7462
BP 323
EP +
DI 10.1038/nature12398
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 201AF
UT WOS:000323112400030
PM 23955232
DA 2026-03-09
ER

PT J
AU Shcheglovitov, A
   Shcheglovitova, O
   Yazawa, M
   Portmann, T
   Shu, R
   Sebastiano, V
   Krawisz, A
   Froehlich, W
   Bernstein, JA
   Hallmayer, JF
   Dolmetsch, RE
AF Shcheglovitov, Aleksandr
   Shcheglovitova, Olesya
   Yazawa, Masayuki
   Portmann, Thomas
   Shu, Rui
   Sebastiano, Vittorio
   Krawisz, Anna
   Froehlich, Wendy
   Bernstein, Jonathan A.
   Hallmayer, Joachim F.
   Dolmetsch, Ricardo E.
TI SHANK3 and IGF1 restore synaptic deficits in neurons from 22q13 deletion syndrome patients
SO NATURE
LA English
DT Article
ID scaffolding protein shank3; cortical-neurons; human fibroblasts; mutations; haploinsufficiency; generation; conversion; behaviors; family; cells
AB Phelan-McDermid syndrome (PMDS) is a complex neurodevelopmental disorder characterized by global developmental delay, severely impaired speech, intellectual disability, and an increased risk of autism spectrum disorders (ASDs)(1). PMDS is caused by heterozygous deletions of chromosome 22q13.3. Among the genes in the deleted region is SHANK3, which encodes a protein in the postsynaptic density (PSD)(2,3). Rare mutations in SHANK3 have been associated with idiopathic ASDs(4-7), non-syndromic intellectual disability(8), and schizophrenia(9). Although SHANK3 is considered to be the most likely candidate gene for the neurological abnormalities in PMDS patients(10), the cellular and molecular phenotypes associated with this syndrome in human neurons are unknown. We generated induced pluripotent stem (iPS) cells from individuals with PMDS and autism and used them to produce functional neurons. We show that PMDS neurons have reduced SHANK3 expression and major defects in excitatory, but not inhibitory, synaptic transmission. Excitatory synaptic transmission in PMDS neurons can be corrected by restoring SHANK3 expression or by treating neurons with insulin-like growth factor 1 (IGF1). IGF1 treatment promotes formation of mature excitatory synapses that lack SHANK3 but contain PSD95 and N-methyl-D-aspartate (NMDA) receptors with fast deactivation kinetics. Our findings provide direct evidence for a disruption in the ratio of cellular excitation and inhibition in PMDS neurons, and point to a molecular pathway that can be recruited to restore it.
C1 [Shcheglovitov, Aleksandr; Shcheglovitova, Olesya; Yazawa, Masayuki; Portmann, Thomas; Shu, Rui; Krawisz, Anna] Stanford Univ, Dept Neurobiol, Stanford, CA 94305 USA.
   [Sebastiano, Vittorio] Stanford Univ, Dept Obstet & Gynecol, Stanford, CA 94305 USA.
   [Sebastiano, Vittorio] Stanford Univ, Inst Stem Cell Biol & Regenerat Med, Stanford, CA 94305 USA.
   [Froehlich, Wendy; Bernstein, Jonathan A.] Stanford Univ, Dept Pediat, Stanford, CA 94305 USA.
   [Froehlich, Wendy; Hallmayer, Joachim F.] Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA.
   [Dolmetsch, Ricardo E.] Novartis Inst Biomed Res, Cambridge, MA 02139 USA.
C3 Stanford University; Stanford University; Stanford University; Stanford University; Stanford University; Novartis; Novartis USA
RP Dolmetsch, RE (corresponding author), Novartis Inst Biomed Res, Cambridge, MA 02139 USA.
EM Ricardo.dolmetsch@novartis.com
FU National Institutes of Health (NIH) [NS069375]; California Institute for Regenerative Medicine CIRM; Autism Science Foundation; Phelan-McDermid Syndrome Foundation; Swiss National Science Foundation; Japan Society for the Promotion of Research Abroad; American Heart Association; National Institute of Mental Health (NIMH) [R33MH087898]; NIH [5DP1OD3889]; CIRM [RT2-01906]; Simons Foundation; JDH; Flora foundation
NR 32
TC 360
Z9 445
U1 2
U2 79
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 14
PY 2013
VL 503
IS 7475
BP 267
EP +
DI 10.1038/nature12618
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 250YX
UT WOS:000326894200052
PM 24132240
DA 2026-03-09
ER

PT J
AU Peters, SE
   Kelly, DC
   Fraass, AJ
AF Peters, Shanan E.
   Kelly, Daniel C.
   Fraass, Andrew J.
TI Oceanographic controls on the diversity and extinction of planktonic foraminifera
SO NATURE
LA English
DT Article
ID global distribution; species-diversity; origination; macrostratigraphy; history; trends; record
AB Understanding the links between long-term biological evolution, the ocean-atmosphere system and plate tectonics is a central goal of Earth science. Although environmental perturbations of many different kinds are known to have affected long-term biological evolution, particularly during major mass extinction events(1,2), the relative importance of physical environmental factors versus biological interactions in governing rates of extinction and origination through geological time remains unknown(2). Here we use macrostratigraphic data from the Atlantic Ocean basin to show that changes in global species diversity and rates of extinction among planktonic foraminifera have been linked to tectonically and climatically forced changes in ocean circulation and chemistry from the Jurassic period to the present. Transient environmental perturbations, such as those that occurred after the asteroid impact at the end of the Cretaceous period(1) approximately 66 million years ago, and the Eocene/Oligocene greenhouse-icehouse transition(3,4) approximately 34 million years ago, are superimposed on this general long-term relationship. Rates of species origination, by contrast, are not correlated with corresponding macrostratigraphic quantities, indicating that physiochemical changes in the ocean-atmosphere system affect evolution principally by driving the synchronous extinction of lineages that originated owing to more protracted and complex interactions between biological and environmental factors.
C1 [Peters, Shanan E.; Kelly, Daniel C.; Fraass, Andrew J.] Univ Wisconsin, Dept Geosci, Madison, WI 53706 USA.
C3 University of Wisconsin System; University of Wisconsin Madison
RP Peters, SE (corresponding author), Univ Wisconsin, Dept Geosci, Madison, WI 53706 USA.
EM peters@geology.wisc.edu
FU National Science Foundation Division of Earth Sciences (NSF EAR) [EAR 0819931]; NSF [EAR 0628719]
NR 56
TC 44
Z9 48
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 JAN 17
PY 2013
VL 493
IS 7432
BP 398
EP U140
DI 10.1038/nature11815
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 071TA
UT WOS:000313615900050
PM 23302802
DA 2026-03-09
ER

PT J
AU Pedersen, VK
   Egholm, DL
AF Pedersen, Vivi Kathrine
   Egholm, David Lundbek
TI Glaciations in response to climate variations preconditioned by evolving topography
SO NATURE
LA English
DT Article
ID ice masses; erosion; relief; denudation; morphology; mechanism; buzzsaw; limits; alps
AB Landscapes modified by glacial erosion show a distinct distribution of surface area with elevation(1-3) (hypsometry). In particular, the height of these regions is influenced by climatic gradients controlling the altitude where glacial and periglacial processes are the most active, and as a result, surface area is focused just below the snowline altitude(1-9). Yet the effect of this distinct glacial hypsometric signature on glacial extent and therefore on continued glacial erosion has not previously been examined. Here we show how this topographic configuration influences the climatic sensitivity of Alpine glaciers, and how the development of a glacial hypsometric distribution influences the intensity of glaciations on timescales of more than a few glacial cycles. We find that the relationship between variations in climate and the resulting variation in areal extent of glaciation changes drastically with the degree of glacial modification in the landscape. First, in landscapes with novel glaciations, a nearly linear relationship between climate and glacial area exists. Second, in previously glaciated landscapes with extensive area at a similar elevation, highly nonlinear and rapid glacial expansions occur with minimal climate forcing, once the snowline reaches the hypsometric maximum. Our results also show that erosion associated with glaciations before the mid-Pleistocene transition at around 950,000 years ago probably preconditioned the landscape-producing glacial landforms and hypsometric maxima-such that ongoing cooling led to a significant change in glacial extent and erosion, resulting in more extensive glaciations and valley deepening in the late Pleistocene epoch. We thus provide a mechanism that explains previous observations from exposure dating(10) and low-temperature thermochronology(11) in the European Alps, and suggest that there is a strong topographic control on the most recent Quaternary period glaciations.
C1 [Pedersen, Vivi Kathrine] Univ Bergen, Dept Earth Sci, N-5007 Bergen, Norway.
   [Egholm, David Lundbek] Aarhus Univ, Dept Geosci, DK-8000 Aarhus, Denmark.
C3 University of Bergen; Aarhus University
RP Pedersen, VK (corresponding author), Univ Bergen, Dept Earth Sci, Allegaten 41, N-5007 Bergen, Norway.
EM vivi.pedersen@geo.uib.no
FU Danish Council for Independent Research; Inge Lehmanns Fund; Danish Council for Independent Research under the Sapere Aude Programme
NR 30
TC 106
Z9 124
U1 1
U2 107
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 10
PY 2013
VL 493
IS 7431
BP 206
EP 210
DI 10.1038/nature11786
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 066YY
UT WOS:000313259600036
PM 23302860
DA 2026-03-09
ER

PT J
AU Daniel, R
   Rubens, JR
   Sarpeshkar, R
   Lu, TK
AF Daniel, Ramiz
   Rubens, Jacob R.
   Sarpeshkar, Rahul
   Lu, Timothy K.
TI Synthetic analog computation in living cells
SO NATURE
LA English
DT Article
ID biology; circuit; network; motifs
AB A central goal of synthetic biology is to achieve multi-signal integration and processing in living cells for diagnostic, therapeutic and biotechnology applications(1). Digital logic has been used to build small-scale circuits, but other frameworks may be needed for efficient computation in the resource-limited environments of cells(2,3). Here we demonstrate that synthetic analog gene circuits can be engineered to execute sophisticated computational functions in living cells using just three transcription factors. Such synthetic analog gene circuits exploit feedback to implement logarithmically linear sensing, addition, ratiometric and power-law computations. The circuits exhibit Weber's law behaviour as in natural biological systems(4), operate over a wide dynamic range of up to four orders of magnitude and can be designed to have tunable transfer functions. Our circuits can be composed to implement higher-order functions that are well described by both intricate biochemical models and simple mathematical functions. By exploiting analog building-block functions that are already naturally present in cells(3,5), this approach efficiently implements arithmetic operations and complex functions in the logarithmic domain. Such circuits may lead to new applications for synthetic biology and biotechnology that require complex computations with limited parts, need wide-dynamic-range biosensing or would benefit from the fine control of gene expression.
C1 [Daniel, Ramiz; Sarpeshkar, Rahul] MIT, Elect Res Lab, Analog Circuits & Biol Syst Grp, Cambridge, MA 02139 USA.
   [Daniel, Ramiz; Rubens, Jacob R.; Lu, Timothy K.] MIT, Elect Res Lab, Synthet Biol Grp, Cambridge, MA 02139 USA.
   [Daniel, Ramiz; Rubens, Jacob R.; Sarpeshkar, Rahul; Lu, Timothy K.] MIT, Synthet Biol Ctr, Cambridge, MA 02139 USA.
   [Rubens, Jacob R.; Sarpeshkar, Rahul; Lu, Timothy K.] MIT, MIT Microbiol Program, Cambridge, MA 02139 USA.
   [Sarpeshkar, Rahul; Lu, Timothy K.] MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA.
   [Sarpeshkar, Rahul; Lu, Timothy K.] MIT, MIT Computat & Syst Biol Program, Cambridge, MA 02139 USA.
   [Sarpeshkar, Rahul] MIT, MIT Biophys Program, Cambridge, MA 02139 USA.
   [Lu, Timothy K.] MIT, Dept Biol Engn, Cambridge, MA 02139 USA.
C3 Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT)
RP Sarpeshkar, R (corresponding author), MIT, Elect Res Lab, Analog Circuits & Biol Syst Grp, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
EM rahuls@mit.edu; timlu@mit.edu
FU campus collaboration initiative from Lincoln Labs; US National Science Foundation [1124247]; Office of Naval Research [N000141110725]; Division of Computing and Communication Foundations; Direct For Computer & Info Scie & Enginr [1124247] Funding Source: National Science Foundation
NR 30
TC 332
Z9 411
U1 1
U2 178
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 30
PY 2013
VL 497
IS 7451
BP 619
EP +
DI 10.1038/nature12148
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 152UF
UT WOS:000319556100044
PM 23676681
DA 2026-03-09
ER

PT J
AU Smith, G
   Smolin, JA
AF Smith, Graeme
   Smolin, John A.
TI An exactly solvable model for quantum communications
SO NATURE
LA English
DT Article
ID classical capacity; gaussian channels
AB Information theory establishes the ultimate limits on performance for noisy communication systems(1). Accurate models of physical communication devices must include quantum effects, but these typically make the theory intractable(2-5). As a result, communication capacities-the maximum possible rates of data transmission-are not known, even for transmission between two users connected by an electromagnetic waveguide with Gaussian noise(6). Here we present an exactly solvable model of communication with a fully quantum electromagnetic field. This gives explicit expressions for all point-to-point capacities of noisy quantum channels, with implications for quantum key distribution and fibre-optic communications. We also develop a theory of quantum communication networks by solving some rudimentary models including broadcast and multiple-access channels. We compare the predictions of our model with the orthodox Gaussian model and in all cases find agreement to within a few bits. At high signal-to-noise ratios, our simple model captures the relevant physics while remaining amenable to exact solution.
C1 [Smith, Graeme; Smolin, John A.] IBM TJ Watson Res Ctr, Yorktown Hts, NY 10598 USA.
C3 International Business Machines (IBM); IBM USA
RP Smith, G (corresponding author), IBM TJ Watson Res Ctr, Yorktown Hts, NY 10598 USA.
EM gsbsmith@gmail.com
FU DARPA QUEST programme [HR0011-09-C-0047]
NR 29
TC 4
Z9 6
U1 1
U2 48
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 12
PY 2013
VL 504
IS 7479
BP 263
EP 267
DI 10.1038/nature12669
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 267TQ
UT WOS:000328121500033
PM 24240277
DA 2026-03-09
ER

PT J
AU Flesken-Nikitin, A
   Hwang, CI
   Cheng, CY
   Michurina, TV
   Enikolopov, G
   Nikitin, AY
AF Flesken-Nikitin, Andrea
   Hwang, Chang-Il
   Cheng, Chieh-Yang
   Michurina, Tatyana V.
   Enikolopov, Grigori
   Nikitin, Alexander Yu
TI Ovarian surface epithelium at the junction area contains a cancer-prone stem cell niche
SO NATURE
LA English
DT Article
ID aldehyde dehydrogenase-activity; self-renewal; origin; marker; carcinogenesis; identification; carcinomas; p53
AB Epithelial ovarian cancer (EOC) is the fifth leading cause of cancer deaths among women in the United States, but its pathogenesis is poorly understood(1-3). Some epithelial cancers are known to occur in transitional zones between two types of epithelium, whereas others have been shown to originate in epithelial tissue stem cells'. The stem cell niche of the ovarian surface epithelium (OSE), which is ruptured and regenerates during ovulation, has not yet been defined unequivocally. Here we identify the hilum region of the mouse ovary, the transitional (or junction) area between the OSE, mesothelium and tubal (oviductal) epithelium, as a previously unrecognized stem cell niche of the OSE. We find that cells of the hilum OSE are cycling slowly and express stem and/or progenitor cell markers ALDH1, LGR5, LEF1, CD 133 and CK6B. These cells display long-term stem cell properties ex vivo and in vivo, as shown by our serial sphere generation and long-term lineage-tracing assays. Importantly, the hilum cells show increased transformation potential after inactivation of tumour suppressor genes Trp53 and Rb1, whose pathways are altered frequently in the most aggressive and common type of human EOC, high-grade serous adenocarcinomea(7,8). Our study supports experimentally the idea that susceptibility of transitional zones to malignant transformation may be explained by the presence of stem cell niches in those areas. Identification of a stem cell niche for the OSE may have important implications for understanding EOC pathogenesis.
C1 [Flesken-Nikitin, Andrea; Hwang, Chang-Il; Cheng, Chieh-Yang; Nikitin, Alexander Yu] Cornell Univ, Dept Biomed Sci, Ithaca, NY 14853 USA.
   [Flesken-Nikitin, Andrea; Hwang, Chang-Il; Cheng, Chieh-Yang; Nikitin, Alexander Yu] Cornell Univ, Cornell Stem Cell Program, Ithaca, NY 14853 USA.
   [Michurina, Tatyana V.; Enikolopov, Grigori] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA.
   [Michurina, Tatyana V.; Enikolopov, Grigori] Moscow Inst Phys & Technol, NBIC, Moscow 123182, Russia.
C3 Cornell University; Cornell University; Cold Spring Harbor Laboratory; Moscow Institute of Physics & Technology
RP Nikitin, AY (corresponding author), Cornell Univ, Dept Biomed Sci, Ithaca, NY 14853 USA.
EM an58@cornell.edu
FU NYSTEM; US National Institutes of Health (NIH); National Cancer Institute (NCI) [CA096823, CA112354]; NYSTEM [CO23050, N1 1G-160]; Marsha Rivkin Center for Ovarian Cancer Research; NIH National Institute of Mental Health [MH092928]; NIH National Institute on Aging [AG040209]; Russian Ministry of Education and Science;  [NIH NICHD T32HD052471]
NR 30
TC 275
Z9 329
U1 0
U2 104
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 14
PY 2013
VL 495
IS 7440
BP 241
EP 245
DI 10.1038/nature11979
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 113FP
UT WOS:000316652300052
PM 23467088
DA 2026-03-09
ER

PT J
AU Vrontou, S
   Wong, AM
   Rau, KK
   Koerber, HR
   Anderson, DJ
AF Vrontou, Sophia
   Wong, Allan M.
   Rau, Kristofer K.
   Koerber, H. Richard
   Anderson, David J.
TI Genetic identification of C fibres that detect massage-like stroking of hairy skin in vivo
SO NATURE
LA English
DT Article
ID unmyelinated tactile afferents; sensory neurons; mice; touch; pain; populations; preference; paradigm; subsets; reward
AB Stroking of the skin produces pleasant sensations that can occur during social interactions with conspecifics, such as grooming(1). Despite numerous physiological studies (reviewed in ref. 2), molecularly defined sensory neurons that detect pleasant stroking of hairy skin(3,4) in vivo have not been reported. Previously, we identified a rare population of unmyelinated sensory neurons in mice that express the G-protein-coupled receptor MRGPRB4 (refs 5, 6). These neurons exclusively innervate hairy skin with large terminal arborizations(7) that resemble the receptive fields of C-tactile (CT) afferents in humans(8). Unlike other molecularly defined mechanosensory C-fibre subtypes(9,10), MRGPRB(+) neurons could not be detectably activated by sensory stimulation of the skin ex vivo. Therefore, we developed a preparation for calcium imaging in the spinal projections of these neurons during stimulation of the periphery in intact mice. Here we show that MRGPRB41 neurons are activated by massage-like stroking of hairy skin, but not by noxious punctate mechanical stimulation. By contrast, a different population of C fibres expressing MRGPRD(11) was activated by pinching but not by stroking, consistent with previous physiological and behavioural data(10,12). Pharmacogenetic activation of Mrgprb4-expressing neurons in freely behaving mice promoted conditioned place preference(13), indicating that such activation is positively reinforcing and/or anxiolytic. These data open the way to understanding the function of MRGPRB4 neurons during natural behaviours, and provide a general approach to the functional chargenetically identified subsets of somatosensory neurons in vivo.
C1 [Vrontou, Sophia; Wong, Allan M.; Anderson, David J.] CALTECH, Div Biol 156 29, Pasadena, CA 91125 USA.
   [Wong, Allan M.; Anderson, David J.] CALTECH, Howard Hughes Med Inst, Pasadena, CA 91125 USA.
   [Rau, Kristofer K.] Univ Louisville, Dept Anat Sci & Neurobiol, Louisville, KY 40202 USA.
   [Koerber, H. Richard] Univ Pittsburgh, Dept Neurobiol, Pittsburgh, PA 15261 USA.
C3 California Institute of Technology; California Institute of Technology; Howard Hughes Medical Institute; University of Louisville; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh
RP Anderson, DJ (corresponding author), CALTECH, Div Biol 156 29, Pasadena, CA 91125 USA.
EM wuwei@caltech.edu
FU NIH [5PO1NS-48499, 5R01 NS023476]; EMBO; Human Frontiers Science Program; Helen Hay Whitney Foundation
NR 39
TC 206
Z9 249
U1 4
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 JAN 31
PY 2013
VL 493
IS 7434
BP 669
EP +
DI 10.1038/nature11810
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 080CU
UT WOS:000314219600056
PM 23364746
DA 2026-03-09
ER

PT J
AU Noinaj, N
   Kuszak, AJ
   Gumbart, JC
   Lukacik, P
   Chang, HS
   Easley, NC
   Lithgow, T
   Buchanan, SK
AF Noinaj, Nicholas
   Kuszak, Adam J.
   Gumbart, James C.
   Lukacik, Petra
   Chang, Hoshing
   Easley, Nicole C.
   Lithgow, Trevor
   Buchanan, Susan K.
TI Structural insight into the biogenesis of β-barrel membrane proteins
SO NATURE
LA English
DT Article
ID outer-membrane; crystal-structure; molecular-dynamics; essential component; assembly machinery; bama; bacteria; flexibility; evolution; insertion
AB beta-barrel membrane proteins are essential for nutrient import, signalling, motility and survival. InGram-negative bacteria, the beta-barrel assembly machinery (BAM) complex is responsible for the biogenesis of beta-barrel membrane proteins, with homologous complexes found in mitochondria and chloroplasts. Here we describe the structure of BamA, the central and essential component of the BAM complex, from two species of bacteria: Neisseria gonorrhoeae and Haemophilus ducreyi. BamA consists of a large periplasmic domain attached to a 16-strand transmembrane beta-barrel domain. Three structural features shed light on the mechanism by which BamA catalyses beta-barrel assembly. First, the interior cavity is accessible in one BamA structure and conformationally closed in the other. Second, an exterior rim of the beta-barrel has a distinctly narrowed hydrophobic surface, locally destabilizing the outer membrane. And third, the beta-barrel can undergo lateral opening, suggesting a route from the interior cavity in BamA into the outer membrane.
C1 [Noinaj, Nicholas; Kuszak, Adam J.; Chang, Hoshing; Easley, Nicole C.; Buchanan, Susan K.] NIDDK, NIH, Bethesda, MD 20892 USA.
   [Gumbart, James C.] Georgia Inst Technol, Sch Phys, Atlanta, GA 30332 USA.
   [Lukacik, Petra] Diamond Light Source Ltd, Oxford OX11 0DE, England.
   [Lithgow, Trevor] Monash Univ, Dept Biochem & Mol Biol, Clayton, Vic 3800, Australia.
C3 National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK); University System of Georgia; Georgia Institute of Technology; Diamond Light Source; Monash University
RP Buchanan, SK (corresponding author), NIDDK, NIH, Bethesda, MD 20892 USA.
EM skbuchan@helix.nih.gov
FU National Institutes of Health (NIH), National Institute of Diabetes and Digestive and Kidney Diseases; NIH [K22-AI100927, R01-GM67887]; Diamond Light Source; ARC Discovery Project [DP120101878]; ARC Linkage International Grant [LX0776170]; 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]; Pittsburgh Supercomputing Center [RC2GM093307]; Australian Research Council [LX0776170] Funding Source: Australian Research Council; National Institute of Diabetes and Digestive and Kidney Diseases [ZIADK036139] Funding Source: NIH RePORTER
NR 60
TC 364
Z9 442
U1 3
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 SEP 19
PY 2013
VL 501
IS 7467
BP 385
EP +
DI 10.1038/nature12521
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 219XT
UT WOS:000324545700038
PM 23995689
DA 2026-03-09
ER

PT J
AU Niehuis, O
   Buellesbach, J
   Gibson, JD
   Pothmann, D
   Hanner, C
   Mutti, NS
   Judson, AK
   Gadau, J
   Ruther, J
   Schmitt, T
AF Niehuis, Oliver
   Buellesbach, Jan
   Gibson, Joshua D.
   Pothmann, Daniela
   Hanner, Christian
   Mutti, Navdeep S.
   Judson, Andrea K.
   Gadau, Juergen
   Ruther, Joachim
   Schmitt, Thomas
TI Behavioural and genetic analyses of Nasonia shed light on the evolution of sex pheromones
SO NATURE
LA English
DT Article
ID wasp; biosynthesis; genm
AB Sex pheromones play a pivotal role in the communication of many sexually reproducing organisms(1). Accordingly, speciation is often accompanied by pheromone diversification enabling proper mate finding and recognition(2). Current theory implies that chemical signals are under stabilizing selection by the receivers who thereby maintain the integrity of the signals(3). How the tremendous diversity of sex pheromones seen today evolved is poorly understood(4,5). Here we unravel the genetics of a newly evolved pheromone phenotype in wasps and present results from behavioural experiments indicating how the evolution of a new pheromone component occurred in an established sender-receiver system. We show that male Nasonia vitripennis evolved an additional pheromone compound differing only in its stereochemistry from a pre-existing one. Comparative behavioural studies show that conspecific females responded neutrally to the new pheromone phenotype when it evolved. Genetic mapping and gene knockdown show that a cluster of three closely linked genes accounts for the ability to produce this new pheromone phenotype. Our data suggest that new pheromone compounds can persist in a sender's population, without being selected against by the receiver and without the receiver having a pre-existing preference for the new pheromone phenotype, by initially remaining unperceived. Out results thus contribute valuable new insights into the evolutionary mechanisms underlying the diversification of sex pheromones: Furthermore, they indicate that the genetic basis of new pheromone compounds can be simple, allowing them to persist long enough in a population for receivers to evolve chemosensory adaptations for their exploitation.
C1 [Niehuis, Oliver] Zool Res Museum Alexander Koenig, Ctr Mol Biodivers Res, D-53113 Bonn, Germany.
   [Niehuis, Oliver; Buellesbach, Jan; Gibson, Joshua D.; Mutti, Navdeep S.; Judson, Andrea K.; Gadau, Juergen] Arizona State Univ, Sch Life Sci, Tempe, AZ 85287 USA.
   [Buellesbach, Jan; Hanner, Christian; Schmitt, Thomas] Univ Freiburg, D-79104 Freiburg, Germany.
   [Buellesbach, Jan; Schmitt, Thomas] Univ Freiburg, Spemann Grad Sch Biol & Med, D-79104 Freiburg, Germany.
   [Pothmann, Daniela; Ruther, Joachim] Univ Regensburg, Dept Zool, D-93053 Regensburg, Germany.
   [Mutti, Navdeep S.] DuPont Pioneer Agr Biotechnol, DuPont Expt Stn, Wilmington, DE 19880 USA.
   [Schmitt, Thomas] Tech Univ Darmstadt, Ecol Network Grp, D-64287 Darmstadt, Germany.
C3 Zoologisches Forschungsmuseum Alexander Koenig (ZFMK); Arizona State University; Arizona State University-Tempe; University of Freiburg; University of Freiburg; University of Regensburg; DuPont; DuPont USA; Technical University of Darmstadt
RP Niehuis, O (corresponding author), Zool Res Museum Alexander Koenig, Ctr Mol Biodivers Res, D-53113 Bonn, Germany.
EM o.niehuis.zfmk@uni-bonn.de
FU Alexander von Humboldt foundation; Excellence Initiative of the German Research Foundation (Spemann Graduate School) [GSC-4]; German Research Foundation (DFG) [RU 717/10-1]
NR 29
TC 105
Z9 124
U1 3
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 FEB 21
PY 2013
VL 494
IS 7437
BP 345
EP 348
DI 10.1038/nature11838
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 095CS
UT WOS:000315312900036
PM 23407492
DA 2026-03-09
ER

PT J
AU Shi, XS
   Bi, YC
   Yang, W
   Guo, XD
   Jiang, Y
   Wan, CJ
   Li, LY
   Bai, YB
   Guo, J
   Wang, YJ
   Chen, XJ
   Wu, B
   Sun, HB
   Liu, WL
   Wang, JF
   Xu, CQ
AF Shi, Xiaoshan
   Bi, Yunchen
   Yang, Wei
   Guo, Xingdong
   Jiang, Yan
   Wan, Chanjuan
   Li, Lunyi
   Bai, Yibing
   Guo, Jun
   Wang, Yujuan
   Chen, Xiangjun
   Wu, Bo
   Sun, Hongbin
   Liu, Wanli
   Wang, Junfeng
   Xu, Chenqi
TI Ca2+ regulates T-cell receptor activation by modulating the charge property of lipids
SO NATURE
LA English
DT Article
ID immunological synapse; plasma-membrane; crac channel; k+ channel; proteins; binding; orai; phosphorylation; recognition; signals
AB Ionic protein-lipid interactions are critical for the structure and function of membrane receptors, ion channels, integrins and many other proteins(1-7). However, the regulatory mechanism of these interactions is largely unknown. Here we show that Ca2+ can bind directly to anionic phospholipids and thus modulate membrane protein function. The activation of T-cell antigen receptor-CD3 complex (TCR), a key membrane receptor for adaptive immunity, is regulated by ionic interactions between positively charged CD3 epsilon/zeta cytoplasmic domains (CD3(CD)) and negatively charged phospholipids in the plasma membrane(1,8-10). Crucial tyrosines are buried in the membrane and are largely protected from phosphorylation in resting T cells. It is not clear how CD3CD dissociates from the membrane in antigen-stimulated T cells. The antigen engagement of even a single TCR triggers a Ca2+ influx(11) and TCR-proximal Ca2+ concentration is higher than the average cytosolic Ca2+ concentration(12). Our biochemical, live-cell fluorescence resonance energy transfer and NMR experiments showed that an increase in Ca2+ concentration induced the dissociation of CD3CD from the membrane and the solvent exposure of tyrosine residues. As a consequence, CD3 tyrosine phosphorylation was significantly enhanced by Ca2+ influx. Moreover, when compared with wild-type cells, Ca2+ channel-deficient T cells had substantially lower levels of CD3 phosphorylation after stimulation. The effect of Ca2+ on facilitating CD3 phosphorylation is primarily due to the charge of this ion, as demonstrated by the fact that replacing Ca2+ with the non-physiological ion Sr2+ resulted in the same feedback effect. Finally, P-31 NMR spectroscopy showed that Ca2+ bound to the phosphate group in anionic phospholipids at physiological concentrations, thus neutralizing the negative charge of phospholipids. Rather than initiating CD3 phosphorylation, this regulatory pathway of Ca2+ has a positive feedback effect on amplifying and sustaining CD3 phosphorylation and should enhance T-cell sensitivity to foreign antigens. Our study thus provides a new regulatory mechanism of Ca2+ to T-cell activation involving direct lipid manipulation.
C1 [Bi, Yunchen; Wan, Chanjuan; Wang, Yujuan; Wu, Bo; Sun, Hongbin; Wang, Junfeng] Chinese Acad Sci, High Magnet Field Lab, Hefei Inst Phys Sci, Hefei 230031, Anhui, Peoples R China.
   [Shi, Xiaoshan; Yang, Wei; Guo, Xingdong; Jiang, Yan; Li, Lunyi; Bai, Yibing; Guo, Jun; Xu, Chenqi] Chinese Acad Sci, State Key Lab Mol Biol, Inst Biochem & Cell Biol, Shanghai Inst Biol Sci, Shanghai 200031, Peoples R China.
   [Shi, Xiaoshan; Yang, Wei; Guo, Xingdong; Jiang, Yan; Li, Lunyi; Bai, Yibing; Guo, Jun; Xu, Chenqi] Chinese Acad Sci, Natl Ctr Prot Sci, Inst Biochem & Cell Biol, Shanghai Inst Biol Sci, Shanghai 201203, Peoples R China.
   [Chen, Xiangjun; Liu, Wanli] Tsinghua Univ, Sch Life Sci, Beijing 100084, Peoples R China.
C3 Chinese Academy of Sciences; Hefei Institutes of Physical Science, CAS; Chinese Academy of Sciences; Center for Excellence in Molecular Cell Science, CAS; Chinese Academy of Sciences; Center for Excellence in Molecular Cell Science, CAS; Tsinghua University
RP Wang, JF (corresponding author), Chinese Acad Sci, High Magnet Field Lab, Hefei Inst Phys Sci, 350 Shushanhu Rd, Hefei 230031, Anhui, Peoples R China.
EM junfeng@hmfl.ac.cn; cqxu@sibcb.ac.cn
FU National Basic Research Program of China (973 Program) [2011CB910901, 2012CB910804, 2012CB917202]; National Science Foundation of China [31070738]; Chinese Academy of Sciences [KSCX2-EW-J-11]; Shanghai Municipal Commission for Science and Technology [10PJ1411500]; Young Talent Program of Shanghai Institutes for Biological Sciences, CAS [2010KIP101]
NR 31
TC 226
Z9 269
U1 2
U2 319
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 3
PY 2013
VL 493
IS 7430
BP 111
EP +
DI 10.1038/nature11699
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 062QC
UT WOS:000312933800041
PM 23201688
DA 2026-03-09
ER

PT J
AU Kanekiyo, M
   Wei, CJ
   Yassine, HM
   McTamney, PM
   Boyington, JC
   Whittle, JRR
   Rao, SS
   Kong, WP
   Wang, LS
   Nabel, GJ
AF Kanekiyo, Masaru
   Wei, Chih-Jen
   Yassine, Hadi M.
   McTamney, Patrick M.
   Boyington, Jeffrey C.
   Whittle, James R. R.
   Rao, Srinivas S.
   Kong, Wing-Pui
   Wang, Lingshu
   Nabel, Gary J.
TI Self-assembling influenza nanoparticle vaccines elicit broadly neutralizing H1N1 antibodies
SO NATURE
LA English
DT Article
ID a virus; hemagglutinin; epitope; immunogenicity; vaccination; recognizes; induction; ferritin; immunity; protein
AB Influenza viruses pose a significant threat to the public and are a burden on global health systems(1,2). Each year, influenza vaccines must be rapidly produced to match circulating viruses, a process constrained by dated technology and vulnerable to unexpected strains emerging from humans and animal reservoirs. Here we use knowledge of protein structure to design self-assembling nanoparticles that elicit broader and more potent immunity than traditional influenza vaccines. The viral haemagglutinin was genetically fused to ferritin, a protein that naturally forms nanoparticles composed of 24 identical polypeptides(3). Haemagglutinin was inserted at the interface of adjacent subunits so that it spontaneously assembled and generated eight trimeric viral spikes on its surface. Immunization with this influenza nanoparticle vaccine elicited haemagglutination inhibition antibody titres more than tenfold higher than those from the licensed inactivated vaccine. Furthermore, it elicited neutralizing antibodies to two highly conserved vulnerable haemagglutinin structures that are targets of universal vaccines: the stem(4,5) and the receptor binding site on the head(6,7). Antibodies elicited by a 1999 haemagglutinin-nanoparticle vaccine neutralized H1N1 viruses from 1934 to 2007 and protected ferrets from an unmatched 2007 H1N1 virus challenge. This structure-based, self-assembling synthetic nanoparticle vaccine improves the potency and breadth of influenza virus immunity, and it provides a foundation for building broader vaccine protection against emerging influenza viruses and other pathogens.
C1 [Kanekiyo, Masaru; Wei, Chih-Jen; Yassine, Hadi M.; McTamney, Patrick M.; Boyington, Jeffrey C.; Whittle, James R. R.; Rao, Srinivas S.; Kong, Wing-Pui; Wang, Lingshu; 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), Sanofi, 640 Mem Dr, Cambridge, MA 02139 USA.
EM Gary.Nabel@sanofi.com
FU Intramural Research Program of the Vaccine Research Center, NIAID, National Institutes of Health; National Institute of Allergy and Infectious Diseases [ZIAAI005003] Funding Source: NIH RePORTER
NR 33
TC 732
Z9 912
U1 7
U2 378
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 4
PY 2013
VL 499
IS 7456
BP 102
EP +
DI 10.1038/nature12202
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 176ED
UT WOS:000321285600042
PM 23698367
DA 2026-03-09
ER

PT J
AU Cao, Y
   Pan, YP
   Huang, H
   Jin, XS
   Levin, EJ
   Kloss, B
   Zhou, M
AF Cao, Yu
   Pan, Yaping
   Huang, Hua
   Jin, Xiangshu
   Levin, Elena J.
   Kloss, Brian
   Zhou, Ming
TI Gating of the TrkH ion channel by its associated RCK protein TrkA
SO NATURE
LA English
DT Article
ID membrane region m-2c2; k+-uptake system; escherichia-coli; ktrab system; mechanism; transport; domains; binding; ring; flux
AB TrkH belongs to a superfamily of K+ transport proteins required for growth of bacteria in low external K+ concentrations. The crystal structure of TrkH from Vibrio parahaemolyticus showed that TrkH resembles a K+ channel and may have a gating mechanism substantially different from K+ channels. TrkH assembles with TrkA, a cytosolic protein comprising two RCK (regulate the conductance of K+) domains, which are found in certain K+ channels and control their gating. However, fundamental questions on whether TrkH is an ion channel and how it is regulated by TrkA remain unresolved. Here we show single-channel activity of TrkH that is upregulated by ATP via TrkA. We report two structures of the tetrameric TrkA ring, one in complex with TrkH and one in isolation, in which the ring assumes two markedly different conformations. These results suggest a mechanism for how ATP increases TrkH activity by inducing conformational changes in TrkA.
C1 [Cao, Yu; Pan, Yaping; Huang, Hua; Levin, Elena J.; Zhou, Ming] Columbia Univ, Coll Phys & Surg, Dept Physiol & Cellular Biophys, New York, NY 10032 USA.
   [Pan, Yaping; Huang, Hua; Levin, Elena J.; Zhou, Ming] Baylor Coll Med, Verna & Marrs McLean Dept Biochem & Mol Biol, Houston, TX 77030 USA.
   [Jin, Xiangshu] Natl Inst Biol Sci, Beijing 102206, Peoples R China.
   [Kloss, Brian] New York Struct Biol Ctr, New York Consortium Membrane Prot Struct, New York, NY 10027 USA.
C3 Columbia University; Baylor College of Medicine; National Institute of Biological Sciences, Beijing
RP Zhou, M (corresponding author), Columbia Univ, Coll Phys & Surg, Dept Physiol & Cellular Biophys, 630 W 168th St, New York, NY 10032 USA.
EM mzhou@bcm.edu
FU US National Institutes of Health [DK088057, GM098878, HL086392]; PSI: Biology grant [5808, U54GM095315]; American Heart Association [12EIA8850017, 0826067D]; Irma T. Hirschl Trust; American Heart Association (AHA) [0826067D, 12EIA8850017] Funding Source: American Heart Association (AHA)
NR 33
TC 91
Z9 113
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 APR 18
PY 2013
VL 496
IS 7445
BP 317
EP +
DI 10.1038/nature12056
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 126FV
UT WOS:000317599200028
PM 23598339
DA 2026-03-09
ER

PT J
AU Tang, ZM
   Lin, MG
   Stowe, TR
   Chen, S
   Zhu, MY
   Stearns, T
   Franco, B
   Zhong, Q
AF Tang, Zaiming
   Lin, Mary Grace
   Stowe, Timothy Richard
   Chen, She
   Zhu, Muyuan
   Stearns, Tim
   Franco, Brunella
   Zhong, Qing
TI Autophagy promotes primary ciliogenesis by removing OFD1 from centriolar satellites
SO NATURE
LA English
DT Article
ID primary cilia; selective autophagy; joubert-syndrome; bbs proteins; disease; ubiquitin; gene; identification; degradation; mechanisms
AB The primary cilium is a microtubule-based organelle that functions in sensory and signalling pathways. Defects in ciliogenesis can lead to a group of genetic syndromes known as ciliopathies(1-3). However, the regulatory mechanisms of primary ciliogenesis in normal and cancer cells are incompletely understood. Here we demonstrate that autophagic degradation of a ciliopathy protein, OFD1 (oral-facial-digital syndrome 1), at centriolar satellites promotes primary cilium biogenesis. Autophagy is a catabolic pathway in which cytosol, damaged organelles and protein aggregates are engulfed in autophagosomes and delivered to lysosomes for destruction(4). We show that the population of OFD1 at the centriolar satellites is rapidly degraded by autophagy upon serum starvation. In autophagy-deficient Atg5 or Atg3 null mouse embryonic fibroblasts, OFD1 accumulates at centriolar satellites, leading to fewer and shorter primary cilia and a defective recruitment of BBS4 (Bardet-Biedl syndrome 4) to cilia. These defects are fully rescued by OFD1 partial knockdown that reduces the population of OFD1 at centriolar satellites. More strikingly, OFD1 depletion at centriolar satellites promotes cilia formation in both cycling cells and transformed breast cancer MCF7 cells that normally do not form cilia. This work reveals that removal of OFD1 by autophagy at centriolar satellites represents a general mechanism to promote ciliogenesis in mammalian cells. These findings define a newly recognized role of autophagy in organelle biogenesis.
C1 [Tang, Zaiming; Zhong, Qing] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Ctr Autophagy Res, Dallas, TX 75390 USA.
   [Tang, Zaiming; Zhong, Qing] Univ Texas SW Med Ctr Dallas, Dept Biochem, Dallas, TX 75390 USA.
   [Tang, Zaiming; Lin, Mary Grace; Zhong, Qing] Univ Calif Berkeley, Dept Mol & Cell Biol, Div Biochem Biophys & Struct Biol, Berkeley, CA 94720 USA.
   [Tang, Zaiming; Zhu, Muyuan] Zhejiang Univ, Coll Life Sci, State Key Lab Plant Physiol & Biochem, Hangzhou 310058, Zhejiang, Peoples R China.
   [Stowe, Timothy Richard; Stearns, Tim] Stanford Univ, Dept Biol, Stanford, CA 94305 USA.
   [Chen, She] Natl Inst Biol Sci, Beijing 102206, Peoples R China.
   [Franco, Brunella] Univ Naples Federico II, Dept Translat Med Sci, Med Genet Serv, Naples, Italy.
   [Franco, Brunella] Telethon Inst Genet & Med TIGEM, Naples, Italy.
C3 University of Texas System; University of Texas Southwestern Medical Center; University of Texas System; University of Texas Southwestern Medical Center; University of California System; University of California Berkeley; Zhejiang University; Stanford University; National Institute of Biological Sciences, Beijing; University of Naples Federico II; Fondazione Telethon; Telethon Institute of Genetics & Medicine (TIGEM)
RP Zhong, Q (corresponding author), Univ Texas SW Med Ctr Dallas, Dept Internal Med, Ctr Autophagy Res, Dallas, TX 75390 USA.
EM qing.zhong@utsouthwestern.edu
FU Polycystic Kidney Disease Foundation; American Cancer Society [RSG-11-274-01-CCG]; National Cancer Institute [CA133228]; Italian Telethon Foundation [TGM11CB3]; EU [241955]; China Scholarship Council
NR 34
TC 338
Z9 386
U1 2
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 10
PY 2013
VL 502
IS 7470
BP 254
EP +
DI 10.1038/nature12606
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 231RU
UT WOS:000325436100055
PM 24089205
DA 2026-03-09
ER

PT J
AU Sigloch, K
   Mihalynuk, MG
AF Sigloch, Karin
   Mihalynuk, Mitchell G.
TI Intra-oceanic subduction shaped the assembly of Cordilleran North America
SO NATURE
LA English
DT Article
ID cretaceous strata; reference frames; central sonora; plate motions; lower-mantle; ocean; slab; accretion; pacific; arc
AB The western quarter of North America consists of accreted terranes-crustal blocks added over the past 200 million years-but the reason for this is unclear. The widely accepted explanation posits that the oceanic Farallon plate acted as a conveyor belt, sweeping terranes into the continental margin while subducting under it. Here we show that this hypothesis, which fails to explain many terrane complexities, is also inconsistent with new tomographic images of lower-mantle slabs, and with their locations relative to plate reconstructions. We offer a reinterpretation of North American palaeogeography and test it quantitatively: collision events are clearly recorded by slab geometry, and can be time calibrated and reconciled with plate reconstructions and surface geology. The seas west of Cretaceous North America must have resembled today's western Pacific, strung with island arcs. All proto-Pacific plates initially subducted into almost stationary, intra-oceanic trenches, and accumulated below as massive vertical slab walls. Above the slabs, long-lived volcanic archipelagos and subduction complexes grew. Crustal accretion occurred when North America overrode the archipelagos, causing major episodes of Cordilleran mountain building.
C1 [Sigloch, Karin] Univ Munich, Dept Earth & Environm Sci, D-80333 Munich, Germany.
   [Mihalynuk, Mitchell G.] British Columbia Geol Survey, Victoria, BC V8W 9N3, Canada.
C3 University of Munich
RP Sigloch, K (corresponding author), Univ Munich, Dept Earth & Environm Sci, Theresienstr 41, D-80333 Munich, Germany.
EM sigloch@geophysik.uni-muenchen.de; Mitch.Mihalynuk@gov.bc.ca
NR 52
TC 234
Z9 258
U1 0
U2 132
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 4
PY 2013
VL 496
IS 7443
BP 50
EP +
DI 10.1038/nature12019
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 117ZZ
UT WOS:000316993400023
PM 23552944
DA 2026-03-09
ER

PT J
AU Ebert, DH
   Gabel, HW
   Robinson, ND
   Kastan, NR
   Hu, LS
   Cohen, S
   Navarro, AJ
   Lyst, MJ
   Ekiert, R
   Bird, AP
   Greenberg, ME
AF Ebert, Daniel H.
   Gabel, Harrison W.
   Robinson, Nathaniel D.
   Kastan, Nathaniel R.
   Hu, Linda S.
   Cohen, Sonia
   Navarro, Adrija J.
   Lyst, Matthew J.
   Ekiert, Robert
   Bird, Adrian P.
   Greenberg, Michael E.
TI Activity-dependent phosphorylation of MeCP2 threonine 308 regulates interaction with NCoR
SO NATURE
LA English
DT Article
ID methyl-cpg; bdnf transcription; rett-syndrome; binding; repression; chromatin; association; inhibition; mutations; disorder
AB Rett syndrome (RTT) is an X-linked human neurodevelopmental disorder with features of autism and severe neurological dysfunction in females. RTT is caused by mutations in methyl-CpG-binding protein 2 (MeCP2), a nuclear protein that, in neurons, regulates transcription, is expressed at high levels similar to that of histones, and binds to methylated cytosines broadly across the genome(1-5). By phosphotryptic mapping, we identify three sites (S86, S274 and T308) of activity-dependent MeCP2 phosphorylation. Phosphorylation of these sites is differentially induced by neuronal activity, brain-derived neurotrophic factor, or agents that elevate the intracellular level of 3',5'-cyclic AMP (cAMP), indicating that MeCP2 may function as an epigenetic regulator of gene expression that integrates diverse signals from the environment. Here we show that the phosphorylation of T308 blocks the interaction of the repressor domain of MeCP2 with the nuclear receptor co-repressor (NCoR) complex and suppresses the ability of MeCP2 to repress transcription. In knock-in mice bearing the common human RTT missense mutation R306C, neuronal activity fails to induce MeCP2 T308 phosphorylation, suggesting that the loss of T308 phosphorylation might contribute to RTT. Consistent with this possibility, the mutation of MeCP2 T308A in mice leads to a decrease in the induction of a subset of activity-regulated genes and to RTT-like symptoms. These findings indicate that the activity-dependent phosphorylation of MeCP2 at T308 regulates the interaction of MeCP2 with the NCoR complex, and that RTT in humans may be due, in part, to the loss of activity-dependent MeCP2 T308 phosphorylation and a disruption of the phosphorylation-regulated interaction of MeCP2 with the NCoR complex.
C1 [Ebert, Daniel H.; Gabel, Harrison W.; Robinson, Nathaniel D.; Kastan, Nathaniel R.; Hu, Linda S.; Cohen, Sonia; Navarro, Adrija J.; Greenberg, Michael E.] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA.
   [Ebert, Daniel H.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02114 USA.
   [Lyst, Matthew J.; Ekiert, Robert; Bird, Adrian P.] Univ Edinburgh, Wellcome Trust Ctr Cell Biol, Edinburgh EH9 3JR, Midlothian, Scotland.
C3 Harvard University; Harvard Medical School; Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Massachusetts General Hospital; University of Edinburgh
RP Greenberg, ME (corresponding author), Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA.
EM michael_greenberg@hms.harvard.edu
FU NIH [RO1NS048276, K08MH90306, P30-HD 18655]; Rett Syndrome Research Trust; Dupont-Warren Fellowship in the Department of Psychiatry at Harvard Medical School; Nancy Lurie Marks Fellowship in Autism at Harvard Medical School; Damon Runyon Cancer Research Foundation [DRG-2048-10]; National Institute of General Medical Sciences [T32GM007753] Funding Source: NIH RePORTER
NR 26
TC 179
Z9 219
U1 0
U2 57
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 18
PY 2013
VL 499
IS 7458
BP 341
EP U116
DI 10.1038/nature12348
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 184RJ
UT WOS:000321910700037
PM 23770587
DA 2026-03-09
ER

PT J
AU Santoso, A
   McGregor, S
   Jin, FF
   Cai, WJ
   England, MH
   An, SI
   McPhaden, MJ
   Guilyardi, E
AF Santoso, Agus
   McGregor, Shayne
   Jin, Fei-Fei
   Cai, Wenju
   England, Matthew H.
   An, Soon-Il
   McPhaden, Michael J.
   Guilyardi, Eric
TI Late-twentieth-century emergence of the El Nino propagation asymmetry and future projections
SO NATURE
LA English
DT Article
ID tropical pacific; surface-temperature; enso dynamics; ocean; feedback; oscillation; impact
AB The El Nino/Southern Oscillation (ENSO) is the Earth's most prominent source of interannual climate variability, exerting profound worldwide effects(1-7). Despite decades of research, its behaviour continues to challenge scientists. In the eastern equatorial Pacific Ocean, the anomalously cool sea surface temperatures (SSTs) found during La Nina events and the warm waters of modest El Nino events both propagate westwards, as in the seasonal cycle(7). In contrast, SST anomalies propagate eastwards during extreme El Nino events, prominently in the post-1976 period(7-10), spurring unusual weather events worldwide with costly consequences(3-6,11). The cause of this propagation asymmetry is currently unknown(10). Here we trace the cause of the asymmetry to the variations in upper ocean currents in the equatorial Pacific, whereby the westward-flowing currents are enhanced during La Nina events but reversed during extreme El Nino events. Our results highlight that propagation asymmetry is favoured when the westward mean equatorial currents weaken, as is projected to be the case under global warming(12-14). By analysing past and future climate simulations of an ensemble of models with more realistic propagation, we find a doubling in the occurrences of El Nino events that feature prominent eastward propagation characteristics in a warmer world. Our analysis thus suggests that more frequent emergence of propagation asymmetry will be an indication of the Earth's warming climate.
C1 [Santoso, Agus; McGregor, Shayne; England, Matthew H.] Univ New S Wales, Australian Res Council ARC Ctr Excellence Climate, Sydney, NSW 2052, Australia.
   [Santoso, Agus; McGregor, Shayne; England, Matthew H.] Univ New S Wales, Climate Change Res Ctr, Sydney, NSW 2052, Australia.
   [Jin, Fei-Fei] Univ Hawaii Manoa, SOEST, Dept Meteorol, Honolulu, HI 96822 USA.
   [Cai, Wenju] CSIRO, Marine & Atmospher Res, Aspendale, Vic 3195, Australia.
   [An, Soon-Il] Yonsei Univ, Dept Atmospher Sci, Seoul 120749, South Korea.
   [McPhaden, Michael J.] NOAA, Pacific Marine Environm Lab, Seattle, WA 98115 USA.
   [Guilyardi, Eric] Univ Paris 06, CNRS, IPSL, Lab Oceanog & Climat Experimentat & Approches Num, F-75252 Paris 05, France.
   [Guilyardi, Eric] Univ Reading, Dept Meteorol, Natl Ctr Atmospher Sci NCAS Climate, Reading RG6 6BB, Berks, England.
C3 University of New South Wales Sydney; University of New South Wales Sydney; University of Hawaii System; University of Hawaii Manoa; Commonwealth Scientific & Industrial Research Organisation (CSIRO); Yonsei University; National Oceanic Atmospheric Admin (NOAA) - USA; Institut Polytechnique de Paris; Ecole Polytechnique; Museum National d'Histoire Naturelle (MNHN); Centre National de la Recherche Scientifique (CNRS); Sorbonne Universite; Universite Paris Cite; University of Reading; UK Research & Innovation (UKRI); Natural Environment Research Council (NERC); NERC National Centre for Atmospheric Science
RP Santoso, A (corresponding author), Univ New S Wales, Australian Res Council ARC Ctr Excellence Climate, Level 4 Mathews Bldg, Sydney, NSW 2052, Australia.
EM a.santoso@unsw.edu.au
FU Australian Research Council; Australian Climate Change Science Programme; National Research Foundation of Korea; Korean government (MEST) [NRF-2009-C1AAA001-2009-0093042]; NOAA; Directorate For Geosciences [1034798] Funding Source: National Science Foundation; Div Atmospheric & Geospace Sciences [1034798] Funding Source: National Science Foundation; Natural Environment Research Council [ncas10009] Funding Source: researchfish
NR 44
TC 116
Z9 125
U1 0
U2 93
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 5
PY 2013
VL 504
IS 7478
BP 126
EP +
DI 10.1038/nature12683
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 264BK
UT WOS:000327851700044
PM 24240279
DA 2026-03-09
ER

PT J
AU Depoorter, MA
   Bamber, JL
   Griggs, JA
   Lenaerts, JTM
   Ligtenberg, SRM
   van den Broeke, MR
   Moholdt, G
AF Depoorter, M. A.
   Bamber, J. L.
   Griggs, J. A.
   Lenaerts, J. T. M.
   Ligtenberg, S. R. M.
   van den Broeke, M. R.
   Moholdt, G.
TI Calving fluxes and basal melt rates of Antarctic ice shelves
SO NATURE
LA English
DT Article
ID southern-ocean; mass-balance; beneath; greenland; icebergs; iron; flow
AB Iceberg calving has been assumed to be the dominant cause of mass loss for the Antarctic ice sheet, with previous estimates of the calving flux exceeding 2,000 gigatonnes per year(1,2). More recently, the importance of melting by the ocean has been demonstrated close to the grounding line and near the calving front(3-5). So far, however, no study has reliably quantified the calving flux and the basal mass balance (the balance between accretion and ablation at the ice-shelf base) for the whole of Antarctica. The distribution of fresh water in the Southern Ocean and its partitioning between the liquid and solid phases is therefore poorly constrained. Here we estimate the mass balance components for all ice shelves in Antarctica, using satellite measurements of calving flux and grounding-line flux, modelled ice-shelf snow accumulation rates(6) and a regional scaling that accounts for unsurveyed areas. We obtain a total calving flux of 1,321 +/- 144 gigatonnes per year and a total basal mass balance of -1,454 +/- 174 gigatonnes per year. This means that about half of the ice-sheet surface mass gain is lost through oceanic erosion before reaching the ice front, and the calving flux is about 34 per cent less than previous estimates derived from iceberg tracking(1,2,7). In addition, the fraction of mass loss due to basal processes varies from about 10 to 90 per cent between ice shelves. We find a significant positive correlation between basal mass loss and surface elevation change for ice shelves experiencing surface lowering(8) and enhanced discharge(9). We suggest that basal mass loss is a valuable metric for predicting future ice-shelf vulnerability to oceanic forcing.
C1 [Depoorter, M. A.; Bamber, J. L.; Griggs, J. A.] Univ Bristol, Sch Geog Sci, Bristol Glaciol Ctr, Bristol BS8 1SS, Avon, England.
   [Lenaerts, J. T. M.; Ligtenberg, S. R. M.; van den Broeke, M. R.] Univ Utrecht, Inst Marine & Atmospher Res Utrecht, NL-3584 CC Utrecht, Netherlands.
   [Moholdt, G.] Univ Calif San Diego, Scripps Inst Oceanog, La Jolla, CA 92093 USA.
C3 University of Bristol; Utrecht University; University of California System; University of California San Diego; Scripps Institution of Oceanography
RP Depoorter, MA (corresponding author), Univ Bristol, Sch Geog Sci, Bristol Glaciol Ctr, Bristol BS8 1SS, Avon, England.
EM mathieu.depoorter@bristol.ac.uk; j.bamber@bristol.ac.uk
FU European Union [226375]; Netherlands Polar Programme; NERC [NE/I027401/1]; NERC [NE/I027401/1] Funding Source: UKRI; Natural Environment Research Council [NE/I027401/1] Funding Source: researchfish
NR 31
TC 562
Z9 632
U1 1
U2 203
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 3
PY 2013
VL 502
IS 7469
BP 89
EP +
DI 10.1038/nature12567
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 227IM
UT WOS:000325106000036
PM 24037377
DA 2026-03-09
ER

PT J
AU Ho, CY
   Jaalouk, DE
   Vartiainen, MK
   Lammerding, J
AF Ho, Chin Yee
   Jaalouk, Diana E.
   Vartiainen, Maria K.
   Lammerding, Jan
TI Lamin A/C and emerin regulate MKL1-SRF activity by modulating actin dynamics
SO NATURE
LA English
DT Article
ID a-type lamins; nuclear-envelope; dilated cardiomyopathy; transcription factors; muscle regeneration; muscular-dystrophy; cell-nucleus; rpel motifs; binding; localization
AB Laminopathies, caused by mutations in the LMNA gene encoding the nuclear envelope proteins lamins A and C, represent a diverse group of diseases that include Emery-Dreifuss muscular dystrophy (EDMD), dilated cardiomyopathy (DCM), limb-girdle muscular dystrophy, and Hutchison-Gilford progeria syndrome(1). Most LMNA mutations affect skeletal and cardiac muscle by mechanisms that remain incompletely understood. Loss of structural function and altered interaction of mutant lamins with (tissue-specific) transcription factors have been proposed to explain the tissue-specific phenotypes(1). Here we report in mice that lamin-A/C-deficient (Lmna(-/-)) and Lmna(N195K/N195K) mutant cells have impaired nuclear translocation and downstream signalling of the mechanosensitive transcription factor megakaryoblastic leukaemia 1 (MKL1), a myocardin family member that is pivotal in cardiac development and function(2). Altered nucleo-cytoplasmic shuttling of MKL1 was caused by altered actin dynamics in Lmna(-/-) and Lmna(N195K/N195K) mutant cells. Ectopic expression of the nuclear envelope protein emerin, which is mislocalized in Lmna mutant cells and also linked to EDMD and DCM, restored MKL1 nuclear translocation and rescued actin dynamics in mutant cells. These findings present a novel mechanism that could provide insight into the disease aetiology for the cardiac phenotype in many laminopathies, whereby lamin A/C and emerin regulate gene expression through modulation of nuclear and cytoskeletal actin polymerization.
C1 [Ho, Chin Yee; Lammerding, Jan] Cornell Univ, Dept Biomed Engn, Weill Inst Cell & Mol Biol, Ithaca, NY 14853 USA.
   [Ho, Chin Yee; Jaalouk, Diana E.; Lammerding, Jan] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA.
   [Vartiainen, Maria K.] Univ Helsinki, Inst Biotechnol, Helsinki 00014, Finland.
C3 Cornell University; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard Medical School; University of Helsinki
RP Lammerding, J (corresponding author), Cornell Univ, Dept Biomed Engn, Weill Inst Cell & Mol Biol, Ithaca, NY 14853 USA.
EM jan.lammerding@cornell.edu
FU National Institutes of Health [R01 NS059348, R01 HL082792]; Department of Defense Breast Cancer Idea Award [BC102152]; Progeria Research Foundation [PRF 2011-035]; American Heart Association [09POST2320042]; Academy of Finland; Sigrid Juselius Foundation; National Heart Lung and Blood Institute [R01HL082792] Funding Source: NIH RePORTER; CDMRP [545346, BC102152] Funding Source: Federal RePORTER; American Heart Association (AHA) [09POST2320042] Funding Source: American Heart Association (AHA)
NR 33
TC 368
Z9 432
U1 3
U2 103
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 23
PY 2013
VL 497
IS 7450
BP 507
EP +
DI 10.1038/nature12105
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 148OG
UT WOS:000319254000052
PM 23644458
DA 2026-03-09
ER

PT J
AU Murch, KW
   Weber, SJ
   Beck, KM
   Ginossar, E
   Siddiqi, I
AF Murch, K. W.
   Weber, S. J.
   Beck, K. M.
   Ginossar, E.
   Siddiqi, I.
TI Reduction of the radiative decay of atomic coherence in squeezed vacuum
SO NATURE
LA English
DT Article
ID quantum-noise; light; cavity; excitation; amplification; resonance; states; limit
AB Quantum fluctuations of the electromagnetic vacuum are responsible for physical effects such as the Casimir force and the radiative decay of atoms, and set fundamental limits on the sensitivity of measurements. Entanglement between photons can produce correlations that result in a reduction of these fluctuations below the ordinary vacuum level, allowing measurements that surpass the standard quantum limit in sensitivity(1-5). The effects of such 'squeezed states' of light on matter were first considered in a prediction(6) of the radiative decay rates of atoms in squeezed vacuum. Despite efforts to demonstrate such effects in experiments with natural atoms(7-9), a direct quantitative observation of this prediction has remained elusive. Here we report a twofold reduction of the transverse radiative decay rate of a superconducting artificial atom coupled to continuum squeezed vacuum. The artificial atom is effectively a two-level system formed by the strong interaction between a superconducting circuit and a microwave-frequency cavity. A Josephson parametric amplifier is used to generate quadrature-squeezed electromagnetic vacuum. The observed twofold reduction in the decay rate of the atom allows the transverse coherence time, T-2, to exceed the ordinary vacuum decay limit, 2T(1). We demonstrate that the measured radiative decay dynamics can be used to reconstruct the Wigner distribution of the itinerant squeezed state. Our results confirm a canonical prediction(6) of quantum optics and should enable new studies of the quantum light-matter interaction.
C1 [Murch, K. W.; Weber, S. J.; Siddiqi, I.] Univ Calif Berkeley, Dept Phys, Quantum Nanoelect Lab, Berkeley, CA 94720 USA.
   [Beck, K. M.] MIT, Dept Phys, MIT Harvard Ctr Ultracold Atoms, Cambridge, MA 02139 USA.
   [Beck, K. M.] MIT, Elect Res Lab, Cambridge, MA 02139 USA.
   [Ginossar, E.] Univ Surrey, Adv Technol Inst, Guildford GU2 7XH, Surrey, England.
   [Ginossar, E.] Univ Surrey, Dept Phys, Guildford GU2 7XH, Surrey, England.
C3 University of California System; University of California Berkeley; Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); University of Surrey; University of Surrey
RP Murch, KW (corresponding author), Univ Calif Berkeley, Dept Phys, Quantum Nanoelect Lab, Berkeley, CA 94720 USA.
EM katerm@berkeley.edu
FU Office of Naval Research [N00014-13-1-0150]; Office of the Director of National Intelligence (ODNI), Intelligence Advanced Research Projects Activity (IARPA), through the Army Research Office [W911NF-11-1-0029]; EPSRC [EP/I026231/1]; US NSF GRFP [0645960]; IGERT [0801525]; Division Of Graduate Education; Direct For Education and Human Resources [0801525] Funding Source: National Science Foundation; Engineering and Physical Sciences Research Council [EP/I026231/1] Funding Source: researchfish; EPSRC [EP/I026231/1] Funding Source: UKRI
NR 32
TC 130
Z9 146
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 4
PY 2013
VL 499
IS 7456
BP 62
EP 65
DI 10.1038/nature12264
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 176ED
UT WOS:000321285600033
PM 23823794
DA 2026-03-09
ER

PT J
AU Zhou, CF
   Wu, SY
   Martin, T
   Luo, ZX
AF Zhou, Chang-Fu
   Wu, Shaoyuan
   Martin, Thomas
   Luo, Zhe-Xi
TI A Jurassic mammaliaform and the earliest mammalian evolutionary adaptations
SO NATURE
LA English
DT Article
ID allotherian mammals; northeastern china; middle-ear; teeth; diversification; eutriconodont
AB The earliest evolution of mammals and origins of mammalian features can be traced to the mammaliaforms of the Triassic and Jurassic periods that are extinct relatives to living mammals. Here we describe a new fossil from the Middle Jurassic that has a mandibular middle ear, a gradational transition of thoracolumbar vertebrae and primitive ankle features, but highly derived molars with a high crown and multiple roots that are partially fused. The upper molars have longitudinal cusp rows that occlude alternately with those of the lower molars. This specialization for masticating plants indicates that herbivory evolved among mammaliaforms, before the rise of crown mammals. The new species shares the distinctive dental features of the eleutherodontid clade, previously represented only by isolated teeth despite its extensive geographic distribution during the Jurassic. This eleutherodontid was terrestrial and had ambulatory gaits, analogous to extant terrestrial mammals such as armadillos or rock hyrax. Its fur corroborates that mammalian integument had originated well before the common ancestor of living mammals.
C1 [Zhou, Chang-Fu; Wu, Shaoyuan] Shenyang Normal Univ, Paleontol Museum Liaoning, Shenyang 110034, Liaoning, Peoples R China.
   [Martin, Thomas; Luo, Zhe-Xi] Univ Bonn, Steinmann Inst Geol Mineral & Palaontol, D-53115 Bonn, Germany.
   [Luo, Zhe-Xi] Univ Chicago, Dept Organismal Biol & Anat, Chicago, IL 60637 USA.
C3 Shenyang Normal University; University of Bonn; University of Chicago
RP Luo, ZX (corresponding author), Univ Bonn, Steinmann Inst Geol Mineral & Palaontol, Nussallee 8, D-53115 Bonn, Germany.
EM zxluo@uchicago.edu
FU Key Lab for Paleobiological Evolution of Northeastern Asia, Ministry of Land Resources of China; Shenyang Normal University and Paleontological Museum of Liaoning; Deutsche Forschungsmeinschaft (DFG); Alexander von Humboldt-Foundation; National Science Foundation; University of Chicago
NR 40
TC 141
Z9 169
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 AUG 8
PY 2013
VL 500
IS 7461
BP 163
EP 167
DI 10.1038/nature12429
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 197CH
UT WOS:000322825500026
PM 23925238
DA 2026-03-09
ER

PT J
AU Anger, AM
   Armache, JP
   Berninghausen, O
   Habeck, M
   Subklewe, M
   Wilson, DN
   Beckmann, R
AF Anger, Andreas M.
   Armache, Jean-Paul
   Berninghausen, Otto
   Habeck, Michael
   Subklewe, Marion
   Wilson, Daniel N.
   Beckmann, Roland
TI Structures of the human and Drosophila 80S ribosome
SO NATURE
LA English
DT Article
ID secondary structure; electron-microscopy; atomic structures; crystal-structure; messenger-rna; sequence; subunit; initiation; visualization; translation
AB Protein synthesis in all cells is carried out by macromolecular machines called ribosomes. Although the structures of prokaryotic, yeast and protist ribosomes have been determined, the more complex molecular architecture of metazoan 80S ribosomes has so far remained elusive. Here we present structures of Drosophila melanogaster and Homo sapiens 80S ribosomes in complex with the translation factor eEF2, E-site transfer RNA and Stm1-like proteins, based on high-resolution cryo-electron-microscopy density maps. These structures not only illustrate the co-evolution of metazoan-specific ribosomal RNA with ribosomal proteins but also reveal the presence of two additional structural layers in metazoan ribosomes, a well-ordered inner layer covered by a flexible RNA outer layer. The human and Drosophila ribosome structures will provide the basis for more detailed structural, biochemical and genetic experiments.
C1 [Anger, Andreas M.; Armache, Jean-Paul; Berninghausen, Otto; Wilson, Daniel N.; Beckmann, Roland] Univ Munich, Dept Biochem, Gene Ctr, D-81377 Munich, Germany.
   [Anger, Andreas M.; Armache, Jean-Paul; Berninghausen, Otto; Wilson, Daniel N.; Beckmann, Roland] Univ Munich, Ctr Integrated Prot Sci Munich CiPSM, D-81377 Munich, Germany.
   [Habeck, Michael] Max Planck Inst Biol Cybernet, Dept Empir Inference, D-72076 Tubingen, Germany.
   [Habeck, Michael] Max Planck Inst Dev Biol, Dept Prot Evolut, D-72076 Tubingen, Germany.
   [Subklewe, Marion] Klinikum Univ Munchen, Dept Internal Med 3, D-81377 Munich, Germany.
   [Subklewe, Marion] Helmholtz Inst Munich, Clin Cooperat Grp Immunotherapy, D-81377 Munich, Germany.
C3 University of Munich; University of Munich; Max Planck Society; Max Planck Society; University of Munich
RP Beckmann, R (corresponding author), Univ Munich, Dept Biochem, Gene Ctr, Feodor Lynen Str 25, D-81377 Munich, Germany.
EM beckmann@lmb.uni-muenchen.de
FU Deutsche Forschungsgemeinschaft [SFB594, SFB646, GRK 1721, FOR1805]; European Molecular Biology Organization (EMBO); European Research Council (ERC)
NR 72
TC 469
Z9 709
U1 0
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 2
PY 2013
VL 497
IS 7447
BP 80
EP +
DI 10.1038/nature12104
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 134OK
UT WOS:000318221500037
PM 23636399
DA 2026-03-09
ER

PT J
AU Jagoutz, O
   Behn, MD
AF Jagoutz, Oliver
   Behn, Mark D.
TI Foundering of lower island-arc crust as an explanation for the origin of the continental Moho
SO NATURE
LA English
DT Article
ID seismic velocity structure; northern honshu; japan; mantle; wave; crystallization; constraints; evolution; pressure; terrane
AB A long-standing theory for the genesis of continental crust is that it is formed in subduction zones(1). However, the observed seismic properties of lower crust and upper mantle in oceanic island arcs(2,3) differ significantly from those in the continental crust(4). Accordingly, significant modifications of lower arc crust must occur, if continental crust is indeed formed from island arcs. Here we investigate how the seismic characteristics of arc crust are transformed into those of the continental crust by calculating the density and seismic structure of two exposed sections of island arc (Kohistan and Talkeetna). The Kohistan crustal section is negatively buoyant with respect to the underlying depleted upper mantle at depths exceeding 40 kilometres and is characterized by a steady increase in seismic velocity similar to that observed in active arcs. In contrast, the lower Talkeetna crust is density sorted, preserving only relicts (about ten to a hundred metres thick) of rock with density exceeding that of the underlying mantle. Specifically, the foundering of the lower Talkeetna crust resulted in the replacement of dense mafic and ultramafic cumulates by residual upper mantle, producing a sharp seismic discontinuity at depths of around 38 to 42 kilometres, characteristic of the continental Mohorovicic discontinuity (the Moho). Dynamic calculations indicate that foundering is an episodic process that occurs in most arcs with a periodicity of half a million to five million years. Moreover, because foundering will continue after arc magmatism ceases, this process ultimately results in the formation of the continental Moho.
C1 [Jagoutz, Oliver] MIT, Dept Earth Atmospher & Planetary Sci, Cambridge, MA 02139 USA.
   [Behn, Mark D.] Woods Hole Oceanog Inst, Dept Geol & Geophys, Woods Hole, MA 02543 USA.
C3 Massachusetts Institute of Technology (MIT); Woods Hole Oceanographic Institution
RP Jagoutz, O (corresponding author), MIT, Dept Earth Atmospher & Planetary Sci, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
EM jagoutz@mit.edu
FU NSF [EAR 0910644, EAR 1316333]
NR 48
TC 133
Z9 148
U1 1
U2 89
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 5
PY 2013
VL 504
IS 7478
BP 131
EP +
DI 10.1038/nature12758
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 264BK
UT WOS:000327851700045
PM 24305163
DA 2026-03-09
ER

PT J
AU Howe, MW
   Tierney, PL
   Sandberg, SG
   Phillips, PEM
   Graybiel, AM
AF Howe, Mark W.
   Tierney, Patrick L.
   Sandberg, Stefan G.
   Phillips, Paul E. M.
   Graybiel, Ann M.
TI Prolonged dopamine signalling in striatum signals proximity and value of distant rewards
SO NATURE
LA English
DT Article
ID nucleus-accumbens dopamine; neurons; prediction; navigation; depletion
AB Predictions about future rewarding events have a powerful influence on behaviour. The phasic spike activity of dopamine-containing neurons, and corresponding dopamine transients in the striatum, are thought to underlie these predictions, encoding positive and negative reward prediction errors(1-5). However, many behaviours are directed towards distant goals, for which transient signals may fail to provide sustained drive. Here we report an extended mode of reward-predictive dopamine signalling in the striatum that emerged as rats moved towards distant goals. These dopamine signals, which were detected with fast-scan cyclic voltammetry (FSCV), gradually increased or-in rare instances-decreased as the animals navigated mazes to reach remote rewards, rather than having phasic or steady tonic profiles. These dopamine increases (ramps) scaled flexibly with both the distance and size of the rewards. During learning, these dopamine signals showed spatial preferences for goals in different locations and readily changed in magnitude to reflect changing values of the distant rewards. Such prolonged dopamine signalling could provide sustained motivational drive, a control mechanism that may be important for normal behaviour and that can be impaired in a range of neurologic and neuropsychiatric disorders.
C1 [Howe, Mark W.; Tierney, Patrick L.; Graybiel, Ann M.] MIT, McGovern Inst Brain Res, Cambridge, MA 02139 USA.
   [Howe, Mark W.; Tierney, Patrick L.; Graybiel, Ann M.] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA.
   [Sandberg, Stefan G.; Phillips, Paul E. M.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA.
   [Sandberg, Stefan G.; Phillips, Paul E. M.] Univ Washington, Dept Pharmacol, Seattle, WA 98195 USA.
C3 Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); University of Washington; University of Washington Seattle; University of Washington; University of Washington Seattle
RP Graybiel, AM (corresponding author), MIT, McGovern Inst Brain Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
EM graybiel@mit.edu
FU US National Institutes of Health (NIH) [R01 MH060379]; National Parkinson Foundation; CHDI Foundation [A-5552]; Stanley H. and Sheila G. Sydney Fund; Mark Gorenberg fellowship; NIH [R01 DA027858, R01 MH079292]; National Institute of Mental Health [R01MH060379] Funding Source: NIH RePORTER
NR 28
TC 393
Z9 504
U1 3
U2 112
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 29
PY 2013
VL 500
IS 7464
BP 575
EP +
DI 10.1038/nature12475
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 207TD
UT WOS:000323625900034
PM 23913271
DA 2026-03-09
ER

PT J
AU Thibault, P
   Menzel, A
AF Thibault, Pierre
   Menzel, Andreas
TI Reconstructing state mixtures from diffraction measurements
SO NATURE
LA English
DT Article
ID phase retrieval; ray; microscopy; coherence
AB Progress in imaging and metrology depends on exquisite control over and comprehensive characterization of wave fields. As reflected in its name, coherent diffractive imaging relies on high coherence when reconstructing highly resolved images from diffraction intensities alone without the need for image-forming lenses(1-3). Fully coherent light can be described adequately by a single pure state. Yet partial coherence and imperfect detection often need to be accounted for, requiring statistical optics or the superposition of states(4,5). Furthermore, the dynamics of samples are increasingly the very objectives of experiments(6). Here we provide a general analytic approach to the characterization of diffractive imaging systems that can be described as low-rank mixed states. We use experimental data and simulations to show how the reconstruction technique compensates for and characterizes various sources of decoherence quantitatively. Based on ptychography(7,8), the procedure is closely related to quantum state tomography and is equally applicable to high-resolution microscopy, wave sensing and fluctuation measurements. As a result, some of the most stringent experimental conditions in ptychography can be relaxed, and susceptibility to imaging artefacts is reduced. Furthermore, the method yields high-resolution images of mixed states within the sample, which may include quantum mixtures or fast stationary stochastic processes such as vibrations, switching or steady flows.
C1 [Thibault, Pierre] Tech Univ Munich, Dept Phys, D-85748 Garching, Germany.
   [Menzel, Andreas] Paul Scherrer Inst, CH-5232 Villigen, Switzerland.
C3 Technical University of Munich; Swiss Federal Institutes of Technology Domain; Paul Scherrer Institute
RP Thibault, P (corresponding author), Tech Univ Munich, Dept Phys, D-85748 Garching, Germany.
EM pierre.thibault@tum.de
FU European Research Council [279753]; European Research Council (ERC) [279753] Funding Source: European Research Council (ERC)
NR 32
TC 539
Z9 629
U1 6
U2 302
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 7
PY 2013
VL 494
IS 7435
BP 68
EP 71
DI 10.1038/nature11806
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 087DJ
UT WOS:000314741200035
PM 23389541
DA 2026-03-09
ER

PT J
AU Jiang, LB
   Mu, JB
   Zhang, QF
   Ni, T
   Srinivasan, P
   Rayavara, K
   Yang, WJ
   Turner, L
   Lavstsen, T
   Theander, TG
   Peng, WQ
   Wei, GY
   Jing, QQ
   Wakabayashi, Y
   Bansal, A
   Luo, Y
   Ribeiro, JMC
   Scherf, A
   Aravind, L
   Zhu, J
   Zhao, KJ
   Miller, LH
AF Jiang, Lubin
   Mu, Jianbing
   Zhang, Qingfeng
   Ni, Ting
   Srinivasan, Prakash
   Rayavara, Kempaiah
   Yang, Wenjing
   Turner, Louise
   Lavstsen, Thomas
   Theander, Thor G.
   Peng, Weiqun
   Wei, Guiying
   Jing, Qingqing
   Wakabayashi, Yoshiyuki
   Bansal, Abhisheka
   Luo, Yan
   Ribeiro, Jose M. C.
   Scherf, Artur
   Aravind, L.
   Zhu, Jun
   Zhao, Keji
   Miller, Louis H.
TI PfSETvs methylation of histone H3K36 represses virulence genes in Plasmodium falciparum
SO NATURE
LA English
DT Article
ID antigenic variation; lysine 36; transcription; erythrocytes; parasites; targets; protein
AB The variant antigen Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1), which is expressed on the surface of P. falciparum-infected red blood cells, is a critical virulence factor for malaria(1). Each parasite has 60 antigenically distinct var genes that each code for a different PfEMP1 protein. During infection the clonal parasite population expresses only one gene at a time before switching to the expression of a new variant antigen as an immune-evasion mechanism to avoid the host antibody response(2,3). The mechanism by which 59 of the 60 var genes are silenced remains largely unknown(4-7). Here we show that knocking out the P. falciparum variant-silencing SET gene (here termed PfSETvs), which encodes an orthologue of Drosophila melanogaster ASH1 and controls histone H3 lysine 36 trimethylation (H3K36me3) on var genes, results in the transcription of virtually all var genes in the single parasite nuclei and their expression as proteins on the surface of individual infected red blood cells. PfSETvs-dependent H3K36me3 is present along the entire gene body, including the transcription start site, to silence var genes. With low occupancy of PfSETvs at both the transcription start site of var genes and the intronic promoter, expression of var genes coincides with transcription of their corresponding antisense long noncoding RNA. These results uncover a previously unknown role of PfSETvs-dependent H3K36me3 in silencing var genes in P. falciparum that might provide a general mechanism by which orthologues of PfSETvs repress gene expression in other eukaryotes. PfSETvs knockout parasites expressing all PfEMP1 proteins may also be applied to the development of a malaria vaccine.
C1 [Jiang, Lubin; Jing, Qingqing] Chinese Acad Sci, Inst Pasteur Shanghai, Unit Human Parasite Mol & Cell Biol, Key Lab Mol Virol & Immunol, Shanghai 200031, Peoples R China.
   [Jiang, Lubin; Jing, Qingqing] Chinese Acad Sci, Shanghai Inst Biol Sci, Shanghai 200031, Peoples R China.
   [Mu, Jianbing; Srinivasan, Prakash; Rayavara, Kempaiah; Bansal, Abhisheka; Ribeiro, Jose M. C.; Miller, Louis H.] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA.
   [Zhang, Qingfeng; Wei, Guiying] Tongji Univ, Sch Med, Inst Infect Dis & Vaccine Dev, Shanghai 200092, Peoples R China.
   [Zhang, Qingfeng; Scherf, Artur] Inst Pasteur, Dept Parasitol & Mycol, Unite Biol Interact Hote Parasite, F-75015 Paris, France.
   [Zhang, Qingfeng; Scherf, Artur] CNRS, URA 2581, F-75015 Paris, France.
   [Ni, Ting] Fudan Univ, Sch Life Sci, State Key Lab Genet Engn, Shanghai 200433, Peoples R China.
   [Ni, Ting] Fudan Univ, Sch Life Sci, MOE Key Lab Contemporary Anthropol, Shanghai 200433, Peoples R China.
   [Yang, Wenjing; Wakabayashi, Yoshiyuki; Luo, Yan; Zhu, Jun] NHLBI, Genet & Dev Biol Ctr, NIH, Bethesda, MD 20892 USA.
   [Turner, Louise; Lavstsen, Thomas; Theander, Thor G.] Univ Copenhagen, Fac Hlth Sci, Dept Int Hlth Immunol & Microbiol, Ctr Med Parasitol, DK-1014 Copenhagen, Denmark.
   [Turner, Louise; Lavstsen, Thomas; Theander, Thor G.] Rigshosp, Copenhagen Univ Hosp, Dept Infect Dis, DK-1014 Copenhagen, Denmark.
   [Peng, Weiqun] George Washington Univ, Dept Phys, Washington, DC 20052 USA.
   [Aravind, L.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
   [Zhao, Keji] NHLBI, Syst Biol Ctr, NIH, Bethesda, MD 20892 USA.
C3 Pasteur Network; Chinese Academy of Sciences; Shanghai Institute of Immunity and Infection, CAS; Chinese Academy of Sciences; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID); Tongji University; Pasteur Network; Universite Paris Cite; Institut Pasteur Paris; Centre National de la Recherche Scientifique (CNRS); Fudan University; Fudan University; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI); University of Copenhagen; University of Copenhagen; Copenhagen University Hospital; Rigshospitalet; George Washington University; National Institutes of Health (NIH) - USA; NIH National Library of Medicine (NLM); National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI)
RP Jiang, LB (corresponding author), Chinese Acad Sci, Inst Pasteur Shanghai, Unit Human Parasite Mol & Cell Biol, Key Lab Mol Virol & Immunol, 320 Yueyang Rd, Shanghai 200031, Peoples R China.
EM lbjiang@ips.ac.cn; lmiller@niaid.nih.gov
FU Intramural Research Program of the National Institute of Allergy and Infectious Disease; National Heart, Lung, and Blood Institute, National Institutes of Health; National Natural Science Foundation of China [81271863]; Key Research Program of the Chinese Academy of Sciences [KSZD-EW-Z-003-1-2]; ERC [250320]; National Heart Lung and Blood Institute [ZIAHL005801] Funding Source: NIH RePORTER; National Institute of Allergy and Infectious Diseases [ZIAAI000241, ZIAAI000810] Funding Source: NIH RePORTER; Lundbeck Foundation [R140-2013-13448, R108-2012-10328] Funding Source: researchfish; European Research Council (ERC) [250320] Funding Source: European Research Council (ERC)
NR 36
TC 200
Z9 244
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 JUL 11
PY 2013
VL 499
IS 7457
BP 223
EP +
DI 10.1038/nature12361
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 179YA
UT WOS:000321557600065
PM 23823717
DA 2026-03-09
ER

PT J
AU Heinz, S
   Romanoski, CE
   Benner, C
   Allison, KA
   Kaikkonen, MU
   Orozco, LD
   Glass, CK
AF Heinz, S.
   Romanoski, C. E.
   Benner, C.
   Allison, K. A.
   Kaikkonen, M. U.
   Orozco, L. D.
   Glass, C. K.
TI Effect of natural genetic variation on enhancer selection and function
SO NATURE
LA English
DT Article
ID regulatory elements; open chromatin; transcription; binding; macrophage; responses; alignment; snps; map
AB The mechanisms by which genetic variation affects transcription regulation and phenotypes at the nucleotide level are incompletely understood. Here we use natural genetic variation as an in vivo mutagenesis screen to assess the genome-wide effects of sequence variation on lineage-determining and signal-specific transcription factor binding, epigenomics and transcriptional outcomes in primary macrophages from different mouse strains. We find substantial genetic evidence to support the concept that lineage-determining transcription factors define epigenetic and transcriptomic states by selecting enhancer-like regions in the genome in a collaborative fashion and facilitating binding of signal-dependent factors. This hierarchical model of transcription factor function suggests that limited sets of genomic data for lineage-determining transcription factors and informative histone modifications can be used for the prioritization of disease-associated regulatory variants.
C1 [Heinz, S.; Romanoski, C. E.; Benner, C.; Allison, K. A.; Kaikkonen, M. U.; Glass, C. K.] Univ Calif San Diego, Dept Cellular & Mol Med, La Jolla, CA 92093 USA.
   [Benner, C.] Salk Inst Biol Studies, Integrat Genom & Bioinformat Core, La Jolla, CA 92037 USA.
   [Benner, C.; Glass, C. K.] Univ Calif San Diego, San Diego Ctr Syst Biol, La Jolla, CA 92093 USA.
   [Kaikkonen, M. U.] Univ Eastern Finland, AI Virtanen Inst Mol Sci, Dept Biotechnol & Mol Med, Kuopio 70211, Finland.
   [Orozco, L. D.] Univ Calif Los Angeles, Dept Mol Cell & Dev Biol, Los Angeles, CA 90095 USA.
   [Glass, C. K.] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA.
C3 University of California System; University of California San Diego; Salk Institute; University of California System; University of California San Diego; University of Eastern Finland; University of California System; University of California Los Angeles; University of California System; University of California San Diego
RP Glass, CK (corresponding author), Univ Calif San Diego, Dept Cellular & Mol Med, 9500 Gilman Dr,Mail Code 0651, La Jolla, CA 92093 USA.
EM ckg@ucsd.edu
FU National Institutes of Health (NIH) [DK091183, CA17390, DK063491]; Foundation Leducq; Academy of Finland; Finnish Foundation for Cardiovascular Research; Finnish Cultural Foundation; American Heart Association Western States Affiliates [12POST11760017]; NIH [5T32DK007494]; American Heart Association (AHA) [12POST11760017] Funding Source: American Heart Association (AHA); National Cancer Institute [P30CA023100] Funding Source: NIH RePORTER; National Institute of Arthritis and Musculoskeletal and Skin Diseases [T32AR059033] Funding Source: NIH RePORTER; National Institute of Diabetes and Digestive and Kidney Diseases [P30DK063491, T32DK007494, R01DK091183] Funding Source: NIH RePORTER
NR 39
TC 254
Z9 301
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 28
PY 2013
VL 503
IS 7477
BP 487
EP +
DI 10.1038/nature12615
PG 20
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 258MU
UT WOS:000327464200035
PM 24121437
DA 2026-03-09
ER

PT J
AU Herman, F
   Seward, D
   Valla, PG
   Carter, A
   Kohn, B
   Willett, SD
   Ehlers, TA
AF Herman, Frederic
   Seward, Diane
   Valla, Pierre G.
   Carter, Andrew
   Kohn, Barry
   Willett, Sean D.
   Ehlers, Todd A.
TI Worldwide acceleration of mountain erosion under a cooling climate
SO NATURE
LA English
DT Article
ID glacial erosion; neighborhood algorithm; geophysical inversion; closure temperature; temporal variations; apatite; rates; thermochronology; sediment; alps
AB Climate influences the erosion processes acting at the Earth's surface. However, the effect of cooling during the Late Cenozoic era, including the onset of Pliocene-Pleistocene Northern Hemisphere glaciation (about two to three million years ago), on global erosion rates remains unclear(1-4). The uncertainty arises mainly from a lack of consensus on the use of the sedimentary record as a proxy for erosion(3,4) and the difficulty of isolating the respective contributions of tectonics and climate to erosion(5-7). Here we compile 18,000 bedrock thermochronometric ages from around the world and use a formal inversion procedure(8) to estimate temporal and spatial variations in erosion rates. This allows for the quantification of erosion for the source areas that ultimately produce the sediment record on a timescale of millions of years. We find that mountain erosion rates have increased since about six million years ago and most rapidly since two million years ago. The increase of erosion rates is observed at all latitudes, but is most pronounced in glaciated mountain ranges, indicating that glacial processes played an important part. Because mountains represent a considerable fraction of the global production of sediments(9), our results imply an increase in sediment flux at a global scale that coincides closely with enhanced cooling during the Pliocene and Pleistocene epochs(10,11).
C1 [Herman, Frederic; Valla, Pierre G.] Univ Lausanne, Inst Earth Sci, CH-1015 Lausanne, Switzerland.
   [Herman, Frederic; Valla, Pierre G.; Willett, Sean D.] Swiss Fed Inst Technol, Dept Earth Sci, CH-8092 Zurich, Switzerland.
   [Seward, Diane] Victoria Univ, Sch Geog Environm & Earth Sci, Wellington, New Zealand.
   [Carter, Andrew] Birkbeck Univ London, Dept Earth & Planetary Sci, London WC1E 7HX, England.
   [Kohn, Barry] Univ Melbourne, Sch Earth Sci, Melbourne, Vic 3010, Australia.
   [Ehlers, Todd A.] Univ Tubingen, Dept Geosci, D-72074 Tubingen, Germany.
C3 University of Lausanne; Swiss Federal Institutes of Technology Domain; ETH Zurich; Victoria University Wellington; University of London; Birkbeck University London; University of Melbourne; Eberhard Karls University of Tubingen
RP Herman, F (corresponding author), Univ Lausanne, Inst Earth Sci, CH-1015 Lausanne, Switzerland.
EM frederic.herman@unil.ch
FU SNF [PP00P2_138956]; Swiss National Science Foundation (SNF) [PP00P2_138956] Funding Source: Swiss National Science Foundation (SNF)
NR 57
TC 434
Z9 494
U1 8
U2 281
PU NATURE PUBLISHING 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 19
PY 2013
VL 504
IS 7480
BP 423
EP +
DI 10.1038/nature12877
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 273ZR
UT WOS:000328575300049
PM 24352288
DA 2026-03-09
ER

PT J
AU Cooper, A
   García, M
   Petrovas, C
   Yamamoto, T
   Koup, RA
   Nabel, GJ
AF Cooper, Arik
   Garcia, Mayra
   Petrovas, Constantinos
   Yamamoto, Takuya
   Koup, Richard A.
   Nabel, Gary J.
TI HIV-1 causes CD4 cell death through DNA-dependent protein kinase during viral integration
SO NATURE
LA English
DT Article
ID immunodeficiency-virus type-1; infectious molecular clone; t-cells; in-vivo; retroviral infection; quantitative assay; lymphocytes; inhibitor; depletion; dynamics
AB Human immunodeficiency virus-1 (HIV-1) has infected more than 60 million people and caused nearly 30 million deaths worldwide(1), ultimately the consequence of cytolytic infection of CD4(+) T cells. In humans and in macaque models, most of these cells contain viral DNA and are rapidly eliminated at the peak of viraemia(2-4), yet the mechanism by which HIV-1 induces helper T-cell death has not been defined. Here we show that virus-induced cell killing is triggered by viral integration. Infection by wild-type HIV-1, but not an integrase-deficient mutant, induced the death of activated primary CD4 lymphocytes. Similarly, raltegravir, a pharmacologic integrase inhibitor, abolished HIV-1-induced cell killing both in cell culture and in CD4(+) T cells from acutely infected subjects. The mechanism of killing during viral integration involved the activation of DNA-dependent protein kinase (DNA-PK), a central integrator of the DNA damage response, which caused phosphorylation of p53 and histone H2AX. Pharmacological inhibition of DNA-PK abolished cell death during HIV-1 infection in vitro, suggesting that processes which reduce DNA-PK activation in CD4 cells could facilitate the formation of latently infected cells that give rise to reservoirs in vivo. We propose that activation of DNA-PK during viral integration has a central role in CD4(+) T-cell depletion, raising the possibility that integrase inhibitors and interventions directed towards DNA-PK may improve T-cell survival and immune function in infected individuals.
C1 [Cooper, Arik; Garcia, Mayra; Nabel, Gary J.] NIAID, Virol Lab, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
   [Petrovas, Constantinos; Yamamoto, Takuya; Koup, Richard A.] NIAID, Immunol Lab, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
C3 National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID); National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID)
RP Nabel, GJ (corresponding author), NIAID, Virol Lab, Vaccine Res Ctr, NIH, Bldg 40,Room 4502,MSC 3005,40 Convent Dr, Bethesda, MD 20892 USA.
EM Gary.Nabel@sanofi.com
FU Intramural Research Program of the Vaccine Research Center, NIAID, National Institutes of Health; National Institute of Allergy and Infectious Diseases [ZIAAI005014] Funding Source: NIH RePORTER
NR 39
TC 178
Z9 216
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 JUN 20
PY 2013
VL 498
IS 7454
BP 376
EP +
DI 10.1038/nature12274
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 166XI
UT WOS:000320592900043
PM 23739328
DA 2026-03-09
ER

PT J
AU Jarenwattananon, NN
   Glöggler, S
   Otto, T
   Melkonian, A
   Morris, W
   Burt, SR
   Yaghi, OM
   Bouchard, LS
AF Jarenwattananon, Nanette N.
   Gloeggler, Stefan
   Otto, Trenton
   Melkonian, Arek
   Morris, William
   Burt, Scott R.
   Yaghi, Omar M.
   Bouchard, Louis-S.
TI Thermal maps of gases in heterogeneous reactions
SO NATURE
LA English
DT Article
ID para-hydrogen; parahydrogen; polarization; catalyst
AB More than 85 per cent of all chemical industry products are made using catalysts(1,2), the overwhelming majority of which are heterogeneous catalysts(2) that function at the gas-solid interface(3). Consequently, much effort is invested in optimizing the design of catalytic reactors, usually by modelling(4) the coupling between heat transfer, fluid dynamics and surface reactionkinetics. The complexity involved requires a calibration of model approximations against experimental observations(5,6), with temperature maps being particularly valuable because temperature control is often essential for optimal operation and because temperature gradients contain information about the energetics of a reaction. However, it is challenging to probe the behaviour of a gas inside a reactor without disturbing its flow, particularly when trying also to map the physical parameters and gradients that dictate heat and mass flow and catalytic efficiency(1-9). Although optical techniques(10-12) and sensors(13,14) have been used for that purpose, the former perform poorly in opaque media and the latter perturb the flow. NMR thermometry can measure temperature non-invasively, but traditional approaches applied to gases produce signals that depend only weakly on temperature(15,16) are rapidly attenuated by diffusion(16,17) or require contrast agents(18) that may interfere with reactions. Here we present a new NMR thermometry technique that circumvents these problems by exploiting the inverse relationship between NMR line-widths and temperature caused by motional averaging in a weak magnetic field gradient. We demonstrate the concept by non-invasively mapping gas temperatures during the hydrogenation of propylene in reactors packed with metal nanoparticles and metal-organic framework catalysts, with measurement errors of less than four per cent of the absolute temperature. These results establish our technique as a non-invasive tool for locating hot and cold spots in catalyst-packed gas-solid reactors, with unprecedented capabilities for testing the approximations used in reactor modelling.
C1 [Jarenwattananon, Nanette N.; Gloeggler, Stefan; Otto, Trenton; Melkonian, Arek; Morris, William; Yaghi, Omar M.; Bouchard, Louis-S.] Univ Calif Los Angeles, Dept Chem & Biochem, Los Angeles, CA 90095 USA.
   [Burt, Scott R.] Brigham Young Univ, Dept Chem & Biochem, Provo, UT 84602 USA.
   [Yaghi, Omar M.] Univ Calif Berkeley, Dept Chem, Berkeley, CA 94720 USA.
   [Yaghi, Omar M.] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Div Mat Sci, Berkeley, CA 94720 USA.
   [Yaghi, Omar M.] NanoCentury KAIST Inst, Taejon 305701, South Korea.
   [Yaghi, Omar M.] World Class Univ, Grad Sch Energy Environm Water & Sustainabil, Taejon 305701, South Korea.
   [Bouchard, Louis-S.] Univ Calif Los Angeles, Calif NanoSyst Inst, Los Angeles, CA 90095 USA.
   [Bouchard, Louis-S.] Univ Calif Los Angeles, Dept Bioengn, Los Angeles, CA 90095 USA.
C3 University of California System; University of California Los Angeles; Brigham Young University; University of California System; University of California Berkeley; University of California System; University of California Berkeley; United States Department of Energy (DOE); Lawrence Berkeley National Laboratory; Korea Advanced Institute of Science & Technology (KAIST); University of California System; University of California Los Angeles; University of California System; University of California Los Angeles
RP Bouchard, LS (corresponding author), Univ Calif Los Angeles, Dept Chem & Biochem, 607 Charles E Young Dr East, Los Angeles, CA 90095 USA.
EM bouchard@chem.ucla.edu
FU Dreyfus New Faculty Award; Beckman Young Investigator Award; US NSF [CHE-1153159]; BASF, Germany (synthesis); US DOE; Direct For Mathematical & Physical Scien [1153159] Funding Source: National Science Foundation; Division Of Chemistry [1153159] Funding Source: National Science Foundation
NR 30
TC 54
Z9 62
U1 1
U2 287
PU NATURE PUBLISHING 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 24
PY 2013
VL 502
IS 7472
BP 537
EP +
DI 10.1038/nature12568
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 238YN
UT WOS:000325988400051
PM 24153305
DA 2026-03-09
ER

PT J
AU Atarashi, K
   Tanoue, T
   Oshima, K
   Suda, W
   Nagano, Y
   Nishikawa, H
   Fukuda, S
   Saito, T
   Narushima, S
   Hase, K
   Kim, S
   Fritz, JV
   Wilmes, P
   Ueha, S
   Matsushima, K
   Ohno, H
   Olle, B
   Sakaguchi, S
   Taniguchi, T
   Morita, H
   Hattori, M
   Honda, K
AF Atarashi, Koji
   Tanoue, Takeshi
   Oshima, Kenshiro
   Suda, Wataru
   Nagano, Yuji
   Nishikawa, Hiroyoshi
   Fukuda, Shinji
   Saito, Takuro
   Narushima, Seiko
   Hase, Koji
   Kim, Sangwan
   Fritz, Joelle V.
   Wilmes, Paul
   Ueha, Satoshi
   Matsushima, Kouji
   Ohno, Hiroshi
   Olle, Bernat
   Sakaguchi, Shimon
   Taniguchi, Tadatsugu
   Morita, Hidetoshi
   Hattori, Masahira
   Honda, Kenya
TI Treg induction by a rationally selected mixture of Clostridia strains from the human microbiota
SO NATURE
LA English
DT Article
ID gut microbiota; cells; colonization; disease
AB Manipulation of the gut microbiota holds great promise for the treatment of inflammatory and allergic diseases(1,2). Although numerous probiotic microorganisms have been identified(3), there remains a compelling need to discover organisms that elicit more robust therapeutic responses, are compatible with the host, and can affect a specific arm of the host immune system in a well-controlled, physiological manner. Here we use a rational approach to isolate CD4(+)FOXP3(+) regulatory T (T-reg)-cell-inducing bacterial strains from the human indigenous microbiota. Starting with a healthy human faecal sample, a sequence of selection steps was applied to obtain mice colonized with human microbiota enriched in T-reg-cell-inducing species. From these mice, we isolated and selected 17 strains of bacteria on the basis of their high potency in enhancing T-reg cell abundance and inducing important anti-inflammatory molecules-including interleukin-10 (IL-10) and inducible T-cell co-stimulator (ICOS)-in T-reg cells upon inoculation into germ-free mice. Genome sequencing revealed that the 17 strains fall within clusters IV, XIVa and XVIII of Clostridia, which lack prominent toxins and virulence factors. The 17 strains act as a community to provide bacterial antigens and a TGF-beta-rich environment to help expansion and differentiation of T-reg cells. Oral administration of the combination of 17 strains to adult mice attenuated disease in models of colitis and allergic diarrhoea. Use of the isolated strains may allow for tailored therapeutic manipulation of human immune disorders.
C1 [Atarashi, Koji; Tanoue, Takeshi; Nagano, Yuji; Fukuda, Shinji; Narushima, Seiko; Hase, Koji; Ohno, Hiroshi; Honda, Kenya] RIKEN Ctr Integrat Med Sci IMS RCAI, Tsurumi Ku, Yokohama, Kanagawa 2300045, Japan.
   [Atarashi, Koji; Tanoue, Takeshi; Nagano, Yuji; Taniguchi, Tadatsugu; Honda, Kenya] Univ Tokyo, Grad Sch Med, Dept Immunol, Bunkyo Ku, Tokyo 1130033, Japan.
   [Atarashi, Koji; Hase, Koji] Japan Sci & Technol Agcy, PRESTO, Kawaguchi, Saitama 3320012, Japan.
   [Oshima, Kenshiro; Morita, Hidetoshi; Honda, Kenya] Japan Sci & Technol Agcy, CREST, Kawaguchi, Saitama 3320012, Japan.
   [Oshima, Kenshiro; Suda, Wataru; Kim, Sangwan; Hattori, Masahira] Univ Tokyo, Grad Sch Frontier Sci, Kashiwa, Chiba 2778561, Japan.
   [Nishikawa, Hiroyoshi; Saito, Takuro; Sakaguchi, Shimon] Osaka Univ, Immunol Frontier Res Ctr, Suita, Osaka 5650871, Japan.
   [Fukuda, Shinji] Keio Univ, Inst Adv Biosci, Tsuruoka, Yamagata 9970052, Japan.
   [Fritz, Joelle V.; Wilmes, Paul] Univ Luxembourg, Luxembourg Ctr Syst Biomed, L-4362 Esch Sur Alzette, Luxembourg.
   [Ueha, Satoshi; Matsushima, Kouji] Univ Tokyo, Grad Sch Med, Dept Mol Prevent Med, Bunkyo Ku, Tokyo 1130033, Japan.
   [Olle, Bernat] PureTech Ventures, Boston, MA 02116 USA.
   [Morita, Hidetoshi] Azabu Univ, Sch Vet Med, Sagamihara, Kanagawa 2525201, Japan.
C3 RIKEN; University of Tokyo; Japan Science & Technology Agency (JST); Japan Science & Technology Agency (JST); University of Tokyo; University of Osaka; Keio University; University of Luxembourg; University of Tokyo; Azabu University
RP Hattori, M (corresponding author), Univ Tokyo, Grad Sch Frontier Sci, 5-1-5 Kashiwanoha, Kashiwa, Chiba 2778561, Japan.
EM hattori@k.u-tokyo.ac.jp; kenya@rcai.riken.jp
FU JSPS NEXT program; Ministry of Education, Culture, Sports, Science and Technology of Japan [221S0002]; global COE project of 'Genome Information Big Bang'; Waksman Foundation of Japan Inc.; Grants-in-Aid for Scientific Research [25460491, 22114007, 25293114, 13J04058, 23300354, 221S0002, 24117723] Funding Source: KAKEN
NR 28
TC 2265
Z9 2767
U1 13
U2 441
PU NATURE PUBLISHING 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 8
PY 2013
VL 500
IS 7461
BP 232
EP +
DI 10.1038/nature12331
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 197CH
UT WOS:000322825500040
PM 23842501
DA 2026-03-09
ER

PT J
AU DeCaen, PG
   Delling, M
   Vien, TN
   Clapham, DE
AF DeCaen, Paul G.
   Delling, Markus
   Vien, Thuy N.
   Clapham, David E.
TI Direct recording and molecular identification of the calcium channel of primary cilia
SO NATURE
LA English
DT Article
ID ca2+ channel; trp; currents; cells
AB A primary cilium is a solitary, slender, non-motile protuberance of structured microtubules (9+0) enclosed by plasma membrane(1). Housing components of the cell division apparatus between cell divisions, primary cilia also serve as specialized compartments for calcium signalling(2) and hedgehog signalling pathways(3). Specialized sensory cilia such as retinal photoreceptors and olfactory cilia use diverse ion channels(4-7). An ion current has been measured from primary cilia of kidney cells(8), but the responsible genes have not been identified. The polycystin proteins (PC and PKD), identified in linkage studies of polycystic kidney disease(9), are candidate channels divided into two structural classes: 11-transmembrane proteins (PKD1, PKD1L1 and PKD1L2) remarkable for a large extracellular amino terminus of putative cell adhesion domains and a G-protein-coupled receptor proteolytic site, and the 6-transmembrane channel proteins (PKD2, PKD2L1 and PKD2L2; TRPPs). Evidence indicates that the PKD1 proteins associate with the PKD2 proteins via coiled-coil domains(10-12). Here we use a transgenic mouse in which only cilia express a fluorophore and use it to record directly from primary cilia, and demonstrate that PKD1L1 and PKD2L1 form ion channels at high densities in several cell types. In conjunction with an accompanying manuscript(2), we show that the PKD1L1-PKD2L1 heteromeric channel establishes the cilia as a unique calcium compartment within cells that modulates established hedgehog pathways.
C1 [DeCaen, Paul G.; Delling, Markus; Clapham, David E.] Childrens Hosp Boston, Howard Hughes Med Inst, Dept Cardiol, Boston, MA 02115 USA.
   [Vien, Thuy N.] Tufts Univ, Sackler Sch Grad Biomed Sci, Dept Neurosci, Boston, MA 02111 USA.
   [Clapham, David E.] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA.
C3 Howard Hughes Medical Institute; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Tufts University; Harvard University; Harvard Medical School
RP Clapham, DE (corresponding author), Childrens Hosp Boston, Howard Hughes Med Inst, Dept Cardiol, 320 Longwood Ave, Boston, MA 02115 USA.
EM dclapham@enders.tch.harvard.edu
FU NIH [T32 HL007572, P30 HD18655]; National Heart Lung and Blood Institute [T32HL007572] Funding Source: NIH RePORTER
NR 29
TC 254
Z9 300
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 DEC 12
PY 2013
VL 504
IS 7479
BP 315
EP +
DI 10.1038/nature12832
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 267TQ
UT WOS:000328121500044
PM 24336289
DA 2026-03-09
ER

PT J
AU Song, RS
   Peng, W
   Zhang, Y
   Lv, FX
   Wu, HK
   Guo, JJ
   Cao, YX
   Pi, YB
   Zhang, X
   Jin, L
   Zhang, M
   Jiang, P
   Liu, FH
   Meng, SS
   Zhang, XQ
   Jiang, P
   Cao, CM
   Xiao, RP
AF Song, Ruisheng
   Peng, Wei
   Zhang, Yan
   Lv, Fengxiang
   Wu, Hong-Kun
   Guo, Jiaojiao
   Cao, Yongxing
   Pi, Yanbin
   Zhang, Xin
   Jin, Li
   Zhang, Mao
   Jiang, Peng
   Liu, Fenghua
   Meng, Shaoshuai
   Zhang, Xiuqin
   Jiang, Ping
   Cao, Chun-Mei
   Xiao, Rui-Ping
TI Central role of E3 ubiquitin ligase MG53 in insulin resistance and metabolic disorders
SO NATURE
LA English
DT Article
ID skeletal-muscle; negative regulator; receptor; glucose; obese; degradation; irs1; cbl
AB Insulin resistance is a fundamental pathogenic factor present in various metabolic disorders including obesity and type 2 diabetes(1). Although skeletal muscle accounts for 70-90% of insulin-stimulated glucose disposal(2,3), the mechanism underlying muscle insulin resistance is poorly understood. Here we show in mice that muscle-specific mitsugumin 53 (MG53; also called TRIM72) mediates the degradation of the insulin receptor and insulin receptor substrate 1 (IRS1); and when upregulated, causes metabolic syndrome featuring insulin resistance, obesity, hypertension and dyslipidaemia. MG53 expression is markedly elevated in models of insulin resistance, and MG53 overexpression suffices to trigger muscle insulin resistance and metabolic syndrome sequentially. Conversely, ablation of MG53 prevents diet-induced metabolic syndrome by preserving the insulin receptor, IRS1 and insulin signalling integrity. Mechanistically, MG53 acts as an E3 ligase targeting the insulin receptor and IRS1 for ubiquitin-dependent degradation, comprising a central mechanism controlling insulin signal strength in skeletal muscle. These findings define MG53 as a novel therapeutic target for treating metabolic disorders and associated cardiovascular complications.
C1 [Song, Ruisheng; Peng, Wei; Zhang, Yan; Lv, Fengxiang; Wu, Hong-Kun; Guo, Jiaojiao; Jin, Li; Zhang, Mao; Jiang, Peng; Liu, Fenghua; Meng, Shaoshuai; Zhang, Xiuqin; Jiang, Ping; Cao, Chun-Mei; Xiao, Rui-Ping] Peking Univ, Inst Mol Med, State Key Lab Biomembrane & Membrane Biotechnol, Beijing 100871, Peoples R China.
   [Song, Ruisheng] Peking Univ, Hlth Sci Ctr, Inst Cardiovasc Sci, Beijing 100083, Peoples R China.
   [Cao, Yongxing; Pi, Yanbin; Zhang, Xin] Peking Univ, Hosp 3, Inst Sports Med, Beijing 100191, Peoples R China.
   [Xiao, Rui-Ping] Peking Univ, Ctr Life Sci, Beijing 100871, Peoples R China.
C3 Peking University; Peking University; Peking University; Peking University
RP Xiao, RP (corresponding author), Peking Univ, Inst Mol Med, State Key Lab Biomembrane & Membrane Biotechnol, Beijing 100871, Peoples R China.
EM caochunmei@pku.edu.cn; xiaor@pku.edu.cn
FU National Basic Research Program of China [2012CB518000, 2013CB531200, 2012CB944501]; National Natural Science Foundation of China [81070674, 81070116, 3/22/002, 81130073]
NR 29
TC 253
Z9 296
U1 1
U2 194
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 21
PY 2013
VL 494
IS 7437
BP 375
EP 379
DI 10.1038/nature11834
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 095CS
UT WOS:000315312900043
PM 23354051
DA 2026-03-09
ER

PT J
AU Bastien, FA
   Stassun, KG
   Basri, G
   Pepper, J
AF Bastien, Fabienne A.
   Stassun, Keivan G.
   Basri, Gibor
   Pepper, Joshua
TI An observational correlation between stellar brightness variations and surface gravity
SO NATURE
LA English
DT Article
ID solar-like oscillations; kepler input catalog; photometric variability; stars; 1st; asteroseismology; amplitudes; mission; giants; classification
AB Surface gravity is a basic stellar property, but it is difficult to measure accurately, with typical uncertainties of 25 to 50 per cent if measured spectroscopically(1,2) and 90 to 150 per cent if measured photometrically(3). Asteroseismology measures gravity with an uncertainty of about 2 per cent but is restricted to relatively small samples of bright stars, most of which are giants(4-6). The availability of high-precision measurements of brightness variations for more than 150,000 stars(7,8) provides an opportunity to investigate whether the variations can be used to determine surface gravities. The Fourier power of granulation on a star's surface correlates physically with surface gravity(9,10): if brightness variations on timescales of hours arise from granulation(11), then such variations should correlate with surface gravity. Here we report an analysis of archival data that reveals an observational correlation between surface gravity and root mean squared brightness variations on timescales of less than eight hours for stars with temperatures of 4,500 to 6,750 kelvin, log surface gravities of 2.5 to 4.5 (cgs units) and overall brightness variations of less than three parts per thousand. A straightforward observation of optical brightness variations therefore allows a determination of the surface gravity with a precision of better than 25 per cent for inactive Sun-like stars at main-sequence to giant stages of evolution.
C1 [Bastien, Fabienne A.; Stassun, Keivan G.; Pepper, Joshua] Vanderbilt Univ, Dept Phys & Astron, Nashville, TN 37235 USA.
   [Stassun, Keivan G.] Fisk Univ, Dept Phys, Nashville, TN 37208 USA.
   [Basri, Gibor] Univ Calif Berkeley, Dept Astron, Berkeley, CA 94720 USA.
   [Pepper, Joshua] Lehigh Univ, Dept Phys, Bethlehem, PA 18015 USA.
C3 Vanderbilt University; Fisk University; University of California System; University of California Berkeley; Lehigh University
RP Bastien, FA (corresponding author), Vanderbilt Univ, Dept Phys & Astron, 1807 Stn B, Nashville, TN 37235 USA.
EM fabienne.a.bastien@vanderbilt.edu
FU NASA; Vanderbilt Provost Graduate Fellowship; NSF PAARE [AST-0849736]; Direct For Mathematical & Physical Scien; Division Of Astronomical Sciences [0849736] Funding Source: National Science Foundation
NR 30
TC 113
Z9 131
U1 0
U2 17
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 22
PY 2013
VL 500
IS 7463
BP 427
EP 430
DI 10.1038/nature12419
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 203TJ
UT WOS:000323316100028
PM 23969460
DA 2026-03-09
ER

PT J
AU Pietrzynski, G
   Graczyk, D
   Gieren, W
   Thompson, IB
   Pilecki, B
   Udalski, A
   Soszynski, I
   Kozlowski, S
   Konorski, P
   Suchomska, K
   Bono, G
   Moroni, PGP
   Villanova, S
   Nardetto, N
   Bresolin, F
   Kudritzki, RP
   Storm, J
   Gallenne, A
   Smolec, R
   Minniti, D
   Kubiak, M
   Szymanski, MK
   Poleski, R
   Wyrzykowski, L
   Ulaczyk, K
   Pietrukowicz, P
   Górski, M
   Karczmarek, P
AF Pietrzynski, G.
   Graczyk, D.
   Gieren, W.
   Thompson, I. B.
   Pilecki, B.
   Udalski, A.
   Soszynski, I.
   Kozlowski, S.
   Konorski, P.
   Suchomska, K.
   Bono, G.
   Moroni, P. G. Prada
   Villanova, S.
   Nardetto, N.
   Bresolin, F.
   Kudritzki, R. P.
   Storm, J.
   Gallenne, A.
   Smolec, R.
   Minniti, D.
   Kubiak, M.
   Szymanski, M. K.
   Poleski, R.
   Wyrzykowski, L.
   Ulaczyk, K.
   Pietrukowicz, P.
   Gorski, M.
   Karczmarek, P.
TI An eclipsing-binary distance to the Large Magellanic Cloud accurate to two per cent
SO NATURE
LA English
DT Article
ID hubble-space-telescope; parallaxes; project; stars; light
AB In the era of precision cosmology, it is essential to determine the Hubble constant to an accuracy of three per cent or better(1,2). At present, its uncertainty is dominated by the uncertainty in the distance to the Large Magellanic Cloud (LMC), which, being our second-closest galaxy, serves as the best anchor point for the cosmic distance scale(2,3). Observations of eclipsing binaries offer a unique opportunity to measure stellar parameters and distances precisely and accurately(4,5). The eclipsing-binary method was previously applied to the LMC6,7, but the accuracy of the distance results was lessened by the need to model the bright, early-type systems used in those studies. Here we report determinations of the distances to eight long-period, late-type eclipsing systems in the LMC, composed of cool, giant stars. For these systems, we can accurately measure both the linear and the angular sizes of their components and avoid the most important problems related to the hot, early-type systems. The LMC distance that we derive from these systems (49.97 +/- 0.19 (statistical) +/- 1:11 (systematic) kiloparsecs) is accurate to 2.2 per cent and provides a firm base for a 3-per-cent determination of the Hubble constant, with prospects for improvement to 2 per cent in the future.
C1 [Pietrzynski, G.; Graczyk, D.; Gieren, W.; Pilecki, B.; Villanova, S.; Gallenne, A.] Univ Concepcion, Dept Astron, Concepcion, Chile.
   [Pietrzynski, G.; Pilecki, B.; Udalski, A.; Soszynski, I.; Kozlowski, S.; Konorski, P.; Suchomska, K.; Kubiak, M.; Szymanski, M. K.; Poleski, R.; Wyrzykowski, L.; Ulaczyk, K.; Pietrukowicz, P.; Gorski, M.; Karczmarek, P.] Univ Warsaw Observ, PL-00478 Warsaw, Poland.
   [Thompson, I. B.] Carnegie Observ, Pasadena, CA 91101 USA.
   [Bono, G.] Univ Roma Tor Vergata, Dipartimento Fis, I-00133 Rome, Italy.
   [Bono, G.] INAF Osservatorio Astron Roma, I-00040 Monte Porzio Catone, Italy.
   [Moroni, P. G. Prada] Univ Pisa, Dipartimento Fis, 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.
   [Bresolin, F.; Kudritzki, R. P.] Univ Hawaii, Inst Astron, Honolulu, HI 96822 USA.
   [Storm, J.] Leibniz Inst Astrophys, D-14482 Potsdam, Germany.
   [Smolec, R.] Nicolaus Copernicus Astron Ctr, PL-00716 Warsaw, Poland.
   [Minniti, D.] Pontificia Univ Catolica Chile, Dept Astron & Astrofis, Santiago 22, Chile.
   [Minniti, D.] Vatican Observ, I-00120 Vatican City, Vatican.
   [Poleski, R.] Ohio State Univ, Columbus, OH 43210 USA.
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); Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Earth Sciences & Astronomy (INSU); Universite Cote d'Azur; Observatoire de la Cote d'Azur; University of Hawaii System; Leibniz Association; Leibniz Institut fur Astrophysik Potsdam (AIP); Polish Academy of Sciences; Nicolaus Copernicus Astronomical Center of the Polish Academy of Sciences; Pontificia Universidad Catolica de Chile; Vatican Observatory; University System of Ohio; Ohio State University
RP Pietrzynski, G (corresponding author), Univ Concepcion, Dept Astron, Casilla 160-C, Concepcion, Chile.
EM pietrzyn@astrouw.edu.pl
FU BASAL Centro de Astrofisica y Tecnologias Afines (CATA); Polish Ministry of Science; Polish National Science Centre; GEMINI-CONICYT fund; European Research Council; Foundation for Polish Science (FOCUS, TEAM); Division Of Astronomical Sciences; Direct For Mathematical & Physical Scien [1008798] Funding Source: National Science Foundation
NR 28
TC 582
Z9 627
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 MAR 7
PY 2013
VL 495
IS 7439
BP 76
EP 79
DI 10.1038/nature11878
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 105BE
UT WOS:000316039800042
PM 23467166
DA 2026-03-09
ER

PT J
AU Batterman, SA
   Hedin, LO
   van Breugel, M
   Ransijn, J
   Craven, DJ
   Hall, JS
AF Batterman, Sarah A.
   Hedin, Lars O.
   van Breugel, Michiel
   Ransijn, Johannes
   Craven, Dylan J.
   Hall, Jefferson S.
TI Key role of symbiotic dinitrogen fixation in tropical forest secondary succession
SO NATURE
LA English
DT Article
ID nitrogen-fixation; phosphorus limitation; biomass; dynamics; growth; land
AB Forests contribute a significant portion of the land carbon sink, but their ability to sequester CO2 may be constrained by nitrogen(1-6), a major plant-limiting nutrient. Many tropical forests possess tree species capable of fixing atmospheric dinitrogen (N-2)(7), but it is unclear whether this functional group can supply the nitrogen needed as forests recover from disturbance or previous land use(1), or expand in response to rising CO2 (refs 6, 8). Here we identify a powerful feedback mechanism in which N-2 fixation can overcome ecosystem-scale deficiencies in nitrogen that emerge during periods of rapid biomass accumulation in tropical forests. Over a 300-year chronosequence in Panama, N-2-fixing tree species accumulated carbon up to nine times faster per individual than their non-fixing neighbours (greatest difference in youngest forests), and showed species-specific differences in the amount and timing of fixation. As a result of fast growth and high fixation, fixers provided a large fraction of the nitrogen needed to support net forest growth (50,000 kg carbon per hectare) in the first 12 years. A key element of ecosystem functional diversity was ensured by the presence of different N-2-fixing tree species across the entire forest age sequence. These findings show that symbiotic N-2 fixation can have a central role in nitrogen cycling during tropical forest stand development, with potentially important implications for the ability of tropical forests to sequester CO2.
C1 [Batterman, Sarah A.; Hedin, Lars O.] Princeton Univ, Dept Ecol & Evolutionary Biol, Princeton, NJ 08544 USA.
   [van Breugel, Michiel; Hall, Jefferson S.] Smithsonian Trop Res Inst, Panama City, Panama.
   [Ransijn, Johannes] Wageningen Univ, Ctr Ecosyst Studies, Forest Ecol & Forest Management Grp, NL-6700 AA Wageningen, Netherlands.
   [Ransijn, Johannes] Univ Copenhagen, Dept Geosci & Nat Resource Management, DK-1958 Frederiksberg C, Denmark.
   [Craven, Dylan J.] Yale Univ, Sch Forestry & Environm Studies, New Haven, CT 06511 USA.
C3 Princeton University; Smithsonian Institution; Smithsonian Tropical Research Institute; Wageningen University & Research; University of Copenhagen; Yale University
RP Batterman, SA (corresponding author), Princeton Univ, Dept Ecol & Evolutionary Biol, Princeton, NJ 08544 USA.
EM sbatterm@princeton.edu
FU National Science Foundation (NSF) [DEB-0614116]; National Oceanic and Atmospheric Association (NOAA) [NA17RJ262-344]; Cooperative Institute for Climate Science of Princeton University; Carbon Mitigation Initiative of Princeton University; Smithsonian Tropical Research Institute (STRI); HSBC; STRI; Frank Levinson Family Foundation; Motta Family Foundation
NR 40
TC 327
Z9 365
U1 9
U2 390
PU NATURE PUBLISHING 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 10
PY 2013
VL 502
IS 7470
BP 224
EP +
DI 10.1038/nature12525
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 231RU
UT WOS:000325436100048
PM 24037375
DA 2026-03-09
ER

PT J
AU Tanaka, Y
   Hipolito, CJ
   Maturana, AD
   Ito, K
   Kuroda, T
   Higuchi, T
   Katoh, T
   Kato, HE
   Hattori, M
   Kumazaki, K
   Tsukazaki, T
   Ishitani, R
   Suga, H
   Nureki, O
AF Tanaka, Yoshiki
   Hipolito, Christopher J.
   Maturana, Andres D.
   Ito, Koichi
   Kuroda, Teruo
   Higuchi, Takashi
   Katoh, Takayuki
   Kato, Hideaki E.
   Hattori, Motoyuki
   Kumazaki, Kaoru
   Tsukazaki, Tomoya
   Ishitani, Ryuichiro
   Suga, Hiroaki
   Nureki, Osamu
TI Structural basis for the drug extrusion mechanism by a MATE multidrug transporter
SO NATURE
LA English
DT Article
ID in-vitro selection; vibrio-parahaemolyticus; staphylococcus-aureus; efflux protein; norm; resistance; family; antiporter; metformin; homolog
AB Multidrug and toxic compound extrusion(MATE) family transporters are conserved in the three primary domains of life (Archaea, Bacteria and Eukarya), and export xenobiotics using an electro-chemical gradient of H+ or Na+ across the membrane(1,2). MATE transporters confer multidrug resistance to bacterial pathogens(3-6) and cancer cells(7), thus causing critical reductions in the therapeutic efficacies of antibiotics and anti-cancer drugs, respectively. Therefore, the development of MATE inhibitors has long been awaited in the field of clinical medicine(8,9). Here we present the crystal structures of the H+-driven MATE transporter from Pyrococcus furiosus in two distinct apo-form conformations, and in complexes with a derivative of the antibacterial drug norfloxacin and three in vitro selected thioether-macrocyclic peptides, at 2.1-3.0 angstrom resolutions. The structures, combined with functional analyses, show that the protonation of Asp 41 on the amino (N)-terminal lobe induces the bending of TM1, which in turn collapses the N-lobe cavity, thereby extruding the substrate drug to the extracellular space. Moreover, the macrocyclic peptides bind the central cleft in distinct manners, which correlate with their inhibitory activities. The strongest inhibitory peptide that occupies the N-lobe cavity may pave the way towards the development of efficient inhibitors against MATE transporters.
C1 [Tanaka, Yoshiki; Kato, Hideaki E.; Hattori, Motoyuki; Kumazaki, Kaoru; Tsukazaki, Tomoya; Ishitani, Ryuichiro; Nureki, Osamu] RIKEN Adv Sci Inst, Wako, Saitama 3510198, Japan.
   [Tanaka, Yoshiki; Kato, Hideaki E.; Hattori, Motoyuki; Kumazaki, Kaoru; Tsukazaki, Tomoya; Ishitani, Ryuichiro; Nureki, Osamu] Univ Tokyo, Grad Sch Sci, Dept Biophys & Biochem, Bunkyo Ku, Tokyo 1130032, Japan.
   [Hipolito, Christopher J.; Higuchi, Takashi; Katoh, Takayuki; Suga, Hiroaki] Univ Tokyo, Grad Sch Sci, Dept Chem, Bunkyo Ku, Tokyo 1130033, Japan.
   [Maturana, Andres D.] Nagoya Univ, Grad Sch Bioagr Sci, Dept Bioengn Sci, Chikusa Ku, Nagoya, Aichi 4648601, Japan.
   [Ito, Koichi] Univ Tokyo, Grad Sch Frontier Sci, Dept Med Genome Sci, Chiba 2778562, Japan.
   [Kuroda, Teruo] Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Genome Appl Microbiol, Okayama 7008530, Japan.
   [Hattori, Motoyuki; Tsukazaki, Tomoya] Japan Sci & Technol Agcy, Precursory Res Embryon Sci & Technol PRESTO, Kawaguchi, Saitama 3320012, Japan.
C3 RIKEN; University of Tokyo; University of Tokyo; Nagoya University; University of Tokyo; Okayama University; Japan Science & Technology Agency (JST)
RP Nureki, O (corresponding author), RIKEN Adv Sci Inst, 2-1 Hirosawa, Wako, Saitama 3510198, Japan.
EM hsuga@chem.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 Program 'The Creation of Basic Medical Technologies to Clarify and Control the Mechanisms Underlying Chronic Inflammation' of Japan Science and Technology Agency; MEXT [24227004, 22687007, P11344]; JSPS [21000005]; Austrian Science Fund (FWF) [P11344] Funding Source: Austrian Science Fund (FWF); Grants-in-Aid for Scientific Research [21000005, 11J06643, 22117007, 22687007, 24687016, 24121704, 24681047, 11F01344] Funding Source: KAKEN
NR 42
TC 218
Z9 246
U1 1
U2 154
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 11
PY 2013
VL 496
IS 7444
BP 247
EP +
DI 10.1038/nature12014
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 122VM
UT WOS:000317346300047
PM 23535598
DA 2026-03-09
ER

PT J
AU Ablasser, A
   Goldeck, M
   Cavlar, T
   Deimling, T
   Witte, G
   Röhl, I
   Hopfner, KP
   Ludwig, J
   Hornung, V
AF Ablasser, Andrea
   Goldeck, Marion
   Cavlar, Taner
   Deimling, Tobias
   Witte, Gregor
   Roehl, Ingo
   Hopfner, Karl-Peter
   Ludwig, Janos
   Hornung, Veit
TI cGAS produces a 2′-5′-linked cyclic dinucleotide second messenger that activates STING
SO NATURE
LA English
DT Article
ID gmp-amp synthase; c-di-gmp; cytosolic dna; recognition; adapter; reveals; disease; signals; binding; sensor
AB Detection of cytoplasmic DNA represents one of the most fundamental mechanisms of the innate immune system to sense the presence of microbial pathogens(1). Moreover, erroneous detection of endogenous DNA by the same sensing mechanisms has an important pathophysiological role in certain sterile inflammatory conditions(2,3). The endoplasmic-reticulum-resident protein STING is critically required for the initiation of type I interferon signalling upon detection of cytosolic DNA of both exogenous and endogenous origin(4-8). Next to its pivotal role in DNA sensing, STING also serves as a direct receptor for the detection of cyclic dinucleotides, which function as second messenger molecules in bacteria(9-13). DNA recognition, however, is triggered in an indirect fashion that depends on a recently characterized cytoplasmic nucleotidyl transferase, termed cGAMP synthase (cGAS), which upon interaction with DNA synthesizes a dinucleotide molecule that in turn binds to and activates STING(14,15). We here show in vivo and in vitro that the cGAS-catalysed reaction product is distinct from previously characterized cyclic dinucleotides. Using a combinatorial approach based on mass spectrometry, enzymatic digestion, NMR analysis and chemical synthesis we demonstrate that cGAS produces a cyclic GMP-AMP dinucleotide, which comprises a 2'-5' and a 3'-5' phosphodiester linkage. Gp(2'-5') Ap(3'-5')>. We found that the presence of this 2'-5' linkage was required to exert potent activation of human STING. Moreover, we show that cGAS first catalyses the synthesis of a linear 2'-5'-linked dinucleotide, which is then subject to cGAS-dependent cyclization in a second step through a 3'-5' phosphodiester linkage. This 13-membered ring structure defines a novel class of second messenger molecules, extending the family of 2'-5'-linked antiviral biomolecules.
C1 [Ablasser, Andrea; Goldeck, Marion; Cavlar, Taner; Ludwig, Janos; Hornung, Veit] Univ Bonn, Univ Hosp, Inst Clin Chem & Clin Pharmacol, D-53127 Bonn, Germany.
   [Deimling, Tobias; Witte, Gregor; Hopfner, Karl-Peter] Univ Munich, Dept Biochem, D-81377 Munich, Germany.
   [Deimling, Tobias; Witte, Gregor; Hopfner, Karl-Peter] Univ Munich, Gene Ctr, D-81377 Munich, Germany.
   [Roehl, Ingo] Axolabs GmbH, D-95326 Kulmbach, Germany.
   [Hopfner, Karl-Peter] Ctr Integrated Prot Sci, D-81377 Munich, Germany.
C3 University of Bonn; University of Munich; University of Munich; University of Munich
RP Ablasser, A (corresponding author), Univ Bonn, Univ Hosp, Inst Clin Chem & Clin Pharmacol, D-53127 Bonn, Germany.
EM andrea.ablasser@uni-bonn.de; veit.hornung@uni-bonn.de
FU National Institutes of Health [U19AI083025]; European Research Council [322869, ERC 243046]; Center for Integrated Protein Science Munich (CIPSM); German Research Foundation [SFB670]; European Research Council (ERC) [322869] Funding Source: European Research Council (ERC)
NR 24
TC 1386
Z9 1655
U1 8
U2 375
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 20
PY 2013
VL 498
IS 7454
BP 380
EP +
DI 10.1038/nature12306
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 166XI
UT WOS:000320592900044
PM 23722158
DA 2026-03-09
ER

PT J
AU Lapinaite, A
   Simon, B
   Skjaerven, L
   Rakwalska-Bange, M
   Gabel, F
   Carlomagno, T
AF Lapinaite, Audrone
   Simon, Bernd
   Skjaerven, Lars
   Rakwalska-Bange, Magdalena
   Gabel, Frank
   Carlomagno, Teresa
TI The structure of the box C/D enzyme reveals regulation of RNA methylation
SO NATURE
LA English
DT Article
ID x-ray; biological macromolecules; solution scattering; ribose methylation; site; resonance; fibrillarin; resolution; proteins; system
AB Post-transcriptional modifications are essential to the cell life cycle, as they affect both pre-ribosomal RNA processing and ribosome assembly. The box C/D ribonucleoprotein enzyme that methylates ribosomal RNA at the 2'-O-ribose uses a multitude of guide RNAs as templates for the recognition of rRNA target sites. Two methylation guide sequences are combined on each guide RNA, the significance of which has remained unclear. Here we use a powerful combination of NMR spectroscopy and small-angle neutron scattering to solve the structure of the 390 kDa archaeal RNP enzyme bound to substrate RNA. We show that the two methylation guide sequences are located in different environments in the complex and that the methylation of physiological substrates targeted by the same guide RNA occurs sequentially. This structure provides a means for differential control of methylation levels at the two sites and at the same time offers an unexpected regulatory mechanism for rRNA folding.
C1 [Lapinaite, Audrone; Simon, Bernd; Skjaerven, Lars; Rakwalska-Bange, Magdalena; Carlomagno, Teresa] European Mol Biol Lab, Struct & Computat Biol Unit, D-69117 Heidelberg, Germany.
   [Gabel, Frank] Univ Grenoble Alpes, Inst Biol Struct, F-38027 Grenoble, France.
   [Gabel, Frank] Commisariat Energie Atom, Direct Sci Vivant, Inst Biol Struct, F-38027 Grenoble, France.
   [Gabel, Frank] Ctr Natl Rech Sci, Inst Biol Struct, F-38027 Grenoble, France.
   [Gabel, Frank] Inst Max Von Laue Paul Langevin, F-38042 Grenoble, France.
C3 European Molecular Biology Laboratory (EMBL); Communaute Universite Grenoble Alpes; Universite Grenoble Alpes (UGA); CEA; Centre National de la Recherche Scientifique (CNRS); Communaute Universite Grenoble Alpes; Universite Grenoble Alpes (UGA); CEA; Centre National de la Recherche Scientifique (CNRS); Communaute Universite Grenoble Alpes; Universite Grenoble Alpes (UGA); CEA; Centre National de la Recherche Scientifique (CNRS); Institut Laue-Langevin (ILL)
RP Carlomagno, T (corresponding author), European Mol Biol Lab, Struct & Computat Biol Unit, Meyerhofstr 1, D-69117 Heidelberg, Germany.
EM teresa.carlomagno@embl.de
FU DFG [CA294/3-1]; EU FP7 ITN project RNPnet [289007]; EMBL
NR 49
TC 148
Z9 168
U1 0
U2 91
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 24
PY 2013
VL 502
IS 7472
BP 519
EP +
DI 10.1038/nature12581
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 238YN
UT WOS:000325988400047
PM 24121435
DA 2026-03-09
ER

PT J
AU Kaib, NA
   Raymond, SN
   Duncan, M
AF Kaib, Nathan A.
   Raymond, Sean N.
   Duncan, Martin
TI Planetary system disruption by Galactic perturbations to wide binary stars
SO NATURE
LA English
DT Article
ID extrasolar planets; eccentricity; companions; search; scattering; evolution; origin; orbits
AB Nearly half the exoplanets found within binary star systems reside(1) in very wide binaries with average stellar separations greater than 1,000 astronomical units (one astronomical unit (AU) being the Earth-Sun distance), yet the influence of such distant binary companions on planetary evolution remains largely unstudied. Unlike their tighter counterparts, the stellar orbits of wide binaries continually change under the influence of the Milky Way's tidal field and impulses from other passing stars. Here we report numerical simulations demonstrating that the variable nature of wide binary star orbits dramatically reshapes the planetary systems they host, typically billions of years after formation. Contrary to previous understanding(2), wide binary companions may often strongly perturb planetary systems, triggering planetary ejections and increasing the orbital eccentricities of surviving planets. Although hitherto not recognized, orbits of giant exoplanets within wide binaries are statistically more eccentric than those around isolated stars. Both eccentricity distributions are well reproduced when we assume that isolated stars and wide binaries host similar planetary systems whose outermost giant planets are scattered beyond about 10 AU from their parent stars by early internal instabilities. Consequently, our results suggest that although wide binaries eventually remove the most distant planets from many planetary systems, most isolated giant exoplanet systems harbour additional distant, still undetected planets.
C1 [Kaib, Nathan A.; Duncan, Martin] Queens Univ, Dept Phys, Kingston, ON K7L 3N6, Canada.
   [Kaib, Nathan A.] Univ Toronto, Canadian Inst Theoret Astrophys, Toronto, ON M5S 3H8, Canada.
   [Raymond, Sean N.] Univ Bordeaux, Observ Aquitain Sci Univers, F-33271 Floirac, France.
   [Raymond, Sean N.] CNRS, UMR 5804, Lab Astrophys Bordeaux, F-33271 Floirac, France.
C3 Queens University - Canada; University of Toronto; Universite de Bordeaux; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Earth Sciences & Astronomy (INSU); Universite de Bordeaux
RP Kaib, NA (corresponding author), Northwestern Univ, Ctr Interdisciplinary Explorat & Res Astrophys, 2131 Tech Dr, Evanston, IL 60208 USA.
EM nkaib@astro.queensu.ca
FU CITA National Fellowship; Canada's NSERC
NR 30
TC 148
Z9 166
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 JAN 17
PY 2013
VL 493
IS 7432
BP 381
EP 384
DI 10.1038/nature11780
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 071TA
UT WOS:000313615900046
PM 23292514
DA 2026-03-09
ER

PT J
AU Clavería, C
   Giovinazzo, G
   Sierra, R
   Torres, M
AF Claveria, Cristina
   Giovinazzo, Giovanna
   Sierra, Rocio
   Torres, Miguel
TI Myc-driven endogenous cell competition in the early mammalian embryo
SO NATURE
LA English
DT Article
ID compartments; growth; stem; apoptosis; patterns; death; leads; size
AB The epiblast is the mammalian embryonic tissue that contains the pluripotent stem cells that generate the whole embryo. We have established a method for inducing functional genetic mosaics in the mouse. Using this system, here we show that induction of a mosaic imbalance of Myc expression in the epiblast provokes the expansion of cells with higher Myc levels through the apoptotic elimination of cells with lower levels, without disrupting development. In contrast, homogeneous shifts in Myc levels did not affect epiblast cell viability, indicating that the observed competition results from comparison of relative Myc levels between epiblast cells. During normal development we found that Myc levels are intrinsically heterogeneous among epiblast cells, and that endogenous cell competition refines the epiblast cell population through the elimination of cells with low relative Myc levels. These results show that natural cell competition in the early mammalian embryo contributes to the selection of the epiblast cell pool.
C1 [Claveria, Cristina; Giovinazzo, Giovanna; Sierra, Rocio; Torres, Miguel] CNIC, Dept Desarrollo & Reparac Cardiovasc, E-28029 Madrid, Spain.
C3 Centro Nacional de Investigaciones Cardiovasculares (CNIC)
RP Torres, M (corresponding author), CNIC, Dept Desarrollo & Reparac Cardiovasc, E-28029 Madrid, Spain.
EM mtorres@cnic.es
FU Ministerio de Economia y Competitividad (MINECO); Pro-CNIC Foundation; MINECO/ISCIII TerCel [RD06/0010/0008]; Human Frontiers Science Program [RGP0008/2004]; Madrid Regional Government [S-SAL-0190-2006, P2010/BMD-2315]
NR 31
TC 296
Z9 335
U1 1
U2 46
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 1
PY 2013
VL 500
IS 7460
BP 39
EP U53
DI 10.1038/nature12389
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 192VK
UT WOS:000322514800023
PM 23842495
DA 2026-03-09
ER

PT J
AU Ferrero, DM
   Moeller, LM
   Osakada, T
   Horio, N
   Li, Q
   Roy, DS
   Cichy, A
   Spehr, M
   Touhara, K
   Liberles, SD
AF Ferrero, David M.
   Moeller, Lisa M.
   Osakada, Takuya
   Horio, Nao
   Li, Qian
   Roy, Dheeraj S.
   Cichy, Annika
   Spehr, Marc
   Touhara, Kazushige
   Liberles, Stephen D.
TI A juvenile mouse pheromone inhibits sexual behaviour through the vomeronasal system
SO NATURE
LA English
DT Article
ID chemosensory receptors; olfactory epithelium; aggressive-behavior; protein pheromones; mutant mice; neurons; organ; peptides; hypothalamus; expression
AB Animals display a repertoire of different social behaviours. Appropriate behavioural responses depend on sensory input received during social interactions. In mice, social behaviour is driven by pheromones, chemical signals that encode information related to age, sex and physiological state(1). However, although mice show different social behaviours towards adults, juveniles and neonates, sensory cues that enable specific recognition of juvenile mice are unknown. Here we describe a juvenile pheromone produced by young mice before puberty, termed exocrine-gland secreting peptide 22 (ESP22). ESP22 is secreted from the lacrimal gland and released into tears of 2- to 3-week-old mice. Upon detection, ESP22 activates high-affinity sensory neurons in the vomeronasal organ, and down-stream limbic neurons in the medial amygdala. Recombinant ESP22, painted on mice, exerts a powerful inhibitory effect on adult male mating behaviour, which is abolished in knockout mice lacking TRPC2, a key signalling component of the vomeronasal organ(2,3). Furthermore, knockout of TRPC2 or loss of ESP22 production results in increased sexual behaviour of adult males towards juveniles, and sexual responses towards ESP22-deficient juveniles are suppressed by ESP22 painting. Thus, we describe a pheromone of sexually immature mice that controls an innate social behaviour, a response pathway through the accessory olfactory system and a new role for vomeronasal organ signalling in inhibiting sexual behaviour towards young. These findings provide a molecular framework for understanding how a sensory system can regulate behaviour.
C1 [Ferrero, David M.; Li, Qian; Roy, Dheeraj S.; Liberles, Stephen D.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA.
   [Moeller, Lisa M.; Cichy, Annika; Spehr, Marc] Rhein Westfal TH Aachen, Dept Chemosensat, Inst Biol 2, Aachen, Germany.
   [Osakada, Takuya; Horio, Nao; Touhara, Kazushige] Univ Tokyo, Grad Sch Agr & Life Sci, Dept Appl Biol Chem, Tokyo 1138657, Japan.
   [Touhara, Kazushige] Univ Tokyo, Japan Sci & Technol Agcy, ERATO Touhara Chemosensory Signal Project, Tokyo 1138657, Japan.
C3 Harvard University; Harvard Medical School; RWTH Aachen University; University of Tokyo; Japan Science & Technology Agency (JST); University of Tokyo
RP Liberles, SD (corresponding author), Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA.
EM Stephen_Liberles@hms.harvard.edu
FU National Institutes of Health [R01 DC010155]; Japan Society for the Promotion of Science; ERATO Touhara Chemosensory Signal Project from the Japan Science and Technology Agency; Boehringer Ingelheim Fonds PhD Fellowship
NR 32
TC 128
Z9 152
U1 0
U2 100
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 17
PY 2013
VL 502
IS 7471
BP 368
EP +
DI 10.1038/nature12579
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 235GY
UT WOS:000325706300052
PM 24089208
DA 2026-03-09
ER

PT J
AU Juncadella, IJ
   Kadl, A
   Sharma, AK
   Shim, YM
   Hochreiter-Hufford, A
   Borish, L
   Ravichandran, KS
AF Juncadella, Ignacio J.
   Kadl, Alexandra
   Sharma, Ashish K.
   Shim, Yun M.
   Hochreiter-Hufford, Amelia
   Borish, Larry
   Ravichandran, Kodi S.
TI Apoptotic cell clearance by bronchial epithelial cells critically influences airway inflammation
SO NATURE
LA English
DT Article
ID dust mite allergen; asthma; responses; family; engulfment; mechanism; mimicry; protein; innate; mouse
AB Lung epithelial cells can influence immune responses to airway allergens(1,2). Airway epithelial cells also undergo apoptosis after encountering environmental allergens(3); yet, relatively little is known about how these are cleared, and their effect on airway inflammation. Here we show that airway epithelial cells efficiently engulf apoptotic epithelial cells and secrete anti-inflammatory cytokines, dependent upon intracellular signalling by the small GTPase Rac1. Inducible deletion of Rac1 expression specifically in airway epithelial cells in a mouse model resulted in defective engulfment by epithelial cells and aberrant anti-inflammatory cytokine production. Intranasal priming and challenge of these mice with house dust mite extract or ovalbumin as allergens led to exacerbated inflammation, augmented Th2 cytokines and airway hyper-responsiveness, with decreased interleukin (IL)-10 in bronchial lavages. Rac1-deficient epithelial cells produced much higher IL-33 upon allergen or apoptotic cell encounter, with increased numbers of nuocyte-like cells(1,4,5). Administration of exogenous IL-10 'rescued' the airway inflammation phenotype in Rac1-deficient mice, with decreased IL-33. Collectively, these genetic and functional studies suggest a new role for Rac1-dependent engulfment by airway epithelial cells and in establishing the anti-inflammatory environment, and that defects in cell clearance in the airways could contribute to inflammatory responses towards common allergens.
C1 [Juncadella, Ignacio J.; Hochreiter-Hufford, Amelia; Borish, Larry; Ravichandran, Kodi S.] Univ Virginia, Beirne Carter Ctr Immunol Res, Charlottesville, VA 22908 USA.
   [Juncadella, Ignacio J.; Hochreiter-Hufford, Amelia; Ravichandran, Kodi S.] Univ Virginia, Dept Microbiol, Charlottesville, VA 22908 USA.
   [Juncadella, Ignacio J.; Hochreiter-Hufford, Amelia; Ravichandran, Kodi S.] Univ Virginia, Ctr Cell Clearance, Charlottesville, VA 22908 USA.
   [Kadl, Alexandra; Shim, Yun M.; Borish, Larry] Univ Virginia, Dept Med, Charlottesville, VA 22908 USA.
   [Sharma, Ashish K.] Univ Virginia, Dept Surg, Charlottesville, VA 22908 USA.
   [Borish, Larry] Univ Virginia, Ctr Asthma & Allerg Dis, Charlottesville, VA 22908 USA.
C3 University of Virginia; University of Virginia; University of Virginia; University of Virginia; University of Virginia; University of Virginia
RP Ravichandran, KS (corresponding author), Univ Virginia, Beirne Carter Ctr Immunol Res, Charlottesville, VA 22908 USA.
EM Ravi@virginia.edu
FU Immunology Training Grant; NHLBI; American Asthma Foundation; National Institutes of Health; National Institute of Allergy and Infectious Diseases [T32AI007496] Funding Source: NIH RePORTER
NR 30
TC 232
Z9 274
U1 1
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 JAN 24
PY 2013
VL 493
IS 7433
BP 547
EP +
DI 10.1038/nature11714
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 075GF
UT WOS:000313871400041
PM 23235830
DA 2026-03-09
ER

PT J
AU Yang, WT
   Wang, JG
   Moore, DC
   Liang, HP
   Dooner, M
   Wu, Q
   Terek, R
   Chen, Q
   Ehrlich, MG
   Quesenberry, PJ
   Neel, BG
AF Yang, Wentian
   Wang, Jianguo
   Moore, Douglas C.
   Liang, Haipei
   Dooner, Mark
   Wu, Qian
   Terek, Richard
   Chen, Qian
   Ehrlich, Michael G.
   Quesenberry, Peter J.
   Neel, Benjamin G.
TI Ptpn11 deletion in a novel progenitor causes metachondromatosis by inducing hedgehog signalling
SO NATURE
LA English
DT Article
ID ossification groove; ranvier; chondrogenesis; osteogenesis; receptor; pathway; growth; mutant; cells; model
AB The tyrosine phosphatase SHP2, encoded by PTPN11, is required for the survival, proliferation and differentiation of various cell types(1,2). Germline activating mutations in PTPN11 cause Noonan syndrome, whereas somatic PTPN11 mutations cause childhood myeloproliferative disease and contribute to some solid tumours. Recently, heterozygous inactivating mutations in PTPN11 were found in metachondromatosis, a rare inherited disorder featuring multiple exostoses, enchondromas, joint destruction and bony deformities(3,4). The detailed pathogenesis of this disorder has remained unclear. Here we use a conditional knockout (floxed) Ptpn11 allele (Ptpn11(fl)) and Cre recombinase transgenic mice to delete Ptpn11 specifically in monocytes, macrophages and osteoclasts (lysozyme M-Cre; LysMCre) or in cathepsin K (Ctsk)-expressing cells, previously thought to be osteoclasts. LysMCre; Ptpn11(fl/fl) mice had mild osteopetrosis. Notably, however, CtskCre; Ptpn11(fl/fl) mice developed features very similar to metachondromatosis. Lineage tracing revealed a novel population of CtskCre-expressing cells in the perichondrial groove of Ranvier that display markers and functional properties consistent with mesenchymal progenitors. Chondroid neoplasms arise from these cells and show decreased extracellular signal-regulated kinase (ERK) pathway activation, increased Indian hedgehog (Ihh) and parathyroid hormone-related protein (Pthrp, also known as Pthlh) expression and excessive proliferation. Shp2-deficient chondroprogenitors had decreased fibroblast growth factor-evoked ERK activation and enhanced Ihh and Pthrp expression, whereas fibroblast growth factor receptor (FGFR) or mitogen-activated protein kinase kinase (MEK) inhibitor treatment of chondroid cells increased Ihh and Pthrp expression. Importantly, smoothened inhibitor treatment ameliorated metachondromatosis features in CtskCre; Ptpn11(fl/fl) mice. Thus, in contrast to its pro-oncogenic role in haematopoietic and epithelial cells, Ptpn11 is a tumour suppressor in cartilage, acting through a FGFR/MEK/ERK-dependent pathway in a novel progenitor cell population to prevent excessive Ihh production.
C1 [Yang, Wentian; Wang, Jianguo; Moore, Douglas C.; Liang, Haipei; Terek, Richard; Chen, Qian; Ehrlich, Michael G.] Brown Univ, Alpert Med Sch, Dept Orthopaed, Providence, RI 02903 USA.
   [Yang, Wentian; Wang, Jianguo; Moore, Douglas C.; Liang, Haipei; Terek, Richard; Chen, Qian; Ehrlich, Michael G.] Rhode Isl Hosp, Providence, RI 02903 USA.
   [Dooner, Mark; Quesenberry, Peter J.] Rhode Isl Hosp, Dept Med, Providence, RI 02903 USA.
   [Dooner, Mark; Quesenberry, Peter J.] Rhode Isl Hosp, COBRE Ctr Stem Cell Biol, Providence, RI 02903 USA.
   [Dooner, Mark; Quesenberry, Peter J.] Brown Univ, Alpert Med Sch, Providence, RI 02903 USA.
   [Wu, Qian] Univ Connecticut, Ctr Hlth, Dept Pathol & Lab Med, Farmington, CT 06030 USA.
   [Neel, Benjamin G.] Univ Toronto, Univ Hlth Network, Princess Margaret Canc Ctr, Toronto, ON M5G 1L7, Canada.
   [Neel, Benjamin G.] Univ Toronto, Dept Med Biophys, Toronto, ON M5G 1L7, Canada.
C3 Brown University; Lifespan Health Rhode Island; Rhode Island Hospital; Lifespan Health Rhode Island; Rhode Island Hospital; Lifespan Health Rhode Island; Rhode Island Hospital; Brown University; University of Connecticut; University of Toronto; University Health Network Toronto; Princess Margaret Cancer Centre; University of Toronto
RP Yang, WT (corresponding author), Brown Univ, Alpert Med Sch, Dept Orthopaed, Providence, RI 02903 USA.
EM wyang@lifespan.org
FU National Institute for General Medicine Sciences (NIGMS) [8P20GM103468]; NIH [R21AR57156, R37CA49152]; Rhode Island Hospital Orthopaedic Foundation; Pediatric Orthopaedic Society of North America; Orthopaedic Research and Education Foundation; Ontario Ministry of Health and Long Term Care; Princess Margaret Cancer Foundation
NR 33
TC 193
Z9 225
U1 0
U2 45
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 25
PY 2013
VL 499
IS 7459
BP 491
EP +
DI 10.1038/nature12396
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 187YP
UT WOS:000322157900043
PM 23863940
DA 2026-03-09
ER

PT J
AU Hickman, MA
   Zeng, GS
   Forche, A
   Hirakawa, MP
   Abbey, D
   Harrison, BD
   Wang, YM
   Su, CH
   Bennett, RJ
   Wang, Y
   Berman, J
AF Hickman, Meleah A.
   Zeng, Guisheng
   Forche, Anja
   Hirakawa, Matthew P.
   Abbey, Darren
   Harrison, Benjamin D.
   Wang, Yan-Ming
   Su, Ching-hua
   Bennett, Richard J.
   Wang, Yue
   Berman, Judith
TI The 'obligate diploid' Candida albicans forms mating-competent haploids
SO NATURE
LA English
DT Article
ID gene disruption; chromosome loss; ploidy; heterozygosity; morphogenesis; proteins; mutants; reveal; system
AB Candida albicans, the most prevalent human fungal pathogen, is considered to be an obligate diploid that carries recessive lethal mutations throughout the genome. Here we demonstrate that C. albicans has a viable haploid state that can be derived from diploid cells under in vitro and in vivo conditions, and that seems to arise through a concerted chromosome loss mechanism. Haploids undergo morphogenetic changes like those of diploids, including the yeast-hyphal transition, chlamydospore formation and a white-opaque switch that facilitates mating. Haploid opaque cells of opposite mating type mate efficiently to regenerate the diploid form, restoring heterozygosity and fitness. Homozygous diploids arise spontaneously by auto-diploidization, and both haploids and auto-diploids show a similar reduction in fitness, in vitro and in vivo, relative to heterozygous diploids, indicating that homozygous cell types are transient in mixed populations. Finally, we constructed stable haploid strains with multiple auxotrophies that will facilitate molecular and genetic analyses of this important pathogen.
C1 [Hickman, Meleah A.; Abbey, Darren; Harrison, Benjamin D.; Berman, Judith] Univ Minnesota, Dept Genet Cell Biol & Dev, Minneapolis, MN 55455 USA.
   [Zeng, Guisheng; Wang, Yan-Ming; Wang, Yue] Agcy Sci Technol & Res, Inst Mol & Cell Biol, Singapore 138673, Singapore.
   [Forche, Anja] Bowdoin Coll, Brunswick, ME 04011 USA.
   [Hirakawa, Matthew P.; Bennett, Richard J.] Brown Univ, Dept Mol Microbiol & Immunol, Providence, RI 02912 USA.
   [Su, Ching-hua] Taipei Med Univ, Dept Microbiol & Immunol, Taipei, Taiwan.
   [Berman, Judith] Tel Aviv Univ, George Wise Fac Life Sci, Dept Mol Microbiol & Biotechnol, IL-69978 Ramat Aviv, Israel.
C3 University of Minnesota System; University of Minnesota Twin Cities; Agency for Science Technology & Research (A*STAR); A*STAR - Institute of Molecular & Cell Biology (IMCB); Bowdoin College; Brown University; Taipei Medical University; Tel Aviv University
RP Berman, J (corresponding author), Univ Minnesota, Dept Genet Cell Biol & Dev, Minneapolis, MN 55455 USA.
EM jberman@umn.edu
FU NRSA [F32GM096536-02]; National Institute of Allergy and Infectious Diseases (NIAID) [R15-AI090633-01A1, R01 AI0624273, AI081560, AI081704, AI0624273]; training grant for Graduate Assistance in Areas of National Need [P200A100100]; National Institute of Dental & Craniofacial Research [T32DE007288]; Burroughs Wellcome Fund; Agency for Science, Technology, & Research, Singapore; National Institute of Allergy and Infectious Diseases [R01AI081704] Funding Source: NIH RePORTER
NR 50
TC 232
Z9 279
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 FEB 7
PY 2013
VL 494
IS 7435
BP 55
EP 59
DI 10.1038/nature11865
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 087DJ
UT WOS:000314741200032
PM 23364695
DA 2026-03-09
ER

PT J
AU Beeler, MC
   Williams, RA
   Jiménez-García, K
   LeBlanc, LJ
   Perry, AR
   Spielman, IB
AF Beeler, M. C.
   Williams, R. A.
   Jimenez-Garcia, K.
   LeBlanc, L. J.
   Perry, A. R.
   Spielman, I. B.
TI The spin Hall effect in a quantum gas
SO NATURE
LA English
DT Article
ID neutral atoms
AB Electronic properties such as current flow are generally independent of the electron's spin angular momentum, an internal degree of freedom possessed by quantum particles. The spin Hall effect, first proposed 40 years ago(1), is an unusual class of phenomena in which flowing particles experience orthogonally directed, spin-dependent forces-analogous to the conventional Lorentz force that gives the Hall effect, but opposite in sign for two spin states. Spin Hall effects have been observed for electrons flowing in spin-orbit-coupled materials such as GaAs and InGaAs (refs 2, 3) and for laser light traversing dielectric junctions(4). Here we observe the spin Hall effect in a quantum-degenerate Bose gas, and use the resulting spin-dependent Lorentz forces to realize a cold-atom spin transistor. By engineering a spatially inhomogeneous spin-orbit coupling field for our quantum gas, we explicitly introduce and measure the requisite spin-dependent Lorentz forces, finding them to be in excellent agreement with our calculations. This 'atomtronic' transistor behaves as a type of velocity-insensitive adiabatic spin selector, with potential application in devices such as magnetic(5) or inertial(6) sensors. In addition, such techniques for creating and measuring the spin Hall effect are clear prerequisites for engineering topological insulators(7,8) and detecting their associated quantized spin Hall effects in quantum gases. As implemented, our system realizes a laser-actuated analogue to the archetypal semiconductor spintronic device, the Datta-Das spin transistor(9,10).
C1 [Beeler, M. C.; Williams, R. A.; Jimenez-Garcia, K.; LeBlanc, L. J.; Perry, A. R.; Spielman, I. B.] NIST, Joint Quantum Inst, Gaithersburg, MD 20899 USA.
   [Beeler, M. C.; Williams, R. A.; Jimenez-Garcia, K.; LeBlanc, L. J.; Perry, A. R.; Spielman, I. B.] Univ Maryland, Gaithersburg, MD 20899 USA.
   [Jimenez-Garcia, K.] Inst Politecn Nacl, Ctr Invest & Estudios Avanzados, Dept Fis, Mexico City 07360, DF, Mexico.
C3 National Institute of Standards & Technology (NIST) - USA; University System of Maryland; University of Maryland College Park; Instituto Politecnico Nacional - Mexico; CINVESTAV - Centro de Investigacion y de Estudios Avanzados del Instituto Politecnico Nacional
RP Spielman, IB (corresponding author), NIST, Joint Quantum Inst, Gaithersburg, MD 20899 USA.
EM ian.spielman@nist.gov
FU DARPA OLE programme; ARO atomtronics MURI; NIST; US NSF through the PFC at the JQI; NSERC; Direct For Mathematical & Physical Scien; Division Of Physics [0822671] Funding Source: National Science Foundation
NR 40
TC 180
Z9 200
U1 1
U2 220
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 13
PY 2013
VL 498
IS 7453
BP 201
EP +
DI 10.1038/nature12185
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 162RR
UT WOS:000320283400041
PM 23739329
DA 2026-03-09
ER

PT J
AU Han, H
   Irimia, M
   Ross, PJ
   Sung, HK
   Alipanahi, B
   David, L
   Golipour, A
   Gabut, M
   Michael, IP
   Nachman, EN
   Wang, E
   Trcka, D
   Thompson, T
   O'Hanlon, D
   Slobodeniuc, V
   Barbosa-Morais, NL
   Burge, CB
   Moffat, J
   Frey, BJ
   Nagy, A
   Ellis, J
   Wrana, JL
   Blencowe, BJ
AF Han, Hong
   Irimia, Manuel
   Ross, P. Joel
   Sung, Hoon-Ki
   Alipanahi, Babak
   David, Laurent
   Golipour, Azadeh
   Gabut, Mathieu
   Michael, Iacovos P.
   Nachman, Emil N.
   Wang, Eric
   Trcka, Dan
   Thompson, Tadeo
   O'Hanlon, Dave
   Slobodeniuc, Valentina
   Barbosa-Morais, Nuno L.
   Burge, Christopher B.
   Moffat, Jason
   Frey, Brendan J.
   Nagy, Andras
   Ellis, James
   Wrana, Jeffrey L.
   Blencowe, Benjamin J.
TI MBNL proteins repress ES-cell-specific alternative splicing and reprogramming
SO NATURE
LA English
DT Article
ID pluripotent stem-cells; large gene lists; transcriptional network; muscleblind proteins; self-renewal; differentiation; fibroblasts; integration; regulators; pathways
AB Previous investigations of the core gene regulatory circuitry that controls the pluripotency of embryonic stem (ES) cells have largely focused on the roles of transcription, chromatin and non-coding RNA regulators(1-3). Alternative splicing represents a widely acting mode of gene regulation(4-8), yet its role in regulating ES-cell pluripotency and differentiation is poorly understood. Here we identify the muscleblind-like RNA binding proteins, MBNL1 and MBNL2, as conserved and direct negative regulators of a large program of cassette exon alternative splicing events that are differentially regulated between ES cells and other cell types. Knockdown of MBNL proteins in differentiated cells causes switching to an ES-cell-like alternative splicing pattern for approximately half of these events, whereas overexpression of MBNL proteins in ES cells promotes differentiated-cell-like alternative splicing patterns. Among the MBNL-regulated events is an ES-cell-specific alternative splicing switch in the forkhead family transcription factor FOXP1 that controls pluripotency(9). Consistent with a central and negative regulatory role for MBNL proteins in pluripotency, their knockdown significantly enhances the expression of key pluripotency genes and the formation of induced pluripotent stem cells during somatic cell reprogramming.
C1 [Han, Hong; Irimia, Manuel; Gabut, Mathieu; Nachman, Emil N.; O'Hanlon, Dave; Slobodeniuc, Valentina; Barbosa-Morais, Nuno L.; Moffat, Jason; Frey, Brendan J.; Blencowe, Benjamin J.] Univ Toronto, Banting & Best Dept Med Res, Toronto, ON M5S 3E1, Canada.
   [Han, Hong; Irimia, Manuel; Gabut, Mathieu; Nachman, Emil N.; O'Hanlon, Dave; Slobodeniuc, Valentina; Barbosa-Morais, Nuno L.; Moffat, Jason; Frey, Brendan J.; Blencowe, Benjamin J.] Univ Toronto, Donnelly Ctr, Toronto, ON M5S 3E1, Canada.
   [Han, Hong; Golipour, Azadeh; Nachman, Emil N.; Moffat, Jason; Ellis, James; Wrana, Jeffrey L.; Blencowe, Benjamin J.] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A8, Canada.
   [Ross, P. Joel; Thompson, Tadeo; Ellis, James] Hosp Sick Children, Toronto, ON M5G 1L7, Canada.
   [Sung, Hoon-Ki; Michael, Iacovos P.; Nagy, Andras] Mt Sinai Hosp, Ctr Stem Cells & Tissue Engn, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada.
   [Alipanahi, Babak; Frey, Brendan J.] Univ Toronto, Dept Elect & Comp Engn, Toronto, ON M5S 3G4, Canada.
   [David, Laurent; Golipour, Azadeh; Trcka, Dan; Wrana, Jeffrey L.] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Ctr Syst Biol, Toronto, ON M5G 1X5, Canada.
   [Wang, Eric; Burge, Christopher B.] MIT, Dept Biol, Cambridge, MA 02142 USA.
   [Barbosa-Morais, Nuno L.] Univ Lisbon, Fac Med, Inst Mol Med, P-1649028 Lisbon, Portugal.
   [Nagy, Andras] Univ Toronto, Dept Obstet & Gynecol, Toronto, ON M5S 1A8, Canada.
C3 University of Toronto; University of Toronto; University of Toronto; University of Toronto; Hospital for Sick Children (SickKids); University of Toronto; Sinai Health System Toronto; Lunenfeld Tanenbaum Research Institute; University of Toronto; University of Toronto; Sinai Health System Toronto; Lunenfeld Tanenbaum Research Institute; Massachusetts Institute of Technology (MIT); Universidade de Lisboa; University of Toronto
RP Blencowe, BJ (corresponding author), Univ Toronto, Banting & Best Dept Med Res, Toronto, ON M5S 3E1, Canada.
EM b.blencowe@utoronto.ca
FU Canadian Institutes of Health Research (CIHR); Ontario Research Fund; Canadian Stem Cell Network; National Institutes of Health [R33MH087908]; University of Toronto; Ontario Stem Cell Initiative; Human Frontiers Science Program Organization; Marie Curie Actions; National Human Genome Research Institute [R01HG002439] Funding Source: NIH RePORTER
NR 38
TC 253
Z9 298
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 JUN 13
PY 2013
VL 498
IS 7453
BP 241
EP +
DI 10.1038/nature12270
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 162RR
UT WOS:000320283400051
PM 23739326
DA 2026-03-09
ER

PT J
AU Orlando, L
   Ginolhac, A
   Zhang, GJ
   Froese, D
   Albrechtsen, A
   Stiller, M
   Schubert, M
   Cappellini, E
   Petersen, B
   Moltke, I
   Johnson, PLF
   Fumagalli, M
   Vilstrup, JT
   Raghavan, M
   Korneliussen, T
   Malaspinas, AS
   Vogt, J
   Szklarczyk, D
   Kelstrup, CD
   Vinther, J
   Dolocan, A
   Stenderup, J
   Velazquez, AMV
   Cahill, J
   Rasmussen, M
   Wang, XL
   Min, JM
   Zazula, GD
   Seguin-Orlando, A
   Mortensen, C
   Magnussen, K
   Thompson, JF
   Weinstock, J
   Gregersen, K
   Roed, KH
   Eisenmann, V
   Rubin, CJ
   Miller, DC
   Antczak, DF
   Bertelsen, MF
   Brunak, S
   Al-Rasheid, KAS
   Ryder, O
   Andersson, L
   Mundy, J
   Krogh, A
   Gilbert, MTP
   Kjær, K
   Sicheritz-Ponten, T
   Jensen, LJ
   Olsen, JV
   Hofreiter, M
   Nielsen, R
   Shapiro, B
   Wang, J
   Willerslev, E
AF Orlando, Ludovic
   Ginolhac, Aurelien
   Zhang, Guojie
   Froese, Duane
   Albrechtsen, Anders
   Stiller, Mathias
   Schubert, Mikkel
   Cappellini, Enrico
   Petersen, Bent
   Moltke, Ida
   Johnson, Philip L. F.
   Fumagalli, Matteo
   Vilstrup, Julia T.
   Raghavan, Maanasa
   Korneliussen, Thorfinn
   Malaspinas, Anna-Sapfo
   Vogt, Josef
   Szklarczyk, Damian
   Kelstrup, Christian D.
   Vinther, Jakob
   Dolocan, Andrei
   Stenderup, Jesper
   Velazquez, Amhed M. V.
   Cahill, James
   Rasmussen, Morten
   Wang, Xiaoli
   Min, Jiumeng
   Zazula, Grant D.
   Seguin-Orlando, Andaine
   Mortensen, Cecilie
   Magnussen, Kim
   Thompson, John F.
   Weinstock, Jacobo
   Gregersen, Kristian
   Roed, Knut H.
   Eisenmann, Vera
   Rubin, Carl J.
   Miller, Donald C.
   Antczak, Douglas F.
   Bertelsen, Mads F.
   Brunak, Soren
   Al-Rasheid, Khaled A. S.
   Ryder, Oliver
   Andersson, Leif
   Mundy, John
   Krogh, Anders
   Gilbert, M. Thomas P.
   Kjaer, Kurt
   Sicheritz-Ponten, Thomas
   Jensen, Lars Juhl
   Olsen, Jesper V.
   Hofreiter, Michael
   Nielsen, Rasmus
   Shapiro, Beth
   Wang, Jun
   Willerslev, Eske
TI Recalibrating Equus evolution using the genome sequence of an early Middle Pleistocene horse
SO NATURE
LA English
DT Article
ID read alignment; dna; history; likelihood; reveal; performance; patterns; climate; damage; marker
AB The rich fossil record of equids has made them a model for evolutionary processes(1). Here we present a 1.12-times coverage draft genome from a horse bone recovered from permafrost dated to approximately 560-780 thousand years before present (kyr BP)(2,3). Our data represent the oldest full genome sequence determined so far by almost an order of magnitude. For comparison, we sequenced the genome of a Late Pleistocene horse (43 kyr BP), and modern genomes of five domestic horse breeds (Equus ferus caballus), a Przewalski's horse (E. f. prze-walskii) and a donkey (E. asinus). Our analyses suggest that the Equus lineage giving rise to all contemporary horses, zebras and donkeys originated 4.0-4.5 million years before present (Myr BP), twice the conventionally accepted time to the most recent common ancestor of the genus Equus(4,5). We also find that horse population size fluctuated multiple times over the past 2 Myr, particularly during periods of severe climatic changes. We estimate that the Przewalski's and domestic horse populations diverged 38-72 kyr BP, and find no evidence of recent admixture between the domestic horse breeds and the Przewalski's horse investigated. This supports the contention that Przewalski's horses represent the last surviving wild horse population(6). We find similar levels of genetic variation among Przewalski's and domestic populations, indicating that the former are genetically viable and worthy of conservation efforts. We also find evidence for continuous selection on the immune system and olfaction throughout horse evolution. Finally, we identify 29 genomic regions among horse breeds that deviate from neutrality and show low levels of genetic variation compared to the Przewalski's horse. Such regions could correspond to loci selected early during domestication.
C1 [Orlando, Ludovic; Ginolhac, Aurelien; Schubert, Mikkel; Cappellini, Enrico; Vilstrup, Julia T.; Raghavan, Maanasa; Korneliussen, Thorfinn; Malaspinas, Anna-Sapfo; Stenderup, Jesper; Velazquez, Amhed M. V.; Rasmussen, Morten; Seguin-Orlando, Andaine; Mortensen, Cecilie; Magnussen, Kim; Gregersen, Kristian; Krogh, Anders; Gilbert, M. Thomas P.; Kjaer, Kurt; Willerslev, Eske] Univ Copenhagen, Nat Hist Museum Denmark, Ctr GeoGenet, DK-1350 Copenhagen K, Denmark.
   [Zhang, Guojie; Wang, Xiaoli; Min, Jiumeng; Wang, Jun] BGI Shenzhen, Shenzhen Key Lab Trans Biotechnol, Shenzhen 518083, Peoples R China.
   [Froese, Duane] Univ Alberta, Dept Earth & Atmospher Sci, Edmonton, AB T6G 2E3, Canada.
   [Albrechtsen, Anders; Moltke, Ida; Krogh, Anders] Univ Copenhagen, Dept Biol, Bioinformat Ctr, DK-2200 Copenhagen, Denmark.
   [Stiller, Mathias; Cahill, James; Shapiro, Beth] Univ Calif Santa Cruz, Dept Ecol & Evolutionary Biol, Santa Cruz, CA 95064 USA.
   [Petersen, Bent; Vogt, Josef; Brunak, Soren; Sicheritz-Ponten, Thomas] Tech Univ Denmark, Dept Syst Biol, Ctr Biol Sequence Anal, DK-2800 Lyngby, Denmark.
   [Moltke, Ida] Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA.
   [Johnson, Philip L. F.] Emory Univ, Dept Biol, Atlanta, GA 30322 USA.
   [Fumagalli, Matteo; Nielsen, Rasmus] Univ Calif Berkeley, Dept Integrat Biol, Berkeley, CA 94720 USA.
   [Szklarczyk, Damian; Kelstrup, Christian D.; Jensen, Lars Juhl; Olsen, Jesper V.] Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Prot Res, DK-2200 Copenhagen, Denmark.
   [Vinther, Jakob] Univ Texas Austin, Jackson Sch Geosci, Austin, TX 78712 USA.
   [Dolocan, Andrei] Univ Texas Austin, Texas Mat Inst, Austin, TX 78712 USA.
   [Zazula, Grant D.] Govt Yukon, Dept Tourism & Culture, Yukon Palaeontol Program, Whitehorse, YT Y1A 2C6, Canada.
   [Seguin-Orlando, Andaine; Mortensen, Cecilie; Magnussen, Kim] Univ Copenhagen, Danish Natl High Throughput DNA Sequencing Ctr, DK-1353 Copenhagen K, Denmark.
   [Thompson, John F.] NABsys Inc, Providence, RI 02903 USA.
   [Weinstock, Jacobo] Univ Southampton, Southampton SO17 1BF, Hants, England.
   [Gregersen, Kristian] Univ Copenhagen, Nat Hist Museum Denmark, Zool Museum, DK-2100 Copenhagen, Denmark.
   [Roed, Knut H.] Norwegian Sch Vet Sci, Dept Basic Sci & Aquat Med, N-0033 Oslo, Norway.
   [Eisenmann, Vera] CNRS, MNHN, Dept Hist Terre, UMR 5143,CP 38, F-75005 Paris, France.
   [Rubin, Carl J.; Andersson, Leif] Uppsala Univ, Dept Med Biochem & Microbiol, Sci Life Lab, SE-75123 Uppsala, Sweden.
   [Miller, Donald C.; Antczak, Douglas F.] Cornell Univ, Baker Inst Anim Hlth, Ithaca, NY 14853 USA.
   [Bertelsen, Mads F.] Copenhagen Zoo, Ctr Zoo & Wild Anim Hlth, DK-2000 Frederiksberg, Denmark.
   [Brunak, Soren; Sicheritz-Ponten, Thomas] Tech Univ Denmark, Novo Nordisk Fdn Ctr Biosustainabil, DK-2970 Horsholm, Denmark.
   [Al-Rasheid, Khaled A. S.] King Saud Univ, Coll Sci, Dept Zool, Riyadh 11451, Saudi Arabia.
   [Ryder, Oliver] San Diego Zoos Inst Conservat Res, Escondido, CA 92027 USA.
   [Mundy, John; Wang, Jun] Univ Copenhagen, Dept Biol, DK-2200 Copenhagen, Denmark.
   [Hofreiter, Michael] Univ York, Dept Biol, York YO10 5DD, N Yorkshire, England.
   [Nielsen, Rasmus] Univ Calif Berkeley, Dept Stat, Berkeley, CA 94720 USA.
   [Wang, Jun] King Abdulaziz Univ, Jeddah 21589, Saudi Arabia.
   [Wang, Jun] Macau Univ Sci & Technol, Taipa 999078, Macau, Peoples R China.
C3 University of Copenhagen; Beijing Genomics Institute (BGI); University of Alberta; University of Copenhagen; University of California System; University of California Santa Cruz; Technical University of Denmark; University of Chicago; Emory University; University of California System; University of California Berkeley; University of Copenhagen; University of Texas System; University of Texas Austin; University of Texas System; University of Texas Austin; University of Copenhagen; University of Southampton; University of Copenhagen; Norwegian University of Life Sciences; Centre National de la Recherche Scientifique (CNRS); Museum National d'Histoire Naturelle (MNHN); Uppsala University; Cornell University; Technical University of Denmark; King Saud University; Zoological Society of San Diego; University of Copenhagen; University of York - UK; University of California System; University of California Berkeley; King Abdulaziz University; Macau University of Science & Technology
RP Orlando, L (corresponding author), Univ Copenhagen, Nat Hist Museum Denmark, Ctr GeoGenet, Oster Voldgade 5-7, DK-1350 Copenhagen K, Denmark.
EM Lorlando@snm.ku.dk; wangjun30@gmail.com; ewillerslev@snm.ku.dk
FU Danish Council for Independent Research, Natural Sciences (FNU); Danish National Research Foundation; Novo Nordisk Foundation; Lundbeck Foundation [R52-A5062, R82-5062]; Marie-Curie Career Integration grant [FP7 CIG-293845]; National Science Foundation [ARC-0909456, DBI-0906041]; Searle Scholars Program; King Saud University Distinguished Scientist Fellowship Program (DSFP); Natural Science and Engineering Research Council of Canada; US National Science Foundation [DMR-0923096]; National Human Genetics Research Institute (NHGRI) [RC2 HG005598]; Marie-Curie Intra-European Fellowship [FP7 IEF-299176]; EMBO Long-Term Post-doctoral Fellowship [ALTF 229-2011]; Swiss National Science Foundation (SNSF); Lundbeck Foundation [R24-2008-2527, R70-2010-6286, R155-2013-16338, R38-2008-3048, R109-2012-9995] Funding Source: researchfish; Novo Nordisk Fonden [NNF10CC1016517] Funding Source: researchfish; Novo Nordisk Foundation Center for Protein Research [PI Jesper Velgaard Olsen, PI Søren Brunak, PI Lars Juhl Jensen] Funding Source: researchfish; Villum Fonden [00007171] Funding Source: researchfish
NR 65
TC 612
Z9 715
U1 4
U2 587
PU NATURE PUBLISHING 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 4
PY 2013
VL 499
IS 7456
BP 74
EP +
DI 10.1038/nature12323
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 176ED
UT WOS:000321285600036
PM 23803765
DA 2026-03-09
ER

PT J
AU Braumüller, H
   Wieder, T
   Brenner, E
   Assmann, S
   Hahn, M
   Alkhaled, M
   Schilbach, K
   Essmann, F
   Kneilling, M
   Griessinger, C
   Ranta, F
   Ullrich, S
   Mocikat, R
   Braungart, K
   Mehra, T
   Fehrenbacher, B
   Berdel, J
   Niessner, H
   Meier, F
   van den Broek, M
   Häring, HU
   Handgretinger, R
   Quintanilla-Martinez, L
   Fend, F
   Pesic, M
   Bauer, J
   Zender, L
   Schaller, M
   Schulze-Osthoff, K
   Röcken, M
AF Braumueller, Heidi
   Wieder, Thomas
   Brenner, Ellen
   Assmann, Sonja
   Hahn, Matthias
   Alkhaled, Mohammed
   Schilbach, Karin
   Essmann, Frank
   Kneilling, Manfred
   Griessinger, Christoph
   Ranta, Felicia
   Ullrich, Susanne
   Mocikat, Ralph
   Braungart, Kilian
   Mehra, Tarun
   Fehrenbacher, Birgit
   Berdel, Julia
   Niessner, Heike
   Meier, Friedegund
   van den Broek, Maries
   Haering, Hans-Ulrich
   Handgretinger, Rupert
   Quintanilla-Martinez, Leticia
   Fend, Falko
   Pesic, Marina
   Bauer, Juergen
   Zender, Lars
   Schaller, Martin
   Schulze-Osthoff, Klaus
   Roecken, Martin
TI T-helper-1-cell cytokines drive cancer into senescence
SO NATURE
LA English
DT Article
ID oncogene-induced senescence; cd4(+) t-cells; tumor; surveillance; regression; pathway; p53
AB Cancer control by adaptive immunity involves a number of defined death(1-8) and clearance(9-11) mechanisms. However, efficient inhibition of exponential cancer growth by T cells and interferon-gamma (IFN-gamma) requires additional undefined mechanisms that arrest cancer cell proliferation(1-5,12,13). Here we show that the combined action of the T-helper-1-cell cytokines IFN-gamma and tumour necrosis factor (TNF) directly induces permanent growth arrest in cancers. To safely separate senescence induced by tumour immunity from oncogene-induced senescence(9-11,14-17), we used a mouse model in which the Simian virus 40 large T antigen (Tag) expressed under the control of the rat insulin promoter creates tumours by attenuating p53- and Rb-mediated cell cycle control(18,19). When combined, IFN-gamma and TNF drive Tag-expressing cancers into senescence by inducing permanent growth arrest in G1/G0, activation of p16INK4a (also known as CDKN2A), and downstream Rb hypophosphorylation at serine 795. This cytokine-induced senescence strictly requires STAT1 and TNFR1 (also known as TNFRSF1A) signalling in addition to p16INK4a. In vivo, Tag-specific T-helper 1 cells permanently arrest Tag-expressing cancers by inducing IFN-gamma- and TNFR1-dependent senescence. Conversely, Tnfr1(-/-) Tag-expressing cancers resist cytokine-induced senescence and grow aggressively, even in TNFR1-expressing hosts. Finally, as IFN-gamma and TNF induce senescence in numerous murine and human cancers, this may be a general mechanism for arresting cancer progression.
C1 [Braumueller, Heidi; Wieder, Thomas; Brenner, Ellen; Assmann, Sonja; Hahn, Matthias; Kneilling, Manfred; Griessinger, Christoph; Braungart, Kilian; Mehra, Tarun; Fehrenbacher, Birgit; Berdel, Julia; Niessner, Heike; Meier, Friedegund; Bauer, Juergen; Schaller, Martin; Roecken, Martin] Univ Tubingen, Dept Dermatol, D-72076 Tubingen, Germany.
   [Alkhaled, Mohammed; Schilbach, Karin; Handgretinger, Rupert] Univ Tubingen, Dept Gen Pediat, D-72076 Tubingen, Germany.
   [Essmann, Frank] Univ Tubingen, Interfac Inst Biochem, D-72076 Tubingen, Germany.
   [Griessinger, Christoph] Univ Tubingen, Dept Preclin Imaging & Radiopharm, Werner Siemens Fdn, Lab Preclin Imaging & Imaging Technol, D-72076 Tubingen, Germany.
   [Ranta, Felicia; Ullrich, Susanne; Haering, Hans-Ulrich] Univ Tubingen, Dept Internal Med 6, D-72076 Tubingen, Germany.
   [Mocikat, Ralph] Deutsch Forschungszentrum Gesundheit & Umwelt, Helmholtz Zentrum Munchen, Inst Mol Immunol, D-81377 Munich, Germany.
   [van den Broek, Maries] Univ Zurich Hosp, Clin Oncol, CH-8091 Zurich, Switzerland.
   [Handgretinger, Rupert; Fend, Falko; Schulze-Osthoff, Klaus; Roecken, Martin] German Canc Consortium DKTK, Comprehens Canc Ctr Tubingen, D-72070 Tubingen, Germany.
   [Quintanilla-Martinez, Leticia; Fend, Falko] Univ Tubingen, Dept Pathol, D-72076 Tubingen, Germany.
   [Pesic, Marina; Zender, Lars] Univ Tubingen, Dept Internal Med 1, Div Mol Oncol Solid Tumors, D-72076 Tubingen, Germany.
C3 Eberhard Karls University of Tubingen; Eberhard Karls University Hospital; Eberhard Karls University of Tubingen; Eberhard Karls University of Tubingen; Eberhard Karls University of Tubingen; Siemens AG; Siemens Germany; Eberhard Karls University of Tubingen; Helmholtz Association; Helmholtz-Center Munich - German Research Center for Environmental Health; University of Zurich; University Zurich Hospital; Eberhard Karls University of Tubingen; Eberhard Karls University Hospital; Comprehensive Cancer Center Tubingen; Helmholtz Association; German Cancer Research Center (DKFZ); Eberhard Karls University of Tubingen; Eberhard Karls University Hospital; Eberhard Karls University of Tubingen
RP Röcken, M (corresponding author), Univ Tubingen, Dept Dermatol, Liebermeister Str 25, D-72076 Tubingen, Germany.
EM mrocken@med.uni-tuebingen.de
FU Sander Stiftung [2005.043.2, 2005.043.3]; Deutsche Krebshilfe [109037]; IZKF-Promotionskolleg 'Molekulare Medizin' [1886-0-0, PK 2011-3, PK 2012-1]; Deutsche Forschungsgemeinschaft [SFB 685, SFB 773, Wi 1279/3-1]; German Federal Ministry of Education and Research (BMBF)
NR 30
TC 600
Z9 707
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 FEB 21
PY 2013
VL 494
IS 7437
BP 361
EP 365
DI 10.1038/nature11824
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 095CS
UT WOS:000315312900040
PM 23376950
DA 2026-03-09
ER

PT J
AU Singh, R
   Ong-Abdullah, M
   Low, ETL
   Manaf, MAA
   Rosli, R
   Nookiah, R
   Ooi, LCL
   Ooi, SE
   Chan, KL
   Halim, MA
   Azizi, N
   Nagappan, J
   Bacher, B
   Lakey, N
   Smith, SW
   He, D
   Hogan, M
   Budiman, MA
   Lee, EK
   DeSalle, R
   Kudrna, D
   Goicoechea, JL
   Wing, RA
   Wilson, RK
   Fulton, RS
   Ordway, JM
   Martienssen, RA
   Sambanthamurthi, R
AF Singh, Rajinder
   Ong-Abdullah, Meilina
   Low, Eng-Ti Leslie
   Manaf, Mohamad Arif Abdul
   Rosli, Rozana
   Nookiah, Rajanaidu
   Ooi, Leslie Cheng-Li
   Ooi, Siew-Eng
   Chan, Kuang-Lim
   Halim, Mohd Amin
   Azizi, Norazah
   Nagappan, Jayanthi
   Bacher, Blaire
   Lakey, Nathan
   Smith, Steven W.
   He, Dong
   Hogan, Michael
   Budiman, Muhammad A.
   Lee, Ernest K.
   DeSalle, Rob
   Kudrna, David
   Goicoechea, Jose Luis
   Wing, Rod A.
   Wilson, Richard K.
   Fulton, Robert S.
   Ordway, Jared M.
   Martienssen, Robert A.
   Sambanthamurthi, Ravigadevi
TI Oil palm genome sequence reveals divergence of interfertile species in Old and New Worlds
SO NATURE
LA English
DT Article
ID linkage maps; mesocarp; identification; construction; annotation; maturation; generation; software; insights; protein
AB Oil palm is the most productive oil-bearing crop. Although it is planted on only 5% of the total world vegetable oil acreage, palm oil accounts for 33% of vegetable oil and 45% of edible oil worldwide, but increased cultivation competes with dwindling rainforest reserves. We report the 1.8-gigabase (Gb) genome sequence of the African oil palm Elaeis guineensis, the predominant source of worldwide oil production. A total of 1.535 Gb of assembled sequence and transcriptome data from 30 tissue types were used to predict at least 34,802 genes, including oil biosynthesis genes and homologues of WRINKLED1 (WRI1), and other transcriptional regulators(1), which are highly expressed in the kernel. We also report the draft sequence of the South American oil palm Elaeis oleifera, which has the same number of chromosomes (2n=32) and produces fertile interspecific hybrids with E. guineensis(2) but seems to have diverged in the New World. Segmental duplications of chromosome arms define the palaeotetraploid origin of palm trees. The oil palm sequence enables the discovery of genes for important traits as well as somaclonal epigenetic alterations that restrict the use of clones in commercial plantings(3), and should therefore help to achieve sustainability for biofuels and edible oils, reducing the rainforest footprint of this tropical plantation crop.
C1 [Singh, Rajinder; Ong-Abdullah, Meilina; Low, Eng-Ti Leslie; Manaf, Mohamad Arif Abdul; Rosli, Rozana; Nookiah, Rajanaidu; Ooi, Leslie Cheng-Li; Ooi, Siew-Eng; Chan, Kuang-Lim; Halim, Mohd Amin; Azizi, Norazah; Nagappan, Jayanthi; Sambanthamurthi, Ravigadevi] Persiaran Inst, Malaysian Palm Oil Board, Kajang 43000, Selangor, Malaysia.
   [Bacher, Blaire; Lakey, Nathan; Smith, Steven W.; He, Dong; Hogan, Michael; Budiman, Muhammad A.; Ordway, Jared M.] Orion Genom, St Louis, MO 63108 USA.
   [Lee, Ernest K.; DeSalle, Rob] Amer Museum Nat Hist, Sackler Inst Comparat Genom, New York, NY 10024 USA.
   [Kudrna, David; Goicoechea, Jose Luis; Wing, Rod A.] Univ Arizona, Arizona Genom Inst, Tucson, AZ 85705 USA.
   [Wilson, Richard K.; Fulton, Robert S.] Washington Univ, Sch Med, Genome Inst, St Louis, MO 63108 USA.
   [Martienssen, Robert A.] Cold Spring Harbor Lab, Howard Hughes Med Inst, Gordon & Betty Moore Fdn, Cold Spring Harbor, NY 11724 USA.
C3 Malaysian Palm Oil Board; American Museum of Natural History (AMNH); University of Arizona; Washington University (WUSTL); Cold Spring Harbor Laboratory; Howard Hughes Medical Institute
RP Martienssen, RA (corresponding author), Cold Spring Harbor Lab, Howard Hughes Med Inst, Gordon & Betty Moore Fdn, Cold Spring Harbor, NY 11724 USA.
EM martiens@cshl.edu; raviga@mpob.gov.my
FU Malaysian Palm Oil Board; NSF [0421604]; Direct For Biological Sciences; Division Of Integrative Organismal Systems [0922738, 0421604] Funding Source: National Science Foundation
NR 42
TC 438
Z9 495
U1 1
U2 182
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 15
PY 2013
VL 500
IS 7462
BP 335
EP +
DI 10.1038/nature12309
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 201AF
UT WOS:000323112400033
PM 23883927
DA 2026-03-09
ER

PT J
AU Abbas, YM
   Pichmair, A
   Górna, MW
   Superti-Furga, G
   Nagar, B
AF Abbas, Yazan M.
   Pichmair, Andreas
   Gorna, Maria W.
   Superti-Furga, Giulio
   Nagar, Bhushan
TI Structural basis for viral 5′-PPP-RNA recognition by human IFIT proteins
SO NATURE
LA English
DT Article
ID rig-i; pattern-recognition; crystal-structure; rna recognition; stranded-rna; activation; insights; isg54
AB Interferon-induced proteins with tetratricopeptide repeats (IFITs) are innate immune effector molecules that are thought to confer antiviral defence through disruption of protein-protein interactions in the host translation-initiation machinery. However, it was recently discovered that IFITs can directly recognize viral RNA bearing a 5'-triphosphate group (PPP-RNA), which is a molecular signature that distinguishes it from host RNA. Here we report crystal structures of human IFIT5, its complex with PPP-RNAs, and an amino-terminal fragment of IFIT1. The structures reveal a new helical domain that houses a positively charged cavity designed to specifically engage only single-stranded PPP-RNA, thus, distinguishing it from the canonical cytosolic sensor of double-stranded viral PPP-RNA, retinoic acid-inducible gene I (RIG-I, also known as DDX58). Mutational analysis, proteolysis and gel-shift assays reveal that PPP-RNA is bound in a non-sequence-specific manner and requires a 5'-overhang of approximately three nucleotides. Abrogation of PPP-RNA binding in Inn and IFIT5 was found to cause a defect in the antiviral response by human embryonic kidney cells. These results demonstrate the mechanism by which IFIT proteins selectively recognize viral RNA, and lend insight into their downstream effector function.
C1 [Abbas, Yazan M.; Nagar, Bhushan] McGill Univ, Dept Biochem, Montreal, PQ H3G 0B1, Canada.
   [Abbas, Yazan M.; Nagar, Bhushan] McGill Univ, Grp Rech Axe Struct Prot, Montreal, PQ H3G 0B1, Canada.
   [Pichmair, Andreas; Gorna, Maria W.; Superti-Furga, Giulio] Austrian Acad Sci, CeMM Res Ctr Mol Med, A-1090 Vienna, Austria.
   [Pichmair, Andreas] Max Planck Inst Biochem, D-82152 Martinsried, Germany.
C3 McGill University; McGill University; Austrian Academy of Sciences; CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences; Max Planck Society
RP Nagar, B (corresponding author), McGill Univ, Dept Biochem, Montreal, PQ H3G 0B1, Canada.
EM gsuperti@cemm.oeaw.ac.at; bhushan.nagar@mcgill.ca
FU Natural Sciences and Engineering Research Council of Canada; National Research Council Canada; Canadian Institutes of Health Research (CIHR) [MOP-82929]; Province of Saskatchewan, Western Economic Diversification Canada; University of Saskatchewan; Canada Research Chair; Career Development Award from the Human Frontiers Science Program [CDA 0018/2006-C/1]; Austrian Academy of Sciences; i-FIVE ERC grant; EMBO [ATLF 463-2008]; CIHR Strategic Training Initiative in Chemical Biology
NR 28
TC 201
Z9 232
U1 1
U2 74
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 7
PY 2013
VL 494
IS 7435
BP 60
EP 64
DI 10.1038/nature11783
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 087DJ
UT WOS:000314741200033
PM 23334420
DA 2026-03-09
ER

PT J
AU Hsu, CW
   Zhen, B
   Lee, J
   Chua, SL
   Johnson, SG
   Joannopoulos, JD
   Soljacic, M
AF Hsu, Chia Wei
   Zhen, Bo
   Lee, Jeongwon
   Chua, Song-Liang
   Johnson, Steven G.
   Joannopoulos, John D.
   Soljacic, Marin
TI Observation of trapped light within the radiation continuum
SO NATURE
LA English
DT Article
ID bound-states; waves
AB The ability to confine light is important both scientifically and technologically. Many light confinement methods exist, but they all achieve confinement with materials or systems that forbid outgoing waves. These systems can be implemented by metallic mirrors, by photonic band-gap materials(1), by highly disordered media (Anderson localization(2)) and, for a subset of outgoing waves, by translational symmetry (total internal reflection1) or by rotational or reflection symmetry(3,4). Exceptions to these examples exist only in theoretical proposals(5-8). Here we predict and show experimentally that light can be perfectly confined in a patterned dielectric slab, even though outgoing waves are allowed in the surrounding medium. Technically, this is an observation of an 'embedded eigenvalue' 9-namely, a bound state in a continuum of radiation modes-that is not due to symmetry incompatibility(5-8,10-16). Such a bound state can exist stably in a general class of geometries in which all of its radiation amplitudes vanish simultaneously as a result of destructive interference. This method to trap electromagnetic waves is also applicable to electronic(12) and mechanical waves(14,15).
C1 [Hsu, Chia Wei; Zhen, Bo; Lee, Jeongwon; Chua, Song-Liang; Johnson, Steven G.; Joannopoulos, John D.; Soljacic, Marin] MIT, Elect Res Lab, Cambridge, MA 02139 USA.
   [Hsu, Chia Wei] Harvard Univ, Dept Phys, Cambridge, MA 02138 USA.
   [Johnson, Steven G.] MIT, Dept Math, Cambridge, MA 02139 USA.
C3 Massachusetts Institute of Technology (MIT); Harvard University; Massachusetts Institute of Technology (MIT)
RP Hsu, CW (corresponding author), MIT, Elect Res Lab, Cambridge, MA 02139 USA.
EM cwhsu@mit.edu
FU Army Research Office through the Institute for Soldier Nanotechnologies [W911NF-07-D0004]; S3TEC, an Energy Frontier Research Center; US Department of Energy [DE-SC0001299]; Materials Research Science and Engineering Centers of the National Science Foundation [DMR-0819762]; U.S. Department of Energy (DOE) [DE-SC0001299] Funding Source: U.S. Department of Energy (DOE)
NR 20
TC 1288
Z9 1418
U1 44
U2 685
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 11
PY 2013
VL 499
IS 7457
BP 188
EP 191
DI 10.1038/nature12289
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 179YA
UT WOS:000321557600057
PM 23846657
DA 2026-03-09
ER

PT J
AU Zhao, GP
   Perilla, JR
   Yufenyuy, EL
   Meng, X
   Chen, B
   Ning, JY
   Ahn, J
   Gronenborn, AM
   Schulten, K
   Aiken, C
   Zhang, PJ
AF Zhao, Gongpu
   Perilla, Juan R.
   Yufenyuy, Ernest L.
   Meng, Xin
   Chen, Bo
   Ning, Jiying
   Ahn, Jinwoo
   Gronenborn, Angela M.
   Schulten, Klaus
   Aiken, Christopher
   Zhang, Peijun
TI Mature HIV-1 capsid structure by cryo-electron microscopy and all-atom molecular dynamics
SO NATURE
LA English
DT Article
ID protein; core; reconstructions; domain
AB Retroviral capsid proteins are conserved structurally but assemble into different morphologies(1). The mature human immunodeficiency virus-1 (HIV-1) capsid is best described by a 'fullerene cone' model(2,3), in which hexamers of the capsid protein are linked to form a hexagonal surface lattice that is closed by incorporating 12 capsid-protein pentamers. HIV-1 capsid protein contains an amino-terminal domain (NTD) comprising seven alpha-helices and a beta-hairpin(4,5), a carboxy-terminal domain (CTD) comprising four alpha-helices(6,7), and a flexible linker with a 3(10)-helix connecting the two structural domains(8). Structures of the capsid-protein assembly units have been determined by X-ray crystallography(9,10); however, structural information regarding the assembled capsid and the contacts between the assembly units is incomplete. Here we report the cryo-electron microscopy structure of a tubular HIV-1 capsid-protein assembly at 8 angstrom resolution and the three-dimensional structure of a native HIV-1 core by cryo-electron tomography. The structure of the tubular assembly shows, at the three-fold interface(11), a three-helix bundle with critical hydrophobic interactions. Mutagenesis studies confirm that hydrophobic residues in the centre of the three-helix bundle are crucial for capsid assembly and stability, and for viral infectivity. The cryo-electron-microscopy structures enable modelling by large-scale molecular dynamics simulation, resulting in all-atom models for the hexamer-of-hexamer and pentamer-of-hexamer elements as well as for the entire capsid. Incorporation of pentamers results in closer trimer contacts and induces acute surface curvature. The complete atomic HIV-1 capsid model provides a platform for further studies of capsid function and for targeted pharmacological intervention.
C1 [Zhao, Gongpu; Meng, Xin; Ning, Jiying; Ahn, Jinwoo; Gronenborn, Angela M.; Zhang, Peijun] Univ Pittsburgh, Sch Med, Dept Biol Struct, Pittsburgh, PA 15260 USA.
   [Zhao, Gongpu; Yufenyuy, Ernest L.; Meng, Xin; Ning, Jiying; Ahn, Jinwoo; Gronenborn, Angela M.; Aiken, Christopher; Zhang, Peijun] Univ Pittsburgh, Sch Med, Pittsburgh Ctr HIV Prot Interact, Pittsburgh, PA 15260 USA.
   [Perilla, Juan R.; Schulten, Klaus] Univ Illinois, Dept Phys, Urbana, IL 61801 USA.
   [Perilla, Juan R.; Schulten, Klaus] Univ Illinois, Beckman Inst, Urbana, IL 61801 USA.
   [Yufenyuy, Ernest L.; Aiken, Christopher] Vanderbilt Univ, Sch Med, Dept Pathol Microbiol & Immunol, Nashville, TN 37232 USA.
   [Chen, Bo] Univ Cent Florida, Dept Phys, Orlando, FL 32816 USA.
   [Zhang, Peijun] Univ Pittsburgh, Swanson Sch Engn, Dept Mech Engn & Mat Sci, Pittsburgh, PA 15260 USA.
C3 Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh; University of Illinois System; University of Illinois Urbana-Champaign; University of Illinois System; University of Illinois Urbana-Champaign; Vanderbilt University; State University System of Florida; University of Central Florida; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh
RP Zhang, PJ (corresponding author), Univ Pittsburgh, Sch Med, Dept Biol Struct, Pittsburgh, PA 15260 USA.
EM kschulte@ks.uiuc.edu; chris.aiken@vanderbilt.edu; pez7@pitt.edu
FU National Institutes of Health [GM082251, GM085043, GM104601]; National Science Foundation [PHY0822613, MCB0744057, OCI 07-25070]; National Institute of General Medical Sciences [P41GM104601] Funding Source: NIH RePORTER
CR Agulleiro JI, 2011, BIOINFORMATICS, V27, P582, DOI 10.1093/bioinformatics/btq692
   Bharat TAM, 2012, NATURE, V487, P385, DOI 10.1038/nature11169
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   Byeon IJL, 2012, J AM CHEM SOC, V134, P6455, DOI 10.1021/ja300937v
   Byeon IJL, 2009, CELL, V139, P780, DOI 10.1016/j.cell.2009.10.010
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   Yeager M, 2011, J MOL BIOL, V410, P534, DOI 10.1016/j.jmb.2011.04.073
NR 28
TC 667
Z9 825
U1 0
U2 333
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 30
PY 2013
VL 497
IS 7451
BP 643
EP 646
DI 10.1038/nature12162
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 152UF
UT WOS:000319556100049
PM 23719463
DA 2026-03-09
ER

PT J
AU Busby, JN
   Panjikar, S
   Landsberg, MJ
   Hurst, MRH
   Lott, JS
AF Busby, Jason N.
   Panjikar, Santosh
   Landsberg, Michael J.
   Hurst, Mark R. H.
   Lott, J. Shaun
TI The BC component of ABC toxins is an RHS-repeat-containing protein encapsulation device
SO NATURE
LA English
DT Article
ID biological macromolecules; solution scattering; crystal-structure; escherichia-coli; family; system; acquisition; teneurins; elements; complex
AB The ABC toxin complexes produced by certain bacteria are of interest owing to their potent insecticidal activity(1,2) and potential role in human disease(3). These complexes comprise at least three proteins (A, B and C), which must assemble to be fully toxic(4). The carboxyterminal region of the C protein is the main cytotoxic component(5), and is poorly conserved between different toxin complexes. A general model of action has been proposed, in which the toxin complex binds to the cell surface via the A protein, is endocytosed, and subsequently forms a pH-triggered channel, allowing the translocation of C into the cytoplasm, where it can cause cytoskeletal disruption in both insect and mammalian cells(5). Toxin complexes have been visualized using single-particle electron microscopy(6,7), but no high-resolution structures of the components are available, and the role of the B protein in the mechanism of toxicity remains unknown. Here we report the three-dimensional structure of the complex formed between the B and C proteins, determined to 2.5 angstrom by X-ray crystallography. These proteins assemble to form an unprecedented, large hollow structure that encapsulates and sequesters the cytotoxic, C-terminal region of the C protein like the shell of an egg. The shell is decorated on one end by a beta-propeller domain, which mediates attachment of the B-C heterodimer to the A protein in the native complex. The structure reveals how C auto-proteolyses when folded in complex with B. The C protein is the first example, to our knowledge, of a structure that contains rearrangement hotspot (RHS) repeats(8), and illustrates a marked structural architecture that is probably conserved across both this widely distributed bacterial protein family and the related eukaryotic tyrosine-aspartate (YD)-repeat-containing protein family, which includes the teneurins(9). The structure provides the first clues about the function of these protein repeat families, and suggests a generic mechanism for protein encapsulation and delivery.
C1 [Busby, Jason N.; Lott, J. Shaun] Univ Auckland, Sch Biol Sci, AgRes Struct Biol Lab, Auckland 1142, New Zealand.
   [Panjikar, Santosh] Australian Synchrotron, Clayton, Vic 3168, Australia.
   [Panjikar, Santosh] Monash Univ, Dept Biochem & Mol Biol, Clayton, Vic 3800, Australia.
   [Landsberg, Michael J.] Univ Queensland, Inst Mol Biosci, St Lucia, Qld 4072, Australia.
   [Hurst, Mark R. H.] AgResearch, Lincoln Res Ctr, Innovat Farming Syst, Christchurch 8140, New Zealand.
C3 University of Auckland; Australian Synchrotron; Monash University; University of Queensland; AgResearch - New Zealand
RP Lott, JS (corresponding author), Univ Auckland, Sch Biol Sci, AgRes Struct Biol Lab, Auckland 1142, New Zealand.
EM mark.hurst@agresearch.co.nz; s.lott@auckland.ac.nz
FU New Zealand Foundation for Research, Science and Technology [C10X0804]; New Zealand Ministry of Business, Innovation & Employment (MBIE) [C10X0804] Funding Source: New Zealand Ministry of Business, Innovation & Employment (MBIE)
NR 35
TC 130
Z9 156
U1 1
U2 56
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 26
PY 2013
VL 501
IS 7468
BP 547
EP +
DI 10.1038/nature12465
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 223RP
UT WOS:000324826300058
PM 23913273
DA 2026-03-09
ER

PT J
AU Jennings, JH
   Sparta, DR
   Stamatakis, AM
   Ung, RL
   Pleil, KE
   Kash, TL
   Stuber, GD
AF Jennings, Joshua H.
   Sparta, Dennis R.
   Stamatakis, Alice M.
   Ung, Randall L.
   Pleil, Kristen E.
   Kash, Thomas L.
   Stuber, Garret D.
TI Distinct extended amygdala circuits for divergent motivational states
SO NATURE
LA English
DT Article
ID ventral tegmental area; stria terminalis; bed nucleus; induced reinstatement; dopamine neurons; gaba neurons; reward; activation; afferents; behavior
AB The co-morbidity of anxiety and dysfunctional reward processing in illnesses such as addiction(1) and depression(2) suggests that common neural circuitry contributes to these disparate neuropsychiatric symptoms. The extended amygdala, including the bed nucleus of the stria terminalis (BNST), modulates fear and anxiety(3,4), but also projects to the ventral tegmental area (VTA)(5,6), a region implicated in reward and aversion(7-13), thus providing a candidate neural substrate for integrating diverse emotional states. However, the precise functional connectivity between distinct BNST projection neurons and their postsynaptic targets in the VTA, as well as the role of this circuit in controlling motivational states, have not been described. Here we record and manipulate the activity of genetically and neurochemically identified VTA-projecting BNST neurons in freely behaving mice. Collectively, aversive stimuli exposure produced heterogeneous firing patterns in VTA-projecting BNST neurons. By contrast, in vivo optically identified glutamatergic projection neurons displayed a net enhancement of activity to aversive stimuli, whereas the firing rate of identified GABAergic (gamma-aminobutyric acid-containing) projection neurons was suppressed. Channelrhodopsin-2-assisted circuit mapping revealed that both BNST glutamatergic and GABAergic projections preferentially innervate postsynaptic non-dopaminergic VTA neurons, thus providing a mechanistic framework for in vivo circuit perturbations. In vivo photostimulation of BNST glutamatergic projections resulted in aversive and anxiogenic behavioural phenotypes. Conversely, activation of BNST GABAergic projections produced rewarding and anxiolytic phenotypes, which were also recapitulated by direct inhibition of VTA GABAergic neurons. These data demonstrate that functionally opposing BNST to VTA circuits regulate rewarding and aversive motivational states, and may serve as a crucial circuit node for bidirectionally normalizing maladaptive behaviours.
C1 [Jennings, Joshua H.; Sparta, Dennis R.; Stamatakis, Alice M.; Ung, Randall L.; Stuber, Garret D.] Univ N Carolina, Dept Psychiat, Chapel Hill, NC 27599 USA.
   [Jennings, Joshua H.; Stamatakis, Alice M.; Kash, Thomas L.; Stuber, Garret D.] Univ N Carolina, Neurobiol Curriculum, Chapel Hill, NC 27599 USA.
   [Sparta, Dennis R.; Pleil, Kristen E.; Kash, Thomas L.; Stuber, Garret D.] Univ N Carolina, Bowles Ctr Alcohol Studies, Chapel Hill, NC 27599 USA.
   [Pleil, Kristen E.; Kash, Thomas L.] Univ N Carolina, Dept Pharmacol, Chapel Hill, NC 27599 USA.
   [Kash, Thomas L.; Stuber, Garret D.] Univ N Carolina, Ctr Neurosci, Chapel Hill, NC 27599 USA.
   [Stuber, Garret D.] Univ N Carolina, Dept Cell Biol & Physiol, 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; 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
RP Stuber, GD (corresponding author), Univ N Carolina, Dept Psychiat, Chapel Hill, NC 27599 USA.
EM gstuber@med.unc.edu
FU Whitehall Foundation; Foundation of Hope; National Institutes of Health [DA029325, DA032750, AA018610, AA007573, NS007431, DA034472, AA021043]; UNC NIAAA alcohol research center [AA011605]; National Institute of Neurological Disorders and Stroke [P30NS045892] Funding Source: NIH RePORTER; National Institute of Neurological Disorders and Stroke; National Institute on Drug Abuse [T32NS007431] Funding Source: NIH RePORTER; National Institute on Alcohol Abuse and Alcoholism [T32AA007573, P60AA011605] Funding Source: NIH RePORTER; National Institute on Drug Abuse [R37DA032750] Funding Source: NIH RePORTER
NR 32
TC 556
Z9 715
U1 2
U2 135
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 11
PY 2013
VL 496
IS 7444
BP 224
EP +
DI 10.1038/nature12041
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 122VM
UT WOS:000317346300042
PM 23515155
DA 2026-03-09
ER

PT J
AU Fica, SM
   Tuttle, N
   Novak, T
   Li, NS
   Lu, J
   Koodathingal, P
   Dai, Q
   Staley, JP
   Piccirilli, JA
AF Fica, Sebastian M.
   Tuttle, Nicole
   Novak, Thaddeus
   Li, Nan-Sheng
   Lu, Jun
   Koodathingal, Prakash
   Dai, Qing
   Staley, Jonathan P.
   Piccirilli, Joseph A.
TI RNA catalyses nuclear pre-mRNA splicing
SO NATURE
LA English
DT Article
ID metal-ion coordination; tetrahymena ribozyme; crystal-structure; exon-ligation; active-site; agc triad; spliceosome; mechanism; protein; steps
AB In nuclear pre-messenger RNA splicing, introns are excised by the spliceosome, a dynamic machine composed of both proteins and small nuclear RNAs (snRNAs). Over thirty years ago, after the discovery of self-splicing group II intron RNAs, the snRNAs were proposed to catalyse splicing. However, no definitive evidence for a role of either RNA or protein in catalysis by the spliceosome has been reported so far. By using metal rescue strategies in spliceosomes from budding yeast, here we show that the U6 snRNA catalyses both of the two splicing reactions by positioning divalent metals that stabilize the leaving groups during each reaction. Notably, all of the U6 catalytic metal ligands we identified correspond to the ligands observed to position catalytic, divalent metals in crystal structures of a group II intron RNA. These findings indicate that group II introns and the spliceosome share common catalytic mechanisms and probably common evolutionary origins. Our results demonstrate that RNA mediates catalysis within the spliceosome.
C1 [Fica, Sebastian M.] Univ Chicago, Grad Program Cell & Mol Biol, Chicago, IL 60637 USA.
   [Fica, Sebastian M.; Koodathingal, Prakash; Staley, Jonathan P.] Univ Chicago, Cummings Life Sci Ctr, Dept Mol Genet & Cell Biol, Chicago, IL 60637 USA.
   [Tuttle, Nicole; Lu, Jun; Dai, Qing; Piccirilli, Joseph A.] Univ Chicago, Dept Chem, Chicago, IL 60637 USA.
   [Novak, Thaddeus; Li, Nan-Sheng; Piccirilli, Joseph A.] Univ Chicago, Gordon Ctr Integrat Sci, Dept Biochem & Mol Biol, Chicago, IL 60637 USA.
C3 University of Chicago; University of Chicago; University of Chicago; University of Chicago
RP Piccirilli, JA (corresponding author), Univ Chicago, Dept Chem, 929 East 57th St, Chicago, IL 60637 USA.
EM jstaley@uchicago.edu; jpicciri@uchicago.edu
FU NSF; CBI Training Grant [5T32GM008720]; Chicago Biomedical Consortium; The Searle Funds at the Chicago Community Trust; National Institutes of Health [R01GM088656]
NR 61
TC 269
Z9 344
U1 1
U2 166
PU NATURE PUBLISHING 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 14
PY 2013
VL 503
IS 7475
BP 229
EP +
DI 10.1038/nature12734
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 250YX
UT WOS:000326894200044
PM 24196718
DA 2026-03-09
ER

PT J
AU Nel, A
   Roques, P
   Nel, P
   Prokin, AA
   Bourgoin, T
   Prokop, J
   Szwedo, J
   Azar, D
   Desutter-Grandcolas, L
   Wappler, T
   Garrouste, R
   Coty, D
   Huang, DY
   Engel, MS
   Kirejtshuk, AG
AF Nel, Andre
   Roques, Patrick
   Nel, Patricia
   Prokin, Alexander A.
   Bourgoin, Thierry
   Prokop, Jakub
   Szwedo, Jacek
   Azar, Dany
   Desutter-Grandcolas, Laure
   Wappler, Torsten
   Garrouste, Romain
   Coty, David
   Huang, Diying
   Engel, Michael S.
   Kirejtshuk, Alexander G.
TI The earliest known holometabolous insects
SO NATURE
LA English
DT Article
ID evolution; diversification; insights; fossils; land; size
AB The Eumetabola (Endopterygota (alsoknown as Holometabola) plus Paraneoptera)(1) have the highest number of species of any clade, and greatly contribute to animal species biodiversity(2,3). The palaeoeco-logical circumstances that favoured their emergence and success remain an intriguing question(3-6). Recent molecular phylogenetic analyses have suggested a wide range of dates for the initial appearance of the Holometabola, from the Middle Devonian epoch (391 million years (Myr) ago) to the Late Pennsylvanian epoch (311 Myr ago(7-12)), and Hemiptera (310 Myr ago(13)). Palaeoenvironments greatly changed over these periods, with global cooling and increasing complexity of green forests(14). The Pennsylvanian-period crown-eumetabolan fossil record remains notably incomplete(15-1)9, particularly as several fossils have been erroneously considered to be stemHolometabola(1,15,20,21) (Supplementary Information); the earliest definitive beetles are from the start of the Permian period(21,22). The emergence of the hymenopterids, sister group to other Holometabola, is dated between 350 and 309 Myr ago(8,9,12), incongruent with their current earliest record(Middle Triassic epoch)(1,20). Here we describe five fossils-aGzhelian-age stem coleopterid, a holometabolous larva of uncertain ordinal affinity, a stem hymenopterid, and early Hemiptera and Psocodea, all from the Moscovian age-and reveal a notable penecontemporaneous breadth of early eumetabolan insects. These discoveries are more congruent with current hypotheses of clade divergence. Eumetabola experienced episodes of diversification during the Bashkirian-Moscovian and the Kasimovian-Gzhelian ages. This cladogenetic activity is perhaps related to notable episodes of drying resulting from glaciations, leading to the eventual demise in Euramerica of coal-swamp ecosystems, evidenced by floral turnover during this interval(23,24). These ancient species were of very small size, living in the shadow of Palaeozoic-era 'giant' insects. Although these discoveries reveal unexpected Pennsylvanian eumetabolan diversity, the lineage radiated more successfully only after the mass extinctions at the end of the Permian period, giving rise to the familiar crown groups of their respective clades.
C1 [Nel, Andre; Roques, Patrick; Nel, Patricia; Bourgoin, Thierry; Azar, Dany; Desutter-Grandcolas, Laure; Garrouste, Romain; Coty, David; Kirejtshuk, Alexander G.] Museum Natl Hist Nat, CNRS, UMR 7205, F-75231 Paris, France.
   [Nel, Patricia] AgroParisTech, Dept Sci Vie & Sante, F-75231 Paris 05, France.
   [Prokin, Alexander A.] Russian Acad Sci, Papanin Inst Biol Inland Waters, Borok 152742, Yaroslavl Oblas, Russia.
   [Prokop, Jakub] Charles Univ Prague, Fac Sci, Dept Zool, CZ-12844 Prague 2, Czech Republic.
   [Szwedo, Jacek] Polish Acad Sci, Museum & Inst Zool, Dept Palaeozool, PL-00679 Warsaw, Poland.
   [Azar, Dany] Lebanese Univ, Fac Sci 2, Dept Nat Sci, Fanar, Fanar Matn, Lebanon.
   [Wappler, Torsten] Univ Bonn, Steinmann Inst Geol Mineral & Palaontol, D-53115 Bonn, Germany.
   [Huang, Diying] Chinese Acad Sci, Nanjing Inst Geol & Palaeontol, State Key Lab Palaeobiol & Stratig, Nanjing 210008, Jiangsu, Peoples R China.
   [Engel, Michael S.] Univ Kansas, Div Entomol, Nat Hist Museum, Lawrence, KS 66045 USA.
   [Engel, Michael S.] Univ Kansas, Dept Ecol Evolutionary Biol, Lawrence, KS 66045 USA.
   [Kirejtshuk, Alexander G.] Russian Acad Sci, Zool Inst, St Petersburg, Russia.
C3 Sorbonne Universite; Centre National de la Recherche Scientifique (CNRS); CNRS - Institute of Ecology & Environment (INEE); Museum National d'Histoire Naturelle (MNHN); AgroParisTech; Russian Academy of Sciences; Papanin Institute for Biology of Inland Waters; Charles University Prague; Polish Academy of Sciences; Museum & Institute of Zoology of the Polish Academy of Sciences; Lebanese University; University of Bonn; Chinese Academy of Sciences; University of Kansas; University of Kansas; Russian Academy of Sciences; Zoological Institute of the Russian Academy of Sciences
RP Nel, A (corresponding author), Museum Natl Hist Nat, CNRS, UMR 7205, CP 50,45 Rue Buffon, F-75231 Paris, France.
EM anel@mnhn.fr
FU Grant Agency of the Czech Republic [P210/10/0633]; German Science Foundation [WA 1492/6-1]; Russian Foundation of Basic Research [12-04-00663-a]
NR 30
TC 194
Z9 206
U1 0
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 NOV 14
PY 2013
VL 503
IS 7475
BP 257
EP +
DI 10.1038/nature12629
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 250YX
UT WOS:000326894200050
PM 24132233
DA 2026-03-09
ER

PT J
AU Manolaridis, I
   Kulkarni, K
   Dodd, RB
   Ogasawara, S
   Zhang, ZG
   Bineva, G
   O'Reilly, N
   Hanrahan, SJ
   Thompson, AJ
   Cronin, N
   Iwata, S
   Barford, D
AF Manolaridis, Ioannis
   Kulkarni, Kiran
   Dodd, Roger B.
   Ogasawara, Satoshi
   Zhang, Ziguo
   Bineva, Ganka
   O'Reilly, Nicola
   Hanrahan, Sarah J.
   Thompson, Andrew J.
   Cronin, Nora
   Iwata, So
   Barford, David
TI Mechanism of farnesylated CAAX protein processing by the intramembrane protease Rce1
SO NATURE
LA English
DT Article
ID secondary structure; structural basis; a-factor; crystal-structure; ras; endoproteolysis; localization; trafficking; specificity; reveals
AB CAAX proteins have essential roles in multiple signalling pathways, controlling processes such as proliferation, differentiation and carcinogenesis(1). The similar to 120 mammalian CAAX proteins function at cellular membranes and include the Ras superfamily of small GTPases, nuclear lamins, the gamma-subunit of heterotrimeric GTPases, and several protein kinases and phosphatases(2). The proper localization of CAAX proteins to cell membranes is orchestrated by a series of post-translational modifications of the carboxy-terminal CAAX motifs(3) (where C is cysteine, A is an aliphatic amino acid and X is any amino acid). These reactions involve prenylation of the cysteine residue, cleavage at the AAX tripeptide and methylation of the carboxyl-prenylated cysteine residue. The major CAAX protease activity is mediated by Rce1 (Ras and a-factor converting enzyme 1), an intramembrane protease (IMP) of the endoplasmic reticulum(4,5). Information on the architecture and proteolytic mechanism of Rce1 has been lacking. Here we report the crystal structure of a Methano-coccus maripaludis homologue of Rce1, whose endopeptidase specificity for farnesylated peptides mimics that of eukaryotic Rce1. Its structure, comprising eight transmembrane alpha-helices, and catalytic site are distinct from those of other IMPs. The catalytic residues are located similar to 10 angstrom into the membrane and are exposed to the cytoplasm and membrane through a conical cavity that accommodates the prenylated CAAX substrate. We propose that the farnesyl lipid binds to a site at the opening of two transmembrane alpha-helices, which results in the scissile bond being positioned adjacent to a glutamate-activated nucleophilic water molecule. This study suggests that Rce1 is the founding member of a novel IMP family, the glutamate IMPs.
C1 [Manolaridis, Ioannis; Kulkarni, Kiran; Dodd, Roger B.; Zhang, Ziguo; Hanrahan, Sarah J.; Thompson, Andrew J.; Cronin, Nora; Barford, David] Inst Canc Res, London SW3 6JB, England.
   [Ogasawara, Satoshi; Iwata, So] Kyoto Univ, Grad Sch Med, Dept Cell Biol, Sakyo Ku, Kyoto 6068501, Japan.
   [Ogasawara, Satoshi; Iwata, So] JST, Res Accelerat Program, Membrane Prot Crystallog Project, Sakyo Ku, Kyoto 6068501, Japan.
   [Bineva, Ganka; O'Reilly, Nicola] Canc Res UK London Res Inst, London WC2A 3LY, England.
   [Iwata, So] Univ London Imperial Coll Sci Technol & Med, Dept Life Sci, London SW7 2AZ, England.
C3 Royal Marsden NHS Foundation Trust; University of London; Institute of Cancer Research - UK; Kyoto University; Japan Science & Technology Agency (JST); Cancer Research UK; Imperial College London
RP Barford, D (corresponding author), Inst Canc Res, 237 Fulham Rd, London SW3 6JB, England.
EM dbarford@mrc-lmb.cam.ac.uk
FU Cancer Research UK; Japan Science and Technology agency; BBSRC [BB/G023425/1]; Biotechnology and Biological Sciences Research Council [BB/G023425/1] Funding Source: researchfish; Cancer Research UK [14109] Funding Source: researchfish; Medical Research Council [MC_UP_1201/6] Funding Source: researchfish; BBSRC [BB/G023425/1] Funding Source: UKRI; MRC [MC_UP_1201/6] Funding Source: UKRI
NR 51
TC 146
Z9 199
U1 0
U2 80
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 12
PY 2013
VL 504
IS 7479
BP 301
EP +
DI 10.1038/nature12754
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 267TQ
UT WOS:000328121500041
PM 24291792
DA 2026-03-09
ER

PT J
AU Amador, A
   Perl, YS
   Mindlin, GB
   Margoliash, D
AF Amador, Ana
   Sanz Perl, Yonatan
   Mindlin, Gabriel B.
   Margoliash, Daniel
TI Elemental gesture dynamics are encoded by song premotor cortical neurons
SO NATURE
LA English
DT Article
ID brain-stem; generation; integration; mechanisms; frequency; responses; nucleus; network; sleep; model
AB Quantitative biomechanical models can identify control parameters that are used during movements, and movement parameters that are encoded by premotor neurons. We fit a mathematical dynamical systems model including subsyringeal pressure, syringeal biomechanics and upper-vocal-tract filtering to the songs of zebra finches. This reduces the dimensionality of singing dynamics, described as trajectories (motor 'gestures') in a space of syringeal pressure and tension. Here we assess model performance by characterizing the auditory response 'replay' of song premotor HVC neurons to the presentation of song variants in sleeping birds, and by examining HVC activity in singing birds. HVC projection neurons were excited and interneurons were suppressed within a few milliseconds of the extreme time points of the gesture trajectories. Thus, the HVC precisely encodes vocal motor output through activity at the times of extreme points of movement trajectories. We propose that the sequential activity of HVC neurons is used as a 'forward' model, representing the sequence of gestures in song to make predictions on expected behaviour and evaluate feedback.
C1 [Amador, Ana; Margoliash, Daniel] Univ Chicago, Dept Organismal Biol & Anat, Chicago, IL 60637 USA.
   [Sanz Perl, Yonatan; Mindlin, Gabriel B.] Univ Buenos Aires, FCEN, Dept Phys, RA-1428 Buenos Aires, DF, Argentina.
C3 University of Chicago; University of Buenos Aires
RP Margoliash, D (corresponding author), Univ Chicago, Dept Organismal Biol & Anat, 1027 East 57th St, Chicago, IL 60637 USA.
EM dan@bigbird.uchicago.edu
FU Human Frontiers Science Program cross-disciplinary fellowship; ANCyT; CONICET; UBA; NIDCD; NSF/CRCNS;  [NIDCD006876]
NR 40
TC 140
Z9 170
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 MAR 7
PY 2013
VL 495
IS 7439
BP 59
EP 64
DI 10.1038/nature11967
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 105BE
UT WOS:000316039800039
PM 23446354
DA 2026-03-09
ER

PT J
AU Nagano, T
   Lubling, Y
   Stevens, TJ
   Schoenfelder, S
   Yaffe, E
   Dean, W
   Laue, ED
   Tanay, A
   Fraser, P
AF Nagano, Takashi
   Lubling, Yaniv
   Stevens, Tim J.
   Schoenfelder, Stefan
   Yaffe, Eitan
   Dean, Wendy
   Laue, Ernest D.
   Tanay, Amos
   Fraser, Peter
TI Single-cell Hi-C reveals cell-to-cell variability in chromosome structure
SO NATURE
LA English
DT Article
ID gene-regulation; nuclear-organization; yeast genome; conformation; architecture; transcription; associations; territory; principles; landscape
AB Large-scale chromosome structure and spatial nuclear arrangement have been linked to control of gene expression and DNA replication and repair. Genomic techniques based on chromosome conformation capture (3C) assess contacts for millions of loci simultaneously, but do so by averaging chromosome conformations from millions of nuclei. Here we introduce single-cell Hi-C, combined with genome-wide statistical analysis and structural modelling of single-copy X chromosomes, to show that individual chromosomes maintain domain organization at the megabase scale, but show variable cell-to-cell chromosome structures at larger scales. Despite this structural stochasticity, localization of active gene domains to boundaries of chromosome territories is a hallmark of chromosomal conformation. Single-cell Hi-C data bridge current gaps between genomics and microscopy studies of chromosomes, demonstrating how modular organization underlies dynamic chromosome structure, and how this structure is probabilistically linked with genome activity patterns.
C1 [Nagano, Takashi; Schoenfelder, Stefan; Fraser, Peter] Babraham Inst, Nucl Dynam Programme, Cambridge CB22 3AT, England.
   [Lubling, Yaniv; Yaffe, Eitan; Tanay, Amos] Weizmann Inst Sci, Dept Comp Sci & Appl Math, IL-76100 Rehovot, Israel.
   [Lubling, Yaniv; Yaffe, Eitan; Tanay, Amos] Weizmann Inst Sci, Dept Regulat Biol, IL-76100 Rehovot, Israel.
   [Stevens, Tim J.; Laue, Ernest D.] Univ Cambridge, Dept Biochem, Cambridge CB2 1GA, England.
   [Dean, Wendy] Babraham Inst, Epigenet Programme, Cambridge CB22 3AT, England.
C3 UK Research & Innovation (UKRI); Biotechnology and Biological Sciences Research Council (BBSRC); Babraham Institute; Weizmann Institute of Science; Weizmann Institute of Science; University of Cambridge; UK Research & Innovation (UKRI); Biotechnology and Biological Sciences Research Council (BBSRC); Babraham Institute
RP Fraser, P (corresponding author), Babraham Inst, Nucl Dynam Programme, Cambridge CB22 3AT, England.
EM e.d.laue@bioc.cam.ac.uk; amos.tanay@weizmann.ac.il; peter.fraser@babraham.ac.uk
FU Medical Research Council; Biotechnology and Biological Sciences Research Council; MODHEP project; Israel Science Foundation; Wellcome Trust; Biotechnology and Biological Sciences Research Council [BBS/E/B/0000C151, BBS/E/B/000C0404] Funding Source: researchfish; Medical Research Council [G117/530, G0800036] Funding Source: researchfish; BBSRC [BBS/E/B/000C0404, BBS/E/B/0000C151] Funding Source: UKRI; MRC [G0800036, G117/530] Funding Source: UKRI
NR 32
TC 1175
Z9 1552
U1 0
U2 259
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 3
PY 2013
VL 502
IS 7469
BP 59
EP +
DI 10.1038/nature12593
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 227IM
UT WOS:000325106000030
PM 24067610
DA 2026-03-09
ER

PT J
AU Bhatt, S
   Gething, PW
   Brady, OJ
   Messina, JP
   Farlow, AW
   Moyes, CL
   Drake, JM
   Brownstein, JS
   Hoen, AG
   Sankoh, O
   Myers, MF
   George, DB
   Jaenisch, T
   Wint, GRW
   Simmons, CP
   Scott, TW
   Farrar, JJ
   Hay, SI
AF Bhatt, Samir
   Gething, Peter W.
   Brady, Oliver J.
   Messina, Jane P.
   Farlow, Andrew W.
   Moyes, Catherine L.
   Drake, John M.
   Brownstein, John S.
   Hoen, Anne G.
   Sankoh, Osman
   Myers, Monica F.
   George, Dylan B.
   Jaenisch, Thomas
   Wint, G. R. William
   Simmons, Cameron P.
   Scott, Thomas W.
   Farrar, Jeremy J.
   Hay, Simon I.
TI The global distribution and burden of dengue
SO NATURE
LA English
DT Article
ID plasmodium-falciparum; yellow-fever; disease; transmission; endemicity; vaccine; vector; virus
AB Dengue is a systemic viral infection transmitted between humans by Aedes mosquitoes(1). For some patients, dengue is a life-threatening illness(2). There are currently no licensed vaccines or specific therapeutics, and substantial vector control efforts have not stopped its rapid emergence and global spread(3). The contemporary worldwide distribution of the risk of dengue virus infection(4) and its public health burden are poorly known(2,5). Here we undertake an exhaustive assembly of known records of dengue occurrence worldwide, and use a formal modelling framework to map the global distribution of dengue risk. We then pair the resulting risk map with detailed longitudinal information from dengue cohort studies and population surfaces to infer the public health burden of dengue in 2010. We predict dengue to be ubiquitous throughout the tropics, with local spatial variations in risk influenced strongly by rainfall, temperature and the degree of urbanization. Using cartographic approaches, we estimate there to be 390 million (95% credible interval 284-528) dengue infections per year, of which 96 million (67-136) manifest apparently (any level of disease severity). This infection total is more than three times the dengue burden estimate of the World Health Organization(2). Stratification of our estimates by country allows comparison with national dengue reporting, after taking into account the probability of an apparent infection being formally reported. The most notable differences are discussed. These new risk maps and infection estimates provide novel insights into the global, regional and national public health burden imposed by dengue. We anticipate that they will provide a starting point for a wider discussion about the global impact of this disease and will help to guide improvements in disease control strategies using vaccine, drug and vector control methods, and in their economic evaluation.
C1 [Bhatt, Samir; Gething, Peter W.; Brady, Oliver J.; Messina, Jane P.; Farlow, Andrew W.; Moyes, Catherine L.; Drake, John M.; Myers, Monica F.; Wint, G. R. William; Hay, Simon I.] Univ Oxford, Dept Zool, Spatial Ecol & Epidemiol Grp, Oxford OX1 3PS, England.
   [Brady, Oliver J.] Oxitec Ltd, Abingdon OX14 4RX, Oxon, England.
   [Drake, John M.] Univ Georgia, Odum Sch Ecol, Athens, GA 30602 USA.
   [Brownstein, John S.] Harvard Univ, Sch Med, Dept Phys, Boston, MA 02115 USA.
   [Brownstein, John S.] Boston Childrens Hosp, Childrens Hosp Informat Program, Boston, MA 02115 USA.
   [Hoen, Anne G.] Dartmouth Coll, Geisel Sch Med, Dept Community & Family Med, Hanover, NH 03755 USA.
   [Sankoh, Osman] INDEPTH Network Secretariat, East Legon, Accra, Ghana.
   [Sankoh, Osman] Univ Witwatersrand, Sch Publ Hlth, ZA-2000 Johannesburg, South Africa.
   [Sankoh, Osman] Heidelberg Univ, Inst Publ Hlth, D-69120 Heidelberg, Germany.
   [George, Dylan B.; Scott, Thomas W.; Hay, Simon I.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
   [Jaenisch, Thomas] Univ Heidelberg Hosp, Dept Infect Dis, Sect Clin Trop Med, INF 324, D-69120 Heidelberg, Germany.
   [Wint, G. R. William] Univ Oxford, Dept Zool, ERGO, Oxford OX1 3PS, England.
   [Simmons, Cameron P.; Farrar, Jeremy J.] Oxford Univ Clin Res Unit, Hosp Trop Dis, Ho Chi Minh City, Vietnam.
   [Simmons, Cameron P.; Farrar, Jeremy J.] Univ Oxford, Churchill Hosp, Ctr Trop Med, Oxford OX3 7LJ, England.
   [Scott, Thomas W.] Univ Calif Davis, Dept Entomol, Davis, CA 95616 USA.
   [Farrar, Jeremy J.] Natl Univ Singapore, Dept Med, Singapore 119228, Singapore.
C3 University of Oxford; University System of Georgia; University of Georgia; Harvard University; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Dartmouth College; INDEPTH Network; University of Witwatersrand; Ruprecht Karls University Heidelberg; National Institutes of Health (NIH) - USA; NIH Fogarty International Center (FIC); Ruprecht Karls University Heidelberg; University of Oxford; University of Oxford; University of California System; University of California Davis; National University of Singapore
RP Hay, SI (corresponding author), Univ Oxford, Dept Zool, Spatial Ecol & Epidemiol Grp, Tinbergen Bldg,South Parks Rd, Oxford OX1 3PS, England.
EM simon.hay@zoo.ox.ac.uk
FU Wellcome Trust [095066, 084368]; BBSRC Industrial CASE studentship; International Research Consortium on Dengue Risk Assessment Management and Surveillance (IDAMS) [21803]; EU [2011-261504 EDENEXT]; RAPIDD program of the Science & Technology Directorate, Department of Homeland Security; Fogarty International Center, National Institutes of Health; Biotechnology and Biological Sciences Research Council [1090403] Funding Source: researchfish; National Health and Medical Research Council (NHMRC) [1090403] Funding Source: National Health and Medical Research Council (NHMRC)
NR 30
TC 7192
Z9 8407
U1 38
U2 1578
PU NATURE PUBLISHING 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 25
PY 2013
VL 496
IS 7446
BP 504
EP 507
DI 10.1038/nature12060
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 131HU
UT WOS:000317984400041
PM 23563266
DA 2026-03-09
ER

PT J
AU Winther, AML
   Bublitz, M
   Karlsen, JL
   Moller, JV
   Hansen, JB
   Nissen, P
   Buch-Pedersen, MJ
AF Winther, Anne-Marie L.
   Bublitz, Maike
   Karlsen, Jesper L.
   Moller, Jesper V.
   Hansen, John B.
   Nissen, Poul
   Buch-Pedersen, Morten J.
TI The sarcolipin-bound calcium pump stabilizes calcium sites exposed to the cytoplasm
SO NATURE
LA English
DT Article
ID sarcoplasmic-reticulum; ca-2+ pump; phospholamban; ca2+-atpase; ca2+; binding; mechanism; atpase; phosphorylation; association
AB The contraction and relaxation of muscle cells is controlled by the successive rise and fall of cytosolic Ca2+, initiated by the release of Ca2+ from the sarcoplasmic reticulum and terminated by re-sequestration of Ca2+ into the sarcoplasmic reticulum. as the main mechanism of Ca2+ removal. Re-sequestration requires active transport and is catalysed by the sarcoplasmic reticulum Ca2+-ATPase (SERCA), which has a key role in defining the contractile properties of skeletal and heart muscle tissue. The activity of SERCA is regulated by two small, homologous membrane proteins called phospholamban (PLB, also known as PLN) and sarcolipin (SLN)(1,2). Detailed structural information explaining this regulatory mechanism has been lacking, and the structural features defining the pathway through which cytoplasmic Ca2+ enters the intramembranous binding sites of SERCA have remained unknown. Here we report the crystal structure of rabbit SERCA1a (also known as ATP2A1) in complex with SLN at 3.1 angstrom resolution. The regulatory SLN traps the Ca2+-ATPase in a previously undescribed E1 state, with exposure of the Ca2+ sites through an open cytoplasmic pathway stabilized by Mg2+. The structure suggests a mechanism for selective Ca2+ loading and activation of SERCA, and provides new insight into how SLN and PLB inhibition arises from stabilization of this E1 intermediate state without bound Ca2+. These findings may prove useful in studying how autoinhibitory domains of other ion pumps modulate transport across biological membranes.
C1 [Winther, Anne-Marie L.; Hansen, John B.; Buch-Pedersen, Morten J.] Pcovery, DK-1871 Frederiksberg, Denmark.
   [Winther, Anne-Marie L.; Bublitz, Maike; Karlsen, Jesper L.; Moller, Jesper V.; Nissen, Poul] Danish Natl Res Fdn, Ctr Membrane Pumps Cells & Dis PUMPkin, DK-8000 Aarhus C, Denmark.
   [Winther, Anne-Marie L.; Bublitz, Maike; Karlsen, Jesper L.; Nissen, Poul] Aarhus Univ, Dept Mol Biol & Genet, DK-8000 Aarhus, Denmark.
   [Moller, Jesper V.] Aarhus Univ, Dept Biomed, DK-8000 Aarhus, Denmark.
C3 Danmarks Grundforskningsfond; Aarhus University; Aarhus University
RP Nissen, P (corresponding author), Danish Natl Res Fdn, Ctr Membrane Pumps Cells & Dis PUMPkin, DK-8000 Aarhus C, Denmark.
EM pn@mb.au.dk; mbp@pcovery.com
FU Danish Council for Independent Research (Technology and Production Sciences); Danish National Advanced Technology Foundation; ERC; Danish Research Council for Strategic Research
NR 30
TC 170
Z9 186
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 MAR 14
PY 2013
VL 495
IS 7440
BP 265
EP 269
DI 10.1038/nature11900
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 113FP
UT WOS:000316652300057
PM 23455424
DA 2026-03-09
ER

PT J
AU Montagnac, G
   Meas-Yedid, V
   Irondelle, M
   Castro-Castro, A
   Franco, M
   Shida, T
   Nachury, MV
   Benmerah, A
   Olivo-Marin, JC
   Chavrier, P
AF Montagnac, Guillaume
   Meas-Yedid, Vannary
   Irondelle, Marie
   Castro-Castro, Antonio
   Franco, Michel
   Shida, Toshinobu
   Nachury, Maxence V.
   Benmerah, Alexandre
   Olivo-Marin, Jean-Christophe
   Chavrier, Philippe
TI αTAT1 catalyses microtubule acetylation at clathrin-coated pits
SO NATURE
LA English
DT Article
ID posttranslational modifications; tubulin; hdac6; acetyltransferase; stabilization; trafficking; endocytosis; migration; proteins; integrin
AB In most eukaryotic cells microtubules undergo post-translational modifications such as acetylation of alpha-tubulin on lysine 40, a wide-spread modification restricted to a subset of microtubules that turns over slowly(1). This subset of stable microtubules accumulates in cell protrusions(2) and regulates cell polarization(3), migration and invasion(4-7). However, mechanisms restricting acetylation to these microtubules are unknown. Here we report that clathrin-coated pits (CCPs) control microtubule acetylation through a direct interaction of the alpha-tubulin acetyltransferase alpha TAT1 (refs 8, 9) with the clathrin adaptor AP2. We observe that about one-third of growing microtubule ends contact and pause at CCPs and that loss of CCPs decreases lysine 40 acetylation levels. We show that alpha TAT1 localizes to CCPs through a direct interaction with AP2 that is required for microtubule acetylation. In migrating cells, the polarized orientation of acetylated microtubules correlates with CCP accumulation at the leading edge(10), and interaction of alpha TAT1 with AP2 is required for directional migration. We conclude that microtubules contacting CCPs become acetylated by alpha TAT1. In migrating cells, this mechanism ensures the acetylation of microtubules oriented towards the leading edge, thus promoting directional cell locomotion and chemotaxis.
C1 [Montagnac, Guillaume; Irondelle, Marie; Castro-Castro, Antonio; Chavrier, Philippe] Inst Curie, Res Ctr, F-75005 Paris, France.
   [Montagnac, Guillaume; Irondelle, Marie; Castro-Castro, Antonio; Chavrier, Philippe] CNRS, UMR 144, F-75005 Paris, France.
   [Meas-Yedid, Vannary; Olivo-Marin, Jean-Christophe] Inst Pasteur, CNRS, URA 2582, Unite Anal Images Quantitat, F-75015 Paris, France.
   [Franco, Michel] Univ Nice Sophia Antipolis, CNRS, UMR 6097, Inst Pharmacol Mol & Cellulaire, F-06560 Valbonne, France.
   [Shida, Toshinobu; Nachury, Maxence V.] Stanford Univ, Sch Med, Dept Mol & Cellular Physiol, Stanford, CA 94305 USA.
   [Benmerah, Alexandre] Hop Necker Enfants Malad, INSERM, U983, F-75015 Paris, France.
   [Benmerah, Alexandre] Univ Paris 05, Sorbonne Paris Cite, Inst Imagine, F-75015 Paris, France.
C3 UNICANCER; Universite PSL; Institut Curie; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB); Sorbonne Universite; Universite PSL; UNICANCER; Institut Curie; Pasteur Network; Universite Paris Cite; Institut Pasteur Paris; Centre National de la Recherche Scientifique (CNRS); Universite Cote d'Azur; Centre National de la Recherche Scientifique (CNRS); Stanford University; Assistance Publique Hopitaux Paris (APHP); Universite Paris Cite; Hopital Universitaire Necker-Enfants Malades - APHP; Institut National de la Sante et de la Recherche Medicale (Inserm); Institut National de la Sante et de la Recherche Medicale (Inserm); Universite Paris Cite
RP Montagnac, G (corresponding author), Inst Curie, Res Ctr, F-75005 Paris, France.
EM guillaume.montagnac@curie.fr; philippe.chavrier@curie.fr
FU Institut Curie; CNRS; Fondation ARC pour la Recherche contre le Cancer [SL220100601356]; Institut National du Cancer [2009-1-PL BIO-12-IC-1]; National Institute of General Medical Sciences [R01GM089933] Funding Source: NIH RePORTER
NR 34
TC 92
Z9 112
U1 1
U2 39
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 24
PY 2013
VL 502
IS 7472
BP 567
EP +
DI 10.1038/nature12571
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 238YN
UT WOS:000325988400058
PM 24097348
DA 2026-03-09
ER

PT J
AU Haydon, MJ
   Mielczarek, O
   Robertson, FC
   Hubbard, KE
   Webb, AAR
AF Haydon, Michael J.
   Mielczarek, Olga
   Robertson, Fiona C.
   Hubbard, Katharine E.
   Webb, Alex A. R.
TI Photosynthetic entrainment of the Arabidopsis thaliana circadian clock
SO NATURE
LA English
DT Article
ID pseudo-response regulators; signal-transduction; gene-expression; phytochrome-a; protein; encodes; light; transcription; oscillators; homeostasis
AB Circadian clocks provide a competitive advantage in an environment that is heavily influenced by the rotation of the Earth(1,2), by driving daily rhythms in behaviour, physiology and metabolism in bacteria, fungi, plants and animals(3,4). Circadian clocks comprise transcription-translation feedback loops, which are entrained by environmental signals such as light and temperature to adjust the phase of rhythms to match the local environment(3). The production of sugars by photosynthesis is a key metabolic output of the circadian clock in plants(2,5). Here we show that these rhythmic, endogenous sugar signals can entrain circadian rhythms in Arabidopsis thaliana by regulating the gene expression of circadian clock components early in the photoperiod, thus defining a 'metabolic dawn'. By inhibiting photosynthesis, we demonstrate that endogenous oscillations in sugar levels provide metabolic feedback to the circadian oscillator through the morning-expressed gene PSEUDO-RESPONSE REGULATOR 7 (PRR7), and we identify that prr7 mutants are insensitive to the effects of sucrose on the circadian period. Thus, photosynthesis has a marked effect on the entrainment and maintenance of robust circadian rhythms in A. thaliana, demonstrating that metabolism has a crucial role in regulation of the circadian clock.
C1 [Haydon, Michael J.; Mielczarek, Olga; Robertson, Fiona C.; Hubbard, Katharine E.; Webb, Alex A. R.] Univ Cambridge, Dept Plant Sci, Cambridge CB2 3EA, England.
C3 University of Cambridge
RP Webb, AAR (corresponding author), Univ Cambridge, Dept Plant Sci, Cambridge CB2 3EA, England.
EM aarw2@cam.ac.uk
FU BBSRC [BB/H006826/1]; BBSRC [BB/H006826/1, BB/D017904/1] Funding Source: UKRI; Biotechnology and Biological Sciences Research Council [BB/D017904/1, BB/H006826/1] Funding Source: researchfish
NR 45
TC 320
Z9 360
U1 3
U2 320
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 31
PY 2013
VL 502
IS 7473
BP 689
EP +
DI 10.1038/nature12603
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 243CC
UT WOS:000326293200049
PM 24153186
DA 2026-03-09
ER

PT J
AU Pla, JJ
   Tan, KY
   Dehollain, JP
   Lim, WH
   Morton, JJL
   Zwanenburg, FA
   Jamieson, DN
   Dzurak, AS
   Morello, A
AF Pla, Jarryd J.
   Tan, Kuan Y.
   Dehollain, Juan P.
   Lim, Wee H.
   Morton, John J. L.
   Zwanenburg, Floris A.
   Jamieson, David N.
   Dzurak, Andrew S.
   Morello, Andrea
TI High-fidelity readout and control of a nuclear spin qubit in silicon
SO NATURE
LA English
DT Article
ID single-shot readout; electron-spin; quantum; memory; storage
AB Detection of nuclear spin precession is critical for a wide range of scientific techniques that have applications in diverse fields including analytical chemistry, materials science, medicine and biology. Fundamentally, it is possible because of the extreme isolation of nuclear spins from their environment. This isolation also makes single nuclear spins desirable for quantum-information processing, as shown by pioneering studies on nitrogen-vacancy centres in diamond(1-4). The nuclear spin of a P-31 donor in silicon is very promising as a quantum bit(5): bulk measurements indicate that it has excellent coherence times(6,7) and silicon is the dominant material in the microelectronics industry. Here we demonstrate electrical detection and coherent manipulation of a single P-31 nuclear spin qubit with sufficiently high fidelities for fault-tolerant quantum computing(8). By integrating single-shot readout of the electron spin(9) with on-chip electron spin resonance(10), we demonstrate quantum non-demolition(11) and electrical single-shot readout of the nuclear spin with a readout fidelity higher than 99.8 per cent-the highest so far reported for any solid-state qubit. The single nuclear spin is then operated as a qubit by applying coherent radio-frequency pulses. For an ionized P-31 donor, we find a nuclear spin coherence time of 60 milliseconds and a one-qubit gate control fidelity exceeding 98 per cent. These results demonstrate that the dominant technology of modern electronics can be adapted to host a complete electrical measurement and control platform for nuclear-spin-based quantum-information processing.
C1 [Pla, Jarryd J.; Tan, Kuan Y.; Dehollain, Juan P.; Lim, Wee H.; Zwanenburg, Floris A.; Dzurak, Andrew S.; Morello, Andrea] Univ New S Wales, Sch Elect Engn & Telecommun, Ctr Quantum Computat & Commun Technol, Sydney, NSW 2052, Australia.
   [Morton, John J. L.] UCL, London Ctr Nanotechnol, London WC1H 0AH, England.
   [Jamieson, David N.] Univ Melbourne, Sch Phys, Ctr Quantum Computat & Commun Technol, Melbourne, Vic 3010, Australia.
C3 University of New South Wales Sydney; University of London; University College London; University of Melbourne
RP Morello, A (corresponding author), Univ New S Wales, Sch Elect Engn & Telecommun, Ctr Quantum Computat & Commun Technol, Sydney, NSW 2052, Australia.
EM a.morello@unsw.edu.au
FU Australian Research Council Centre of Excellence for Quantum Computation and Communication Technology [CE11E0096]; US Army Research Office [W911NF-13-1-0024]; Australian National Fabrication Facility; Engineering and Physical Sciences Research Council [EP/H025952/1, EP/H025952/2, EP/I035536/2, EP/I035536/1] Funding Source: researchfish; EPSRC [EP/H025952/2, EP/H025952/1, EP/I035536/2, EP/I035536/1] Funding Source: UKRI
NR 30
TC 466
Z9 516
U1 2
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 APR 18
PY 2013
VL 496
IS 7445
BP 334
EP 338
DI 10.1038/nature12011
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 126FV
UT WOS:000317599200031
PM 23598342
DA 2026-03-09
ER

PT J
AU Finkelstein, SL
   Papovich, C
   Dickinson, M
   Song, M
   Tilvi, V
   Koekemoer, AM
   Finkelstein, KD
   Mobasher, B
   Ferguson, HC
   Giavalisco, M
   Reddy, N
   Ashby, MLN
   Dekel, A
   Fazio, GG
   Fontana, A
   Grogin, NA
   Huang, JS
   Kocevski, D
   Rafelski, M
   Weiner, BJ
   Willner, SP
AF Finkelstein, S. L.
   Papovich, C.
   Dickinson, M.
   Song, M.
   Tilvi, V.
   Koekemoer, A. M.
   Finkelstein, K. D.
   Mobasher, B.
   Ferguson, H. C.
   Giavalisco, M.
   Reddy, N.
   Ashby, M. L. N.
   Dekel, A.
   Fazio, G. G.
   Fontana, A.
   Grogin, N. A.
   Huang, J. -S.
   Kocevski, D.
   Rafelski, M.
   Weiner, B. J.
   Willner, S. P.
TI A galaxy rapidly forming stars 700 million years after the Big Bang at redshift 7.51
SO NATURE
LA English
DT Article
ID lyman break galaxy; extragalactic legacy survey; ly-alpha emitters; ultra-deep-field; spectroscopic confirmation; keck spectroscopy; reionization; candels; evolution; emission
AB Of several dozen galaxies observed spectroscopically that are candidates for having a redshift (z) in excess of seven, only five have had their redshifts confirmed via Lyman alpha emission, at z = 7.008, 7.045, 7.109, 7.213 and 7.215 (refs 1-4). The small fraction of confirmed galaxies may indicate that the neutral fraction in the intergalactic medium rises quickly at z > 6.5, given that Lyman alpha is resonantly scattered by neutral gas(3,5-8). The small samples and limited depth of previous observations, however, makes these conclusions tentative. Here we report a deep near-infrared spectroscopic survey of 43 photometrically-selected galaxies with z > 6.5. We detect a near-infrared emission line from only a single galaxy, confirming that some process is making Lyman alpha difficult to detect. The detected emission line at a wavelength of 1.0343 micrometres is likely to be Lyman alpha emission, placing this galaxy at a redshift z = 7.51, an epoch 700 million years after the Big Bang. This galaxy's colours are consistent with significant metal content, implying that galaxies become enriched rapidly. We calculate a surprisingly high star-formation rate of about 330 solar masses per year, which is more than a factor of 100 greater than that seen in the Milky Way. Such a galaxy is unexpected in a survey of our size(9), suggesting that the early Universe may harbour a larger number of intense sites of star formation than expected.
C1 [Finkelstein, S. L.; Song, M.; Finkelstein, K. D.] Univ Texas Austin, Austin, TX 78712 USA.
   [Papovich, C.; Tilvi, V.] Texas A&M Univ, George P & Cynthia Woods Mitchell Inst Fundamenta, College Stn, TX 78743 USA.
   [Dickinson, M.] Natl Opt Astron Observ, Tucson, AZ 85719 USA.
   [Koekemoer, A. M.; Ferguson, H. C.; Grogin, N. A.] Space Telescope Sci Inst, Baltimore, MD 21218 USA.
   [Mobasher, B.; Reddy, N.] Univ Calif Riverside, Riverside, CA 92521 USA.
   [Giavalisco, M.] Univ Massachusetts, Amherst, MA 01003 USA.
   [Ashby, M. L. N.; Fazio, G. G.; Huang, J. -S.; Willner, S. P.] Harvard Smithsonian Ctr Astrophys, Cambridge, MA 02138 USA.
   [Dekel, A.] Hebrew Univ Jerusalem, Racah Inst Phys, IL-91904 Jerusalem, Israel.
   [Fontana, A.] INAF Osservatorio Roma, I-00040 Monte Porzio Catone, Italy.
   [Kocevski, D.] Univ Kentucky, Lexington, KY 40506 USA.
   [Rafelski, M.] CALTECH, Ctr Infrared Proc & Anal, Pasadena, CA 91125 USA.
   [Weiner, B. J.] Univ Arizona, Steward Observ, Tucson, AZ 85721 USA.
C3 University of Texas System; University of Texas Austin; Texas A&M University System; Texas A&M University College Station; National Optical Astronomy Observatory; Space Telescope Science Institute; University of California System; University of California Riverside; University of Massachusetts System; University of Massachusetts Amherst; Harvard University; Smithsonian Institution; Smithsonian Astrophysical Observatory; Hebrew University of Jerusalem; Istituto Nazionale Astrofisica (INAF); University of Kentucky; California Institute of Technology; University of Arizona
RP Finkelstein, SL (corresponding author), Univ Texas Austin, 2515 Speedway,Stop C1400, Austin, TX 78712 USA.
EM stevenf@astro.as.utexas.edu
FU W. M. Keck Foundation; NASA [NAS 5-26555]; Spitzer Space Telescope
NR 26
TC 226
Z9 256
U1 0
U2 23
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 24
PY 2013
VL 502
IS 7472
BP 524
EP 527
DI 10.1038/nature12657
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 238YN
UT WOS:000325988400048
PM 24153304
DA 2026-03-09
ER

PT J
AU Park, JH
   Coy, JM
   Kasirga, TS
   Huang, CM
   Fei, ZY
   Hunter, S
   Cobden, DH
AF Park, Jae Hyung
   Coy, Jim M.
   Kasirga, T. Serkan
   Huang, Chunming
   Fei, Zaiyao
   Hunter, Scott
   Cobden, David H.
TI Measurement of a solid-state triple point at the metal-insulator transition in VO2
SO NATURE
LA English
DT Article
ID vanadium dioxide; phase-transition; organization; domains; stress
AB First-order phase transitions in solids are notoriously challenging to study. The combination of change in unit cell shape, long range of elastic distortion and flow of latent heat leads to large energy barriers resulting in domain structure, hysteresis and cracking. The situation is worse near a triple point, where more than two phases are involved. The well-known metal-insulator transition in vanadium dioxide(1), a popular candidate for ultrafast optical and electrical switching applications, is a case in point. Even though VO2 is one of the simplest strongly correlated materials, experimental difficulties posed by the first-order nature of the metal-insulator transition as well as the involvement of at least two competing insulating phases have led to persistent controversy about its nature(1-4). Here we show that studying single-crystal VO2 nanobeams(5-16) in a purpose-built nanomechanical strain apparatus allows investigation of this prototypical phase transition with unprecedented control and precision. Our results include the striking finding that the triple point of the metallic phase and two insulating phases is at the transition temperature, T-tr = T-c, which we determine to be 65.0 +/- 0.1 degrees C. The findings have profound implications for the mechanism of the metal-insulator transition in VO2, but they also demonstrate the importance of this approach for mastering phase transitions in many other strongly correlated materials, such as manganites(17) and iron-based superconductors(18).
C1 [Park, Jae Hyung; Coy, Jim M.; Kasirga, T. Serkan; Huang, Chunming; Fei, Zaiyao; Hunter, Scott; Cobden, David H.] Univ Washington, Dept Phys, Seattle, WA 98195 USA.
C3 University of Washington; University of Washington Seattle
RP Cobden, DH (corresponding author), Univ Washington, Dept Phys, Seattle, WA 98195 USA.
EM cobden@uw.edu
FU US Department of Energy, Office of Basic Energy Sciences, Division of Materials Sciences and Engineering [DE-SC0002197]
NR 30
TC 422
Z9 496
U1 5
U2 589
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 22
PY 2013
VL 500
IS 7463
BP 431
EP 434
DI 10.1038/nature12425
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 203TJ
UT WOS:000323316100029
PM 23969461
DA 2026-03-09
ER

PT J
AU Takemura, S
   Bharioke, A
   Lu, ZY
   Nern, A
   Vitaladevuni, S
   Rivlin, PK
   Katz, WT
   Olbris, DJ
   Plaza, SM
   Winston, P
   Zhao, T
   Horne, JA
   Fetter, RD
   Takemura, S
   Blazek, K
   Chang, LA
   Ogundeyi, O
   Saunders, MA
   Shapiro, V
   Sigmund, C
   Rubin, GM
   Scheffer, LK
   Meinertzhagen, IA
   Chklovskii, DB
AF Takemura, Shin-ya
   Bharioke, Arjun
   Lu, Zhiyuan
   Nern, Aljoscha
   Vitaladevuni, Shiv
   Rivlin, Patricia K.
   Katz, William T.
   Olbris, Donald J.
   Plaza, Stephen M.
   Winston, Philip
   Zhao, Ting
   Horne, Jane Anne
   Fetter, Richard D.
   Takemura, Satoko
   Blazek, Katerina
   Chang, Lei-Ann
   Ogundeyi, Omotara
   Saunders, Mathew A.
   Shapiro, Victor
   Sigmund, Christopher
   Rubin, Gerald M.
   Scheffer, Louis K.
   Meinertzhagen, Ian A.
   Chklovskii, Dmitri B.
TI A visual motion detection circuit suggested by Drosophila connectomics
SO NATURE
LA English
DT Article
ID optic lobe; sensitive pathways; selective units; movement; fly; melanogaster; cells; interneurons; medulla; signals
AB Animal behaviour arises from computations in neuronal circuits, but our understanding of these computations has been frustrated by the lack of detailed synaptic connection maps, or connectomes. For example, despite intensive investigations over half a century, the neuronal implementation of local motion detection in the insect visual system remains elusive. Here we develop a semi-automated pipeline using electron microscopy to reconstruct a connectome, containing 379 neurons and 8,637 chemical synaptic contacts, within the Drosophila optic medulla. By matching reconstructed neurons to examples from light microscopy, we assigned neurons to cell types and assembled a connectome of the repeating module of the medulla. Within this module, we identified cell types constituting a motion detection circuit, and showed that the connections onto individual motion-sensitive neurons in this circuit were consistent with their direction selectivity. Our results identify cellular targets for future functional investigations, and demonstrate that connectomes can provide key insights into neuronal computations.
C1 [Takemura, Shin-ya; Bharioke, Arjun; Lu, Zhiyuan; Nern, Aljoscha; Vitaladevuni, Shiv; Rivlin, Patricia K.; Katz, William T.; Olbris, Donald J.; Plaza, Stephen M.; Winston, Philip; Zhao, Ting; Fetter, Richard D.; Takemura, Satoko; Blazek, Katerina; Chang, Lei-Ann; Ogundeyi, Omotara; Saunders, Mathew A.; Shapiro, Victor; Sigmund, Christopher; Rubin, Gerald M.; Scheffer, Louis K.; Meinertzhagen, Ian A.; Chklovskii, Dmitri B.] HHMI, Ashburn, VA 20147 USA.
   [Lu, Zhiyuan; Horne, Jane Anne; Meinertzhagen, Ian A.] Dalhousie Univ, Dept Psychol & Neurosci, Halifax, NS B3H 4R2, Canada.
C3 Howard Hughes Medical Institute; Dalhousie University
RP Chklovskii, DB (corresponding author), HHMI, Janelia Farm Res Campus, Ashburn, VA 20147 USA.
EM iam@dal.ca; mitya@janelia.hhmi.org
FU Howard Hughes Medical Institute Funding Source: Medline
NR 59
TC 506
Z9 608
U1 0
U2 181
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 8
PY 2013
VL 500
IS 7461
BP 175
EP +
DI 10.1038/nature12450
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 197CH
UT WOS:000322825500028
PM 23925240
DA 2026-03-09
ER

PT J
AU Moosmann, J
   Ershov, A
   Altapova, V
   Baumbach, T
   Prasad, MS
   LaBonne, C
   Xiao, XH
   Kashef, J
   Hofmann, R
AF Moosmann, Julian
   Ershov, Alexey
   Altapova, Venera
   Baumbach, Tilo
   Prasad, Maneeshi S.
   LaBonne, Carole
   Xiao, Xianghui
   Kashef, Jubin
   Hofmann, Ralf
TI X-ray phase-contrast in vivo microtomography probes new aspects of Xenopus gastrulation
SO NATURE
LA English
DT Article
ID bottle cells; embryo; internalization; microscopy; extension; movement; mesoderm; image
AB An ambitious goal in biology is to understand the behaviour of cells during development by imaging-in vivo and with subcellular resolution-changes of the embryonic structure. Important morphogenetic movements occur throughout embryogenesis, but in particular during gastrulation when a series of dramatic, coordinated cell movements drives the reorganization of a simple ball or sheet of cells into a complex multi-layered organism(1). In Xenopus laevis, the South African clawed frog and also in zebrafish, cell and tissue movements have been studied in explants(2,3), in fixed embryos(4), in vivo using fluorescence microscopy(5,6) or microscopic magnetic resonance imaging(7). None of these methods allows cell behaviours to be observed with micrometre-scale resolution throughout the optically opaque, living embryo over developmental time. Here we use non-invasive in vivo, time-lapse X-ray microtomography, based on single-distance phase contrast and combined with motion analysis, to examine the course of embryonic development. We demonstrate that this powerful four-dimensional imaging technique provides high-resolution views of gastrulation processes in wildtype X. laevis embryos, including vegetal endoderm rotation, archenteron formation, changes in the volumes of cavities within the porous interstitial tissue between archenteron and blastocoel, migration/confrontation of mesendoderm and closure of the blastopore. Differential flow analysis separates collective from relative cell motion to assign propulsion mechanisms. Moreover, digitally determined volume balances confirm that early archenteron inflation occurs through the uptake of external water. A transient ectodermal ridge, formed in association with the confrontation of ventral and head mesendoderm on the blastocoel roof, is identified. When combined with perturbation experiments to investigate molecular and biomechanical underpinnings of morphogenesis, our technique should help to advance our understanding of the fundamentals of development.
C1 [Moosmann, Julian; Ershov, Alexey; Baumbach, Tilo; Hofmann, Ralf] Karlsruhe Inst Technol, Inst Photon Sci & Synchrotron Radiat, D-76344 Eggenstein Leopoldshafen, Germany.
   [Ershov, Alexey] Natl Res Tomsk Polytech Univ, Inst Phys & Technol, Dept Gen Phys, Tomsk 634050, Russia.
   [Altapova, Venera; Baumbach, Tilo] Karlsruhe Inst Technol, Lab Applicat Synchrotron Radiat, D-76128 Karlsruhe, Germany.
   [Prasad, Maneeshi S.; LaBonne, Carole] Northwestern Univ, Dept Mol Biosci, Evanston, IL 60208 USA.
   [Xiao, Xianghui] Argonne Natl Lab, Adv Photon Source, Argonne, IL 60439 USA.
   [Kashef, Jubin] Karlsruhe Inst Technol, Inst Zool 2, D-76131 Karlsruhe, Germany.
C3 Helmholtz Association; Karlsruhe Institute of Technology; Tomsk Polytechnic University; Helmholtz Association; Karlsruhe Institute of Technology; Northwestern University; United States Department of Energy (DOE); Argonne National Laboratory; Helmholtz Association; Karlsruhe Institute of Technology
RP Hofmann, R (corresponding author), Karlsruhe Inst Technol, Inst Photon Sci & Synchrotron Radiat, Hermann von Helmholtz Pl 1, D-76344 Eggenstein Leopoldshafen, Germany.
EM jubin.kashef@kit.edu; ralf.hofmann2@kit.edu
FU US DOE [DE-AC02-06CH11357]; Karlsruhe Institute of Technology within the framework of the German Excellence Initiative; German Federal Ministry of Education and Research [05K12CK2, 05K12VH1]
NR 34
TC 84
Z9 95
U1 1
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 MAY 16
PY 2013
VL 497
IS 7449
BP 374
EP +
DI 10.1038/nature12116
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 144PN
UT WOS:000318952000039
PM 23676755
DA 2026-03-09
ER

PT J
AU Nakashima, R
   Sakurai, K
   Yamasaki, S
   Hayashi, K
   Nagata, C
   Hoshino, K
   Onodera, Y
   Nishino, K
   Yamaguchi, A
AF Nakashima, Ryosuke
   Sakurai, Keisuke
   Yamasaki, Seiji
   Hayashi, Katsuhiko
   Nagata, Chikahiro
   Hoshino, Kazuki
   Onodera, Yoshikuni
   Nishino, Kunihiko
   Yamaguchi, Akihito
TI Structural basis for the inhibition of bacterial multidrug exporters
SO NATURE
LA English
DT Article
ID efflux pump inhibitors; gram-negative bacteria; pseudomonas-aeruginosa; crystal-structure; resistance; acrb; transporter; strategy; reveal; system
AB The multidrug efflux transporter AcrB and its homologues are important in the multidrug resistance of Gram-negative pathogens(1,2). However, despite efforts to develop efflux inhibitors(3), clinically useful inhibitors are not available at present(4,5). Pyridopyrimidine derivatives are AcrB- and MexB-specific inhibitors that do not inhibit MexY(6,7); MexB and MexY are principal multidrug exporters in Pseudomonas aeruginosa(8-10). We have previously determined the crystal structure of AcrB in the absence and presence of antibiotics(11-13). Drugs were shown to be exported by a functionally rotating mechanism(12) through tandem proximal and distal multisite drug-binding pockets(13). Here we describe the first inhibitor-bound structures of AcrB and MexB, in which these proteins are bound by a pyridopyrimidine derivative. The pyridopyrimidine derivative binds tightly to a narrow pit composed of a phenylalanine cluster located in the distal pocket and sterically hinders the functional rotation. This pit is a hydrophobic trap that branches off from the substrate-translocation channel. Phe 178 is located at the edge of this trap in AcrB and MexB and contributes to the tight binding of the inhibitor molecule through a pi-pi interaction with the pyridopyrimidine ring. The voluminous side chain of Trp 177 located at the corresponding position in MexY prevents inhibitor binding. The structure of the hydrophobic trap described in this study will contribute to the development of universal inhibitors of MexB and MexY in P. aeruginosa.
C1 [Nakashima, Ryosuke; Sakurai, Keisuke; Yamaguchi, Akihito] Osaka Univ, Inst Sci & Ind Res, Dept Cell Membrane Biol, Ibaraki, Osaka 5670047, Japan.
   [Yamasaki, Seiji; Hayashi, Katsuhiko; Yamaguchi, Akihito] Osaka Univ, Grad Sch Pharmaceut Sci, Suita, Osaka 5650871, Japan.
   [Nagata, Chikahiro; Hoshino, Kazuki; Onodera, Yoshikuni] Daiichi Sankyo Co Ltd, Edogawa Ku, Tokyo 1348630, Japan.
   [Nishino, Kunihiko] Osaka Univ, Inst Sci & Ind Res, Lab Microbiol & Infect Dis, Ibaraki, Osaka 5670047, Japan.
C3 University of Osaka; University of Osaka; Daiichi Sankyo Company Limited; University of Osaka
RP Yamaguchi, A (corresponding author), Osaka Univ, Inst Sci & Ind Res, Dept Cell Membrane Biol, Ibaraki, Osaka 5670047, Japan.
EM akihito@sanken.osaka-u.ac.jp
FU Academia Sinica; National Synchrotron Radiation Research Center (Taiwan); CREST from the Japan Science and Technology Agency; Program for the Promotion of Fundamental Studies in Health Sciences of the National Institute of Biomedical Innovation; Ministry of Education, Culture, Sports, Science and Technology of Japan
NR 33
TC 246
Z9 289
U1 0
U2 112
PU NATURE RESEARCH
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 1
PY 2013
VL 500
IS 7460
BP 102
EP U131
DI 10.1038/nature12300
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 192VK
UT WOS:000322514800037
PM 23812586
DA 2026-03-09
ER

PT J
AU Makino, DL
   Baumgärtner, M
   Conti, E
AF Makino, Debora Lika
   Baumgaertner, Marc
   Conti, Elena
TI Crystal structure of an RNA-bound 11-subunit eukaryotic exosome complex
SO NATURE
LA English
DT Article
ID human pm-scl; yeast exosome; archaeal exosome; core exosome; degradation; subunit; exoribonuclease; reconstitution; purification; recruitment
AB The exosome is the major 3'-5' RNA-degradation complex in eukaryotes. The ubiquitous core of the yeast exosome (Exo-10) is formed by nine catalytically inert subunits (Exo-9) and a single active RNase, Rrp44. In the nucleus, the Exo-10 core recruits another nuclease, Rrp6. Here we crystallized an approximately 440-kilodalton complex of Saccharomyces cerevisiae Exo-10 bound to a carboxy-terminal region of Rrp6 and to an RNA duplex with a 3'-overhang of 31 ribonucleotides. The 2.8 angstrom resolution structure shows how RNA is funnelled into the Exo-9 channel in a single-stranded conformation by an unwinding pore. Rrp44 adopts a closed conformation and captures the RNA 3'-end that exits from the side of Exo-9. Exo-9 subunits bind RNA with-sequence-unspecific interactions reminiscent of archaeal exosomes. The substrate binding and channelling mechanisms of 3'-5' RNA degradation complexes are conserved in all kingdoms of life.
C1 [Makino, Debora Lika; Baumgaertner, Marc; Conti, Elena] MPI Biochem, Dept Struct Cell Biol, D-82152 Martinsried, Germany.
C3 Max Planck Society
RP Conti, E (corresponding author), MPI Biochem, Dept Struct Cell Biol, Klopferspitz 18, D-82152 Martinsried, Germany.
EM conti@biochem.mpg.de
FU Max Planck Gesellschaft; ERC [294371]; Deutsche Forschungsgemeinschaft [SFB646, SFB1035, GRK1721, CIPSM]; Max Planck Institute Biochemistry Core Facility and Crystallization Facility; European Research Council (ERC) [294371] Funding Source: European Research Council (ERC)
NR 28
TC 204
Z9 235
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 7
PY 2013
VL 495
IS 7439
BP 70
EP 75
DI 10.1038/nature11870
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 105BE
UT WOS:000316039800041
PM 23376952
DA 2026-03-09
ER

PT J
AU Cabral, RA
   Jackson, MG
   Rose-Koga, EF
   Koga, KT
   Whitehouse, MJ
   Antonelli, MA
   Farquhar, J
   Day, JMD
   Hauri, EH
AF Cabral, Rita A.
   Jackson, Matthew G.
   Rose-Koga, Estelle F.
   Koga, Kenneth T.
   Whitehouse, Martin J.
   Antonelli, Michael A.
   Farquhar, James
   Day, James M. D.
   Hauri, Erik H.
TI Anomalous sulphur isotopes in plume lavas reveal deep mantle storage of Archaean crust
SO NATURE
LA English
DT Article
ID microbial sulfate reduction; oceanic island basalts; melt inclusions; origin; geochemistry; lithosphere; evolution; plateau; diamond; himu
AB Basaltic lavas erupted at some oceanic intraplate hotspot volcanoes are thought to sample ancient subducted crustal materials(1,2). However, the residence time of these subducted materials in the mantle is uncertain and model-dependent(3), and compelling evidence for their return to the surface in regions of mantle upwelling beneath hotspots is lacking. Here we report anomalous sulphur isotope signatures indicating mass-independent fractionation (MIF) in olivine-hosted sulphides from 20-million-year-old ocean island basalts from Mangaia, Cook Islands (Polynesia), which have been suggested to sample recycled oceanic crust(3,4). Terrestrial MIF sulphur isotope signatures (in which the amount of fractionation does not scale in proportion with the difference in the masses of the isotopes) were generated exclusively through atmospheric photochemical reactions until about 2.45 billion years ago(5-7). Therefore, the discovery of MIF sulphur in these young plume lavas suggests that sulphur-probably derived from hydrothermally altered oceanic crust-was subducted into the mantle before 2.45 billion years ago and recycled into the mantle source of Mangaia lavas. These new data provide evidence for ancient materials, with negative Delta S-33 values, in the mantle source for Mangaia lavas. Our data also complement evidence for recycling of the sulphur content of ancient sedimentary materials to the subcontinental lithospheric mantle that has been identified in diamond-hosted sulphide inclusions(8,9). This Archaean age for recycled oceanic crust also provides key constraints on the length of time that subducted crustal material can survive in the mantle, and on the timescales of mantle convection from subduction to upwelling beneath hotspots.
C1 [Cabral, Rita A.; Jackson, Matthew G.] Boston Univ, Dept Earth & Environm, Boston, MA 02215 USA.
   [Rose-Koga, Estelle F.; Koga, Kenneth T.] Univ Blaise Pascal, CNRS, UMR6524, Lab Magmas & Volcans,IRD R163, F-63038 Clermont Ferrand, France.
   [Whitehouse, Martin J.] Swedish Museum Nat Hist, SE-10405 Stockholm, Sweden.
   [Whitehouse, Martin J.] Stockholm Univ, Dept Geol Sci, SE-10691 Stockholm, Sweden.
   [Antonelli, Michael A.; Farquhar, James] Univ Maryland, Dept Geol, College Pk, MD 20742 USA.
   [Antonelli, Michael A.; Farquhar, James] Univ Maryland, ESSIC, College Pk, MD 20742 USA.
   [Day, James M. D.] Univ Calif San Diego, Scripps Inst Oceanog, Geosci Res Div, La Jolla, CA 92093 USA.
   [Hauri, Erik H.] Carnegie Inst Sci, Dept Terr Magnetism, Washington, DC 20015 USA.
C3 Boston University; 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); Swedish Museum of Natural History; Stockholm University; University System of Maryland; University of Maryland College Park; University System of Maryland; University of Maryland College Park; University of California System; University of California San Diego; Scripps Institution of Oceanography; Carnegie Institution for Science
RP Cabral, RA (corresponding author), Boston Univ, Dept Earth & Environm, 675 Commonwealth Ave, Boston, MA 02215 USA.
EM racabral@bu.edu
FU Boston University; NSF [EAR-1145202]; EU SYNTHESYS; French ANR SlabFlux; joint Nordic contract; Directorate For Geosciences [1430610] Funding Source: National Science Foundation; Directorate For Geosciences; Division Of Earth Sciences [1145202, 1116089] Funding Source: National Science Foundation; Division Of Earth Sciences [1430610] Funding Source: National Science Foundation
NR 35
TC 225
Z9 253
U1 4
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 APR 25
PY 2013
VL 496
IS 7446
BP 490
EP +
DI 10.1038/nature12020
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 131HU
UT WOS:000317984400038
PM 23619695
DA 2026-03-09
ER

PT J
AU Ziller, MJ
   Gu, HC
   Müller, F
   Donaghey, J
   Tsai, LTY
   Kohlbacher, O
   De Jager, PL
   Rosen, ED
   Bennett, DA
   Bernstein, BE
   Gnirke, A
   Meissner, A
AF Ziller, Michael J.
   Gu, Hongcang
   Mueller, Fabian
   Donaghey, Julie
   Tsai, Linus T. -Y.
   Kohlbacher, Oliver
   De Jager, Philip L.
   Rosen, Evan D.
   Bennett, David A.
   Bernstein, Bradley E.
   Gnirke, Andreas
   Meissner, Alexander
TI Charting a dynamic DNA methylation landscape of the human genome
SO NATURE
LA English
DT Article
ID mammalian development; cells; wide; methylome; disease; mouse; pluripotent; selection; traits; loci
AB DNA methylation is a defining feature of mammalian cellular identity and is essential for normal development(1,2). Most cell types, except germ cells and pre-implantation embryos(3-5), display relatively stable DNA methylation patterns, with 70-80% of all CpGs being methylated(6). Despite recent advances, we still have a limited understanding of when, where and how many CpGs participate in genomic regulation. Here we report the in-depth analysis of 42 whole-genome bisulphite sequencing data sets across 30 diverse human cell and tissue types. We observe dynamic regulation for only 21.8% of autosomal CpGs within a normal developmental context, most of which are distal to transcription start sites. These dynamic CpGs co-localize with gene regulatory elements, particularly enhancers and transcription-factor-binding sites, which allow identification of key lineage-specific regulators. In addition, differentially methylated regions (DMRs) often contain single nucleotide polymorphisms associated with cell-type-related diseases as determined by genome-wide association studies. The results also highlight the general inefficiency of whole-genome bisulphite sequencing, as 70-80% of the sequencing reads across these data sets provided little or no relevant information about CpG methylation. To demonstrate further the utility of our DMR set, we use it to classify unknown samples and identify representative signature regions that recapitulate major DNA methylation dynamics. In summary, although in theory every CpG can change its methylation state, our results suggest that only a fraction does so as part of coordinated regulatory programs. Therefore, our selected DMRs can serve as a starting point to guide new, more effective reduced representation approaches to capture the most informative fraction of CpGs, as well as further pinpoint putative regulatory elements.
C1 [Ziller, Michael J.; Gu, Hongcang; Donaghey, Julie; De Jager, Philip L.; Rosen, Evan D.; Bernstein, Bradley E.; Gnirke, Andreas; Meissner, Alexander] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.
   [Ziller, Michael J.; Donaghey, Julie; Meissner, Alexander] Harvard Stem Cell Inst, Cambridge, MA 02138 USA.
   [Ziller, Michael J.; Mueller, Fabian; Donaghey, Julie; Meissner, Alexander] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA.
   [Tsai, Linus T. -Y.; Rosen, Evan D.] Beth Israel Deaconess Med Ctr, Div Endocrinol, Boston, MA 02215 USA.
   [Kohlbacher, Oliver] Univ Tubingen, Ctr Bioinformat, D-72074 Tubingen, Germany.
   [Kohlbacher, Oliver] Univ Tubingen, Quantitat Biol Ctr, D-72074 Tubingen, Germany.
   [De Jager, Philip L.] Brigham & Womens Hosp, Inst Neurosci, Program Translat NeuroPsychiat Genom, Dept Neurol, Boston, MA 02115 USA.
   [De Jager, Philip L.] Brigham & Womens Hosp, Inst Neurosci, Program Translat NeuroPsychiat Genom, Dept Psychiat, Boston, MA 02115 USA.
   [Bennett, David A.] Rush Univ, Med Ctr, Rush Alzheimers Dis Ctr, Chicago, IL 60612 USA.
   [Bernstein, Bradley E.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
C3 Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Harvard University; Harvard University; Harvard University; Harvard University Medical Affiliates; Beth Israel Deaconess Medical Center; Eberhard Karls University of Tubingen; Eberhard Karls University of Tubingen; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Rush University; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital
RP Meissner, A (corresponding author), Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.
EM alexander_meissner@harvard.edu
FU National Institutes of Health (NIH) Roadmap Epigenomics Project [ES017690]; NIH [P30AG10161, R01AG17917, R01AG15819, R01AG36042, U01ES017155, P01GM099117]; Pew Charitable Trusts; New York Stem Cell Foundation; National Institute of General Medical Sciences [P01GM099117] Funding Source: NIH RePORTER; National Institute on Aging [R01AG015819, R01AG017917] Funding Source: NIH RePORTER
NR 30
TC 1032
Z9 1223
U1 0
U2 182
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 22
PY 2013
VL 500
IS 7463
BP 477
EP 481
DI 10.1038/nature12433
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 203TJ
UT WOS:000323316100039
PM 23925113
DA 2026-03-09
ER

PT J
AU Sanjuan-Pla, A
   Macaulay, IC
   Jensen, CT
   Woll, PS
   Luis, TC
   Mead, A
   Moore, S
   Carella, C
   Matsuoka, S
   Jones, TB
   Chowdhury, O
   Stenson, L
   Lutteropp, M
   Green, JCA
   Facchini, R
   Boukarabila, H
   Grover, A
   Gambardella, A
   Thongjuea, S
   Carrelha, J
   Tarrant, P
   Atkinson, D
   Clark, SA
   Nerlov, C
   Jacobsen, SEW
AF Sanjuan-Pla, Alejandra
   Macaulay, Iain C.
   Jensen, Christina T.
   Woll, Petter S.
   Luis, Tiago C.
   Mead, Adam
   Moore, Susan
   Carella, Cintia
   Matsuoka, Sahoko
   Jones, Tiphaine Bouriez
   Chowdhury, Onima
   Stenson, Laura
   Lutteropp, Michael
   Green, Joanna C. A.
   Facchini, Raffaella
   Boukarabila, Hanane
   Grover, Amit
   Gambardella, Adriana
   Thongjuea, Supat
   Carrelha, Joana
   Tarrant, Paul
   Atkinson, Deborah
   Clark, Sally-Ann
   Nerlov, Claus
   Jacobsen, Sten Eirik W.
TI Platelet-biased stem cells reside at the apex of the haematopoietic stem-cell hierarchy
SO NATURE
LA English
DT Article
ID self-renewal; in-vivo; differentiation; thrombopoietin; reconstitution; heterogeneity; progenitors; generation
AB The blood system is maintained by a small pool of haematopoietic stem cells (HSCs), which are required and sufficient for replenishing all human blood cell lineages at millions of cells per second throughout life. Megakaryocytes in the bone marrow are responsible for the continuous production of platelets in the blood, crucial for preventing bleeding-a common and life-threatening side effect of many cancer therapies-and major efforts are focused at identifying the most suitable cellular and molecular targets to enhance platelet production after bone marrow transplantation or chemotherapy(1). Although it has become clear that distinct HSC subsets exist that are stably biased towards the generation of lymphoid or myeloid blood cells(2-4), we are yet to learn whether other types of lineage-biased HSC exist or understand their inter-relationships and how differently lineage-biased HSCs are generated and maintained. The functional relevance of notable phenotypic and molecular similarities between megakaryocytes and bone marrow cells with an HSC cell-surface phenotype(5-8) remains unclear. Here we identify and prospectively isolate a molecularly and functionally distinct mouse HSC subset primed for platelet-specific gene expression, with enhanced propensity for short-and long-term reconstitution of platelets. Maintenance of platelet-biased HSCs crucially depends on thrombopoietin, the primary extrinsic regulator of platelet development(9). Platelet-primed HSCs also frequently have a long-term myeloid lineage bias, can self-renew and give rise to lymphoid-biased HSCs. These findings show that HSC subtypes can be organized into a cellular hierarchy, with platelet-primed HSCs at the apex. They also demonstrate that molecular and functional priming for platelet development initiates already in a distinct HSC population. The identification of a platelet-primed HSC population should enable the rational design of therapies enhancing platelet output.
C1 [Sanjuan-Pla, Alejandra; Moore, Susan; Nerlov, Claus] Univ Edinburgh, Inst Stem Cell Res, Edinburgh EH9 16UU, Midlothian, Scotland.
   [Sanjuan-Pla, Alejandra; Moore, Susan; Nerlov, Claus] Univ Edinburgh, MRC Ctr Regenerat Med, Edinburgh EH9 16UU, Midlothian, Scotland.
   [Sanjuan-Pla, Alejandra; Moore, Susan; Carella, Cintia; Nerlov, Claus] EMBL Mouse Biol Program, I-00015 Monterotondo, Italy.
   [Macaulay, Iain C.; Jensen, Christina T.; Woll, Petter S.; Luis, Tiago C.; Mead, Adam; Matsuoka, Sahoko; Jones, Tiphaine Bouriez; Chowdhury, Onima; Stenson, Laura; Lutteropp, Michael; Green, Joanna C. A.; Facchini, Raffaella; Boukarabila, Hanane; Grover, Amit; Gambardella, Adriana; Thongjuea, Supat; Carrelha, Joana; Tarrant, Paul; Atkinson, Deborah; Clark, Sally-Ann; Nerlov, Claus; Jacobsen, Sten Eirik W.] Univ Oxford, Weatherall Inst Mol Med, MRC Mol Haematol Unit, Oxford OX3 9DS, England.
   [Macaulay, Iain C.; Jensen, Christina T.; Woll, Petter S.; Luis, Tiago C.; Mead, Adam; Matsuoka, Sahoko; Jones, Tiphaine Bouriez; Chowdhury, Onima; Stenson, Laura; Lutteropp, Michael; Green, Joanna C. A.; Facchini, Raffaella; Boukarabila, Hanane; Carrelha, Joana; Tarrant, Paul; Atkinson, Deborah; Clark, Sally-Ann; Jacobsen, Sten Eirik W.] Univ Oxford, Weatherall Inst Mol Med, Haematopoiet Stem Cell Biol Lab, Oxford OX3 9DS, England.
C3 University of Edinburgh; University of Edinburgh; European Molecular Biology Laboratory (EMBL); University of Oxford; University of Oxford
RP Jacobsen, SEW (corresponding author), Univ Oxford, Weatherall Inst Mol Med, MRC Mol Haematol Unit, Oxford OX3 9DS, England.
EM claus.nerlov@imm.ox.ac.uk; sten.jacobsen@imm.ox.ac.uk
FU Medical Research Council, UK [H4RPLK0]; MRC; European Commission; Association for International Cancer Research; Spanish Ministry of Education and Science; MRC [G0801073, G0900892, MC_UU_12009/7, G84/6443, MC_UU_12009/5, MC_PC_12020, G0701761, G0501838] Funding Source: UKRI; Medical Research Council [MC_UU_12009/7, MC_UU_12009/5, G84/6443, G0900892, MC_PC_12020, G0701761, G0801073, G0501838, G0700711B] Funding Source: researchfish
NR 28
TC 489
Z9 595
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 10
PY 2013
VL 502
IS 7470
BP 232
EP +
DI 10.1038/nature12495
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 231RU
UT WOS:000325436100050
PM 23934107
DA 2026-03-09
ER

PT J
AU Goldman, N
   Bertone, P
   Chen, SY
   Dessimoz, C
   LeProust, EM
   Sipos, B
   Birney, E
AF Goldman, Nick
   Bertone, Paul
   Chen, Siyuan
   Dessimoz, Christophe
   LeProust, Emily M.
   Sipos, Botond
   Birney, Ewan
TI Towards practical, high-capacity, low-maintenance information storage in synthesized DNA
SO NATURE
LA English
DT Article
ID chain
AB Digital production, transmission and storage have revolutionized how we access and use information but have also made archiving an increasingly complex task that requires active, continuing maintenance of digital media. This challenge has focused some interest on DNA as an attractive target for information storage(1) because of its capacity for high-density information encoding, longevity under easily achieved conditions(2-4) and proven track record as an information bearer. Previous DNA-based information storage approaches have encoded only trivial amounts of information(5-7) or were not amenable to scaling-up(8), and used no robust error-correction and lacked examination of their cost-efficiency for large-scale information archival(9). Here we describe a scalable method that can reliably store more information than has been handled before. We encoded computer files totalling 739 kilobytes of hard-disk storage and with an estimated Shannon information(10) of 5.2 x 10(6) bits into a DNA code, synthesized this DNA, sequenced it and reconstructed the original files with 100% accuracy. Theoretical analysis indicates that our DNA-based storage scheme could be scaled far beyond current global information volumes and offers a realistic technology for large-scale, long-term and infrequently accessed digital archiving. In fact, current trends in technological advances are reducing DNA synthesis costs at a pace that should make our scheme cost-effective for sub-50-year archiving within a decade.
C1 [Goldman, Nick; Bertone, Paul; Dessimoz, Christophe; Sipos, Botond; Birney, Ewan] European Bioinformat Inst, Hinxton CB10 1SD, England.
   [Chen, Siyuan; LeProust, Emily M.] Genom LSSU, Agilent Technol, Santa Clara, CA 95051 USA.
C3 European Molecular Biology Laboratory (EMBL); European Bioinformatics Institute; Agilent Technologies
RP Goldman, N (corresponding author), European Bioinformat Inst, Wellcome Trust Genome Campus, Hinxton CB10 1SD, England.
EM goldman@ebi.ac.uk
FU Swiss National Science Foundation [136461]; EMBL
NR 28
TC 863
Z9 1126
U1 4
U2 517
PU NATURE PUBLISHING 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 7
PY 2013
VL 494
IS 7435
BP 77
EP 80
DI 10.1038/nature11875
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 087DJ
UT WOS:000314741200037
PM 23354052
DA 2026-03-09
ER

PT J
AU Li, L
   Dudin, YO
   Kuzmich, A
AF Li, L.
   Dudin, Y. O.
   Kuzmich, A.
TI Entanglement between light and an optical atomic excitation
SO NATURE
LA English
DT Article
ID single-photon; rydberg blockade; quantum memory; gas
AB The generation, distribution and control of entanglement across quantum networks is one of the main goals of quantum information science(1,2). In previous studies, hyperfine ground states of single atoms or atomic ensembles have been entangled with spontaneously emitted light(3-6). The probabilistic character of the spontaneous emission process leads to long entanglement generation times, limiting realized network implementations to just two nodes(7-10). The success probability for atom-photon entanglement protocols can be increased by confining a single atom in a high-finesse optical cavity(11,12). Alternatively, quantum networks with superior scaling properties could be achieved using entanglement between light fields and atoms in quantum superpositions of the ground and highly excited (Rydberg) electronic states(2,13,14). Here we report the generation of such entanglement. The dephasing of the optical atomic coherence is inhibited by state-insensitive confinement of both the ground and Rydberg states of an ultracold atomic gas in an optical lattice(15). Our results pave the way for functional, many-node quantum networks capable of deterministic quantum logic operations between long-lived atomic memories.
C1 [Li, L.; Dudin, Y. O.; Kuzmich, A.] Georgia Inst Technol, Sch Phys, Atlanta, GA 30332 USA.
C3 University System of Georgia; Georgia Institute of Technology
RP Kuzmich, A (corresponding author), Georgia Inst Technol, Sch Phys, Atlanta, GA 30332 USA.
EM alex.kuzmich@physics.gatech.edu
FU Atomic Physics Program; Quantum Memories MURI of the Air Force Office of Scientific Research; National Science Foundation; Division Of Physics; Direct For Mathematical & Physical Scien [1360597] Funding Source: National Science Foundation
NR 31
TC 177
Z9 200
U1 1
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 JUN 27
PY 2013
VL 498
IS 7455
BP 466
EP 469
DI 10.1038/nature12227
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 171LH
UT WOS:000320929400048
PM 23783514
DA 2026-03-09
ER

PT J
AU Temmerman, S
   Meire, P
   Bouma, TJ
   Herman, PMJ
   Ysebaert, T
   De Vriend, HJ
AF Temmerman, Stijn
   Meire, Patrick
   Bouma, Tjeerd J.
   Herman, Peter M. J.
   Ysebaert, Tom
   De Vriend, Huib J.
TI Ecosystem-based coastal defence in the face of global change
SO NATURE
LA English
DT Article
ID marsh restoration; sea-level; management; sedimentation; carbon
AB The risk of flood disasters is increasing for many coastal societies owing to global and regional changes in climate conditions, sea-level rise, land subsidence and sediment supply. At the same time, in many locations, conventional coastal engineering solutions such as sea walls are increasingly challenged by these changes and their maintenance may become unsustainable. We argue that flood protection by ecosystem creation and restoration can provide a more sustainable, cost-effective and ecologically sound alternative to conventional coastal engineering and that, in suitable locations, it should be implemented globally and on a large scale.
C1 [Temmerman, Stijn; Meire, Patrick] Univ Antwerp, Ecosyst Management Res Grp, B-2610 Antwerp, Belgium.
   [Bouma, Tjeerd J.; Herman, Peter M. J.; Ysebaert, Tom] Royal Netherlands Inst Sea Res, Spatial Ecol Res Grp, NL-4400 AC Yerseke, Netherlands.
   [Ysebaert, Tom] Inst Marine Resources & Ecosyst Studies IMARES, NL-4400 AB Yerseke, Netherlands.
   [De Vriend, Huib J.] Delft Univ Technol, NL-3311 JG Dordrecht, Netherlands.
   [De Vriend, Huib J.] EcoShape, NL-3311 JG Dordrecht, Netherlands.
C3 University of Antwerp; Utrecht University; Royal Netherlands Institute for Sea Research (NIOZ); Wageningen University & Research; Delft University of Technology
RP Temmerman, S (corresponding author), Univ Antwerp, Ecosyst Management Res Grp, B-2610 Antwerp, Belgium.
EM stijn.temmerman@uantwerpen.be
FU Research Foundation - Flanders (FWO); Research Fund of the University of Antwerp (BOF); Waterwegen Zeekanaal NV; EU [FP7.2009-1, 244104]; STW [07324]; Singapore-Delft Water Alliance; innovation program Building
NR 35
TC 1347
Z9 1535
U1 25
U2 804
PU NATURE PUBLISHING 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 5
PY 2013
VL 504
IS 7478
BP 79
EP 83
DI 10.1038/nature12859
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 264BK
UT WOS:000327851700028
PM 24305151
DA 2026-03-09
ER

PT J
AU Driskell, RR
   Lichtenberger, BM
   Hoste, E
   Kretzschmar, K
   Simons, BD
   Charalambous, M
   Ferron, SR
   Herault, Y
   Pavlovic, G
   Ferguson-Smith, AC
   Watt, FM
AF Driskell, Ryan R.
   Lichtenberger, Beate M.
   Hoste, Esther
   Kretzschmar, Kai
   Simons, Ben D.
   Charalambous, Marika
   Ferron, Sacri R.
   Herault, Yann
   Pavlovic, Guillaume
   Ferguson-Smith, Anne C.
   Watt, Fiona M.
TI Distinct fibroblast lineages determine dermal architecture in skin development and repair
SO NATURE
LA English
DT Article
ID stem-cells; papilla cells; beta-catenin; mouse skin; in-vivo; regeneration; differentiation; epidermis; recruitment; activation
AB Fibroblasts are the major mesenchymal cell type in connective tissue and deposit the collagen and elastic fibres of the extracellular matrix (ECM)(1). Even within a single tissue, fibroblasts exhibit considerable functional diversity, but it is not known whether this reflects the existence of a differentiation hierarchy or is a response to different environmental factors. Here we show, using transplantation assays and lineage tracing in mice, that the fibroblasts of skin connective tissue arise from two distinct lineages. One forms the upper dermis, including the dermal papilla that regulates hair growth and the arrector pili muscle, which controls piloerection. The other forms the lower dermis, including the reticular fibroblasts that synthesize the bulk of the fibrillar ECM, and the preadipocytes and adipocytes of the hypodermis. The upper lineage is required for hair follicle formation. In wounded adult skin, the initial wave of dermal repair is mediated by the lower lineage and upper dermal fibroblasts are recruited only during re-epithelialization. Epidermal beta-catenin activation stimulates the expansion of the upper dermal lineage, rendering wounds permissive for hair follicle formation. Our findings explain why wounding is linked to formation of ECM-rich scar tissue that lacks hair follicles(2-4). They also forma platform for discovering fibroblast lineages in other tissues and for examining fibroblast changes in ageing and disease.
C1 [Driskell, Ryan R.; Lichtenberger, Beate M.; Kretzschmar, Kai] Univ Cambridge, Wellcome Trust Ctr Stem Cell Res, Cambridge CB2 1QR, England.
   [Driskell, Ryan R.; Lichtenberger, Beate M.; Hoste, Esther; Kretzschmar, Kai; Watt, Fiona M.] Kings Coll London, Ctr Stem Cells & Regenerat Med, Guys Hosp, London SE1 9RT, England.
   [Hoste, Esther] Li Ka Shing Ctr, Canc Res UK Cambridge Res Inst, Cambridge CB2 0RE, England.
   [Simons, Ben D.] Univ Cambridge, Cavendish Lab, Dept Phys, Cambridge CB3 0HE, England.
   [Charalambous, Marika; Ferron, Sacri R.; Ferguson-Smith, Anne C.] Univ Cambridge, Dept Physiol Dev & Neurosci, Cambridge CB2 3EG, England.
   [Herault, Yann; Pavlovic, Guillaume] Inst Clin Souris, F-67404 Illkrich Graffenstaden, France.
C3 University of Cambridge; Guy's & St Thomas' NHS Foundation Trust; University of London; King's College London; CRUK Cambridge Institute; Cancer Research UK; University of Cambridge; University of Cambridge
RP Watt, FM (corresponding author), Kings Coll London, Ctr Stem Cells & Regenerat Med, Guys Hosp, 28th Floor,Tower Wing, London SE1 9RT, England.
EM fiona.watt@kcl.ac.uk
FU Wellcome Trust; Medical Research Council (MRC); European Union; FEBS long-term fellowship; MRC; Department of Health via the National Institute for Health Research (NIHR) comprehensive Biomedical Research Centre; King's College Hospital NHS Foundation Trust; Medical Research Council [G0600796, MR/J001597/1] Funding Source: researchfish; Wellcome Trust [098357/Z/12/Z, 095606/Z/11/Z] Funding Source: researchfish; MRC [MR/J001597/1, G0600796] Funding Source: UKRI
CR Arwert EN, 2010, P NATL ACAD SCI USA, V107, P19903, DOI 10.1073/pnas.1007404107
   Collins CA, 2011, DEVELOPMENT, V138, P5189, DOI 10.1242/dev.064592
   Driskell RR, 2012, J INVEST DERMATOL, V132, P1084, DOI 10.1038/jid.2011.428
   Driskell RR, 2009, DEVELOPMENT, V136, P2815, DOI 10.1242/dev.038620
   Dulauroy S, 2012, NAT MED, V18, P1262, DOI 10.1038/nm.2848
   Egawa G, 2009, J INVEST DERMATOL, V129, P2386, DOI 10.1038/jid.2009.105
   Festa E, 2011, CELL, V146, P761, DOI 10.1016/j.cell.2011.07.019
   Gay D, 2013, NAT MED, V19, P916, DOI 10.1038/nm.3181
   Giangreco A, 2008, AGING CELL, V7, P250, DOI 10.1111/j.1474-9726.2008.00372.x
   Gomez C, 2013, STEM CELL REP, V1, P19, DOI 10.1016/j.stemcr.2013.04.001
   Gurtner GC, 2008, NATURE, V453, P314, DOI 10.1038/nature07039
   Hamilton TG, 2003, MOL CELL BIOL, V23, P4013, DOI 10.1128/MCB.23.11.4013-4025.2003
   Horsley V, 2006, CELL, V126, P597, DOI 10.1016/j.cell.2006.06.048
   Ito M, 2007, NATURE, V447, P316, DOI 10.1038/nature05766
   Janson DG, 2012, J INVEST DERMATOL, V132, P2565, DOI 10.1038/jid.2012.192
   Jensen KB, 2010, NAT PROTOC, V5, P898, DOI 10.1038/nprot.2010.39
   Kalluri R, 2006, NAT REV CANCER, V6, P392, DOI 10.1038/nrc1877
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   Lesko MH, 2013, DEV BIOL, V382, P15, DOI 10.1016/j.ydbio.2013.08.004
   Magnúsdóttir E, 2007, P NATL ACAD SCI USA, V104, P14988, DOI 10.1073/pnas.0707323104
   Martin P, 1997, SCIENCE, V276, P75, DOI 10.1126/science.276.5309.75
   Page ME, 2013, CELL STEM CELL, V13, P471, DOI 10.1016/j.stem.2013.07.010
   Plikus MV, 2008, NATURE, V451, P340, DOI 10.1038/nature06457
   Rivers LE, 2008, NAT NEUROSCI, V11, P1392, DOI 10.1038/nn.2220
   Robertson EJ, 2007, DEVELOPMENT, V134, P4335, DOI 10.1242/dev.012047
   Schmidt BA, 2013, DEVELOPMENT, V140, P1517, DOI 10.1242/dev.087593
   SHAH M, 1994, J CELL SCI, V107, P1137
   Silva-Vargas V, 2005, DEV CELL, V9, P121, DOI 10.1016/j.devcel.2005.04.013
   Staal FJT, 2008, NAT REV IMMUNOL, V8, P581, DOI 10.1038/nri2360
   VANEXAN RJ, 1984, AM J ANAT, V169, P149, DOI 10.1002/aja.1001690204
NR 30
TC 977
Z9 1152
U1 9
U2 358
PU NATURE PUBLISHING 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 12
PY 2013
VL 504
IS 7479
BP 277
EP +
DI 10.1038/nature12783
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 267TQ
UT WOS:000328121500036
PM 24336287
DA 2026-03-09
ER

PT J
AU Warner, M
   Din, S
   Tupitsyn, IS
   Morley, GW
   Stoneham, AM
   Gardener, JA
   Wu, ZL
   Fisher, AJ
   Heutz, S
   Kay, CWM
   Aeppli, G
AF Warner, Marc
   Din, Salahud
   Tupitsyn, Igor S.
   Morley, Gavin W.
   Stoneham, A. Marshall
   Gardener, Jules A.
   Wu, Zhenlin
   Fisher, Andrew J.
   Heutz, Sandrine
   Kay, Christopher W. M.
   Aeppli, Gabriel
TI Potential for spin-based information processing in a thin-film molecular semiconductor
SO NATURE
LA English
DT Article
ID copper phthalocyanine; relaxation; transport; crystal; epr; temperature; coherence; magnets; silicon; echo
AB Organic semiconductors are studied intensively for applications in electronics and optics(1), and even spin-based information technology, or spintronics(2). Fundamental quantities in spintronics are the population relaxation time (T-1) and the phase memory time (T-2): T-1 measures the lifetime of a classical bit, in this case embodied by a spin oriented either parallel or antiparallel to an external magnetic field, and T-2 measures the corresponding lifetime of a quantum bit, encoded in the phase of the quantum state. Here we establish that these times are surprisingly long for a common, low-cost and chemically modifiable organic semiconductor, the blue pigment copper phthalocyanine(3), in easily processed thin-film form of the type used for device fabrication. At 5 K, a temperature reachable using inexpensive closed-cycle refrigerators, T-1 and T-2 are respectively 59 ms and 2.6 mu s, and at 80 K, which is just above the boiling point of liquid nitrogen, they are respectively 10 ms and 1 ms, demonstrating that the performance of thin-film copper phthalocyanine is superior to that of single-molecule magnets over the same temperature range(4). T-2 is more than two orders of magnitude greater than the duration of the spin manipulation pulses, which suggests that copper phthalocyanine holds promise for quantum information processing, and the long T-1 indicates possibilities for medium-term storage of classical bits in all-organic devices on plastic substrates.
C1 [Warner, Marc; Morley, Gavin W.; Stoneham, A. Marshall; Gardener, Jules A.; Fisher, Andrew J.; Aeppli, Gabriel] UCL, London Ctr Nanotechnol, London WC1H 0AH, England.
   [Warner, Marc; Morley, Gavin W.; Stoneham, A. Marshall; Gardener, Jules A.; Fisher, Andrew J.; Aeppli, Gabriel] UCL, Dept Phys & Astron, London WC1H 0AH, England.
   [Din, Salahud; Wu, Zhenlin; Heutz, Sandrine] Univ London Imperial Coll Sci Technol & Med, London Ctr Nanotechnol, London SW7 2AZ, England.
   [Din, Salahud; Wu, Zhenlin; Heutz, Sandrine] Univ London Imperial Coll Sci Technol & Med, Dept Mat, London SW7 2AZ, England.
   [Tupitsyn, Igor S.] Univ British Columbia, Pacific Inst Theoret Phys, Vancouver, BC V6T 1Z1, Canada.
   [Kay, Christopher W. M.] UCL, Inst Struct & Mol Biol, London WC1E 6BT, England.
   [Kay, Christopher W. M.] UCL, London Ctr Nanotechnol, London WC1E 6BT, England.
C3 University of London; University College London; University of London; University College London; Imperial College London; University of London; University College London; Imperial College London; University of British Columbia; University of London; University College London; Birkbeck University London; University of London; University College London
RP Warner, M (corresponding author), Harvard Univ, Dept Phys, Cambridge, MA 02138 USA.
EM marc.warner@ucl.ac.uk; gabriel.aeppli@ucl.ac.uk
FU EPSRC [EP/F039948/1, EP/F041349/1, EP/F04139X/1]; Royal Society; IARPA; NSERC [CNXP 22R81695]; PITP; EPSRC [EP/F04139X/1, EP/F039948/1, EP/H026622/1, EP/F041349/1, EP/K032526/1, EP/H002022/1, EP/H002367/1] Funding Source: UKRI; Engineering and Physical Sciences Research Council [EP/H002022/1, EP/H026622/1, EP/F041349/1, EP/F04139X/1, EP/K032526/1, EP/H002367/1, EP/F039948/1] Funding Source: researchfish
NR 35
TC 258
Z9 277
U1 2
U2 461
PU NATURE PUBLISHING 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 28
PY 2013
VL 503
IS 7477
BP 504
EP +
DI 10.1038/nature12597
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 258MU
UT WOS:000327464200038
PM 24162849
DA 2026-03-09
ER

PT J
AU Marchi, S
   Chapman, CR
   Fassett, CI
   Head, JW
   Bottke, WF
   Strom, RG
AF Marchi, Simone
   Chapman, Clark R.
   Fassett, Caleb I.
   Head, James W.
   Bottke, W. F.
   Strom, Robert G.
TI Global resurfacing of Mercury 4.0-4.1 billion years ago by heavy bombardment and volcanism
SO NATURE
LA English
DT Article
ID crater chronology; lunar; stratigraphy; impacts; origin; moon; ages
AB The most heavily cratered terrains on Mercury have been estimated to be about 4 billion years (Gyr) old(1-4), but this was based on images of only about 45 per cent of the surface; even older regions could have existed in the unobserved portion. These terrains have a lower density of craters less than 100 km in diameter than does the Moon(1,3,5), an observation attributed to preferential resurfacing on Mercury. Here we report global crater statistics of Mercury's most heavily cratered terrains on the entire surface. Applying a recent model for early lunar crater chronology(6) and an updated dynamical extrapolation to Mercury(7), we find that the oldest surfaces were emplaced just after the start of the Late Heavy Bombardment (LHB) about 4.0-4.1 Gyr ago. Mercury's global record of large impact basins(8), which has hitherto not been dated, yields a similar surface age. This agreement implies that resurfacing was global and was due to volcanism, as previously suggested(1,5). This activity ended during the tail of the LHB, within about 300-400 million years after the emplacement of the oldest terrains on Mercury. These findings suggest that persistent volcanism could have been aided by the surge of basin-scale impacts during this bombardment.
C1 [Marchi, Simone] NASA, Lunar Sci Inst, SW Res Inst, Boulder, CO 80302 USA.
   [Chapman, Clark R.; Bottke, W. F.] SW Res Inst, Boulder, CO 80302 USA.
   [Fassett, Caleb I.] Mt Holyoke Coll, Dept Astron, S Hadley, MA 01075 USA.
   [Head, James W.] Brown Univ, Dept Geol Sci, Providence, RI 02912 USA.
   [Strom, Robert G.] Univ Arizona, Dept Planetary Sci, Tucson, AZ 85721 USA.
C3 National Aeronautics & Space Administration (NASA); Mount Holyoke College; Brown University; University of Arizona
RP Marchi, S (corresponding author), NASA, Lunar Sci Inst, SW Res Inst, Boulder, CO 80302 USA.
EM marchi@boulder.swri.edu
FU NASA Lunar Science Institute (Center for Lunar Origin and Evolution at the Southwest Research Institute in Boulder, Colorado-NASA) [NNA09DB32A]; NASA [NASW-00002, NAS5-97271]; NASA Lunar Science Institute (Center for Lunar Science and Exploration at the Lunar and Planetary Institute in Houston, Texas)
NR 31
TC 154
Z9 169
U1 0
U2 56
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 4
PY 2013
VL 499
IS 7456
BP 59
EP 61
DI 10.1038/nature12280
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 176ED
UT WOS:000321285600032
PM 23823793
DA 2026-03-09
ER

PT J
AU Peralta, EA
   Soong, K
   England, RJ
   Colby, ER
   Wu, Z
   Montazeri, B
   McGuinness, C
   McNeur, J
   Leedle, KJ
   Walz, D
   Sozer, EB
   Cowan, B
   Schwartz, B
   Travish, G
   Byer, RL
AF Peralta, E. A.
   Soong, K.
   England, R. J.
   Colby, E. R.
   Wu, Z.
   Montazeri, B.
   McGuinness, C.
   McNeur, J.
   Leedle, K. J.
   Walz, D.
   Sozer, E. B.
   Cowan, B.
   Schwartz, B.
   Travish, G.
   Byer, R. L.
TI Demonstration of electron acceleration in a laser-driven dielectric microstructure
SO NATURE
LA English
DT Article
AB The enormous size and cost of current state-of-the-art accelerators based on conventional radio-frequency technology has spawned great interest in the development of new acceleration concepts that are more compact and economical. Micro-fabricated dielectric laser accelerators (DLAs) are an attractive approach, because such dielectric microstructures can support accelerating fields one to two orders of magnitude higher than can radio-frequency cavity-based accelerators. DLAs use commercial lasers as a power source, which are smaller and less expensive than the radio-frequency klystrons that power today's accelerators. In addition, DLAs are fabricated via low-cost, lithographic techniques that can be used for mass production. However, despite several DLA structures having been proposed recently(1-4), no successful demonstration of acceleration in these structures has so far been shown. Here we report high-gradient (beyond 250 MeV m(-1)) acceleration of electrons in a DLA. Relativistic (60-MeV) electrons are energy-modulated over 563 +/- 104 optical periods of a fused silica grating structure, powered by a 800-nm-wavelength mode-locked Ti:sapphire laser. The observed results are in agreement with analytical models and electrodynamic simulations. By comparison, conventional modern linear accelerators operate at gradients of 10-30 MeV m(-1), and the first linear radio-frequency cavity accelerator was ten radio-frequency periods (one metre) long with a gradient of approximately 1.6 MeV m(-1) (ref. 5). Our results set the stage for the development of future multi-staged DLA devices composed of integrated on-chip systems. This would enable compact table-top accelerators on the MeV-GeV (10(6)-10(9) eV) scale for security scanners and medical therapy, university-scale X-ray light sources for biological and materials research, and portable medical imaging devices, and would substantially reduce the size and cost of a future collider on the multi-TeV (10(12) eV) scale.
C1 [Peralta, E. A.; Soong, K.; McGuinness, C.; Byer, R. L.] Stanford Univ, Dept Appl Phys, Stanford, CA 94305 USA.
   [England, R. J.; Colby, E. R.; Wu, Z.; Walz, D.] SLAC Natl Accelerator Lab, Menlo Pk, CA 94025 USA.
   [Montazeri, B.; Leedle, K. J.] Stanford Univ, Dept Elect Engn, Stanford, CA 94305 USA.
   [McNeur, J.; Sozer, E. B.; Travish, G.] Univ Calif Los Angeles, Dept Phys & Astron, Los Angeles, CA 90024 USA.
   [Cowan, B.; Schwartz, B.] Tech X Corp, Boulder, CO 80303 USA.
C3 Stanford University; Stanford University; United States Department of Energy (DOE); SLAC National Accelerator Laboratory; Stanford University; University of California System; University of California Los Angeles; Tech-X Corporation
RP Byer, RL (corresponding author), Stanford Univ, Dept Appl Phys, Stanford, CA 94305 USA.
EM rlbyer@stanford.edu
FU US DoE [DE-FG03-92ER40693]; DARPA [N66001-11-1-4199]; NSF [ECS-9731293]; US Defense Threat Reduction Agency (DTRA) [HDTRA1-09-1-0043]
NR 27
TC 383
Z9 436
U1 0
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 NOV 7
PY 2013
VL 503
IS 7474
BP 91
EP +
DI 10.1038/nature12664
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 247AS
UT WOS:000326585600037
PM 24077116
DA 2026-03-09
ER

PT J
AU Cox, PM
   Pearson, D
   Booth, BB
   Friedlingstein, P
   Huntingford, C
   Jones, CD
   Luke, CM
AF Cox, Peter M.
   Pearson, David
   Booth, Ben B.
   Friedlingstein, Pierre
   Huntingford, Chris
   Jones, Chris D.
   Luke, Catherine M.
TI Sensitivity of tropical carbon to climate change constrained by carbon dioxide variability
SO NATURE
LA English
DT Article
ID cycle; feedback; drought; biomass; risk
AB The release of carbon from tropical forests may exacerbate future climate change(1), but the magnitude of the effect in climate models remains uncertain(2). Coupled climate-carbon-cycle models generally agree that carbon storage on land will increase as a result of the simultaneous enhancement of plant photosynthesis and water use efficiency under higher atmospheric CO2 concentrations, but will decrease owing to higher soil and plant respiration rates associated with warming temperatures(3). At present, the balance between these effects varies markedly among coupled climate-carbon-cycle models, leading to a range of 330 gigatonnes in the projected change in the amount of carbon stored on tropical land by 2100. Explanations for this large uncertainty include differences in the predicted change in rainfall in Amazonia(4,5) and variations in the responses of alternative vegetation models to warming(6). Here we identify an emergent linear relationship, across an ensemble of models(7), between the sensitivity of tropical land carbon storage to warming and the sensitivity of the annual growth rate of atmospheric CO2 to tropical temperature anomalies(8). Combined with contemporary observations of atmospheric CO2 concentration and tropical temperature, this relationship provides a tight constraint on the sensitivity of tropical land carbon to climate change. We estimate that over tropical land from latitude 30 degrees north to 30 degrees south, warming alone will release 53 +/- 17 gigatonnes of carbon per kelvin. Compared with the unconstrained ensemble of climate-carbon-cycle projections, this indicates a much lower risk of Amazon forest die-back under CO2-induced climate change if CO2 fertilization effects are as large as suggested by current models(9). Our study, however, also implies greater certainty that carbon will be lost from tropical land if warming arises from reductions in aerosols(10) or increases in other greenhouse gases(11).
C1 [Cox, Peter M.; Friedlingstein, Pierre; Luke, Catherine M.] Univ Exeter, Coll Engn Math & Phys Sci, Exeter EX4 4QF, Devon, England.
   [Pearson, David; Booth, Ben B.; Jones, Chris D.] Hadley Ctr, Met Off, Exeter EX1 3PB, Devon, England.
   [Huntingford, Chris] Ctr Ecol & Hydrol, Wallingford OX10 8BB, Oxon, England.
C3 University of Exeter; Met Office - UK; Hadley Centre; UK Centre for Ecology & Hydrology (UKCEH)
RP Cox, PM (corresponding author), Univ Exeter, Coll Engn Math & Phys Sci, Exeter EX4 4QF, Devon, England.
EM p.m.cox@exeter.ac.uk
FU NERC NCEO; EU; DECC/Defra Met Office Hadley Centre [GA01101]; CEH Science Budget; Newton Institute; Natural Environment Research Council [earth010002] Funding Source: researchfish; NERC [earth010002] Funding Source: UKRI
NR 29
TC 597
Z9 681
U1 11
U2 789
PU NATURE PUBLISHING 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 21
PY 2013
VL 494
IS 7437
BP 341
EP 344
DI 10.1038/nature11882
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 095CS
UT WOS:000315312900035
PM 23389447
DA 2026-03-09
ER

PT J
AU Rompolas, P
   Mesa, KR
   Greco, V
AF Rompolas, Panteleimon
   Mesa, Kailin R.
   Greco, Valentina
TI Spatial organization within a niche as a determinant of stem-cell fate
SO NATURE
LA English
DT Article
ID hair follicle bulge; label-retaining cells; self-renewal; wound repair; in-vivo; homeostasis; distinct; skin; lgr5; identification
AB Stem-cell niches in mammalian tissues are often heterogeneous and compartmentalized; however, whether distinct niche locations determine different stem-cell fates remains unclear. To test this hypothesis, here we use the mouse hair follicle niche and combine intravital microscopy with genetic lineage tracing to re-visit the same stem-cell lineages, from their exact place of origin, throughout regeneration in live mice. Using this method, we show directly that the position of a stem cell within the hair follicle niche can predict whether it is likely to remain uncommitted, generate precursors or commit to a differentiated fate. Furthermore, using laser ablation we demonstrate that hair follicle stem cells are dispensable for regeneration, and that epithelial cells, which do not normally participate in hair growth, re-populate the lost stem-cell compartment and sustain hair regeneration. This study provides a general model for niche-induced fate determination in adult tissues.
C1 [Rompolas, Panteleimon; Mesa, Kailin R.; Greco, Valentina] Yale Univ, Sch Med, Dept Genet, Dept Dermatol,Yale Stem Cell Ctr,Yale Canc Ctr, New Haven, CT 06510 USA.
C3 Yale University; Yale New Haven Hospital
RP Greco, V (corresponding author), Yale Univ, Sch Med, Dept Genet, Dept Dermatol,Yale Stem Cell Ctr,Yale Canc Ctr, New Haven, CT 06510 USA.
EM valentina.greco@yale.edu
FU New York Stem Cell Foundation; American Cancer Society [RGS-12-059-01-DCC]; National Institute of Arthritis and Musculoskeletal and Skin Diseases [1RO1AR063663-01]; National Institute of Arthritis and Musculoskeletal and Skin Diseases [R01AR063663] Funding Source: NIH RePORTER
NR 49
TC 329
Z9 398
U1 3
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 OCT 24
PY 2013
VL 502
IS 7472
BP 513
EP +
DI 10.1038/nature12602
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 238YN
UT WOS:000325988400046
PM 24097351
DA 2026-03-09
ER

PT J
AU Huang, DY
   Nel, A
   Cai, CY
   Li, QB
   Engel, MS
AF Huang, Diying
   Nel, Andre
   Cai, Chenyang
   Li, Qibin
   Engel, Michael S.
TI Amphibious flies and paedomorphism in the Jurassic period
SO NATURE
LA English
DT Article
ID nymphomyiidae diptera; larva; fly
AB The species of the Strashilidae (strashilids) have been the most perplexing of fossil insects from the Jurassic period of Russia and China(1,2). They have been widely considered to be ectoparasites of pterosaurs or feathered dinosaurs, based on the putative presence of piercing and sucking mouthparts and hind tibio-basitarsal pincers purportedly used to fix onto the host's hairs or feathers(1-6). Both the supposed host and parasite occur in the Daohugou beds from the Middle Jurassic epoch of China (approximately 165 million years ago)(7,8). Here we analyse the morphology of strashilids from the Daohugou beds, and reach markedly different conclusions; namely that strashilids are highly specialized flies (Diptera) bearing large membranous wings, with substantial sexual dimorphism of the hind legs and abdominal extensions. The idea that they belong to an extinct order(2) is unsupported, and the lineage can be placed within the true flies. In terms of major morphological and inferred behavioural features, strashilids resemble the recent (extant) and relict members of the aquatic fly family Nymphomyiidae. Their ontogeny are distinguished by the persistence in adult males of larval abdominal respiratory gills, representing a unique case of paedomorphism among endopterygote insects. Adult strashilids were probably aquatic or amphibious, shedding their wings after emergence and mating in the water.
C1 [Huang, Diying; Cai, Chenyang; Li, Qibin] Chinese Acad Sci, Nanjing Inst Geol & Palaeontol, State Key Lab Palaeobiol & Stratig, Nanjing 210008, Jiangsu, Peoples R China.
   [Nel, Andre] Museum Natl Hist Nat, CNRS UMR 7205, CP 50, 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.
C3 Chinese Academy of Sciences; Museum National d'Histoire Naturelle (MNHN); Centre National de la Recherche Scientifique (CNRS); CNRS - Institute of Ecology & Environment (INEE); University of Kansas; University of Kansas
RP Huang, DY (corresponding author), Chinese Acad Sci, Nanjing Inst Geol & Palaeontol, State Key Lab Palaeobiol & Stratig, Nanjing 210008, Jiangsu, Peoples R China.
EM dyhuang@nigpas.ac.cn
FU National Basic Research Program of China [2012CB821903]; National Natural Science Foundation of China [91114201, J1210006]; Outstanding Youth Foundation of Jiangsu Province [BK2012049]; Chinese Academy of Sciences [KZCX2-YW-QN104]; US National Science Foundation [DEB-0542909]
NR 27
TC 35
Z9 40
U1 1
U2 78
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 7
PY 2013
VL 495
IS 7439
BP 94
EP 97
DI 10.1038/nature11898
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 105BE
UT WOS:000316039800046
PM 23426262
DA 2026-03-09
ER

PT J
AU Wang, TL
   Fu, GB
   Pan, XJ
   Wu, JP
   Gong, XQ
   Wang, JW
   Shi, YG
AF Wang, Tingliang
   Fu, Guobin
   Pan, Xiaojing
   Wu, Jianping
   Gong, Xinqi
   Wang, Jiawei
   Shi, Yigong
TI Structure of a bacterial energy-coupling factor transporter
SO NATURE
LA English
DT Article
ID maltose transporter; crystal-structure; binding; intermediate; prokaryotes; complex
AB The energy-coupling factor (ECF) transporters constitute a novel family of conserved membrane transporters in prokaryotes that have a similar domain organization to the ATP-binding cassette transporters(1-3). Each ECF transporter comprises a pair of cytosolic ATPases (the A and A' components, or EcfA and EcfA'), a membrane-embedded substrate-binding protein (the S component, or EcfS) and a transmembrane energy-coupling component (the T component, or EcfT) that links the EcfA-EcfA' subcomplex to EcfS. The structure and transport mechanism of the quaternary ECF transporter remain largely unknown. Here we report the crystal structure of a nucleotide-free ECF transporter from Lactobacillus brevis at a resolution of 3.5 angstrom. The T component has a horseshoe-shaped open architecture, with five alpha-helices as transmembrane segments and two cytoplasmic alpha-helices as coupling modules connecting to the A and A' components. Strikingly, the S component, thought to be specific for hydroxymethyl pyrimidine, lies horizontally along the lipid membrane and is bound exclusively by the five transmembrane segments and the two cytoplasmic helices of the T component. These structural features suggest a plausible working model for the transport cycle of the ECF transporters.
C1 [Wang, Tingliang; Fu, Guobin; Pan, Xiaojing; Wu, Jianping; Gong, Xinqi; Shi, Yigong] Tsinghua Univ, Minist Educ Key Lab Prot Sci, Beijing 100084, Peoples R China.
   [Wang, Tingliang; Fu, Guobin; Pan, Xiaojing; Wu, Jianping; Gong, Xinqi; Shi, Yigong] Tsinghua Univ, Sch Life Sci, Struct Biol Ctr, Tsinghua Peking Joint Ctr Life Sci, Beijing 100084, Peoples R China.
   [Wang, Tingliang; Fu, Guobin; Pan, Xiaojing; Wu, Jianping; Gong, Xinqi; Shi, Yigong] Tsinghua Univ, Sch Med, Beijing 100084, Peoples R China.
   [Wang, Jiawei] Tsinghua Univ, State Key Lab Biomembrane & Membrane Biotechnol, Beijing 100084, Peoples R China.
C3 Tsinghua University; Tsinghua University; Tsinghua University; Tsinghua University
RP Shi, YG (corresponding author), Tsinghua Univ, Minist Educ Key Lab Prot Sci, Beijing 100084, Peoples R China.
EM shi-lab@tsinghua.edu.cn
FU Ministry of Science and Technology (973 Programs) [2009CB918801, 2013CB910602]; National Natural Science Foundation of China [31021002, 31130002]
NR 32
TC 61
Z9 76
U1 3
U2 163
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 9
PY 2013
VL 497
IS 7448
BP 272
EP +
DI 10.1038/nature12045
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 139CD
UT WOS:000318558200043
PM 23584587
DA 2026-03-09
ER

PT J
AU Liu, SY
   Selck, C
   Friedrich, B
   Lutz, R
   Vila-Farré, M
   Dahl, A
   Brandl, H
   Lakshmanaperumal, N
   Henry, I
   Rink, JC
AF Liu, S. -Y.
   Selck, C.
   Friedrich, B.
   Lutz, R.
   Vila-Farre, M.
   Dahl, A.
   Brandl, H.
   Lakshmanaperumal, N.
   Henry, I.
   Rink, J. C.
TI Reactivating head regrowth in a regeneration-deficient planarian species
SO NATURE
LA English
DT Article
ID dendrocoelum-lacteum; polarity; neoblasts; alignment; region; cells
AB Species capable of regenerating lost body parts occur throughout the animal kingdom, yet close relatives are often regeneration incompetent(1,2). Why in the face of 'survival of the fittest' some animals regenerate but others do not remains a fascinating question(3). Planarian flatworms are well known and studied for their ability to regenerate from minute tissue pieces, yet species with limited regeneration abilities have been described even amongst planarians(4). Here we report the characterization of the regeneration defect in the planarian Dendrocoelum lacteum and its successful rescue. Tissue fragments cut from the posterior half of the body of this species are unable to regenerate a head and ultimately die(5). We find that this defect originates during the early stages of head specification, which require inhibition of canonical Wnt signalling in other planarian species(6-8). Notably, RNA interference (RNAi)-mediated knockdown of Dlac-beta-catenin-1, the Wnt signal transducer, restored the regeneration of fully functional heads on tail pieces, rescuing D. lacteum's regeneration defect. Our results demonstrate the utility of comparative studies towards the reactivation of regenerative abilities in regeneration-deficient animals. Furthermore, the availability of D. lacteum as a regeneration-impaired planarian model species provides a first step towards elucidating the evolutionary mechanisms that ultimately determine why some animals regenerate and others do not.
C1 [Liu, S. -Y.; Vila-Farre, M.; Brandl, H.; Lakshmanaperumal, N.; Henry, I.; Rink, J. C.] Max Planck Inst Mol Cell Biol & Genet, D-01307 Dresden, Germany.
   [Selck, C.; Friedrich, B.; Lutz, R.; Rink, J. C.] Tech Univ Dresden, DFG Ctr Regenerat Therapies Dresden CRTD, D-01307 Dresden, Germany.
   [Dahl, A.] Tech Univ Dresden, Biotechnol Ctr Biotec, DFG Ctr Regenerat Therapies Dresden CRTD, Deep Sequencing Grp SFB655, D-01307 Dresden, Germany.
C3 Max Planck Society; Technische Universitat Dresden; Technische Universitat Dresden
RP Rink, JC (corresponding author), Max Planck Inst Mol Cell Biol & Genet, Pfotenhauerstr 108, D-01307 Dresden, Germany.
EM rink@mpi-cbg.de
NR 39
TC 149
Z9 172
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 AUG 1
PY 2013
VL 500
IS 7460
BP 81
EP U103
DI 10.1038/nature12414
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 192VK
UT WOS:000322514800032
PM 23883932
DA 2026-03-09
ER

PT J
AU Hirose, T
   Horvitz, HR
AF Hirose, Takashi
   Horvitz, H. Robert
TI An Sp1 transcription factor coordinates caspase-dependent and -independent apoptotic pathways
SO NATURE
LA English
DT Article
ID programmed cell-death; c-elegans; protein; genetics; encodes; egl-1
AB During animal development, the proper regulation of apoptosis requires the precise spatial and temporal execution of cell-death programs, which can include both caspase-dependent and caspase-independent pathways(1,2). Although the mechanisms of caspase-dependent and -independent cell killing have been examined extensively, how these pathways are coordinated within a single cell that is fated to die is unknown. Here we show that the Caenorhabditis elegans Sp1 transcription factor SPTF-3 specifies the programmed cell deaths of at least two cells-the sisters of the pharyngeal M4 motor neuron and the AQR sensory neuron-by transcriptionally activating both caspase-dependent and -independent apoptotic pathways. SPTF-3 directly drives the transcription of the geneegl-1, which encodes a BH3-only protein that promotes apoptosis through the activation of the CED-3 caspase(3). In addition, SPTF-3 directly drives the transcription of the AMP-activated protein kinase-related gene pig-1, which encodes a protein kinase and functions in apoptosis of the M4 sister and AQR sister independently of the pathway that activates-CED-3 (refs 4, 5). Thus, a single transcription factor controls two distinct cell-killing programs that act in parallel to drive apoptosis. Our findings reveal a bivalent regulatory node for caspase-dependent and -independent pathways in the regulation of cell-type-specific apoptosis. We propose that such nodes might act as features of a general mechanism for regulating cell-type-specific apoptosis and could be therapeutic targets for diseases involving the dysregulation of apoptosis through multiple cell-killing mechanisms.
C1 [Hirose, Takashi; Horvitz, H. Robert] MIT, Dept Biol, Howard Hughes Med Inst, Cambridge, MA 02139 USA.
C3 Massachusetts Institute of Technology (MIT); Howard Hughes Medical Institute
RP Horvitz, HR (corresponding author), MIT, Dept Biol, Howard Hughes Med Inst, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
EM horvitz@mit.edu
FU NIH Office of Research Infrastructure Programs [P40 OD010440]; National BioResource project for strains; Howard Hughes Medical Institute; Ministry of Education, Science, Technology, Sports and Culture of Japan; National Institute of General Medical Sciences; NIH Office of the Director [P40OD010440] Funding Source: NIH RePORTER
NR 28
TC 52
Z9 72
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 15
PY 2013
VL 500
IS 7462
BP 354
EP +
DI 10.1038/nature12329
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 201AF
UT WOS:000323112400037
PM 23851392
DA 2026-03-09
ER

PT J
AU Chen, TW
   Wardill, TJ
   Sun, Y
   Pulver, SR
   Renninger, SL
   Baohan, A
   Schreiter, ER
   Kerr, RA
   Orger, MB
   Jayaraman, V
   Looger, LL
   Svoboda, K
   Kim, DS
AF Chen, Tsai-Wen
   Wardill, Trevor J.
   Sun, Yi
   Pulver, Stefan R.
   Renninger, Sabine L.
   Baohan, Amy
   Schreiter, Eric R.
   Kerr, Rex A.
   Orger, Michael B.
   Jayaraman, Vivek
   Looger, Loren L.
   Svoboda, Karel
   Kim, Douglas S.
TI Ultrasensitive fluorescent proteins for imaging neuronal activity
SO NATURE
LA English
DT Article
ID primary visual-cortex; encoded ca2+ indicators; in-vivo; neural activity; orientation selectivity; cortical-neurons; calcium transients; target recognition; dendritic spines; structural basis
AB Fluorescent calcium sensors are widely used to image neural activity. Using structure-based mutagenesis and neuron-based screening, we developed a family of ultrasensitive protein calcium sensors (GCaMP6) that outperformed other sensors in cultured neurons and in zebrafish, flies and mice in vivo. In layer 2/3 pyramidal neurons of the mouse visual cortex, GCaMP6 reliably detected single action potentials in neuronal somata and orientation-tuned synaptic calcium transients in individual dendritic spines. The orientation tuning of structurally persistent spines was largely stable over timescales of weeks. Orientation tuning averaged across spine populations predicted the tuning of their parent cell. Although the somata of GABAergic neurons showed little orientation tuning, their dendrites included highly tuned dendritic segments (5-40-mm long). GCaMP6 sensors thus provide new windows into the organization and dynamics of neural circuits over multiple spatial and temporal scales.
C1 [Chen, Tsai-Wen; Wardill, Trevor J.; Sun, Yi; Pulver, Stefan R.; Baohan, Amy; Schreiter, Eric R.; Kerr, Rex A.; Jayaraman, Vivek; Looger, Loren L.; Svoboda, Karel; Kim, Douglas S.] Howard Hughes Med Inst, Ashburn, VA 20147 USA.
   [Renninger, Sabine L.; Orger, Michael B.] Champalimaud Ctr Unknown, Champalimaud Neurosci Programme, P-1400038 Lisbon, Portugal.
   [Baohan, Amy] Univ Calif Los Angeles, Dept Neurobiol, Los Angeles, CA 90095 USA.
C3 Howard Hughes Medical Institute; Fundacao Champalimaud; University of California System; University of California Los Angeles
RP Orger, MB (corresponding author), Champalimaud Ctr Unknown, Champalimaud Neurosci Programme, Ave Brasilia, P-1400038 Lisbon, Portugal.
EM michael.orger@neuro.fchampalimaud.org; jayaramanv@janelia.hhmi.org; loogerl@janelia.hhmi.org; svobodak@janelia.hhmi.org; kimd@janelia.hhmi.org
FU Swiss National Science Foundation; Marie Curie Career Integration Grant [PCIG09-GA-2011-294049]; National Institute of General Medical Sciences [T32GM008042] Funding Source: NIH RePORTER
NR 64
TC 4540
Z9 5683
U1 11
U2 912
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 18
PY 2013
VL 499
IS 7458
BP 295
EP +
DI 10.1038/nature12354
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 184RJ
UT WOS:000321910700027
PM 23868258
DA 2026-03-09
ER

PT J
AU Kondo, T
   Hayashi, S
AF Kondo, Takefumi
   Hayashi, Shigeo
TI Mitotic cell rounding accelerates epithelial invagination
SO NATURE
LA English
DT Article
ID apical constriction; adherens junctions; drosophila; tracheal; morphogenesis; shape; integration; migration; tribbles; homolog
AB Mitotic cells assume a spherical shape by increasing their surface tension and osmotic pressure by extensively reorganizing their interphase actin cytoskeleton into a cortical meshwork and their microtubules into the mitotic spindle(1,2). Mitotic entry is known to interfere with tissue morphogenetic events that require cell-shape changes controlled by the interphase cytoskeleton, such as apical constriction(3-5). However, here we show that mitosis plays an active role in the epithelial invagination of the Drosophila melanogaster tracheal placode. Invagination begins with a slow phase under the control of epidermal growth factor receptor (EGFR) signalling; in this process, the central apically constricted cells, which are surrounded by intercalating cells(6,7), form a shallow pit. This slow phase is followed by a fast phase, in which the pit is rapidly depressed, accompanied by mitotic entry, which leads to the internalization of all the cells in the placode. We found that mitotic cell rounding, but not cell division, of the central cells in the placode is required to accelerate invagination, in conjunction with EGFR-induced myosin II contractility in the surrounding cells. We propose that mitotic cell rounding causes the epithelium to buckle under pressure and acts as a switch for morphogenetic transition at the appropriate time.
C1 [Kondo, Takefumi; Hayashi, Shigeo] RIKEN Ctr Dev Biol, Lab Morphogenet Signaling, Chuo Ku, Kobe, Hyogo 6500047, Japan.
   [Hayashi, Shigeo] Kobe Univ, Dept Biol, Grad Sch Sci, Kobe, Hyogo 6578501, Japan.
C3 RIKEN; Kobe University
RP Hayashi, S (corresponding author), RIKEN Ctr Dev Biol, Lab Morphogenet Signaling, Chuo Ku, 2-2-3 Minatojima Minamimachi, Kobe, Hyogo 6500047, Japan.
EM shayashi@cdb.riken.jp
FU Ministry of Education, Culture, Sports, Science and Technology, Japan [22111007, 23770624]; RIKEN Special Postdoctoral Researcher Program; Grants-in-Aid for Scientific Research [22111007, 22111001] Funding Source: KAKEN
NR 27
TC 126
Z9 144
U1 0
U2 57
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 7
PY 2013
VL 494
IS 7435
BP 125
EP 129
DI 10.1038/nature11792
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 087DJ
UT WOS:000314741200047
PM 23334416
DA 2026-03-09
ER

PT J
AU Kim, YJ
   Hofmann, KP
   Ernst, OP
   Scheerer, P
   Choe, HW
   Sommer, ME
AF Kim, Yong Ju
   Hofmann, Klaus Peter
   Ernst, Oliver P.
   Scheerer, Patrick
   Choe, Hui-Woog
   Sommer, Martha E.
TI Crystal structure of pre-activated arrestin p44
SO NATURE
LA English
DT Article
ID splice variant; rhodopsin interactions; visual arrestin; 48-kda protein; beta-arrestin; binding; dynamics; mechanism; model
AB Arrestins interact with G-protein-coupled receptors (GPCRs) to block interaction with G proteins(1,2) and initiate G-protein-independent signalling(3). Arrestins have a bi-lobed structure that is stabilized by a long carboxy-terminal tail (C-tail), and displacement of the C-tail by receptor-attached phosphates activates arrestins for binding active GPCRs(4). Structures of the inactive state of arrestin are available(5,6), but it is not known how C-tail displacement activates arrestin for receptor coupling. Here we present a 3.0 angstrom crystal structure of the bovine arrestin-1 splice variant p44, in which the activation step is mimicked by C-tail truncation. The structure of this pre-activated arrestin is profoundly different from the basal state and gives insight into the activation mechanism. p44 displays breakage of the central polar core and other interlobe hydrogen-bond networks, leading to a 216 rotation of the two lobes as compared to basal arrestin-1. Rearrangements in key receptor-binding loops in the central crest region include the finger loop(7-9), loop 139 (refs 8, 10, 11) and the sequence Asp 296-Asn 305 (or gate loop), here identified as controlling the polar core. We verified the role of these conformational alterations in arrestin activation and receptor binding by site-directed fluorescence spectroscopy. The data indicate a mechanism for arrestin activation in which C-tail displacement releases critical central-crest loops from restricted to extended receptor-interacting conformations. In parallel, increased flexibility between the two lobes facilitates a proper fitting of arrestin to the active receptor surface. Our results provide a snapshot of an arrestin ready to bind the active receptor, and give an insight into the role of naturally occurring truncated arrestins in the visual system.
C1 [Kim, Yong Ju; Hofmann, Klaus Peter; Choe, Hui-Woog; Sommer, Martha E.] Charite, Inst Med Phys & Biophys CC2, D-10117 Berlin, Germany.
   [Hofmann, Klaus Peter] Humboldt Univ, Zentrum Biophys & Bioinformat, D-10115 Berlin, Germany.
   [Ernst, Oliver P.] Univ Toronto, Dept Biochem, Toronto, ON M5S 1A8, Canada.
   [Ernst, Oliver P.] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A8, Canada.
   [Scheerer, Patrick] Charite, AG Prot Xray Crystallog, Inst Med Phys & Biophys CC2, D-10117 Berlin, Germany.
   [Choe, Hui-Woog] Chonbuk Natl Univ, Coll Nat Sci, Dept Chem, Chonju 561756, South Korea.
C3 Free University of Berlin; Humboldt University of Berlin; Charite Universitatsmedizin Berlin; Humboldt University of Berlin; University of Toronto; University of Toronto; Free University of Berlin; Humboldt University of Berlin; Charite Universitatsmedizin Berlin; Jeonbuk National University
RP Sommer, ME (corresponding author), Charite, Inst Med Phys & Biophys CC2, Charitepl 1, D-10117 Berlin, Germany.
EM patrick.scheerer@charite.de; hwchoe@chonbuk.ac.kr; martha.sommer@charite.de
FU Deutsche Forschungsgemeinschaft [SFB449, SFB740, SFB1078-B6, SO1037/1-2]; DFG Cluster of Excellence 'Unifying Concepts in Catalysis' [D3/E3-1]; European Research Council [ERC-2009/249910-TUDOR]; Canada Excellence Research Chair program; Basic Science Research Program through the National Research Foundation of Korea; Ministry of Education, Science and Technology [2012R1A1A2044752]
NR 47
TC 123
Z9 150
U1 0
U2 33
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 2
PY 2013
VL 497
IS 7447
BP 142
EP +
DI 10.1038/nature12133
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 134OK
UT WOS:000318221500050
PM 23604253
DA 2026-03-09
ER

PT J
AU Tye, KM
   Mirzabekov, JJ
   Warden, MR
   Ferenczi, EA
   Tsai, HC
   Finkelstein, J
   Kim, SY
   Adhikari, A
   Thompson, KR
   Andalman, AS
   Gunaydin, LA
   Witten, IB
   Deisseroth, K
AF Tye, Kay M.
   Mirzabekov, Julie J.
   Warden, Melissa R.
   Ferenczi, Emily A.
   Tsai, Hsing-Chen
   Finkelstein, Joel
   Kim, Sung-Yon
   Adhikari, Avishek
   Thompson, Kimberly R.
   Andalman, Aaron S.
   Gunaydin, Lisa A.
   Witten, Ilana B.
   Deisseroth, Karl
TI Dopamine neurons modulate neural encoding and expression of depression-related behaviour
SO NATURE
LA English
DT Article
ID stress-induced anhedonia; ventral tegmental area; social defeat; animal-model; aversive stimuli; reward circuit; gaba neurons; susceptibility; mice; inhibition
AB Major depression is characterized by diverse debilitating symptoms that include hopelessness and anhedonia(1). Dopamine neurons involved in reward and motivation(2-9) are among many neural populations that have been hypothesized to be relevant(10), and certain antidepressant treatments, including medications and brain stimulation therapies, can influence the complex dopamine system. Until now it has not been possible to test this hypothesis directly, even in animal models, as existing therapeutic interventions are unable to specifically target dopamine neurons. Here we investigated directly the causal contributions of defined dopamine neurons to multidimensional depression-like phenotypes induced by chronic mild stress, by integrating behavioural, pharmacological, optogenetic and electrophysiological methods in freely moving rodents. We found that bidirectional control (inhibition or excitation) of specified midbrain dopamine neurons immediately and bidirectionally modulates (induces or relieves) multiple independent depression symptoms caused by chronic stress. By probing the circuit implementation of these effects, we observed that optogenetic recruitment of these dopamine neurons potently alters the neural encoding of depression-related behaviours in the downstream nucleus accumbens of freely moving rodents, suggesting that processes affecting depression symptoms may involve alterations in the neural encoding of action in limbic circuitry.
C1 [Tye, Kay M.] MIT, Picower Inst Learning & Memory Brain & Cognit Sci, Cambridge, MA 02139 USA.
   [Tye, Kay M.; Mirzabekov, Julie J.; Warden, Melissa R.; Ferenczi, Emily A.; Tsai, Hsing-Chen; Finkelstein, Joel; Kim, Sung-Yon; Adhikari, Avishek; Thompson, Kimberly R.; Andalman, Aaron S.; Gunaydin, Lisa A.; Witten, Ilana B.; Deisseroth, Karl] Stanford Univ, Dept Bioengn, Stanford, CA 94305 USA.
   [Ferenczi, Emily A.; Tsai, Hsing-Chen; Kim, Sung-Yon; Deisseroth, Karl] Stanford Univ, Neurosci Program, Stanford, CA 94305 USA.
   [Deisseroth, Karl] Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA.
   [Deisseroth, Karl] Stanford Univ, Howard Hughes Med Inst, Stanford, CA 94305 USA.
   [Deisseroth, Karl] Stanford Univ, CNC Program, Stanford, CA 94305 USA.
C3 Massachusetts Institute of Technology (MIT); Stanford University; Stanford University; Stanford University; Howard Hughes Medical Institute; Stanford University; Stanford University
RP Tye, KM (corresponding author), MIT, Picower Inst Learning & Memory Brain & Cognit Sci, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
EM kaytye@mit.edu; deissero@stanford.edu
FU Helen Hay Whitney Foundation; NRSA [F32 MH880102]; JPB Foundation; NARSAD; Wiegers Family Fund; NIMH; NIDA; DARPA REPAIR Program; Keck Foundation; McKnight Foundation; Gatsby Charitable Foundation; Snyder Foundation; Woo Foundation; Albert Yu and Mary Bechman Foundation; Division Of Integrative Organismal Systems; Direct For Biological Sciences [1247950] Funding Source: National Science Foundation
NR 34
TC 855
Z9 1044
U1 4
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 JAN 24
PY 2013
VL 493
IS 7433
BP 537
EP +
DI 10.1038/nature11740
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 075GF
UT WOS:000313871400039
PM 23235822
DA 2026-03-09
ER

PT J
AU Bloodgood, BL
   Sharma, N
   Browne, HA
   Trepman, AZ
   Greenberg, ME
AF Bloodgood, Brenda L.
   Sharma, Nikhil
   Browne, Heidi Adlman
   Trepman, Alissa Z.
   Greenberg, Michael E.
TI The activity-dependent transcription factor NPAS4 regulates domain-specific inhibition
SO NATURE
LA English
DT Article
ID factor messenger-rna; neurotrophic factor; neuronal-activity; synapses; interneurons; expression; memory; cells
AB A heterogeneous population of inhibitory neurons controls the flow of information through a neural circuit(1-3). Inhibitory synapses that form on pyramidal neuron dendrites modulate the summation of excitatory synaptic potentials(4-6) and prevent the generation of dendritic calcium spikes(7,8). Precisely timed somatic inhibition limits both the number of action potentials and the time window during which firing can occur(8,9). The activity-dependent transcription factor NPAS4 regulates inhibitory synapse number and function in cell culture(10), but how this transcription factor affects the inhibitory inputs that form on distinct domains of a neuron in vivo was unclear. Here we show that in the mouse hippocampus behaviourally driven expression of NPAS4 coordinates the redistribution of inhibitory synapses made onto a CA1 pyramidal neuron, simultaneously increasing inhibitory synapse number on the cell body while decreasing the number of inhibitory synapses on the apical dendrites. This rearrangement of inhibition is mediated in part by the NPAS4 target gene brain derived neurotrophic factor (Bdnf), which specifically regulates somatic, and not dendritic, inhibition. These findings indicate that sensory stimuli, by inducing NPAS4 and its target genes, differentially control spatial features of neuronal inhibition in a way that restricts the output of the neuron while creating a dendritic environment that is permissive for plasticity.
C1 [Bloodgood, Brenda L.; Sharma, Nikhil; Browne, Heidi Adlman; Trepman, Alissa Z.; Greenberg, Michael E.] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA.
   [Bloodgood, Brenda L.] Univ Calif San Diego, Div Biol Sci, La Jolla, CA 92093 USA.
   [Sharma, Nikhil] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA.
C3 Harvard University; Harvard Medical School; University of California System; University of California San Diego; Harvard University
RP Greenberg, ME (corresponding author), Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA.
EM Michael_Greenberg@hms.harvard.edu
FU Helen Hay Whitney Foundation; L'Oreal USA Fellowship for Women in Science; Medical Foundation/Charles A. King Trust Postdoctoral Fellowship; NSF graduate student research fellowship; National Institutes of Health [NS028829];  [P30 NS047101]; National Institute of Neurological Disorders and Stroke [P30NS047101, R01NS028829] Funding Source: NIH RePORTER
CR Adesnik H, 2008, P NATL ACAD SCI USA, V105, P5597, DOI 10.1073/pnas.0800946105
   Atallah BV, 2012, NEURON, V73, P159, DOI 10.1016/j.neuron.2011.12.013
   Baldelli P, 2005, J NEUROSCI, V25, P3358, DOI 10.1523/JNEUROSCI.4227-04.2005
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   Chiu CQ, 2013, SCIENCE, V340, P759, DOI 10.1126/science.1234274
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NR 30
TC 245
Z9 291
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 7
PY 2013
VL 503
IS 7474
BP 121
EP +
DI 10.1038/nature12743
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 247AS
UT WOS:000326585600044
PM 24201284
DA 2026-03-09
ER

PT J
AU Arai, S
   Saijo, S
   Suzuki, K
   Mizutani, K
   Kakinuma, Y
   Ishizuka-Katsura, Y
   Ohsawa, N
   Terada, T
   Shirouzu, M
   Yokoyama, S
   Iwata, S
   Yamato, I
   Murata, T
AF Arai, Satoshi
   Saijo, Shinya
   Suzuki, Kano
   Mizutani, Kenji
   Kakinuma, Yoshimi
   Ishizuka-Katsura, Yoshiko
   Ohsawa, Noboru
   Terada, Takaho
   Shirouzu, Mikako
   Yokoyama, Shigeyuki
   Iwata, So
   Yamato, Ichiro
   Murata, Takeshi
TI Rotation mechanism of Enterococcus hirae V1-ATPase based on asymmetric crystal structures
SO NATURE
LA English
DT Article
ID rotor ring; v-atpase; na+-atpase; f-1-atpase; complex; f-1; validation; resolution; f1-atpase; binding
AB In various cellular membrane systems, vacuolar ATPases (V-ATPases) function as proton pumps, which are involved in many processes such as bone resorption and cancer metastasis, and these membrane proteins represent attractive drug targets for osteoporosis and cancer(1). The hydrophilic V-1 portion is known as a rotary motor, in which a central axis DF complex rotates inside a hexagonally arranged catalytic A(3)B(3) complex using ATP hydrolysis energy, but the molecular mechanism is not well defined owing to a lack of high-resolution structural information. We previously reported on the in vitro expression, purification and reconstitution of Enterococcus hirae V-1-ATPase from the A(3)B(3) and DF complexes(2,3). Here we report the asymmetric structures of the nucleotide-free (2.8 angstrom) and nucleotide-bound (3.4 angstrom) A(3)B(3) complex that demonstrate conformational changes induced by nucleotide binding, suggesting a binding order in the right-handed rotational orientation in a cooperative manner. The crystal structures of the nucleotide-free (2.2 angstrom) and nucleotide-bound (2.7 angstrom) V-1-ATPase are also reported. The more tightly packed nucleotide-binding site seems to be induced by DF binding, and ATP hydrolysis seems to be stimulated by the approach of a conserved arginine residue. To our knowledge, these asymmetric structures represent the first high-resolution view of the rotational mechanism of V-1-ATPase.
C1 [Arai, Satoshi; Suzuki, Kano; Mizutani, Kenji; Murata, Takeshi] Chiba Univ, Grad Sch Sci, Dept Chem, Inage Ku, Chiba 2638522, Japan.
   [Arai, Satoshi; Saijo, Shinya; Mizutani, Kenji; Yamato, Ichiro] Tokyo Univ Sci, Dept Biol Sci & Technol, Noda, Chiba 2788510, Japan.
   [Saijo, Shinya] RIKEN SPring 8 Ctr, Sayo, Hyogo 6795148, Japan.
   [Mizutani, Kenji; Iwata, So] Kyoto Univ, Fac Med, Dept Cell Biol, Sakyo Ku, Kyoto 6068501, Japan.
   [Kakinuma, Yoshimi] Ehime Univ, Fac Agr, Lab Mol Physiol & Genet, Matsuyama, Ehime 7908566, Japan.
   [Ishizuka-Katsura, Yoshiko; Ohsawa, Noboru; Terada, Takaho; Shirouzu, Mikako; Yokoyama, Shigeyuki; Iwata, So; Murata, Takeshi] RIKEN Syst & Struct Biol Ctr, Yokohama, Kanagawa 2300045, Japan.
   [Yokoyama, Shigeyuki] Univ Tokyo, Grad Sch Sci, Dept Biophys & Biochem, Bunkyo Ku, Tokyo 1130033, Japan.
   [Yokoyama, Shigeyuki] Univ Tokyo, Grad Sch Sci, Struct Biol Lab, Bunkyo Ku, Tokyo 1130033, Japan.
   [Murata, Takeshi] JST, PRESTO, Inage Ku, Chiba 2638522, Japan.
C3 Chiba University; Tokyo University of Science; RIKEN; Kyoto University; Ehime University; RIKEN; University of Tokyo; University of Tokyo; Japan Science & Technology Agency (JST)
RP Murata, T (corresponding author), Chiba Univ, Grad Sch Sci, Dept Chem, Inage Ku, 1-33 Yayoi Cho, Chiba 2638522, Japan.
EM t.murata@faculty.chiba-u.jp
FU Targeted Proteins Research Program [23370047, 23118705]; Special Coordination Funds for Promoting Science and Technology from the Ministry of Education, Culture, Sports, Science and Technology of the Japanese government; Grants-in-Aid for Scientific Research [23370047, 24570162] Funding Source: KAKEN; Biotechnology and Biological Sciences Research Council [BBS/B/06458] Funding Source: researchfish
NR 42
TC 106
Z9 116
U1 0
U2 62
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 31
PY 2013
VL 493
IS 7434
BP 703
EP +
DI 10.1038/nature11778
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 080CU
UT WOS:000314219600063
PM 23334411
DA 2026-03-09
ER

PT J
AU Davis, TA
   Bureau, M
   Cappellari, M
   Sarzi, M
   Blitz, L
AF Davis, Timothy A.
   Bureau, Martin
   Cappellari, Michele
   Sarzi, Marc
   Blitz, Leo
TI A black-hole mass measurement from molecular gas kinematics in NGC4526
SO NATURE
LA English
DT Article
ID sauron project; star-formation; iv
AB The masses of the supermassive black holes found in galaxy bulges are correlated with a multitude of galaxy properties(1,2), leading to suggestions that galaxies and black holes may evolve together(3). The number of reliably measured black-hole masses is small, and the number of methods for measuring them is limited(4), holding back attempts to understand this co-evolution. Directly measuring black-hole masses is currently possible with stellar kinematics (in early-type galaxies), ionized-gas kinematics (in some spiral and early-type galaxies(5-7)) and in rare objects that have central maser emission(8). Here we report that by modelling the effect of a black hole on the kinematics of molecular gas it is possible to fit interferometric observations of CO emission and thereby accurately estimate black-hole masses. We study the dynamics of the gas in the early-type galaxy NGC 4526, and obtain a best fit that requires the presence of a central dark object of 4.5(-3.1)(+4.2) x 10(8) solar masses, (3 sigma confidence limit). With the next-generation millimetre-wavelength interferometers these observations could be reproduced in galaxies out to 75 megaparsecs in less than 5 hours of observing time. The use of molecular gas as a kinematic tracer should thus allow one to estimate black-hole masses in hundreds of galaxies in the local Universe, many more than are accessible with current techniques.
C1 [Davis, Timothy A.] European So Observ, D-85748 Garching, Germany.
   [Bureau, Martin; Cappellari, Michele] Univ Oxford, Dept Phys, Subdept Astrophys, Oxford OX1 3RH, England.
   [Sarzi, Marc] Univ Hertfordshire, Ctr Astrophys Res, Hatfield AL1 9AB, Herts, England.
   [Blitz, Leo] Univ Calif Berkeley, Dept Astron, Berkeley, CA 94720 USA.
C3 European Southern Observatory; University of Oxford; University of Hertfordshire; University of California System; University of California Berkeley
RP Davis, TA (corresponding author), European So Observ, Karl Schwarzschild Str 2, D-85748 Garching, Germany.
EM tdavis@eso.org
FU European Community; 'Astrophysics at Oxford' and from the UK Research Councils; Royal Society University Research Fellowship; Science and Technology Facilities Council; National Science Foundation; CARMA partner universities; Direct For Mathematical & Physical Scien [0838258] Funding Source: National Science Foundation; Direct For Mathematical & Physical Scien; Division Of Astronomical Sciences [1140031] Funding Source: National Science Foundation; Division Of Astronomical Sciences [0838258] Funding Source: National Science Foundation; Science and Technology Facilities Council [ST/G004331/1, ST/H002456/1, ST/K00106X/1, ST/I003673/1, PP/E003427/1, ST/F009186/1] Funding Source: researchfish; STFC [ST/I003673/1, ST/F009186/1, ST/G004331/1, ST/H002456/1, PP/E003427/1, ST/K00106X/1] Funding Source: UKRI
NR 24
TC 93
Z9 103
U1 0
U2 15
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 21
PY 2013
VL 494
IS 7437
BP 328
EP 330
DI 10.1038/nature11819
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 095CS
UT WOS:000315312900032
PM 23364690
DA 2026-03-09
ER

PT J
AU Bretheau, L
   Girit, ÇÖ
   Pothier, H
   Esteve, D
   Urbina, C
AF Bretheau, L.
   Girit, C. Oe
   Pothier, H.
   Esteve, D.
   Urbina, C.
TI Exciting Andreev pairs in a superconducting atomic contact
SO NATURE
LA English
DT Article
ID josephson current; spectroscopy; supercurrent; resonator; junctions; channel; states; qubit
AB The Josephson effect describes the flow of supercurrent in a weak link-such as a tunnel junction, nanowire or molecule-between two superconductors(1). It is the basis for a variety of circuits and devices, with applications ranging from medicine(2) to quantum information(3). Experiments using Josephson circuits that behave like artificial atoms(4) are now revolutionizing the way we probe and exploit the laws of quantum physics(5,6). Microscopically, the supercurrent is carried by Andreev pair states, which are localized at the weak link. These states come in doublets and have energies inside the superconducting gap(7-10). Existing Josephson circuits are based on properties of just the ground state of each doublet, and so far the excited states have not been directly detected. Here we establish their existence through spectroscopic measurements of superconducting atomic contacts. The spectra, which depend on the atomic configuration and on the phase difference between the superconductors, are in complete agreement with theory. Andreev doublets could be exploited to encode information in novel types of superconducting qubits(11-13).
C1 [Bretheau, L.; Girit, C. Oe; Pothier, H.; Esteve, D.; Urbina, C.] CEA Saclay, IRAMIS, Serv Phys Etat Condense, Quantron Grp,CNRS,URA 2464, F-91191 Gif Sur Yvette, France.
C3 CEA; Centre National de la Recherche Scientifique (CNRS); Universite Paris Saclay
RP Urbina, C (corresponding author), CEA Saclay, IRAMIS, Serv Phys Etat Condense, Quantron Grp,CNRS,URA 2464, F-91191 Gif Sur Yvette, France.
EM cristian.urbina@cea.fr
FU People Programme (Marie Curie Actions) of the European Union's Seventh Framework Programme (FP7) under REA grant [PIIF-GA-2011-298415]; ANR contract DOCFLUC; ANR contract MASH; C'Nano
NR 30
TC 154
Z9 168
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 JUL 18
PY 2013
VL 499
IS 7458
BP 312
EP 315
DI 10.1038/nature12315
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 184RJ
UT WOS:000321910700030
PM 23868261
DA 2026-03-09
ER

PT J
AU Shirey, KA
   Lai, WD
   Scott, AJ
   Lipsky, M
   Mistry, P
   Pletneva, LM
   Karp, CL
   McAlees, J
   Gioannini, TL
   Weiss, J
   Chen, WH
   Ernst, RK
   Rossignol, DP
   Gusovsky, F
   Blanco, JCG
   Vogel, SN
AF Shirey, Kari Ann
   Lai, Wendy
   Scott, Alison J.
   Lipsky, Michael
   Mistry, Pragnesh
   Pletneva, Lioubov M.
   Karp, Christopher L.
   McAlees, Jaclyn
   Gioannini, Theresa L.
   Weiss, Jerrold
   Chen, Wilbur H.
   Ernst, Robert K.
   Rossignol, Daniel P.
   Gusovsky, Fabian
   Blanco, Jorge C. G.
   Vogel, Stefanie N.
TI The TLR4 antagonist Eritoran protects mice from lethal influenza infection
SO NATURE
LA English
DT Article
ID 1918 spanish influenza; endotoxin antagonist; tetrasodium e5564; crystal-structure; united-states; severe sepsis; virus; lipopolysaccharide; activation; inhibitors
AB There is a pressing need to develop alternatives to annual influenza vaccines and antiviral agents licensed for mitigating influenza infection. Previous studies reported that acute lung injury caused by chemical or microbial insults is secondary to the generation of host-derived, oxidized phospholipid that potently stimulates Toll-like receptor 4 (TLR4)-dependent inflammation(1). Subsequently, we reported that Tlr4(-/-) mice are highly refractory to influenza-induced lethality(2), and proposed that therapeutic antagonism of TLR4 signalling would protect against influenza-induced acute lung injury. Here we report that therapeutic administration of Eritoran (also known as E5564)-a potent, well-tolerated, synthetic TLR4 antagonist(3,4)-blocks influenza-induced lethality in mice, as well as lung pathology, clinical symptoms, cytokine and oxidized phospholipid expression, and decreases viral titres. CD14 and TLR2 are also required for Eritoran-mediated protection, and CD14 directly binds Eritoran and inhibits ligand binding to MD2. Thus, Eritoran blockade of TLR signalling represents a novel therapeutic approach for inflammation associated with influenza, and possibly other infections.
C1 [Shirey, Kari Ann; Lai, Wendy; Mistry, Pragnesh; Vogel, Stefanie N.] Univ Maryland, Dept Microbiol & Immunol, Baltimore, MD 21201 USA.
   [Scott, Alison J.; Ernst, Robert K.] Univ Maryland, Dept Microbial Pathogenesis, Baltimore, MD 21201 USA.
   [Lipsky, Michael] Univ Maryland, Dept Pathol, Baltimore, MD 21201 USA.
   [Pletneva, Lioubov M.; Blanco, Jorge C. G.] Sigmovir Biosyst Inc, Rockville, MD 20850 USA.
   [Karp, Christopher L.; McAlees, Jaclyn] Cincinnati Childrens Hosp Res Fdn, Div Mol Immunol, Cincinnati, OH 45229 USA.
   [Gioannini, Theresa L.; Weiss, Jerrold] Univ Iowa, Inflammat Program, Coralville, IA 52241 USA.
   [Gioannini, Theresa L.] Dept Vet Affairs Med Ctr, Iowa City, IA 52241 USA.
   [Chen, Wilbur H.] Univ Maryland, Ctr Vaccine Dev, Baltimore, MD 21201 USA.
   [Rossignol, Daniel P.; Gusovsky, Fabian] Eisai Inc, Andover, MA 01810 USA.
C3 University System of Maryland; University of Maryland Baltimore; University System of Maryland; University of Maryland Baltimore; University System of Maryland; University of Maryland Baltimore; Cincinnati Children's Hospital Medical Center; Cincinnati Children's Hospital Research Foundation; University System of Ohio; University of Cincinnati; University of Iowa; US Department of Veterans Affairs; Veterans Health Administration (VHA); Iowa City VA Health Care System; University System of Maryland; University of Maryland Baltimore; Eisai Co Ltd
RP Vogel, SN (corresponding author), Univ Maryland, Dept Microbiol & Immunol, Baltimore, MD 21201 USA.
EM svogel@som.umaryland.edu
FU National Institutes of Health [AI057575, AI018797, AI059372]; NCRR [K12-RR-023250]; VA Merit Award [1I01BX0000949-01A1]; Cystic Fibrosis Foundation RDP Center
NR 30
TC 374
Z9 416
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 23
PY 2013
VL 497
IS 7450
BP 498
EP +
DI 10.1038/nature12118
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 148OG
UT WOS:000319254000050
PM 23636320
DA 2026-03-09
ER

PT J
AU Meibom, S
   Torres, G
   Fressin, F
   Latham, DW
   Rowe, JF
   Ciardi, DR
   Bryson, ST
   Rogers, LA
   Henze, CE
   Janes, K
   Barnes, SA
   Marcy, GW
   Isaacson, H
   Fischer, DA
   Howell, SB
   Horch, EP
   Jenkins, JM
   Schuler, SC
   Crepp, J
AF Meibom, Soren
   Torres, Guillermo
   Fressin, Francois
   Latham, David W.
   Rowe, Jason F.
   Ciardi, David R.
   Bryson, Steven T.
   Rogers, Leslie A.
   Henze, Christopher E.
   Janes, Kenneth
   Barnes, Sydney A.
   Marcy, Geoffrey W.
   Isaacson, Howard
   Fischer, Debra A.
   Howell, Steve B.
   Horch, Elliott P.
   Jenkins, Jon M.
   Schuler, Simon C.
   Crepp, Justin
TI The same frequency of planets inside and outside open clusters of stars
SO NATURE
LA English
DT Article
ID intermediate-mass stars; kepler; systems; isochrones; dynamics
AB Most stars and their planets form in open clusters. Over 95 per cent of such clusters have stellar densities too low (less than a hundred stars per cubic parsec) to withstand internal and external dynamical stresses and fall apart within a few hundred million years(1). Older open clusters have survived by virtue of being richer and denser in stars (1,000 to 10,000 per cubic parsec) when they formed. Such clusters represent a stellar environment very different from the birthplace of the Sun and other planet-hosting field stars. So far more than 800 planets have been found around Sun-like stars in the field(2). The field planets are usually the size of Neptune or smaller(3-5). In contrast, only four planets have been found orbiting stars in open clusters(6-8), all with masses similar to or greater than that of Jupiter. Here we report observations of the transits of two Sun-like stars by planets smaller than Neptune in the billion-year-old open cluster NGC6811. This demonstrates that small planets can form and survive in a dense cluster environment, and implies that the frequency and properties of planets in open clusters are consistent with those of planets around field stars in the Galaxy.
C1 [Meibom, Soren; Torres, Guillermo; Fressin, Francois; Latham, David W.] Harvard Smithsonian Ctr Astrophys, Cambridge, MA 02138 USA.
   [Rowe, Jason F.; Bryson, Steven T.; Henze, Christopher E.; Howell, Steve B.] NASA, Ames Res Ctr, Moffett Field, CA 94035 USA.
   [Ciardi, David R.] CALTECH, NASA, Exoplanet Sci Inst, Pasadena, CA 91125 USA.
   [Rogers, Leslie A.] CALTECH, Pasadena, CA 91125 USA.
   [Janes, Kenneth] Boston Univ, Boston, MA 02215 USA.
   [Barnes, Sydney A.] Leibniz Inst Astrophys, D-14467 Potsdam, Germany.
   [Barnes, Sydney A.] Space Sci Inst, Boulder, CO 80301 USA.
   [Marcy, Geoffrey W.; Isaacson, Howard] Univ Calif Berkeley, Berkeley, CA 94720 USA.
   [Fischer, Debra A.] Yale Univ, New Haven, CT 06520 USA.
   [Horch, Elliott P.] So Connecticut State Univ, New Haven, CT 06515 USA.
   [Jenkins, Jon M.] NASA, SETI Inst, Ames Res Ctr, Moffett Field, CA 94035 USA.
   [Schuler, Simon C.] Natl Opt Astron Observ, Tucson, AZ 85719 USA.
   [Crepp, Justin] Univ Notre Dame, Notre Dame, IN 46556 USA.
C3 Harvard University; Smithsonian Astrophysical Observatory; Smithsonian Institution; National Aeronautics & Space Administration (NASA); NASA Ames Research Center; National Aeronautics & Space Administration (NASA); California Institute of Technology; California Institute of Technology; Boston University; Leibniz Association; Leibniz Institut fur Astrophysik Potsdam (AIP); University of California System; University of California Berkeley; Yale University; Connecticut State University System; Southern Connecticut State University; SETI Institute; National Aeronautics & Space Administration (NASA); NASA Ames Research Center; National Optical Astronomy Observatory; University of Notre Dame
RP Meibom, S (corresponding author), Harvard Smithsonian Ctr Astrophys, 60 Garden St, Cambridge, MA 02138 USA.
EM smeibom@cfa.harvard.edu
FU NASA's Science Mission Directorate; NASA [NNX09AH18A, HF-51313.01-A, NAS 5-26555]; Kepler mission via NASA Cooperative Agreement [NCC2-1390]; NASA's Kepler Participating Scientist Program [NNX12AC75G]; Space Telescope Science Institute; NASA [NNX09AH18A, 118004, NNX12AC75G, 52421] Funding Source: Federal RePORTER
NR 27
TC 89
Z9 104
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 JUL 4
PY 2013
VL 499
IS 7456
BP 55
EP 58
DI 10.1038/nature12279
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 176ED
UT WOS:000321285600031
PM 23803764
DA 2026-03-09
ER

PT J
AU O'Donoghue, J
   Stallard, TS
   Melin, H
   Jones, GH
   Cowley, SWH
   Miller, S
   Baines, KH
   Blake, JSD
AF O'Donoghue, J.
   Stallard, T. S.
   Melin, H.
   Jones, G. H.
   Cowley, S. W. H.
   Miller, S.
   Baines, K. H.
   Blake, J. S. D.
TI The domination of Saturn's low-latitude ionosphere by ring 'rain'
SO NATURE
LA English
DT Article
ID model
AB Saturn's ionosphere is produced when the otherwise neutral atmosphere is exposed to a flow of energetic charged particles or solar radiation(1). At low latitudes the solar radiation should result in a weak planet-wide glow in the infrared, corresponding to the planet's uniform illumination by the Sun(2). The observed electron density of the low-latitude ionosphere, however, is lower and its temperature higher than predicted by models(3-5). A planet-to-ring magnetic connection has been previously suggested, in which an influx of water from the rings could explain the lower-than-expected electron densities in Saturn's atmosphere(6-8). Here we report the detection of a pattern of features, extending across a broad latitude band from 25 to 60 degrees, that is superposed on the lower-latitude background glow, with peaks in emission that map along the planet's magnetic field lines to gaps in Saturn's rings. This pattern implies the transfer of charged species derived from water from the ring-plane to the ionosphere, an influx on a global scale, flooding between 30 to 43 per cent of the surface of Saturn's upper atmosphere. This ring 'rain' is important in modulating ionospheric emissions and suppressing electron densities.
C1 [O'Donoghue, J.; Stallard, T. S.; Melin, H.; Cowley, S. W. H.; Blake, J. S. D.] Univ Leicester, Dept Phys & Astron, Leicester LE1 7RH, Leics, England.
   [Jones, G. H.] Univ Coll London, Mullard Space Sci Lab, Dorking RH5 6NT, Surrey, England.
   [Jones, G. H.; Miller, S.] Univ London Birkbeck Coll, Ctr Planetary Sci, London WC1E 6BT, England.
   [Miller, S.] UCL, Dept Phys & Astron, Atmospher Phys Lab, London WC1E 6BT, England.
   [Baines, K. H.] CALTECH, Jet Prop Lab, Pasadena, CA 91109 USA.
C3 University of Leicester; University of London; University College London; University of London; Birkbeck University London; University of London; University College London; California Institute of Technology; National Aeronautics & Space Administration (NASA); NASA Jet Propulsion Laboratory (JPL)
RP O'Donoghue, J (corresponding author), Univ Leicester, Dept Phys & Astron, Leicester LE1 7RH, Leics, England.
EM jod3@ion.le.ac.uk
FU UK Science and Technology Facilities Council (STFC); Science and Technology Facilities Council [ST/K000977/1, ST/G002223/1, PP/D005213/1, ST/K001000/1, ST/I505780/1, ST/H002480/1] Funding Source: researchfish; STFC [ST/I505780/1, ST/K000977/1, ST/G002223/1, ST/H002480/1, ST/K001000/1, PP/D005213/1] Funding Source: UKRI
NR 18
TC 73
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 APR 11
PY 2013
VL 496
IS 7444
BP 193
EP 195
DI 10.1038/nature12049
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 122VM
UT WOS:000317346300035
PM 23579676
DA 2026-03-09
ER

PT J
AU Zhu, J
   Peng, T
   Johnston, C
   Phasouk, K
   Kask, AS
   Klock, A
   Jin, L
   Diem, K
   Koelle, DM
   Wald, A
   Robins, H
   Corey, L
AF Zhu, Jia
   Peng, Tao
   Johnston, Christine
   Phasouk, Khamsone
   Kask, Angela S.
   Klock, Alexis
   Jin, Lei
   Diem, Kurt
   Koelle, David M.
   Wald, Anna
   Robins, Harlan
   Corey, Lawrence
TI Immune surveillance by CD8αα+ skin-resident T cells in human herpes virus infection
SO NATURE
LA English
DT Article
ID simplex-virus; reactivation; tissue; exit
AB Most herpes simplex virus 2 (HSV-2) reactivations in humans are subclinical and associated with rapid expansion and containment of virus. Previous studies have shown that CD8(+) T cells persist in genital skin and mucosa at the dermal-epidermal junction (DEJ)-the portal of neuronal release of reactivating virus-for prolonged time periods after herpes lesions are cleared(1,2). The phenotype and function of this persistent CD8(+) T-cell population remain unknown. Here, using cell-type-specific laser capture microdissection, transcriptional profiling and T-cell antigen receptor beta-chain (TCR beta) genotyping on sequential genital skin biopsies, we show that CD8 alpha alpha(+) T cells are the dominant resident population of DEJ CD8(+) T cells that persist at the site of previous HSV-2 reactivation. CD8 alpha alpha(+) T cells located at the DEJ lack chemokine-receptor expression required for lymphocyte egress and recirculation, express gene signatures of T-cell activation and antiviral activity, and produce cytolytic granules during clinical and virological quiescent time periods. Sequencing of the TCR beta-chain repertoire reveals that the DEJ CD8 alpha alpha(+) T cells are oligoclonal with diverse usage of TCR variable-beta genes, which differ from those commonly described for mucosa-associated invariant T cells and natural killer T cells. Dominant clonotypes are shown to overlap among multiple recurrences over a period of two-and-a-half years. Episodes of rapid asymptomatic HSV-2 containment were also associated with a high CD8 effector-to-target ratio and focal enrichment of CD8 alpha alpha(+) T cells. These studies indicate that DEJ CD8 alpha alpha(+) T cells are tissue-resident cells that seem to have a fundamental role in immune surveillance and in initial containment of HSV-2 reactivation in human peripheral tissue. Elicitation of CD8 alpha alpha(+) T cells may be a critical component for developing effective vaccines against skin and mucosal infections.
C1 [Zhu, Jia; Kask, Angela S.; Klock, Alexis; Jin, Lei; Diem, Kurt; Koelle, David M.; Wald, Anna; Corey, Lawrence] Univ Washington, Dept Lab Med, Seattle, WA 98195 USA.
   [Zhu, Jia; Peng, Tao; Phasouk, Khamsone; Koelle, David M.; Wald, Anna; Corey, Lawrence] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, Seattle, WA 98109 USA.
   [Peng, Tao; Johnston, Christine; Koelle, David M.; Wald, Anna; Corey, Lawrence] Univ Washington, Dept Med, Seattle, WA 98195 USA.
   [Koelle, David M.; Corey, Lawrence] Univ Washington, Dept Pathobiol, Seattle, WA 98195 USA.
   [Koelle, David M.] Benaroya Res Inst, Seattle, WA 98104 USA.
   [Wald, Anna] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
   [Robins, Harlan] Fred Hutchinson Canc Res Ctr, Program Computat Biol, Seattle, WA 98109 USA.
C3 University of Washington; University of Washington Seattle; Fred Hutchinson Cancer Center; University of Washington; University of Washington Seattle; University of Washington; University of Washington Seattle; Benaroya Research Institute; University of Washington; University of Washington Seattle; Fred Hutchinson Cancer Center
RP Zhu, J (corresponding author), Univ Washington, Dept Lab Med, Seattle, WA 98195 USA.
EM jiazhu@u.washington.edu; lcorey@fhcrc.org
FU National Institutes of Health [R37AI042528, R01AI04252815, P01AI030731, R56AI093746]; James B. Pendleton Charitable Trust
NR 30
TC 238
Z9 291
U1 1
U2 41
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 23
PY 2013
VL 497
IS 7450
BP 494
EP +
DI 10.1038/nature12110
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 148OG
UT WOS:000319254000049
PM 23657257
DA 2026-03-09
ER

PT J
AU Styrkarsdottir, U
   Thorleifsson, G
   Sulem, P
   Gudbjartsson, DF
   Sigurdsson, A
   Jonasdottir, A
   Jonasdottir, A
   Oddsson, A
   Helgason, A
   Magnusson, OT
   BragiWalters, G
   Frigge, ML
   Helgadottir, HT
   Johannsdottir, H
   Bergsteinsdottir, K
   Ogmundsdottir, MH
   Center, JR
   Nguyen, TV
   Eisman, JA
   Christiansen, C
   Steingrimsson, E
   Jonasson, JG
   Tryggvadottir, L
   Eyjolfsson, GI
   Theodors, A
   Jonsson, T
   Ingvarsson, T
   Olafsson, I
   Rafnar, T
   Kong, A
   Sigurdsson, G
   Masson, G
   Thorsteinsdottir, U
   Stefansson, K
AF Styrkarsdottir, Unnur
   Thorleifsson, Gudmar
   Sulem, Patrick
   Gudbjartsson, Daniel F.
   Sigurdsson, Asgeir
   Jonasdottir, Aslaug
   Jonasdottir, Adalbjorg
   Oddsson, Asmundur
   Helgason, Agnar
   Magnusson, Olafur T.
   BragiWalters, G.
   Frigge, Michael L.
   Helgadottir, Hafdis T.
   Johannsdottir, Hrefna
   Bergsteinsdottir, Kristin
   Ogmundsdottir, Margret H.
   Center, Jacqueline R.
   Nguyen, Tuan V.
   Eisman, John A.
   Christiansen, Claus
   Steingrimsson, Erikur
   Jonasson, Jon G.
   Tryggvadottir, Laufey
   Eyjolfsson, Gudmundur I.
   Theodors, Asgeir
   Jonsson, Thorvaldur
   Ingvarsson, Thorvaldur
   Olafsson, Isleifur
   Rafnar, Thorunn
   Kong, Augustine
   Sigurdsson, Gunnar
   Masson, Gisli
   Thorsteinsdottir, Unnur
   Stefansson, Kari
TI Nonsense mutation in the LGR4 gene is associated with several human diseases and other traits
SO NATURE
LA English
DT Article
ID bone-mineral density; osteoporosis; gpr48; receptors; knockout; leads; loci
AB Low bone mineral density (BMD) is used as a parameter of osteoporosis. Genome-wide association studies of BMD have hitherto focused on BMD as a quantitative trait, yielding common variants of small effects that contribute to the population diversity in BMD1-7. Here we use BMD as a dichotomous trait, searching for variants that may have a direct effect on the risk of pathologically low BMD rather than on the regulation of BMD in the healthy population. Through whole-genome sequencing of Icelandic individuals, we found a rare nonsense mutation within the leucinerich-repeat-containing G-protein-coupled receptor 4 (LGR4) gene (c.376C>T) that is strongly associated with low BMD, and with osteoporotic fractures. This mutation leads to termination of LGR4 at position 126 and fully disrupts its function. The c.376C>T mutation is also associated with electrolyte imbalance, late onset of menarche and reduced testosterone levels, as well as an increased risk of squamous cell carcinoma of the skin and biliary tract cancer. Interestingly, the phenotype of carriers of the c.376C>T mutation overlaps that of Lgr4 mutant mice.
C1 [Styrkarsdottir, Unnur; Thorleifsson, Gudmar; Sulem, Patrick; Gudbjartsson, Daniel F.; Sigurdsson, Asgeir; Jonasdottir, Aslaug; Jonasdottir, Adalbjorg; Oddsson, Asmundur; Helgason, Agnar; Magnusson, Olafur T.; BragiWalters, G.; Frigge, Michael L.; Helgadottir, Hafdis T.; Johannsdottir, Hrefna; Rafnar, Thorunn; Kong, Augustine; Masson, Gisli; Thorsteinsdottir, Unnur; Stefansson, Kari] deCODE Genet Amgen, IS-101 Reykjavik, Iceland.
   [Oddsson, Asmundur] Karolinska Inst, Dept Med Biochem & Biophys, S-17177 Stockholm, Sweden.
   [Bergsteinsdottir, Kristin; Ogmundsdottir, Margret H.; Steingrimsson, Erikur] Univ Iceland, Biomed Ctr, Fac Med, Dept Biochem & Mol Biol, IS-101 Reykjavik, Iceland.
   [Center, Jacqueline R.; Nguyen, Tuan V.; Eisman, John A.] Garvan Inst Med Res, Sydney, NSW 2010, Australia.
   [Center, Jacqueline R.; Eisman, John A.] St Vincents Hosp, Sydney, NSW 2010, Australia.
   [Center, Jacqueline R.; Nguyen, Tuan V.; Eisman, John A.] Univ New S Wales, Sydney, NSW 2010, Australia.
   [Eisman, John A.] UNDA, Sydney, NSW 2010, Australia.
   [Christiansen, Claus] CCBR, DK-2750 Ballerup, Denmark.
   [Jonasson, Jon G.] Natl Univ Hosp Iceland, Landspitali, Dept Pathol, IS-101 Reykjavik, Iceland.
   [Jonasson, Jon G.; Tryggvadottir, Laufey; Jonsson, Thorvaldur; Sigurdsson, Gunnar; Thorsteinsdottir, Unnur; Stefansson, Kari] Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland.
   [Jonasson, Jon G.; Tryggvadottir, Laufey] Iceland Canc Registry, IS-105 Reykjavik, Iceland.
   [Eyjolfsson, Gudmundur I.] Iceland Med Ctr Laeknasetrid, Lab Mjodd RAM, IS-109 Reykjavik, Iceland.
   [Theodors, Asgeir] Natl Univ Hosp Iceland, Landspitali, Dept Gastroenterol, IS-101 Reykjavik, Iceland.
   [Jonsson, Thorvaldur] Natl Univ Hosp Iceland, Landspitali, Dept Surg, IS-101 Reykjavik, Iceland.
   [Ingvarsson, Thorvaldur] Akureyri Hosp, Dept Orthoped Surg, IS-600 Akureyri, Iceland.
   [Ingvarsson, Thorvaldur] Univ Akureyri, Inst Hlth Sci, IS-600 Akureyri, Iceland.
   [Olafsson, Isleifur] Natl Univ Hosp Iceland, Landspitali, Dept Clin Biochem, IS-101 Reykjavik, Iceland.
   [Sigurdsson, Gunnar] Natl Univ Hosp Iceland, Landspitali, Dept Endocrinol & Metab, IS-101 Reykjavik, Iceland.
C3 Decode Genetics; Karolinska Institutet; University of Iceland; Garvan Institute of Medical Research; NSW Health; St Vincents Hospital Sydney; University of New South Wales Sydney; The University of Notre Dame Australia; University of Notre Dame Australia - Sydney; Synarc; Center Clinical & Basic Research; Landspitali National University Hospital; University of Iceland; Landspitali National University Hospital; Landspitali National University Hospital; University of Akureyri; Landspitali National University Hospital; Landspitali National University Hospital
RP Thorsteinsdottir, U (corresponding author), deCODE Genet Amgen, IS-101 Reykjavik, Iceland.
EM unnurth@decode.is; kstefans@decode.is
FU European Commission [HEALTH-F2-2008-201865-GEFOS]; 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 29
TC 217
Z9 242
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 MAY 23
PY 2013
VL 497
IS 7450
BP 517
EP 520
DI 10.1038/nature12124
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 148OG
UT WOS:000319254000054
PM 23644456
DA 2026-03-09
ER

PT J
AU Ferguson, DJ
   Maclennan, J
   Bastow, ID
   Pyle, DM
   Jones, SM
   Keir, D
   Blundy, JD
   Plank, T
   Yirgu, G
AF Ferguson, D. J.
   Maclennan, J.
   Bastow, I. D.
   Pyle, D. M.
   Jones, S. M.
   Keir, D.
   Blundy, J. D.
   Plank, T.
   Yirgu, G.
TI Melting during late-stage rifting in Afar is hot and deep
SO NATURE
LA English
DT Article
ID continental margins; sedimentary basins; flood basalts; mantle; extension; lithosphere; transition; generation; earth; segmentation
AB Investigations of a variety of continental rifts and margins worldwide have revealed that a considerable volume of melt can intrude into the crust during continental breakup(1-8), modifying its composition and thermal structure. However, it is unclear whether the cause of voluminous melt production at volcanic rifts is primarily increased mantle temperature or plate thinning(1,2,8-12). Also disputed is the extent to which plate stretching or thinning is uniform or varies with depth with the entire continental lithospheric mantle potentially being removed before plate rupture(13-16). Here we show that the extensive magmatism during rifting along the southern Red Sea rift in Afar, a unique region of sub-aerial transition from continental to oceanic rifting, is driven by deep melting of hotter-than-normal asthenosphere. Petrogenetic modelling shows that melts are predominantly generated at depths greater than 80 kilometres, implying the existence of a thick upper thermo-mechanical boundary layer in a rift system approaching the point of plate rupture. Numerical modelling of rift development shows that when breakup occurs at the slow extension rates observed in Afar, the survival of a thick plate is an inevitable consequence of conductive cooling of the lithosphere, even when the underlying asthenosphere is hot. Sustained magmatic activity during rifting in Afar thus requires persistently high mantle temperatures, which would allow melting at high pressure beneath the thick plate. If extensive plate thinning does occur during breakup it must do so abruptly at a late stage, immediately before the formation of the new ocean basin(16).
C1 [Ferguson, D. J.; Plank, T.] Columbia Univ, Lamont Doherty Earth Observ, Palisades, NY 10964 USA.
   [Maclennan, J.] Univ Cambridge, Dept Earth Sci, Cambridge CB2 3EQ, England.
   [Bastow, I. D.] Univ London Imperial Coll Sci Technol & Med, Dept Earth Sci & Engn, London SW7 2AZ, England.
   [Pyle, D. M.] Univ Oxford, Dept Earth Sci, Oxford OX1 3AN, England.
   [Jones, S. M.] Univ Birmingham, Sch Geog Earth & Environm Sci, Birmingham B15 2TT, W Midlands, England.
   [Keir, D.] Univ Southampton, Natl Oceanog Ctr Southampton, Southampton SO14 3ZH, Hants, England.
   [Blundy, J. D.] Univ Bristol, Dept Earth Sci, Bristol BS8 1RJ, Avon, England.
   [Yirgu, G.] Univ Addis Ababa, Dept Earth Sci, Addis Ababa, Ethiopia.
C3 Columbia University; University of Cambridge; Imperial College London; University of Oxford; University of Birmingham; NERC National Oceanography Centre; University of Southampton; University of Bristol; Addis Ababa University
RP Ferguson, DJ (corresponding author), Columbia Univ, Lamont Doherty Earth Observ, Palisades, NY 10964 USA.
EM davef@ldeo.columbia.edu
FU NERC; LDEO; NERC [NE/E006469/1, NE/E007414/1, NE/E005284/1] Funding Source: UKRI; Natural Environment Research Council [NE/E005284/1, NE/E007414/1, NE/E006469/1] Funding Source: researchfish
NR 42
TC 96
Z9 107
U1 1
U2 71
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 4
PY 2013
VL 499
IS 7456
BP 70
EP +
DI 10.1038/nature12292
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 176ED
UT WOS:000321285600035
PM 23823795
DA 2026-03-09
ER

PT J
AU Hu, LC
   Kim, TM
   Son, MY
   Kim, SA
   Holland, CL
   Tateishi, S
   Kim, DH
   Yew, PR
   Montagna, C
   Dumitrache, LC
   Hasty, P
AF Hu, Lingchuan
   Kim, Tae Moon
   Son, Mi Young
   Kim, Sung-A
   Holland, Cory L.
   Tateishi, Satoshi
   Kim, Dong Hyun
   Yew, P. Renee
   Montagna, Cristina
   Dumitrache, Lavinia C.
   Hasty, Paul
TI Two replication fork maintenance pathways fuse inverted repeats to rearrange chromosomes
SO NATURE
LA English
DT Article
ID genomic instability; hprt minigene; dna; gene; brca2; recombination; amplification; repair; hltf; polyubiquitination
AB Replication fork maintenance pathways preserve chromosomes, but their faulty application at nonallelic repeats could generate rearrangements causing cancer, genomic disorders and speciation(1-3). Potential causal mechanisms are homologous recombination and error-free postreplication repair (EF-PRR). Homologous recombination repairs damage-induced DNA double-strand breaks (DSBs) and single-ended DSBs within replication. To facilitate homologous recombination, the recombinase RAD51 and mediator BRCA2 forma filament on the 3' DNA strand at a break to enable annealing to the complementary sister chromatid(4) while the RecQ helicase, BLM (Bloom syndrome mutated) suppresses crossing over to prevent recombination(5). Homologous recombination also stabilizes(6,7) and restarts(8,9) replication forks without a DSB10,11. EF-PRR bypasses DNA incongruities that impede replication by ubiquitinating PCNA (proliferating cell nuclear antigen) using the RAD6-RAD18 and UBC13-MMS2-RAD5 ubiquitin ligase complexes(12). Some components are common to both homologous recombination and EF-PRR such as RAD51 and RAD18(13,14). Here we delineate two pathways that spontaneously fuse inverted repeats to generate unstable chromosomal rearrangements in wild-type mouse embryonic stem (ES) cells. Gamma-radiation induced a BLM-regulated pathway that selectively fused identical, but not mismatched, repeats. By contrast, ultraviolet light induced a RAD18-dependent pathway that efficiently fused mismatched repeats. Furthermore, TREX2 (a 3'-> 5' exonuclease) suppressed identical repeat fusion but enhanced mismatched repeat fusion, clearly separating these pathways. TREX2 associated with UBC13 and enhanced PCNA ubiquitination in response to ultraviolet light, consistent with it being a novel member of EF-PRR. RAD18 and TREX2 also suppressed replication fork stalling in response to nucleotide depletion. Interestingly, replication fork stalling induced fusion for identical and mismatched repeats, implicating faulty replication as a causal mechanism for both pathways.
C1 [Hu, Lingchuan; Kim, Tae Moon; Son, Mi Young; Kim, Sung-A; Holland, Cory L.; Kim, Dong Hyun; Yew, P. Renee; Dumitrache, Lavinia C.; Hasty, Paul] Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, Inst Biotechnol, Dept Mol Med, San Antonio, TX 78245 USA.
   [Tateishi, Satoshi] Kumamoto Univ, IMEG, Kumamoto 8600811, Japan.
   [Montagna, Cristina] Yeshiva Univ Albert Einstein Coll Med, Dept Genet, Bronx, NY 10461 USA.
C3 University of Texas System; University of Texas at San Antonio; Kumamoto University; Yeshiva University; Montefiore Medical Center; Albert Einstein College of Medicine
RP Hasty, P (corresponding author), Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, Inst Biotechnol, Dept Mol Med, 15355 Lambda Dr, San Antonio, TX 78245 USA.
EM hastye@uthscsa.edu
FU National Institutes of Health [1 RO1 CA123203-01A1, 2P01AG017242-12, P30CA013330]; Cancer Therapy & Research Center at The University of Texas at San Antonio (CTRC) [P30 CA054174]; National Cancer Institute [P30CA054174, P30CA013330] Funding Source: NIH RePORTER; National Institute on Aging [P01AG017242] Funding Source: NIH RePORTER
NR 47
TC 37
Z9 42
U1 0
U2 30
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 26
PY 2013
VL 501
IS 7468
BP 569
EP +
DI 10.1038/nature12500
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 223RP
UT WOS:000324826300063
PM 24013173
DA 2026-03-09
ER

PT J
AU Ma, D
   Gulani, V
   Seiberlich, N
   Liu, KC
   Sunshine, JL
   Duerk, JL
   Griswold, MA
AF Ma, Dan
   Gulani, Vikas
   Seiberlich, Nicole
   Liu, Kecheng
   Sunshine, Jeffrey L.
   Duerk, Jeffrey L.
   Griswold, Mark A.
TI Magnetic resonance fingerprinting
SO NATURE
LA English
DT Article
ID state free precession; signal recovery; spiral trajectory; sensing mri; time; t-2; brain; quantification; truefisp; t2
AB Magnetic resonance is an exceptionally, powerful and versatile measurement technique. The basic structure of a magnetic resonance experiment has remained largely unchanged for almost 50 years, being mainly restricted to the qualitative probing of only a limited set of the properties that can in principle be accessed by this technique. Here we introduce an approach to data acquisition, post-processing and visualization which we term 'magnetic resonance fingerprinting' (MRF) - that permits the simultaneous non-invasive quantification of multiple important properties of a material or tissue. MRF thus provides an alternative way to quantitatively detect and analyse complex changes that can represent physical alterations of a substance or early indicators of disease. MRF can also be used to identify the presence of a specific target material or tissue, which will increase the sensitivity, specificity and speed of a magnetic resonance study, and potentially lead to new diagnostic testing methodologies. When-paired with an appropriate pattern-recognition algorithm, MRF inherently suppresses measurement errors and can thus improve measurement accuracy.
C1 [Ma, Dan; Gulani, Vikas; Seiberlich, Nicole; Duerk, Jeffrey L.; Griswold, Mark A.] Case Western Reserve Univ, Dept Biomed Engn, Cleveland, OH 44106 USA.
   [Gulani, Vikas; Sunshine, Jeffrey L.; Duerk, Jeffrey L.; Griswold, Mark A.] Case Western Reserve Univ, Dept Radiol, Cleveland, OH 44106 USA.
   [Gulani, Vikas; Sunshine, Jeffrey L.; Duerk, Jeffrey L.; Griswold, Mark A.] Univ Hosp Cleveland, Cleveland, OH 44106 USA.
   [Liu, Kecheng] Siemens Healthcare USA, Malvern, PA 19355 USA.
C3 University System of Ohio; Case Western Reserve University; University System of Ohio; Case Western Reserve University; University Hospitals of Cleveland; Siemens AG; Siemens USA
RP Griswold, MA (corresponding author), Case Western Reserve Univ, Dept Biomed Engn, 10900 Euclid Ave, Cleveland, OH 44106 USA.
EM mark.griswold@case.edu
FU NIH [R01HL094557]; Siemens Healthcare
NR 52
TC 1250
Z9 1558
U1 4
U2 340
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 14
PY 2013
VL 495
IS 7440
BP 187
EP 192
DI 10.1038/nature11971
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 113FP
UT WOS:000316652300041
PM 23486058
DA 2026-03-09
ER

PT J
AU Seelig, JD
   Jayaraman, V
AF Seelig, Johannes D.
   Jayaraman, Vivek
TI Feature detection and orientation tuning in the Drosophila central complex
SO NATURE
LA English
DT Article
ID mouse visual-cortex; receptive-fields; ellipsoid body; locust brain; neurons; pattern; organization; behavior; insect; memory
AB Many animals, including insects, are known to use visual landmarks to orient in their environment. In Drosophila melanogaster, behavioural genetics studies have identified a higher brain structure called the central complex as being required for the fly's innate responses to vertical visual features(1) and its short-and long-term memory for visual patterns(2-4). But whether and how neurons of the fly central complex represent visual features are unknown. Here we use two-photon calcium imaging in head-fixed walking and flying flies to probe visuomotor responses of ring neurons-a class of central complex neurons that have been implicated in landmark-driven spatial memory in walking flies(2,3) and memory for visual patterns in tethered flying flies(5). We show that dendrites of ring neurons are visually responsive and arranged retinotopically. Ring neuron receptive fields comprise both excitatory and inhibitory subfields, resembling those of simple cells in the mammalian primary visual cortex. Ring neurons show strong and, in some cases, direction-selective orientation tuning, with a notable preference for vertically oriented features similar to those that evoke innate responses in flies(1,2). Visual responses were diminished during flight, but, in contrast with the hypothesized role of the central complex in the control of locomotion(6), not modulated during walking. Taken together, these results indicate that ring neurons represent behaviourally relevant visual features in the fly's environment, enabling downstream central complex circuits to produce appropriate motor commands(6). More broadly, this study opens the door to mechanistic investigations of circuit computations underlying visually guided action selection in the Drosophila central complex.
C1 [Seelig, Johannes D.; Jayaraman, Vivek] Howard Hughes Med Inst, Ashburn, VA 20147 USA.
C3 Howard Hughes Medical Institute
RP Jayaraman, V (corresponding author), Howard Hughes Med Inst, Janelia Farm Res Campus,19700 Helix Dr, Ashburn, VA 20147 USA.
EM vivek@janelia.hhmi.org
FU Howard Hughes Medical Institute
NR 44
TC 222
Z9 272
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 NOV 14
PY 2013
VL 503
IS 7475
BP 262
EP +
DI 10.1038/nature12601
PG 23
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 250YX
UT WOS:000326894200051
PM 24107996
DA 2026-03-09
ER

PT J
AU Tian, X
   Azpurua, J
   Hine, C
   Vaidya, A
   Myakishev-Rempel, M
   Ablaeva, J
   Mao, ZY
   Nevo, E
   Gorbunova, V
   Seluanov, A
AF Tian, Xiao
   Azpurua, Jorge
   Hine, Christopher
   Vaidya, Amita
   Myakishev-Rempel, Max
   Ablaeva, Julia
   Mao, Zhiyong
   Nevo, Eviatar
   Gorbunova, Vera
   Seluanov, Andrei
TI High-molecular-mass hyaluronan mediates the cancer resistance of the naked mole rat
SO NATURE
LA English
DT Article
ID contact inhibition; cd44; transformation; insights; growth; cells
AB The naked mole rat (Heterocephalus glaber) displays exceptional longevity, with a maximum lifespan exceeding 30 years(1-3). This is the longest reported lifespan for a rodent species and is especially striking considering the small body mass of the naked mole rat. In comparison, a similarly sized house mouse has a maximum lifespan of 4 years(4,5). In addition to their longevity, naked mole rats show an unusual resistance to cancer. Multi-year observations of large naked mole-rat colonies did not detect a single incidence of cancer(2,6). Here we identify a mechanism responsible for the naked mole rat's cancer resistance. We found that naked mole-rat fibroblasts secrete extremely high-molecular-mass hyaluronan (HA), which is over five times larger than human or mouse HA. This high-molecular-mass HA accumulates abundantly in naked mole-rat tissues owing to the decreased activity of HA-degrading enzymes and a unique sequence of hyaluronan synthase 2 (HAS2). Furthermore, the naked mole-rat cells are more sensitive to HA signalling, as they have a higher affinity to HA compared with mouse or human cells. Perturbation of the signalling pathways sufficient for malignant transformation of mouse fibroblasts fails to transform naked mole-rat cells. However, once high molecular-mass HA is removed by either knocking down HAS2 or overexpressing the HA-degrading enzyme, HYAL2, naked mole-rat cells become susceptible to malignant transformation and readily form tumours in mice. We speculate that naked mole rats have evolved a higher concentration of HA in the skin to provide skin elasticity needed for life in underground tunnels. This trait may have then been co-opted to provide cancer resistance and longevity to this species.
C1 [Tian, Xiao; Azpurua, Jorge; Hine, Christopher; Vaidya, Amita; Myakishev-Rempel, Max; Ablaeva, Julia; Mao, Zhiyong; Gorbunova, Vera; Seluanov, Andrei] Univ Rochester, Dept Biol, Rochester, NY 14627 USA.
   [Mao, Zhiyong] Tongji Univ, Sch Life Sci & Technol, Shanghai 200092, Peoples R China.
   [Nevo, Eviatar] Univ Haifa, Inst Evolut, IL-31905 Haifa, Israel.
C3 University of Rochester; Tongji University; University of Haifa
RP Gorbunova, V (corresponding author), Univ Rochester, Dept Biol, Rochester, NY 14627 USA.
EM vera.gorbunova@rochester.edu; andrei.seluanov@rochester.edu
FU US National Institutes of Health; Ellison Medical Foundation; National Institute on Aging [R01AG027237] Funding Source: NIH RePORTER
NR 21
TC 592
Z9 710
U1 5
U2 406
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 18
PY 2013
VL 499
IS 7458
BP 346
EP U122
DI 10.1038/nature12234
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 184RJ
UT WOS:000321910700038
PM 23783513
DA 2026-03-09
ER

PT J
AU Sundaram, GM
   Common, JEA
   Gopal, FE
   Srikanta, S
   Lakshman, K
   Lunny, DP
   Lim, TC
   Tanavde, V
   Lane, EB
   Sampath, P
AF Sundaram, Gopinath M.
   Common, John E. A.
   Gopal, Felicia E.
   Srikanta, Satyanarayana
   Lakshman, Krishnaswamy
   Lunny, Declan P.
   Lim, Thiam C.
   Tanavde, Vivek
   Lane, E. Birgitte
   Sampath, Prabha
TI 'See-saw' expression of microRNA-198 and FSTL1 from a single transcript in wound healing
SO NATURE
LA English
DT Article
ID diabetic foot ulcers; cell-migration; keratinocytes; pathway
AB Post-transcriptional switches are flexible effectors of dynamic changes in gene expression(1). Here we report a new post-transcriptional switch that dictates the spatiotemporal and mutually exclusive expression of two alternative gene products from a single transcript. Expression of primate-specific exonic microRNA-198 (miR-198)(2), located in the 3'-untranslated region of follistatin-like 1 (FSTL1)(3) messenger RNA, switches to expression of the linked open reading frame of FSTL1 upon wounding in a human ex vivo organ culture system. We show that binding of a KH-type splicing regulatory protein (KSRP, also known as KHSRP) to the primary transcript determines the fate of the transcript and is essential for the processing of miR-198: transforming growth factor-beta signalling switches off miR-198 expression by downregulating KSRP, and promotes FSTL1 protein expression. We also show that FSTL1 expression promotes keratinocyte migration, whereas miR-198 expression has the opposite effect by targeting and inhibiting DIAPH1, PLAU and LAMC2. A clear inverse correlation between the expression pattern of FSTL1 (pro-migratory) and miR-198 (anti-migratory) highlights the importance of this regulatory switch in controlling context-specific gene expression to orchestrate wound re-epithelialization. The deleterious effect of failure of this switch is apparent in non-healing chronic diabetic ulcers, in which expression of miR-198 persists, FSTL1 is absent, and keratinocyte migration, re-epithelialization and wound healing all fail to occur.
C1 [Sundaram, Gopinath M.; Common, John E. A.; Gopal, Felicia E.; Lunny, Declan P.; Tanavde, Vivek; Lane, E. Birgitte; Sampath, Prabha] ASTAR, Inst Med Biol, Singapore 138648, Singapore.
   [Srikanta, Satyanarayana; Lakshman, Krishnaswamy] Jnana Sanjeevini Diabet Ctr, Bangalore 560078, Karnataka, India.
   [Lim, Thiam C.] Natl Univ Hlth Syst, Div Plast Reconstruct & Aesthet Surg, Singapore 119074, Singapore.
   [Lim, Thiam C.] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Surg, Singapore 119228, Singapore.
   [Tanavde, Vivek] ASTAR, Bioinformat Inst, Singapore 138671, Singapore.
   [Lane, E. Birgitte] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Pathol, Singapore 119074, Singapore.
   [Lane, E. Birgitte; Sampath, Prabha] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Biochem, Singapore 117597, Singapore.
C3 Agency for Science Technology & Research (A*STAR); A*STAR - Institute of Medical Biology (IMB); National University of Singapore; National University of Singapore; Agency for Science Technology & Research (A*STAR); A*STAR - Bioinformatics Institute (BII); National University of Singapore; National University of Singapore
RP Sampath, P (corresponding author), ASTAR, Inst Med Biol, Singapore 138648, Singapore.
EM prabha.sampath@imb.a-star.edu.sg
FU A*STAR Investigatorship award; Biomedical Research Council of Singapore; Skin Biology Cluster Platform, A*STAR
NR 28
TC 188
Z9 219
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 MAR 7
PY 2013
VL 495
IS 7439
BP 103
EP 106
DI 10.1038/nature11890
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 105BE
UT WOS:000316039800048
PM 23395958
DA 2026-03-09
ER

PT J
AU Zhao, YL
   Temperton, B
   Thrash, JC
   Schwalbach, MS
   Vergin, KL
   Landry, ZC
   Ellisman, M
   Deerinck, T
   Sullivan, MB
   Giovannoni, SJ
AF Zhao, Yanlin
   Temperton, Ben
   Thrash, J. Cameron
   Schwalbach, Michael S.
   Vergin, Kevin L.
   Landry, Zachary C.
   Ellisman, Mark
   Deerinck, Tom
   Sullivan, Matthew B.
   Giovannoni, Stephen J.
TI Abundant SAR11 viruses in the ocean
SO NATURE
LA English
DT Article
ID marine; population; diversity; dynamics
AB Several reports proposed that the extraordinary dominance of the SAR11 bacterial clade in ocean ecosystems could be a consequence of unusual mechanisms of resistance to bacteriophage infection, including 'cryptic escape' through reduced cell size(1) and/or K-strategist defence specialism(2). Alternatively, the evolution of high surface-to-volume ratios coupled with minimal genomes containing high-affinity transporters enables unusually efficient metabolism for oxidizing dissolved organic matter in the world's oceans that could support vast population sizes despite phage susceptibility. These ideas are important for understanding plankton ecology because they emphasize the potentially important role of top-down mechanisms in predation, thus determining the size of SAR11 populations and their concomitant role in biogeochemical cycling. Here we report the isolation of diverse SAR11 viruses belonging to two virus families in culture, for which we propose the name 'pelagiphage', after their host. Notably; the pelagiphage genomes were highly represented in marine viral metagenomes, demonstrating their importance in nature. One of the new phages, HTVC010P, represents a new podovirus subfamily more abundant than any seen previously, in all data sets tested, and may represent one of the most abundant virus subfamilies in the biosphere. This discovery disproves the theory that SAR11 cells are immune to viral predation and is consistent with the interpretation that the success of this highly abundant microbial clade is the result of successfully evolved adaptation to resource competition.
C1 [Zhao, Yanlin; Temperton, Ben; Thrash, J. Cameron; Vergin, Kevin L.; Landry, Zachary C.; Giovannoni, Stephen J.] Oregon State Univ, Dept Microbiol, Corvallis, OR 97331 USA.
   [Schwalbach, Michael S.] Univ Wisconsin, Great Lakes Bioenergy Res Ctr, Madison, WI 53706 USA.
   [Ellisman, Mark; Deerinck, Tom] Univ Calif San Diego, Natl Ctr Microscopy & Imaging Res, San Diego, CA 92093 USA.
   [Sullivan, Matthew B.] Univ Arizona, Dept Ecol & Evolutionary Biol, Tucson, AZ 85721 USA.
C3 Oregon State University; University of Wisconsin System; University of Wisconsin Madison; United States Department of Energy (DOE); University of California System; University of California San Diego; University of Arizona
RP Giovannoni, SJ (corresponding author), Oregon State Univ, Dept Microbiol, Corvallis, OR 97331 USA.
EM steve.giovannoni@oregonstate.edu
FU Gordon and Betty Moore Foundation Marine Microbiology Initiative; Directorate For Geosciences; Division Of Ocean Sciences [0961947] Funding Source: National Science Foundation
NR 30
TC 275
Z9 308
U1 2
U2 178
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 21
PY 2013
VL 494
IS 7437
BP 357
EP 360
DI 10.1038/nature11921
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 095CS
UT WOS:000315312900039
PM 23407494
DA 2026-03-09
ER

PT J
AU Shankar, S
   Hatridge, M
   Leghtas, Z
   Sliwa, KM
   Narla, A
   Vool, U
   Girvin, SM
   Frunzio, L
   Mirrahimi, M
   Devoret, MH
AF Shankar, S.
   Hatridge, M.
   Leghtas, Z.
   Sliwa, K. M.
   Narla, A.
   Vool, U.
   Girvin, S. M.
   Frunzio, L.
   Mirrahimi, M.
   Devoret, M. H.
TI Autonomously stabilized entanglement between two superconducting quantum bits
SO NATURE
LA English
DT Article
ID photon
AB Quantum error correction codes are designed to protect an arbitrary state of a multi-qubit register from decoherence-induced errors(1), but their implementation is an outstanding challenge in the development of large-scale quantum computers. The first step is to stabilize a non-equilibrium state of a simple quantum system, such as a quantum bit (qubit) or a cavity mode, in the presence of decoherence. This has recently been accomplished using measurement-based feedback schemes(2-5). The next step is to prepare and stabilize a state of a composite system(6-8). Here we demonstrate the stabilization of an entangled Bell state of a quantum register of two superconducting qubits for an arbitrary time. Our result is achieved using an autonomous feedback scheme that combines continuous drives along with a specifically engineered coupling between the two-qubit register and a dissipative reservoir. Similar autonomous feedback techniques have been used for qubit reset(9), single-qubit state stabilization(10), and the creation(11) and stabilization(6) of states of multipartite quantum systems. Unlike conventional, measurement-based schemes, the autonomous approach uses engineered dissipation to counteract decoherence(12-15), obviating the need for a complicated external feedback loop to correct errors. Instead, the feedback loop is built into the Hamiltonian such that the steady state of the system in the presence of drives and dissipation is a Bell state, an essential building block for quantum information processing. Such autonomous schemes, which are broadly applicable to a variety of physical systems, as demonstrated by the accompanying paper on trapped ion qubits(16), will be an essential tool for the implementation of quantum error correction.
C1 [Shankar, S.; Hatridge, M.; Leghtas, Z.; Sliwa, K. M.; Narla, A.; Vool, U.; Girvin, S. M.; Frunzio, L.; Mirrahimi, M.; Devoret, M. H.] Yale Univ, Dept Phys & Appl Phys, New Haven, CT 06520 USA.
   [Mirrahimi, M.] INRIA Paris Rocquencourt, F-78153 Le Chesnay, France.
C3 Yale University
RP Shankar, S (corresponding author), Yale Univ, Dept Phys & Appl Phys, New Haven, CT 06520 USA.
EM shyam.shankar@yale.edu; michel.devoret@yale.edu
FU Yale Institute for Nanoscience and Quantum Engineering; National Science Foundation (NSF) MRSEC [DMR 1119826]; Office of the Director of National Intelligence (ODNI), Intelligence Advanced Research Projects Activity (IARPA) [W911NF-09-1-0369]; US Army Research Office [W911NF-09-1-0514]; NSF [DMR 1006060, DMR 0653377, DMR 1004406]; Agence National de la Recherche [EPOQ2ANR-09-JCJC-0070]; Direct For Mathematical & Physical Scien; Division Of Materials Research [1004406] Funding Source: National Science Foundation; National Health and Medical Research Council (NHMRC) [1004406] Funding Source: National Health and Medical Research Council (NHMRC)
NR 41
TC 309
Z9 364
U1 0
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 DEC 19
PY 2013
VL 504
IS 7480
BP 419
EP +
DI 10.1038/nature12802
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 273ZR
UT WOS:000328575300048
PM 24270808
DA 2026-03-09
ER

PT J
AU Gulev, SK
   Latif, M
   Keenlyside, N
   Park, W
   Koltermann, KP
AF Gulev, Sergey K.
   Latif, Mojib
   Keenlyside, Noel
   Park, Wonsun
   Koltermann, Klaus Peter
TI North Atlantic Ocean control on surface heat flux on multidecadal timescales
SO NATURE
LA English
DT Article
ID thermohaline circulation; interdecadal variations; decadal variability; climate; impact; oscillation; anomaly; trends
AB Nearly 50 years ago Bjerknes(1) suggested that the character of large-scale air-sea interaction over the mid-latitude North Atlantic Ocean differs with timescales: the atmosphere was thought to drive directly most short-term-interannual-sea surface temperature (SST) variability, and the ocean to contribute significantly to long-term-multidecadal-SST and potentially atmospheric variability. Although the conjecture for short timescales is well accepted, understanding Atlantic multidecadal variability (AMV) of SST2,3 remains a challenge as a result of limited ocean observations. AMV is nonetheless of major socio-economic importance because it is linked to important climate phenomena such as Atlantic hurricane activity and Sahel rainfall, and it hinders the detection of anthropogenic signals in the North Atlantic sector(4-6). Direct evidence of the oceanic influence of AMV can only be provided by surface heat fluxes, the language of ocean-atmosphere communication. Here we provide observational evidence that in the mid-latitude North Atlantic and on timescales longer than 10 years, surface turbulent heat fluxes are indeed driven by the ocean and may force the atmosphere, whereas on shorter timescales the converse is true, thereby confirming the Bjerknes conjecture. This result, although strongest in boreal winter, is found in all seasons. Our findings suggest that the predictability of mid-latitude North Atlantic air-sea interaction could extend beyond the ocean to the climate of surrounding continents.
C1 [Gulev, Sergey K.] PP Shirshov Inst Oceanol, Moscow 117997, Russia.
   [Gulev, Sergey K.; Latif, Mojib; Park, Wonsun] GEOMAR Helmholtz Zentrum Ozeanforsch Kiel, D-24105 Kiel, Germany.
   [Gulev, Sergey K.; Koltermann, Klaus Peter] Moscow MV Lomonosov State Univ, Fac Geog, Moscow 119991, Russia.
   [Latif, Mojib] Univ Kiel, Cluster Excellence Future Ocean, D-24118 Kiel, Germany.
   [Keenlyside, Noel] Univ Bergen, Inst Geophys, N-5007 Bergen, Norway.
   [Keenlyside, Noel] Univ Bergen, Bjerknes Ctr Climate Res, N-5007 Bergen, Norway.
C3 Russian Academy of Sciences; Shirshov Institute of Oceanology; Helmholtz Association; GEOMAR Helmholtz Center for Ocean Research Kiel; Lomonosov Moscow State University; University of Kiel; University of Bergen; University of Bergen; Bjerknes Centre for Climate Research
RP Gulev, SK (corresponding author), PP Shirshov Inst Oceanol, 36 Nakhimovsky Prospect, Moscow 117997, Russia.
EM gul@sail.msk.ru
FU Deutsche Forschungsgemeinschaft [KE 1471/2-1]; Russian Ministry of Education and Science through the Special Grant for establishing excellence at Russian Universities [11.G34.31.0007]; Russian Ministry of Education and Science; RACE project of the German Federal Ministry of Education and Research;  [2011-16-420-1-001];  [11.519.11.6034]
NR 33
TC 260
Z9 287
U1 4
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 JUL 25
PY 2013
VL 499
IS 7459
BP 464
EP +
DI 10.1038/nature12268
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 187YP
UT WOS:000322157900037
PM 23887431
DA 2026-03-09
ER

PT J
AU Almada, AE
   Wu, XB
   Kriz, AJ
   Burge, CB
   Sharp, PA
AF Almada, Albert E.
   Wu, Xuebing
   Kriz, Andrea J.
   Burge, Christopher B.
   Sharp, Phillip A.
TI Promoter directionality is controlled by U1 snRNP and polyadenylation signals
SO NATURE
LA English
DT Article
ID pre-messenger-rnas; divergent transcription; upstream; cleavage; sequence; reveals; termination; downstream; exosome
AB Transcription of the mammalian genome is pervasive, but productive transcription outside of protein-coding genes is limited by unknown mechanisms(1). In particular, although RNA polymerase II (RNAPII) initiates divergently from most active gene promoters, productive elongation occurs primarily in the sense-coding direction(2-4). Here we show in mouse embryonic stem cells that asymmetric sequence determinants flanking gene transcription start sites control promoter directionality by regulating promoter-proximal cleavage and polyadenylation. We find that upstream antisense RNAs are cleaved and polyadenylated at poly(A) sites (PASs) shortly after initiation. De novo motif analysis shows PAS signals and U1 small nuclear ribonucleoprotein (snRNP) recognition sites to be the most depleted and enriched sequences, respectively, in the sense direction relative to the upstream antisense direction. These U1 snRNP sites and PAS sites are progressively gained and lost, respectively, at the 5' end of coding genes during vertebrate evolution. Functional disruption of U1 snRNP activity results in a dramatic increase in promoter-proximal cleavage events in the sense direction with slight increases in the antisense direction. These data suggest that a U1-PAS axis characterized by low U1 snRNP recognition and a high density of PASs in the upstream antisense region reinforces promoter directionality by promoting early termination in upstream antisense regions, whereas proximal sense PAS signals are suppressed by U1 snRNP. We propose that the U1-PAS axis limits pervasive transcription throughout the genome.
C1 [Almada, Albert E.; Wu, Xuebing; Sharp, Phillip A.] MIT, David H Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA.
   [Almada, Albert E.; Kriz, Andrea J.; Burge, Christopher B.; Sharp, Phillip A.] MIT, Dept Biol, Cambridge, MA 02139 USA.
   [Wu, Xuebing; Burge, Christopher B.] MIT, Computat & Syst Biol Grad Program, Cambridge, MA 02139 USA.
C3 Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT)
RP Sharp, PA (corresponding author), MIT, David H Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
EM sharppa@mit.edu
FU United States Public Health Service grants from the National Institutes of Health [RO1-GM34277, R01-CA133404]; National Cancer Institute [P30-CA14051]; Public Health Service research grant from the National Institute of General Medical Sciences [M-085319]; National Cancer Institute [P30CA014051, P01CA042063] Funding Source: NIH RePORTER; National Human Genome Research Institute [R01HG002439] Funding Source: NIH RePORTER; National Institute of General Medical Sciences [R01GM034277, R01GM085319] Funding Source: NIH RePORTER
NR 34
TC 313
Z9 390
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 JUL 18
PY 2013
VL 499
IS 7458
BP 360
EP U141
DI 10.1038/nature12349
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 184RJ
UT WOS:000321910700041
PM 23792564
DA 2026-03-09
ER

PT J
AU Kakar, K
   Zhang, HT
   Scheres, B
   Dhonukshe, P
AF Kakar, Klementina
   Zhang, Hongtao
   Scheres, Ben
   Dhonukshe, Pankaj
TI RETRACTED: CLASP-mediated cortical microtubule organization guides PIN polarization axis (Retracted article. See vol. 508, 2014)
SO NATURE
LA English
DT Article; Retracted Publication
ID auxin-efflux; plant development; arabidopsis root; plasma-membrane; cell-division; endocytosis; proteins; localization; cytokinesis; transport
AB Recent evidence indicates a correlation between orientation of the plant cortical microtubule cytoskeleton and localization of polar cargoes(1). However, the molecules and mechanisms that create this correlation have remained unknown. Here we show that, in Arabidopsis thaliana, the microtubule orientation regulators CLASP(2,3) and MAP65 (refs 3, 4) control the abundance of polarity regulator PINOID kinase(5,6) at the plasma membrane. By localized upregulation of clathrin-dependent endocytosis(7) at cortical microtubule- and clathrin-rich domains orthogonal to the axis of polarity, PINOID accelerates the removal of auxin transporter PIN proteins(8-10) from those sites. This mechanism links directional microtubule organization to the polar localization of auxin transporter PIN proteins, and clarifies how microtubule-enriched cell sides are kept distinct from polar delivery domains. Our results identify the molecular machinery that connects microtubule organization to the regulation of the axis of PIN polarization.
C1 [Kakar, Klementina; Zhang, Hongtao; Scheres, Ben; Dhonukshe, Pankaj] Univ Utrecht, Dept Biol, NL-3584 CH Utrecht, Netherlands.
   [Zhang, Hongtao] Univ Utrecht, Bijvoet Ctr Biomol Res, NL-3584 CH Utrecht, Netherlands.
   [Zhang, Hongtao] Univ Utrecht, Utrecht Inst Pharmaceut Sci, NL-3584 CH Utrecht, Netherlands.
   [Zhang, Hongtao; Scheres, Ben] Netherlands Prote Ctr, NL-3584 CH Utrecht, Netherlands.
   [Scheres, Ben] Wageningen Univ Res, NL-6708 PB Wageningen, Netherlands.
   [Dhonukshe, Pankaj] VIB, Dept Plant Syst Biol, B-9052 Ghent, Belgium.
   [Dhonukshe, Pankaj] Univ Ghent, Dept Plant Biotechnol & Bioinformat, B-9052 Ghent, Belgium.
C3 Utrecht University; Utrecht University; Utrecht University; Wageningen University & Research; Flanders Institute for Biotechnology (VIB); Ghent University
RP Dhonukshe, P (corresponding author), Univ Utrecht, Dept Biol, NL-3584 CH Utrecht, Netherlands.
EM pankaj.dhonukshe@psb.ugent.be
FU Utrecht University; Netherlands Organisation for Scientific Research VIDI; European Research Council; European Research Council Advanced Investigator grant; Netherlands Organisation for Scientific Research Spinoza; Netherlands Proteomics Centre
NR 34
TC 23
Z9 32
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 28
PY 2013
VL 495
IS 7442
BP 529
EP +
DI 10.1038/nature11980
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 113QN
UT WOS:000316682800050
PM 23515161
DA 2026-03-09
ER

PT J
AU Antonyuk, SV
   Han, C
   Eady, RR
   Hasnain, SS
AF Antonyuk, Svetlana V.
   Han, Cong
   Eady, Robert R.
   Hasnain, S. Samar
TI Structures of protein-protein complexes involved in electron transfer
SO NATURE
LA English
DT Article
ID atomic-resolution structures; copper nitrite reductase; active-site; binding
AB Electron transfer reactions are essential for life because they underpin oxidative phosphorylation and photosynthesis, processes leading to the generation of ATP, and are involved in many reactions of intermediary metabolism(1). Key to these roles is the formation of transient inter-protein electron transfer complexes. The structural basis for the control of specificity between partner proteins is lacking because these weak transient complexes have remained largely intractable for crystallographic studies(2,3). Inter-protein electron transfer processes are central to all of the key steps of denitrification, an alternative form of respiration in which bacteria reduce nitrate or nitrite to N-2 through the gaseous intermediates nitric oxide (NO) and nitrous oxide (N2O) when oxygen concentrations are limiting. The one-electron reduction of nitrite to NO, a precursor to N2O, is performed by either a haem-or copper-containing nitrite reductase (CuNiR) where they receive an electron from redox partner proteins a cupredoxin or a c-type cytochrome(4,5). Here we report the structures of the newly characterized three-domain haem-c-Cu nitrite reductase from Ralstonia pickettii (RpNiR) at 1.01 angstrom resolution and its M92A and P93A mutants. Very high resolution provides the first view of the atomic detail of the interface between the core trimeric cupredoxin structure of CuNiR and the tethered cytochrome c domain that allows the enzyme to function as an effective self-electron transfer system where the donor and acceptor proteins are fused together by genomic acquisition for functional advantage. Comparison of RpNiR with the binary complex of a CuNiR with a donor protein, AxNiR-cytc551 (ref. 6), and mutagenesis studies provide direct evidence for the importance of a hydrogen-bonded water at the interface in electron transfer. The structure also provides an explanation for the preferential binding of nitrite to the reduced copper ion at the active site in RpNiR, in contrast to other CuNiRs where reductive inactivation occurs, preventing substrate binding.
C1 [Antonyuk, Svetlana V.; Han, Cong; Eady, Robert R.; Hasnain, S. Samar] Univ Liverpool, Fac Hlth & Life Sci, Inst Integrat Biol, Mol Biophys Grp, Liverpool L69 7ZX, Merseyside, England.
C3 University of Liverpool
RP Hasnain, SS (corresponding author), Univ Liverpool, Fac Hlth & Life Sci, Inst Integrat Biol, Mol Biophys Grp, Liverpool L69 7ZX, Merseyside, England.
EM antonyuk@liverpool.ac.uk; s.s.hasnain@liverpool.ac.uk
FU Biotechnology and Biological Sciences Research Council, UK [BB/G005869/1]; Wellcome Trust [097826/Z/11/Z]; Biotechnology and Biological Sciences Research Council [BB/G005869/1] Funding Source: researchfish; BBSRC [BB/G005869/1] Funding Source: UKRI; Wellcome Trust [097826/Z/11/Z] Funding Source: Wellcome Trust
NR 31
TC 65
Z9 67
U1 1
U2 200
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 4
PY 2013
VL 496
IS 7443
BP 123
EP 127
DI 10.1038/nature11996
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 117ZZ
UT WOS:000316993400038
PM 23535590
DA 2026-03-09
ER

PT J
AU Yin, CM
   Rancic, M
   de Boo, GG
   Stavrias, N
   McCallum, JC
   Sellars, MJ
   Rogge, S
AF Yin, Chunming
   Rancic, Milos
   de Boo, Gabriele G.
   Stavrias, Nikolas
   McCallum, Jeffrey C.
   Sellars, Matthew J.
   Rogge, Sven
TI Optical addressing of an individual erbium ion in silicon
SO NATURE
LA English
DT Article
ID single-shot readout; electron-spin; er3+; atom; entanglement; donor
AB The detection of electron spins associated with single defects in solids is a critical operation for a range of quantum information and measurement applications under development(1-9). So far, it has been accomplished for only two defect centres in crystalline solids: phosphorus dopants in silicon, for which electrical read-out based on a single-electron transistor is used(1), and nitrogen-vacancy centres in diamond, for which optical read-out is used(4-6). A spin readout fidelity of about 90 per cent has been demonstrated with both electrical read-out(1) and optical read-out(10,11); however, the thermal limitations of the former and the poor photon collection efficiency of the latter make it difficult to achieve the higher fidelities required for quantum information applications. Here we demonstrate a hybrid approach in which optical excitation is used to change the charge state (conditional on its spin state) of an erbium defect centre in a silicon-based single-electron transistor, and this change is then detected electrically. The high spectral resolution of the optical frequency-addressing step overcomes the thermal broadening limitation of the previous electrical read-out scheme, and the charge-sensing step avoids the difficulties of efficient photon collection. This approach could lead to new architectures for quantum information processing devices and could drastically increase the range of defect centres that can be exploited. Furthermore, the efficient electrical detection of the optical excitation of single sites in silicon represents a significant step towards developing interconnects between optical-based quantum computing and silicon technologies.
C1 [Yin, Chunming; de Boo, Gabriele G.; Rogge, Sven] Univ New S Wales, Sch Phys, Ctr Excellence Quantum Computat & Commun Technol, Sydney, NSW 2052, Australia.
   [Rancic, Milos; Sellars, Matthew J.] Australian Natl Univ, RSPE, Ctr Excellence Quantum Computat & Commun Technol, Canberra, ACT 0200, Australia.
   [Stavrias, Nikolas; McCallum, Jeffrey C.] Univ Melbourne, Sch Phys, Ctr Excellence Quantum Computat & Commun Technol, Melbourne, Vic 3010, Australia.
C3 University of New South Wales Sydney; Australian National University; University of Melbourne
RP Rogge, S (corresponding author), Univ New S Wales, Sch Phys, Ctr Excellence Quantum Computat & Commun Technol, Sydney, NSW 2052, Australia.
EM s.rogge@unsw.edu.au
FU ARC Centre of Excellence for Quantum Computation and Communication Technology [CE110001027]; Future Fellowships [FT100100589, FT110100919]
NR 33
TC 163
Z9 181
U1 2
U2 144
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 2
PY 2013
VL 497
IS 7447
BP 91
EP 94
DI 10.1038/nature12081
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 134OK
UT WOS:000318221500039
PM 23636400
DA 2026-03-09
ER

PT J
AU Zhang, JW
   Ferré-D'Amaré, AR
AF Zhang, Jinwei
   Ferre-D'Amare, Adrian R.
TI Co-crystal structure of a T-box riboswitch stem I domain in complex with its cognate tRNA
SO NATURE
LA English
DT Article
ID aminoacyl-transfer-rna; ribosomal-rna; antitermination; recognition; features; systems; motifs
AB In Gram-positive bacteria, T-box riboswitches regulate the expression of aminoacyl-tRNA synthetases and other proteins in response to fluctuating transfer RNA aminoacylation levels under various nutritional states(1). T-boxes reside in the 5'-untranslated regions of the messenger RNAs they regulate, and consist of two conserved domains. Stem I contains the specifier trinucleotide that base pairs with the anticodon of cognate tRNA. 3' to stem I is the antiterminator domain, which base pairs with the tRNA acceptor end and evaluates its aminoacylation state(2). Despite high phylogenetic conservation and widespread occurrence in pathogens, the structural basis of tRNA recognition(3,4) by this riboswitch remains ill defined. Here we demonstrate that the similar to 100-nucleotide T-box stem I is necessary and sufficient for specific, high-affinity (dissociation constant (K-d) similar to 150 nM) tRNA binding, and report the structure of Oceanobacillus iheyensis glyQ stem I in complex with its cognate tRNA at 3.2 angstrom resolution. Stem I recognizes the overall architecture of tRNA in addition to its anticodon, something accomplished by large ribonucleoproteins such as the ribosome, or proteins such as aminoacyl-tRNA synthetases(5), but is unprecedented for a compact mRNA domain. The C-shaped stem I cradles the L-shaped tRNA, forming an extended (1,604 angstrom(2)) intermolecular interface. In addition to the specifier-anticodon interaction, two interdigitated T-loops near the apex of stem I stack on the tRNA elbow in a manner analogous to those of the J11/12-J12/11 motif(6) of RNase P and the L1 stalk(7) of the ribosomal E-site. Because these ribonucleoproteins and T-boxes are unrelated, this strategy to recognize a universal tRNA feature probably evolved convergently. Mutually induced fit of stem I and the tRNA exploiting the intrinsic flexibility of tRNA and its conserved post-transcriptional modifications results in high shape complementarity, which in addition to providing specificity and affinity, globally organizes the T-box to orchestrate tRNA-dependent transcription regulation.
C1 [Zhang, Jinwei; Ferre-D'Amare, Adrian R.] NHLBI, Bethesda, MD 20892 USA.
C3 National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI)
RP Ferré-D'Amaré, AR (corresponding author), NHLBI, 50 South Dr,MSC 8012, Bethesda, MD 20892 USA.
EM adrian.ferre@nih.gov
FU National Institute for General Medical Sciences, National Institutes of Health (NIH); US Department of Energy; intramural program of the National Heart, Lung, and Blood Institute, NIH; National Heart Lung and Blood Institute [ZIAHL006102] Funding Source: NIH RePORTER
NR 52
TC 124
Z9 153
U1 0
U2 72
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 15
PY 2013
VL 500
IS 7462
BP 363
EP +
DI 10.1038/nature12440
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 201AF
UT WOS:000323112400039
PM 23892783
DA 2026-03-09
ER

PT J
AU Wang, ZC
   Becker, H
AF Wang, Zaicong
   Becker, Harry
TI Ratios of S, Se and Te in the silicate Earth require a volatile-rich late veneer
SO NATURE
LA English
DT Article
ID highly siderophile elements; orogenic peridotites; terrestrial planets; mantle; tellurium; accretion; xenoliths; systematics; selenium; temperatures
AB The excess of highly siderophile (iron-loving) elements (HSEs) and the chondritic ratios of most HSEs in the bulk silicate Earth (BSE) may reflect the accretion of a chondritic 'late veneer' of about 0.5 per cent of Earth's mass after core formation(1,2). The amount of volatiles contained in the late veneer is a key constraint on the budget and the origin of the volatiles in Earth. At high pressures and temperatures, the moderately volatile chalcogen elements sulphur (S), selenium (Se) and tellurium (Te) are moderately to highly siderophile; thus, if depleted by core formation their mantle abundances should reflect the volatile composition of the late veneer(3,4). Here we report ratios and abundances of S, Se and Te in the mantle determined from new isotope dilution data for post-Archaean mantle peridotites. The mean S/Se and Se/Te ratios of mantle lherzolites overlap with CI (Ivuna-type) carbonaceous chondrite values(5,6). The Se/Te ratios of ordinary and enstatite chondrites are significantly different. The chalcogen/HSE ratio of the BSE is similar to that of CM (Mighei-type) carbonaceous chondrites, consistent with the view that the HSE signature of the BSE reflects a predominance of slightly volatile-depleted, carbonaceous-chondrite-like material, possibly with a minor proportion of non-chondritic material(7). Depending on the estimates for the abundances of water and carbon in the BSE8, the late veneer may have supplied 20 to 100 per cent of the budget of hydrogen and carbon in the BSE.
C1 [Wang, Zaicong; Becker, Harry] Free Univ Berlin, Inst Geol Wissensch, D-12249 Berlin, Germany.
C3 Free University of Berlin
RP Wang, ZC (corresponding author), Free Univ Berlin, Inst Geol Wissensch, Malteserstr 74-100, D-12249 Berlin, Germany.
EM zaicongwang@gmail.com; hbecker@zedat.fu-berlin.de
FU Freie Universitat Berlin; China Scholarship Council fellowship
NR 31
TC 220
Z9 247
U1 1
U2 185
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 18
PY 2013
VL 499
IS 7458
BP 328
EP +
DI 10.1038/nature12285
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 184RJ
UT WOS:000321910700034
PM 23868263
DA 2026-03-09
ER

PT J
AU Zhang, S
   Gilbert, I
   Nisoli, C
   Chern, GW
   Erickson, MJ
   O'Brien, L
   Leighton, C
   Lammert, PE
   Crespi, VH
   Schiffer, P
AF Zhang, Sheng
   Gilbert, Ian
   Nisoli, Cristiano
   Chern, Gia-Wei
   Erickson, Michael J.
   O'Brien, Liam
   Leighton, Chris
   Lammert, Paul E.
   Crespi, Vincent H.
   Schiffer, Peter
TI Crystallites of magnetic charges in artificial spin ice
SO NATURE
LA English
DT Article
ID monopoles
AB Artificial spin ice(1) is a class of lithographically created arrays of interacting ferromagnetic nanometre-scale islands. It was introduced to investigate many-body phenomena related to frustration and disorder in a material that could be tailored to precise specifications and imaged directly. Because of the large magnetic energy scales of these nanoscale islands, it has so far been impossible to thermally anneal artificial spin ice into desired thermodynamic ensembles; nearly all studies of artificial spin ice have either treated it as a granular material activated by alternating fields(2) or focused on the as-grown state of the arrays(3). This limitation has prevented experimental investigation of novel phases that can emerge from the nominal ground states of frustrated lattices. For example, artificial kagome spin ice, in which the islands are arranged on the edges of a hexagonal net, is predicted to support states with monopolar charge order at entropies below that of the previously observed pseudo-ice manifold(4). Here we demonstrate a method for thermalizing artificial spin ices with square and kagome lattices by heating above the Curie temperature of the constituent material. In this manner, artificial square spin ice achieves unprecedented thermal ordering of the moments. In artificial kagome spin ice, we observe incipient crystallization of the magnetic charges embedded in pseudo-ice, with crystallites of magnetic charges whose size can be controlled by tuning the lattice constant. We find excellent agreement between experimental data and Monte Carlo simulations of emergent charge-charge interactions.
C1 [Zhang, Sheng; Lammert, Paul E.; Crespi, Vincent H.] Penn State Univ, Dept Phys, University Pk, PA 16802 USA.
   [Zhang, Sheng; Lammert, Paul E.; Crespi, Vincent H.] Penn State Univ, Mat Res Inst, University Pk, PA 16802 USA.
   [Gilbert, Ian; Schiffer, Peter] Univ Illinois, Dept Phys, Urbana, IL 61801 USA.
   [Gilbert, Ian; Schiffer, Peter] Univ Illinois, Frederick Seitz Mat Res Lab, Urbana, IL 61801 USA.
   [Nisoli, Cristiano; Chern, Gia-Wei] Los Alamos Natl Lab, Div Theoret, Los Alamos, NM 87545 USA.
   [Erickson, Michael J.; O'Brien, Liam; Leighton, Chris] Univ Minnesota, Dept Chem Engn & Mat Sci, Minneapolis, MN 55455 USA.
   [O'Brien, Liam] Univ Cambridge, Cavendish Lab, Dept Phys, Thin Film Magnetism Grp, Cambridge CB3 0HE, England.
C3 Pennsylvania Commonwealth System of Higher Education (PCSHE); Pennsylvania State University; Pennsylvania State University - University Park; Pennsylvania Commonwealth System of Higher Education (PCSHE); Pennsylvania State University; Pennsylvania State University - University Park; University of Illinois System; University of Illinois Urbana-Champaign; University of Illinois System; University of Illinois Urbana-Champaign; United States Department of Energy (DOE); Los Alamos National Laboratory; University of Minnesota System; University of Minnesota Twin Cities; University of Cambridge
RP Schiffer, P (corresponding author), Univ Illinois, Dept Phys, 1110 W Green St, Urbana, IL 61801 USA.
EM pschiffe@illinois.edu
FU US Department of Energy, Office of Basic Energy Sciences, Materials Sciences and Engineering Division [DE-SC0005313]; US Department of Energy at LANL [DE-AC52-06NA253962]; NSF MRSEC [DMR-0819885, DMR-0820404]; EU Marie Curie IOF [299376]; Academy of Finland (AKA) [299376] Funding Source: Academy of Finland (AKA)
NR 30
TC 207
Z9 226
U1 1
U2 148
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 29
PY 2013
VL 500
IS 7464
BP 553
EP 557
DI 10.1038/nature12399
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 207TD
UT WOS:000323625900029
PM 23985872
DA 2026-03-09
ER

PT J
AU Salazar-Ciudad, I
   Marín-Riera, M
AF Salazar-Ciudad, Isaac
   Marin-Riera, Miquel
TI Adaptive dynamics under development-based genotype-phenotype maps
SO NATURE
LA English
DT Article
ID pattern-formation; evolution; model; adaptation; mechanisms; rna
AB It is not known whether natural selection can encounter any given phenotype that can be produced by genetic variation. There has been a long-lasting debate about the processes that limit adaptation(1-6) and, consequently, about how well adapted phenotypes are. Here we examine how development may affect adaptation, by decomposing the genotype-fitness map-the association between each genotype and its fitness-into two: one mapping genotype to phenotype by means of a computational model of organ development(7), and one mapping phenotype to fitness. In the map of phenotype and fitness, the fitness of each individual is based on the similarity between realized morphology and optimal morphology. We use three different simulations to map phenotype to fitness, and these differ in the way in which similarity is calculated: similarity is calculated for each trait (in terms of each cell position individually), for a large or a small number of phenotypic landmarks (the 'many-traits' and 'few-traits' phenotype-fitness maps), and by measuring the overall surface roughness of morphology (the 'roughness' phenotype-fitness map). Evolution is simulated by applying the genotype-phenotype map and one phenotype-fitness map to each individual in the population, as well as random mutation and drift. We show that the complexity of the genotype-phenotype map prevents substantial adaptation in some of the phenotype-fitness maps: sustained adaptation is only possible using 'roughness' or 'few-traits' phenotype-fitness maps. The results contribute developmental understanding to the long-standing question of which aspects of phenotype can be effectively optimized by natural selection.
C1 [Salazar-Ciudad, Isaac] Univ Helsinki, Inst Biotechnol, Dev Biol Program, Evolutionary Phen Grp, FIN-00014 Helsinki, Finland.
   [Salazar-Ciudad, Isaac; Marin-Riera, Miquel] Univ Autonoma Barcelona, Dept Genet & Microbiol, Genom Bioinformat & Evolut Grp, Cerdanyola Del Valles 08193, Spain.
C3 University of Helsinki; Autonomous University of Barcelona
RP Salazar-Ciudad, I (corresponding author), Univ Helsinki, Inst Biotechnol, Dev Biol Program, Evolutionary Phen Grp, POB 56, FIN-00014 Helsinki, Finland.
EM isaac.salazar@uab.cat
FU Finnish Academy [WBS 1250271]; Spanish Ministry of Science and Innovation [BFU2010-17044]
NR 29
TC 85
Z9 99
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 MAY 16
PY 2013
VL 497
IS 7449
BP 361
EP +
DI 10.1038/nature12142
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 144PN
UT WOS:000318952000036
PM 23636325
DA 2026-03-09
ER

PT J
AU Kleinewietfeld, M
   Manzel, A
   Titze, J
   Kvakan, H
   Yosef, N
   Linker, RA
   Muller, DN
   Hafler, DA
AF Kleinewietfeld, Markus
   Manzel, Arndt
   Titze, Jens
   Kvakan, Heda
   Yosef, Nir
   Linker, Ralf A.
   Muller, Dominik N.
   Hafler, David A.
TI Sodium chloride drives autoimmune disease by the induction of pathogenic TH17 cells
SO NATURE
LA English
DT Article
ID threonine protein-kinase; t-cells; osmotic-stress; transcriptional target; p38 mapk; tgf-beta; sgk; gene; inflammation; activation
AB There has been a marked increase in the incidence of autoimmune diseases in the past half-century. Although the underlying genetic basis of this class of diseases has recently been elucidated, implicating predominantly immune-response genes(1), changes in environmental factors must ultimately be driving this increase. The newly identified population of interleukin (IL)-17-producing CD4(+) helper T cells (T(H)17 cells) has a pivotal role in autoimmune diseases(2). Pathogenic IL-23-dependent T(H)17 cells have been shown to be critical for the development of experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis, and genetic risk factors associated with multiple sclerosis are related to the IL-23-T(H)17 pathway(1,2). However, little is known about the environmental factors that directly influence T(H)17 cells. Here we show that increased salt (sodium chloride, NaCl) concentrations found locally under physiological conditions in vivo markedly boost the induction of murine and human T(H)17 cells. High-salt conditions activate the p38/MAPK pathway involving nuclear factor of activated T cells 5 (NFAT5; also called TONEBP) and serum/glucocorticoid-regulated kinase 1 (SGK1) during cytokine-induced T(H)17 polarization. Gene silencing or chemical inhibition of p38/MAPK, NFAT5 or SGK1 abrogates the high-salt-induced T(H)17 cell development. The T(H)17 cells generated under high-salt conditions display a highly pathogenic and stable phenotype characterized by the upregulation of the pro-inflammatory cytokines GM-CSF, TNF-alpha and IL-2. Moreover, mice fed with a high-salt diet develop a more severe form of EAE, in line with augmented central nervous system infiltrating and peripherally induced antigen-specific T(H)17 cells. Thus, increased dietary salt intake might represent an environmental risk factor for the development of autoimmune diseases through the induction of pathogenic T(H)17 cells.
C1 [Kleinewietfeld, Markus; Hafler, David A.] Yale Univ, Sch Med, Dept Neurol, New Haven, CT 06520 USA.
   [Kleinewietfeld, Markus; Hafler, David A.] Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT 06520 USA.
   [Kleinewietfeld, Markus; Yosef, Nir; Hafler, David A.] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.
   [Manzel, Arndt; Linker, Ralf A.] Univ Erlangen Nurnberg, Dept Neurol, D-91054 Erlangen, Germany.
   [Manzel, Arndt] Ruhr Univ Bochum, Int Grad Sch Neurosci, D-44801 Bochum, Germany.
   [Titze, Jens] Vanderbilt Univ, Div Clin Pharmacol, Nashville, TN 37232 USA.
   [Titze, Jens] Univ Erlangen Nurnberg, Interdisciplinary Ctr Clin Res, D-91054 Erlangen, Germany.
   [Titze, Jens] Univ Erlangen Nurnberg, Dept Hypertens & Nephrol, D-91054 Erlangen, Germany.
   [Kvakan, Heda; Muller, Dominik N.] Expt & Clin Res Ctr, D-13125 Berlin, Germany.
   [Kvakan, Heda] Helios Klinikum Berlin Buch, D-13125 Berlin, Germany.
   [Muller, Dominik N.] Univ Erlangen Nurnberg, Nikolaus Fiebiger Ctr Mol Med, D-91054 Erlangen, Germany.
C3 Yale University; Yale University; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; University of Erlangen Nuremberg; Ruhr University Bochum; Vanderbilt University; University of Erlangen Nuremberg; University of Erlangen Nuremberg; Helios Kliniken; University of Erlangen Nuremberg
RP Kleinewietfeld, M (corresponding author), Yale Univ, Sch Med, Dept Neurol, 15 York St, New Haven, CT 06520 USA.
EM markus.kleinewietfeld@yale.edu; david.hafler@yale.edu
FU National MS Society Collaborative Research Center [CA1061-A-18]; National Institutes of Health [P01 AI045757, U19 AI046130, U19 AI070352, P01 AI039671]; National Institute of Neurological Disorders and Stroke [NS2427]; Penates Foundation; Nancy Taylor Foundation for Chronic Diseases, Inc.; ELAN programme, University of Erlangen; German Research Foundation (DFG); German Center for Cardiovascular Research (DZHK); Interdisciplinary Center for Clinical Research at University of Erlangen; German Research Foundation; National Institute of Allergy and Infectious Diseases [P01AI039671] Funding Source: NIH RePORTER
NR 38
TC 1117
Z9 1269
U1 4
U2 270
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 25
PY 2013
VL 496
IS 7446
BP 518
EP +
DI 10.1038/nature11868
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 131HU
UT WOS:000317984400044
PM 23467095
DA 2026-03-09
ER

PT J
AU McLauchlan, KK
   Williams, JJ
   Craine, JM
   Jeffers, ES
AF McLauchlan, Kendra K.
   Williams, Joseph J.
   Craine, Joseph M.
   Jeffers, Elizabeth S.
TI Changes in global nitrogen cycling during the Holocene epoch
SO NATURE
LA English
DT Article
ID recent environmental-changes; regional paleolimnological assessment; sedimentary geochemical record; lacustrine organic-matter; mountain national-park; lake-sediments; stable-isotopes; climate-change; alpine lakes; east-africa
AB Human activities have doubled the pre-industrial supply of reactive nitrogen on Earth, and future rates of increase are expected to accelerate(1). Yet little is known about the capacity of the biosphere to buffer increased nitrogen influx. Past changes in global ecosystems following deglaciation at the end of the Pleistocene epoch provide an opportunity to understand better how nitrogen cycling in the terrestrial biosphere responded to changes in carbon cycling. We analysed published records of stable nitrogen isotopic values (delta N-15) in sediments from 86 lakes on six continents. Here we show that the value of sedimentary delta N-15 declined from 15,000 years before present to 7,056 +/- 597 years before present, a period of increasing atmospheric carbon dioxide concentrations and terrestrial carbon accumulation(2). Comparison of the nitrogen isotope record with concomitant carbon accumulation on land and nitrous oxide in the atmosphere suggests millennia of declining nitrogen availability in terrestrial ecosystems during the Pleistocene-Holocene transition around 11,000 years before present. In contrast, we do not observe a consistent change in global sedimentary delta N-15 values during the past 500 years, despite the potential effects of changing temperature and nitrogen influx from anthropogenic sources. We propose that the lack of a single response may indicate that modern increases in atmospheric carbon dioxide and net carbon sequestration in the biosphere have the potential to offset recent increased supplies of reactive nitrogen in some ecosystems.
C1 [McLauchlan, Kendra K.; Williams, Joseph J.] Kansas State Univ, Dept Geog, Manhattan, KS 66506 USA.
   [Craine, Joseph M.] Kansas State Univ, Div Biol, Manhattan, KS 66506 USA.
   [Jeffers, Elizabeth S.] Univ Oxford, Biodivers Inst, Dept Zool, Oxford OX1 3PS, England.
C3 Kansas State University; Kansas State University; University of Oxford
RP McLauchlan, KK (corresponding author), Kansas State Univ, Dept Geog, Manhattan, KS 66506 USA.
EM mclauch@ksu.edu
FU National Science Foundation [BCS-0955225, EPS-0903806]; James Martin Fellowship at the University of Oxford; Direct For Social, Behav & Economic Scie; Division Of Behavioral and Cognitive Sci [0955225] Funding Source: National Science Foundation; Office Of The Director; Office of Integrative Activities [0903806] Funding Source: National Science Foundation
NR 105
TC 124
Z9 143
U1 9
U2 444
PU NATURE PUBLISHING 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 21
PY 2013
VL 495
IS 7441
BP 352
EP 355
DI 10.1038/nature11916
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 113EY
UT WOS:000316650500039
PM 23518563
DA 2026-03-09
ER

PT J
AU Kaspi, Y
   Showman, AP
   Hubbard, WB
   Aharonson, O
   Helled, R
AF Kaspi, Yohai
   Showman, Adam P.
   Hubbard, William B.
   Aharonson, Oded
   Helled, Ravit
TI Atmospheric confinement of jet streams on Uranus and Neptune
SO NATURE
LA English
DT Article
ID deep zonal flows; interior structure; cloud features; giant planets; jupiter; circulation; models; saturn; winds; dynamics
AB The observed cloud-level atmospheric circulation on the outer planets of the Solar System is dominated by strong east-west jet streams. The depth of these winds is a crucial unknown in constraining their overall dynamics, energetics and internal structures. There are two approaches to explaining the existence of these strong winds. The first suggests that the jets are driven by shallow atmospheric processes near the surface(1-3), whereas the second suggests that the atmospheric dynamics extend deeply into the planetary interiors(4,5). Here we report that on Uranus and Neptune the depth of the atmospheric dynamics can be revealed by the planets' respective gravity fields. We show that the measured fourth-order gravity harmonic, J(4), constrains the dynamics to the outermost 0.15 per cent of the total mass of Uranus and the outermost 0.2 per cent of the total mass of Neptune. This provides a stronger limit to the depth of the dynamical atmosphere than previously suggested(6), and shows that the dynamics are confined to a thin weather layer no more than about 1,000 kilometres deep on both planets.
C1 [Kaspi, Yohai; Aharonson, Oded] Weizmann Inst Sci, Dept Environm Sci, IL-76100 Rehovot, Israel.
   [Kaspi, Yohai; Aharonson, Oded] Weizmann Inst Sci, Ctr Planetary Sci, IL-76100 Rehovot, Israel.
   [Showman, Adam P.; Hubbard, William B.] Univ Arizona, Lunar & Planetary Lab, Tucson, AZ 85721 USA.
   [Aharonson, Oded] CALTECH, Dept Geol & Planetary Sci, Pasadena, CA 91125 USA.
   [Helled, Ravit] Tel Aviv Univ, Dept Geophys & Planetary Sci, IL-69978 Tel Aviv, Israel.
C3 Weizmann Institute of Science; Weizmann Institute of Science; University of Arizona; California Institute of Technology; Tel Aviv University
RP Kaspi, Y (corresponding author), Weizmann Inst Sci, Dept Environm Sci, IL-76100 Rehovot, Israel.
EM yohai.kaspi@weizmann.ac.il
FU Helen Kimmel Center for Planetary Science at the Weizmann Institute of Science; NASA
NR 30
TC 76
Z9 80
U1 0
U2 26
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 16
PY 2013
VL 497
IS 7449
BP 344
EP 347
DI 10.1038/nature12131
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 144PN
UT WOS:000318952000032
PM 23676751
DA 2026-03-09
ER

PT J
AU Cooper, KL
   Oh, S
   Sung, Y
   Dasari, RR
   Kirschner, MW
   Tabin, CJ
AF Cooper, Kimberly L.
   Oh, Seungeun
   Sung, Yongjin
   Dasari, Ramachandra R.
   Kirschner, Marc W.
   Tabin, Clifford J.
TI Multiple phases of chondrocyte enlargement underlie differences in skeletal proportions
SO NATURE
LA English
DT Article
ID longitudinal bone-growth; plate chondrocytes; volume increase; factor-i; hypertrophy; performance; mechanisms; hindlimb; rats; age
AB The wide diversity of skeletal proportions in mammals is evident upon a survey of any natural history museum's collections and allows us to distinguish between species even when reduced to their calcified components. Similarly, each individual is comprised of a variety of bones of differing lengths. The largest contribution to the lengthening of a skeletal element, and to the differential elongation of elements, comes from a dramatic increase in the volume of hypertrophic chondrocytes in the growth plate as they undergo terminal differentiation(1-7). However, the mechanisms of chondrocyte volume enlargement have remained a mystery(8-11). Here we use quantitative phase microscopy(12) to show that mammalian chondrocytes undergo three distinct phases of volume increase, including a phase of massive cell swelling in which the cellular dry mass is significantly diluted. In light of the tight fluid regulatory mechanisms known to control volume in many cell types(13), this is a remarkable mechanism for increasing cell size and. regulating growth rate. It is, however, the duration of the final phase of volume enlargement by proportional dry mass increase at low density that varies most between rapidly and slowly elongating growth plates. Moreover, we find that this third phase is locally regulated through a mechanism dependent on insulin-like growth factor. This study provides a framework for understanding how skeletal size is regulated and for exploring how cells sense, modify and establish a volume set point.
C1 [Cooper, Kimberly L.; Tabin, Clifford J.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
   [Oh, Seungeun; Kirschner, Marc W.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA.
   [Sung, Yongjin; Dasari, Ramachandra R.] MIT, George R Harrison Spect Lab, Cambridge, MA 02139 USA.
C3 Harvard University; Harvard Medical School; Harvard University; Harvard Medical School; Massachusetts Institute of Technology (MIT)
RP Cooper, KL (corresponding author), Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
EM kcooper@genetics.med.harvard.edu
FU NIH [P01DK056246, R01GM026875, P41RR02594]; National Science Foundation (NSF) [DBI0754339]; Hamamatsu Corporation; National Institute of Biomedical Imaging and Bioengineering [P41EB015871] Funding Source: NIH RePORTER
NR 23
TC 298
Z9 356
U1 1
U2 72
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 21
PY 2013
VL 495
IS 7441
BP 375
EP 378
DI 10.1038/nature11940
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 113EY
UT WOS:000316650500044
PM 23485973
DA 2026-03-09
ER

PT J
AU Maxted, PFL
   Serenelli, AM
   Miglio, A
   Marsh, TR
   Heber, U
   Dhillon, VS
   Littlefair, S
   Copperwheat, C
   Smalley, B
   Breedt, E
   Schaffenroth, V
AF Maxted, Pierre F. L.
   Serenelli, Aldo M.
   Miglio, Andrea
   Marsh, Thomas R.
   Heber, Ulrich
   Dhillon, Vikram S.
   Littlefair, Stuart
   Copperwheat, Chris
   Smalley, Barry
   Breedt, Elme
   Schaffenroth, Veronika
TI Multi-periodic pulsations of a stripped red-giant star in an eclipsing binary system
SO NATURE
LA English
DT Article
ID white-dwarf companion; helium-rich; evolution; core; discovery; ages; cool; hot
AB Low-mass white-dwarf stars are the remnants of disrupted red-giant stars in binary millisecond pulsars(1) and other exotic binary star systems(2-4). Some low-mass white dwarfs cool rapidly, whereas others stay bright for millions of years because of stable fusion in thick surface hydrogen layers(5). This dichotomy is not well understood, so the potential use of low-mass white dwarfs as independent clocks with which to test the spin-down ages of pulsars(6,7) or as probes of the extreme environments in which low-mass white dwarfs form(8-10) cannot fully be exploited. Here we report precise mass and radius measurements for the precursor to a low-mass white dwarf. We find that only models in which this disrupted red-giant star has a thick hydrogen envelope can match the strong constraints provided by our data. Very cool low-mass white dwarfs must therefore have lost their thick hydrogen envelopes by irradiation from pulsar companions(11,12) or by episodes of unstable hydrogen fusion (shell flashes). We also find that this low-mass white-dwarf precursor is a type of pulsating star not hitherto seen. The observed pulsation frequencies are sensitive to internal processes that determine whether this star will undergo shell flashes.
C1 [Maxted, Pierre F. L.; Smalley, Barry] Keele Univ, Astrophys Grp, Keele ST5 5BG, Staffs, England.
   [Serenelli, Aldo M.] Fac Ciencias, Inst Ciencias Espacio CSIC IEEC, Bellaterra 08193, Spain.
   [Miglio, Andrea] Univ Birmingham, Sch Phys & Astron, Birmingham B15 2TT, W Midlands, England.
   [Marsh, Thomas R.; Breedt, Elme] Univ Warwick, Dept Phys, Coventry CV4 7AL, W Midlands, England.
   [Heber, Ulrich; Schaffenroth, Veronika] Univ Erlangen Nurnberg, Dr Karl Remeis Observ, D-96049 Bamberg, Germany.
   [Heber, Ulrich; Schaffenroth, Veronika] Univ Erlangen Nurnberg, ECAP, Astron Inst, D-96049 Bamberg, Germany.
   [Dhillon, Vikram S.; Littlefair, Stuart] Univ Sheffield, Dept Phys & Astron, Sheffield S3 7RH, S Yorkshire, England.
   [Copperwheat, Chris] Liverpool John Moores Univ, Astrophys Res Inst, Wirral CH41 1LD, Merseyside, England.
   [Schaffenroth, Veronika] Univ Innsbruck, Inst Astrophys & Particle Phys, A-6020 Innsbruck, Austria.
C3 Keele University; Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Instituto de Ciencias del Espacio (ICE); Institut d'Estudis Espacials de Catalunya (IEEC); University of Birmingham; University of Warwick; University of Erlangen Nuremberg; University of Erlangen Nuremberg; University of Sheffield; Liverpool John Moores University; University of Innsbruck
RP Maxted, PFL (corresponding author), Keele Univ, Astrophys Grp, Keele ST5 5BG, Staffs, England.
EM p.maxted@keele.ac.uk
FU Re-integration Grant [PIRG-GA-2009-247732]; MICINN grant [AYA2011-24704]; Deutsches Zentrum fur Luft- und Raumfahrt [50 OR 1110]; Erika-Giehrl-Stiftung; UK Science and Technology Facilities Council [ST/I001719/1]; Science and Technology Facilities Council [ST/J000035/1, ST/G002355/1, ST/K002783/1, ST/I005773/1, ST/J001163/1, PP/F000057/1, ST/J001384/1, PP/D000955/1, ST/I001719/1, ST/J001589/1] Funding Source: researchfish; STFC [PP/D000955/1, ST/K002783/1, ST/J000035/1, ST/J001589/1, ST/J001384/1, PP/F000057/1, ST/I005773/1, ST/G002355/1, ST/I001719/1] Funding Source: UKRI
NR 28
TC 91
Z9 96
U1 0
U2 23
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 27
PY 2013
VL 498
IS 7455
BP 463
EP 465
DI 10.1038/nature12192
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 171LH
UT WOS:000320929400047
PM 23803845
DA 2026-03-09
ER

PT J
AU Yefsah, T
   Sommer, AT
   Ku, MJH
   Cheuk, LW
   Ji, WJ
   Bakr, WS
   Zwierlein, MW
AF Yefsah, Tarik
   Sommer, Ariel T.
   Ku, Mark J. H.
   Cheuk, Lawrence W.
   Ji, Wenjie
   Bakr, Waseem S.
   Zwierlein, Martin W.
TI Heavy solitons in a fermionic superfluid
SO NATURE
LA English
DT Article
ID dark solitons; condensate; depletion; dynamics; states; waves
AB Solitons-solitary waves that maintain their shape as they propagate-occur as water waves in narrow canals, as light pulses in optical fibres and as quantum mechanical matter waves in superfluids and superconductors. Their highly nonlinear and localized nature makes them very sensitive probes of the medium in which they propagate. Here we create long-lived solitons in a strongly interacting superfluid of fermionic atoms and directly observe their motion. As the interactions are tuned from the regime of Bose-Einstein condensation of tightly bound molecules towards the Bardeen-Cooper-Schrieffer limit of long-range Cooper pairs, the solitons' effective mass increases markedly, to more than 200 times their bare mass, signalling strong quantum fluctuations. This mass enhancement is more than 50 times larger than the theoretically predicted value. Our work provides a benchmark for theories of non-equilibrium dynamics of strongly interacting fermions.
C1 [Yefsah, Tarik; Sommer, Ariel T.; Ku, Mark J. H.; Cheuk, Lawrence W.; Ji, Wenjie; Bakr, Waseem S.; Zwierlein, Martin W.] MIT, Dept Phys, Elect Res Lab, MIT Harvard Ctr Ultracold Atoms, Cambridge, MA 02139 USA.
C3 Massachusetts Institute of Technology (MIT)
RP Zwierlein, MW (corresponding author), MIT, Dept Phys, Elect Res Lab, MIT Harvard Ctr Ultracold Atoms, Cambridge, MA 02139 USA.
EM zwierlein@mit.edu
FU NSF; ARO MURI on Atomtronics; AFOSR PECASE; ONR; Army Research Office; DARPA OLE programme; David and Lucile Packard Foundation; Direct For Mathematical & Physical Scien; Division Of Physics [0969311] Funding Source: National Science Foundation; Direct For Mathematical & Physical Scien; Division Of Physics [1125846] Funding Source: National Science Foundation
NR 50
TC 147
Z9 163
U1 0
U2 64
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 25
PY 2013
VL 499
IS 7459
BP 426
EP 430
DI 10.1038/nature12338
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 187YP
UT WOS:000322157900030
PM 23863930
DA 2026-03-09
ER

PT J
AU Sainsbury, S
   Niesser, J
   Cramer, P
AF Sainsbury, Sarah
   Niesser, Juergen
   Cramer, Patrick
TI Structure and function of the initially transcribing RNA polymerase II-TFIIB complex
SO NATURE
LA English
DT Article
ID transcription factor iib; saccharomyces-cerevisiae; preinitiation complex; angstrom resolution; promoter clearance; in-vivo; initiation; mechanism; dna; architecture
AB The general transcription factor (TF) IIB is required for RNA polymerase (Pol) II initiation and extends with its B-reader element into the Pol II active centre cleft. Low-resolution structures of the Pol II-TFIIB complex(1,2) indicated how TFIIB functions in DNA recruitment, but they lacked nucleic acids and half of the B-reader, leaving other TFIIB functions(3,4) enigmatic. Here we report crystal structures of the Pol II-TFIIB complex from the yeast Saccharomyces cerevisiae at 3.4 angstrom resolution and of an initially transcribing complex that additionally contains the DNA template and a 6-nucleotide RNA product. The structures reveal the entire B-reader and protein-nucleic acid interactions, and together with functional data lead to a more complete understanding of transcription initiation. TFIIB partially closes the polymerase cleft to position DNA and assist in its opening. The B-reader does not reach the active site but binds the DNA template strand upstream to assist in the recognition of the initiator sequence and in positioning the transcription start site. TFIIB rearranges active-site residues, induces binding of the catalytic metal ion B, and stimulates initial RNA synthesis allosterically. TFIIB then prevents the emerging DNA-RNA hybrid duplex from tilting, which would impair RNA synthesis. When the RNA grows beyond 6 nucleotides, it is separated from DNA and is directed to its exit tunnel by the B-reader loop. Once the RNA grows to 12-13 nucleotides, it clashes with TFIIB, triggering TFIIB displacement and elongation complex formation. Similar mechanisms may underlie all cellular transcription because all eukaryotic and archaeal RNA polymerases use TFIIB-like factors(5), and the bacterial initiation factor sigma has TFIIB-like topology(1,2) and contains the loop region 3.2 that resembles the B-reader loop in location, charge and function(6-8). TFIIB and its counterparts may thus account for the two fundamental properties that distinguish RNA from DNA polymerases: primer-independent chain initiation and product separation from the template.
C1 [Sainsbury, Sarah; Niesser, Juergen; Cramer, Patrick] Univ Munich, Gene Ctr, D-81377 Munich, Germany.
   [Sainsbury, Sarah; Niesser, Juergen; Cramer, Patrick] Univ Munich, Dept Biochem, Ctr Integrated Prot Sci CIPSM, D-81377 Munich, Germany.
C3 University of Munich; University of Munich
RP Cramer, P (corresponding author), Univ Munich, Gene Ctr, Feodor Lynen Str 25, D-81377 Munich, Germany.
EM cramer@lmb.uni-muenchen.de
FU Alexander-von-Humboldt Foundation; Deutsche Forschungsgemeinschaft [SFB646, TR5, GraKo1721, SFB960]; CIPSM; NIM; European Research Council; LMUinnovativ project Bioimaging Network; Jung-Stiftung; Vallee Foundation
NR 34
TC 148
Z9 190
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 JAN 17
PY 2013
VL 493
IS 7432
BP 437
EP U191
DI 10.1038/nature11715
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 071TA
UT WOS:000313615900059
PM 23151482
DA 2026-03-09
ER

PT J
AU Simakov, O
   Marletaz, F
   Cho, SJ
   Edsinger-Gonzales, E
   Havlak, P
   Hellsten, U
   Kuo, DH
   Larsson, T
   Lv, J
   Arendt, D
   Savage, R
   Osoegawa, K
   de Jong, P
   Grimwood, J
   Chapman, JA
   Shapiro, H
   Aerts, A
   Otillar, RP
   Terry, AY
   Boore, JL
   Grigoriev, IV
   Lindberg, DR
   Seaver, EC
   Weisblat, DA
   Putnam, NH
   Rokhsar, DS
AF Simakov, Oleg
   Marletaz, Ferdinand
   Cho, Sung-Jin
   Edsinger-Gonzales, Eric
   Havlak, Paul
   Hellsten, Uffe
   Kuo, Dian-Han
   Larsson, Tomas
   Lv, Jie
   Arendt, Detlev
   Savage, Robert
   Osoegawa, Kazutoyo
   de Jong, Pieter
   Grimwood, Jane
   Chapman, Jarrod A.
   Shapiro, Harris
   Aerts, Andrea
   Otillar, Robert P.
   Terry, Astrid Y.
   Boore, Jeffrey L.
   Grigoriev, Igor V.
   Lindberg, David R.
   Seaver, Elaine C.
   Weisblat, David A.
   Putnam, Nicholas H.
   Rokhsar, Daniel S.
TI Insights into bilaterian evolution from three spiralian genomes
SO NATURE
LA English
DT Article
ID schmidtea-mediterranea; schistosoma-mansoni; genes; tree; repertoire; resolution; organism; life
AB Current genomic perspectives on animal diversity neglect two prominent phyla, the molluscs and annelids, that together account for nearly one-third of known marine species and are important both ecologically and as experimental systems in classical embryology(1-3). Here we describe the draft genomes of the owl limpet (Lottia gigantea), a marine polychaete (Capitella teleta) and a freshwater leech (Helobdella robusta), and compare them with other animal genomes to investigate the origin and diversification of bilaterians from a genomic perspective. We find that the genome organization, gene structure and functional content of these species are more similar to those of some invertebrate deuterostome genomes (for example, amphioxus and sea urchin) than those of other protostomes that have been sequenced to date (flies, nematodes and flatworms). The conservation of these genomic features enables us to expand the inventory of genes present in the last common bilaterian ancestor, establish the tripartite diversification of bilaterians using multiple genomic characteristics and identify ancient conserved long-and short-range genetic linkages across metazoans. Superimposed on this broadly conserved pan-bilaterian background we find examples of lineage-specific genome evolution, including varying rates of rearrangement, intron gain and loss, expansions and contractions of gene families, and the evolution of clade-specific genes that produce the unique content of each genome.
C1 [Simakov, Oleg; Marletaz, Ferdinand; Larsson, Tomas; Arendt, Detlev] European Mol Biol Lab, D-69117 Heidelberg, Germany.
   [Simakov, Oleg; Cho, Sung-Jin; Edsinger-Gonzales, Eric; Kuo, Dian-Han; Weisblat, David A.; Rokhsar, Daniel S.] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA.
   [Havlak, Paul; Lv, Jie; Putnam, Nicholas H.] Rice Univ, Dept Ecol & Evolutionary Biol, Houston, TX 77251 USA.
   [Hellsten, Uffe; Grimwood, Jane; Chapman, Jarrod A.; Shapiro, Harris; Aerts, Andrea; Otillar, Robert P.; Terry, Astrid Y.; Boore, Jeffrey L.; Grigoriev, Igor V.; Rokhsar, Daniel S.] US DOE, Joint Genome Inst, Walnut Creek, CA 94598 USA.
   [Savage, Robert] Williams Coll, Dept Biol, Thompson Biol Lab, Williamstown, MA 01267 USA.
   [Osoegawa, Kazutoyo; de Jong, Pieter] Childrens Hosp Oakland, Res Inst, Oakland, CA 94609 USA.
   [Grimwood, Jane] Hudson Alpha Inst Biotechnol, Huntsville, AL 35806 USA.
   [Lindberg, David R.] Univ Calif Berkeley, Dept Integrat Biol, Berkeley, CA 94720 USA.
   [Seaver, Elaine C.] Univ Hawaii Manoa, Kewalo Marine Lab, Honolulu, HI 96813 USA.
   [Putnam, Nicholas H.] Rice Univ, Dept Biochem & Cell Biol, Houston, TX 77251 USA.
   [Rokhsar, Daniel S.] Okinawa Inst Sci & Technol, Onna Son, Okinawa 9040495, Japan.
C3 European Molecular Biology Laboratory (EMBL); University of California System; University of California Berkeley; Rice University; United States Department of Energy (DOE); Joint BioEnergy Institute - JBEI; Joint Genome Institute - JGI; Williams College; University of California System; University of California San Francisco; UCSF Medical Center; UCSF Benioff Children's Hospital Oakland; Children's Hospital Oakland Research Institute; University of California System; University of California Berkeley; University of Hawaii System; University of Hawaii Manoa; Rice University; Okinawa Institute of Science & Technology Graduate University
RP Putnam, NH (corresponding author), Rice Univ, Dept Ecol & Evolutionary Biol, POB 1892, Houston, TX 77251 USA.
EM nputnam@gmail.com; dsrokhsar@gmail.com
FU Office of Science of the US Department of Energy [DE-AC02-05CH11231]; Gordon and Betty Moore Foundation; National Science Foundation (NSF) [EF-0850294, I0S-0922792]; National Institutes of Health (NIH) [RO1 GM 074619]; Boehringer Ingelheim Fonds; US National Human Genome Research Institute; Direct For Biological Sciences; Emerging Frontiers [0850294] Funding Source: National Science Foundation; Division Of Integrative Organismal Systems; Direct For Biological Sciences [1318772] Funding Source: National Science Foundation
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   Putnam NH, 2008, NATURE, V453, P1064, DOI 10.1038/nature06967
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   Srivastava M, 2008, NATURE, V454, P955, DOI 10.1038/nature07191
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NR 28
TC 512
Z9 577
U1 3
U2 203
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 24
PY 2013
VL 493
IS 7433
BP 526
EP 531
DI 10.1038/nature11696
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 075GF
UT WOS:000313871400037
PM 23254933
DA 2026-03-09
ER

PT J
AU Reichstein, M
   Bahn, M
   Ciais, P
   Frank, D
   Mahecha, MD
   Seneviratne, SI
   Zscheischler, J
   Beer, C
   Buchmann, N
   Frank, DC
   Papale, D
   Rammig, A
   Smith, P
   Thonicke, K
   van der Velde, M
   Vicca, S
   Walz, A
   Wattenbach, M
AF Reichstein, Markus
   Bahn, Michael
   Ciais, Philippe
   Frank, Dorothea
   Mahecha, Miguel D.
   Seneviratne, Sonia I.
   Zscheischler, Jakob
   Beer, Christian
   Buchmann, Nina
   Frank, David C.
   Papale, Dario
   Rammig, Anja
   Smith, Pete
   Thonicke, Kirsten
   van der Velde, Marijn
   Vicca, Sara
   Walz, Ariane
   Wattenbach, Martin
TI Climate extremes and the carbon cycle
SO NATURE
LA English
DT Article
ID precipitation manipulation experiments; agricultural soil-erosion; europe-wide reduction; tree mortality; fire emissions; dioxide uptake; ice storms; land-use; forest; drought
AB The terrestrial biosphere is a key component of the global carbon cycle and its carbon balance is strongly influenced by climate. Continuing environmental changes are thought to increase global terrestrial carbon uptake. But evidence is mounting that climate extremes such as droughts or storms can lead to a decrease in regional ecosystem carbon stocks and therefore have the potential to negate an expected increase in terrestrial carbon uptake. Here we explore the mechanisms and impacts of climate extremes on the terrestrial carbon cycle, and propose a pathway to improve our understanding of present and future impacts of climate extremes on the terrestrial carbon budget.
C1 [Reichstein, Markus; Frank, Dorothea; Mahecha, Miguel D.; Zscheischler, Jakob; Beer, Christian] Max Planck Inst Biogeochem, D-07745 Jena, Germany.
   [Bahn, Michael] Univ Innsbruck, Inst Ecol, A-6020 Innsbruck, Austria.
   [Ciais, Philippe] UVSQ, CNRS, CEA, IPSL,Lab Sci Climat & Environm, F-91191 Gif Sur Yvette, France.
   [Seneviratne, Sonia I.; Zscheischler, Jakob; Buchmann, Nina] ETH, CH-8092 Zurich, Switzerland.
   [Zscheischler, Jakob] Max Planck Inst Intelligent Syst, D-72076 Tubingen, Germany.
   [Beer, Christian] Stockholm Univ, Dept Appl Environm Sci ITM, S-10691 Stockholm, Sweden.
   [Beer, Christian] Bert Bolin Ctr Climate Res, S-10691 Stockholm, Sweden.
   [Frank, David C.] Swiss Fed Res Inst WSL, CH-8903 Birmensdorf, Switzerland.
   [Frank, David C.] Univ Bern, Oeschger Ctr Climate Change Res, CH-3012 Bern, Switzerland.
   [Papale, Dario] Univ Tuscia, Dept Innovat Biol Agrofood & Forest Syst DIBAF, I-01100 Viterbo, Italy.
   [Rammig, Anja; Thonicke, Kirsten] Potsdam Inst Climate Impact Res PIK, D-14773 Potsdam, Germany.
   [Smith, Pete] Univ Aberdeen, Inst Biol & Environm Sci, Aberdeen AB24 3UU, Scotland.
   [van der Velde, Marijn] Int Inst Appl Syst Anal, Ecosyst Serv & Management Program, A-2361 Laxenburg, Austria.
   [Vicca, Sara] Univ Antwerp, Dept Biol, Res Grp Plant & Vegetat Ecol, B-2610 Antwerp, Belgium.
   [Walz, Ariane] Univ Potsdam, Inst Earth & Environm Sci, D-14476 Potsdam, Germany.
   [Wattenbach, Martin] GFZ German Res Ctr Geosci, Helmholtz Ctr Potsdam, Sect Hydrol 5 4, D-14473 Potsdam, Germany.
C3 Max Planck Society; University of Innsbruck; Universite Paris Saclay; Universite Paris Cite; Centre National de la Recherche Scientifique (CNRS); CEA; Swiss Federal Institutes of Technology Domain; ETH Zurich; Max Planck Society; Stockholm University; Swiss Federal Institutes of Technology Domain; Swiss Federal Institute for Forest, Snow & Landscape Research; University of Bern; Tuscia University; Potsdam Institut fur Klimafolgenforschung; University of Aberdeen; International Institute for Applied Systems Analysis (IIASA); University of Antwerp; University of Potsdam; Helmholtz Association; GFZ Helmholtz Centre for Geosciences
RP Reichstein, M (corresponding author), Max Planck Inst Biogeochem, D-07745 Jena, Germany.
EM markus.reichstein@bgc-jena.mpg.de
FU European Community [FP7-ENV-2008-1-226701]; Royal Society-Wolfson Research Merit Award; Austrian Science Fund (FWF) [P 22214] Funding Source: researchfish
NR 99
TC 1604
Z9 1844
U1 70
U2 2186
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 15
PY 2013
VL 500
IS 7462
BP 287
EP 295
DI 10.1038/nature12350
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 201AF
UT WOS:000323112400023
PM 23955228
DA 2026-03-09
ER

PT J
AU Xu, HP
   Li, XY
   Liu, D
   Li, JF
   Zhang, X
   Chen, X
   Hou, SY
   Peng, LX
   Xu, CG
   Liu, WL
   Zhang, LF
   Qi, H
AF Xu, Heping
   Li, Xuanying
   Liu, Dan
   Li, Jianfu
   Zhang, Xu
   Chen, Xin
   Hou, Shiyue
   Peng, Lixia
   Xu, Chenguang
   Liu, Wanli
   Zhang, Lianfeng
   Qi, Hai
TI Follicular T-helper cell recruitment governed by bystander B cells and ICOS-driven motility
SO NATURE
LA English
DT Article
ID inducible costimulator; lymph-node; differentiation; chemotaxis; receptor; 3-kinase; protein; b7rp-1; bcl6
AB Germinal centres support antibody affinity maturation and memory formation(1). Follicular T-helper cells promote proliferation and differentiation of antigen-specific B cells inside the follicle(2,3). A genetic deficiency in the inducible co-stimulator (ICOS), a classic CD28 family co-stimulatory molecule highly expressed by follicular T-helper cells, causes profound germinal centre defects(4,5), leading to the view that ICOS specifically co-stimulates the follicular T-helper cell differentiation program(2,6,7). Here we show that ICOS directly controls follicular recruitment of activated T-helper cells in mice. This effect is independent from ICOS ligand (ICOSL)-mediated co-stimulation provided by antigen-presenting dendritic cells or cognate B cells, and does not rely on Bcl6-mediated programming as an intermediate step. Instead, it requires ICOSL expression by follicular bystander B cells, which do not present cognate antigen to T-helper cells but collectively form an ICOS-engaging field. Dynamic imaging reveals ICOS engagement drives coordinated pseudopod formation and promotes persistent T-cell migration at the border between the T-cell zone and the B-cell follicle in vivo. When follicular bystander B cells cannot express ICOSL, otherwise competent T-helper cells fail to develop into follicular T-helper cells normally, and fail to promote optimal germinal centre responses. These results demonstrate a co-stimulation-independent function of ICOS, uncover a key role for bystander B cells in promoting the development of follicular T-helper cells, and reveal unsuspected sophistication in dynamic T-cell positioning in vivo.
C1 [Xu, Heping; Li, Xuanying; Liu, Dan; Zhang, Xu; Chen, Xin; Hou, Shiyue; Peng, Lixia; Qi, Hai] Tsinghua Univ, Sch Med, Lab Dynam Immunobiol, Tsinghua Peking Ctr Life Sci, Beijing 100084, Peoples R China.
   [Li, Jianfu] Tsinghua Univ, Sch Med, Dept Biomed Engn, Beijing 100084, Peoples R China.
   [Xu, Chenguang; Liu, Wanli] Tsinghua Univ, Sch Life Sci, Beijing 100084, Peoples R China.
   [Zhang, Lianfeng] Chinese Acad Med Sci, Inst Lab Anim Sci, Minist Hlth, Key Lab Human Dis Comparat Med, Beijing 100021, Peoples R China.
   [Zhang, Lianfeng] Peking Union Med Coll, Comparat Med Ctr, Beijing 100021, Peoples R China.
C3 Tsinghua University; Tsinghua University; Tsinghua University; Chinese Academy of Medical Sciences - Peking Union Medical College; Institute of Laboratory Animal Science - CAMS; Chinese Academy of Medical Sciences - Peking Union Medical College; Peking Union Medical College
RP Qi, H (corresponding author), Tsinghua Univ, Sch Med, Lab Dynam Immunobiol, Tsinghua Peking Ctr Life Sci, Beijing 100084, Peoples R China.
EM qihai@biomed.tsinghua.edu.cn
FU National Natural Science Foundation of China [81072464, 81161120405]; Program for New Century Excellent Talents in University [20091042000]; Tsinghua-Yu-Yuan Medical Sciences Fund [20240000585]; Tsinghua University Initiative Scientific Research Program [2010Z02150]; Institut Merieux; Tsinghua-Peking Center for Life Sciences
NR 29
TC 324
Z9 409
U1 2
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 APR 25
PY 2013
VL 496
IS 7446
BP 523
EP +
DI 10.1038/nature12058
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 131HU
UT WOS:000317984400045
PM 23619696
DA 2026-03-09
ER

PT J
AU Yamaguchi, S
   Shen, L
   Liu, YT
   Sendler, D
   Zhang, Y
AF Yamaguchi, Shinpei
   Shen, Li
   Liu, Yuting
   Sendler, Damian
   Zhang, Yi
TI Role of Tet1 in erasure of genomic imprinting
SO NATURE
LA English
DT Article
ID primordial germ-cells; dna methylation; postnatal-development; gene; 5-hydroxymethylcytosine; demethylation; dynamics; 5-methylcytosine; deficiency; expression
AB Genomic imprinting is an allele-specific gene expression system that is important for mammalian development and function(1). The molecular basis of genomic imprinting is allele-specific DNA methylation(1,2). Although it is well known that the de novo DNA methyltransferases Dnmt3a and Dnmt3b are responsible for the establishment of genomic imprinting(3), how the methylation mark is erased during primordial germ cell (PGC) reprogramming remains unclear. Tet1 is one of the ten-eleven translocation family proteins, which have the capacity to oxidize 5-methylcytosine (5mC)(4-6), specifically expressed in reprogramming PGCs(7). Here we report that Tet1 has a critical role in the erasure of genomic imprinting. We show that despite their identical genotype, progenies derived from mating between Tet1 knockout males and wild-type females exhibit a number of variable phenotypes including placental, fetal and postnatal growth defects, and early embryonic lethality. These defects are, at least in part, caused by the dysregulation of imprinted genes, such as Peg10 and Peg3, which exhibit aberrant hypermethylation in the paternal allele of differential methylated regions (DMRs). RNA-seq reveals extensive dysregulation of imprinted genes in the next generation due to paternal loss of Tet1 function. Genome-wide DNA methylation analysis of embryonic day 13.5 PGCs and sperm of Tet1 knockout mice revealed hypermethylation of DMRs of imprinted genes in sperm, which can be traced back to PGCs. Analysis of the DNA methylation dynamics in reprogramming PGCs indicates that Tet1 functions to wipe out remaining methylation, including imprinted genes, at the late reprogramming stage. Furthermore, we provide evidence supporting the role of Tet1 in the erasure of paternal imprints in the female germ line. Thus, our study establishes a critical function of Tet1 in the erasure of genomic imprinting.
C1 [Yamaguchi, Shinpei; Shen, Li; Liu, Yuting; Sendler, Damian; Zhang, Yi] Boston Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA.
   [Yamaguchi, Shinpei; Liu, Yuting; Zhang, Yi] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA.
   [Yamaguchi, Shinpei; Liu, Yuting; Zhang, Yi] Boston Childrens Hosp, Dept Pediat, Div Hematol Oncol, Boston, MA 02115 USA.
   [Zhang, Yi] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
   [Zhang, Yi] Harvard Stem Cell Inst, Boston, MA 02115 USA.
C3 Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Howard Hughes Medical Institute; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Program in Cellular & Molecular Medicine (PCMM); Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Harvard University; Harvard Medical School; Harvard University
RP Zhang, Y (corresponding author), Boston Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA.
EM yzhang@genetics.med.harvard.edu
FU NIH [U01DK089565]; Japan Society for the Promotion of Science (JSPS)
NR 30
TC 197
Z9 239
U1 0
U2 91
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 19
PY 2013
VL 504
IS 7480
BP 460
EP +
DI 10.1038/nature12805
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 273ZR
UT WOS:000328575300057
PM 24291790
DA 2026-03-09
ER

PT J
AU Houtkooper, RH
   Mouchiroud, L
   Ryu, D
   Moullan, N
   Katsyuba, E
   Knott, G
   Williams, RW
   Auwerx, J
AF Houtkooper, Riekelt H.
   Mouchiroud, Laurent
   Ryu, Dongryeol
   Moullan, Norman
   Katsyuba, Elena
   Knott, Graham
   Williams, Robert W.
   Auwerx, Johan
TI Mitonuclear protein imbalance as a conserved longevity mechanism
SO NATURE
LA English
DT Article
ID extends life-span; systematic rnai screen; caenorhabditis-elegans; dietary restriction; gene-expression; c-elegans; mitochondrial-function; caloric restriction; mice; extension
AB Longevity is regulated by a network of closely linked metabolic systems. We used a combination of mouse population genetics and RNA interference in Caenorhabditis elegans to identify mitochondrial ribosomal protein S5 (Mrps5) and other mitochondrial ribosomal proteins as metabolic and longevity regulators. MRP knockdown triggers mitonuclear protein imbalance, reducing mitochondrial respiration and activating the mitochondrial unfolded protein response. Specific antibiotics targeting mitochondrial translation and ethidium bromide (which impairs mitochondrial DNA transcription) pharmacologically mimic mrp knockdown and extend worm lifespan by inducing mitonuclear protein imbalance, a stoichiometric imbalance between nuclear and mitochondrially encoded proteins. This mechanism was also conserved in mammalian cells. In addition, resveratrol and rapamycin, longevity compounds acting on different molecular targets, similarly induced mitonuclear protein imbalance, the mitochondrial unfolded protein response and lifespan extension in C. elegans. Collectively these data demonstrate that MRPs represent an evolutionarily conserved protein family that ties the mitochondrial ribosome and mitonuclear protein imbalance to the mitochondrial unfolded protein response, an overarching longevity pathway across many species.
C1 [Houtkooper, Riekelt H.; Mouchiroud, Laurent; Ryu, Dongryeol; Moullan, Norman; Katsyuba, Elena; Auwerx, Johan] Ecole Polytech Fed Lausanne, Lab Integrat & Syst Physiol, CH-1015 Lausanne, Switzerland.
   [Houtkooper, Riekelt H.] Univ Amsterdam, Acad Med Ctr, Lab Genet Metab Dis, NL-1105 AZ Amsterdam, Netherlands.
   [Knott, Graham] Ecole Polytech Fed Lausanne, BioEM Facil, CH-1015 Lausanne, Switzerland.
   [Williams, Robert W.] Univ Tennessee, Ctr Hlth Sci, Dept Anat & Neurobiol, Memphis, TN 38163 USA.
   [Williams, Robert W.] Ctr Integrat & Translat Genom, Memphis, TN 38163 USA.
C3 Swiss Federal Institutes of Technology Domain; Ecole Polytechnique Federale de Lausanne; University of Amsterdam; Academic Medical Center Amsterdam; Swiss Federal Institutes of Technology Domain; Ecole Polytechnique Federale de Lausanne; University of Tennessee System; University of Tennessee Health Science Center
RP Auwerx, J (corresponding author), Ecole Polytech Fed Lausanne, Lab Integrat & Syst Physiol, CH-1015 Lausanne, Switzerland.
EM admin.auwerx@epfl.ch
FU NWO-Rubicon; AMC; FRM fellowship; EPFL; ERC [2008-AdG-23138]; Velux Stiftung; SNSF; National Institutes of Health (NIH) [P20-DA 21131, UO1AA13499, U01AA14425]; UT Center for Integrative and Translational Genomics; NIH [R01AG043930]
NR 48
TC 841
Z9 944
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 MAY 23
PY 2013
VL 497
IS 7450
BP 451
EP +
DI 10.1038/nature12188
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 148OG
UT WOS:000319254000039
PM 23698443
DA 2026-03-09
ER

PT J
AU Han, K
   Holder, JL
   Schaaf, CP
   Lu, H
   Chen, HM
   Kang, H
   Tang, JR
   Wu, ZY
   Hao, S
   Cheung, SW
   Yu, P
   Sun, H
   Breman, AM
   Patel, A
   Lu, HC
   Zoghbi, HY
AF Han, Kihoon
   Holder, J. Lloyd, Jr.
   Schaaf, Christian P.
   Lu, Hui
   Chen, Hongmei
   Kang, Hyojin
   Tang, Jianrong
   Wu, Zhenyu
   Hao, Shuang
   Cheung, Sau Wai
   Yu, Peng
   Sun, Hao
   Breman, Amy M.
   Patel, Ankita
   Lu, Hui-Chen
   Zoghbi, Huda Y.
TI SHANK3 overexpression causes manic-like behaviour with unique pharmacogenetic properties
SO NATURE
LA English
DT Article
ID autism spectrum disorder; scaffolding protein shank3; 22q13.3 deletion syndrome; bipolar disorder; psychiatric-disorders; postsynaptic density; gene; mutations; dysfunction; profilin
AB Mutations in SHANK3 and large duplications of the region spanning SHANK3 both cause a spectrum of neuropsychiatric disorders, indicating that proper SHANK3 dosage is critical for normal brain function. However, SHANK3 overexpression per se has not been established as a cause of human disorders because 22q13 duplications involve several genes. Here we report that Shank3 transgenic mice modelling a human SHANK3 duplication exhibit manic-like behaviour and seizures consistent with synaptic excitatory/inhibitory imbalance. We also identified two patients with hyperkinetic disorders carrying the smallest SHANK3-spanning duplications reported so far. These findings indicate that SHANK3 overexpression causes a hyperkinetic neuropsychiatric disorder. To probe the mechanism underlying the phenotype, we generated a Shank3 in vivo interactome and found that Shank3 directly interacts with the Arp2/3 complex to increase F-actin levels in Shank3 transgenic mice. The mood-stabilizing drug valproate, but not lithium, rescues the manic-like behaviour of Shank3 transgenic mice raising the possibility that this hyperkinetic disorder has a unique pharmacogenetic profile.
C1 [Han, Kihoon; Schaaf, Christian P.; Lu, Hui; Kang, Hyojin; Cheung, Sau Wai; Yu, Peng; Breman, Amy M.; Patel, Ankita; Zoghbi, Huda Y.] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA.
   [Han, Kihoon; Lu, Hui; Zoghbi, Huda Y.] Baylor Coll Med, Howard Hughes Med Inst, Houston, TX 77030 USA.
   [Han, Kihoon; Holder, J. Lloyd, Jr.; Schaaf, Christian P.; Lu, Hui; Chen, Hongmei; Kang, Hyojin; Tang, Jianrong; Wu, Zhenyu; Hao, Shuang; Yu, Peng; Sun, Hao; Lu, Hui-Chen; Zoghbi, Huda Y.] Texas Childrens Hosp, Jan & Dan Duncan Neurol Res Inst, Houston, TX 77030 USA.
   [Holder, J. Lloyd, Jr.; Chen, Hongmei; Tang, Jianrong; Wu, Zhenyu; Hao, Shuang; Sun, Hao; Lu, Hui-Chen; Zoghbi, Huda Y.] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA.
   [Holder, J. Lloyd, Jr.] Baylor Coll Med, Div Neurol & Dev Neurosci, Houston, TX 77030 USA.
   [Chen, Hongmei; Sun, Hao; Lu, Hui-Chen] Texas Childrens Hosp, Cain Fdn Labs, Houston, TX 77030 USA.
   [Cheung, Sau Wai; Breman, Amy M.; Patel, Ankita] Baylor Coll Med, Med Genet Labs, Houston, TX 77030 USA.
   [Lu, Hui-Chen; Zoghbi, Huda Y.] Baylor Coll Med, Program Dev Biol, Houston, TX 77030 USA.
   [Lu, Hui-Chen; Zoghbi, Huda Y.] Baylor Coll Med, Dept Neurosci, Houston, TX 77030 USA.
C3 Baylor College of Medicine; Howard Hughes Medical Institute; Baylor College of Medicine; Baylor College of Medicine; Baylor College Medical Hospital; Baylor College of Medicine; Baylor College of Medicine; Baylor College of Medicine; Baylor College Medical Hospital; Baylor College of Medicine; Baylor College of Medicine; Baylor College of Medicine
RP Zoghbi, HY (corresponding author), Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA.
EM hzoghbi@bcm.edu
FU Howard Hughes Medical Institute; National Institutes of Health (NIH) ARRA grant [1R01NS070302]; Baylor Intellectual and Developmental Disabilities Research Center [P30HD024064]; Cancer Prevention and Research Institute of Texas (CPRIT) [RP110784]; Thrasher Research Fund; NIH [2T32NS043124]; Ting Tsung and Wei Fong Chao Foundation; Joan and Stanford Alexander family; Doris Duke Clinical Scientist Development Award; National Institute of Neurological Disorders and Stroke [T32NS043124] Funding Source: NIH RePORTER
NR 55
TC 304
Z9 356
U1 3
U2 70
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 7
PY 2013
VL 503
IS 7474
BP 72
EP +
DI 10.1038/nature12630
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 247AS
UT WOS:000326585600034
PM 24153177
DA 2026-03-09
ER

PT J
AU Hamano, K
   Abe, Y
   Genda, H
AF Hamano, Keiko
   Abe, Yutaka
   Genda, Hidenori
TI Emergence of two types of terrestrial planet on solidification of magma ocean
SO NATURE
LA English
DT Article
ID hydrodynamic escape; venus; earth; evolution; atmosphere; water; tectonics; dynamics; runaway; model
AB Understanding the origins of the diversity in terrestrial planets is a fundamental goal in Earth and planetary sciences. In the Solar System, Venus has a similar size and bulk composition to those of Earth, but it lacks water(1-3). Because a richer variety of exoplanets is expected to be discovered, prediction of their atmospheres and surface environments requires a general framework for planetary evolution. Here we show that terrestrial planets can be divided into two distinct types on the basis of their evolutionary history during solidification from the initially hot molten state expected from the standard formation model(4,5). Even if, apart from their orbits, they were identical just after formation, the solidified planets can have different characteristics. A type I planet, which is formed beyond a certain critical distance from the host star, solidifies within several million years. If the planet acquires water during formation, most of this water is retained and forms the earliest oceans. In contrast, on a type II planet, which is formed inside the critical distance, a magma ocean can be sustained for longer, even with a larger initial amount of water. Its duration could be as long as 100 million years if the planet is formed together with a mass of water comparable to the total inventory of the modern Earth. Hydrodynamic escape desiccates type II planets during the slow solidification process. Although Earth is categorized as type I, it is not clear which type Venus is because its orbital distance is close to the critical distance. However, because the dryness of the surface and mantle predicted for type II planets is consistent with the characteristics of Venus, it may be representative of type II planets. Also, future observations may have a chance to detect not only terrestrial exoplanets covered with water ocean but also those covered with magma ocean around a young star.
C1 [Hamano, Keiko; Abe, Yutaka; Genda, Hidenori] Univ Tokyo, Dept Earth & Planetary Sci, Bunkyo Ku, Tokyo 1130033, Japan.
   [Genda, Hidenori] Tokyo Inst Technol, Earth Life Sci Inst, Meguro Ku, Tokyo 1528551, Japan.
C3 University of Tokyo; Institute of Science Tokyo; Tokyo Institute of Technology
RP Hamano, K (corresponding author), Univ Tokyo, Dept Earth & Planetary Sci, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1130033, Japan.
EM keiko@eps.s.u-tokyo.ac.jp
FU Ministry of Education, Culture, Sports, Science and Technology [23103003]; Japan Society for the Promotion of Science [23340168, 22740291]; Grants-in-Aid for Scientific Research [23340168, 22740291, 23103003] Funding Source: KAKEN
NR 34
TC 302
Z9 324
U1 2
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 MAY 30
PY 2013
VL 497
IS 7451
BP 607
EP +
DI 10.1038/nature12163
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 152UF
UT WOS:000319556100041
PM 23719462
DA 2026-03-09
ER

PT J
AU Moutanabbir, O
   Isheim, D
   Blumtritt, H
   Senz, S
   Pippel, E
   Seidman, DN
AF Moutanabbir, Oussama
   Isheim, Dieter
   Blumtritt, Horst
   Senz, Stephan
   Pippel, Eckhard
   Seidman, David N.
TI Colossal injection of catalyst atoms into silicon nanowires
SO NATURE
LA English
DT Article
ID group-iii; growth; germanium; nucleation; elements
AB The incorporation of impurities during the growth of nanowires from the vapour phase alters their basic properties substantially, and this process is critical in an extended range of emerging nanometre-scale technologies(1-4). In particular, achieving precise control of the behaviour of group III and group V dopants has been a crucial step in the development of silicon (Si) nanowire-based devices(5-7). Recently(8-11) it has been demonstrated that the use of aluminium (Al) as a growth catalyst, instead of the usual gold, also yields an effective p-type doping, thereby enabling a novel and efficient route to functionalizing Si nanowires. Besides the technological implications, this self-doping implies the detachment of Al from the catalyst and its injection into the growing nanowire, involving atomic-scale processes that are crucial for the fundamental understanding of the catalytic assembly of nanowires. Here we present an atomic-level, quantitative study of this phenomenon of catalyst dissolution by three-dimensional atom-by-atom mapping of individual Al-catalysed Si nanowires using highly focused ultraviolet-laser-assisted atom-probe tomography. Although the observed incorporation of the catalyst atoms into nanowires exceeds by orders of magnitude the equilibrium solid solubility(12) and solid-solution concentrations in known non-equilibrium processes(13,14), the Al impurities are found to be homogeneously distributed in the nanowire and do not form precipitates or clusters. As well as the anticipated effect on the electrical properties, this kinetics-driven colossal injection also has direct implications for nanowire morphology. We discuss the observed strong deviation from equilibrium using a model of solute trapping at step edges, and identify the key growth parameters behind this phenomenon on the basis of a kinetic model of step-flow growth of nanowires. The control of this phenomenon provides opportunities to create a new class of nanoscale devices by precisely tailoring the shape and composition of metal-catalysed nanowires.
C1 [Moutanabbir, Oussama] Ecole Polytech, Dept Engn Phys, Montreal, PQ H3C 3A7, Canada.
   [Isheim, Dieter; Seidman, David N.] Northwestern Univ, Dept Mat Sci & Engn, Evanston, IL 60208 USA.
   [Isheim, Dieter; Seidman, David N.] Northwestern Univ, NUCAPT, Evanston, IL 60208 USA.
   [Blumtritt, Horst; Senz, Stephan; Pippel, Eckhard] Max Planck Inst Microstruct Phys, D-06120 Halle, Saale, Germany.
C3 Universite de Montreal; Polytechnique Montreal; Northwestern University; Northwestern University; Max Planck Society
RP Moutanabbir, O (corresponding author), Ecole Polytech, Dept Engn Phys, CP 6079,Succursale Ctr Ville, Montreal, PQ H3C 3A7, Canada.
EM oussama.moutanabbir@polymtl.ca
FU NSERC; Canada Research Chair; Ecole Polytechnique de Montreal (PIED); US-Israel Binational Science Foundation; Max Planck Institute of Microstructure Physics
NR 32
TC 132
Z9 153
U1 1
U2 299
PU NATURE PUBLISHING 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 4
PY 2013
VL 496
IS 7443
BP 78
EP 82
DI 10.1038/nature11999
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 117ZZ
UT WOS:000316993400028
PM 23552946
DA 2026-03-09
ER

PT J
AU Arnon, TI
   Horton, RM
   Grigorova, IL
   Cyster, JG
AF Arnon, Tal I.
   Horton, Robert M.
   Grigorova, Irina L.
   Cyster, Jason G.
TI Visualization of splenic marginal zone B-cell shuttling and follicular B-cell egress
SO NATURE
LA English
DT Article
ID immune-complexes; lymphocytes; antigen; absence; activation; expression; retention; transport; selection; cd19
AB The splenic marginal zone is a unique microenvironment where resident immune cells are exposed to the open blood circulation(1,2). Even though it has an important role in responses against bloodborne antigens, lymphocyte migration in the marginal zone has not been intravitally visualized due to challenges associated with achieving adequate imaging depth in this abdominal organ. Here we develop a two-photon microscopy procedure to study marginal zone and follicular B-cell movement in the live mouse spleen. We show that marginal zone B cells are highly motile and exhibit long membrane extensions. Marginal zone B cells shuttle between the marginal zone and follicles with at least one-fifth of the cells exchanging between compartments per hour, a behaviour that explains their ability to deliver antigens rapidly from the open blood circulation to the secluded follicles. Follicular B cells also transit from follicles to the marginal zone, but unlike marginal zone B cells, they fail to undergo integrin-mediated adhesion, become caught in fluid flow and are carried into the red pulp. Follicular B-cell egress via the marginal zone is sphingosine-1-phosphate receptor-1 (S1PR1)-dependent. This study shows that marginal zone B cells migrate continually between marginal zone and follicles and establishes the marginal zone as a site of S1PR1-dependent B-cell exit from follicles. The results also show how adhesive differences of similar cells critically influence their behaviour in the same microenvironment.
C1 [Arnon, Tal I.; Horton, Robert M.; Grigorova, Irina L.; Cyster, Jason G.] Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94143 USA.
   [Arnon, Tal I.; Horton, Robert M.; Grigorova, Irina L.; Cyster, Jason G.] Univ Calif San Francisco, Dept Microbiol & Immunol, 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 Cyster, JG (corresponding author), Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94143 USA.
EM Jason.Cyster@ucsf.edu
FU Jane Coffin Child's fellowship; National Institutes of Health [AI74847]
NR 36
TC 183
Z9 215
U1 0
U2 45
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 31
PY 2013
VL 493
IS 7434
BP 684
EP +
DI 10.1038/nature11738
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 080CU
UT WOS:000314219600059
PM 23263181
DA 2026-03-09
ER

PT J
AU Bolton, CT
   Stoll, HM
AF Bolton, Clara T.
   Stoll, Heather M.
TI Late Miocene threshold response of marine algae to carbon dioxide limitation
SO NATURE
LA English
DT Article
ID concentrating mechanisms; co2; impact; photosynthesis; phytoplankton; fractionation; evolution
AB Coccolithophores are marine algae that use carbon for calcification and photosynthesis. The long-term adaptation of these and other marine algae to decreasing carbon dioxide levels during the Cenozoic era(1) has resulted in modern algae capable of actively enhancing carbon dioxide at the site of photosynthesis. This enhancement occurs through the transport of dissolved bicarbonate (HCO3-) and with the help of enzymes whose expression can be modulated by variable aqueous carbon dioxide concentration, [CO2], in laboratory cultures(2,3). Coccolithophores preserve the geological history of this adaptation because the stable carbon and oxygen isotopic compositions of their calcite plates (coccoliths), which are preserved in the fossil record, are sensitive to active carbon uptake and transport by the cell. Here we use a model of cellular carbon fluxes and show that at low [CO2] the increased demand for HCO3- at the site of photosynthesis results in a diminished allocation of HCO3- to calcification, which is most pronounced in larger cells. This results in a large divergence between the carbon isotopic compositions of small versus large coccoliths only at low [CO2]. Our evaluation of the oxygen and carbon isotope record of size-separated fossil coccoliths reveals that this isotopic divergence first arose during the late Miocene to the earliest Pliocene epoch (about 7-5 million years ago). We interpret this to be a threshold response of the cells' carbon acquisition strategies to decreasing [CO2]. The documented coccolithophore response is synchronous with a global shift in terrestrial vegetation distribution between 8 and 5 Myr ago, which has been interpreted by some studies as a floral response to decreasing partial pressures of carbon dioxide (p(CO2)) in the atmosphere(4-6). We infer a global decrease in carbon dioxide levels for this time interval that has not yet been identified in the sparse p(CO2) proxy record(7) but is synchronous with global cooling and progressive glaciations(8,9).
C1 [Bolton, Clara T.; Stoll, Heather M.] Univ Oviedo, Dept Geol, E-33005 Oviedo, Asturias, Spain.
C3 University of Oviedo
RP Bolton, CT (corresponding author), Univ Oviedo, Dept Geol, Jesus Arias de Velasco S-N, E-33005 Oviedo, Asturias, Spain.
EM cbolton@geol.uniovi.es; hstoll@geol.uniovi.es
FU US National Science Foundation; European Research Council [UE-09-ERC-2009-STG-240222-PACE]; DuPont Young Professor Award
NR 31
TC 140
Z9 155
U1 3
U2 145
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 29
PY 2013
VL 500
IS 7464
BP 558
EP 562
DI 10.1038/nature12448
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 207TD
UT WOS:000323625900030
PM 23985873
DA 2026-03-09
ER

PT J
AU Paeschke, K
   Bochman, ML
   Garcia, PD
   Cejka, P
   Friedman, KL
   Kowalczykowski, SC
   Zakian, VA
AF Paeschke, Katrin
   Bochman, Matthew L.
   Garcia, P. Daniela
   Cejka, Petr
   Friedman, Katherine L.
   Kowalczykowski, Stephen C.
   Zakian, Virginia A.
TI Pif1 family helicases suppress genome instability at G-quadruplex motifs
SO NATURE
LA English
DT Article
ID gross-chromosomal rearrangements; replication fork progression; saccharomyces-cerevisiae; dna helicase; yeast; rrm3p; telomerase; proteins; genes; loci
AB The Saccharomyces cerevisiae Pif1 helicase is the prototypical member of the Pif1 DNA helicase family, which is conserved from bacteria to humans. Here we show that exceptionally potent G-quadruplex unwinding is conserved among Pif1 helicases. Moreover, Pif1 helicases from organisms separated by more than 3 billion years of evolution suppressed DNA damage at G-quadruplex motifs in yeast. The G-quadruplex-induced damage generated in the absence of Pif1 helicases led to new genetic and epigenetic changes. Furthermore, when expressed in yeast, human PIF1 suppressed both G-quadruplex-associated DNA damage and telomere lengthening.
C1 [Paeschke, Katrin; Bochman, Matthew L.; Garcia, P. Daniela; Zakian, Virginia A.] Princeton Univ, Dept Mol Biol, Princeton, NJ 08544 USA.
   [Cejka, Petr; Kowalczykowski, Stephen C.] Univ Calif Davis, Dept Microbiol, Davis, CA 95616 USA.
   [Cejka, Petr; Kowalczykowski, Stephen C.] Univ Calif Davis, Dept Mol Genet, Davis, CA 95616 USA.
   [Cejka, Petr; Kowalczykowski, Stephen C.] Univ Calif Davis, Dept Mol & Cellular Biol, Davis, CA 95616 USA.
   [Friedman, Katherine L.] Vanderbilt Univ, Dept Biol Sci, Nashville, TN 37232 USA.
C3 Princeton University; University of California System; University of California Davis; University of California System; University of California Davis; University of California System; University of California Davis; Vanderbilt University
RP Zakian, VA (corresponding author), Princeton Univ, Dept Mol Biol, Princeton, NJ 08544 USA.
EM vzakian@princeton.edu
FU National Institutes of Health; National Science Foundation; DFG; NJCCR; American Cancer Society
NR 45
TC 398
Z9 473
U1 0
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 23
PY 2013
VL 497
IS 7450
BP 458
EP +
DI 10.1038/nature12149
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 148OG
UT WOS:000319254000040
PM 23657261
DA 2026-03-09
ER

PT J
AU Conlon, BP
   Nakayasu, ES
   Fleck, LE
   LaFleur, MD
   Isabella, VM
   Coleman, K
   Leonard, SN
   Smith, RD
   Adkins, JN
   Lewis, K
AF Conlon, B. P.
   Nakayasu, E. S.
   Fleck, L. E.
   LaFleur, M. D.
   Isabella, V. M.
   Coleman, K.
   Leonard, S. N.
   Smith, R. D.
   Adkins, J. N.
   Lewis, K.
TI Activated ClpP kills persisters and eradicates a chronic biofilm infection
SO NATURE
LA English
DT Article
ID tandem mass-spectra; escherichia-coli; staphylococcus-aureus; multidrug tolerance; pseudomonas-aeruginosa; bacterial persistence; in-vivo; cells; antibiotics; resistance
AB Chronic infections are difficult to treat with antibiotics but are caused primarily by drug-sensitive pathogens. Dormant persister cells that are tolerant to killing by antibiotics are responsible for this apparent paradox. Persisters are phenotypic variants of normal cells and pathways leading to dormancy are redundant, making it challenging to develop anti-persister compounds. Biofilms shield persisters from the immune system, suggesting that an antibiotic for treating a chronic infection should be able to eradicate the infection on its own. We reasoned that a compound capable of corrupting a target in dormant cells will kill persisters. The acyldepsipeptide antibiotic (ADEP4) has been shown to activate the ClpP protease, resulting in death of growing cells. Here we show that ADEP4-activated ClpP becomes a fairly nonspecific protease and kills persisters by degrading over 400 proteins, forcing cells to self-digest. Null mutants of clpP arise with high probability, but combining ADEP4 with rifampicin produced complete eradication of Staphylococcus aureus biofilms in vitro and in a mouse model of a chronic infection. Our findings indicate a general principle for killing dormant cells-activation and corruption of a target, rather than conventional inhibition. Eradication of a biofilm in an animal model by activating a protease suggests a realistic path towards developing therapies to treat chronic infections.
C1 [Conlon, B. P.; Fleck, L. E.; Isabella, V. M.; Lewis, K.] Northeastern Univ, Dept Biol, Antimicrobial Discovery Ctr, Boston, MA 02115 USA.
   [Nakayasu, E. S.; Smith, R. D.; Adkins, J. N.] Pacific NW Natl Lab, Div Biol Sci, Richland, WA 99352 USA.
   [LaFleur, M. D.; Coleman, K.] Arietis Corp, Boston, MA 02118 USA.
   [Leonard, S. N.] Northeastern Univ, Sch Pharm, Bouve Coll Hlth Sci, Boston, MA 02115 USA.
C3 Northeastern University; United States Department of Energy (DOE); Pacific Northwest National Laboratory; Northeastern University
RP Lewis, K (corresponding author), Northeastern Univ, Dept Biol, Antimicrobial Discovery Ctr, Boston, MA 02115 USA.
EM k.lewis@neu.edu
FU NIH [T-RO1 AI085585]; Arietis Corporation; NIH-NIAID IAA [Y1-AI-8401, P41 GM103493-11]; DOE [DE-AC05-76RLO 1830]; National Institute of General Medical Sciences [P41GM103493] Funding Source: NIH RePORTER
NR 50
TC 550
Z9 679
U1 8
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 NOV 21
PY 2013
VL 503
IS 7476
BP 365
EP +
DI 10.1038/nature12790
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 254KG
UT WOS:000327163200034
PM 24226776
DA 2026-03-09
ER

PT J
AU Allanore, A
   Yin, L
   Sadoway, DR
AF Allanore, Antoine
   Yin, Lan
   Sadoway, Donald R.
TI A new anode material for oxygen evolution in molten oxide electrolysis
SO NATURE
LA English
DT Article
ID iron-oxide; corrosion; chromium
AB Molten oxide electrolysis (MOE) is an electrometallurgical technique that enables the direct production of metal in the liquid state from oxide feedstock(1,2), and compared with traditional methods of extractive metallurgy offers both a substantial simplification of the process and a significant reduction in energy consumption(3). MOE is also considered a promising route for mitigation of CO2 emissions in steelmaking(3-5), production of metals free of carbon(6), and generation of oxygen for extra-terrestrial exploration(7,8). Until now, MOE has been demonstrated using anode materials that are consumable (graphite for use with ferro-alloys and titanium(6,9)) or unaffordable for terrestrial applications (iridium for use with iron(10,11)). To enable metal production without process carbon, MOE requires an anode material that resists depletion while sustaining oxygen evolution. The challenges for iron production are threefold. First, the process temperature is in excess of 1,538 degrees Celsius (ref. 10). Second, under anodic polarization most metals inevitably corrode in such conditions(11-13). Third, iron oxide undergoes spontaneous reduction on contact with most refractory metals(14) and even carbon. Here we show that anodes comprising chromium-based alloys exhibit limited consumption during iron extraction and oxygen evolution by MOE. The anode stability is due to the formation of an electronically conductive solid solution of chromium(III) and aluminium oxides in the corundum structure. These findings make practicable larger-scale evaluation of MOE for the production of steel, and potentially provide a key material component enabling mitigation of greenhouse-gas emissions while producing metal of superior metallurgical quality.
C1 [Allanore, Antoine; Yin, Lan; Sadoway, Donald R.] MIT, Dept Mat Sci & Engn, Cambridge, MA 02139 USA.
C3 Massachusetts Institute of Technology (MIT)
RP Allanore, A (corresponding author), MIT, Dept Mat Sci & Engn, Cambridge, MA 02139 USA.
EM allanore@mit.edu
FU American Iron and Steel Institute
NR 18
TC 198
Z9 251
U1 11
U2 542
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 16
PY 2013
VL 497
IS 7449
BP 353
EP +
DI 10.1038/nature12134
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 144PN
UT WOS:000318952000034
PM 23657254
DA 2026-03-09
ER

PT J
AU Fröhlich, B
   Dynes, JF
   Lucamarini, M
   Sharpe, AW
   Yuan, ZL
   Shields, AJ
AF Froehlich, Bernd
   Dynes, James F.
   Lucamarini, Marco
   Sharpe, Andrew W.
   Yuan, Zhiliang
   Shields, Andrew J.
TI A quantum access network
SO NATURE
LA English
DT Article
ID key distribution; field-test; communication
AB The theoretically proven security of quantum key distribution(QKD) could revolutionize the way in which information exchange is protected in the future(1,2). Several field tests of QKD have proven it to be a reliable technology for cryptographic key exchange and have demonstrated nodal networks of point-to-point links(3-5). However, until now no convincing answer has been given to the question of how to extend the scope of QKD beyond niche applications in dedicated high security networks. Here we introduce and experimentally demonstrate the concept of a 'quantum access network': based on simple and cost-effective telecommunication technologies, the scheme can greatly expand the number of users in quantum networks and therefore vastly broaden their appeal. We show that a high-speed single-photon detector positioned at a network node can be shared between up to 64 users for exchanging secret keys with the node, thereby significantly reducing the hardware requirements for each user added to the network. This point-to-multipoint architecture removes one of the main obstacles restricting the widespread application of QKD. It presents a viable method for realizing multi-user QKD networks with efficient use of resources, and brings QKD closer to becoming a widespread technology.
C1 [Froehlich, Bernd; Dynes, James F.; Lucamarini, Marco; Sharpe, Andrew W.; Yuan, Zhiliang; Shields, Andrew J.] Toshiba Res Europe Ltd, Cambridge CB4 0GZ, England.
   [Froehlich, Bernd; Dynes, James F.; Lucamarini, Marco; Yuan, Zhiliang; Shields, Andrew J.] Toshiba Co Ltd, Corp Res & Dev Ctr, Saiwai Ku, Kawasaki, Kanagawa 2128582, Japan.
C3 Toshiba Corporation; Toshiba Corporation
RP Shields, AJ (corresponding author), Toshiba Res Europe Ltd, 208 Cambridge Sci Pk, Cambridge CB4 0GZ, England.
EM bernd.frohlich@crl.toshiba.co.uk; zhiliang.yuan@crl.toshiba.co.uk; andrew.shields@crl.toshiba.co.uk
FU Research and Development of Secure Photonic Network Technologies; Commissioned Research of the National Institute of Information and Communications Technology (NICT), Japan
NR 30
TC 273
Z9 307
U1 3
U2 103
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 5
PY 2013
VL 501
IS 7465
BP 69
EP +
DI 10.1038/nature12493
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 211ER
UT WOS:000323888300033
PM 24005413
DA 2026-03-09
ER

PT J
AU Steinacher, M
   Joos, F
   Stocker, TF
AF Steinacher, Marco
   Joos, Fortunat
   Stocker, Thomas F.
TI Allowable carbon emissions lowered by multiple climate targets
SO NATURE
LA English
DT Article
ID ocean acidification; sensitivity; mitigation; calcification; temperature; model; 21st-century; scenarios; risk
AB Climate targets are designed to inform policies that would limit the magnitude and impacts of climate change caused by anthropogenic emissions of greenhouse gases and other substances. The target that is currently recognized by most world governments(1) places a limit of two degrees Celsius on the global mean warming since preindustrial times. This would require large sustained reductions in carbon dioxide emissions during the twenty-first century and beyond(2-4). Such a global temperature target, however, is not sufficient to control many other quantities, such as transient sea level rise(5), ocean acidification(6,7) and net primary production on land(8,9). Here, using an Earth system model of intermediate complexity (EMIC) in an observation-informed Bayesian approach, we show that allowable carbon emissions are substantially reduced when multiple climate targets are set. We take into account uncertainties in physical and carbon cycle model parameters, radiative efficiencies(10), climate sensitivity(11) and carbon cycle feedbacks(12,13) along with a large set of observational constraints. Within this framework, we explore a broad range of economically feasible greenhouse gas scenarios from the integrated assessment community(14-17) to determine the likelihood of meeting a combination of specific global and regional targets under various assumptions. For any given likelihood of meeting a set of such targets, the allowable cumulative emissions are greatly reduced from those inferred from the temperature target alone. Therefore, temperature targets alone are unable to comprehensively limit the risks from anthropogenic emissions.
C1 [Steinacher, Marco; Joos, Fortunat; Stocker, Thomas F.] Univ Bern, CH-3012 Bern, Switzerland.
   [Steinacher, Marco; Joos, Fortunat; Stocker, Thomas F.] Univ Bern, Oeschger Ctr Climate Change Res, CH-3012 Bern, Switzerland.
C3 University of Bern; University of Bern
RP Steinacher, M (corresponding author), Univ Bern, CH-3012 Bern, Switzerland.
EM steinacher@climate.unibe.ch
FU Swiss National Science Foundation; European Commission [EPOCA 211384, 264879]
NR 49
TC 91
Z9 96
U1 1
U2 195
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 11
PY 2013
VL 499
IS 7457
BP 197
EP +
DI 10.1038/nature12269
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 179YA
UT WOS:000321557600059
PM 23823728
DA 2026-03-09
ER

PT J
AU Murtaza, M
   Dawson, SJ
   Tsui, DWY
   Gale, D
   Forshew, T
   Piskorz, AM
   Parkinson, C
   Chin, SF
   Kingsbury, Z
   Wong, ASC
   Marass, F
   Humphray, S
   Hadfield, J
   Bentley, D
   Chin, TM
   Brenton, JD
   Caldas, C
   Rosenfeld, N
AF Murtaza, Muhammed
   Dawson, Sarah-Jane
   Tsui, Dana W. Y.
   Gale, Davina
   Forshew, Tim
   Piskorz, Anna M.
   Parkinson, Christine
   Chin, Suet-Feung
   Kingsbury, Zoya
   Wong, Alvin S. C.
   Marass, Francesco
   Humphray, Sean
   Hadfield, James
   Bentley, David
   Chin, Tan Min
   Brenton, James D.
   Caldas, Carlos
   Rosenfeld, Nitzan
TI Non-invasive analysis of acquired resistance to cancer therapy by sequencing of plasma DNA
SO NATURE
LA English
DT Article
ID tumor-cells; evolution; mutations; heterogeneity; activation
AB Cancers acquire resistance to systemic treatment as a result of clonal evolution and selection(1,2). Repeat biopsies to study genomic evolution as a result of therapy are difficult, invasive and may be confounded by intra-tumour heterogeneity(3,4). Recent studies have shown that genomic alterations in solid cancers can be characterized by massively parallel sequencing of circulating cell-free tumour DNA released from cancer cells into plasma, representing a noninvasive liquid biopsy(5-7). Here we report sequencing of cancer exomes in serial plasma samples to track genomic evolution of metastatic cancers in response to therapy. Six patients with advanced breast, ovarian and lung cancers were followed over 1-2 years. For each case, exome sequencing was performed on 2-5 plasma samples (19 in total) spanning multiple courses of treatment, at selected time points when the allele fraction of tumour mutations in plasma was high, allowing improved sensitivity. For two cases, synchronous biopsies were also analysed, confirming genome-wide representation of the tumour genome in plasma. Quantification of allele fractions in plasma identified increased representation of mutant alleles in association with emergence of therapy resistance. These included an activating mutation in PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha) following treatment with paclitaxel(8); a truncating mutation in RB1 (retinoblastoma 1) following treatment with cisplatin(9); a truncating mutation in MED1 (mediator complex subunit 1) following treatment with tamoxifen and trastuzumab(10,11), and following subsequent treatment with lapatinib(12,13), a splicing mutation in GAS6 (growth arrest-specific 6) in the same patient; and a resistance-conferring mutation in EGFR (epidermal growth factor receptor; T790M) following treatment with gefitinib(14). These results establish proof of principle that exome-wide analysis of circulating tumour DNA could complement current invasive biopsy approaches to identify mutations associated with acquired drug resistance in advanced cancers. Serial analysis of cancer genomes in plasma constitutes a new paradigm for the study of clonal evolution in human cancers.
C1 [Murtaza, Muhammed; Dawson, Sarah-Jane; Tsui, Dana W. Y.; Gale, Davina; Forshew, Tim; Piskorz, Anna M.; Parkinson, Christine; Chin, Suet-Feung; Marass, Francesco; Hadfield, James; Brenton, James D.; Caldas, Carlos; Rosenfeld, Nitzan] Canc Res UK Cambridge Inst, Cambridge CB2 0RE, England.
   [Murtaza, Muhammed; Dawson, Sarah-Jane; Tsui, Dana W. Y.; Gale, Davina; Forshew, Tim; Piskorz, Anna M.; Parkinson, Christine; Chin, Suet-Feung; Marass, Francesco; Hadfield, James; Brenton, James D.; Caldas, Carlos; Rosenfeld, Nitzan] Univ Cambridge, Li Ka Shing Ctr, Cambridge CB2 0RE, England.
   [Dawson, Sarah-Jane; Parkinson, Christine; Brenton, James D.; Caldas, Carlos] Cambridge Univ Hosp NHS Fdn Trust, Addenbrookes Hosp, Cambridge CB2 2QQ, England.
   [Dawson, Sarah-Jane; Parkinson, Christine; Brenton, James D.; Caldas, Carlos] NIHR Cambridge Biomed Res Ctr, Cambridge CB2 2QQ, England.
   [Kingsbury, Zoya] Illumina Inc, Saffron Walden CB10 1XL, England.
   [Wong, Alvin S. C.; Chin, Tan Min] Natl Univ Hlth Syst, Natl Univ Canc Inst, Dept Haematol Oncol, Singapore 119074, Singapore.
   [Chin, Tan Min] Natl Univ Singapore, Ctr Translat Med, Canc Sci Inst, Singapore 117599, Singapore.
   [Brenton, James D.; Caldas, Carlos] Cambridge Expt Canc Med Ctr, Cambridge CB2 0RE, England.
C3 Cancer Research UK; CRUK Cambridge Institute; University of Cambridge; CRUK Cambridge Institute; Cambridge University Hospitals NHS Foundation Trust; Addenbrooke's Hospital; University of Cambridge; University of Cambridge; Illumina; National University of Singapore; National University of Singapore
RP Brenton, JD (corresponding author), Canc Res UK Cambridge Inst, Robinson Way, Cambridge CB2 0RE, England.
EM james.brenton@cruk.cam.ac.uk; carlos.caldas@cruk.cam.ac.uk; nitzan.rosenfeld@cruk.cam.ac.uk
FU NIHR Cambridge Biomedical Research Centre; Cancer Science Institute; National University of Singapore; Hematology-Oncology Research Group, National University Health System, Singapore; Cancer Research UK; University of Cambridge; National Institute for Health Research Cambridge Biomedical Research Centre; Cambridge Experimental Cancer Medicine Centre; Hutchison Whampoa Limited; National Medical Research Council, Singapore; Australian NHMRC/RG Menzies Early Career Fellowship; Cancer Research UK [11906, 16942, 22310, 15601] Funding Source: researchfish; National Institute for Health Research [NF-SI-0611-10154] Funding Source: researchfish
NR 29
TC 1372
Z9 1622
U1 3
U2 413
PU NATURE PUBLISHING 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 2
PY 2013
VL 497
IS 7447
BP 108
EP 112
DI 10.1038/nature12065
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 134OK
UT WOS:000318221500043
PM 23563269
DA 2026-03-09
ER

PT J
AU Sikes, JM
   Newmark, PA
AF Sikes, James M.
   Newmark, Phillip A.
TI Restoration of anterior regeneration in a planarian with limited regenerative ability
SO NATURE
LA English
DT Article
ID polarity; head; system; wounds
AB Variability of regenerative potential among animals has long perplexed biologists(1). On the basis of their exceptional regenerative abilities, planarians have become important models for understanding the molecular basis of regeneration(2). However, planarian species with limited regenerative abilities are also found(3,4). Despite the importance of understanding the differences between closely related, regenerating and non-regenerating organisms, few studies have focused on the evolutionary loss of regeneration(5), and the molecular mechanisms leading to such regenerative loss remain obscure. Here we examine Procotyla fluviatilis, a planarian with restricted ability to replace missing tissues(6), using next-generation sequencing to define the gene expression programs active in regeneration-permissive and regeneration-deficient tissues. We found that Wnt signalling is aberrantly activated in regeneration-deficient tissues. Notably, downregulation of canonical Wnt signalling in regeneration-deficient regions restores regenerative abilities: blastemas form and new heads regenerate in tissues that normally never regenerate. This work reveals that manipulating a single signalling pathway can reverse the evolutionary loss of regenerative potential.
C1 [Sikes, James M.; Newmark, Phillip A.] Univ Illinois, Howard Hughes Med Inst, Urbana, IL 61801 USA.
   [Sikes, James M.; Newmark, Phillip A.] Univ Illinois, Dept Cell & Dev Biol, Urbana, IL 61801 USA.
C3 University of Illinois System; University of Illinois Urbana-Champaign; Howard Hughes Medical Institute; University of Illinois System; University of Illinois Urbana-Champaign
RP Sikes, JM (corresponding author), Univ San Francisco, Dept Biol, San Francisco, CA 94117 USA.
EM jsikes@usfca.edu
FU National Institute of General Medicine Sciences [F32GM097921]
NR 31
TC 109
Z9 133
U1 0
U2 50
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 1
PY 2013
VL 500
IS 7460
BP 77
EP U98
DI 10.1038/nature12403
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 192VK
UT WOS:000322514800031
PM 23883929
DA 2026-03-09
ER

PT J
AU Kurth, I
   Georgescu, RE
   O'Donnell, ME
AF Kurth, Isabel
   Georgescu, Roxana E.
   O'Donnell, Mike E.
TI A solution to release twisted DNA during chromosome replication by coupled DNA polymerases
SO NATURE
LA English
DT Article
ID lagging-strand synthesis; sliding clamps; topoisomerase-i; fork; mechanism; processivity; bacterial; dynamics; holoenzyme; viability
AB Chromosomal replication machines contain coupled DNA polymerases that simultaneously replicate the leading and lagging strands(1). However, coupled replication presents a largely unrecognized topological problem. Because DNA polymerase must travel a helical path during synthesis, the physical connection between leading- and lagging-strand polymerases causes the daughter strands to entwine, or produces extensive build-up of negative supercoils in the newly synthesized DNA(2-4). How DNA polymerases maintain their connection during coupled replication despite these topological challenges is unknown. Here we examine the dynamics of the Escherichia coli replisome, using ensemble and single-molecule methods, and show that the replisome may solve the topological problem independent of topoisomerases. We find that the lagging-strand polymerase frequently releases from an Okazaki fragment before completion, leaving single-strand gaps behind. Dissociation of the polymerase does not result in loss from the replisome because of its contact with the leading-strand polymerase. This behaviour, referred to as 'signal release', had been thought to require a protein, possibly primase, to pry polymerase from incompletely extended DNA fragments(5-7). However, we observe that signal release is independent of primase and does not seem to require a protein trigger at all. Instead, the lagging-strand polymerase is simply less processive in the context of a replisome. Interestingly, when the lagging-strand polymerase is supplied with primed DNA in trans, uncoupling it from the fork, high processivity is restored. Hence, we propose that coupled polymerases introduce topological changes, possibly by accumulation of superhelical tension in the newly synthesized DNA, that cause lower processivity and transient lagging-strand polymerase dissociation from DNA.
C1 [Kurth, Isabel; Georgescu, Roxana E.; O'Donnell, Mike E.] Rockefeller Univ, Howard Hughes Med Inst, New York, NY 10065 USA.
C3 Howard Hughes Medical Institute; Rockefeller University
RP O'Donnell, ME (corresponding author), Rockefeller Univ, Howard Hughes Med Inst, 1230 York Ave, New York, NY 10065 USA.
EM odonnel@rockefeller.edu
FU National Institutes of Health [GM 38839]
NR 29
TC 35
Z9 45
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 APR 4
PY 2013
VL 496
IS 7443
BP 119
EP +
DI 10.1038/nature11988
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 117ZZ
UT WOS:000316993400037
PM 23535600
DA 2026-03-09
ER

PT J
AU Adolph, TE
   Tomczak, MF
   Niederreiter, L
   Ko, HJ
   Böck, J
   Martinez-Naves, E
   Glickman, JN
   Tschurtschenthaler, M
   Hartwig, J
   Hosomi, S
   Flak, MB
   Cusick, JL
   Kohno, K
   Iwawaki, T
   Billmann-Born, S
   Raine, T
   Bharti, R
   Lucius, R
   Kweon, MN
   Marciniak, SJ
   Choi, A
   Hagen, SJ
   Schreiber, S
   Rosenstiel, P
   Kaser, A
   Blumberg, RS
AF Adolph, Timon E.
   Tomczak, Michal F.
   Niederreiter, Lukas
   Ko, Hyun-Jeong
   Boeck, Janne
   Martinez-Naves, Eduardo
   Glickman, Jonathan N.
   Tschurtschenthaler, Markus
   Hartwig, John
   Hosomi, Shuhei
   Flak, Magdalena B.
   Cusick, Jennifer L.
   Kohno, Kenji
   Iwawaki, Takao
   Billmann-Born, Susanne
   Raine, Tim
   Bharti, Richa
   Lucius, Ralph
   Kweon, Mi-Na
   Marciniak, Stefan J.
   Choi, Augustine
   Hagen, Susan J.
   Schreiber, Stefan
   Rosenstiel, Philip
   Kaser, Arthur
   Blumberg, Richard S.
TI Paneth cells as a site of origin for intestinal inflammation
SO NATURE
LA English
DT Article
ID endoplasmic-reticulum stress; genome-wide association; factor-kappa-b; er stress; susceptibility loci; epithelial-cells; crohn-disease; gene atg16l1; autophagy; activation
AB The recognition of autophagy related 16-like 1 (ATG16L1) as a genetic risk factor has exposed the critical role of autophagy in Crohn's disease(1). Homozygosity for the highly prevalent ATG16L1 risk allele, or murine hypomorphic (HM) activity, causes Paneth cell dysfunction(2,3). As Atg16l1(HM) mice do not develop spontaneous intestinal inflammation, the mechanism(s) by which ATG16L1 contributes to disease remains obscure. Deletion of the unfolded protein response (UPR) transcription factor X-box binding protein-1 (Xbp1) in intestinal epithelial cells, the human orthologue of which harbours rare inflammatory bowel disease risk variants, results in endoplasmic reticulum (ER) stress, Paneth cell impairment and spontaneous enteritis4. Unresolved ER stress is a common feature of inflammatory bowel disease epithelium(4,5), and several genetic risk factors of Crohn's disease affect Paneth cells(2,4,6-9). Here we show that impairment in either UPR (Xbp1(Delta IEC)) or autophagy function (Atg16l1(Delta IEC) or Atg7(Delta IEC)) in intestinal epithelial cells results in each other's compensatory engagement, and severe spontaneous Crohn's-disease-like transmural ileitis if both mechanisms are compromised. Xbp1DIEC mice show autophagosome formation in hypomorphic Paneth cells, which is linked to ER stress via protein kinase RNA-like endoplasmic reticulum kinase (PERK), elongation initiation factor 2 alpha (eIF2 alpha) and activating transcription factor 4 (ATF4). Ileitis is dependent on commensal microbiota and derives from increased intestinal epithelial cell death, inositol requiring enzyme 1 alpha (IRE1 alpha)-regulated NF-kappa B activation and tumour-necrosis factor signalling, which are synergistically increased when autophagy is deficient. ATG16L1 restrains IRE1a activity, and augmentation of autophagy in intestinal epithelial cells ameliorates ER stress-induced intestinal inflammation and eases NF-kappa B overactivation and intestinal epithelial cell death. ER stress, autophagy induction and spontaneous ileitis emerge from Paneth-cell-specific deletion of Xbp1. Genetically and environmentally controlled UPR function within Paneth cells may therefore set the threshold for the development of intestinal inflammation upon hypomorphic ATG16L1 function and implicate ileal Crohn's disease as a specific disorder of Paneth cells.
C1 [Adolph, Timon E.; Niederreiter, Lukas; Tschurtschenthaler, Markus; Raine, Tim; Kaser, Arthur] Univ Cambridge, Addenbrookes Hosp, Dept Med, Div Gastroenterol & Hepatol, Cambridge CB2 0QQ, England.
   [Tomczak, Michal F.; Ko, Hyun-Jeong; Hosomi, Shuhei; Flak, Magdalena B.; Cusick, Jennifer L.; Blumberg, Richard S.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Gastroenterol,Dept Med, Boston, MA 02115 USA.
   [Boeck, Janne; Billmann-Born, Susanne; Bharti, Richa; Schreiber, Stefan; Rosenstiel, Philip] Univ Kiel, Inst Clin Mol Biol, D-24105 Kiel, Germany.
   [Martinez-Naves, Eduardo] Univ Complutense Madrid, Fac Med, Dept Microbiol & Immunol, E-28040 Madrid, Spain.
   [Glickman, Jonathan N.] Miraca Life Sci, GI Pathol Div, Newton, MA 02464 USA.
   [Tschurtschenthaler, Markus] Med Univ Innsbruck, Dept Med, A-6020 Innsbruck, Austria.
   [Hartwig, John] Harvard Univ, Brigham & Womens Hosp, Sch Med, Translat Med Div,Dept Med, Boston, MA 02115 USA.
   [Kohno, Kenji] Nara Inst Sci & Technol NAIST, Grad Sch Biol Sci, Lab Mol & Cell Genet, Nara 6300192, Japan.
   [Iwawaki, Takao] Gunma Univ, Adv Sci Res Leaders Dev Unit, Maebashi, Gunma 3718511, Japan.
   [Iwawaki, Takao] RIKEN, Adv Sci Inst, Iwawaki Initiat Res Unit, Wako, Saitama 3510198, Japan.
   [Lucius, Ralph] Univ Kiel, Anat Inst, D-24098 Kiel, Germany.
   [Kweon, Mi-Na] Int Vaccine Inst, Div Sci Lab, Mucosal Immunol Sect, Seoul 151818, South Korea.
   [Marciniak, Stefan J.] Univ Cambridge, Dept Med, Cambridge Inst Med Res CIMR, Cambridge CB2 0XY, England.
   [Choi, Augustine] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Pulm & Crit Care Med,Dept Med, Boston, MA 02115 USA.
   [Hagen, Susan J.] Beth Israel Deaconess Med Ctr, Dept Surg, Boston, MA 02215 USA.
C3 Cambridge University Hospitals NHS Foundation Trust; Addenbrooke's Hospital; University of Cambridge; Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Brigham & Women's Hospital; University of Kiel; Complutense University of Madrid; Medical University of Innsbruck; Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Brigham & Women's Hospital; Nara Institute of Science & Technology; Gunma University; RIKEN; University of Kiel; International Vaccine Institute; University of Cambridge; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Beth Israel Deaconess Medical Center
RP Blumberg, RS (corresponding author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Gastroenterol,Dept Med, 75 Francis St, Boston, MA 02115 USA.
EM ak729@cam.ac.uk; rblumberg@partners.org
FU NIH [DK044319, DK051362, DK053056, DK088199]; Harvard Digestive Diseases Center (HDDC) [DK0034854]; European Research Council under the European Community/ERC [260961]; National Institute for Health Research Cambridge Biomedical Research Centre; Austrian Science Fund; Ministry of Science [P21530-B18, START Y446-B18]; Addenbrooke's Charitable Trust; BMBF NGFN Animal Model grant; DFG Cluster of Excellence Inflammation at Interfaces; EU; Hans-Dietrich Bruhn Memorial Foundation; DFG [RO2994/5-1, SFB 877]; Inflammatory Bowel Disease Working Group; Crohn's and Colitis Foundation of America; European Crohn's and Colitis Organization; Crohn's in Childhood Research Association; National Research Foundation of Korea; Korean government [KRF-2008-357-E00022, 2011-0009018]; Grants-in-Aid for Scientific Research [24390049] Funding Source: KAKEN; Austrian Science Fund (FWF) [P21530] Funding Source: Austrian Science Fund (FWF); MRC [G1002610, G0601840] Funding Source: UKRI; Austrian Science Fund (FWF) [P 21530] Funding Source: researchfish; Medical Research Council [G0601840, G1002610] Funding Source: researchfish; National Institute of Diabetes and Digestive and Kidney Diseases [P30DK034854, R01DK053056, R01DK088199, R01DK051362, R01DK044319] Funding Source: NIH RePORTER
NR 50
TC 595
Z9 669
U1 2
U2 154
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 14
PY 2013
VL 503
IS 7475
BP 272
EP +
DI 10.1038/nature12599
PG 22
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 250YX
UT WOS:000326894200053
PM 24089213
DA 2026-03-09
ER

PT J
AU Dykhuizen, EC
   Hargreaves, DC
   Miller, EL
   Cui, KR
   Korshunov, A
   Kool, M
   Pfister, S
   Cho, YJ
   Zhao, KJ
   Crabtree, GR
AF Dykhuizen, Emily C.
   Hargreaves, Diana C.
   Miller, Erik L.
   Cui, Kairong
   Korshunov, Andrey
   Kool, Marcel
   Pfister, Stefan
   Cho, Yoon-Jae
   Zhao, Keji
   Crabtree, Gerald R.
TI BAF complexes facilitate decatenation of DNA by topoisomerase IIα
SO NATURE
LA English
DT Article
ID chromatin remodeling complex; genetic landscape; genome; esbaf; beta; pluripotency; resolution; mutations; polycomb; exome
AB Recent exon-sequencing studies of human tumours have revealed that subunits of BAF (mammalian SWI/SNF) complexes are mutated in more than 20% of all human malignancies(1,2), but the mechanisms involved in tumour suppression are unclear. BAF chromatin-remodelling complexes are polymorphic assemblies that use energy provided by ATP hydrolysis to regulate transcription through the control of chromatin structure(3) and the placement of Polycomb repressive complex 2 (PRC2) across the genome(4,5). Several proteins dedicated to this multisubunit complex, including BRG1 (also known as SMARCA4) and BAF250a (also known as ARID1A), are mutated at frequencies similar to those of recognized tumour suppressors. In particular, the core ATPase BRG1 is mutated in 5-10% of childhood medulloblastomas(6-9) and more than 15% of Burkitt's lymphomas(10,11). Here we show a previously unknown function of BAF complexes in decatenating newly replicated sister chromatids, a requirement for proper chromosome segregation during mitosis. We find that deletion of Brg1 in mouse cells, as well as the expression of BRG1 point mutants identified in human tumours, leads to anaphase bridge formation (in which sister chromatids are linked by catenated strands of DNA) and a G2/M-phase block characteristic of the decatenation checkpoint. Endogenous BAF complexes interact directly with endogenous topoisomerase II alpha (TOP2A) through BAF250a and are required for the binding of TOP2A to approximately 12,000 sites across the genome. Our results demonstrate that TOP2A chromatin binding is dependent on the ATPase activity of BRG1, which is compromised in oncogenic BRG1 mutants. These studies indicate that the ability of TOP2A to prevent DNA entanglement at mitosis requires BAF complexes and suggest that this activity contributes to the role of BAF subunits as tumour suppressors.
C1 [Dykhuizen, Emily C.; Hargreaves, Diana C.; Miller, Erik L.; Crabtree, Gerald R.] Stanford Univ, Sch Med, Howard Hughes Med Inst, Stanford, CA 94305 USA.
   [Dykhuizen, Emily C.; Hargreaves, Diana C.; Crabtree, Gerald R.] Stanford Univ, Sch Med, Dept Pathol, Stanford, CA 94305 USA.
   [Miller, Erik L.] Stanford Univ, Sch Med, Dept Genet, Stanford, CA 94305 USA.
   [Cui, Kairong; Zhao, Keji] NIH, Bethesda, MD 20892 USA.
   [Korshunov, Andrey] German Canc Res Ctr, CCU Neuropathol, D-69120 Heidelberg, Germany.
   [Kool, Marcel; Pfister, Stefan] German Canc Res Ctr, Div Pediat Neurooncol, D-69120 Heidelberg, Germany.
   [Pfister, Stefan] Univ Heidelberg Hosp, Dept Pediat Oncol, D-69120 Heidelberg, Germany.
   [Cho, Yoon-Jae] Stanford Univ, Sch Med, Dept Neurol & Neurosurg, Stanford, CA 94305 USA.
C3 Stanford University; Howard Hughes Medical Institute; Stanford University; Stanford University; National Institutes of Health (NIH) - USA; Helmholtz Association; German Cancer Research Center (DKFZ); Helmholtz Association; German Cancer Research Center (DKFZ); Ruprecht Karls University Heidelberg; Stanford University
RP Crabtree, GR (corresponding author), Stanford Univ, Sch Med, Howard Hughes Med Inst, Stanford, CA 94305 USA.
EM crabtree@stanford.edu
FU NIH; American Cancer Society; Helen Hay Whitney Foundation; NHLBI; National Cancer Institute [R01CA163915] Funding Source: NIH RePORTER; National Heart Lung and Blood Institute [ZIAHL006031, ZIAHL005801] Funding Source: NIH RePORTER
NR 37
TC 222
Z9 260
U1 1
U2 78
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 30
PY 2013
VL 497
IS 7451
BP 624
EP +
DI 10.1038/nature12146
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 152UF
UT WOS:000319556100045
PM 23698369
DA 2026-03-09
ER

PT J
AU Zhou, JF
   Wang, DY
   Gao, RB
   Zhao, BH
   Song, JD
   Qi, X
   Zhang, YJ
   Shi, YL
   Yang, L
   Zhu, WF
   Bai, T
   Qin, K
   Lan, Y
   Zou, SM
   Guo, JF
   Dong, J
   Dong, LB
   Zhang, Y
   Wei, HJ
   Li, XD
   Lu, J
   Liu, LQ
   Zhao, X
   Li, XY
   Huang, WJ
   Wen, LY
   Bo, H
   Xin, L
   Chen, YK
   Xu, CL
   Pei, YQ
   Yang, Y
   Zhang, XD
   Wang, SW
   Feng, ZJ
   Han, J
   Yang, WZ
   Gao, GF
   Wu, GZ
   Li, DX
   Wang, Y
   Shu, YL
AF Zhou, Jianfang
   Wang, Dayan
   Gao, Rongbao
   Zhao, Baihui
   Song, Jingdong
   Qi, Xian
   Zhang, Yanjun
   Shi, Yonglin
   Yang, Lei
   Zhu, Wenfei
   Bai, Tian
   Qin, Kun
   Lan, Yu
   Zou, Shumei
   Guo, Junfeng
   Dong, Jie
   Dong, Libo
   Zhang, Ye
   Wei, Hejiang
   Li, Xiaodan
   Lu, Jian
   Liu, Liqi
   Zhao, Xiang
   Li, Xiyan
   Huang, Weijuan
   Wen, Leying
   Bo, Hong
   Xin, Li
   Chen, Yongkun
   Xu, Cuilin
   Pei, Yuquan
   Yang, Yue
   Zhang, Xiaodong
   Wang, Shiwen
   Feng, Zijian
   Han, Jun
   Yang, Weizhong
   Gao, George F.
   Wu, Guizhen
   Li, Dexin
   Wang, Yu
   Shu, Yuelong
TI Biological features of novel avian influenza A (H7N9) virus
SO NATURE
LA English
DT Article
ID obstructive pulmonary-disease; increased expression; infection; binding; cells; hemagglutinin; transmission; specificity; adaptation; ferrets
AB Human infection associated with a novel reassortant avian influenza H7N9 virus has recently been identified in China(1). A total of 132 confirmed cases and 39 deaths have been reported(2). Most patients presented with severe pneumonia and acute respiratory distress syndrome(3,4). Although the first epidemic has subsided, the presence of a natural reservoir and the disease severity highlight the need to evaluate its risk on human public health and to understand the possible pathogenesis mechanism. Here we show that the emerging H7N9 avian influenza virus poses a potentially high risk to humans. We discover that the H7N9 virus can bind to both avian-type (alpha 2,3-linked sialic acid) and human-type (alpha 2,6-linked sialic acid) receptors. It can invade epithelial cells in the human lower respiratory tract and type II pneumonocytes in alveoli, and replicated efficiently in ex vivo lung and trachea explant culture and several mammalian cell lines. In acute serum samples of H7N9-infected patients, increased levels of the chemokines and cytokines IP-10, MIG, MIP-1 beta, MCP-1, IL-6, IL-8 and IFN-alpha were detected. We note that the human population is naive to the H7N9 virus, and current seasonal vaccination could not provide protection.
C1 [Zhou, Jianfang; Wang, Dayan; Gao, Rongbao; Song, Jingdong; Yang, Lei; Zhu, Wenfei; Bai, Tian; Qin, Kun; Lan, Yu; Zou, Shumei; Guo, Junfeng; Dong, Jie; Dong, Libo; Zhang, Ye; Wei, Hejiang; Li, Xiaodan; Lu, Jian; Liu, Liqi; Zhao, Xiang; Li, Xiyan; Huang, Weijuan; Wen, Leying; Bo, Hong; Xin, Li; Chen, Yongkun; Xu, Cuilin; Wang, Shiwen; Wu, Guizhen; Li, Dexin; Shu, Yuelong] Natl Hlth & Family Planning Commiss, Key Lab Med Virol, China CDC, Nat Inst Viral Dis Control & Prevent, Beijing 102206, Peoples R China.
   [Zhao, Baihui] Shanghai Municipal Dis Control & Prevent, Shanghai 200336, Peoples R China.
   [Qi, Xian] Jiangsu Prov Dis Control & Prevent, Nanjing 210009, Jiangsu, Peoples R China.
   [Zhang, Yanjun] Zhejiang Prov Dis Control & Prevent, Hangzhou 310051, Zhejiang, Peoples R China.
   [Shi, Yonglin] Anhui Prov Dis Control & Prevent, Hefei 230601, Peoples R China.
   [Pei, Yuquan; Yang, Yue; Zhang, Xiaodong] Peking Univ, Canc Hosp, Key Lab Carcinogenesis & Translat Res, Beijing 100142, Peoples R China.
   [Feng, Zijian; Han, Jun; Yang, Weizhong; Gao, George F.; Wang, Yu] Chinese Ctr Dis Control & Prevent, Beijing 102206, Peoples R China.
C3 Chinese Center for Disease Control & Prevention; Shanghai Center for Disease Control & Prevention; Anhui Provincial center for Disease Control & Prevention; Peking University; Chinese Center for Disease Control & Prevention
RP Shu, YL (corresponding author), Natl Hlth & Family Planning Commiss, Key Lab Med Virol, China CDC, Nat Inst Viral Dis Control & Prevent, Beijing 102206, Peoples R China.
EM yshu@cnic.org.cn
FU National Basic Research Program (973) of China [2011CB504704]; National Ministry of Science and Technology [KJYJ-2013-01-01]; National Mega-projects for Infectious Diseases [2013ZX10004611]
NR 30
TC 318
Z9 380
U1 1
U2 235
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 25
PY 2013
VL 499
IS 7459
BP 500
EP +
DI 10.1038/nature12379
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 187YP
UT WOS:000322157900045
PM 23823727
DA 2026-03-09
ER

PT J
AU Hu, HB
   Brittain, GC
   Chang, JH
   Puebla-Osorio, N
   Jin, J
   Zal, A
   Xiao, YC
   Cheng, XH
   Chang, MY
   Fu, YX
   Zal, T
   Zhu, CM
   Sun, SC
AF Hu, Hongbo
   Brittain, George C.
   Chang, Jae-Hoon
   Puebla-Osorio, Nahum
   Jin, Jin
   Zal, Anna
   Xiao, Yichuan
   Cheng, Xuhong
   Chang, Mikyoung
   Fu, Yang-Xin
   Zal, Tomasz
   Zhu, Chengming
   Sun, Shao-Cong
TI OTUD7B controls non-canonical NF-κB activation through deubiquitination of TRAF3
SO NATURE
LA English
DT Article
ID lymphotoxin-beta-receptor; homeostasis; pathway; kinase; responses; cezanne; nik
AB The non-canonical NF-kappa B pathway forms a major arm of NF-kappa B signalling that mediates important biological functions, including lymphoid organogenesis, B-lymphocyte function, and cell growth and survival(1-3). Activation of the non-canonical NF-kappa B pathway involves degradation of an inhibitory protein, TNF receptor-associated factor 3 (TRAF3), but how this signalling event is controlled is still unknown(1,2). Here we have identified the deubiquitinase OTUD7B as a pivotal regulator of the non-canonical NF-kappa B pathway. OTUD7B deficiency in mice has no appreciable effect on canonical NF-kappa B activation but causes hyperactivation of non-canonical NF-kappa B. In response to non-canonical NF-kappa B stimuli, OTUD7B binds and deubiquitinates TRAF3, thereby inhibiting TRAF3 proteolysis and preventing aberrant non-canonical NF-kappa B activation. Consequently, the OTUD7B deficiency results in B-cell hyper-responsiveness to antigens, lymphoid follicular hyperplasia in the intestinal mucosa, and elevated host-defence ability against an intestinal bacterial pathogen, Citrobacter rodentium. These findings establish OTUD7B as a crucial regulator of signal-induced non-canonical NF-kappa B activation and indicate a mechanism of immune regulation that involves OTUD7B-mediated deubiquitination and stabilization of TRAF3.
C1 [Hu, Hongbo; Brittain, George C.; Chang, Jae-Hoon; Puebla-Osorio, Nahum; Jin, Jin; Zal, Anna; Xiao, Yichuan; Cheng, Xuhong; Chang, Mikyoung; Zal, Tomasz; Zhu, Chengming; Sun, Shao-Cong] Univ Texas MD Anderson Canc Ctr, Dept Immunol, Houston, TX 77030 USA.
   [Fu, Yang-Xin] Univ Chicago, Dept Pathol, Chicago, IL 60637 USA.
   [Zal, Tomasz; Zhu, Chengming; Sun, Shao-Cong] Univ Texas Houston, Grad Sch Biomed Sci, Houston, TX 77030 USA.
C3 University of Texas System; UTMD Anderson Cancer Center; University of Chicago; University of Texas System; University of Texas Health Science Center Houston
RP Sun, SC (corresponding author), Univ Texas MD Anderson Canc Ctr, Dept Immunol, 7455 Fannin St,Box 902, Houston, TX 77030 USA.
EM ssun@mdanderson.org
FU National Institutes of Health [AI057555, AI064639, GM84459, CA137059, T32CA009598]; Sister Institution Network Fund of MD Anderson Cancer Center; National Cancer Institute [P30CA016672] Funding Source: NIH RePORTER; National Institute of Allergy and Infectious Diseases [R01AI057555, R37AI064639] Funding Source: NIH RePORTER; National Institute of General Medical Sciences [R01GM084459] Funding Source: NIH RePORTER
NR 27
TC 196
Z9 220
U1 1
U2 57
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 21
PY 2013
VL 494
IS 7437
BP 371
EP 374
DI 10.1038/nature11831
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 095CS
UT WOS:000315312900042
PM 23334419
DA 2026-03-09
ER

PT J
AU Ermolaeva, MA
   Segref, A
   Dakhovnik, A
   Ou, HL
   Schneider, JI
   Utermöhlen, O
   Hoppe, T
   Schumacher, B
AF Ermolaeva, Maria A.
   Segref, Alexandra
   Dakhovnik, Alexander
   Ou, Hui-Ling
   Schneider, Jennifer I.
   Utermoehlen, Olaf
   Hoppe, Thorsten
   Schumacher, Bjoern
TI DNA damage in germ cells induces an innate immune response that triggers systemic stress resistance
SO NATURE
LA English
DT Article
ID caenorhabditis-elegans; c-elegans; pathway; activation; evolution; infection; apoptosis; daf-16
AB DNA damage responses have been well characterized with regard to their cell-autonomous checkpoint functions leading to cell cycle arrest, senescence and apoptosis(1). In contrast, systemic responses to tissue-specific genome instability remain poorly understood. In adult Caenorhabditis elegans worms germ cells undergo mitotic and meiotic cell divisions, whereas somatic tissues are entirely post-mitotic. Consequently, DNA damage checkpoints function specifically in the germ line(2), whereas somatic tissues in adult C. elegans are highly radio-resistant(3). Some DNA repair systems such as global-genome nucleotide excision repair (GG-NER) remove lesions specifically in germ cells(4). Here we investigated how genome instability in germ cells affects somatic tissues in C. elegans. We show that exogenous and endogenous DNA damage in germ cells evokes elevated resistance to heat and oxidative stress. The somatic stress resistance is mediated by the ERK MAP kinase MPK-1 in germ cells that triggers the induction of putative secreted peptides associated with innate immunity. The innate immune response leads to activation of the ubiquitin-proteasome system (UPS) in somatic tissues, which confers enhanced proteostasis and systemic stress resistance. We propose that elevated systemic stress resistance promotes endurance of somatic tissues to allow delay of progeny production when germ cells are genomically compromised.
C1 [Ermolaeva, Maria A.; Segref, Alexandra; Dakhovnik, Alexander; Ou, Hui-Ling; Schneider, Jennifer I.; Hoppe, Thorsten; Schumacher, Bjoern] Univ Cologne, Inst Genet, Cologne Excellence Cluster Cellular Stress Respon, D-50674 Cologne, Germany.
   [Utermoehlen, Olaf] Univ Cologne, Med Ctr, Inst Med Microbiol Immunol & Hyg, D-50935 Cologne, Germany.
   [Utermoehlen, Olaf] Univ Cologne, Ctr Mol Med Cologne CMMC, D-50931 Cologne, Germany.
   [Schumacher, Bjoern] Univ Cologne, D-50937 Cologne, Germany.
C3 University of Cologne; University of Cologne; University of Cologne; University of Cologne
RP Schumacher, B (corresponding author), Univ Cologne, Inst Genet, Cologne Excellence Cluster Cellular Stress Respon, Zulpicher Str 47A, D-50674 Cologne, Germany.
EM bjoern.schumacher@uni-koeln.de
FU US National Institutes of Health (NIH) Office of Research Infrastructure Programs [P40 OD010440]; Mitani laboratory; Deutsche Forschungsgemeinschaft (DFG) [SFB 670-TP4]; EC Network of Excellence RUBICON [LSHC-CT-2005-018683]; DFG [CECAD, FOR885, SFB635, KFO286, HO2541/4-1, SFB 829, KFO 286]; European Research Council [260383]; Marie Curie [FP7 ITN CodeAge 316354, aDDRess 316390, MARRIAGE 316964, ERG239330]; German-Israeli Foundation [GIF 2213-1935.13/2008, 1104-68.11/2010]; Deutsche Krebshilfe [109453]; BMBF (SyBaCol); NIH Office of the Director; National Institute of General Medical Sciences [P40OD010440] Funding Source: NIH RePORTER; European Research Council (ERC) [260383] Funding Source: European Research Council (ERC)
NR 34
TC 179
Z9 197
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 SEP 19
PY 2013
VL 501
IS 7467
BP 416
EP +
DI 10.1038/nature12452
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 219XT
UT WOS:000324545700045
PM 23975097
DA 2026-03-09
ER

PT J
AU Meckler, AN
   Sigman, DM
   Gibson, KA
   François, R
   Martínez-García, A
   Jaccard, SL
   Röhl, U
   Peterson, LC
   Tiedemann, R
   Haug, GH
AF Meckler, A. N.
   Sigman, D. M.
   Gibson, K. A.
   Francois, R.
   Martinez-Garcia, A.
   Jaccard, S. L.
   Roehl, U.
   Peterson, L. C.
   Tiedemann, R.
   Haug, G. H.
TI Deglacial pulses of deep-ocean silicate into the subtropical North Atlantic Ocean
SO NATURE
LA English
DT Article
ID african humid period; southern-ocean; last deglaciation; younger dryas; circulation; record; termination; events; cd/ca; water
AB Growing evidence suggests that the low atmospheric CO2 concentration of the ice ages resulted from enhanced storage of CO2 in the ocean interior, largely as a result of changes in the Southern Ocean(1). Early in the most recent deglaciation, a reduction in North Atlantic overturning circulation seems to have driven CO2 release from the Southern Ocean(2-5), but the mechanism connecting the North Atlantic and the Southern Ocean remains unclear. Biogenic opal export in the low-latitude ocean relies on silicate from the underlying thermocline, the concentration of which is affected by the circulation of the ocean interior. Here we report a record of biogenic opal export from a coastal upwelling system off the coast of northwest Africa that shows pronounced opal maxima during each glacial termination over the past 550,000 years. These opal peaks are consistent with a strong deglacial reduction in the formation of silicate-poor glacial North Atlantic intermediate water(2) (GNAIW). The loss of GNAIW allowed mixing with underlying silicate-rich deep water to increase the silicate supply to the surface ocean. An increase in westerly-wind-driven upwelling in the Southern Ocean in response to the North Atlantic change has been proposed to drive the deglacial rise in atmospheric CO2 (refs 3, 4). However, such a circulation change would have accelerated the formation of Antarctic intermediate water and sub-Antarctic mode water, which today have as little silicate as North Atlantic Deep Water and would have thus maintained low silicate concentrations in the Atlantic thermocline. The deglacial opal maxima reported here suggest an alternative mechanism for the deglacial CO2 release(5,6). Just as the reduction in GNAIW led to upward silicate transport, it should also have allowed the downward mixing of warm, low-density surface water to reach into the deep ocean. The resulting decrease in the density of the deep Atlantic relative to the Southern Ocean surface promoted Antarctic overturning, which released CO2 to the atmosphere.
C1 [Meckler, A. N.; Martinez-Garcia, A.; Jaccard, S. L.; Haug, G. H.] ETH, Inst Geol, CH-8092 Zurich, Switzerland.
   [Sigman, D. M.] Princeton Univ, Dept Geosci, Princeton, NJ 08544 USA.
   [Gibson, K. A.; Peterson, L. C.] Univ Miami, Rosenstiel Sch Marine & Atmospher Sci, Miami, FL 33149 USA.
   [Francois, R.] Univ British Columbia, Dept Earth Ocean & Atmospher Sci, Vancouver, BC V6T 1Z4, Canada.
   [Roehl, U.] Univ Bremen, MARUM Ctr Marine Environm Sci, D-28359 Bremen, Germany.
   [Tiedemann, R.] Alfred Wegener Inst, D-27568 Bremerhaven, Germany.
C3 Swiss Federal Institutes of Technology Domain; ETH Zurich; Princeton University; University of Miami; University of British Columbia; University of Bremen; Helmholtz Association; Alfred Wegener Institute, Helmholtz Centre for Polar & Marine Research
RP Meckler, AN (corresponding author), ETH, Inst Geol, CH-8092 Zurich, Switzerland.
EM nele.meckler@erdw.ethz.ch
FU US NSF [OCE-1060947]; DFG-Leibniz Center for Surface Process and Climate Studies at the University of Potsdam; NSERC; CFCAS; Division Of Ocean Sciences; Directorate For Geosciences [1003364, 1060947] Funding Source: National Science Foundation
NR 38
TC 73
Z9 83
U1 1
U2 128
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 28
PY 2013
VL 495
IS 7442
BP 495
EP +
DI 10.1038/nature12006
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 113QN
UT WOS:000316682800042
PM 23538831
DA 2026-03-09
ER

PT J
AU Ruprecht, P
   Plank, T
AF Ruprecht, Philipp
   Plank, Terry
TI Feeding andesitic eruptions with a high-speed connection from the mantle
SO NATURE
LA English
DT Article
ID diffusion-coefficients; trace-elements; irazu volcano; costa-rica; olivine; magma; melts; arc; ni; pressure
AB Convergent margin volcanism is ultimately fed by magmas generated in the mantle, but the connection between the mantle and the eruption at the surface is typically obscured by cooling, crystallization and magma mixing within the crust(1-3). Geophysical techniques are also not very effective in the lower and middle crust, where seismic events are rare and resolution is generally poor(4,5). It has thus been unclear how fast mantle-derived magmas transit the crust and recharge crustal magma chambers. Here we use diffusion modelling of nickel zonation profiles in primitive olivines from diverse primary melts(6-10) to show how mantle recharge may occur on timescales as short as eruptions themselves. In Irazu volcano in Costa Rica, magmas apparently ascend from their source region in the mantle through crust about 35 kilometres thick in just months to years, recharging hybrid basaltic andesites over the course of the eruption. These results show that large stratovolcanoes with shallow magma chambers(11,12) may still preserve the deep record of their mantle origin in olivine crystals. This approach-documenting magma ascent timescales from the mantle beneath a convergent margin stratovolcano-can be applied to other eruptions that record magma mixing with recharge melts. Signs of volcanic unrest are typically monitored at the surface or upper crust; new efforts should look deeper, tracking magma movement from the base of the crust to the surface in the months to years before eruptions.
C1 [Ruprecht, Philipp; Plank, Terry] Columbia Univ, Lamont Doherty Earth Observ, Palisades, NY 10964 USA.
C3 Columbia University
RP Ruprecht, P (corresponding author), Columbia Univ, Lamont Doherty Earth Observ, 61 Route 9W, Palisades, NY 10964 USA.
EM ruprecht@ldeo.columbia.edu
FU Alexander-von-Humboldt foundation; NSF [EAR0948533]
NR 43
TC 140
Z9 157
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 AUG 1
PY 2013
VL 500
IS 7460
BP 68
EP U88
DI 10.1038/nature12342
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 192VK
UT WOS:000322514800029
PM 23903749
DA 2026-03-09
ER

PT J
AU Reaves, ML
   Young, BD
   Hosios, AM
   Xu, YF
   Rabinowitz, JD
AF Reaves, Marshall Louis
   Young, Brian D.
   Hosios, Aaron M.
   Xu, Yi-Fan
   Rabinowitz, Joshua D.
TI Pyrimidine homeostasis is accomplished by directed overflow metabolism
SO NATURE
LA English
DT Article
ID coli aspartate transcarbamoylase; escherichia-coli; ump kinase; inhibition; biosynthesis; quantitation; synthetase; mechanism; evolution; nitrogen
AB Cellular metabolism converts available nutrients into usable energy and biomass precursors. The process is regulated to facilitate efficient nutrient use and metabolic homeostasis. Feedback inhibition of the first committed step of a pathway by its final product is a classical means of controlling biosynthesis(1-4). In a canonical example, the first committed enzyme in the pyrimidine pathway in Escherichia coli is allosterically inhibited by cytidine triphosphate(1,4,5). The physiological consequences of disrupting this regulation, however, have not been previously explored. Here we identify an alternative regulatory strategy that enables precise control of pyrimidine pathway end-product levels, even in the presence of dysregulated biosynthetic flux. The mechanism involves cooperative feedback regulation of the near-terminal pathway enzyme uridine monophosphate kinase(6). Such feedback leads to build-up of the pathway intermediate uridine monophosphate, which is in turn degraded by a conserved phosphatase, here termed UmpH, with previously unknown physiological function(7,8). Such directed overflow metabolism allows homeostasis of uridine triphosphate and cytidine triphosphate levels at the expense of uracil excretion and slower growth during energy limitation. Disruption of the directed overflow regulatory mechanism impairs growth in pyrimidine-rich environments. Thus, pyrimidine homeostasis involves dual regulatory strategies, with classical feedback inhibition enhancing metabolic efficiency and directed overflow metabolism ensuring end-product homeostasis.
C1 [Reaves, Marshall Louis; Young, Brian D.; Hosios, Aaron M.; Xu, Yi-Fan; Rabinowitz, Joshua D.] Princeton Univ, Lewis Sigler Inst Integrat Genom, Princeton, NJ 08544 USA.
   [Reaves, Marshall Louis; Young, Brian D.; Hosios, Aaron M.; Rabinowitz, Joshua D.] Princeton Univ, Dept Mol Biol, Princeton, NJ 08544 USA.
   [Xu, Yi-Fan; Rabinowitz, Joshua D.] Princeton Univ, Dept Chem, Princeton, NJ 08544 USA.
C3 Princeton University; Princeton University; Princeton University
RP Rabinowitz, JD (corresponding author), Princeton Univ, Lewis Sigler Inst Integrat Genom, Princeton, NJ 08544 USA.
EM joshr@genomics.princeton.edu
FU National Science foundation (NSF) [MCB-0643859]; NSF CDI [CBET-0941143]; DOE-AFOSR [DE-SC0002077/FA9550-09-1-0580]; American Heart Association; Directorate For Engineering; Div Of Chem, Bioeng, Env, & Transp Sys [0941143] Funding Source: National Science Foundation
NR 43
TC 94
Z9 107
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 8
PY 2013
VL 500
IS 7461
BP 237
EP +
DI 10.1038/nature12445
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 197CH
UT WOS:000322825500041
PM 23903661
DA 2026-03-09
ER

PT J
AU Watanabe, T
   Kiso, M
   Fukuyama, S
   Nakajima, N
   Imai, M
   Yamada, S
   Murakami, S
   Yamayoshi, S
   Iwatsuki-Horimoto, K
   Sakoda, Y
   Takashita, E
   McBride, R
   Noda, T
   Hatta, M
   Imai, H
   Zhao, DM
   Kishida, N
   Shirakura, M
   de Vries, RP
   Shichinohe, S
   Okamatsu, M
   Tamura, T
   Tomita, Y
   Fujimoto, N
   Goto, K
   Katsura, H
   Kawakami, E
   Ishikawa, I
   Watanabe, S
   Ito, M
   Sakai-Tagawa, Y
   Sugita, Y
   Uraki, R
   Yamaji, R
   Eisfeld, AJ
   Zhong, GX
   Fan, SF
   Ping, JH
   Maher, EA
   Hanson, A
   Uchida, Y
   Saito, T
   Ozawa, M
   Neumann, G
   Kida, H
   Odagiri, T
   Paulson, JC
   Hasegawa, H
   Tashiro, M
   Kawaoka, Y
AF Watanabe, Tokiko
   Kiso, Maki
   Fukuyama, Satoshi
   Nakajima, Noriko
   Imai, Masaki
   Yamada, Shinya
   Murakami, Shin
   Yamayoshi, Seiya
   Iwatsuki-Horimoto, Kiyoko
   Sakoda, Yoshihiro
   Takashita, Emi
   McBride, Ryan
   Noda, Takeshi
   Hatta, Masato
   Imai, Hirotaka
   Zhao, Dongming
   Kishida, Noriko
   Shirakura, Masayuki
   de Vries, Robert P.
   Shichinohe, Shintaro
   Okamatsu, Masatoshi
   Tamura, Tomokazu
   Tomita, Yuriko
   Fujimoto, Naomi
   Goto, Kazue
   Katsura, Hiroaki
   Kawakami, Eiryo
   Ishikawa, Izumi
   Watanabe, Shinji
   Ito, Mutsumi
   Sakai-Tagawa, Yuko
   Sugita, Yukihiko
   Uraki, Ryuta
   Yamaji, Reina
   Eisfeld, Amie J.
   Zhong, Gongxun
   Fan, Shufang
   Ping, Jihui
   Maher, Eileen A.
   Hanson, Anthony
   Uchida, Yuko
   Saito, Takehiko
   Ozawa, Makoto
   Neumann, Gabriele
   Kida, Hiroshi
   Odagiri, Takato
   Paulson, James C.
   Hasegawa, Hideki
   Tashiro, Masato
   Kawaoka, Yoshihiro
TI Characterization of H7N9 influenza A viruses isolated from humans
SO NATURE
LA English
DT Article
ID molecular-basis; avian h5n1; in-vitro; transmission; replication; infection; binding; ferrets; site; pathogenesis
AB Avian influenza A viruses rarely infect humans; however, when human infection and subsequent human-to-human transmission occurs, worldwide outbreaks (pandemics) can result. The recent sporadic infections of humans in China with a previously unrecognized avian influenza A virus of the H7N9 subtype (A(H7N9)) have caused concern owing to the appreciable case fatality rate associated with these infections (more than 25%), potential instances of human-to-human transmission(1), and the lack of pre-existing immunity among humans to viruses of this subtype. Here we characterize two early human A(H7N9) isolates, A/Anhui/1/2013 (H7N9) and A/Shanghai/1/2013 (H7N9); hereafter referred to as Anhui/1 and Shanghai/1, respectively. In mice, Anhui/1 and Shanghai/1 were more pathogenic than a control avian H7N9 virus (A/duck/Gunma/466/2011 (H7N9); Dk/GM466) and a representative pandemic 2009 H1N1 virus (A/California/4/2009 (H1N1pdm09); CA04). Anhui/1, Shanghai/1 and Dk/GM466 replicated well in the nasal turbinates of ferrets. In nonhuman primates, Anhui/1 and Dk/GM466 replicated efficiently in the upper and lower respiratory tracts, whereas the replicative ability of conventional human influenza viruses is typically restricted to the upper respiratory tract of infected primates. By contrast, Anhui/1 did not replicate well in miniature pigs after intranasal inoculation. Critically, Anhui/1 transmitted through respiratory droplets in one of three pairs of ferrets. Glycan arrays showed that Anhui/1, Shanghai/1 and A/Hangzhou/1/2013 (H7N9) (a third human A(H7N9) virus tested in this assay) bind to human virus-type receptors, a property that may be critical for virus transmissibility in ferrets. Anhui/1 was found to be less sensitive in mice to neuraminidase inhibitors than a pandemic H1N1 2009 virus, although both viruses were equally susceptible to an experimental antiviral polymerase inhibitor. The robust replicative ability in mice, ferrets and nonhuman primates and the limited transmissibility in ferrets of Anhui/1 suggest that A(H7N9) viruses have pandemic potential.
C1 [Watanabe, Tokiko; Fukuyama, Satoshi; Zhao, Dongming; Tomita, Yuriko; Fujimoto, Naomi; Goto, Kazue; Kawakami, Eiryo; Ishikawa, Izumi; Watanabe, Shinji; Kawaoka, Yoshihiro] Japan Sci & Technol Agcy, ERATO Infect Induced Host Responses Project, Kawaguchi, Saitama 3320012, Japan.
   [Kiso, Maki; Yamada, Shinya; Yamayoshi, Seiya; Iwatsuki-Horimoto, Kiyoko; Noda, Takeshi; Katsura, Hiroaki; Ito, Mutsumi; Sakai-Tagawa, Yuko; Sugita, Yukihiko; Uraki, Ryuta; Yamaji, Reina; Kawaoka, Yoshihiro] Univ Tokyo, Inst Med Sci, Dept Microbiol & Immunol, Div Virol, Tokyo 1088639, Japan.
   [Nakajima, Noriko; Hasegawa, Hideki] Natl Inst Infect Dis, Dept Pathol, Shinjuku Ku, Tokyo 1628640, Japan.
   [Imai, Masaki; Takashita, Emi; Kishida, Noriko; Shirakura, Masayuki; Odagiri, Takato; Tashiro, Masato] Natl Inst Infect Dis, Influenza Virus Res Ctr, Tokyo 2080011, Japan.
   [Murakami, Shin; Kawaoka, Yoshihiro] Univ Tokyo, Inst Med Sci, Int Res Ctr Infect Dis, Dept Special Pathogens,Minato Ku, Tokyo 1088639, Japan.
   [Sakoda, Yoshihiro; Shichinohe, Shintaro; Okamatsu, Masatoshi; Tamura, Tomokazu; Kida, Hiroshi] Hokkaido Univ, Grad Sch Vet Med, Dept Dis Control, Microbiol Lab, Sapporo, Hokkaido 0600818, Japan.
   [McBride, Ryan; de Vries, Robert P.; Paulson, James C.] Scripps Res Inst, La Jolla, CA 92037 USA.
   [Hatta, Masato; Imai, Hirotaka; Eisfeld, Amie J.; Zhong, Gongxun; Fan, Shufang; Ping, Jihui; Maher, Eileen A.; Hanson, Anthony; Neumann, Gabriele; Kawaoka, Yoshihiro] Univ Wisconsin, Sch Vet Med, Dept Pathobiol Sci, Madison, WI 53711 USA.
   [Watanabe, Shinji] Miyazaki Univ, Dept Vet Sci, Lab Vet Microbiol, Miyazaki 8892192, Japan.
   [Uchida, Yuko; Saito, Takehiko] Natl Inst Anim Hlth, Influenza & Pr Dis Res Ctr, Tsukuba, Ibaraki 3050856, Japan.
   [Ozawa, Makoto] Kagoshima Univ, Joint Fac Vet Med, Lab Anim Hyg, Kagoshima 8900065, Japan.
   [Ozawa, Makoto] Kagoshima Univ, Joint Fac Vet Med, Transboundary Anim Dis Ctr, Kagoshima 8900065, Japan.
   [Kida, Hiroshi] Hokkaido Univ, Res Ctr Zoonosis Control, Sapporo, Hokkaido 0010020, Japan.
   [Kawaoka, Yoshihiro] Kyoto Univ, Inst Virus Res, Dept Biol Responses, Lab Bioresponses Regulat, Kyoto 6068507, Japan.
C3 Japan Science & Technology Agency (JST); University of Tokyo; Japan Institute for Health Security (JIHS); National Institute of Infectious Diseases (NIID); Japan Institute for Health Security (JIHS); National Institute of Infectious Diseases (NIID); University of Tokyo; Hokkaido University; Scripps Research Institute; University of Wisconsin System; University of Wisconsin Madison; University of Miyazaki; National Agriculture & Food Research Organization - Japan; National Institute of Animal Health - Japan; Kagoshima University; Kagoshima University; Hokkaido University; Kyoto University
RP Kawaoka, Y (corresponding author), Japan Sci & Technol Agcy, ERATO Infect Induced Host Responses Project, Kawaguchi, Saitama 3320012, Japan.
EM kawaokay@svm.vetmed.wisc.edu
FU Japan Initiative for Global Research Network on Infectious Diseases from the Ministry of Education, Culture, Sports, Science and Technology, Japan; Ministry of Health, Labour and Welfare, Japan; ERATO (Japan Science and Technology Agency); NIAID Public Health Service [AI099274, AI058113]; NIAID [HHSN266200700010C]; Grants-in-Aid for Scientific Research [24658245, 25450422] Funding Source: KAKEN
NR 36
TC 345
Z9 379
U1 5
U2 161
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 26
PY 2013
VL 501
IS 7468
BP 551
EP +
DI 10.1038/nature12392
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 223RP
UT WOS:000324826300059
PM 23842494
DA 2026-03-09
ER

PT J
AU Xue, ZG
   Huang, K
   Cai, CC
   Cai, LB
   Jiang, CY
   Feng, Y
   Liu, ZS
   Zeng, Q
   Cheng, LM
   Sun, YE
   Liu, JY
   Horvath, S
   Fan, GP
AF Xue, Zhigang
   Huang, Kevin
   Cai, Chaochao
   Cai, Lingbo
   Jiang, Chun-yan
   Feng, Yun
   Liu, Zhenshan
   Zeng, Qiao
   Cheng, Liming
   Sun, Yi E.
   Liu, Jia-yin
   Horvath, Steve
   Fan, Guoping
TI Genetic programs in human and mouse early embryos revealed by single-cell RNA sequencing
SO NATURE
LA English
DT Article
ID zygotic transition; preimplantation; transcriptome; seq; landscape; networks
AB Mammalian pre-implantation development is a complex process involving dramatic changes in the transcriptional architecture(1-4). We report here a comprehensive analysis of transcriptome dynamics from oocyte to morula in both human and mouse embryos, using single-cell RNA sequencing. Based on single-nucleotide variants in human blastomere messenger RNAs and paternal-specific single-nucleotide polymorphisms, we identify novel stage-specific monoallelic expression patterns for a significant portion of polymorphic gene transcripts (25 to 53%). By weighted gene co-expression network analysis(5,6), we find that each developmental stage can be delineated concisely by a small number of functional modules of co-expressed genes. This result indicates a sequential order of transcriptional changes in pathways of cell cycle, gene regulation, translation and metabolism, acting in a step-wise fashion from cleavage to morula. Cross-species comparisons with mouse pre-implantation embryos reveal that the majority of human stage-specific modules (7 out of 9) are notably preserved, but developmental specificity and timing differ between human and mouse. Furthermore, we identify conserved key members (or hub genes) of the human and mouse networks. These genes represent novel candidates that are likely to be key in driving mammalian pre-implantation development. Together, the results provide a valuable resource to dissect gene regulatory mechanisms underlying progressive development of early mammalian embryos.
C1 [Xue, Zhigang; Feng, Yun; Liu, Zhenshan; Zeng, Qiao; Cheng, Liming; Sun, Yi E.] Tongji Univ, Sch Med, Dept Regenerat Med, Translat Ctr Stem Cell Res,Tongji Hosp, Shanghai 200065, Peoples R China.
   [Huang, Kevin; Cai, Chaochao; Horvath, Steve; Fan, Guoping] Univ Calif Los Angeles, David Geffen Sch Med, Dept Human Genet, Los Angeles, CA 90095 USA.
   [Cai, Lingbo; Jiang, Chun-yan; Liu, Jia-yin] Nanjing Med Univ, Affiliated Hosp 1, Ctr Clin Reprod Med, State Key Lab Reprod Med, Nanjing 210029, Jiangsu, Peoples R China.
C3 Tongji University; University of California System; University of California Los Angeles; University of California Los Angeles Medical Center; David Geffen School of Medicine at UCLA; Nanjing Medical University
RP Fan, GP (corresponding author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Human Genet, Los Angeles, CA 90095 USA.
EM xuezhigang75@gmail.com; jyliu_nj@126.com; gfan@mednet.ucla.edu
FU Ministry of Science and Technology in China [2012CB966300, 2011CB966204, 2011CB965102]; International Science and Technology Cooperation Program of China [2011DFB30010]; National Natural Science Foundation of China [81271258]; National Institute on Drug Abuse [P50DA005010] Funding Source: NIH RePORTER
NR 37
TC 759
Z9 915
U1 4
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 AUG 29
PY 2013
VL 500
IS 7464
BP 593
EP +
DI 10.1038/nature12364
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 207TD
UT WOS:000323625900038
PM 23892778
DA 2026-03-09
ER

PT J
AU Li, DF
   Lyons, JA
   Pye, VE
   Vogeley, L
   Aragao, D
   Kenyon, CP
   Shah, STA
   Doherty, C
   Aherne, M
   Caffrey, M
AF Li, Dianfan
   Lyons, Joseph A.
   Pye, Valerie E.
   Vogeley, Lutz
   Aragao, David
   Kenyon, Colin P.
   Shah, Syed T. A.
   Doherty, Christine
   Aherne, Margaret
   Caffrey, Martin
TI Crystal structure of the integral membrane diacylglycerol kinase
SO NATURE
LA English
DT Article
ID protein-structure determination; escherichia-coli; sn-1,2-diacylglycerol kinase; crystallography; enzyme; sequence; design; system; sites; nmr
AB Diacylglycerol kinase catalyses the ATP-dependent phosphorylation of diacylglycerol to phosphatidic acid for use in shuttling water-soluble components to membrane-derived oligosaccharide and lipopolysaccharide in the cell envelope of Gram-negative bacteria(1). For half a century, this 121-residue kinase has served as a model for investigating membrane protein enzymology(1-6), folding(7,8), assembly(9-12) and stability(1,13). Here we present crystal structures for three functional forms of this unique and paradigmatic kinase, one of which is wild type. These reveal a homo-trimeric enzyme with three transmembrane helices and an amino-terminal amphiphilic helix per monomer. Bound lipid substrate and docked ATP identify the putative active site that is of the composite, shared site type. The crystal structures rationalize extensive biochemical and biophysical data on the enzyme. They are, however, at variance with a published solution NMR model(14) in that domain swapping, a key feature of the solution form, is not observed in the crystal structures.
C1 [Li, Dianfan; Lyons, Joseph A.; Pye, Valerie E.; Vogeley, Lutz; Aragao, David; Shah, Syed T. A.; Doherty, Christine; Aherne, Margaret; Caffrey, Martin] Trinity Coll Dublin, Sch Biochem & Immunol, Dublin 2, Ireland.
   [Li, Dianfan; Lyons, Joseph A.; Pye, Valerie E.; Vogeley, Lutz; Aragao, David; Shah, Syed T. A.; Doherty, Christine; Aherne, Margaret; Caffrey, Martin] Trinity Coll Dublin, Sch Med, Dublin 2, Ireland.
   [Kenyon, Colin P.] CSIR, ZA-0184 Pretoria, Gauteng, South Africa.
C3 Trinity College Dublin; Trinity College Dublin; Council for Scientific & Industrial Research (CSIR) - South Africa
RP Caffrey, M (corresponding author), Trinity Coll Dublin, Sch Biochem & Immunol, Dublin 2, Ireland.
EM martin.caffrey@tcd.ie
FU Science Foundation Ireland [07/IN.1/B1836, 12/IA/1255]; National Institutes of Health [GM75915, P50GM073210, U54GM094599]; FP7 [COST CM0902]; Science Foundation Ireland (SFI) [12/IA/1255, 07/IN.1/B1836] Funding Source: Science Foundation Ireland (SFI)
NR 50
TC 81
Z9 98
U1 0
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 23
PY 2013
VL 497
IS 7450
BP 521
EP +
DI 10.1038/nature12179
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 148OG
UT WOS:000319254000055
PM 23676677
DA 2026-03-09
ER

PT J
AU Bava, FA
   Eliscovich, C
   Ferreira, PG
   Miñana, B
   Ben-Dov, C
   Guigó, R
   Valcárcel, J
   Méndez, R
AF Bava, Felice-Alessio
   Eliscovich, Carolina
   Ferreira, Pedro G.
   Minana, Belen
   Ben-Dov, Claudia
   Guigo, Roderic
   Valcarcel, Juan
   Mendez, Raul
TI CPEB1 coordinates alternative 3′ -UTR formation with translational regulation
SO NATURE
LA English
DT Article
ID messenger-rnas; untranslated regions; cytoplasmic polyadenylation; chromosome segregation; cells; mechanisms; insights; complex
AB More than half of mammalian genes generate multiple messenger RNA isoforms that differ in their 3' untranslated regions (3' UTRs) and therefore in regulatory sequences(1), often associated with cell proliferation and cancer(2,3); however, the mechanisms coordinating alternative 3'-UTR processing for specific mRNA populations remain poorly defined. Here we report that the cytoplasmic-polyadenylation element binding protein 1 (CPEB1), an RNA-binding protein that regulates mRNA translation(4), also controls alternative 3'-UTR processing. CPEB1 shuttles to the nudeus(5,6), where it co-localizes with splicing factors and mediates shortening of hundreds of mRNA 3' UTRs, thereby modulating their translation efficiency in the cytoplasm. CPEB1-mediated 3'-UTR shortening correlates with cell proliferation and tumorigenesis. CPEB1 binding to pre-mRNAs not only directs the use of alternative polyadenylation sites, but also changes alternative splicing by preventing U2AF65 recruitment. Our results reveal a novel function of CPEB1 in mediating alternative 3'-UTR processing, which is coordinated with regulation of mRNA translation, through its dual nuclear and cytoplasmic functions.
C1 [Bava, Felice-Alessio; Mendez, Raul] Inst Res Biomed IRB Barcelona, Barcelona 08028, Spain.
   [Eliscovich, Carolina; Ferreira, Pedro G.; Minana, Belen; Ben-Dov, Claudia; Guigo, Roderic; Valcarcel, Juan] UPF, Ctr Genom Regulat CRG, Barcelona 08003, Spain.
   [Valcarcel, Juan; Mendez, Raul] Passeig Lluis Co 23, ICREA, Barcelona 08010, Spain.
C3 Barcelona Institute of Science & Technology; Institute for Research in Biomedicine - IRB Barcelona; Barcelona Institute of Science & Technology; Pompeu Fabra University; Centre de Regulacio Genomica (CRG); ICREA
RP Méndez, R (corresponding author), Inst Res Biomed IRB Barcelona, Baldiri Reixac 10, Barcelona 08028, Spain.
EM raul.mendez@irbbarcelona.org
FU Consolider; MICINN; Generalitat de Catalunya; RNAREG; AICR; EURASNET; Fundacion Marcelino Botin; National Institutes of Health; Instituto de Salud Carlos III; "la Caixa" predoctoral fellowship; FCT-Portugal; Spanish MICINN; ICREA Funding Source: Custom
NR 23
TC 128
Z9 144
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 MAR 7
PY 2013
VL 495
IS 7439
BP 121
EP 125
DI 10.1038/nature11901
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 105BE
UT WOS:000316039800052
PM 23434754
DA 2026-03-09
ER

PT J
AU Ostmeyer, J
   Chakrapani, S
   Pan, AC
   Perozo, E
   Roux, B
AF Ostmeyer, Jared
   Chakrapani, Sudha
   Pan, Albert C.
   Perozo, Eduardo
   Roux, Benoit
TI Recovery from slow inactivation in K+ channels is controlled by water molecules
SO NATURE
LA English
DT Article
ID c-type inactivation; structural basis; quantitative description; dynamics; kcsa; activation
AB Application of a specific stimulus opens the intracellular gate of a K+ channel (activation), yielding a transient period of ion conduction until the selectivity filter spontaneously undergoes a conformational change towards a non-conductive state (inactivation). Removal of the stimulus closes the gate and allows the selectivity filter to interconvert back to its conductive conformation (recovery). Given that the structural differences between the conductive and inactivated filter are very small, it is unclear why the recovery process can take up to several seconds. The bacterial K+ channel KcsA from Streptomyces lividans can be used to help elucidate questions about channel inactivation and recovery at the atomic level. Although KcsA contains only a pore domain, without voltage-sensing machinery, it has the structural elements necessary for ion conduction, activation and inactivation(1-7). Here we reveal, by means of a series of long molecular dynamics simulations, how the selectivity filter is sterically locked in the inactive conformation by buried water molecules bound behind the selectivity filter. Potential of mean force calculations show how the recovery process is affected by the buried water molecules and the rebinding of an external K+ ion. A kinetic model deduced from the simulations shows how releasing the buried water molecules can stretch the timescale of recovery to seconds. This leads to the prediction that reducing the occupancy of the buried water molecules by imposing a high osmotic stress should accelerate the rate of recovery, which was verified experimentally by measuring the recovery rate in the presence of a 2-molar sucrose concentration.
C1 [Ostmeyer, Jared; Pan, Albert C.; Perozo, Eduardo; Roux, Benoit] Univ Chicago, Dept Biochem & Mol Biol, Chicago, IL 60637 USA.
   [Chakrapani, Sudha] Case Western Reserve Univ, Sch Med, Dept Physiol & Biophys, Cleveland, OH 44106 USA.
C3 University of Chicago; University System of Ohio; Case Western Reserve University
RP Roux, B (corresponding author), Univ Chicago, Dept Biochem & Mol Biol, 929 E57th St, Chicago, IL 60637 USA.
EM roux@uchicago.edu
FU National Institute of Health [R01-GM062342, R01-GM57846]; Office of Science of the Department of Energy [DE-AC05-00OR22725]; Pittsburgh Supercomputing Center (PSC) through National Institutes of Health [RC2GM093307]; National Institute of General Medical Sciences [R01GM062342] Funding Source: NIH RePORTER
NR 26
TC 158
Z9 177
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 SEP 5
PY 2013
VL 501
IS 7465
BP 
EP 
DI 10.1038/nature12395
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AL8YC
UT WOS:000339424700003
PM 23892782
DA 2026-03-09
ER

PT J
AU McAleenan, A
   Clemente-Blanco, A
   Cordon-Preciado, V
   Sen, N
   Esteras, M
   Jarmuz, A
   Aragón, L
AF McAleenan, Alexandra
   Clemente-Blanco, Andres
   Cordon-Preciado, Violeta
   Sen, Nicholas
   Esteras, Miguel
   Jarmuz, Adam
   Aragon, Luis
TI Post-replicative repair involves separase-dependent removal of the kleisin subunit of cohesin
SO NATURE
LA English
DT Article
ID double-strand breaks; saccharomyces-cerevisiae; dna-repair; cleavage; pathway; damage; exo1; helicase
AB DNA double-strand break repair is critical for cell viability and involves highly coordinated pathways to restore DNA integrity at the lesion. An early event during homology-dependent repair is resection of the break to generate progressively longer 3' single-strand tails that are used to identify suitable templates for repair(1). Sister chromatids provide near-perfect sequence homology and are therefore the preferred templates during homologous recombination(2,3). To provide a bias for the use of sisters as donors, cohesin-the complex that tethers sister chromatids together(4)-is recruited to the break(5,6) to enforce physical proximity. Here we show that DNA breaks promote dissociation of cohesin loaded during the previous S phase in budding yeast, and that damage-induced dissociation of cohesin requires separase, the protease that dissolves cohesion in anaphase(7). Moreover, a separase-resistant allele of the gene coding for the alpha-kleisin subunit of cohesin, Mcd1 (also known as Scc1), reduces double-strand break resection and compromises the efficiency of repair even when loaded during DNA damage. We conclude that post-replicative DNA repair involves cohesin dissociation by separase to promote accessibility to repair factors during the coordinated cellular response to restore DNA integrity.
C1 [McAleenan, Alexandra; Clemente-Blanco, Andres; Cordon-Preciado, Violeta; Sen, Nicholas; Esteras, Miguel; Jarmuz, Adam; Aragon, Luis] Univ London Imperial Coll Sci Technol & Med, MRC Clin Sci Ctr, Cell Cycle Grp, London W12 0NN, England.
C3 Imperial College London
RP Aragón, L (corresponding author), Univ London Imperial Coll Sci Technol & Med, MRC Clin Sci Ctr, Cell Cycle Grp, Du Cane Rd, London W12 0NN, England.
EM luis.aragon@csc.mrc.ac.uk
FU Intramural Research Program of the Medical Research Council UK; MRC [MC_U120074328] Funding Source: UKRI; Medical Research Council [MC_U120074328] Funding Source: researchfish
CR Baskerville C, 2008, GENETICS, V178, P2361, DOI 10.1534/genetics.107.085308
   Heidinger-Pauli JM, 2008, MOL CELL, V31, P47, DOI 10.1016/j.molcel.2008.06.005
   Heidinger-Pauli JM, 2010, CURR BIOL, V20, P957, DOI 10.1016/j.cub.2010.04.018
   Heidinger-Pauli JM, 2009, MOL CELL, V34, P311, DOI 10.1016/j.molcel.2009.04.008
   Jain S, 2009, GENE DEV, V23, P291, DOI 10.1101/gad.1751209
   Johnson RD, 2000, EMBO J, V19, P3398, DOI 10.1093/emboj/19.13.3398
   KADYK LC, 1992, GENETICS, V132, P387
   Mimitou EP, 2008, NATURE, V455, P770, DOI 10.1038/nature07312
   Nagao K, 2004, NATURE, V430, P1044, DOI 10.1038/nature02803
   Nasmyth K, 2011, NAT CELL BIOL, V13, P1170, DOI 10.1038/ncb2349
   Pâques F, 1999, MICROBIOL MOL BIOL R, V63, P349
   Shim EY, 2010, EMBO J, V29, P3370, DOI 10.1038/emboj.2010.219
   Ström L, 2007, SCIENCE, V317, P242, DOI 10.1126/science.1140649
   Ström L, 2004, MOL CELL, V16, P1003, DOI 10.1016/j.molcel.2004.11.026
   Ünal E, 2007, SCIENCE, V317, P245, DOI 10.1126/science.1140637
   Uhlmann F, 1999, NATURE, V400, P37, DOI 10.1038/21831
   Ünal E, 2004, MOL CELL, V16, P991, DOI 10.1016/j.molcel.2004.11.027
   Vaze MB, 2002, MOL CELL, V10, P373, DOI 10.1016/S1097-2765(02)00593-2
   Zhu Z, 2008, CELL, V134, P981, DOI 10.1016/j.cell.2008.08.037
NR 19
TC 48
Z9 56
U1 0
U2 26
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 10
PY 2013
VL 493
IS 7431
BP 250
EP U270
DI 10.1038/nature11630
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 066YY
UT WOS:000313259600045
PM 23178808
DA 2026-03-09
ER

PT J
AU Furusawa, Y
   Obata, Y
   Fukuda, S
   Endo, TA
   Nakato, G
   Takahashi, D
   Nakanishi, Y
   Uetake, C
   Kato, K
   Kato, T
   Takahashi, M
   Fukuda, NN
   Murakami, S
   Miyauchi, E
   Hino, S
   Atarashi, K
   Onawa, S
   Fujimura, Y
   Lockett, T
   Clarke, JM
   Topping, DL
   Tomita, M
   Hori, S
   Ohara, O
   Morita, T
   Koseki, H
   Kikuchi, J
   Honda, K
   Hase, K
   Ohno, H
AF Furusawa, Yukihiro
   Obata, Yuuki
   Fukuda, Shinji
   Endo, Takaho A.
   Nakato, Gaku
   Takahashi, Daisuke
   Nakanishi, Yumiko
   Uetake, Chikako
   Kato, Keiko
   Kato, Tamotsu
   Takahashi, Masumi
   Fukuda, Noriko N.
   Murakami, Shinnosuke
   Miyauchi, Eiji
   Hino, Shingo
   Atarashi, Koji
   Onawa, Satoshi
   Fujimura, Yumiko
   Lockett, Trevor
   Clarke, Julie M.
   Topping, David L.
   Tomita, Masaru
   Hori, Shohei
   Ohara, Osamu
   Morita, Tatsuya
   Koseki, Haruhiko
   Kikuchi, Jun
   Honda, Kenya
   Hase, Koji
   Ohno, Hiroshi
TI Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells
SO NATURE
LA English
DT Article
ID arabidopsis-thaliana; metabolic dynamics; gut microbiota; inhibition; colonization; inflammation; receptors; responses; colitis; subsets
AB Gut commensal microbes shape the mucosal immune system by regulating the differentiation and expansion of several types of T cell(1-5). Clostridia, a dominant class of commensal microbe, can induce colonic regulatory T (T-reg) cells, which have a central role in the suppression of inflammatory and allergic responses(3). However, the molecular mechanisms by which commensal microbes induce colonic T-reg cells have been unclear. Here we show that a large bowel microbial fermentation product, butyrate, induces the differentiation of colonic T-reg cells in mice. A comparative NMR-based metabolome analysis suggests that the luminal concentrations of short-chain fatty acids positively correlates with the number of T-reg cells in the colon. Among short-chain fatty acids, butyrate induced the differentiation of T-reg cells in vitro and in vivo, and ameliorated the development of colitis induced by adoptive transfer of CD4(+) CD45RB(hi) T cells in Rag1(-/-) mice. Treatment of naive T cells under the T-reg-cell-polarizing conditions with butyrate enhanced histone H3 acetylation in the promoter and conserved non-coding sequence regions of the Foxp3 locus, suggesting a possible mechanism for how microbial-derived butyrate regulates the differentiation of T-reg cells. Our findings provide new insight into the mechanisms by which host-microbe interactions establish immunological homeostasis in the gut.
C1 [Furusawa, Yukihiro; Obata, Yuuki; Fukuda, Shinji; Endo, Takaho A.; Nakato, Gaku; Takahashi, Daisuke; Uetake, Chikako; Kato, Keiko; Kato, Tamotsu; Takahashi, Masumi; Miyauchi, Eiji; Atarashi, Koji; Onawa, Satoshi; Hori, Shohei; Ohara, Osamu; Koseki, Haruhiko; Honda, Kenya; Hase, Koji; Ohno, Hiroshi] RIKEN Ctr Integrat Med Sci IMS RCAI, Wako, Kanagawa 2300045, Japan.
   [Furusawa, Yukihiro; Obata, Yuuki; Fujimura, Yumiko; Hase, Koji] Univ Tokyo, Inst Med Sci, Tokyo 1088639, Japan.
   [Obata, Yuuki; Koseki, Haruhiko; Ohno, Hiroshi] Chiba Univ, Grad Sch Med, Chiba 2608670, Japan.
   [Fukuda, Shinji; Nakanishi, Yumiko; Fukuda, Noriko N.; Murakami, Shinnosuke; Tomita, Masaru] Keio Univ, Inst Adv Biosci, Yamagata 9970052, Japan.
   [Kato, Keiko; Koseki, Haruhiko; Kikuchi, Jun] Yokohama City Univ, Grad Sch Med Life Sci, Yokohama, Kanagawa 2300045, Japan.
   [Hino, Shingo] Shizuoka Univ, Fac Agr, Shizuoka 4228529, Japan.
   [Atarashi, Koji; Hase, Koji] Japan Sci & Technol Agcy, PRESTO, Kawaguchi, Saitama 3320012, Japan.
   [Lockett, Trevor; Clarke, Julie M.; Topping, David L.] CSIRO Food & Nutr Sci, Preventat Hlth Natl Res Flagship, Adelaide, SA 5000, Australia.
   [Kikuchi, Jun] RIKEN Ctr Sustainable Resource Sci, Kanagawa 2300045, Japan.
   [Honda, Kenya] Japan Sci & Technol Agcy, CREST, Kawaguchi, Saitama 3320012, Japan.
C3 RIKEN; University of Tokyo; Chiba University; Keio University; Yokohama City University; Shizuoka University; Japan Science & Technology Agency (JST); Commonwealth Scientific & Industrial Research Organisation (CSIRO); RIKEN; Japan Science & Technology Agency (JST)
RP Ohno, H (corresponding author), RIKEN Ctr Integrat Med Sci IMS RCAI, Wako, Kanagawa 2300045, Japan.
EM sfukuda@sfc.keio.ac.jp; hase@ims.u-tokyo.ac.jp; ohno@rcai.riken.jp
FU Japanese Ministry of Education, Culture, Sports, Science and Technology [24117524, 21022049, 20113003]; The Japan Society for the Promotion of Science [24890293, 252667, 24380072, 24658129, 22689017, 21390155]; The Japan Science and Technology Agency; RIKEN; RIKEN RCAI Young Chief Investigator program; Institute for Fermentation, Osaka; Mishima Kaiun Memorial Foundation; The Takeda Science Foundation; The Mitsubishi Foundation; The Uehara Memorial Foundation; Grants-in-Aid for Scientific Research [23390123, 21390155, 24117524, 25513012, 25660101, 25293114, 23780131, 13J02667, 22689017, 25118733, 24890293, 24658129, 13J05482, 24117723, 21022049] Funding Source: KAKEN
NR 50
TC 4212
Z9 4922
U1 23
U2 713
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 19
PY 2013
VL 504
IS 7480
BP 446
EP +
DI 10.1038/nature12721
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 273ZR
UT WOS:000328575300054
PM 24226770
DA 2026-03-09
ER

PT J
AU Kornfeld, JW
   Baitzel, C
   Könner, AC
   Nicholls, HT
   Vogt, MC
   Herrmanns, K
   Scheja, L
   Haumaitre, C
   Wolf, AM
   Knippschild, U
   Seibler, J
   Cereghini, S
   Heeren, J
   Stoffel, M
   Brüning, JC
AF Kornfeld, Jan-Wilhelm
   Baitzel, Catherina
   Koenner, A. Christine
   Nicholls, Hayley T.
   Vogt, Merly C.
   Herrmanns, Karolin
   Scheja, Ludger
   Haumaitre, Cecile
   Wolf, Anna M.
   Knippschild, Uwe
   Seibler, Jost
   Cereghini, Silvia
   Heeren, Joerg
   Stoffel, Markus
   Bruening, Jens C.
TI Obesity-induced overexpression of miR-802 impairs glucose metabolism through silencing of Hnf1b
SO NATURE
LA English
DT Article
ID insulin; cdkn2a/b; cdkal1; tcf2
AB Insulin resistance represents a hallmark during the development of type 2 diabetes mellitus and in the pathogenesis of obesity-associated disturbances of glucose and lipid metabolism(1-3). MicroRNA (miRNA)-dependent post-transcriptional gene silencing has been recognized recently to control gene expression in disease development and progression, including that of insulin-resistant type 2 diabetes. The deregulation of miRNAs miR-143 (ref. 4), miR-181 (ref. 5), and miR-103 and miR-107 (ref. 6) alters hepatic insulin sensitivity. Here we report that the expression of miR-802 is increased in the liver of two obese mouse models and obese human subjects. Inducible transgenic overexpression of miR-802 in mice causes impaired glucose tolerance and attenuates insulin sensitivity, whereas reduction of miR-802 expression improves glucose tolerance and insulin action. We identify Hnf1b (also known as Tcf2) as a target of miR-802-dependent silencing, and show that short hairpin RNA (shRNA)-mediated reduction of Hnf1b in liver causes glucose intolerance, impairs insulin signalling and promotes hepatic gluconeogenesis. In turn, hepatic overexpression of Hnf1b improves insulin sensitivity in Lepr(db/db) mice. Thus, this study defines a critical role for deregulated expression of miR-802 in the development of obesity-associated impairment of glucose metabolism through targeting of Hnf1b, and assigns Hnf1b an unexpected role in the control of hepatic insulin sensitivity.
C1 [Kornfeld, Jan-Wilhelm; Baitzel, Catherina; Koenner, A. Christine; Nicholls, Hayley T.; Vogt, Merly C.; Bruening, Jens C.] Max Planck Inst Neurol Res, D-50931 Cologne, Germany.
   [Kornfeld, Jan-Wilhelm; Baitzel, Catherina; Koenner, A. Christine; Nicholls, Hayley T.; Vogt, Merly C.; Bruening, Jens C.] Cologne Excellence Cluster Cellular Stress Respon, D-50674 Cologne, Germany.
   [Kornfeld, Jan-Wilhelm; Baitzel, Catherina; Koenner, A. Christine; Nicholls, Hayley T.; Vogt, Merly C.; Bruening, Jens C.] Univ Cologne, Univ Hosp Cologne, Ctr Endocrinol Diabet & Prevent Med CEDP, Dept Mouse Genet & Metab,Inst Genet, D-50674 Cologne, Germany.
   [Kornfeld, Jan-Wilhelm; Baitzel, Catherina; Koenner, A. Christine; Nicholls, Hayley T.; Vogt, Merly C.; Bruening, Jens C.] Ctr Mol Med Cologne, D-50674 Cologne, Germany.
   [Herrmanns, Karolin; Stoffel, Markus] Swiss Fed Inst Technol, Inst Mol Hlth Sci, CH-8093 Zurich, Switzerland.
   [Scheja, Ludger; Heeren, Joerg] Univ Hosp Hamburg Eppendorf, Dept Biochem & Mol Cell Biol, D-20246 Hamburg, Germany.
   [Haumaitre, Cecile; Cereghini, Silvia] INSERM, U969, F-75005 Paris, France.
   [Haumaitre, Cecile; Cereghini, Silvia] Univ Paris 06, CNRS, UMR7622, F-75005 Paris, France.
   [Wolf, Anna M.; Knippschild, Uwe] Univ Hosp Ulm, Dept Gen & Visceral Surg, D-89081 Ulm, Germany.
   [Seibler, Jost] TaconicArtemis GmbH, D-51063 Cologne, Germany.
C3 Max Planck Society; University of Cologne; University of Cologne; University of Cologne; Swiss Federal Institutes of Technology Domain; ETH Zurich; University of Hamburg; University Medical Center Hamburg-Eppendorf; Institut National de la Sante et de la Recherche Medicale (Inserm); Sorbonne Universite; Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB); Ulm University
RP Brüning, JC (corresponding author), Max Planck Inst Neurol Res, Gleueler Str 50A, D-50931 Cologne, Germany.
EM bruening@nf.mpg.de
FU EMBO; CECAD; INSERM; CNRS; EU FP7 (Mane Curie Initial Training Network BOLD); ERC; DFG [SFB 841, Br1492-7]
NR 17
TC 278
Z9 318
U1 0
U2 147
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 7
PY 2013
VL 494
IS 7435
BP 111
EP 115
DI 10.1038/nature11793
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 087DJ
UT WOS:000314741200044
PM 23389544
DA 2026-03-09
ER

PT J
AU Spence, PJ
   Jarra, W
   Lévy, P
   Reid, AJ
   Chappell, L
   Brugat, T
   Sanders, M
   Berriman, M
   Langhorne, J
AF Spence, Philip J.
   Jarra, William
   Levy, Prisca
   Reid, Adam J.
   Chappell, Lia
   Brugat, Thibaut
   Sanders, Mandy
   Berriman, Matthew
   Langhorne, Jean
TI Vector transmission regulates immune control of Plasmodium virulence
SO NATURE
LA English
DT Article
ID mosquito-transmission; expression analysis; antigenic variants; multigene family; malaria; chabaudi; infections; diversity; mice
AB Defining mechanisms by which Plasmodium virulence is regulated is central to understanding the pathogenesis of human malaria. Serial blood passage of Plasmodium through rodents(1-3), primates(4) or humans(5) increases parasite virulence, suggesting that vector transmission regulates Plasmodium virulence within the mammalian host. In agreement, disease severity can be modified by vector transmission(6-8), which is assumed to 'reset' Plasmodium to its original character(3). However, direct evidence that vector transmission regulates Plasmodium virulence is lacking. Here we use mosquito transmission of serially blood passaged (SBP) Plasmodium chabaudi chabaudi(9) to interrogate regulation of parasite virulence. Analysis of SBP P.c. chabaudi before and after mosquito transmission demonstrates that vector transmission intrinsically modifies the asexual blood-stage parasite, which in turn modifies the elicited mammalian immune response, which in turn attenuates parasite growth and associated pathology. Attenuated parasite virulence associates with modified expression of the pir multi-gene family. Vector transmission of Plasmodium therefore regulates gene expression of probable variant antigens in the erythrocytic cycle, modifies the elicited mammalian immune response, and thus regulates parasite virulence. These results place the mosquito at the centre of our efforts to dissect mechanisms of protective immunity to malaria for the development of an effective vaccine.
C1 [Spence, Philip J.; Jarra, William; Levy, Prisca; Brugat, Thibaut; Langhorne, Jean] Natl Inst Med Res, MRC, Div Parasitol, London NW7 1AA, England.
   [Reid, Adam J.; Chappell, Lia; Sanders, Mandy; Berriman, Matthew] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England.
C3 MRC National Institute for Medical Research; Wellcome Trust Sanger Institute
RP Langhorne, J (corresponding author), Natl Inst Med Res, MRC, Div Parasitol, Mill Hill, London NW7 1AA, England.
EM jlangho@nimr.mrc.ac.uk
FU Medical Research Council [U117584248]; Wellcome Trust [089553, 098051]; Leverhulme Trust; MRC [MC_U117584248] Funding Source: UKRI; Medical Research Council [MC_U117584248] Funding Source: researchfish
NR 31
TC 122
Z9 135
U1 0
U2 47
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 13
PY 2013
VL 498
IS 7453
BP 228
EP +
DI 10.1038/nature12231
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 162RR
UT WOS:000320283400048
PM 23719378
DA 2026-03-09
ER

PT J
AU Lawrence, MS
   Stojanov, P
   Polak, P
   Kryukov, GV
   Cibulskis, K
   Sivachenko, A
   Carter, SL
   Stewart, C
   Mermel, CH
   Roberts, SA
   Kiezun, A
   Hammerman, PS
   McKenna, A
   Drier, Y
   Zou, LH
   Ramos, AH
   Pugh, TJ
   Stransky, N
   Helman, E
   Kim, J
   Sougnez, C
   Ambrogio, L
   Nickerson, E
   Shefler, E
   Cortés, ML
   Auclair, D
   Saksena, G
   Voet, D
   Noble, M
   DiCara, D
   Lin, P
   Lichtenstein, L
   Heiman, DI
   Fennell, T
   Imielinski, M
   Hernandez, B
   Hodis, E
   Baca, S
   Dulak, AM
   Lohr, J
   Landau, DA
   Wu, CJ
   Melendez-Zajgla, J
   Hidalgo-Miranda, A
   Koren, A
   McCarroll, SA
   Mora, J
   Lee, RS
   Crompton, B
   Onofrio, R
   Parkin, M
   Winckler, W
   Ardlie, K
   Gabriel, SB
   Roberts, CWM
   Biegel, JA
   Stegmaier, K
   Bass, AJ
   Garraway, LA
   Meyerson, M
   Golub, TR
   Gordenin, DA
   Sunyaev, S
   Lander, ES
   Getz, G
AF Lawrence, Michael S.
   Stojanov, Petar
   Polak, Paz
   Kryukov, Gregory V.
   Cibulskis, Kristian
   Sivachenko, Andrey
   Carter, Scott L.
   Stewart, Chip
   Mermel, Craig H.
   Roberts, Steven A.
   Kiezun, Adam
   Hammerman, Peter S.
   McKenna, Aaron
   Drier, Yotam
   Zou, Lihua
   Ramos, Alex H.
   Pugh, Trevor J.
   Stransky, Nicolas
   Helman, Elena
   Kim, Jaegil
   Sougnez, Carrie
   Ambrogio, Lauren
   Nickerson, Elizabeth
   Shefler, Erica
   Cortes, Maria L.
   Auclair, Daniel
   Saksena, Gordon
   Voet, Douglas
   Noble, Michael
   DiCara, Daniel
   Lin, Pei
   Lichtenstein, Lee
   Heiman, David I.
   Fennell, Timothy
   Imielinski, Marcin
   Hernandez, Bryan
   Hodis, Eran
   Baca, Sylvan
   Dulak, Austin M.
   Lohr, Jens
   Landau, Dan-Avi
   Wu, Catherine J.
   Melendez-Zajgla, Jorge
   Hidalgo-Miranda, Alfredo
   Koren, Amnon
   McCarroll, Steven A.
   Mora, Jaume
   Lee, Ryan S.
   Crompton, Brian
   Onofrio, Robert
   Parkin, Melissa
   Winckler, Wendy
   Ardlie, Kristin
   Gabriel, Stacey B.
   Roberts, Charles W. M.
   Biegel, Jaclyn A.
   Stegmaier, Kimberly
   Bass, Adam J.
   Garraway, Levi A.
   Meyerson, Matthew
   Golub, Todd R.
   Gordenin, Dmitry A.
   Sunyaev, Shamil
   Lander, Eric S.
   Getz, Gad
TI Mutational heterogeneity in cancer and the search for new cancer-associated genes
SO NATURE
LA English
DT Article
ID somatic mutations; human-papillomavirus; dna; genome; landscape; patterns; impact
AB Major international projects are underway that are aimed at creating a comprehensive catalogue of all the genes responsible for the initiation and progression of cancer(1-9). These studies involve the sequencing of matched tumour-normal samples followed by mathematical analysis to identify those genes in which mutations occur more frequently than expected by random chance. Here we describe a fundamental problem with cancer genome studies: as the sample size increases, the list of putatively significant genes produced by current analytical methods burgeons into the hundreds. The list includes many implausible genes (such as those encoding olfactory receptors and the muscle protein titin), suggesting extensive false-positive findings that overshadow true driver events. We show that this problem stems largely from mutational heterogeneity and provide a novel analytical methodology, MutSigCV, for resolving the problem. We apply MutSigCV to exome sequences from 3,083 tumour-normal pairs and discover extraordinary variation in mutation frequency and spectrum within cancer types, which sheds light on mutational processes and disease aetiology, and in mutation frequency across the genome, which is strongly correlated with DNA replication timing and also with transcriptional activity. By incorporating mutational heterogeneity into the analyses, MutSigCV is able to eliminate most of the apparent artefactual findings and enable the identification of genes truly associated with cancer.
C1 [Lawrence, Michael S.; Stojanov, Petar; Polak, Paz; Kryukov, Gregory V.; Cibulskis, Kristian; Sivachenko, Andrey; Carter, Scott L.; Stewart, Chip; Mermel, Craig H.; Kiezun, Adam; Hammerman, Peter S.; McKenna, Aaron; Drier, Yotam; Zou, Lihua; Ramos, Alex H.; Pugh, Trevor J.; Stransky, Nicolas; Helman, Elena; Kim, Jaegil; Sougnez, Carrie; Ambrogio, Lauren; Nickerson, Elizabeth; Shefler, Erica; Cortes, Maria L.; Auclair, Daniel; Saksena, Gordon; Voet, Douglas; Noble, Michael; DiCara, Daniel; Lin, Pei; Lichtenstein, Lee; Heiman, David I.; Fennell, Timothy; Imielinski, Marcin; Hernandez, Bryan; Hodis, Eran; Baca, Sylvan; Dulak, Austin M.; Lohr, Jens; Landau, Dan-Avi; Koren, Amnon; McCarroll, Steven A.; Onofrio, Robert; Parkin, Melissa; Winckler, Wendy; Ardlie, Kristin; Gabriel, Stacey B.; Stegmaier, Kimberly; Bass, Adam J.; Garraway, Levi A.; Meyerson, Matthew; Golub, Todd R.; Sunyaev, Shamil; Lander, Eric S.; Getz, Gad] Broad Inst MIT & Harvard, Cambridge, MA 02141 USA.
   [Stojanov, Petar; Hammerman, Peter S.; Pugh, Trevor J.; Hodis, Eran; Baca, Sylvan; Dulak, Austin M.; Lohr, Jens; Landau, Dan-Avi; Wu, Catherine J.; Lee, Ryan S.; Crompton, Brian; Roberts, Charles W. M.; Stegmaier, Kimberly; Bass, Adam J.; Garraway, Levi A.; Meyerson, Matthew; Golub, Todd R.] Dana Farber Canc Inst, Boston, MA 02215 USA.
   [Polak, Paz; Kryukov, Gregory V.; Drier, Yotam; Pugh, Trevor J.; Wu, Catherine J.; Koren, Amnon; McCarroll, Steven A.; Lee, Ryan S.; Roberts, Charles W. M.; Bass, Adam J.; Garraway, Levi A.; Meyerson, Matthew; Golub, Todd R.; Sunyaev, Shamil; Lander, Eric S.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
   [Polak, Paz; Kryukov, Gregory V.; Sunyaev, Shamil] Brigham & Womens Hosp, Boston, MA 02115 USA.
   [Mermel, Craig H.; Drier, Yotam; Imielinski, Marcin; Getz, Gad] Massachusetts Gen Hosp, Boston, MA 02114 USA.
   [Roberts, Steven A.; Gordenin, Dmitry A.] NIEHS, Lab Mol Genet, NIH, DHHS, Res Triangle Pk, NC 27709 USA.
   [McKenna, Aaron] Univ Washington, Seattle, WA 98195 USA.
   [Drier, Yotam; Golub, Todd R.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA.
   [Stransky, Nicolas] Blueprint Med, Cambridge, MA 02142 USA.
   [Helman, Elena; Lander, Eric S.] MIT, Cambridge, MA 02139 USA.
   [Landau, Dan-Avi] Yale Canc Ctr, Dept Hematol, New Haven, CT 06510 USA.
   [Melendez-Zajgla, Jorge; Hidalgo-Miranda, Alfredo] Inst Nacl Med Genom, Mexico City 14610, DF, Mexico.
   [Mora, Jaume] Hosp St Joan de Deu, Dept Pediat Oncol, Barcelona 08950, Spain.
   [Lee, Ryan S.; Crompton, Brian; Roberts, Charles W. M.; Stegmaier, Kimberly] Boston Childrens Hosp, Boston, MA 02115 USA.
   [Biegel, Jaclyn A.] Childrens Hosp, Philadelphia, PA 19104 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; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; National Institutes of Health (NIH) - USA; NIH National Institute of Environmental Health Sciences (NIEHS); University of Washington; University of Washington Seattle; Howard Hughes Medical Institute; Massachusetts Institute of Technology (MIT); Yale University; Yale New Haven Hospital; Instituto Nacional de Medicina Genomica; University of Barcelona; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; University of Pennsylvania; Pennsylvania Medicine; Childrens Hospital of Philadelphia
RP Lander, ES (corresponding author), Broad Inst MIT & Harvard, Cambridge, MA 02141 USA.
EM lander@broadinstitute.org; gadgetz@broadinstitute.org
FU Intramural Research Program of the National Institute of Environmental Health Sciences (National Institutes of Health, United States Department of Health and Human Services) [ES065073]; National Cancer Institute [T32CA009216, T32CA009172] Funding Source: NIH RePORTER; National Institute of General Medical Sciences [T32GM007753] Funding Source: NIH RePORTER
NR 30
TC 4271
Z9 4866
U1 5
U2 486
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 11
PY 2013
VL 499
IS 7457
BP 214
EP 218
DI 10.1038/nature12213
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 179YA
UT WOS:000321557600063
PM 23770567
DA 2026-03-09
ER

PT J
AU Modi, SR
   Lee, HH
   Spina, CS
   Collins, JJ
AF Modi, Sheetal R.
   Lee, Henry H.
   Spina, Catherine S.
   Collins, James J.
TI Antibiotic treatment expands the resistance reservoir and ecological network of the phage metagenome
SO NATURE
LA English
DT Article
ID human gut microbiota; genes; diversity; virus
AB The mammalian gut ecosystem has considerable influence on host physiology(1-4), but the mechanisms that sustain this complex environment in the face of different stresses remain obscure. Perturbations to the gut ecosystem, such as through antibiotic treatment or diet, are at present interpreted at the level of bacterial phylogeny(5-7). Less is known about the contributions of the abundant population of phages to this ecological network. Here we explore the phageome as a potential genetic reservoir for bacterial adaptation by sequencing murine faecal phage populations following antibiotic perturbation. We show that antibiotic treatment leads to the enrichment of phage-encoded genes that confer resistance via disparate mechanisms to the administered drug, as well as genes that confer resistance to antibiotics unrelated to the administered drug, and we demonstrate experimentally that phages from treated mice provide aerobically cultured naive microbiota with increased resistance. Systems-wide analyses uncovered post-treatment phage-encoded processes related to host colonization and growth adaptation, indicating that the phageome becomes broadly enriched for functionally beneficial genes under stress-related conditions. We also show that antibiotic treatment expands the interactions between phage and bacterial species, leading to a more highly connected phage-bacterial network for gene exchange. Our work implicates the phageome in the emergence of multidrug resistance, and indicates that the adaptive capacity of the phageome may represent a community-based mechanism for protecting the gut microflora, preserving its functional robustness during antibiotic stress.
C1 [Modi, Sheetal R.; Lee, Henry H.; Spina, Catherine S.; Collins, James J.] Boston Univ, Dept Biomed Engn, Howard Hughes Med Inst, Boston, MA 02215 USA.
   [Modi, Sheetal R.; Lee, Henry H.; Spina, Catherine S.; Collins, James J.] Boston Univ, Ctr BioDynam, Boston, MA 02215 USA.
   [Spina, Catherine S.; Collins, James J.] Boston Univ, Sch Med, Boston, MA 02118 USA.
   [Spina, Catherine S.; Collins, James J.] Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02118 USA.
C3 Boston University; Howard Hughes Medical Institute; Boston University; Boston University; Harvard University
RP Collins, JJ (corresponding author), Boston Univ, Dept Biomed Engn, Howard Hughes Med Inst, Boston, MA 02215 USA.
EM jcollins@bu.edu
FU Howard Hughes Medical Institute; National Institutes of Health Director's Pioneer Award Program
NR 31
TC 416
Z9 507
U1 7
U2 402
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 11
PY 2013
VL 499
IS 7457
BP 219
EP +
DI 10.1038/nature12212
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 179YA
UT WOS:000321557600064
PM 23748443
DA 2026-03-09
ER

PT J
AU Gkogkas, CG
   Khoutorsky, A
   Ran, I
   Rampakakis, E
   Nevarko, T
   Weatherill, DB
   Vasuta, C
   Yee, S
   Truitt, M
   Dallaire, P
   Major, F
   Lasko, P
   Ruggero, D
   Nader, K
   Lacaille, JC
   Sonenberg, N
AF Gkogkas, Christos G.
   Khoutorsky, Arkady
   Ran, Israeli
   Rampakakis, Emmanouil
   Nevarko, Tatiana
   Weatherill, Daniel B.
   Vasuta, Cristina
   Yee, Stephanie
   Truitt, Morgan
   Dallaire, Paul
   Major, Francois
   Lasko, Paul
   Ruggero, Davide
   Nader, Karim
   Lacaille, Jean-Claude
   Sonenberg, Nahum
TI Autism-related deficits via dysregulated eIF4E-dependent translational control
SO NATURE
LA English
DT Article
ID fragile-x-syndrome; copy-number variation; tuberous-sclerosis; ultrasonic vocalizations; inhibitory synapses; synaptic plasticity; spectrum disorders; learning-deficits; repressor 4e-bp2; mouse models
AB Hyperconnectivity of neuronal circuits due to increased synaptic protein synthesis is thought to cause autism spectrum disorders (ASDs). The mammalian target of rapamycin (mTOR) is strongly implicated in ASDs by means of upstream signalling; however, downstream regulatory mechanisms are ill-defined. Here we show that knockout of the eukaryotic translation initiation factor 4E-binding protein 2 (4E-BP2)-an eIF4E repressor downstream of mTOR-or eIF4E overexpression leads to increased translation of neuroligins, which are postsynaptic proteins that are causally linked to ASDs. Mice that have the gene encoding 4E-BP2 (Eif4ebp2) knocked out exhibit an increased ratio of excitatory to inhibitory synaptic inputs and autistic-like behaviours (that is, social interaction deficits, altered communication and repetitive/stereotyped behaviours). Pharmacological inhibition of eIF4E activity or normalization of neuroligin 1, but not neuroligin 2, protein levels restores the normal excitation/inhibition ratio and rectifies the social behaviour deficits. Thus, translational control by eIF4E regulates the synthesis of neuroligins, maintaining the excitation-to-inhibition balance, and its dysregulation engenders ASD-like phenotypes.
C1 [Gkogkas, Christos G.; Khoutorsky, Arkady; Rampakakis, Emmanouil; Nevarko, Tatiana; Sonenberg, Nahum] McGill Univ, Dept Biochem, Montreal, PQ H3A 1A3, Canada.
   [Gkogkas, Christos G.; Khoutorsky, Arkady; Rampakakis, Emmanouil; Nevarko, Tatiana; Sonenberg, Nahum] McGill Univ, Goodman Canc Res Ctr, Montreal, PQ H3A 1A3, Canada.
   [Ran, Israeli; Weatherill, Daniel B.; Vasuta, Cristina; Lacaille, Jean-Claude] Univ Montreal, GRSNC, Montreal, PQ H3C 3J7, Canada.
   [Ran, Israeli; Weatherill, Daniel B.; Vasuta, Cristina; Lacaille, Jean-Claude] Univ Montreal, Dept Physiol, Montreal, PQ H3C 3J7, Canada.
   [Rampakakis, Emmanouil] JSS Med Res Inc, Montreal, PQ H4S 1N8, Canada.
   [Yee, Stephanie; Lasko, Paul] McGill Univ, Dept Biol, Montreal, PQ H3G 0B1, Canada.
   [Truitt, Morgan; Ruggero, Davide] Univ Calif San Francisco, Sch Med, San Francisco, CA 94158 USA.
   [Truitt, Morgan; Ruggero, Davide] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, Dept Urol, San Francisco, CA 94158 USA.
   [Dallaire, Paul; Major, Francois] Univ Montreal, Dept Comp Sci, Montreal, PQ H3C 3J7, Canada.
   [Dallaire, Paul; Major, Francois] Univ Montreal, Inst Res Immunol & Canc, Montreal, PQ H3C 3J7, Canada.
   [Nader, Karim] McGill Univ, Dept Psychol, Montreal, PQ H3A 1B1, Canada.
C3 McGill University; McGill University; Universite de Montreal; Universite de Montreal; McGill University; 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; Universite de Montreal; Universite de Montreal; McGill University
RP Sonenberg, N (corresponding author), McGill Univ, Dept Biochem, Montreal, PQ H3A 1A3, Canada.
EM jean-claude.lacaille@umontreal.ca; nahum.sonenberg@mcgill.ca
FU Canadian Institutes of Health Research [MOP-114994, MOP-10848, MOP-93679, MOP-44050]; Autism Speaks [7109]; Fonds de la Recherche en Sante du Quebec (FRSQ; Groupe de Recherche sur le Systeme Nerveux Central); National Institutes of Health [NIH RO1 CA154916, NIH RO1 CA140456]; Canada Research Chair in Cellular and Molecular Neurophysiology; Savoy Foundation
NR 46
TC 427
Z9 515
U1 3
U2 123
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 17
PY 2013
VL 493
IS 7432
BP 371
EP U113
DI 10.1038/nature11628
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 071TA
UT WOS:000313615900044
PM 23172145
DA 2026-03-09
ER

PT J
AU Rechtsman, MC
   Zeuner, JM
   Plotnik, Y
   Lumer, Y
   Podolsky, D
   Dreisow, F
   Nolte, S
   Segev, M
   Szameit, A
AF Rechtsman, Mikael C.
   Zeuner, Julia M.
   Plotnik, Yonatan
   Lumer, Yaakov
   Podolsky, Daniel
   Dreisow, Felix
   Nolte, Stefan
   Segev, Mordechai
   Szameit, Alexander
TI Photonic Floquet topological insulators
SO NATURE
LA English
DT Article
ID states; phase
AB Topological insulators are a new phase of matter(1), with the striking property that conduction of electrons occurs only on their surfaces(1-3). In two dimensions, electrons on the surface of a topological insulator are not scattered despite defects and disorder, providing robustness akin to that of superconductors. Topological insulators are predicted to have wide-ranging applications in fault-tolerant quantum computing and spintronics. Substantial effort has been directed towards realizing topological insulators for electromagnetic waves(4-13). One-dimensional systems with topological edge states have been demonstrated, but these states are zero-dimensional and therefore exhibit no transport properties(11,12,14). Topological protection of microwaves has been observed using a mechanism similar to the quantum Hall effect(15), by placing a gyromagnetic photonic crystal in an external magnetic field(5). But because magnetic effects are very weak at optical frequencies, realizing photonic topological insulators with scatter-free edge states requires a fundamentally different mechanism-one that is free of magnetic fields. A number of proposals for photonic topological transport have been put forward recently(6-10). One suggested temporal modulation of a photonic crystal, thus breaking time-reversal symmetry and inducing one-way edge states(10). This is in the spirit of the proposed Floquet topological insulators(16-19), in which temporal variations in solid-state systems induce topological edge states. Here we propose and experimentally demonstrate a photonic topological insulator free of external fields and with scatter-free edge transport-a photonic lattice exhibiting topologically protected transport of visible light on the lattice edges. Our system is composed of an array of evanescently coupled helical waveguides(20) arranged in a graphene-like honeycomblattice(21-26). Paraxial diffraction of light is described by a Schrodinger equation where the propagation coordinate (z) acts as 'time'(27). Thus the helicity of the waveguides breaks z-reversal symmetry as proposed for Floquet topological insulators. This structure results in one-way edge states that are topologically protected from scattering.
C1 [Rechtsman, Mikael C.; Plotnik, Yonatan; Lumer, Yaakov; Podolsky, Daniel; Segev, Mordechai] Technion Israel Inst Technol, Dept Phys, IL-32000 Haifa, Israel.
   [Rechtsman, Mikael C.; Plotnik, Yonatan; Lumer, Yaakov; Podolsky, Daniel; Segev, Mordechai] Technion Israel Inst Technol, Inst Solid State, IL-32000 Haifa, Israel.
   [Zeuner, Julia M.; Dreisow, Felix; Nolte, Stefan; Szameit, Alexander] Univ Jena, Abbe Ctr Photon, Inst Appl Phys, D-07743 Jena, Germany.
C3 Technion Israel Institute of Technology; Technion Israel Institute of Technology; Friedrich Schiller University of Jena
RP Rechtsman, MC (corresponding author), Technion Israel Inst Technol, Dept Phys, IL-32000 Haifa, Israel.
EM mcrworld@gmail.com; yonatanplotnik@gmail.com
FU Azrieli Foundation; Israel Science Foundation; USA-Israel Binational Science Foundation; European Research Council; German Ministry of Education and Research (Center for Innovation Competence program) [03Z1HN31]; Thuringian Ministry for Education, Science and Culture (Research group Spacetime) [11027-514]
NR 30
TC 2774
Z9 3069
U1 29
U2 1245
PU NATURE PUBLISHING 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 11
PY 2013
VL 496
IS 7444
BP 196
EP 200
DI 10.1038/nature12066
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 122VM
UT WOS:000317346300036
PM 23579677
DA 2026-03-09
ER

PT J
AU Lukens, JM
   Leaird, DE
   Weiner, AM
AF Lukens, Joseph M.
   Leaird, Daniel E.
   Weiner, Andrew M.
TI A temporal cloak at telecommunication data rate
SO NATURE
LA English
DT Article
ID principles; optics; light
AB Through advances in metamaterials-artificially engineered media with exotic properties, including negative refractive index(1-3)-the once fanciful invisibility cloak has now assumed a prominent place in scientific research(4-13). By extending these concepts to the temporal domain(14), investigators have recently described a cloak which hides events in time by creating a temporal gap in a probe beam that is subsequently closed up; any interaction which takes place during this hole in time is not detected(15). However, these results are limited to isolated events that fill a tiny portion of the temporal period, giving a fractional cloaking window of only about 10(-4) per cent at a repetition rate of 41 kilohertz (ref. 15)-which is much too low for applications such as optical communications. Here we demonstrate another technique for temporal cloaking, which operates at telecommunication data rates and, by exploiting temporal self-imaging through the Talbot effect, hides optical data from a receiver. We succeed in cloaking 46 per cent of the entire time axis and conceal pseudorandom digital data at a rate of 12.7 gigabits per second. This potential to cloak real-world messages introduces temporal cloaking into the sphere of practical application, with immediate ramifications in secure communications.
C1 [Lukens, Joseph M.; Leaird, Daniel E.; Weiner, Andrew M.] Purdue Univ, Sch Elect & Comp Engn, W Lafayette, IN 47907 USA.
C3 Purdue University System; Purdue University
RP Weiner, AM (corresponding author), Purdue Univ, Sch Elect & Comp Engn, W Lafayette, IN 47907 USA.
EM amw@purdue.edu
FU National Science Foundation [ECCS-1102110]; Naval Postgraduate School under the National Security Science and Engineering Faculty Fellowship programme [N00244-09-1-0068]; Department of Defense through a National Defense Science and Engineering Graduate Fellowship; Div Of Electrical, Commun & Cyber Sys; Directorate For Engineering [1102110] Funding Source: National Science Foundation
NR 30
TC 105
Z9 122
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 JUN 13
PY 2013
VL 498
IS 7453
BP 205
EP 208
DI 10.1038/nature12224
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 162RR
UT WOS:000320283400042
PM 23739327
DA 2026-03-09
ER

PT J
AU Bouchard, KE
   Mesgarani, N
   Johnson, K
   Chang, EF
AF Bouchard, Kristofer E.
   Mesgarani, Nima
   Johnson, Keith
   Chang, Edward F.
TI Functional organization of human sensorimotor cortex for speech articulation
SO NATURE
LA English
DT Article
ID human motor cortex; larynx area; representation; dynamics; vocalization; generation; movement
AB Speaking is one of the most complex actions that we perform, but nearly all of us learn to do it effortlessly. Production of fluent speech requires the precise, coordinated movement of multiple articulators (for example, the lips, jaw, tongue and larynx) over rapid time scales. Here we used high-resolution, multi-electrode cortical recordings during the production of consonant-vowel syllables to determine the organization of speech sensorimotor cortex in humans. We found speech-articulator representations that are arranged somatotopically on ventral pre- and post-central gyri, and that partially overlap at individual electrodes. These representations were coordinated temporally as sequences during syllable production. Spatial patterns of cortical activity showed an emergent, population-level representation, which was organized by phonetic features. Over tens of milliseconds, the spatial patterns transitioned between distinct representations for different consonants and vowels. These results reveal the dynamic organization of speech sensorimotor cortex during the generation of multi-articulator movements that underlies our ability to speak.
C1 [Bouchard, Kristofer E.; Mesgarani, Nima; Chang, Edward F.] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 94143 USA.
   [Bouchard, Kristofer E.; Mesgarani, Nima; Chang, Edward F.] Univ Calif San Francisco, Dept Physiol, San Francisco, CA 94143 USA.
   [Bouchard, Kristofer E.; Mesgarani, Nima; Chang, Edward F.] Univ Calif San Francisco, Ctr Integrat Neurosci, San Francisco, CA 94158 USA.
   [Johnson, Keith] Univ Calif Berkeley, Dept Linguist, Berkeley, CA 94720 USA.
   [Chang, Edward F.] Univ Calif San Francisco, UCSF Epilepsy Ctr, 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 Berkeley; University of California System; University of California San Francisco
RP Chang, EF (corresponding author), Univ Calif San Francisco, Dept Neurol Surg, 505 Parnassus Ave, San Francisco, CA 94143 USA.
EM ChangEd@neurosurg.ucsf.edu
FU US 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 47
TC 453
Z9 538
U1 2
U2 110
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 21
PY 2013
VL 495
IS 7441
BP 327
EP 332
DI 10.1038/nature11911
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 113EY
UT WOS:000316650500034
PM 23426266
DA 2026-03-09
ER

PT J
AU Abe-Ouchi, A
   Saito, F
   Kawamura, K
   Raymo, ME
   Okuno, J
   Takahashi, K
   Blatter, H
AF Abe-Ouchi, Ayako
   Saito, Fuyuki
   Kawamura, Kenji
   Raymo, Maureen E.
   Okuno, Jun'ichi
   Takahashi, Kunio
   Blatter, Heinz
TI Insolation-driven 100,000-year glacial cycles and hysteresis of ice-sheet volume
SO NATURE
LA English
DT Article
ID carbon-dioxide; climate; model; system; simulations; temperature; growth; phase
AB The growth and reduction of Northern Hemisphere ice sheets over the past million years is dominated by an approximately 100,000-year periodicity and a sawtooth pattern(1,2) (gradual growth and fast termination). Milankovitch theory proposes that summer insolation at high northern latitudes drives the glacial cycles(3), and statistical tests have demonstrated that the glacial cycles are indeed linked to eccentricity, obliquity and precession cycles(4,5). Yet insolation alone cannot explain the strong 100,000-year cycle, suggesting that internal climatic feedbacks may also be at work(4-7). Earlier conceptual models, for example, showed that glacial terminations are associated with the build-up of Northern Hemisphere 'excess ice'(5,8-10), but the physical mechanisms underpinning the 100,000-year cycle remain unclear. Here we show, using comprehensive climate and ice-sheet models, that insolation and internal feedbacks between the climate, the ice sheets and the lithosphere-asthenosphere system explain the 100,000-year periodicity. The responses of equilibrium states of ice sheets to summer insolation show hysteresis(11-13), with the shape and position of the hysteresis loop playing a key part in determining the periodicities of glacial cycles. The hysteresis loop of the North American ice sheet is such that after inception of the ice sheet, its mass balance remains mostly positive through several precession cycles, whose amplitudes decrease towards an eccentricity minimum. The larger the ice sheet grows and extends towards lower latitudes, the smaller is the insolation required to make the mass balance negative. Therefore, once a large ice sheet is established, a moderate increase in insolation is sufficient to trigger a negative mass balance, leading to an almost complete retreat of the ice sheet within several thousand years. This fast retreat is governed mainly by rapid ablation due to the lowered surface elevation resulting from delayed isostatic rebound(14-16), which is the lithosphere-asthenosphere response. Carbon dioxide is involved, but is not determinative, in the evolution of the 100,000-year glacial cycles.
C1 [Abe-Ouchi, Ayako; Okuno, Jun'ichi; Blatter, Heinz] Univ Tokyo, Atmosphere & Ocean Res Inst, Kashiwa, Chiba 2778568, Japan.
   [Abe-Ouchi, Ayako; Saito, Fuyuki; Okuno, Jun'ichi; Takahashi, Kunio] Japan Agcy Marine Earth Sci & Technol, Res Inst Global Change, Yokohama, Kanagawa 2360001, Japan.
   [Abe-Ouchi, Ayako; Kawamura, Kenji; Okuno, Jun'ichi] Natl Inst Polar Res, Tachikawa, Tokyo 1908518, Japan.
   [Kawamura, Kenji] Japan Agcy Marine Earth Sci & Technol, Inst Biogeosci, Yokosuka, Kanagawa 2370061, Japan.
   [Raymo, Maureen E.] Columbia Univ, Lamont Doherty Earth Observ, Palisades, NY 10964 USA.
   [Blatter, Heinz] ETH, Inst Atmospher & Climate Sci, CH-8092 Zurich, Switzerland.
C3 University of Tokyo; Japan Agency for Marine-Earth Science & Technology (JAMSTEC); Research Organization of Information & Systems (ROIS); National Institute of Polar Research (NIPR) - Japan; Japan Agency for Marine-Earth Science & Technology (JAMSTEC); Columbia University; Swiss Federal Institutes of Technology Domain; ETH Zurich
RP Abe-Ouchi, A (corresponding author), Univ Tokyo, Atmosphere & Ocean Res Inst, Kashiwa, Chiba 2778568, Japan.
EM abeouchi@aori.u-tokyo.ac.jp
FU JSPS KAKENHI [25241005, 22101005, 21671001]; MEXT, Japan; Ministry of the Environment, Japan [S-10]; Grants-in-Aid for Scientific Research [22101005, 25241005, 22221002, 22101001, 23501255, 21671001] Funding Source: KAKEN
CR Abe-Ouchi A, 2007, CLIM PAST, V3, P423, DOI 10.5194/cp-3-423-2007
   ABE-OUCHI A, 1993, ANN GLACIOL-SER, V18, P203, DOI 10.1017/S0260305500011514
   Berger A, 1998, CLIM DYNAM, V14, P615, DOI 10.1007/s003820050245
   BERGER AL, 1978, J ATMOS SCI, V35, P2362, DOI 10.1016/0033-5894(78)90064-9
   Braconnot P, 2012, NAT CLIM CHANGE, V2, P417, DOI 10.1038/NCLIMATE1456
   Calov R, 2005, GEOPHYS RES LETT, V32, P0, DOI 10.1029/2005GL024518
   Calov R, 2002, GEOPHYS RES LETT, V29, P0, DOI 10.1029/2002GL016078
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NR 42
TC 330
Z9 384
U1 7
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 8
PY 2013
VL 500
IS 7461
BP 190
EP +
DI 10.1038/nature12374
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 197CH
UT WOS:000322825500031
PM 23925242
DA 2026-03-09
ER

PT J
AU Pijnappel, WWMP
   Esch, D
   Baltissen, MPA
   Wu, GM
   Mischerikow, N
   Bergsma, AJ
   van der Wal, E
   Han, DW
   vom Bruch, H
   Moritz, S
   Lijnzaad, P
   Altelaar, AFM
   Sameith, K
   Zaehres, H
   Heck, AJR
   Holstege, FCP
   Schöler, HR
   Timmers, HTM
AF Pijnappel, W. W. M. Pim
   Esch, Daniel
   Baltissen, Marijke P. A.
   Wu, Guangming
   Mischerikow, Nikolai
   Bergsma, Atze J.
   van der Wal, Erik
   Han, Dong Wook
   vom Bruch, Hermann
   Moritz, Soeren
   Lijnzaad, Phillip
   Altelaar, A. F. Maarten
   Sameith, Katrin
   Zaehres, Holm
   Heck, Albert J. R.
   Holstege, Frank C. P.
   Schoeler, Hans R.
   Timmers, H. T. Marc
TI A central role for TFIID in the pluripotent transcription circuitry
SO NATURE
LA English
DT Article
ID stem-cells; network; mechanisms; survival; genes
AB Embryonic stem (ES) cells are pluripotent and characterized by open chromatin and high transcription levels, achieved through auto-regulatory and feed-forward transcription factor loops(1,2). ES-cell identity is maintained by a core of factors including Oct4 (also known as Pou5f1), Sox2, Klf4, c-Myc (OSKM) and Nanog(2-4), and forced expression of the OSKM factors can reprogram somatic cells into induced pluripotent stem cells (iPSCs) resembling ES cells(5,6). These gene-specific factors for RNA-polymerase-II-mediated transcription recruit transcriptional cofactors and chromatin regulators that control access to and activity of the basal transcription machinery on gene promoters(7,8). How the basal transcription machinery is involved in setting and maintaining the pluripotent state is unclear. Here we show that knockdown of the transcription factor IID (TFIID) complex affects the pluripotent circuitry in mouse ES cells and inhibits reprogramming of fibroblasts. TFIID subunits and the OSKM factors forma feed-forward loop to induce and maintain a stable transcription state. Notably, transient expression of TFIID subunits greatly enhanced reprogramming. These results show that TFIID is critical for transcription-factor-mediated reprogramming. We anticipate that, by creating plasticity in gene expression programs, transcription complexes such as TFIID assist reprogramming into different cellular states.
C1 [Pijnappel, W. W. M. Pim; Baltissen, Marijke P. A.; Bergsma, Atze J.; Lijnzaad, Phillip; Sameith, Katrin; Holstege, Frank C. P.; Timmers, H. T. Marc] Univ Med Ctr Utrecht, Mol Canc Res, NL-3584 CG Utrecht, Netherlands.
   [Pijnappel, W. W. M. Pim; Baltissen, Marijke P. A.; Mischerikow, Nikolai; Altelaar, A. F. Maarten; Heck, Albert J. R.; Timmers, H. T. Marc] Netherlands Prote Ctr, NL-3584 CH Utrecht, Netherlands.
   [Pijnappel, W. W. M. Pim; van der Wal, Erik] Erasmus MC, Dept Pediat, NL-3015 GE Rotterdam, Netherlands.
   [Pijnappel, W. W. M. Pim; van der Wal, Erik] Erasmus MC, Dept Clin Genet, NL-3015 GE Rotterdam, Netherlands.
   [Esch, Daniel; Wu, Guangming; van der Wal, Erik; Han, Dong Wook; vom Bruch, Hermann; Moritz, Soeren; Zaehres, Holm; Schoeler, Hans R.] Max Planck Inst Mol Biomed, D-48149 Munster, Germany.
   [Mischerikow, Nikolai; Altelaar, A. F. Maarten; Heck, Albert J. R.] Univ Utrecht, Bijvoet Ctr Biomol Res, NL-3584 CH Utrecht, Netherlands.
   [Mischerikow, Nikolai; Altelaar, A. F. Maarten; Heck, Albert J. R.] Univ Utrecht, Utrecht Inst Pharmaceut Sci, NL-3584 CH Utrecht, Netherlands.
C3 Utrecht University; Utrecht University Medical Center; Erasmus University Rotterdam; Erasmus MC; Erasmus University Rotterdam; Erasmus MC; Max Planck Society; Utrecht University; Utrecht University
RP Timmers, HTM (corresponding author), Univ Med Ctr Utrecht, Mol Canc Res, NL-3584 CG Utrecht, Netherlands.
EM h.t.m.timmers@umcutrecht.nl
FU Netherlands Proteomics Centre, Netherlands Organization for Scientific Research [700.57.302]; Deutsche Forschungsgemeinschaft (DFG) [SPP 1356/2]; European Union [EUTRACC LSHG-CT-2006-037445]
NR 29
TC 69
Z9 80
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 MAR 28
PY 2013
VL 495
IS 7442
BP 516
EP 519
DI 10.1038/nature11970
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 113QN
UT WOS:000316682800047
PM 23503660
DA 2026-03-09
ER

PT J
AU Shimozono, S
   Iimura, T
   Kitaguchi, T
   Higashijima, S
   Miyawaki, A
AF Shimozono, Satoshi
   Iimura, Tadahiro
   Kitaguchi, Tetsuya
   Higashijima, Shin-ichi
   Miyawaki, Atsushi
TI Visualization of an endogenous retinoic acid gradient across embryonic development
SO NATURE
LA English
DT Article
ID binding proteins; hindbrain development; morphogen gradient; gene-expression; distinct roles; zebrafish; boundary; fgf8; pattern; differentiation
AB In vertebrate development, the body plan is determined by primordial morphogen gradients that suffuse the embryo. Retinoic acid (RA) is an important morphogen involved in patterning the anterior-posterior axis of structures, including the hindbrain(1-6) and paraxial mesoderm(7,8). RA diffuses over long distances, and its activity is spatially restricted by synthesizing and degrading enzymes(9). However, gradients of endogenous morphogens in live embryos have not been directly observed; indeed, their existence, distribution and requirement for correct patterning remain controversial(10). Here we report a family of genetically encoded indicators for RA that we have termed GEPRAs (genetically encoded probes for RA). Using the principle of fluorescence resonance energy transfer we engineered the ligand-binding domains of RA receptors to incorporate cyan-emitting and yellow-emitting fluorescent proteins as fluorescence resonance energy transfer donor and acceptor, respectively, for the reliable detection of ambient free RA. We created three GEPRAs with different affinities for RA, enabling the quantitative measurement of physiological RA concentrations. Live imaging of zebrafish embryos at the gastrula and somitogenesis stages revealed a linear concentration gradient of endogenous RA in a two-tailed source-sink arrangement across the embryo. Modelling of the observed linear RA gradient suggests that the rate of RA diffusion exceeds the spatiotemporal dynamics of embryogenesis, resulting in stability to perturbation. Furthermore, we used GEPRAs in combination with genetic and pharmacological perturbations to resolve competing hypotheses on the structure of the RA gradient during hindbrain formation and somitogenesis. Live imaging of endogenous concentration gradients across embryonic development will allow the precise assignment of molecular mechanisms to developmental dynamics and will accelerate the application of approaches based on morphogen gradients to tissue engineering and regenerative medicine.
C1 [Shimozono, Satoshi; Iimura, Tadahiro; Miyawaki, Atsushi] RIKEN, Brain Sci Inst, Lab Cell Funct Dynam, Wako, Saitama 3510198, Japan.
   [Kitaguchi, Tetsuya; Miyawaki, Atsushi] JST, ERATO, Life Funct & Dynam, Wako, Saitama 3510198, Japan.
   [Higashijima, Shin-ichi] Natl Inst Nat Sci, Okazaki Inst Integrat Biosci, Natl Inst Physiol Sci, Okazaki, Aichi 4448787, Japan.
C3 RIKEN; Japan Science & Technology Agency (JST); National Institutes of Natural Sciences (NINS) - Japan; National Institute for Physiological Sciences (NIPS); Okazaki Institute for Integrative Bioscience (OIIB)
RP Miyawaki, A (corresponding author), RIKEN, Brain Sci Inst, Lab Cell Funct Dynam, 2-1 Hirosawa, Wako, Saitama 3510198, Japan.
EM matsushi@brain.riken.jp
FU Japan Ministry of Education, Culture, Sports, Science and Technology; Human Frontier Science Program; Grants-in-Aid for Scientific Research [23390417, 22113003] Funding Source: KAKEN
NR 37
TC 164
Z9 200
U1 0
U2 162
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 18
PY 2013
VL 496
IS 7445
BP 363
EP +
DI 10.1038/nature12037
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 126FV
UT WOS:000317599200038
PM 23563268
DA 2026-03-09
ER

PT J
AU Bricard, A
   Caussin, JB
   Desreumaux, N
   Dauchot, O
   Bartolo, D
AF Bricard, Antoine
   Caussin, Jean-Baptiste
   Desreumaux, Nicolas
   Dauchot, Olivier
   Bartolo, Denis
TI Emergence of macroscopic directed motion in populations of motile colloids
SO NATURE
LA English
DT Article
ID density-fluctuations; collective motion; active matter; hydrodynamics
AB From the formation of animal flocks to the emergence of coordinated motion in bacterial swarms, populations of motile organisms at all scales display coherent collective motion. This consistent behaviour strongly contrasts with the difference in communication abilities between the individuals. On the basis of this universal feature, it has been proposed that alignment rules at the individual level could solely account for the emergence of unidirectional motion at the group level(1-4). This hypothesis has been supported by agent-based simulations(1,5,6). However, more complex collective behaviours have been systematically found in experiments, including the formation of vortices(7-9), fluctuating swarms(7,10), clustering(11,12) and swirling(13-16). All these (living and man-made) model systems (bacteria(9,10,16), biofilaments and molecular motors(7,8,13), shaken grains(14,15) and reactive colloids(11,12)) predominantly rely on actual collisions to generate collective motion. As a result, the potential local alignment rules are entangled with more complex, and often unknown, interactions. The large-scale behaviour of the populations therefore strongly depends on these uncontrolled microscopic couplings, which are extremely challenging to measure and describe theoretically. Here we report that dilute populations of millions of colloidal rolling particles self-organize to achieve coherentmotion in a unique direction, with very few density and velocity fluctuations. Quantitatively identifying the microscopic interactions between the rollers allows a theoretical description of this polar-liquid state. Comparison of the theory with experiment suggests that hydrodynamic interactions promote the emergence of collective motion either in the form of a single macroscopic 'flock', at low densities, or in that of a homogenous polar phase, at higher densities. Furthermore, hydrodynamics protects the polar-liquid state from the giant density fluctuations that were hitherto considered the hallmark of populations of self-propelled particles(2,3,17). Our experiments demonstrate that genuine physical interactions at the individual level are sufficient to set homogeneous active populations into stable directed motion.
C1 [Bricard, Antoine; Caussin, Jean-Baptiste; Desreumaux, Nicolas; Bartolo, Denis] Univ Paris Diderot, ESPCI ParisTech, CNRS UMR7636, PMMH, F-75005 Paris, France.
   [Bricard, Antoine; Caussin, Jean-Baptiste; Desreumaux, Nicolas; Bartolo, Denis] Univ Paris 06, F-75005 Paris, France.
   [Caussin, Jean-Baptiste; Bartolo, Denis] Ecole Normale Super Lyon, Phys Lab, CNRS UMR5672, F-69007 Lyon, France.
   [Dauchot, Olivier] ESPCI ParisTech, EC2M, CNRS Gulliver UMR7083, F-75005 Paris, France.
C3 Sorbonne Universite; Universite Paris Cite; Centre National de la Recherche Scientifique (CNRS); CNRS - Institute for Engineering & Systems Sciences (INSIS); Universite PSL; Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI); Sorbonne Universite; Centre National de la Recherche Scientifique (CNRS); CNRS - Institute of Physics (INP); Ecole Normale Superieure de Lyon (ENS de LYON); Centre National de la Recherche Scientifique (CNRS); CNRS - Institute of Chemistry (INC); Universite PSL; Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI)
RP Bartolo, D (corresponding author), Univ Paris Diderot, ESPCI ParisTech, CNRS UMR7636, PMMH, 10 Rue Vauquelin, F-75005 Paris, France.
EM denis.bartolo@ens-lyon.fr
FU Paris Emergence programme; C'Nano IdF; Institut Universitaire de France
NR 27
TC 848
Z9 965
U1 3
U2 377
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 7
PY 2013
VL 503
IS 7474
BP 95
EP 98
DI 10.1038/nature12673
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 247AS
UT WOS:000326585600038
PM 24201282
DA 2026-03-09
ER

PT J
AU Steffen, L
   Salathe, Y
   Oppliger, M
   Kurpiers, P
   Baur, M
   Lang, C
   Eichler, C
   Puebla-Hellmann, G
   Fedorov, A
   Wallraff, A
AF Steffen, L.
   Salathe, Y.
   Oppliger, M.
   Kurpiers, P.
   Baur, M.
   Lang, C.
   Eichler, C.
   Puebla-Hellmann, G.
   Fedorov, A.
   Wallraff, A.
TI Deterministic quantum teleportation with feed-forward in a solid state system
SO NATURE
LA English
DT Article
ID entanglement; computation; information; qubits
AB Engineered macroscopic quantum systems based on superconducting electronic circuits are attractive for experimentally exploring diverse questions in quantum information science(1-3). At the current state of the art, quantum bits (qubits) are fabricated, initialized, controlled, read out and coupled to each other in simple circuits. This enables the realization of basic logic gates(4), the creation of complex entangled states(5,6) and the demonstration of algorithms(7) or error correction(8). Using different variants of low-noise parametric amplifiers(9), dispersive quantum non-demolition single-shot readout of single-qubit states with high fidelity has enabled continuous(10) and discrete(11) feedback control of single qubits. Here we realize full deterministic quantum teleportation with feed-forward in a chip-based superconducting circuit architecture(12-14). We use a set of two parametric amplifiers for both joint two-qubit and individual qubit single-shot readout, combined with flexible real-time digital electronics. Our device uses a crossed quantum bus technology that allows us to create complex networks with arbitrary connecting topology in a planar architecture. The deterministic teleportation process succeeds with order unit probability for any input state, as we prepare maximally entangled two-qubit states as a resource and distinguish all Bell states in a single two-qubit measurement with high efficiency and high fidelity. We teleport quantum states between two macroscopic systems separated by 6 mm at a rate of 10(4) s(-1), exceeding other reported implementations. The low transmission loss of superconducting waveguides is likely to enable the range of this and other schemes to be extended to significantly larger distances, enabling tests of non-locality and the realization of elements for quantum communication at microwave frequencies. The demonstrated feed-forward may also find application in error correction schemes.
C1 [Steffen, L.; Salathe, Y.; Oppliger, M.; Kurpiers, P.; Baur, M.; Lang, C.; Eichler, C.; Puebla-Hellmann, G.; Fedorov, A.; Wallraff, A.] ETH, Dept Phys, CH-8093 Zurich, Switzerland.
C3 Swiss Federal Institutes of Technology Domain; ETH Zurich
RP Steffen, L (corresponding author), ETH, Dept Phys, CH-8093 Zurich, Switzerland.
EM lsteffen@phys.ethz.ch; andreas.wallraff@phys.ethz.ch
FU Eidgenossische Technische Hochschule Zurich (ETH Zurich); EU Integrated Project SOLID; EU Integrated Project SCALEQIT; Swiss National Science Foundation's National Centre of Competence in Research 'Quantum Science Technology'
NR 46
TC 225
Z9 253
U1 1
U2 92
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 15
PY 2013
VL 500
IS 7462
BP 319
EP +
DI 10.1038/nature12422
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 201AF
UT WOS:000323112400029
PM 23955231
DA 2026-03-09
ER

PT J
AU Gröschel, AH
   Walther, A
   Löbling, TI
   Schacher, FH
   Schmalz, H
   Müller, AHE
AF Groeschel, Andre H.
   Walther, Andreas
   Loebling, Tina I.
   Schacher, Felix H.
   Schmalz, Holger
   Mueller, Axel H. E.
TI Guided hierarchical co-assembly of soft patchy nanoparticles
SO NATURE
LA English
DT Article
ID multicompartment micelles; block; janus; copolymers; architectures; objects; complex; length
AB The concept of hierarchical bottom-up structuring commonly encountered in naturalmaterials provides inspiration for the design of complex artificial materials with advanced functionalities(1,2). Natural processes have achieved the orchestration of multicomponent systems across many length scales with very high precision(3,4), but man-made self-assemblies still face obstacles in realizing well-defined hierarchical structures(5-11). In particle-based self-assembly, the challenge is to program symmetries and periodicities of superstructures by providing monodisperse building blocks with suitable shape anisotropy or anisotropic interaction patterns ('patches'). Irregularities in particle architecture are intolerable because they generate defects that amplify throughout the hierarchical levels. For patchy microscopic hard colloids, this challenge has been approached by using top-down methods (such as metal shading or microcontact printing), enabling molecule-like directionality during aggregation(12-16). However, both top-down procedures and particulate systems based on molecular assembly struggle to fabricate patchy particles controllably in the desired size regime (10-100 nm). Here we introduce the co-assembly of dynamic patchy nanoparticles-that is, soft patchy nanoparticles that are intrinsically self-assembled and monodisperse-as a modular approach for producing well-ordered binary and ternary supracolloidal hierarchical assemblies. We bridge up to three hierarchical levels by guiding triblock terpolymers (length scale 10 nm) to form soft patchy nanoparticles (20-50 nm) of different symmetries that, in combination, co-assemble into substructured, compartmentalized materials (>10 mu m) with predictable and tunable nanoscale periodicities. We establish how molecular control over polymer composition programs the building block symmetries and regulates particle positioning, offering a route to well-ordered mixed mesostructures of high complexity.
C1 [Groeschel, Andre H.; Loebling, Tina I.; Schmalz, Holger; Mueller, Axel H. E.] Univ Bayreuth, D-95440 Bayreuth, Germany.
   [Walther, Andreas] Rhein Westfal TH Aachen, DWI, Inst Interact Mat Res, D-52056 Aachen, Germany.
   [Schacher, Felix H.] Univ Jena, Inst Organ Chem & Makromol Chem, D-07743 Jena, Germany.
   [Schacher, Felix H.] Univ Jena, Jena Ctr Soft Matter, D-07743 Jena, Germany.
C3 University of Bayreuth; RWTH Aachen University; Friedrich Schiller University of Jena; Friedrich Schiller University of Jena
RP Müller, AHE (corresponding author), Johannes Gutenberg Univ Mainz, Inst Organ Chem, D-55099 Mainz, Germany.
EM andre.groschel@aalto.fi; axel.mueller@uni-mainz.de
FU Deutsche Forschungsgemeinschaft [Sonderforschungsbereich 840]
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NR 36
TC 570
Z9 633
U1 11
U2 1193
PU NATURE PUBLISHING 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 14
PY 2013
VL 503
IS 7475
BP 247
EP +
DI 10.1038/nature12610
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 250YX
UT WOS:000326894200048
PM 24185010
DA 2026-03-09
ER

PT J
AU Waight, AB
   Pedersen, BP
   Schlessinger, A
   Bonomi, M
   Chau, BH
   Roe-Zurz, Z
   Risenmay, AJ
   Sali, A
   Stroud, RM
AF Waight, Andrew B.
   Pedersen, Bjorn Panyella
   Schlessinger, Avner
   Bonomi, Massimiliano
   Chau, Bryant H.
   Roe-Zurz, Zygy
   Risenmay, Aaron J.
   Sali, Andrej
   Stroud, Robert M.
TI Structural basis for alternating access of a eukaryotic calcium/proton exchanger
SO NATURE
LA English
DT Article
ID cation/h+ exchanger; molecular-dynamics; membrane-proteins; internal repeats; vacuolar; ca2+; identification; transport; residues; yeast
AB Eukaryotic Ca2+ regulation involves sequestration into intracellular organelles, and expeditious Ca2+ release into the cytosol is a hallmark of key signalling transduction pathways. Bulk removal of Ca2+ after such signalling events is accomplished by members of the Ca2+: cation (CaCA) superfamily(1-5). The CaCA superfamily includes the Na+/Ca2+ (NCX) and Ca2+/H+ (CAX) antiporters, and in mammals the NCX and related proteins constitute families SLC8 and SLC24, and are responsible for the re-establishment of Ca2+ resting potential in muscle cells, neuronal signalling and Ca2+ reabsorption in the kidney(1,6). The CAX family members maintain cytosolic Ca2+ homeostasis in plants and fungi during steep rises in intracellular Ca2+ due to environmental changes, or following signal transduction caused by events such as hyperosmotic shock, hormone response and response to mating pheromones(7-13). The cytosol-facing conformations within the CaCA superfamily are unknown, and the transport mechanism remains speculative. Here we determine a crystal structure of the Saccharomyces cerevisiae vacuolar Ca2+/H+ exchanger (Vcx1) at 2.3 angstrom resolution in a cytosol-facing, substrate-bound conformation. Vcx1 is the first structure, to our knowledge, within the CAX family, and it describes the key cytosol-facing conformation of the CaCA superfamily, providing the structural basis for a novel alternating access mechanism by which the CaCA superfamily performs high-throughput Ca2+ transport across membranes.
C1 [Waight, Andrew B.; Pedersen, Bjorn Panyella; Chau, Bryant H.; Roe-Zurz, Zygy; Risenmay, Aaron J.; Stroud, Robert M.] Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94158 USA.
   [Schlessinger, Avner; Bonomi, Massimiliano; Sali, Andrej] Univ Calif San Francisco, Dept Bioengn & Therapeut Sci, Dept Pharmaceut Chem, Calif Inst Quantitat Biosci, San Francisco, CA 94158 USA.
C3 University of California System; University of California San Francisco; University of California System; University of California San Francisco
RP Stroud, RM (corresponding author), Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94158 USA.
EM stroud@msg.ucsf.edu
FU Carlsberg Foundation; Danish Cancer Society; NIH [U54 GM094625, U01 GM61390, GM24485, GM073210]; National Institute of General Medical Sciences [T32GM008284, R01GM024485] Funding Source: NIH RePORTER
NR 53
TC 91
Z9 101
U1 1
U2 47
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 4
PY 2013
VL 499
IS 7456
BP 107
EP 110
DI 10.1038/nature12233
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 176ED
UT WOS:000321285600043
PM 23685453
DA 2026-03-09
ER

PT J
AU Boskovski, MT
   Yuan, SAL
   Pedersen, NB
   Goth, CK
   Makova, S
   Clausen, H
   Brueckner, M
   Khokha, MK
AF Boskovski, Marko T.
   Yuan, Shiaulou
   Pedersen, Nis Borbye
   Goth, Christoffer Knak
   Makova, Svetlana
   Clausen, Henrik
   Brueckner, Martina
   Khokha, Mustafa K.
TI The heterotaxy gene GALNT11 glycosylates Notch to orchestrate cilia type and laterality
SO NATURE
LA English
DT Article
ID left-right asymmetry; congenital heart-disease; left-right axis; leftward flow; o-glycosylation; fluid-flow; xenopus embryos; node; protein; mouse
AB Heterotaxy is a disorder of left-right body patterning, or laterality, that is associated with major congenital heart disease(1). The aetiology and mechanisms underlying most cases of human heterotaxy are poorly understood. In vertebrates, laterality is initiated at the embryonic left-right organizer, where motile cilia generate leftward flow that is detected by immotile sensory cilia, which transduce flow into downstream asymmetric signals(2-6). The mechanism that specifies these two cilia types remains unknown. Here we show that the N-acetylgalactosamine-type O-glycosylation enzyme GALNT11 is crucial to such determination. We previously identified GALNT11 as a candidate disease gene in a patient with heterotaxy(7), and now demonstrate, in Xenopus tropicalis, that galnt11 activates Notch signalling. GALNT11 O-glycosylates human NOTCH1 peptides in vitro, thereby supporting a mechanism of Notch activation either by increasing ADAM17-mediated ectodomain shedding of the Notch receptor or by modification of specific EGF repeats. We further developed a quantitative live imaging technique for Xenopus left-right organizer cilia and show that Galnt11-mediated Notch1 signalling modulates the spatial distribution and ratio of motile and immotile cilia at the left-right organizer. galnt11 or notch1 depletion increases the ratio of motile cilia at the expense of immotile cilia and produces a laterality defect reminiscent of loss of the ciliary sensor Pkd2. By contrast, Notch overexpression decreases this ratio, mimicking the ciliopathy primary ciliary dyskinesia. Together our data demonstrate that Galnt11 modifies Notch, establishing an essential balance between motile and immotile cilia at the left-right organizer to determine laterality, and reveal a novel mechanism for human heterotaxy.
C1 [Boskovski, Marko T.; Yuan, Shiaulou; Makova, Svetlana; Brueckner, Martina; Khokha, Mustafa K.] Yale Univ, Sch Med, Dept Pediat & Genet, Program Vertebrate Dev Biol, New Haven, CT 06520 USA.
   [Pedersen, Nis Borbye; Goth, Christoffer Knak; Clausen, Henrik] Univ Copenhagen, Fac Hlth Sci, Dept Cellular & Mol Med, Copenhagen Ctr Glyc, DK-2200 Copenhagen N, Denmark.
C3 Yale University; University of Copenhagen
RP Khokha, MK (corresponding author), Yale Univ, Sch Med, Dept Pediat & Genet, Program Vertebrate Dev Biol, 333 Cedar St, New Haven, CT 06520 USA.
EM mustafa.khokha@yale.edu
FU National Center for Research Resources/National Institutes of Health (NIH) [TL 1 RR024137]; NIH Roadmap for Medical Research; NIH [5T32HD00709436, R01HL093280, DE018825, DE018824]; Danish National Research Foundation [DNRF107]
NR 40
TC 137
Z9 174
U1 1
U2 41
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD DEC 19
PY 2013
VL 504
IS 7480
BP 456
EP +
DI 10.1038/nature12723
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 273ZR
UT WOS:000328575300056
PM 24226769
DA 2026-03-09
ER

PT J
AU Nakajima, Y
   Meyer, EJ
   Kroesen, A
   McKinney, SA
   Gibson, MC
AF Nakajima, Yu-ichiro
   Meyer, Emily J.
   Kroesen, Amanda
   McKinney, Sean A.
   Gibson, Matthew C.
TI Epithelial junctions maintain tissue architecture by directing planar spindle orientation
SO NATURE
LA English
DT Article
ID asymmetric cell-division; transgenic rnai; drosophila; polarity; centrosome; proteins; cancer; misorientation; morphogenesis; zebrafish
AB During epithelial cell proliferation, planar alignment of the mitotic spindle coordinates the local process of symmetric cell cleavage with the global maintenance of polarized tissue architecture(1,2). Although the disruption of planar spindle alignment is proposed to cause epithelial to mesenchymal transition and cancer(3-6), the in vivo mechanisms regulating mitotic spindle orientation remain elusive. Here we demonstrate that the actomyosin cortex and the junction-localized neoplastic tumour suppressors Scribbled and Discs large 1 have essential roles in planar spindle alignment and thus the control of epithelial integrity in the Drosophila imaginal disc. We show that defective alignment of the mitotic spindle correlates with cell delamination and apoptotic death, and that blocking the death of misaligned cells is sufficient to drive the formation of basally localized tumour-like masses. These findings indicate a key role for junction-mediated spindle alignment in the maintenance of epithelial integrity, and also reveal a previously unknown cell-death-mediated tumour-suppressor function inherent in the polarized architecture of epithelia.
C1 [Nakajima, Yu-ichiro; Meyer, Emily J.; Kroesen, Amanda; McKinney, Sean A.; Gibson, Matthew C.] Stowers Inst Med Res, Kansas City, MO 64110 USA.
   [Gibson, Matthew C.] Univ Kansas, Med Ctr, Dept Anat & Cell Biol, Kansas City, KS 66160 USA.
C3 Stowers Institute for Medical Research; University of Kansas; University of Kansas Medical Center
RP Gibson, MC (corresponding author), Stowers Inst Med Res, 1000 East 50th St, Kansas City, MO 64110 USA.
EM MG2@stowers.org
FU Stowers Institute for Medical Research; Burroughs Wellcome Fund for Biomedical Research
NR 41
TC 155
Z9 190
U1 1
U2 51
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 15
PY 2013
VL 500
IS 7462
BP 359
EP +
DI 10.1038/nature12335
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 201AF
UT WOS:000323112400038
PM 23873041
DA 2026-03-09
ER

PT J
AU Maeda, K
   Anand, K
   Chiapparino, A
   Kumar, A
   Poletto, M
   Kaksonen, M
   Gavin, AC
AF Maeda, Kenji
   Anand, Kanchan
   Chiapparino, Antonella
   Kumar, Arun
   Poletto, Mattia
   Kaksonen, Marko
   Gavin, Anne-Claude
TI Interactome map uncovers phosphatidylserine transport by oxysterol-binding proteins
SO NATURE
LA English
DT Article
ID saccharomyces-cerevisiae; plasma-membrane; molecular replacement; global analysis; yeast; identification; sequence; localization; organization; metabolism
AB The internal organization of eukaryotic cells into functionally specialized, membrane-delimited organelles of unique composition implies a need for active, regulated lipid transport. Phosphatidylserine (PS), for example, is synthesized in the endoplasmic reticulum and then preferentially associates-through mechanisms not fully elucidated-with the inner leaflet of the plasma membrane(1-3). Lipids can travel via transport vesicles. Alternatively, several protein families knownas lipid-transfer proteins (LTPs) can extract a variety of specific lipids from biological membranes and transport them, within a hydrophobic pocket, through aqueous phases(4-7). Here we report the development of an integrated approach that combines protein fractionation and lipidomics to characterize the LTP-lipid complexes formed in vivo. We applied the procedure to 13 LTPs in the yeast Saccharomyces cerevisiae: the six Sec14 homology (Sfh) proteins and the seven oxysterol-binding homology (Osh) proteins. We found that Osh6 and Osh7 have an unexpected specificity for PS. In vivo, they participate in PS homeostasis and the transport of this lipid to the plasma membrane. The structure of Osh6 bound to PS reveals unique features that are conserved among other metazoan oxysterol-binding proteins (OSBPs) and are required for PS recognition. Our findings represent the first direct evidence, to our knowledge, for the non-vesicular transfer of PS from its site of biosynthesis (the endoplasmic reticulum) to its site of biological activity (the plasma membrane). We describe a new subfamily of OSBPs, including human ORP5 and ORP10, that transfer PS and propose new mechanisms of action for a protein family that is involved in several human pathologies such as cancer, dyslipidaemia and metabolic syndrome.
C1 [Maeda, Kenji; Anand, Kanchan; Chiapparino, Antonella; Kumar, Arun; Poletto, Mattia; Kaksonen, Marko; Gavin, Anne-Claude] European Mol Biol Lab, D-69117 Heidelberg, Germany.
C3 European Molecular Biology Laboratory (EMBL)
RP Gavin, AC (corresponding author), European Mol Biol Lab, Meyerhofstr 1, D-69117 Heidelberg, Germany.
EM gavin@embl.de
FU Federal Ministry of Education and Research (BMBF) [01GS0865]; European Molecular Biology Laboratory; EU Marie Curie Actions Interdisciplinary Postdoctoral Cofunded Programme; Marie Curie reintegration grant (ERG); Danish Natural Science Research Council [09-064986/FNU]
NR 52
TC 276
Z9 326
U1 1
U2 89
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 12
PY 2013
VL 501
IS 7466
BP 257
EP +
DI 10.1038/nature12430
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 215XR
UT WOS:000324244900048
PM 23934110
DA 2026-03-09
ER

PT J
AU Säterberg, T
   Sellman, S
   Ebenman, B
AF Saterberg, Torbjorn
   Sellman, Stefan
   Ebenman, Bo
TI High frequency of functional extinctions in ecological networks
SO NATURE
LA English
DT Article
ID trophic cascades; food; increases; viability; shifts
AB Intensified exploitation of natural populations and habitats has led to increased mortality rates and decreased abundances of many species(1,2). There is a growing concern that this might cause critical abundance thresholds of species to be crossed(1,3-5), with extinction cascades and state shifts in ecosystems as a consequence(4,6,7). When increased mortality rate and decreased abundance of a given species lead to extinction of other species, this species can be characterized as functionally extinct even though it still exists. Although such functional extinctions have been observed in some ecosystems(3,4,8), their frequency is largely unknown. Here we use a new modelling approach to explore the frequency and pattern of functional extinctions in ecological networks. Specifically, we analytically derive critical abundance thresholds of species by increasing their mortality rates until an extinction occurs in the network. Applying this approach on natural and theoretical food webs, we show that the species most likely to go extinct first is not the one whose mortality rate is increased but instead another species. Indeed, up to 80% of all first extinctions are of another species, suggesting that a species' ecological functionality is often lost before its own existence is threatened. Furthermore, we find that large-bodied species at the top of the food chains can only be exposed to small increases in mortality rate and small decreases in abundance before going functionally extinct compared to small-bodied species lower in the food chains. These results illustrate the potential importance of functional extinctions in ecological networks and lend strong support to arguments advocating a more community-oriented approach in conservation biology, with target levels for populations based on ecological functionality rather than on mere persistence(8-11).
C1 [Saterberg, Torbjorn; Sellman, Stefan; Ebenman, Bo] Linkoping Univ, Dept Phys Chem & Biol, Div Theoret Biol, SE-58183 Linkoping, Sweden.
C3 Linkoping University
RP Ebenman, B (corresponding author), Linkoping Univ, Dept Phys Chem & Biol, Div Theoret Biol, SE-58183 Linkoping, Sweden.
EM boebe@ifm.liu.se
FU Linkoping University
NR 32
TC 165
Z9 197
U1 4
U2 241
PU NATURE PUBLISHING 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 25
PY 2013
VL 499
IS 7459
BP 468
EP +
DI 10.1038/nature12277
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 187YP
UT WOS:000322157900038
PM 23831648
DA 2026-03-09
ER

PT J
AU Tinberg, CE
   Khare, SD
   Dou, JY
   Doyle, L
   Nelson, JW
   Schena, A
   Jankowski, W
   Kalodimos, CG
   Johnsson, K
   Stoddard, BL
   Baker, D
AF Tinberg, Christine E.
   Khare, Sagar D.
   Dou, Jiayi
   Doyle, Lindsey
   Nelson, Jorgen W.
   Schena, Alberto
   Jankowski, Wojciech
   Kalodimos, Charalampos G.
   Johnsson, Kai
   Stoddard, Barry L.
   Baker, David
TI Computational design of ligand-binding proteins with high affinity and selectivity
SO NATURE
LA English
DT Article
ID antibody; optimization; specificity; reveal
AB The ability to design proteins with high affinity and selectivity for any given small molecule is a rigorous test of our understanding of the physiochemical principles that govern molecular recognition. Attempts to rationally design ligand-binding proteins have met with little success, however, and the computational design of protein-small-molecule interfaces remains an unsolved problem(1). Current approaches for designing ligand-binding proteins for medical(2) and biotechnological uses rely on raising antibodies against a target antigen in immunized animals(3,4) and/or performing laboratory-directed evolution of proteins with an existing low affinity for the desired ligand(5-7), neither of which allows complete control over the interactions involved in binding. Here we describe a general computational method for designing pre-organized and shape complementary small-molecule-binding sites, and use it to generate protein binders to the steroid digoxigenin (DIG). Of seventeen experimentally characterized designs, two bind DIG; the model of the higher affinity binder has the most energetically favourable and pre-organized interface in the design set. A comprehensive binding-fitness landscape of this design, generated by library selections and deep sequencing, was used to optimize its binding affinity to a picomolar level, and X-ray co-crystal structures of two variants show atomic-level agreement with the corresponding computational models. The optimized binder is selective for DIG over the related steroids digitoxigenin, progesterone and beta-oestradiol, and this steroid binding preference can be reprogrammed by manipulation of explicitly designed hydrogen-bonding interactions. The computational design method presented here should enable the development of a new generation of biosensors, therapeutics and diagnostics.
C1 [Tinberg, Christine E.; Khare, Sagar D.; Baker, David] Univ Washington, Dept Biochem, Seattle, WA 98195 USA.
   [Dou, Jiayi] Univ Washington, Dept Bioengn, Seattle, WA 98195 USA.
   [Dou, Jiayi] Univ Washington, Grad Program Biol Phys Struct & Design, Seattle, WA 98195 USA.
   [Doyle, Lindsey; Stoddard, Barry L.] Fred Hutchinson Canc Res Ctr, Div Basic Sci, Seattle, WA 98109 USA.
   [Nelson, Jorgen W.] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA.
   [Schena, Alberto; Johnsson, Kai] Ecole Polytech Fed Lausanne, Inst Chem Sci & Engn, Inst Bioengn, Natl Ctr Competence Res NCCR Chem Biol, CH-1015 Lausanne, Switzerland.
   [Jankowski, Wojciech; Kalodimos, Charalampos G.] Rutgers State Univ, Ctr Integrat Prote Res, Dept Chem & Chem Biol, Piscataway, NJ 08854 USA.
   [Baker, David] Univ Washington, Howard Hughes Med Inst, Seattle, WA 98195 USA.
C3 University of Washington; University of Washington Seattle; University of Washington; University of Washington Seattle; University of Washington; University of Washington Seattle; Fred Hutchinson Cancer Center; University of Washington; University of Washington Seattle; Swiss Federal Institutes of Technology Domain; Ecole Polytechnique Federale de Lausanne; Rutgers University System; Rutgers University New Brunswick; University of Washington; University of Washington Seattle; Howard Hughes Medical Institute
RP Baker, D (corresponding author), Univ Washington, Dept Biochem, Seattle, WA 98195 USA.
EM dabaker@u.washington.edu
FU Washington State Life Sciences Discovery Fund; Center for the Intracellular Delivery of Biologics; National Human Genome Research Institute under the Interdisciplinary Training in Genome Sciences program [T32 HG00035]; DTRA; DARPA; Swiss National Science Foundation; National Science Foundation [MCB1121896]; National Human Genome Research Institute [T32HG000035] Funding Source: NIH RePORTER; National Institute of General Medical Sciences [P41GM103533] Funding Source: NIH RePORTER; Div Of Molecular and Cellular Bioscience; Direct For Biological Sciences [1121896] Funding Source: National Science Foundation
NR 38
TC 344
Z9 465
U1 2
U2 331
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD SEP 12
PY 2013
VL 501
IS 7466
BP 212
EP +
DI 10.1038/nature12443
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 215XR
UT WOS:000324244900039
PM 24005320
DA 2026-03-09
ER

PT J
AU Siu, FY
   He, M
   de Graaf, C
   Han, GW
   Yang, DH
   Zhang, ZY
   Zhou, CH
   Xu, QP
   Wacker, D
   Joseph, JS
   Liu, W
   Lau, J
   Cherezov, V
   Katritch, V
   Wang, MW
   Stevens, RC
AF Siu, Fai Yiu
   He, Min
   de Graaf, Chris
   Han, Gye Won
   Yang, Dehua
   Zhang, Zhiyun
   Zhou, Caihong
   Xu, Qingping
   Wacker, Daniel
   Joseph, Jeremiah S.
   Liu, Wei
   Lau, Jesper
   Cherezov, Vadim
   Katritch, Vsevolod
   Wang, Ming-Wei
   Stevens, Raymond C.
TI Structure of the human glucagon class B G-protein-coupled receptor
SO NATURE
LA English
DT Article
ID 2nd transmembrane helix; ligand-binding; peptide-1 receptor; crystallizing membrane; extracellular loop; photolabile probes; opioid receptor; molecular-basis; vpac1 receptor; amino-terminus
AB Binding of the glucagon peptide to the glucagon receptor (GCGR) triggers the release of glucose from the liver during fasting; thus GCGR plays an important role in glucose homeostasis. Here we report the crystal structure of the seven transmembrane helical domain of human GCGR at 3.4 angstrom resolution, complemented by extensive site-specific mutagenesis, and a hybrid model of glucagon bound to GCGR to understand the molecular recognition of the receptor for its native ligand. Beyond the shared seven transmembrane fold, the GCGR transmembrane domain deviates from class A G-protein-coupled receptors witha large ligand-binding pocket and the first transmembrane helix having a 'stalk' region that extends three alpha-helical turns above the plane of the membrane. The stalk positions the extracellular domain (similar to 12 kilodaltons) relative to the membrane to form the glucagon-binding site that captures the peptide and facilitates the insertion of glucagon's amino terminus into the seven transmembrane domain.
C1 [Siu, Fai Yiu; Han, Gye Won; Wacker, Daniel; Joseph, Jeremiah S.; Liu, Wei; Cherezov, Vadim; Katritch, Vsevolod; Stevens, Raymond C.] Scripps Res Inst, Dept Integrat Struct & Computat Biol, La Jolla, CA 92037 USA.
   [He, Min; Yang, Dehua; Zhang, Zhiyun; Zhou, Caihong; Wang, Ming-Wei] Natl Ctr Drug Screening, Shanghai 201203, Peoples R China.
   [He, Min; Yang, Dehua; Zhang, Zhiyun; Zhou, Caihong; Wang, Ming-Wei] Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China.
   [de Graaf, Chris] Vrije Univ Amsterdam, Amsterdam Inst Mol Med & Syst AIMMS, Fac Sci, Div Med Chem, NL-1081 HV Amsterdam, Netherlands.
   [Xu, Qingping] SLAC Natl Accelerator Lab, Joint Ctr Struct Genom, Stanford Synchrotron Radiat Lightsource, Menlo Pk, CA 94025 USA.
   [Lau, Jesper] Novo Nordisk, Prot & Peptide Chem, DK-2760 Malov, Denmark.
C3 Scripps Research Institute; Chinese Academy of Sciences; Chinese Academy of Sciences; Shanghai Institute of Materia Medica, CAS; Vrije Universiteit Amsterdam; Stanford University; United States Department of Energy (DOE); SLAC National Accelerator Laboratory; Novo Nordisk
RP Wang, MW (corresponding author), Natl Ctr Drug Screening, 189 Guo Shou Jing Rd, Shanghai 201203, Peoples R China.
EM wangmw@mail.shcnc.ac.cn; stevens@scripps.edu
FU NIH Road map [P50GM073197, U54 GM094618, U54 GM094586]; Ministry of Health [2012ZX09304-011, 2013ZX09507002]; Shanghai Science and Technology Development Fund [11DZ2292200]; Novo Nordisk-Chinese Academy of Sciences Research Fund [NNCAS-2011-7]; Thousand Talents Program in China; NIH [F32 DK088392]; Netherlands Organization for Scientific Research (NWO) through a VENI [700.59.408]; COST Action [CM1207]; National Cancer Institute [Y1-CO-1020]; National Institute of General Medical Sciences [Y1-GM-1104]
NR 61
TC 323
Z9 373
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 JUL 25
PY 2013
VL 499
IS 7459
BP 444
EP +
DI 10.1038/nature12393
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 187YP
UT WOS:000322157900033
PM 23863937
DA 2026-03-09
ER

PT J
AU Lämmermann, T
   Afonso, PV
   Angermann, BR
   Wang, JM
   Kastenmüller, W
   Parent, CA
   Germain, RN
AF Laemmermann, Tim
   Afonso, Philippe V.
   Angermann, Bastian R.
   Wang, Ji Ming
   Kastenmueller, Wolfgang
   Parent, Carole A.
   Germain, Ronald N.
TI Neutrophil swarms require LTB4 and integrins at sites of cell death in vivo
SO NATURE
LA English
DT Article
ID innate immune-response; imaging reveals; host-defense; mice lacking; lymph-nodes; migration; recruitment; receptor; molecule; leukotriene-b4
AB Neutrophil recruitment from blood to extravascular sites of sterile or infectious tissue damage is a hallmark of early innate immune responses, and the molecular events leading to cell exit from the bloodstream have been well defined(1,2). Once outside the vessel, individual neutrophils often show extremely coordinated chemotaxis and cluster formation reminiscent of the swarming behaviour of insects(3-11). The molecular players that direct this response at the single-cell and population levels within the complexity of an inflamed tissue are unknown. Using two-photon intravital microscopy in mouse models of sterile injury and infection, we show a critical role for intercellular signal relay among neutrophils mediated by the lipid leukotriene B4, which acutely amplifies local cell death signals to enhance the radius of highly directed interstitial neutrophil recruitment. Integrin receptors are dispensable for long-distance migration(12), but have a previously unappreciated role in maintaining dense cellular clusters when congregating neutrophils rearrange the collagenous fibre network of the dermis to form a collagen-free zone at the wound centre. In this newly formed environment, integrins, in concert with neutrophil-derived leukotriene B4 and other chemoattractants, promote local neutrophil interaction while forming a tight wound seal. This wound seal has borders that cease to grow in kinetic concert with late recruitment of monocytes and macrophages at the edge of the displaced collagen fibres. Together, these data provide an initial molecular map of the factors that contribute to neutrophil swarming in the extravascular space of a damaged tissue. They reveal how local events are propagated over large-range distances, and how auto-signalling produces coordinated, self-organized neutrophil-swarming behaviour that isolates the wound or infectious site from surrounding viable tissue.
C1 [Laemmermann, Tim; Angermann, Bastian R.; Kastenmueller, Wolfgang; Germain, Ronald N.] NIAID, Lab Syst Biol, NIH, Bethesda, MD 20892 USA.
   [Afonso, Philippe V.; Parent, Carole A.] NCI, Lab Cellular & Mol Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
   [Wang, Ji Ming] NCI, Lab Mol Immunoregulat, Canc & Inflammat Program, Ctr Canc Res,NIH, Frederick, MD 21702 USA.
   [Kastenmueller, Wolfgang] Univ Bonn, Inst Mol Med, D-53105 Bonn, Germany.
   [Kastenmueller, Wolfgang] Univ Bonn, Inst Expt Immunol, D-53105 Bonn, Germany.
C3 National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID); National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); University of Bonn; University of Bonn
RP Lämmermann, T (corresponding author), NIAID, Lab Syst Biol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM laemmermannt@niaid.nih.gov; rgermain@niaid.nih.gov
FU Human Frontiers Science Program Long-Term Fellowship; Deutsche Forschungsgemeinschaft (DFG); National Institute of Allergy and Infectious Diseases, National Institutes of Health; National Cancer Institute, National Institutes of Health; National Cancer Institute [ZIABC010725] Funding Source: NIH RePORTER; National Institute of Allergy and Infectious Diseases [ZIAAI000545] Funding Source: NIH RePORTER
NR 49
TC 750
Z9 877
U1 1
U2 165
PU NATURE PUBLISHING 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 20
PY 2013
VL 498
IS 7454
BP 371
EP +
DI 10.1038/nature12175
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 166XI
UT WOS:000320592900042
PM 23708969
DA 2026-03-09
ER

PT J
AU Zhou, HY
   Dick, HJB
AF Zhou, Huaiyang
   Dick, Henry J. B.
TI Thin crust as evidence for depleted mantle supporting the Marion Rise
SO NATURE
LA English
DT Article
ID southwest indian ridge; mid-atlantic-ridge; global correlations; gravity-anomaly; basalt chemistry; core complex; axial depth; ocean; origin; peridotite
AB The global ridge system is dominated by oceanic rises reflecting large variations in axial depth associated with mantle hotspots. The little-studied Marion Rise is as large as the Icelandic Rise, considering both length and depth, but has an axial rift (rather than a high) nearly its entire length. Uniquely along the Southwest Indian Ridge systematic sampling allows direct examination of crustal architecture over its full length. Here we show that, unlike the Icelandic Rise, peridotites are extensively exposed high on the rise, revealing that the crust is generally thin, and often missing, over a rifted rise. Therefore the Marion Rise must be largely an isostatic response to ancient melting events that created low-density depleted mantle beneath the Southwest Indian Ridge rather than thickened crust or a large thermal anomaly. The origin of this depleted mantle is probably the mantle emplaced into the African asthenosphere during the Karoo and Madagascar flood basalt events.
C1 [Zhou, Huaiyang] Tongji Univ, State Key Lab Marine Geol, Shanghai 200092, Peoples R China.
   [Dick, Henry J. B.] Woods Hole Oceanog Inst, Woods Hole, MA 02543 USA.
C3 Tongji University; Woods Hole Oceanographic Institution
RP Dick, HJB (corresponding author), Woods Hole Oceanog Inst, Woods Hole, MA 02543 USA.
EM zhouhy@tongji.edu.cn; hdick@whoi.edu
FU Chinese National Key Basic Research Program [2012CB417300]; China Ocean Mineral Resources Research and Development Association; US National Science Foundation [OCE-0526905]
NR 50
TC 144
Z9 173
U1 3
U2 108
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 14
PY 2013
VL 494
IS 7436
BP 195
EP 200
DI 10.1038/nature11842
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 092QS
UT WOS:000315137700031
PM 23389441
DA 2026-03-09
ER

PT J
AU Tabach, Y
   Billi, AC
   Hayes, GD
   Newman, MA
   Zuk, O
   Gabel, H
   Kamath, R
   Yacoby, K
   Chapman, B
   Garcia, SM
   Borowsky, M
   Kim, JK
   Ruvkun, G
AF Tabach, Yuval
   Billi, Allison C.
   Hayes, Gabriel D.
   Newman, Martin A.
   Zuk, Or
   Gabel, Harrison
   Kamath, Ravi
   Yacoby, Keren
   Chapman, Brad
   Garcia, Susana M.
   Borowsky, Mark
   Kim, John K.
   Ruvkun, Gary
TI Identification of small RNA pathway genes using patterns of phylogenetic conservation and divergence
SO NATURE
LA English
DT Article
ID systematic identification; interference; polymerase; proteins; complex; dcr-1; sirna
AB Genetic and biochemical analyses of RNA interference (RNAi) and microRNA (miRNA) pathways have revealed proteins such as Argonaute and Dicer as essential cofactors that process and present small RNAs to their targets. Well-validated small RNA pathway cofactors such as these show distinctive patterns of conservation or divergence in particular animal, plant, fungal and protist species. We compared 86 divergent eukaryotic genome sequences to discern sets of proteins that show similar phylogenetic profiles with known small RNA cofactors. A large set of additional candidate small RNA cofactors have emerged from functional genomic screens for defects in miRNA-or short interfering RNA (siRNA)-mediated repression in Caenorhabditis elegans and Dro-sophila melanogaster(1,2), and from proteomic analyses of proteins co-purifying with validated small RNA pathway proteins(3,4). The phylogenetic profiles of many of these candidate small RNA pathway proteins are similar to those of known small RNA cofactor proteins. We used a Bayesian approach to integrate the phylogenetic profile analysis with predictions from diverse transcriptional coregulation and proteome interaction data sets to assign a probability for each protein for a role in a small RNA pathway. Testing high-confidence candidates from this analysis for defects in RNAi silencing, we found that about one-half of the predicted small RNA cofactors are required for RNAi silencing. Many of the newly identified small RNA pathway proteins are orthologues of proteins implicated in RNA splicing. In support of a deep connection between the mechanism of RNA splicing and small-RNA-mediated gene silencing, the presence of the Argonaute proteins and other small RNA components in the many species analysed strongly correlates with the number of introns in those species.
C1 [Tabach, Yuval; Hayes, Gabriel D.; Newman, Martin A.; Gabel, Harrison; Kamath, Ravi; Yacoby, Keren; Chapman, Brad; Garcia, Susana M.; Borowsky, Mark; Ruvkun, Gary] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
   [Tabach, Yuval; Hayes, Gabriel D.; Newman, Martin A.; Gabel, Harrison; Kamath, Ravi; Garcia, Susana M.; Borowsky, Mark; Ruvkun, Gary] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
   [Billi, Allison C.; Kim, John K.] Univ Michigan, Inst Life Sci, Ann Arbor, MI 48109 USA.
   [Billi, Allison C.; Kim, John K.] Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA.
   [Zuk, Or] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.
C3 Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard Medical School; University of Michigan System; University of Michigan; University of Michigan System; University of Michigan; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute
RP Ruvkun, G (corresponding author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
EM ruvkun@molbio.mgh.harvard.edu
FU NIH [GM088565, GM44619, GM098647]; Pew Charitable Trusts; National Institute of General Medical Sciences [T32GM007544, R01GM044619] Funding Source: NIH RePORTER
NR 28
TC 119
Z9 138
U1 0
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 JAN 31
PY 2013
VL 493
IS 7434
BP 694
EP 698
DI 10.1038/nature11779
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 080CU
UT WOS:000314219600061
PM 23364702
DA 2026-03-09
ER

PT J
AU Duch, A
   Felipe-Abrio, I
   Barroso, S
   Yaakov, G
   García-Rubio, M
   Aguilera, A
   de Nadal, E
   Posas, F
AF Duch, Alba
   Felipe-Abrio, Irene
   Barroso, Sonia
   Yaakov, Gilad
   Garcia-Rubio, Maria
   Aguilera, Andres
   de Nadal, Eulalia
   Posas, Francesc
TI Coordinated control of replication and transcription by a SAPK protects genomic integrity
SO NATURE
LA English
DT Article
ID double-strand breaks; gene-expression; dna-replication; saccharomyces-cerevisiae; fork progression; cell-cycle; stress; mrc1; phase; kinase
AB Upon environmental changes or extracellular signals, cells are subjected to marked changes in gene expression (1,2). Dealing with high levels of transcription during replication is critical to prevent collisions between the transcription and replication pathways and avoid recombination events(3-5). In response to osmostress, hundreds of stress-responsive genes are rapidly induced by the stress-activated protein kinase (SAPK) Hog1 (ref.6), even during S phase(7). Here we show in Saccharomyces cerevisae that a single signalling molecule, Hog1, coordinates both replication and transcription upon osmostress. Hog1 interacts with and phosphorylates Mrc1, a component of the replication complex(8-11). Phosphorylation occurs at different sites to those targeted by Mec1 upon DNA damage(8,9). Mrc1 phosphorylation by Hog1 delays early and late origin firing by preventing Cdc45 loading, as well as slowing down replication-complex progression. Regulation of Mrc1 by Hog1 is completely independent of Mec1 and Rad53. Cells carrying a non-phosphorylatable allele of MRC1 (mrc1(3A)) do not delay replication upon stress and show a marked increase in transcription-associated recombination, genomic instability and Rad52 foci. In contrast, mrc1(3A) induces Rad53 and survival in the presence of hydroxyurea or methyl methanesulphonate. Therefore, Hog1 and Mrc1 define a novel S-phase checkpoint independent of the DNA-damage checkpoint that permits eukaryotic cells to prevent conflicts between DNA replication and transcription, which would otherwise lead to genomic instability when both phenomena are temporally coincident.
C1 [Duch, Alba; Yaakov, Gilad; de Nadal, Eulalia; Posas, Francesc] Univ Pompeu Fabra, Cell Signaling Unit, Dept Ciencies Expt & Salut, E-08003 Barcelona, Spain.
   [Felipe-Abrio, Irene; Barroso, Sonia; Garcia-Rubio, Maria; Aguilera, Andres] Univ Seville, Ctr Andaluz Biol Mol & Med Regenerat CABIMER, Seville 41092, Spain.
C3 Pompeu Fabra University; Consejo Superior de Investigaciones Cientificas (CSIC); Universidad Pablo de Olavide; University of Sevilla; CSIC - Centro Andaluz de Biologia Molecular y Medicina Regenerativa (CABIMER)
RP Posas, F (corresponding author), Univ Pompeu Fabra, Cell Signaling Unit, Dept Ciencies Expt & Salut, E-08003 Barcelona, Spain.
EM francesc.posas@upf.edu
FU Spanish Government [BIO2009-07762, BFU2012-33503, BFU2011-26722, BFU2010-16372, CSD2007-0015]; FP7 UNICELLSYS grant [201142]; Fundacion Marcelino Botin; ICREA Academia (Generalitat de Catalunya); Academy of Finland (AKA) [201142] Funding Source: Academy of Finland (AKA)
NR 32
TC 71
Z9 80
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 JAN 3
PY 2013
VL 493
IS 7430
BP 116
EP +
DI 10.1038/nature11675
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 062QC
UT WOS:000312933800042
PM 23178807
DA 2026-03-09
ER

PT J
AU Ideguchi, T
   Holzner, S
   Bernhardt, B
   Guelachvili, G
   Picqué, N
   Hänsch, TW
AF Ideguchi, Takuro
   Holzner, Simon
   Bernhardt, Birgitta
   Guelachvili, Guy
   Picque, Nathalie
   Haensch, Theodor W.
TI Coherent Raman spectro-imaging with laser frequency combs
SO NATURE
LA English
DT Article
ID scattering microscopy; in-vivo; tissue
AB Advances in optical spectroscopy and microscopy have had a profound impact throughout the physical, chemical and biological sciences. One example is coherent Raman spectroscopy, a versatile technique interrogating vibrational transitions in molecules. It offers high spatial resolution and three-dimensional sectioning capabilities that make it a label-free tool(1,2) for the non-destructive and chemically selective probing of complex systems. Indeed, single-colour Raman bands have been imaged in biological tissue at video rates(3,4) by using ultra-short-pulse lasers. However, identifying multiple, and possibly unknown, molecules requires broad spectral bandwidth and high resolution. Moderate spectral spans combined with high-speed acquisition are now within reach using multichannel detection(5) or frequency-swept laser beams(6-9). Laser frequency combs(10) are finding increasing use for broadband molecular linear absorption spectroscopy(11-15). Here we show, by exploring their potential for nonlinear spectroscopy(16), that they can be harnessed for coherent anti-Stokes Raman spectroscopy and spectro-imaging. The method uses two combs and can simultaneously measure, on the microsecond timescale, all spectral elements over a wide bandwidth and with high resolution on a single photodetector. Although the overall measurement time in our proof-of-principle experiments is limited by the waiting times between successive spectral acquisitions, this limitation can be overcome with further system development. We therefore expect that our approach of using laser frequency combs will not only enable new applications for nonlinear microscopy but also benefit other nonlinear spectroscopic techniques.
C1 [Ideguchi, Takuro; Holzner, Simon; Bernhardt, Birgitta; Picque, Nathalie; Haensch, Theodor W.] Max Planck Inst Quantum Opt, D-85748 Garching, Germany.
   [Guelachvili, Guy; Picque, Nathalie] Univ Paris 11, CNRS, Inst Sci Mol Orsay, F-91405 Orsay, France.
   [Bernhardt, Birgitta; Picque, Nathalie; Haensch, Theodor W.] Univ Munich, Fak Phys, D-80799 Munich, Germany.
C3 Max Planck Society; Universite Paris Saclay; Centre National de la Recherche Scientifique (CNRS); University of Munich
RP Picqué, N (corresponding author), Max Planck Inst Quantum Opt, Hans Kopfermann Str 1, D-85748 Garching, Germany.
EM nathalie.picque@mpq.mpg.de
FU Max Planck Foundation; Munich Center for Advanced Photonics; Eurostars; European Research Council [267854]; European Research Council (ERC) [267854] Funding Source: European Research Council (ERC)
NR 30
TC 383
Z9 440
U1 11
U2 414
PU NATURE PUBLISHING 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 17
PY 2013
VL 502
IS 7471
BP 355
EP +
DI 10.1038/nature12607
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 235GY
UT WOS:000325706300049
PM 24132293
DA 2026-03-09
ER

PT J
AU Zhou, M
   Guo, JH
   Cha, J
   Chae, M
   Chen, S
   Barral, JM
   Sachs, MS
   Liu, Y
AF Zhou, Mian
   Guo, Jinhu
   Cha, Joonseok
   Chae, Michael
   Chen, She
   Barral, Jose M.
   Sachs, Matthew S.
   Liu, Yi
TI Non-optimal codon usage affects expression, structure and function of clock protein FRQ
SO NATURE
LA English
DT Article
ID neurospora circadian clock; feedback loops; phosphorylation; translation; gene; luciferase; mechanism; frequency; rhythms; system
AB Codon-usage bias has been observed in almost all genomes and is thought to result from selection for efficient and accurate translation of highly expressed genes(1-3). Codon usage is also implicated in the control of transcription, splicing and RNA structure(4-6). Many genes exhibit little codon-usage bias, which is thought to reflect a lack of selection for messenger RNA translation. Alternatively, however, non-optimal codon usage may be of biological importance. The rhythmic expression and the proper function of the Neurospora FREQUENCY (FRQ) protein are essential for circadian clock function. Here we show that, unlike most genes in Neurospora, frq exhibits non-optimal codon usage across its entire open reading frame. Optimization of frq codon usage abolishes both overt and molecular circadian rhythms. Codon optimization not only increases FRQ levels but, unexpectedly, also results in conformational changes in FRQ protein, altered FRQ phosphorylation profile and stability, and impaired functions in the circadian feedback loops. These results indicate that non-optimal codon usage of frq is essential for its circadian clock function. Our study provides an example of how non-optimal codon usage functions to regulate protein expression and to achieve optimal protein structure and function.
C1 [Zhou, Mian; Guo, Jinhu; Cha, Joonseok; Chae, Michael; Liu, Yi] Univ Texas SW Med Ctr Dallas, Dept Physiol, Dallas, TX 75390 USA.
   [Chen, She] Natl Inst Biol Sci, Beijing 102206, Peoples R China.
   [Barral, Jose M.] Univ Texas Med Branch, Dept Neurosci & Cell Biol, Galveston, TX 77555 USA.
   [Barral, Jose M.] Univ Texas Med Branch, Dept Biochem & Mol Biol, Galveston, TX 77555 USA.
   [Sachs, Matthew S.] Texas A&M Univ, Dept Biol, College Stn, TX 77843 USA.
C3 University of Texas System; University of Texas Southwestern Medical Center; National Institute of Biological Sciences, Beijing; University of Texas System; University of Texas Medical Branch Galveston; University of Texas System; University of Texas Medical Branch Galveston; Texas A&M University System; Texas A&M University College Station
RP Liu, Y (corresponding author), Univ Texas SW Med Ctr Dallas, Dept Physiol, 5323 Harry Hines Blvd, Dallas, TX 75390 USA.
EM Yi.Liu@UTsouthwestern.edu
FU National Institutes of Health [GM068496, GM062591, GM47498]; Welch Foundation [I-1560]; National Institute of General Medical Sciences [R35GM118118] Funding Source: NIH RePORTER; National Institute on Aging [P30AG024832] Funding Source: NIH RePORTER
NR 29
TC 336
Z9 397
U1 2
U2 121
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 7
PY 2013
VL 495
IS 7439
BP 111
EP 115
DI 10.1038/nature11833
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 105BE
UT WOS:000316039800050
PM 23417067
DA 2026-03-09
ER

PT J
AU Pierce, SE
   Ahlberg, PE
   Hutchinson, JR
   Molnar, JL
   Sanchez, S
   Tafforeau, P
   Clack, JA
AF Pierce, Stephanie E.
   Ahlberg, Per E.
   Hutchinson, John R.
   Molnar, Julia L.
   Sanchez, Sophie
   Tafforeau, Paul
   Clack, Jennifer A.
TI Vertebral architecture in the earliest stem tetrapods
SO NATURE
LA English
DT Article
ID axial skeleton; evolution; ichthyostega; morphology
AB The construction of the vertebral column has been used as a key anatomical character in defining and diagnosing early tetrapod groups(1). Rhachitomous vertebrae(2)-in which there is a dorsally placed neural arch and spine, an anteroventially placed intercentrum and paired, posterodorsally placed pleurocentra have long been considered the ancestral morphology for tetrapods(1,3-6). Nonetheless, very little is known about vertebral anatomy in the earliest stem tetrapods, because most specimens remain trapped in surrounding matrix, obscuring Important anatomical features(7-9). Here we describe the three-dimensional vertebral architecture of the Late Devonian stem tetrapod Ichthyostega using propagation phase-contrast X-ray synchrotron. microtomography. Our scans reveal a diverse array of new morphological, and associated developmental and functional, characteristics, including a possible posterior-to-anterior vertebral ossification sequence and the first evolutionary appearance of ossified sternal elements. One of the most intriguing features relates to the positional relationships between the vertebral elements, with the pleurocentra being unexpectedly sutured or fused to the intercentra that directly succeed them, indicating a 'reverse' rhachitomous design(10). Comparison of Ichthyostega with two other stem tetrapods, Acanthostegi and Pederpess, shows that reverse rhachitomous vertebrae may be the ancestral condition for limbed vertebrates. This study fundamentally revises our current understanding' of vertebral column evolution in the earliest tetrapods and raises questions about the presumed vertebral architecture of tetrapodomorph fish(12,13) and later, more crownward, tetrapods.
C1 [Pierce, Stephanie E.; Clack, Jennifer A.] Univ Cambridge, Dept Zool, Univ Museum Zool, Cambridge CB2 3EJ, England.
   [Pierce, Stephanie E.; Hutchinson, John R.; Molnar, Julia L.] Univ London Royal Vet Coll, Dept Comparat Biomed Sci, Hatfield AL9 7TA, Herts, England.
   [Pierce, Stephanie E.; Hutchinson, John R.; Molnar, Julia L.] Univ London Royal Vet Coll, Struct & Mot Lab, Hatfield AL9 7TA, Herts, England.
   [Ahlberg, Per E.; Sanchez, Sophie] Uppsala Univ, Subdept Evolut & Dev, Dept Organismal Biol, Evolutionary Biol Ctr, S-75236 Uppsala, Sweden.
   [Sanchez, Sophie; Tafforeau, Paul] European Synchrotron Radiat Facil, F-38043 Grenoble, France.
C3 University of Cambridge; University of London; University of London Royal Veterinary College; University of London; University of London Royal Veterinary College; Uppsala University; European Synchrotron Radiation Facility (ESRF)
RP Pierce, SE (corresponding author), Univ Cambridge, Dept Zool, Univ Museum Zool, Downing St, Cambridge CB2 3EJ, England.
EM spierce@rvc.ac.uk
FU NERC [NE/G005877/1, NE/G00711X/1]; ERC [233111]; Natural Environment Research Council [NE/G00711X/1, NE/G005877/1] Funding Source: researchfish; NERC [NE/G005877/1, NE/G00711X/1] Funding Source: UKRI
NR 30
TC 50
Z9 59
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 FEB 14
PY 2013
VL 494
IS 7436
BP 226
EP 229
DI 10.1038/nature11825
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 092QS
UT WOS:000315137700037
PM 23334417
DA 2026-03-09
ER

PT J
AU Tiengo, A
   Esposito, P
   Mereghetti, S
   Turolla, R
   Nobili, L
   Gastaldello, F
   Götz, D
   Israel, GL
   Rea, N
   Stella, L
   Zane, S
   Bignami, GF
AF Tiengo, Andrea
   Esposito, Paolo
   Mereghetti, Sandro
   Turolla, Roberto
   Nobili, Luciano
   Gastaldello, Fabio
   Goetz, Diego
   Israel, Gian Luca
   Rea, Nanda
   Stella, Luigi
   Zane, Silvia
   Bignami, Giovanni F.
TI A variable absorption feature in the X-ray spectrum of a magnetar
SO NATURE
LA English
DT Article
ID soft gamma-repeaters; isolated neutron-stars; sgr 0418+5729; radiative mechanism; giant flare; spin-down; field; atmospheres; emission; pulsars
AB Soft-gamma-ray repeaters (SGRs) and anomalous X-ray pulsars (AXPs) are slowly rotating, isolated neutron stars that sporadically undergo episodes of long-term flux enhancement (outbursts) generally accompanied by the emission of short bursts of hard X-rays(1,2). This behaviour can be understood in the magnetar model(3-5), according to which these sources are mainly powered by their own magnetic energy. This is supported by the fact that the magnetic fields inferred from several observed properties(6-8) of SGRs and AXPs are greater than-or at the high end of the range of-those of radio pulsars. In the peculiar case of SGR 0418+5729, a weak dipole magnetic moment is derived from its timing parameters(9), whereas a strong field has been proposed to reside in the stellar interior(10,11) and in multipole components on the surface(12). Here we show that the X-ray spectrum of SGR 0418+5729 has an absorption line, the properties of which depend strongly on the star's rotational phase. This line is interpreted as a proton cyclotron feature and its energy implies a magnetic field ranging from 2x10(14) gauss to more than 10(15) gauss.
C1 [Tiengo, Andrea; Bignami, Giovanni F.] Ist Univ Super, I-27100 Pavia, Italy.
   [Tiengo, Andrea; Esposito, Paolo; Mereghetti, Sandro; Gastaldello, Fabio; Bignami, Giovanni F.] Ist Astrofis Spaziale & Fis Cosm Milano, INAF, I-20133 Milan, Italy.
   [Tiengo, Andrea] Ist Nazl Fis Nucl, Sez Pavia, I-27100 Pavia, Italy.
   [Turolla, Roberto; Nobili, Luciano] Univ Padua, Dipartimento Fis & Astron, I-35131 Padua, Italy.
   [Turolla, Roberto; Zane, Silvia] Univ Coll London, Mullard Space Sci Lab, Dorking RH5 6NT, Surrey, England.
   [Goetz, Diego] AIM CEA Irfu Serv Astrophys, F-91191 Gif Sur Yvette, France.
   [Israel, Gian Luca; Stella, Luigi] Osserv Astron Roma, INAF, I-00040 Monte Porzio Catone, Italy.
   [Rea, Nanda] Inst Ciencies Espai IEEC CSIC, E-08193 Barcelona, Spain.
C3 Istituto Nazionale Astrofisica (INAF); Istituto Nazionale di Fisica Nucleare (INFN); University of Padua; University of London; University College London; CEA; Universite Paris Saclay; Universite Paris Cite; Istituto Nazionale Astrofisica (INAF); Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Instituto de Ciencias del Espacio (ICE); Institut d'Estudis Espacials de Catalunya (IEEC)
RP Tiengo, A (corresponding author), Ist Univ Super, Piazza Vittoria 15, I-27100 Pavia, Italy.
EM andrea.tiengo@iusspavia.it
FU INAF through a PRIN; ASI [I/032/10/0]; STFC [ST/H00260X/1] Funding Source: UKRI; Science and Technology Facilities Council [ST/H00260X/1] Funding Source: researchfish
NR 29
TC 172
Z9 184
U1 0
U2 12
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 15
PY 2013
VL 500
IS 7462
BP 312
EP 314
DI 10.1038/nature12386
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 201AF
UT WOS:000323112400027
PM 23955229
DA 2026-03-09
ER

PT J
AU Kain, P
   Boyle, SM
   Tharadra, SK
   Guda, T
   Pham, C
   Dahanukar, A
   Ray, A
AF Kain, Pinky
   Boyle, Sean Michael
   Tharadra, Sana Khalid
   Guda, Tom
   Christine Pham
   Dahanukar, Anupama
   Ray, Anandasankar
TI RETRACTED: Odour receptors and neurons for DEET and new insect repellents (Retracted article. See vol. 536, 2016)
SO NATURE
LA English
DT Article; Retracted Publication
ID volatile organic-compounds; anopheles-gambiae; aedes-aegypti; malaria mosquito; cellular basis; drosophila; identification; odors; behavior; mutant
AB There are major impediments to finding improved DEET alternatives because the receptors causing olfactory repellency are unknown, and new chemicals require exorbitant costs to determine safety for human use. Here we identify DEET-sensitive neurons in a pit-like structure in the Drosophila melanogaster antenna called the sacculus. They express a highly conserved receptor, Ir40a, and flies in which these neurons are silenced or Ir40a is knocked down lose avoidance to DEET. We used a computational structure-activity screen of >400,000 compounds that identified >100 natural compounds as candidate repellents. We tested several and found that most activate Ir40a(+) neurons and are repellents for Drosophila. These compounds are also strong repellents for mosquitoes. The candidates contain chemicals that do not dissolve plastic, are affordable and smell mildly like grapes, with three considered safe in human foods. Our findings pave the way to discover new generations of repellents that will help fight deadly insect-borne diseases worldwide.
C1 [Kain, Pinky; Tharadra, Sana Khalid; Guda, Tom; Dahanukar, Anupama; Ray, Anandasankar] Univ Calif Riverside, Dept Entomol, Riverside, CA 92521 USA.
   [Boyle, Sean Michael; Dahanukar, Anupama; Ray, Anandasankar] Univ Calif Riverside, Genet Genom & Bioinformat Program, Riverside, CA 92521 USA.
   [Christine Pham; Dahanukar, Anupama; Ray, Anandasankar] Univ Calif Riverside, Neurosci Program, Riverside, CA 92521 USA.
   [Dahanukar, Anupama; Ray, Anandasankar] Univ Calif Riverside, Inst Integrat Genome Biol, Riverside, CA 92521 USA.
C3 University of California System; University of California Riverside; University of California System; University of California Riverside; University of California System; University of California Riverside; University of California System; University of California Riverside
RP Ray, A (corresponding author), Univ Calif Riverside, Dept Entomol, Riverside, CA 92521 USA.
EM anand.ray@ucr.edu
FU Whitehall Foundation; NINDS [R21NS074332, R56AI099778, R01AI087785]
NR 53
TC 102
Z9 132
U1 1
U2 187
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 24
PY 2013
VL 502
IS 7472
BP 507
EP +
DI 10.1038/nature12594
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 238YN
UT WOS:000325988400045
PM 24089210
DA 2026-03-09
ER

PT J
AU Lam, TTY
   Wang, J
   Shen, YY
   Zhou, BP
   Duan, L
   Cheung, CL
   Ma, C
   Lycett, SJ
   Leung, CYH
   Chen, XC
   Li, LF
   Hong, WS
   Chai, YJ
   Zhou, LL
   Liang, HY
   Ou, ZH
   Liu, YM
   Farooqui, A
   Kelvin, DJ
   Poon, LLM
   Smith, DK
   Pybus, OG
   Leung, GM
   Shu, YL
   Webster, RG
   Webby, RJ
   Peiris, JSM
   Rambaut, A
   Zhu, HC
   Guan, Y
AF Lam, Tommy Tsan-Yuk
   Wang, Jia
   Shen, Yongyi
   Zhou, Boping
   Duan, Lian
   Cheung, Chung-Lam
   Ma, Chi
   Lycett, Samantha J.
   Leung, Connie Yin-Hung
   Chen, Xinchun
   Li, Lifeng
   Hong, Wenshan
   Chai, Yujuan
   Zhou, Linlin
   Liang, Huyi
   Ou, Zhihua
   Liu, Yongmei
   Farooqui, Amber
   Kelvin, David J.
   Poon, Leo L. M.
   Smith, David K.
   Pybus, Oliver G.
   Leung, Gabriel M.
   Shu, Yuelong
   Webster, Robert G.
   Webby, Richard J.
   Peiris, Joseph S. M.
   Rambaut, Andrew
   Zhu, Huachen
   Guan, Yi
TI The genesis and source of the H7N9 influenza viruses causing human infections in China
SO NATURE
LA English
DT Article
ID phylogenetic analysis; receptor-binding; southern china; establishment; transmission; sequences; accuracy; models; origin; ducks
AB A novel H7N9 influenza A virus first detected in March 2013 has since caused more than 130 human infections in China, resulting in 40 deaths(1,2). Preliminary analyses suggest that the virus is a reassortant of H7, N9 and H9N2 avian influenza viruses, and carries some amino acids associated with mammalian receptor binding, raising concerns of a new pandemic(1,3,4). However, neither the source populations of the H7N9 outbreak lineage nor the conditions for its genesis are fully known(5). Using a combination of active surveillance, screening of virus archives, and evolutionary analyses, here we show that H7 viruses probably transferred from domestic duck to chicken populations in China on at least two independent occasions. We show that the H7 viruses subsequently reassorted with enzootic H9N2 viruses to generate the H7N9 outbreak lineage, and a related previously unrecognized H7N7 lineage. The H7N9 outbreak lineage has spread over a large geographic region and is prevalent in chickens at live poultry markets, which are thought to be the immediate source of human infections. Whether the H7N9 outbreak lineage has, or will, become enzootic in China and neighbouring regions requires further investigation. The discovery here of a related H7N7 influenza virus in chickens that has the ability to infect mammals experimentally, suggests that H7 viruses may pose threats beyond the current outbreak. The continuing prevalence of H7 viruses in poultry could lead to the generation of highly pathogenic variants and further sporadic human infections, with a continued risk of the virus acquiring human-to-human transmissibility.
C1 [Lam, Tommy Tsan-Yuk; Wang, Jia; Shen, Yongyi; Ma, Chi; Li, Lifeng; Hong, Wenshan; Liang, Huyi; Ou, Zhihua; Liu, Yongmei; Smith, David K.; Leung, Gabriel M.; Zhu, Huachen; Guan, Yi] Shantou Univ, Coll Med, Joint Influenza Res Ctr SUMC HKU, Shantou 515041, Peoples R China.
   [Lam, Tommy Tsan-Yuk; Zhou, Boping; Duan, Lian; Chen, Xinchun; Li, Lifeng; Chai, Yujuan; Liang, Huyi; Ou, Zhihua; Poon, Leo L. M.; Peiris, Joseph S. M.; Zhu, Huachen; Guan, Yi] Shenzhen Third Peoples Hosp, HKU Shenzhen Branch, State Key Lab Emerging Infect Dis, Shenzhen 518112, Peoples R China.
   [Lam, Tommy Tsan-Yuk; Wang, Jia; Shen, Yongyi; Duan, Lian; Cheung, Chung-Lam; Ma, Chi; Leung, Connie Yin-Hung; Li, Lifeng; Chai, Yujuan; Zhou, Linlin; Liang, Huyi; Ou, Zhihua; Liu, Yongmei; Poon, Leo L. M.; Smith, David K.; Leung, Gabriel M.; Peiris, Joseph S. M.; Zhu, Huachen; Guan, Yi] Univ Hong Kong, Sch Publ Hlth, Influenza Res Ctr, State Key Lab Emerging Infect Dis, Hong Kong, Hong Kong, Peoples R China.
   [Shen, Yongyi] Xiamen Univ, Sch Life Sci, State Key Lab Cellular Stress Biol, Xiamen 361102, Peoples R China.
   [Lycett, Samantha J.; Rambaut, Andrew] Univ Edinburgh, Inst Evolutionary Biol, Edinburgh EH9 3JT, Midlothian, Scotland.
   [Farooqui, Amber; Kelvin, David J.] Shantou Univ, Coll Med, Joint Vaccine Res Ctr SUMC UHN, Shantou 515041, Peoples R China.
   [Pybus, Oliver G.] Univ Oxford, Dept Zool, Oxford OX1 3PS, England.
   [Pybus, Oliver G.] Metabiota, San Francisco, CA 94104 USA.
   [Shu, Yuelong] Natl Hlth & Family Planning Commiss, Chinese Ctr Dis Control & Prevent, Natl Inst Viral Dis Control & Prevent, Key Lab Med Virol, Beijing 102206, Peoples R China.
   [Webster, Robert G.; Webby, Richard J.] St Jude Childrens Res Hosp, Dept Infect Dis, Div Virol, Memphis, TN 38105 USA.
   [Rambaut, Andrew] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
C3 Shantou University; The Third People's Hospital of Shenzhen; University of Hong Kong; Xiamen University; University of Edinburgh; Shantou University; University of Oxford; Chinese Center for Disease Control & Prevention; National Institute for Viral Disease Control & Prevention, Chinese Center for Disease Control & Prevention; St Jude Children's Research Hospital; National Institutes of Health (NIH) - USA; NIH Fogarty International Center (FIC)
RP Zhu, HC (corresponding author), Shantou Univ, Coll Med, Joint Influenza Res Ctr SUMC HKU, Shantou 515041, Peoples R China.
EM zhuhch@hku.hk; yguan@hku.hk
FU National Institutes of Health (National Institute of Allergy and Infectious Diseases) [HSN266200700005C]; Li Ka Shing Foundation; University Grants Committee of the Hong Kong SAR [AoE/M-12/06]; Shenzhen Peacock Plan High-End Talents Program [KQTD201203]; University Development Fund (HKU); Innovation and Technology Commission of the Hong Kong Government; Newton International Fellowship of the Royal Society; US Agency for International Development (USAID) Emerging Pandemic Threats Program, PREDICT project [GHN-A-OO-09-00010-00]; European Union [278433-PREDEMICS]; ERC [260864]; Wellcome Trust [092807]; BBSRC [BB/E009670/1] Funding Source: UKRI; Biotechnology and Biological Sciences Research Council [BB/E009670/1] Funding Source: researchfish
NR 28
TC 395
Z9 462
U1 1
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 OCT 10
PY 2013
VL 502
IS 7470
BP 241
EP +
DI 10.1038/nature12515
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 231RU
UT WOS:000325436100052
PM 23965623
DA 2026-03-09
ER

PT J
AU Zhu, M
   Yu, XB
   Ahlberg, PE
   Choo, B
   Lu, J
   Qiao, T
   Qu, QM
   Zhao, WJ
   Jia, LT
   Blom, H
   Zhu, YA
AF Zhu, Min
   Yu, Xiaobo
   Ahlberg, Per Erik
   Choo, Brian
   Lu, Jing
   Qiao, Tuo
   Qu, Qingming
   Zhao, Wenjin
   Jia, Liantao
   Blom, Henning
   Zhu, You'an
TI A Silurian placoderm with osteichthyan-like marginal jaw bones
SO NATURE
LA English
DT Article
ID fishes; ptyctodontida; information; inference; mrbayes; origin
AB The gnathostome (jawed vertebrate) crown group comprises two extant clades with contrasting character complements. Notably, Chondrichthyes (cartilaginous fish) lack the large dermal bones that characterize Osteichthyes (bony fish and tetrapods). The polarities of these differences, and the morphology of the last common ancestor of crown gnathostomes, are the subject of continuing debate. Here we describe a three-dimensionally preserved 419-million-year-old placoderm fish from the Silurian of China that represents the first stem gnathostome with dermal marginal jaw bones (premaxilla, maxilla and dentary), features previously restricted to Osteichthyes. A phylogenetic analysis places the new form near the top of the gnathostome stem group but does not fully resolve its relationships to other placoderms. The analysis also assigns all acanthodians to the chondrichthyan stem group. These results suggest that the last common ancestor of Chondrichthyes and Osteichthyes had a macromeric dermal skeleton, and provide a new framework for studying crown gnathostome divergence.
C1 [Zhu, Min; Yu, Xiaobo; Choo, Brian; Lu, Jing; Qiao, Tuo; Zhao, Wenjin; Jia, Liantao; Zhu, You'an] Chinese Acad Sci, Inst Vertebrate Paleontol & Paleoanthropol, Key Lab Vertebrate Evolut & Human Origins, Beijing 100044, Peoples R China.
   [Yu, Xiaobo] Kean Univ, Dept Biol Sci, Union, NJ 07083 USA.
   [Ahlberg, Per Erik; Qu, Qingming; Blom, Henning] Uppsala Univ, Dept Organismal Biol, Evolutionary Biol Ctr, Subdept Evolut & Dev, S-75236 Uppsala, Sweden.
C3 Chinese Academy of Sciences; Institute of Vertebrate Paleontology & Paleoanthropology, CAS; Kean University; Uppsala University
RP Zhu, M (corresponding author), Chinese Acad Sci, Inst Vertebrate Paleontol & Paleoanthropol, Key Lab Vertebrate Evolut & Human Origins, Beijing 100044, Peoples R China.
EM zhumin@ivpp.ac.cn
FU Major State Basic Research Projects of MST of China [2012CB821902]; National Natural Science Foundation of China [40930208]; ERC [233111]; Knut and Alice Wallenberg Foundation
NR 40
TC 233
Z9 278
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 OCT 10
PY 2013
VL 502
IS 7470
BP 188
EP +
DI 10.1038/nature12617
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 231RU
UT WOS:000325436100041
PM 24067611
DA 2026-03-09
ER

PT J
AU Morgan, JLW
   Strumillo, J
   Zimmer, J
AF Morgan, Jacob L. W.
   Strumillo, Joanna
   Zimmer, Jochen
TI Crystallographic snapshot of cellulose synthesis and membrane translocation
SO NATURE
LA English
DT Article
ID c-di-gmp; acetobacter-xylinum; structural basis; in-vitro; biosynthesis; synthases; binding; system; glycosyltransferases; microfibrils
AB Cellulose, the most abundant biological macromolecule, is an extracellular, linear polymer of glucose molecules. It represents an essential component of plant cell walls but is also found in algae and bacteria. In bacteria, cellulose production frequently correlates with the formation of biofilms, a sessile, multicellular growth form. Cellulose synthesis and transport across the inner bacterial membrane is mediated by a complex of the membrane-integrated catalytic BcsA subunit and the membrane-anchored, periplasmic BcsB protein. Here we present the crystal structure of a complex of BcsA and BcsB from Rhodobacter sphaeroides containing a translocating polysaccharide. The structure of the BcsA-BcsB translocation intermediate reveals the architecture of the cellulose synthase, demonstrates how BcsA forms a cellulose-conducting channel, and suggests a model for the coupling of cellulose synthesis and translocation in which the nascent polysaccharide is extended by one glucose molecule at a time.
C1 [Morgan, Jacob L. W.; Strumillo, Joanna; Zimmer, Jochen] Univ Virginia, Dept Mol Physiol & Biol Phys, Ctr Membrane Biol, Charlottesville, VA 22908 USA.
   [Strumillo, Joanna] Univ Lodz, Fac Biol & Environm Protect, PL-90231 Lodz, Poland.
C3 University of Virginia; University of Lodz
RP Zimmer, J (corresponding author), Univ Virginia, Dept Mol Physiol & Biol Phys, Ctr Membrane Biol, Charlottesville, VA 22908 USA.
EM jochen_zimmer@virginia.edu
FU US Department of Energy, Office of Science, Office of Basic Energy Sciences [DE-AC02-06CH11357, W-31-109-Eng-38]; National Cancer Institute [Y1-CO-1020]; National Institute of General Medical Sciences [Y1-GM-1104]; Department of Energy [DE-FG02-09ER-20097]; NIH [1R01GM101001]; University of Virginia; University of Virginia School of Medicine; National Institute of General Medical Sciences [R01GM101001] Funding Source: NIH RePORTER
NR 50
TC 462
Z9 551
U1 10
U2 484
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 10
PY 2013
VL 493
IS 7431
BP 181
EP U192
DI 10.1038/nature11744
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 066YY
UT WOS:000313259600031
PM 23222542
DA 2026-03-09
ER

PT J
AU Siponen, MI
   Legrand, P
   Widdrat, M
   Jones, SR
   Zhang, WJ
   Chang, MCY
   Faivre, D
   Arnoux, P
   Pignol, D
AF Siponen, Marina I.
   Legrand, Pierre
   Widdrat, Marc
   Jones, Stephanie R.
   Zhang, Wei-Jia
   Chang, Michelle C. Y.
   Faivre, Damien
   Arnoux, Pascal
   Pignol, David
TI Structural insight into magnetochrome-mediated magnetite biomineralization
SO NATURE
LA English
DT Article
ID c-type cytochrome; magnetospirillum-gryphiswaldense; small-angle; protein; refinement; scattering; reveals
AB Magnetotactic bacteria align along the Earth's magnetic field using an organelle called the magnetosome, a biomineralized magnetite (Fe(II)Fe(III)(2)O-4) or greigite (Fe(II)Fe(III)(2)S-4) crystal embedded in a lipid vesicle. Although the need for both iron(II) and iron(III) is clear, little is known about the biological mechanisms controlling their ratio(1). Here we present the structure of the magnetosome-associated protein MamP and find that it is built on a unique arrangement of a self-plugged PDZ domain fused to two magnetochrome domains, defining a new class of c-type cytochrome exclusively found in magnetotactic bacteria. Mutational analysis, enzyme kinetics, co-crystallization with iron(II) and an in vitro MamP-assisted magnetite production assay establish MamP as an iron oxidase that contributes to the formation of iron(III) ferrihydrite eventually required for magnetite crystal growth in vivo. These results demonstrate the molecular mechanisms of iron management taking place inside the magnetosome and highlight the role of magnetochrome in iron biomineralization.
C1 [Siponen, Marina I.; Arnoux, Pascal; Pignol, David] Commissariat Energie Atom & Energies Alternat, Direct Sci Vivant, Inst Biol Environm & Biotechnol, Lab Bioenerget Cellulaire, F-13108 St Paul Les Durance, France.
   [Siponen, Marina I.; Arnoux, Pascal; Pignol, David] CNRS, Unite Mixte Rech Biol Vegetaleet Microbiol Enviro, F-13108 St Paul Les Durance, France.
   [Siponen, Marina I.; Arnoux, Pascal; Pignol, David] Aix Marseille Univ, F-13108 St Paul Les Durance, France.
   [Legrand, Pierre] Synchrotron SOLEIL, F-91192 Gif Sur Yvette, France.
   [Widdrat, Marc; Faivre, Damien] Max Planck Inst Colloids & Interfaces, Dept Biomat, D-14424 Potsdam, Germany.
   [Jones, Stephanie R.; Chang, Michelle C. Y.] Univ Calif Berkeley, Dept Chem, Berkeley, CA 94720 USA.
   [Jones, Stephanie R.; Chang, Michelle C. Y.] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA.
   [Zhang, Wei-Jia] Aix Marseille Univ, Lab Chim Bacterienne, Inst Microbiol Mediterranee, UMR7283,CNRS, F-13402 Marseille 20, France.
   [Zhang, Wei-Jia; Arnoux, Pascal; Pignol, David] CNRS, Lab Int Assoc Biomineralisat & Nanostruct, F-13402 Marseille 20, France.
C3 CEA; Centre National de la Recherche Scientifique (CNRS); Aix-Marseille Universite; SOLEIL Synchrotron; Max Planck Society; University of California System; University of California Berkeley; University of California System; University of California Berkeley; Aix-Marseille Universite; Centre National de la Recherche Scientifique (CNRS); Centre National de la Recherche Scientifique (CNRS)
RP Pignol, D (corresponding author), Commissariat Energie Atom & Energies Alternat, Direct Sci Vivant, Inst Biol Environm & Biotechnol, Lab Bioenerget Cellulaire, F-13108 St Paul Les Durance, France.
EM pascal.arnoux@cea.fr; david.pignol@cea.fr
FU Eurotalent program; ToxNuc-E program; Max Planck Society; ERC [256915-MB2]; Defense Advanced Research Projects Agency [N66001-12-1-4230]; National Institute of General Medical Sciences [T32GM066698] Funding Source: NIH RePORTER
NR 32
TC 116
Z9 136
U1 0
U2 269
PU NATURE PUBLISHING 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 31
PY 2013
VL 502
IS 7473
BP 681
EP +
DI 10.1038/nature12573
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 243CC
UT WOS:000326293200047
PM 24097349
DA 2026-03-09
ER

PT J
AU Mora, C
   Frazier, AG
   Longman, RJ
   Dacks, RS
   Walton, MM
   Tong, EJ
   Sanchez, JJ
   Kaiser, LR
   Stender, YO
   Anderson, JM
   Ambrosino, CM
   Fernandez-Silva, I
   Giuseffi, LM
   Giambelluca, TW
AF Mora, Camilo
   Frazier, Abby G.
   Longman, Ryan J.
   Dacks, Rachel S.
   Walton, Maya M.
   Tong, Eric J.
   Sanchez, Joseph J.
   Kaiser, Lauren R.
   Stender, Yuko O.
   Anderson, James M.
   Ambrosino, Christine M.
   Fernandez-Silva, Iria
   Giuseffi, Louise M.
   Giambelluca, Thomas W.
TI The projected timing of climate departure from recent variability
SO NATURE
LA English
DT Article
ID global patterns; change impacts; species richness; range shifts; biodiversity; extinction; disease; events; future; face
AB Ecological and societal disruptions by modern climate change are critically determined by the time frame over which climates shift beyond historical analogues. Here we present a new index of the year when the projected mean climate of a given location moves to a state continuously outside the bounds of historical variability under alternative greenhouse gas emissions scenarios. Using 1860 to 2005 as the historical period, this index has a global mean of 2069 (+/- 18 years s.d.) for near-surface air temperature under an emissions stabilization scenario and 2047 (+/- 14 years s.d.) under a 'business-as-usual' scenario. Unprecedented climates will occur earliest in the tropics and among low-income countries, highlighting the vulnerability of global biodiversity and the limited governmental capacity to respond to the impacts of climate change. Our findings shed light on the urgency of mitigating greenhouse gas emissions if climates potentially harmful to biodiversity and society are to be prevented.
C1 [Mora, Camilo; Frazier, Abby G.; Longman, Ryan J.; Sanchez, Joseph J.; Kaiser, Lauren R.; Stender, Yuko O.; Giuseffi, Louise M.; Giambelluca, Thomas W.] Univ Hawaii Manoa, Dept Geog, Honolulu, HI 96822 USA.
   [Dacks, Rachel S.; Walton, Maya M.; Anderson, James M.; Ambrosino, Christine M.] Univ Hawaii Manoa, Dept Biol, Honolulu, HI 96822 USA.
   [Walton, Maya M.; Tong, Eric J.; Stender, Yuko O.; Anderson, James M.; Ambrosino, Christine M.; Fernandez-Silva, Iria] Univ Hawaii Manoa, Hawaii Inst Marine Biol, Kaneohe, HI 96744 USA.
   [Tong, Eric J.] Univ Hawaii Manoa, Dept Oceanog, Honolulu, HI 96822 USA.
   [Fernandez-Silva, Iria] Univ Ryukyus, TRO SIS, Nishihara, Okinawa 9030213, Japan.
C3 University of Hawaii System; University of Hawaii Manoa; University of Hawaii System; University of Hawaii Manoa; University of Hawaii System; University of Hawaii Manoa; University of Hawaii System; University of Hawaii Manoa; University of the Ryukyus
RP Mora, C (corresponding author), Univ Hawaii Manoa, Dept Geog, Honolulu, HI 96822 USA.
EM cmora@hawaii.edu
FU Pacific Islands Climate Change Cooperative (PICCC) [F10AC00077]; National Science Foundation Hawai'i EPSCoR [EPS-0903833]; Pacific Islands Climate Science Center; PICCC [F10A00079]; National Science Foundation; Japanese Society for the Promotion of Science; Office Of The Director; EPSCoR [0903833] Funding Source: National Science Foundation
NR 51
TC 524
Z9 631
U1 2
U2 283
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 10
PY 2013
VL 502
IS 7470
BP 183
EP +
DI 10.1038/nature12540
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 231RU
UT WOS:000325436100040
PM 24108050
DA 2026-03-09
ER

PT J
AU Greenbaum, A
   Hsu, YMS
   Day, RB
   Schuettpelz, LG
   Christopher, MJ
   Borgerding, JN
   Nagasawa, T
   Link, DC
AF Greenbaum, Adam
   Hsu, Yen-Michael S.
   Day, Ryan B.
   Schuettpelz, Laura G.
   Christopher, Matthew J.
   Borgerding, Joshua N.
   Nagasawa, Takashi
   Link, Daniel C.
TI CXCL12 in early mesenchymal progenitors is. required for haematopoietic stem-cell maintenance
SO NATURE
LA English
DT Article
ID bone-marrow; mice; regeneration; engraftment; quiescence; expression; reveals; cxcr4; fetal
AB Haematopoietic stem cells (HSCs) primarily reside in the bone marrow where signals generated by stromal cells regulate their self-renewal, proliferation and trafficking. Endosteal osteoblasts(1,2) and perivascular stromal cells including endothelial cells(3), CXCL12-abundant reticular cells(4,5), leptin-receptor-positive stromal cells(6), and nestin-green fluorescent protein (GFP) -positive mesenchymal progenitors(7) have all been implicated in HSC maintenance. However, it is unclear whether specific haematopoietic progenitor cell (HPC) subsets reside in distinct niches defined by the surrounding stromal cells and the regulatory molecules they produce. CXCL12 (chemokine (C-X-C motif) ligand 12) regulates both HSCs and lymphoid progenitors and is expressed by all of these stromal cell populations(7-11). Here we selectively deleted Cxcl12 from candidate niche stromal cell populations and characterized the effect on HPCs. Deletion of Cxcl12 from mineralizing osteoblasts has no effect on HSCs or lymphoid progenitors. Deletion of Cxcl12 from osterix-expressing stromal cells, which include CXCL12-abundant reticular cells and osteoblasts, results in constitutive HPC mobilization and a loss of B-lymphoid progenitors, but HSC function is normal. Cxcl12 deletion from endothelial cells results in a modest loss of long-term repopulating activity. Strikingly, deletion of Cxcl12 from nestin-negative mesenchymal progenitors using Prx1-cre (Pod also known as Prrx1) is associated with a marked loss of HSCs, long-term repopulating activity, HSC quiescence and common lymphoid progenitors. These data suggest that osterix-expressing stromal cells comprise a distinct niche that supports B-lymphoid progenitors and retains HPCs in the bone marrow, and that expression of CXCL12 from stromal cells in the perivascular region, including endothelial cells and mesenchymal progenitors, supports HSCs.
C1 [Greenbaum, Adam; Day, Ryan B.; Christopher, Matthew J.; Borgerding, Joshua N.; Link, Daniel C.] Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA.
   [Hsu, Yen-Michael S.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA.
   [Schuettpelz, Laura G.] Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA.
   [Nagasawa, Takashi] Kyoto Univ, Inst Frontier Med Sci, Dept Immunobiol & Hematol, Kyoto 6068507, Japan.
   [Nagasawa, Takashi] Japan Sci & Technol Agcy, Core Res Evolutionary Sci & Technol, Tokyo 1020075, Japan.
C3 Washington University (WUSTL); Washington University (WUSTL); Washington University (WUSTL); Kyoto University; Japan Science & Technology Agency (JST)
RP Link, DC (corresponding author), Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA.
EM dlink@dom.wustl.edu
FU NIH [RO1 HL60772, F30 HL097423]; Grants-in-Aid for Scientific Research [22390096, 24111003, 24111001] Funding Source: KAKEN
NR 29
TC 1086
Z9 1291
U1 3
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 MAR 14
PY 2013
VL 495
IS 7440
BP 227
EP 230
DI 10.1038/nature11926
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 113FP
UT WOS:000316652300049
PM 23434756
DA 2026-03-09
ER

PT J
AU Barouch, DH
   Whitney, JB
   Moldt, B
   Klein, F
   Oliveira, TY
   Liu, JY
   Stephenson, KE
   Chang, HW
   Shekhar, K
   Gupta, S
   Nkolola, JP
   Seaman, MS
   Smith, KM
   Borducchi, EN
   Cabral, C
   Smith, JY
   Blackmore, S
   Sanisetty, S
   Perry, JR
   Beck, M
   Lewis, MG
   Rinaldi, W
   Chakraborty, AK
   Poignard, P
   Nussenzweig, MC
   Burton, DR
AF Barouch, Dan H.
   Whitney, James B.
   Moldt, Brian
   Klein, Florian
   Oliveira, Thiago Y.
   Liu, Jinyan
   Stephenson, Kathryn E.
   Chang, Hui-Wen
   Shekhar, Karthik
   Gupta, Sanjana
   Nkolola, Joseph P.
   Seaman, Michael S.
   Smith, Kaitlin M.
   Borducchi, Erica N.
   Cabral, Crystal
   Smith, Jeffrey Y.
   Blackmore, Stephen
   Sanisetty, Srisowmya
   Perry, James R.
   Beck, Matthew
   Lewis, Mark G.
   Rinaldi, William
   Chakraborty, Arup K.
   Poignard, Pascal
   Nussenzweig, Michel C.
   Burton, Dennis R.
TI Therapeutic efficacy of potent neutralizing HIV-1-specific monoclonal antibodies in SHIV-infected rhesus monkeys
SO NATURE
LA English
DT Article
ID recombinant adenovirus vectors; antiretroviral therapy; hiv-1; broad; vaccine; challenges; responses; memory
AB Human immunodeficiency virus type 1 (HIV-1)-specific monoclonal antibodies with extraordinary potency and breadth have recently been described. In humanized mice, combinations of monoclonal antibodies have been shown to suppress viraemia, but the therapeutic potential of these monoclonal antibodies has not yet been evaluated in primates with an intact immune system. Here we show that administration of a cocktail of HIV-1-specific monoclonal antibodies, as well as the single glycan-dependent monoclonal antibody PGT121, resulted in a rapid and precipitous decline of plasma viraemia to undetectable levels in rhesus monkeys chronically infected with the pathogenic simian-human immunodeficiency virus SHIV-SF162P3. A single monoclonal antibody infusion afforded up to a 3.1 log decline of plasma viral RNA in 7 days and also reduced proviral DNA in peripheral blood, gastrointestinal mucosa and lymph nodes without the development of viral resistance. Moreover, after monoclonal antibody administration, host Gag-specific T-lymphocyte responses showed improved functionality. Virus rebounded in most animals after a median of 56 days when serum monoclonal antibody titres had declined to undetectable levels, although, notably, a subset of animals maintained long-term virological control in the absence of further monoclonal antibody infusions. These data demonstrate a profound therapeutic effect of potent neutralizing HIV-1-specific monoclonal antibodies in SHIV-infected rhesus monkeys as well as an impact on host immune responses. Our findings strongly encourage the investigation of monoclonal antibody therapy for HIV-1 in humans.
C1 [Barouch, Dan H.; Whitney, James B.; Liu, Jinyan; Stephenson, Kathryn E.; Chang, Hui-Wen; Nkolola, Joseph P.; Seaman, Michael S.; Smith, Kaitlin M.; Borducchi, Erica N.; Cabral, Crystal; Smith, Jeffrey Y.; Blackmore, Stephen; Sanisetty, Srisowmya; Perry, James R.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Ctr Virol & Vaccine Res, Boston, MA 02215 USA.
   [Barouch, Dan H.; Chakraborty, Arup K.; Burton, Dennis R.] Ragon Inst MGH MIT & Harvard, Cambridge, MA 02139 USA.
   [Moldt, Brian; Poignard, Pascal; Burton, Dennis R.] Scripps Res Inst, La Jolla, CA 92037 USA.
   [Klein, Florian; Oliveira, Thiago Y.; Nussenzweig, Michel C.] Rockefeller Univ, New York, NY 10065 USA.
   [Shekhar, Karthik; Gupta, Sanjana; Chakraborty, Arup K.] MIT, Cambridge, MA 02139 USA.
   [Beck, Matthew] New England Primate Res Ctr, Southborough, MA 01776 USA.
   [Lewis, Mark G.] Bioqual Inc, Rockville, MD 20852 USA.
   [Rinaldi, William] Alpha Genesis Inc, Yemassee, SC 29945 USA.
   [Nussenzweig, Michel C.] Howard Hughes Med Inst, New York, NY 10065 USA.
C3 Harvard University; Harvard University Medical Affiliates; Beth Israel Deaconess Medical Center; Harvard Medical School; Harvard University; Harvard Medical School; Massachusetts Institute of Technology (MIT); Ragon Institute; Harvard University Medical Affiliates; Massachusetts General Hospital; Scripps Research Institute; Rockefeller University; Massachusetts Institute of Technology (MIT); BIOQUAL Inc.; Howard Hughes Medical Institute
RP Barouch, DH (corresponding author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Ctr Virol & Vaccine Res, Boston, MA 02215 USA.
EM dbarouch@bidmc.harvard.edu
FU National Institutes of Health [AI055332, AI060354, AI078526, AI084794, AI095985, AI096040, AI10063, AI100148, AI100663]; Bill and Melinda Gates Foundation [OPP1033091, OPP1033115, OPP1040741, OPP1040753]; Ragon Institute of MGH, MIT, and Harvard; Lundbeck Foundation; Stavros Niarchos Foundation; National Institute of Allergy and Infectious Diseases [T32AI007387, P01AI100148] Funding Source: NIH RePORTER; National Institute on Drug Abuse; National Institute of Diabetes and Digestive and Kidney Diseases; National Institute on Minority Health and Health Disparities; National Institute of Allergy and Infectious Diseases; National Institute of Dental and Craniofacial Research; National Institute of Nursing Research; National Institute on Aging; National Cancer Institute; Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Heart Lung and Blood Institute [P30AI060354] Funding Source: NIH RePORTER; NIH Office of the Director [P40OD012217] Funding Source: NIH RePORTER; Bill and Melinda Gates Foundation [OPP1033115, OPP1040753] Funding Source: Bill and Melinda Gates Foundation
NR 39
TC 549
Z9 693
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 NOV 14
PY 2013
VL 503
IS 7475
BP 224
EP +
DI 10.1038/nature12744
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 250YX
UT WOS:000326894200043
PM 24172905
DA 2026-03-09
ER

PT J
AU Geng, Y
   Bush, M
   Mosyak, L
   Wang, F
   Fan, QR
AF Geng, Yong
   Bush, Martin
   Mosyak, Lidia
   Wang, Feng
   Fan, Qing R.
TI Structural mechanism of ligand activation in human GABAB receptor
SO NATURE
LA English
DT Article
ID aminobutyric acid(b) receptors; protein-coupled receptor; n-terminal domain; extracellular domain; gb2 subunits; glutamate; binding; pharmacology; antagonist; expression
AB Human GABA(B) (gamma-aminobutyric acid class B) receptor is a G-protein-coupled receptor central to inhibitory neurotransmission in the brain. It functions as an obligatory heterodimer of the subunits GBR1 and GBR2. Here we present the crystal structures of a heterodimeric complex between the extracellular domains of GBR1 and GBR2 in the apo, agonist-bound and antagonist-bound forms. The apo and antagonist-bound structures represent the resting state of the receptor; the agonist-bound complex corresponds to the active state. Both subunits adopt an open conformation at rest, and only GBR1 closes on agonist-induced receptor activation. The agonists and antagonists are anchored in the interdomain crevice of GBR1 by an overlapping set of residues. An antagonist confines GBR1 to the open conformation of the inactive state, whereas an agonist induces its domain closure for activation. Our data reveal a unique activation mechanism for GABA(B) receptor that involves the formation of a novel heterodimer interface between subunits.
C1 [Geng, Yong; Bush, Martin; Mosyak, Lidia; Wang, Feng; Fan, Qing R.] Columbia Univ, Dept Pharmacol, New York, NY 10032 USA.
   [Fan, Qing R.] Columbia Univ, Dept Pathol & Cell Biol, New York, NY 10032 USA.
C3 Columbia University; Columbia University
RP Fan, QR (corresponding author), Columbia Univ, Dept Pharmacol, New York, NY 10032 USA.
EM qf13@columbia.edu
FU American Heart Association [SDG0835183N]; National Institute of Health [R01GM088454]
NR 62
TC 168
Z9 203
U1 1
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 DEC 12
PY 2013
VL 504
IS 7479
BP 254
EP +
DI 10.1038/nature12725
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 267TQ
UT WOS:000328121500031
PM 24305054
DA 2026-03-09
ER

PT J
AU Kaplon, J
   Zheng, L
   Meissl, K
   Chaneton, B
   Selivanov, VA
   Mackay, G
   van der Burg, SH
   Verdegaal, EME
   Cascante, M
   Shlomi, T
   Gottlieb, E
   Peeper, DS
AF Kaplon, Joanna
   Zheng, Liang
   Meissl, Katrin
   Chaneton, Barbara
   Selivanov, Vitaly A.
   Mackay, Gillian
   van der Burg, Sjoerd H.
   Verdegaal, Elizabeth M. E.
   Cascante, Marta
   Shlomi, Tomer
   Gottlieb, Eyal
   Peeper, Daniel S.
TI A key role for mitochondrial gatekeeper pyruvate dehydrogenase in oncogene-induced senescence
SO NATURE
LA English
DT Article
ID cell senescence; kinase; complex; cancer
AB In response to tenacious stress signals, such as the unscheduled activation of oncogenes, cells can mobilize tumour suppressor networks to avert the hazard of malignant transformation. A large body of evidence indicates that oncogene-induced senescence (OIS) acts as such a break, withdrawing cells from the proliferative pool almost irreversibly, thus crafting a vital pathophysiological mechanism that protects against cancer(1-5). Despite the widespread contribution of OIS to the cessation of tumorigenic expansion in animal models and humans, we have only just begun to define the underlying mechanism and identify key players(6). Although deregulation of metabolism is intimately linked to the proliferative capacity of cells(7-10), and senescent cells are thought to remain metabolically active(11), little has been investigated in detail about the role of cellular metabolism in OIS. Here we show, by metabolic profiling and functional perturbations, that the mitochondrial gatekeeper pyruvate dehydrogenase (PDH) is a crucial mediator of senescence induced by BRAF(V600E), an oncogene commonly mutated in melanoma and other cancers. BRAF(V600E)-induced senescence was accompanied by simultaneous suppression of the PDH-inhibitory enzyme pyruvate dehydrogenase kinase 1 (PDK1) and induction of the PDH-activating enzyme pyruvate dehydrogenase phosphatase 2 (PDP2). The resulting combined activation of PDH enhanced the use of pyruvate in the tricarboxylic acid cycle, causing increased respiration and redox stress. Abrogation of OIS, a rate-limiting step towards oncogenic transformation, coincided with reversion of these processes. Further supporting a crucial role of PDH in OIS, enforced normalization of either PDK1 or PDP2 expression levels inhibited PDH and abrogated OIS, thereby licensing BRAF(V600E)-driven melanoma development. Finally, depletion of PDK1 eradicated melanoma subpopulations resistant to targeted BRAF inhibition, and caused regression of established melanomas. These results reveal a mechanistic relationship between OIS and a key metabolic signalling axis, which may be exploited therapeutically.
C1 [Kaplon, Joanna; Meissl, Katrin; Peeper, Daniel S.] Netherlands Canc Inst, Div Mol Oncol, NL-1066 CX Amsterdam, Netherlands.
   [Zheng, Liang; Chaneton, Barbara; Mackay, Gillian; Gottlieb, Eyal] Canc Res UK, Beatson Inst Canc Res, Glasgow G61 1BD, Lanark, Scotland.
   [Selivanov, Vitaly A.; Cascante, Marta] Univ Barcelona, Fac Biol, Dept Biochem & Mol Biol, E-08028 Barcelona, Spain.
   [Selivanov, Vitaly A.; Cascante, Marta] Univ Barcelona, Fac Biol, IBUB, E-08028 Barcelona, Spain.
   [Selivanov, Vitaly A.; Cascante, Marta] Inst Invest Biomed August Pi & Sunyer IDIBAPS, Barcelona 08036, Spain.
   [van der Burg, Sjoerd H.; Verdegaal, Elizabeth M. E.] Leiden Univ, Med Ctr, Dept Clin Oncol, NL-2333 ZA Leiden, Netherlands.
   [Shlomi, Tomer] Technion Israel Inst Technol, Dept Comp Sci, IL-32000 Haifa, Israel.
   [Shlomi, Tomer] Princeton Univ, Lewis Sigler Inst Integrat Genom, Princeton, NJ USA.
C3 Netherlands Cancer Institute; Beatson Institute; Cancer Research UK; University of Barcelona; University of Barcelona; University of Barcelona; Hospital Clinic de Barcelona; IDIBAPS; Leiden University - Excl LUMC; Leiden University; Leiden University Medical Center (LUMC); Technion Israel Institute of Technology; Princeton University
RP Gottlieb, E (corresponding author), Canc Res UK, Beatson Inst Canc Res, Glasgow G61 1BD, Lanark, Scotland.
EM e.gottlieb@beatson.gla.ac.uk; d.peeper@nki.nl
FU Cancer Research UK, Spanish Government-EU-FEDER [SAF2011-25726, ISCIII-RTICC-RD6/0020/0046]; ICREA-Academia; Israel Cancer Research Foundation; Israel Science Foundation; Netherlands Organization for Scientific Research (NWO); Dutch Cancer Society (KWF Kankerbestrijding)
NR 33
TC 510
Z9 572
U1 0
U2 147
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 6
PY 2013
VL 498
IS 7452
BP 109
EP +
DI 10.1038/nature12154
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 158DC
UT WOS:000319947800043
PM 23685455
DA 2026-03-09
ER

PT J
AU Kamat, SS
   Williams, HJ
   Dangott, LJ
   Chakrabarti, M
   Raushel, FM
AF Kamat, Siddhesh S.
   Williams, Howard J.
   Dangott, Lawrence J.
   Chakrabarti, Mrinmoy
   Raushel, Frank M.
TI The catalytic mechanism for aerobic formation of methane by bacteria
SO NATURE
LA English
DT Article
ID carbon-phosphorus lyase; structural basis; radical sam; glycyl; degradation; phosphate; enzyme; acid
AB Methane is a potent greenhouse gas that is produced in significant quantities by aerobic marine organisms(1). These bacteria apparently catalyse the formation of methane through the cleavage of the highly unreactive carbon-phosphorus bond inmethylphosphonate(MPn), but the biological or terrestrial source of this compound is unclear(2). However, the ocean-dwelling bacterium Nitrosopumilus maritimus catalyses the biosynthesis of MPn from 2-hydroxyethyl phosphonate(3) and the bacterial C-P lyase complex is known to convert MPn to methane(4-7). In addition to MPn, the bacterial C-P lyase complex catalyses C-P bond cleavage of many alkyl phosphonates when the environmental concentration of phosphate is low(4-7). PhnJ from the C-P lyase complex catalyses an unprecedented C-P bond cleavage reaction of ribose-1-phosphonate-5-phosphate to methane and ribose-1,2-cyclic-phosphate-5-phosphate. This reaction requires a redox-active [4Fe-4S]-cluster and S-adenosyl-L-methionine, which is reductively cleaved to L-methionine and 5'-deoxyadenosine(8). Here we show that PhnJ is a novel radical S-adenosyl-L-methionine enzyme that catalyses C-P bond cleavage through the initial formation of a 5'-deoxyadenosyl radical and two protein-based radicals localized at Gly 32 and Cys 272. During this transformation, the pro-R hydrogen from Gly 32 is transferred to the 5'-deoxyadenosyl radical to form 5'-deoxyadenosine and the pro-S hydrogen is transferred to the radical intermediate that ultimately generates methane. A comprehensive reaction mechanism is proposed for cleavage of the C-P bond by the C-P lyase complex that uses a covalent thiophosphate intermediate for methane and phosphate formation.
C1 [Kamat, Siddhesh S.; Williams, Howard J.; Chakrabarti, Mrinmoy; Raushel, Frank M.] Texas A&M Univ, Dept Chem, College Stn, TX 77843 USA.
   [Dangott, Lawrence J.] Texas A&M Univ, Dept Biochem & Biophys, Prot Chem Lab, College Stn, TX 77843 USA.
C3 Texas A&M University System; Texas A&M University College Station; Texas A&M University System; Texas A&M University College Station
RP Raushel, FM (corresponding author), Texas A&M Univ, Dept Chem, POB 30012, College Stn, TX 77843 USA.
EM raushel@tamu.edu
FU Robert A. Welch Foundation [A-840]
NR 22
TC 83
Z9 105
U1 3
U2 246
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 2
PY 2013
VL 497
IS 7447
BP 132
EP 136
DI 10.1038/nature12061
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 134OK
UT WOS:000318221500048
PM 23615610
DA 2026-03-09
ER

PT J
AU Simanshu, DK
   Kamlekar, RK
   Wijesinghe, DS
   Zou, XQ
   Zhai, XH
   Mishra, SK
   Molotkovsky, JG
   Malinina, L
   Hinchcliffe, EH
   Chalfant, CE
   Brown, RE
   Patel, DJ
AF Simanshu, Dhirendra K.
   Kamlekar, Ravi Kanth
   Wijesinghe, Dayanjan S.
   Zou, Xianqiong
   Zhai, Xiuhong
   Mishra, Shrawan K.
   Molotkovsky, Julian G.
   Malinina, Lucy
   Hinchcliffe, Edward H.
   Chalfant, Charles E.
   Brown, Rhoderick E.
   Patel, Dinshaw J.
TI Non-vesicular trafficking by a ceramide-1-phosphate transfer protein regulates eicosanoids
SO NATURE
LA English
DT Article
ID glycolipid transfer protein; ceramide kinase; structural basis; evolution; complex; localization; organization; 1-phosphate; recognition; transport
AB Phosphorylated sphingolipids ceramide-1-phosphate (C1P) and sphingosine-1-phosphate (S1P) have emerged as key regulators of cell growth, survival, migration and inflammation(1-5). C1P produced by ceramide kinase is an activator of group IVA cytosolic phospholipase A(2)alpha (cPLA(2)alpha), the rate-limiting releaser of arachidonic acid used for pro-inflammatory eicosanoid production(3,6-9), which contributes to disease pathogenesis in asthma or airway hyper-responsiveness, cancer, atherosclerosis and thrombosis. To modulate eicosanoid action and avoid the damaging effects of chronic inflammation, cells require efficient targeting, trafficking and presentation of C1P to specific cellular sites. Vesicular trafficking is likely(10) but non-vesicular mechanisms for C1P sensing, transfer and presentation remain unexplored(11,12). Moreover, the molecular basis for selective recognition and binding among signalling lipids with phosphate headgroups, namely C1P, phosphatidic acid or their lyso-derivatives, remains unclear. Here, a ubiquitously expressed lipid transfer protein, human GLTPD1, named here CPTP, is shown to specifically transfer C1P between membranes. Crystal structures establish C1P binding through a novel surface-localized, phosphate headgroup recognition centre connected to an interior hydrophobic pocket that adaptively expands to ensheath differing-length lipid chains using a cleft-like gating mechanism. The two-layer, alpha-helically-dominated 'sandwich' topology identifies CPTP as the prototype for a new glycolipid transfer protein fold(13) subfamily. CPTP resides in the cell cytosol but associates with the trans-Golgi network, nucleus and plasma membrane. RNA interference-induced CPTP depletion elevates C1P steady-state levels and alters Golgi cisternae stack morphology. The resulting C1P decrease in plasma membranes and increase in the Golgi complex stimulates cPLA(2)alpha release of arachidonic acid, triggering pro-inflammatory eicosanoid generation.
C1 [Simanshu, Dhirendra K.; Patel, Dinshaw J.] Mem Sloan Kettering Canc Ctr, Struct Biol Program, New York, NY 10065 USA.
   [Kamlekar, Ravi Kanth; Zou, Xianqiong; Zhai, Xiuhong; Mishra, Shrawan K.; Hinchcliffe, Edward H.; Brown, Rhoderick E.] Univ Minnesota, Hormel Inst, Austin, MN 55912 USA.
   [Wijesinghe, Dayanjan S.; Chalfant, Charles E.] Virginia Commonwealth Univ, Dept Biochem & Mol Biol, Richmond, VA 23298 USA.
   [Molotkovsky, Julian G.] Russian Acad Sci, Shemyakin Ovchinnikov Inst Bioorgan Chem, Moscow, Russia.
   [Malinina, Lucy] CIC BioGUNE, Struct Biol Unit, Derio Bilbao 48160, Spain.
   [Chalfant, Charles E.] Hunter Holmes McGuire Vet Adm Med Ctr, Richmond, VA 23249 USA.
   [Chalfant, Charles E.] Virginia Commonwealth Univ, Med Coll Virginia, Massey Canc Ctr, Richmond, VA 23298 USA.
C3 Memorial Sloan Kettering Cancer Center; University of Minnesota System; Virginia Commonwealth University; Russian Academy of Sciences; Pushchino Scientific Center for Biological Research (PSCBI) of the Russian Academy of Sciences; Institute of Bioorganic Chemistry of the Russian Academy of Sciences; CIC bioGUNE; Hunter Holmes McGuire Veterinary Affairs Medical Center; Virginia Commonwealth University
RP Brown, RE (corresponding author), Univ Minnesota, Hormel Inst, 801 16th Ave NE, Austin, MN 55912 USA.
EM ehinchcliffe@hi.umn.edu; cechalfant@vcu.edu; reb@umn.edu; pateld@mskcc.org
FU NIH/NCI [CA121493]; NIH/NIGMS [GM45928, GM072754]; VA Merit Award; VA Research Career Scientist Award; VA Career Devel. Award; Spanish Ministerio de Ciencia e Innovacion [BFU2010-17711]; Russian Foundation for Basic Research [12-04-00168]; Hormel Foundation; Abby Rockefeller Mauze Trust; Maloris Foundation;  [NIH/CA154314];  [NRS-T32/NIGMS 008695]; National Cancer Institute [P30CA008748] Funding Source: NIH RePORTER
NR 34
TC 164
Z9 187
U1 0
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 AUG 22
PY 2013
VL 500
IS 7463
BP 463
EP +
DI 10.1038/nature12332
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 203TJ
UT WOS:000323316100036
PM 23863933
DA 2026-03-09
ER

PT J
AU Hansen, TB
   Jensen, TI
   Clausen, BH
   Bramsen, JB
   Finsen, B
   Damgaard, CK
   Kjems, J
AF Hansen, Thomas B.
   Jensen, Trine I.
   Clausen, Bettina H.
   Bramsen, Jesper B.
   Finsen, Bente
   Damgaard, Christian K.
   Kjems, Jorgen
TI Natural RNA circles function as efficient microRNA sponges
SO NATURE
LA English
DT Article
ID messenger-rnas; mouse testis; target; gene; circularization; identification; glioblastoma; transcript; expression; receptor
AB MicroRNAs (miRNAs) are important post-transcriptional regulators of gene expression that act by direct base pairing to target sites within untranslated regions of messenger RNAs1. Recently, miRNA activity has been shown to be affected by the presence of miRNA sponge transcripts, the so-called competing endogenous RNA in humans and target mimicry in plants(2-7). We previously identified a highly expressed circular RNA (circRNA) in human and mouse brain(8). Here we show that this circRNA acts as a miR-7 sponge; we term this circular transcript ciRS-7 (circular RNA sponge for miR-7). ciRS-7 contains more than 70 selectively conserved miRNA target sites, and it is highly and widely associated with Argonaute (AGO) proteins in a miR-7-dependent manner. Although the circRNA is completely resistant to miRNA-mediated target destabilization, it strongly suppresses miR-7 activity, resulting in increased levels of miR-7 targets. In the mouse brain, we observe overlapping co-expression of ciRS-7 and miR-7, particularly in neocortical and hippocampal neurons, suggesting a high degree of endogenous interaction. We further show that the testis-specific circRNA, sex-determining region Y (Sry)(9), serves as a miR-138 sponge, suggesting that miRNA sponge effects achieved by circRNA formation are a general phenomenon. This study serves as the first, to our knowledge, functional analysis of a naturally expressed circRNA.
C1 [Hansen, Thomas B.; Jensen, Trine I.; Bramsen, Jesper B.; Damgaard, Christian K.; Kjems, Jorgen] Aarhus Univ, Dept Mol Biol & Genet, DK-8000 Aarhus C, Denmark.
   [Clausen, Bettina H.; Finsen, Bente] Univ Southern Denmark, Inst Mol Med, DK-5000 Odense C, Denmark.
   [Bramsen, Jesper B.; Kjems, Jorgen] Aarhus Univ, Interdisciplinary Nanosci Ctr iNANO, DK-8000 Aarhus C, Denmark.
C3 Aarhus University; University of Southern Denmark; Aarhus University
RP Kjems, J (corresponding author), Aarhus Univ, Dept Mol Biol & Genet, CF Mollers Alle 3, DK-8000 Aarhus C, Denmark.
EM tbh@mb.au.dk; jk@mb.au.dk
FU SIROCCO EU consortium; Lundbeck Foundation; Danish Council for Independent Research - Natural Sciences; Lundbeck Foundation [R83-2011-8232] Funding Source: researchfish
NR 25
TC 6625
Z9 7362
U1 16
U2 1305
PU NATURE PUBLISHING 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 21
PY 2013
VL 495
IS 7441
BP 384
EP 388
DI 10.1038/nature11993
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 113EY
UT WOS:000316650500046
PM 23446346
DA 2026-03-09
ER

PT J
AU Alexandrov, LB
   Nik-Zainal, S
   Wedge, DC
   Aparicio, SAJR
   Behjati, S
   Biankin, AV
   Bignell, GR
   Bolli, N
   Borg, A
   Borresen-Dale, AL
   Boyault, S
   Burkhardt, B
   Butler, AP
   Caldas, C
   Davies, HR
   Desmedt, C
   Eils, R
   Eyfjörd, JE
   Foekens, JA
   Greaves, M
   Hosoda, F
   Hutter, B
   Ilicic, T
   Imbeaud, S
   Imielinsk, M
   Jäger, N
   Jones, DTW
   Jones, D
   Knappskog, S
   Kool, M
   Lakhani, SR
   López-Otín, C
   Martin, S
   Munshi, NC
   Nakamura, H
   Northcott, PA
   Pajic, M
   Papaemmanuil, E
   Paradiso, A
   Pearson, JV
   Puente, XS
   Raine, K
   Ramakrishna, M
   Richardson, AL
   Richter, J
   Rosenstiel, P
   Schlesner, M
   Schumacher, TN
   Span, PN
   Teague, JW
   Totoki, Y
   Tutt, ANJ
   Valdés-Mas, R
   van Buuren, MM
   van 't Veer, L
   Vincent-Salomon, A
   Waddell, N
   Yates, LR
   Zucman-Rossi, J
   Futreal, PA
   McDermott, U
   Lichter, P
   Meyerson, M
   Grimmond, SM
   Siebert, R
   Campo, E
   Shibata, T
   Pfister, SM
   Campbell, PJ
   Stratton, MR
AF Alexandrov, Ludmil B.
   Nik-Zainal, Serena
   Wedge, David C.
   Aparicio, Samuel A. J. R.
   Behjati, Sam
   Biankin, Andrew V.
   Bignell, Graham R.
   Bolli, Niccolo
   Borg, Ake
   Borresen-Dale, Anne-Lise
   Boyault, Sandrine
   Burkhardt, Birgit
   Butler, Adam P.
   Caldas, Carlos
   Davies, Helen R.
   Desmedt, Christine
   Eils, Roland
   Eyfjord, Jorunn Erla
   Foekens, John A.
   Greaves, Mel
   Hosoda, Fumie
   Hutter, Barbara
   Ilicic, Tomislav
   Imbeaud, Sandrine
   Imielinsk, Marcin
   Jaeger, Natalie
   Jones, David T. W.
   Jones, David
   Knappskog, Stian
   Kool, Marcel
   Lakhani, Sunil R.
   Lopez-Otin, Carlos
   Martin, Sancha
   Munshi, Nikhil C.
   Nakamura, Hiromi
   Northcott, Paul A.
   Pajic, Marina
   Papaemmanuil, Elli
   Paradiso, Angelo
   Pearson, John V.
   Puente, Xose S.
   Raine, Keiran
   Ramakrishna, Manasa
   Richardson, Andrea L.
   Richter, Julia
   Rosenstiel, Philip
   Schlesner, Matthias
   Schumacher, Ton N.
   Span, Paul N.
   Teague, Jon W.
   Totoki, Yasushi
   Tutt, Andrew N. J.
   Valdes-Mas, Rafael
   van Buuren, Marit M.
   van 't Veer, Laura
   Vincent-Salomon, Anne
   Waddell, Nicola
   Yates, Lucy R.
   Zucman-Rossi, Jessica
   Futreal, P. Andrew
   McDermott, Ultan
   Lichter, Peter
   Meyerson, Matthew
   Grimmond, Sean M.
   Siebert, Reiner
   Campo, Elias
   Shibata, Tatsuhiro
   Pfister, Stefan M.
   Campbell, Peter J.
   Stratton, Michael R.
TI Signatures of mutational processes in human cancer
SO NATURE
LA English
DT Article
ID recurrent mutations; somatic mutations; genetic landscape; frequent mutation; driver mutations; mismatch repair; exome; reveals; adenocarcinoma; instability
AB All cancers are caused by somatic mutations; however, understanding of the biological processes generating these mutations is limited. The catalogue of somatic mutations from a cancer genome bears the signatures of the mutational processes that have been operative. Here we analysed 4,938,362 mutations from 7,042 cancers and extracted more than 20 distinct mutational signatures. Some are present in many cancer types, notably a signature attributed to the APOBEC family of cytidine deaminases, whereas others are confined to a single cancer class. Certain signatures are associated with age of the patient at cancer diagnosis, known mutagenic exposures or defects in DNA maintenance, but many are of cryptic origin. In addition to these genome-wide mutational signatures, hypermutation localized to small genomic regions, 'kataegis', is found in many cancer types. The results reveal the diversity of mutational processes underlying the development of cancer, with potential implications for understanding of cancer aetiology, prevention and therapy.
C1 [Alexandrov, Ludmil B.; Nik-Zainal, Serena; Wedge, David C.; Behjati, Sam; Bignell, Graham R.; Bolli, Niccolo; Butler, Adam P.; Davies, Helen R.; Ilicic, Tomislav; Jones, David; Martin, Sancha; Papaemmanuil, Elli; Raine, Keiran; Ramakrishna, Manasa; Teague, Jon W.; Yates, Lucy R.; Futreal, P. Andrew; McDermott, Ultan; Campbell, Peter J.; Stratton, Michael R.] Wellcome Trust Sanger Inst, Canc Genome Project, Hinxton CB10 1SA, Cambs, England.
   [Nik-Zainal, Serena] Addenbrookes Hosp NHS Trust, Dept Med Genet, Cambridge CB2 0QQ, England.
   [Aparicio, Samuel A. J. R.] BC Canc Agcy, Michael Smith Genome Sci Ctr, Vancouver, BC V5Z 1L3, Canada.
   [Aparicio, Samuel A. J. R.] BC Canc Agcy, Michael Smith Genome Sci Ctr, Ctr Translat & Appl Genom, Vancouver, BC V5Z 1L3, Canada.
   [Aparicio, Samuel A. J. R.] Univ British Columbia, Dept Pathol, Vancouver, BC V6T 2B5, Canada.
   [Behjati, Sam] Univ Cambridge, Dept Paediat, Cambridge CB2 2XY, England.
   [Biankin, Andrew V.; Pajic, Marina] Univ Glasgow, Wolfson Wohl Canc Res Ctr, Inst Canc Sci, Glasgow G61 1BD, Lanark, Scotland.
   [Biankin, Andrew V.] Glasgow Royal Infirm, West Scotland Pancreat Unit, Glasgow G4 0SF, Lanark, Scotland.
   [Biankin, Andrew V.] Kinghorn Canc Ctr, Darlinghurst, NSW, Australia.
   [Biankin, Andrew V.] Garvan Inst Med Res, Canc Res Program, Darlinghurst, NSW 2010, Australia.
   [Biankin, Andrew V.] Bankstown Hosp, Dept Surg, Sydney, NSW 2200, Australia.
   [Biankin, Andrew V.] Univ New S Wales, South Western Sydney Clin Sch, Fac Med, Liverpool, NSW 2170, Australia.
   [Bolli, Niccolo; Campbell, Peter J.] Addenbrookes Hosp, Dept Haematol, Cambridge CB2 0QQ, England.
   [Bolli, Niccolo; Campbell, Peter J.] Univ Cambridge, Dept Haematol, Cambridge CB2 2XY, England.
   [Borg, Ake] Lund Univ, Dept Oncol, SE-22185 Lund, Sweden.
   [Borresen-Dale, Anne-Lise] Norwegian Radium Hosp, Oslo Univ Hosp, Dept Genet, Inst Canc Res, N-0310 Oslo, Norway.
   [Borresen-Dale, Anne-Lise] Univ Oslo, Fac Med, Inst Clin Med, KG Jebsen Ctr Breast Canc Res, N-0310 Oslo, Norway.
   [Boyault, Sandrine] Ctr Leon Berard, Plateforme Bioinformat Synergie Lyon Canc, F-69373 Lyon 08, France.
   [Burkhardt, Birgit] Univ Childrens Hosp, NHL BFM Study Ctr, D-48149 Munster, Germany.
   [Burkhardt, Birgit] Univ Childrens Hosp, Dept Pediat Hematol & Oncol, D-48149 Munster, Germany.
   [Burkhardt, Birgit] Univ Childrens Hosp, NHL BFM Study Ctr, D-35392 Giessen, Germany.
   [Burkhardt, Birgit] Univ Childrens Hosp, Dept Pediat Hematol & Oncol, D-35392 Giessen, Germany.
   [Caldas, Carlos] Univ Cambridge, Li Ka Shing Ctr, Canc Res UK Cambridge Inst, Cambridge CB2 0RE, England.
   [Desmedt, Christine] Univ Libre Bruxelles, Inst Jules Bordet, Breast Canc Translat Res Lab BCTL, B-1000 Brussels, Belgium.
   [Eils, Roland; Hutter, Barbara; Jaeger, Natalie; Schlesner, Matthias] German Canc Res Ctr, Dept Theoret Bioinformat B080, D-69120 Heidelberg, Germany.
   [Eyfjord, Jorunn Erla] Univ Iceland, Canc Res Lab, Fac Med, Biomed Ctr, IS-101 Reykjavik, Iceland.
   [Foekens, John A.] Erasmus MC Canc Inst, Dept Med Oncol, NL-3015 CE Rotterdam, Netherlands.
   [Greaves, Mel] Inst Canc Res, Dept Haematooncol, Sutton SM2 5NG, Surrey, England.
   [Hosoda, Fumie; Nakamura, Hiromi; Totoki, Yasushi; Shibata, Tatsuhiro] Natl Canc Ctr, Res Inst, Div Canc Genom, Chuo Ku, Tokyo 1040045, Japan.
   [Imbeaud, Sandrine; Zucman-Rossi, Jessica] IUH, INSERM, UMR 674, F-75475 Paris, France.
   [Imbeaud, Sandrine; Zucman-Rossi, Jessica] Univ Paris 05, Sorbonne Paris Cite, Fac Med, F-75006 Paris, France.
   [Imielinsk, Marcin; Meyerson, Matthew] Broad Inst MIT & Harvard, Cambridge, MA 02141 USA.
   [Jones, David T. W.; Kool, Marcel; Northcott, Paul A.; Pfister, Stefan M.] German Canc Res Ctr, Div Pediat Neurooncol, D-69120 Heidelberg, Germany.
   [Knappskog, Stian] Univ Bergen, Dept Clin Sci, Sect Oncol, N-5020 Bergen, Norway.
   [Knappskog, Stian] Haukeland Hosp, Dept Oncol, N-5021 Bergen, Norway.
   [Lakhani, Sunil R.] Univ Queensland, Royal Brisbane & Womens Hosp, Clin Res Ctr, Sch Med & Pathol Queensland, Brisbane, Qld 4029, Australia.
   [Lopez-Otin, Carlos; Puente, Xose S.; Valdes-Mas, Rafael] Univ Oviedo, IUOPA, Dept Bioquim & Biol Mol, E-33006 Oviedo, Spain.
   [Munshi, Nikhil C.] Harvard Univ, Sch Med, Jerome Lipper Multiple Myeloma Dis Ctr, Dana Farber Canc Inst, Boston, MA 02215 USA.
   [Munshi, Nikhil C.] Boston Vet Adm Healthcare Syst, West Roxbury, MA 02132 USA.
   [Paradiso, Angelo] Natl Canc Inst, Clin Expt Oncol Lab, I-70126 Bari, Italy.
   [Pearson, John V.; Waddell, Nicola; Grimmond, Sean M.] Univ Queensland, Queensland Ctr Med Genom, Inst Mol Biosci, Brisbane, Qld 4072, Australia.
   [Richardson, Andrea L.; Meyerson, Matthew] Dana Farber Canc Inst, Boston, MA 02215 USA.
   [Richardson, Andrea L.; Meyerson, Matthew] Harvard Univ, Sch Med, Boston, MA 02115 USA.
   [Richardson, Andrea L.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
   [Richter, Julia; Siebert, Reiner] Univ Kiel, Inst Human Genet, D-24118 Kiel, Germany.
   [Rosenstiel, Philip] Univ Kiel, Inst Clin Mol Biol, D-24118 Kiel, Germany.
   [Schumacher, Ton N.; van Buuren, Marit M.] Netherlands Canc Inst, Div Immunol, NL-1066 CX Amsterdam, Netherlands.
   [Span, Paul N.] Radboud Univ Nijmegen, Med Ctr, Dept Radiat Oncol, NL-6500 HB Nijmegen, Netherlands.
   [Span, Paul N.] Radboud Univ Nijmegen, Med Ctr, Dept Lab Med, NL-6500 HB Nijmegen, Netherlands.
   [Tutt, Andrew N. J.] Kings Coll London, Sch Med, Breakthrough Breast Canc Res Unit, London SW3 6JB, England.
   [van 't Veer, Laura] Netherlands Canc Inst, NL-1066 CX Amsterdam, Netherlands.
   [Vincent-Salomon, Anne] INSERM, U830, Dept Pathol, Inst Curie, F-75248 Paris 05, France.
   [Lichter, Peter] German Canc Res Ctr, Div Mol Genet, D-69120 Heidelberg, Germany.
   [Campo, Elias] Univ Barcelona, Unidad Hematopatol, Serv Anat Patol, Hosp Clin,IDIBAPS, E-08036 Barcelona, Spain.
   [Pfister, Stefan M.] Dept Pediat Hematol & Oncol, D-69120 Heidelberg, Germany.
C3 Wellcome Trust Sanger Institute; Cambridge University Hospitals NHS Foundation Trust; Addenbrooke's Hospital; British Columbia Cancer Agency; British Columbia Cancer Agency; University of British Columbia; University of Cambridge; University of Glasgow; University of Glasgow; The Kinghorn Cancer Centre; Garvan Institute of Medical Research; NSW Health; Bankstown Lidcombe Hospital; University of New South Wales Sydney; Cambridge University Hospitals NHS Foundation Trust; Addenbrooke's Hospital; University of Cambridge; University of Cambridge; Lund University; University of Oslo; University of Oslo; UNICANCER; Centre Leon Berard; University of Munster; University of Munster; University of Cambridge; Cancer Research UK; CRUK Cambridge Institute; Universite Libre de Bruxelles; Institut Jules Bordet; Helmholtz Association; German Cancer Research Center (DKFZ); University of Iceland; Erasmus University Rotterdam; Erasmus MC; Erasmus MC Cancer Institute; University of London; Institute of Cancer Research - UK; National Cancer Center - Japan; Universite Paris Cite; Institut National de la Sante et de la Recherche Medicale (Inserm); Universite Paris Cite; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Helmholtz Association; German Cancer Research Center (DKFZ); University of Bergen; University of Bergen; Haukeland University Hospital; University of Queensland; Royal Brisbane & Women's Hospital; University of Oviedo; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard Medical School; IRCCS Istituto Tumori Bari Giovanni Paolo II; University of Queensland; 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; University of Kiel; University of Kiel; Netherlands Cancer Institute; Radboud University Nijmegen; Radboud University Nijmegen; University of London; King's College London; Netherlands Cancer Institute; Universite PSL; UNICANCER; Institut Curie; Institut National de la Sante et de la Recherche Medicale (Inserm); Helmholtz Association; German Cancer Research Center (DKFZ); University of Barcelona; Hospital Clinic de Barcelona; IDIBAPS
RP Alexandrov, LB (corresponding author), Wellcome Trust Sanger Inst, Canc Genome Project, Wellcome Trust Genome Campus, Hinxton CB10 1SA, Cambs, England.
EM mrs@sanger.ac.uk
FU Wellcome Trust [098051]; National Cancer Institute [T32CA009216] Funding Source: NIH RePORTER
NR 64
TC 7407
Z9 8303
U1 8
U2 789
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD AUG 22
PY 2013
VL 500
IS 7463
BP 415
EP +
DI 10.1038/nature12477
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 203TJ
UT WOS:000323316100026
PM 23945592
DA 2026-03-09
ER

PT J
AU Lipkind, D
   Marcus, GF
   Bemis, DK
   Sasahara, K
   Jacoby, N
   Takahasi, M
   Suzuki, K
   Feher, O
   Ravbar, P
   Okanoya, K
   Tchernichovski, O
AF Lipkind, Dina
   Marcus, Gary F.
   Bemis, Douglas K.
   Sasahara, Kazutoshi
   Jacoby, Nori
   Takahasi, Miki
   Suzuki, Kenta
   Feher, Olga
   Ravbar, Primoz
   Okanoya, Kazuo
   Tchernichovski, Ofer
TI Stepwise acquisition of vocal combinatorial capacity in songbirds and human infants
SO NATURE
LA English
DT Article
ID sequential movements; song; model
AB Human language, as well as birdsong, relies on the ability to arrange vocal elements in new sequences. However, little is known about the ontogenetic origin of this capacity. Here we track the development of vocal combinatorial capacity in three species of vocal learners, combining an experimental approach in zebra finches (Taeniopygia guttata) with an analysis of natural development of vocal transitions in Bengalese finches (Lonchura striata domestica) and pre-lingual human infants. We find a common, stepwise pattern of acquiring vocal transitions across species. In our first study, juvenile zebra finches were trained to perform one song and then the training target was altered, prompting the birds to swap syllable order, or insert a new syllable into a string. All birds solved these permutation tasks in a series of steps, gradually approximating the target sequence by acquiring new pairwise syllable transitions, sometimes too slowly to accomplish the task fully. Similarly, in the more complex songs of Bengalese finches, branching points and bidirectional transitions in song syntax were acquired in a stepwise fashion, starting from a more restrictive set of vocal transitions. The babbling of pre-lingual human infants showed a similar pattern: instead of a single developmental shift from reduplicated to variegated babbling (that is, from repetitive to diverse sequences), we observed multiple shifts, where each new syllable type slowly acquired a diversity of pairwise transitions, asynchronously over development. Collectively, these results point to a common generative process that is conserved across species, suggesting that the long-noted gap between perceptual versus motor combinatorial capabilities in human infants(1) may arise partly from the challenges in constructing new pairwise vocal transitions.
C1 [Lipkind, Dina; Feher, Olga; Tchernichovski, Ofer] CUNY Hunter Coll, Dept Psychol, New York, NY 10065 USA.
   [Lipkind, Dina; Feher, Olga; Ravbar, Primoz; Tchernichovski, Ofer] CUNY City Coll, Dept Biol, New York, NY 10031 USA.
   [Marcus, Gary F.; Bemis, Douglas K.] NYU, Dept Psychol, New York, NY 10003 USA.
   [Sasahara, Kazutoshi; Takahasi, Miki; Suzuki, Kenta; Okanoya, Kazuo] RIKEN Brain Sci Inst, Lab Biolinguist, Wako, Saitama 3510198, Japan.
   [Jacoby, Nori] Hebrew Univ Jerusalem, Interdisciplinary Ctr Neural Computat, IL-91904 Jerusalem, Israel.
   [Jacoby, Nori] Bar Ilan Univ, Dept Mus, IL-5290002 Ramat Gan, Israel.
   [Suzuki, Kenta; Okanoya, Kazuo] JST ERATO Okanoya Emot Informat Project, Wako, Saitama 3510198, Japan.
   [Feher, Olga; Ravbar, Primoz; Tchernichovski, Ofer] CUNY, Grad Ctr, New York, NY 10016 USA.
C3 City University of New York (CUNY) System; Hunter College (CUNY); City University of New York (CUNY) System; City College of New York (CUNY); New York University; RIKEN; Hebrew University of Jerusalem; Bar Ilan University; City University of New York (CUNY) System
RP Lipkind, D (corresponding author), CUNY Hunter Coll, Dept Psychol, New York, NY 10065 USA.
EM dina.lipkind@gmail.com
FU Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan; US Public Health Service grant; Grants-in-Aid for Scientific Research [23240033] Funding Source: KAKEN
NR 30
TC 158
Z9 186
U1 3
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 JUN 6
PY 2013
VL 498
IS 7452
BP 104
EP +
DI 10.1038/nature12173
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 158DC
UT WOS:000319947800042
PM 23719373
DA 2026-03-09
ER

PT J
AU Amemiya, CT
   Alföldi, J
   Lee, AP
   Fan, SH
   Philippe, H
   MacCallum, I
   Braasch, I
   Manousaki, T
   Schneider, I
   Rohner, N
   Organ, C
   Chalopin, D
   Smith, JJ
   Robinson, M
   Dorrington, RA
   Gerdol, M
   Aken, B
   Biscotti, MA
   Barucca, M
   Baurain, D
   Berlin, AM
   Blatch, GL
   Buonocore, F
   Burmester, T
   Campbell, MS
   Canapa, A
   Cannon, JP
   Christoffels, A
   De Moro, G
   Edkins, AL
   Fan, L
   Fausto, AM
   Feiner, N
   Forconi, M
   Gamieldien, J
   Gnerre, S
   Gnirke, A
   Goldstone, JV
   Haerty, W
   Hahn, ME
   Hesse, U
   Hoffmann, S
   Johnson, J
   Karchner, SI
   Kuraku, S
   Lara, M
   Levin, JZ
   Litman, GW
   Mauceli, E
   Miyake, T
   Mueller, MG
   Nelson, DR
   Nitsche, A
   Olmo, E
   Ota, T
   Pallavicini, A
   Panji, S
   Picone, B
   Ponting, CP
   Prohaska, SJ
   Przybylski, D
   Saha, NR
   Ravi, V
   Ribeiro, FJ
   Sauka-Spengler, T
   Scapigliati, G
   Searle, SMJ
   Sharpe, T
   Simakov, O
   Stadler, PF
   Stegeman, JJ
   Sumiyama, K
   Tabbaa, D
   Tafer, H
   Turner-Maier, J
   van Heusden, P
   White, S
   Williams, L
   Yandell, M
   Brinkmann, H
   Volff, JN
   Tabin, CJ
   Shubin, N
   Schartl, M
   Jaffe, DB
   Postlethwait, JH
   Venkatesh, B
   Di Palma, F
   Lander, ES
   Meyer, A
   Lindblad-Toh, K
AF Amemiya, Chris T.
   Alfoeldi, Jessica
   Lee, Alison P.
   Fan, Shaohua
   Philippe, Herve
   MacCallum, Iain
   Braasch, Ingo
   Manousaki, Tereza
   Schneider, Igor
   Rohner, Nicolas
   Organ, Chris
   Chalopin, Domitille
   Smith, Jeramiah J.
   Robinson, Mark
   Dorrington, Rosemary A.
   Gerdol, Marco
   Aken, Bronwen
   Biscotti, Maria Assunta
   Barucca, Marco
   Baurain, Denis
   Berlin, Aaron M.
   Blatch, Gregory L.
   Buonocore, Francesco
   Burmester, Thorsten
   Campbell, Michael S.
   Canapa, Adriana
   Cannon, John P.
   Christoffels, Alan
   De Moro, Gianluca
   Edkins, Adrienne L.
   Fan, Lin
   Fausto, Anna Maria
   Feiner, Nathalie
   Forconi, Mariko
   Gamieldien, Junaid
   Gnerre, Sante
   Gnirke, Andreas
   Goldstone, Jared V.
   Haerty, Wilfried
   Hahn, Mark E.
   Hesse, Uljana
   Hoffmann, Steve
   Johnson, Jeremy
   Karchner, Sibel I.
   Kuraku, Shigehiro
   Lara, Marcia
   Levin, Joshua Z.
   Litman, Gary W.
   Mauceli, Evan
   Miyake, Tsutomu
   Mueller, M. Gail
   Nelson, David R.
   Nitsche, Anne
   Olmo, Ettore
   Ota, Tatsuya
   Pallavicini, Alberto
   Panji, Sumir
   Picone, Barbara
   Ponting, Chris P.
   Prohaska, Sonja J.
   Przybylski, Dariusz
   Saha, Nil Ratan
   Ravi, Vydianathan
   Ribeiro, Filipe J.
   Sauka-Spengler, Tatjana
   Scapigliati, Giuseppe
   Searle, Stephen M. J.
   Sharpe, Ted
   Simakov, Oleg
   Stadler, Peter F.
   Stegeman, John J.
   Sumiyama, Kenta
   Tabbaa, Diana
   Tafer, Hakim
   Turner-Maier, Jason
   van Heusden, Peter
   White, Simon
   Williams, Louise
   Yandell, Mark
   Brinkmann, Henner
   Volff, Jean-Nicolas
   Tabin, Clifford J.
   Shubin, Neil
   Schartl, Manfred
   Jaffe, David B.
   Postlethwait, John H.
   Venkatesh, Byrappa
   Di Palma, Federica
   Lander, Eric S.
   Meyer, Axel
   Lindblad-Toh, Kerstin
TI The African coelacanth genome provides insights into tetrapod evolution
SO NATURE
LA English
DT Article
ID mitochondrial genome; living fossil; sequence; model; genes; transcription; chromosm; retention; reveals; origin
AB The discovery of a living coelacanth specimen in 1938 was remarkable, as this lineage of lobe-finned fish was thought to have become extinct 70 million years ago. The modern coelacanth looks remarkably similar to many of its ancient relatives, and its evolutionary proximity to our own fish ancestors provides a glimpse of the fish that first walked on land. Here we report the genome sequence of the African coelacanth, Latimeria chalumnae. Through a phylogenomic analysis, we conclude that the lungfish, and not the coelacanth, is the closest living relative of tetrapods. Coelacanth protein-coding genes are significantly more slowly evolving than those of tetrapods, unlike other genomic features. Analyses of changes in genes and regulatory elements during the vertebrate adaptation to land highlight genes involved in immunity, nitrogen excretion and the development of fins, tail, ear, eye, brain and olfaction. Functional assays of enhancers involved in the fin-to-limb transition and in the emergence of extra-embryonic tissues show the importance of the coelacanth genome as a blueprint for understanding tetrapod evolution.
C1 [Amemiya, Chris T.; Robinson, Mark; Saha, Nil Ratan] Benaroya Res Inst, Mol Genet Program, Seattle, WA 98101 USA.
   [Amemiya, Chris T.] Univ Washington, Dept Biol, Seattle, WA 98105 USA.
   [Alfoeldi, Jessica; MacCallum, Iain; Berlin, Aaron M.; Fan, Lin; Gnerre, Sante; Gnirke, Andreas; Johnson, Jeremy; Lara, Marcia; Levin, Joshua Z.; Mauceli, Evan; Przybylski, Dariusz; Ribeiro, Filipe J.; Sharpe, Ted; Tabbaa, Diana; Turner-Maier, Jason; Williams, Louise; Jaffe, David B.; Di Palma, Federica; Lander, Eric S.; Lindblad-Toh, Kerstin] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.
   [Lee, Alison P.; Ravi, Vydianathan; Venkatesh, Byrappa] ASTAR, Inst Mol & Cell Biol, Comparat Genom Lab, Singapore 138673, Singapore.
   [Fan, Shaohua; Manousaki, Tereza; Feiner, Nathalie; Kuraku, Shigehiro; Simakov, Oleg; Meyer, Axel] Univ Konstanz, Dept Biol, D-78464 Constance, Germany.
   [Philippe, Herve; Brinkmann, Henner] Univ Montreal, Ctr Robert Cedergren, Dept Biochim, Montreal, PQ H3T 1J4, Canada.
   [Braasch, Ingo; Postlethwait, John H.] Univ Oregon, Inst Neurosci, Eugene, OR 97403 USA.
   [Manousaki, Tereza; Meyer, Axel] Univ Konstanz, Konstanz Res Sch Chem Biol, D-78464 Constance, Germany.
   [Schneider, Igor] Fed Univ Para, Inst Ciencias Biol, BR-66075110 Belem, Para, Brazil.
   [Rohner, Nicolas; Tabin, Clifford J.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
   [Organ, Chris] Univ Utah, Dept Anthropol, Salt Lake City, UT 84112 USA.
   [Chalopin, Domitille; Volff, Jean-Nicolas] Ecole Normale Super Lyon, Inst Genom Fonct Lyon, F-69007 Lyon, France.
   [Smith, Jeramiah J.] Univ Kentucky, Dept Biol, Lexington, KY 40506 USA.
   [Dorrington, Rosemary A.; Blatch, Gregory L.; Edkins, Adrienne L.] Rhodes Univ, Dept Biochem Microbiol & Biotechnol, Biomed Biotechnol Res Unit BioBRU, ZA-6139 Grahamstown, South Africa.
   [Gerdol, Marco; De Moro, Gianluca; Pallavicini, Alberto] Univ Trieste, Dept Life Sci, I-34128 Trieste, Italy.
   [Aken, Bronwen; Searle, Stephen M. J.; White, Simon] Wellcome Trust Sanger Inst, Dept Informat, Hinxton CB10 1SA, S Cambs, England.
   [Biscotti, Maria Assunta; Barucca, Marco; Canapa, Adriana; Forconi, Mariko; Olmo, Ettore] Polytech Univ Marche, Dept Life & Environm Sci, I-60131 Ancona, Italy.
   [Baurain, Denis] Univ Liege, Dept Life Sci, B-4000 Liege, Belgium.
   [Blatch, Gregory L.] Victoria Univ, Coll Hlth & Biomed, Melbourne, Vic 8001, Australia.
   [Buonocore, Francesco; Fausto, Anna Maria; Scapigliati, Giuseppe] Univ Tuscia, Dept Innovat Biol Agrofood & Forest Syst, I-01100 Viterbo, Italy.
   [Burmester, Thorsten] Univ Hamburg, Dept Biol, D-20146 Hamburg, Germany.
   [Campbell, Michael S.; Yandell, Mark] Univ Utah, Eccles Inst Human Genet, Salt Lake City, UT 84112 USA.
   [Cannon, John P.; Litman, Gary W.] Univ S Florida, Morsani Coll Med, Childrens Res Inst, Dept Pediat, St Petersburg, FL 33701 USA.
   [Christoffels, Alan; Gamieldien, Junaid; Hesse, Uljana; Panji, Sumir; Picone, Barbara; van Heusden, Peter] Univ Western Cape, South African Natl Bioinformat Inst, ZA-7535 Bellville, South Africa.
   [Feiner, Nathalie; Meyer, Axel] Univ Konstanz, Int Max Planck Res Sch Organismal Biol, D-78464 Constance, Germany.
   [Goldstone, Jared V.; Hahn, Mark E.; Karchner, Sibel I.; Stegeman, John J.] Woods Hole Oceanog Inst, Dept Biol, Woods Hole, MA 02543 USA.
   [Haerty, Wilfried; Ponting, Chris P.] Univ Oxford, MRC Funct Genom Unit, Oxford OX1 3PT, England.
   [Hoffmann, Steve] Univ Leipzig, LIFE Res Ctr Civilizat Dis, Transcriptome Bioinformat Grp, D-04109 Leipzig, Germany.
   [Miyake, Tsutomu] Keio Univ, Grad Sch Sci & Technol, Yokohama, Kanagawa 2238522, Japan.
   [Mueller, M. Gail] Univ S Florida, All Childrens Hosp, Dept Mol Genet, St Petersburg, FL 33701 USA.
   [Nelson, David R.] Univ Tennessee, Ctr Hlth Sci, Dept Microbiol Immunol & Biochem, Memphis, TN 38163 USA.
   [Nitsche, Anne; Stadler, Peter F.; Tafer, Hakim] Univ Leipzig, Dept Comp Sci, Bioinformat Grp, D-04109 Leipzig, Germany.
   [Ota, Tatsuya] Grad Univ Adv Studies, Dept Evolutionary Studies Biosyst, Hayama 2400193, Japan.
   [Prohaska, Sonja J.] Univ Leipzig, Dept Comp Sci, Computat EvoDevo Grp, D-04109 Leipzig, Germany.
   [Sauka-Spengler, Tatjana] Univ Oxford, Weatherall Inst Mol Med, Oxford OX1 2JD, England.
   [Simakov, Oleg] European Mol Biol Lab, D-69117 Heidelberg, Germany.
   [Sumiyama, Kenta] Natl Inst Genet, Divis Populat Genet, Mishima, Shizuoka 4118540, Japan.
   [Shubin, Neil] Univ Chicago, Chicago, IL 60637 USA.
   [Schartl, Manfred] Univ Wurzburg, Dept Physiol Chem, D-97070 Wurzburg, Germany.
   [Lindblad-Toh, Kerstin] Uppsala Univ, Dept Med Biochem & Microbiol, Sci Life Lab, S-75123 Uppsala, Sweden.
C3 Benaroya Research Institute; University of Washington; University of Washington Seattle; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Agency for Science Technology & Research (A*STAR); A*STAR - Institute of Molecular & Cell Biology (IMCB); University of Konstanz; Universite de Montreal; University of Oregon; University of Konstanz; Universidade Federal do Para; Harvard University; Harvard Medical School; Utah System of Higher Education; University of Utah; Ecole Normale Superieure de Lyon (ENS de LYON); Centre National de la Recherche Scientifique (CNRS); Universite Lyon 1; CHU Lyon; University of Kentucky; Rhodes University; University of Trieste; Wellcome Trust Sanger Institute; Marche Polytechnic University; University of Liege; Victoria University; Tuscia University; University of Hamburg; Utah System of Higher Education; University of Utah; State University System of Florida; University of South Florida; University of the Western Cape; University of Konstanz; Max Planck Society; Woods Hole Oceanographic Institution; University of Oxford; Leipzig University; Keio University; State University System of Florida; University of South Florida; University of Tennessee System; University of Tennessee Health Science Center; Leipzig University; Graduate University for Advanced Studies - Japan; Leipzig University; University of Oxford; European Molecular Biology Laboratory (EMBL); Research Organization of Information & Systems (ROIS); National Institute of Genetics (NIG) - Japan; University of Chicago; University of Wurzburg; Uppsala University
RP Amemiya, CT (corresponding author), Benaroya Res Inst, Mol Genet Program, Seattle, WA 98101 USA.
EM camemiya@benaroyaresearch.org; jalfoldi@broadinstitute.org; axel.meyer@uni-konstanz.de; kersli@broadinstitute.org
FU South African National Department of Science and Technology; National Human Genome Research Institute (NHGRI); European Science Foundation; Grants-in-Aid for Scientific Research [23370101, 24113520] Funding Source: KAKEN; Biotechnology and Biological Sciences Research Council [BBS/E/T/000PR5885, BBS/E/T/000PR6193] Funding Source: researchfish; Medical Research Council [MC_U137761446] Funding Source: researchfish; BBSRC [BBS/E/T/000PR6193, BBS/E/T/000PR5885] Funding Source: UKRI; MRC [MC_U137761446] Funding Source: UKRI
NR 49
TC 540
Z9 604
U1 3
U2 465
PU NATURE PUBLISHING 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 18
PY 2013
VL 496
IS 7445
BP 311
EP 316
DI 10.1038/nature12027
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 126FV
UT WOS:000317599200027
PM 23598338
DA 2026-03-09
ER

PT J
AU Whorton, MR
   MacKinnon, R
AF Whorton, Matthew R.
   MacKinnon, Roderick
TI X-ray structure of the mammalian GIRK2-βγ G-protein complex
SO NATURE
LA English
DT Article
ID beta-gamma-subunits; sodium-dependent activation; rectifying k+ channels; crystal-structure; potassium channels; receptors; binding; system; pip2; rgs9
AB G-protein-gated inward rectifier K+ (GIRK) channels allow neurotransmitters, through G-protein-coupled receptor stimulation, to control cellular electrical excitability. In cardiac and neuronal cells this control regulates heart rate and neural circuit activity, respectively. Here we present the 3.5 angstrom resolution crystal structure of the mammalian GIRK2 channel in complex with beta gamma G-protein subunits, the central signalling complex that links G-protein-coupled receptor stimulation to K+ channel activity. Short-range atomic and long-range electrostatic interactions stabilize four beta gamma G-protein subunits at the interfaces between four K+ channel subunits, inducing a pre-open state of the channel. The pre-open state exhibits a conformation that is intermediate between the closed conformation and the open conformation of the constitutively active mutant. The resultant structural picture is compatible with 'membrane delimited' activation of GIRK channels by G proteins and the characteristic burst kinetics of channel gating. The structures also permit a conceptual understanding of how the signalling lipid phosphatidylinositol-4,5-bisphosphate (PIP2) and intracellular Na+ ions participate in multi-ligand regulation of GIRK channels.
C1 [Whorton, Matthew R.; MacKinnon, Roderick] Rockefeller Univ, Lab Mol Neurobiol & Biophys, New York, NY 10065 USA.
   [Whorton, Matthew R.; MacKinnon, Roderick] Rockefeller Univ, Howard Hughes Med Inst, New York, NY 10065 USA.
C3 Rockefeller University; Rockefeller University; Howard Hughes Medical Institute
RP MacKinnon, R (corresponding author), Rockefeller Univ, Lab Mol Neurobiol & Biophys, 1230 York Ave, New York, NY 10065 USA.
EM mackinn@rockefeller.edu
FU National Center for Research Resources of the National Institutes of Health (NIH) [1S10RR022321-01, 1S10RR027037-01]
NR 61
TC 261
Z9 310
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 JUN 13
PY 2013
VL 498
IS 7453
BP 190
EP +
DI 10.1038/nature12241
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 162RR
UT WOS:000320283400039
PM 23739333
DA 2026-03-09
ER

PT J
AU Howard, AW
   Sanchis-Ojeda, R
   Marcy, GW
   Johnson, JA
   Winn, JN
   Isaacson, H
   Fischer, DA
   Fulton, BJ
   Sinukoff, E
   Fortney, JJ
AF Howard, Andrew W.
   Sanchis-Ojeda, Roberto
   Marcy, Geoffrey W.
   Johnson, John Asher
   Winn, Joshua N.
   Isaacson, Howard
   Fischer, Debra A.
   Fulton, Benjamin J.
   Sinukoff, Evan
   Fortney, Jonathan J.
TI A rocky composition for an Earth-sized exoplanet
SO NATURE
LA English
DT Article
ID solar-type stars; planet-search; mass; evolution; rotation; kepler; spectrometer; precision; density; radii
AB Planets with sizes between that of Earth (with radius R-circle plus) and Neptune (about 4R(circle plus)) are now known to be common around Sun-like stars(1-3). Most such planets have been discovered through the transit technique, by which the planet's size can be determined from the fraction of starlight blocked by the planet as it passes in front of its star. Measuring the planet's mass-and hence its density, which is a clue to its composition-is more difficult. Planets of size 2-4R(circle plus) have proved to have a wide range of densities, implying a diversity of compositions(4,5), but these measurements did not extend to planets as small as Earth. Here we report Doppler spectroscopic measurements of the mass of the Earth-sized planet Kepler-78b, which orbits its host star every 8.5 hours (ref. 6). Given a radius of 1.20 +/- 0.09R(circle plus) and a mass of 1.69 +/- 0.41M(circle plus), the planet's mean density of 5.3 +/- 1.8 g cm(-3) is similar to Earth's, suggesting a composition of rock and iron.
C1 [Howard, Andrew W.; Fulton, Benjamin J.; Sinukoff, Evan] Univ Hawaii Manoa, Inst Astron, Honolulu, HI 96822 USA.
   [Sanchis-Ojeda, Roberto; Winn, Joshua N.] MIT, Dept Phys, Cambridge, MA 02139 USA.
   [Sanchis-Ojeda, Roberto; Winn, Joshua N.] MIT, Kavli Inst Astrophys & Space Res, Cambridge, MA 02139 USA.
   [Marcy, Geoffrey W.; Isaacson, Howard] Univ Calif Berkeley, Dept Astron, Berkeley, CA 94720 USA.
   [Johnson, John Asher] Harvard Smithsonian Ctr Astrophys, Cambridge, MA 02138 USA.
   [Fischer, Debra A.] Yale Univ, Dept Astron, New Haven, CT 06510 USA.
   [Fortney, Jonathan J.] Univ Calif Santa Cruz, Dept Astron & Astrophys, Santa Cruz, CA 95064 USA.
C3 University of Hawaii System; University of Hawaii Manoa; Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); University of California System; University of California Berkeley; Smithsonian Institution; Harvard University; Smithsonian Astrophysical Observatory; Yale University; University of California System; University of California Santa Cruz
RP Howard, AW (corresponding author), Univ Hawaii Manoa, Inst Astron, 2680 Woodlawn Dr, Honolulu, HI 96822 USA.
EM howard@ifa.hawaii.edu; rsanchis86@gmail.com
FU NASA's Science Mission Directorate; Kepler Participating Scientist programme; NASA [NNX12AJ23G]; NASA [NNX12AJ23G, 43367] Funding Source: Federal RePORTER
NR 43
TC 133
Z9 159
U1 0
U2 55
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 21
PY 2013
VL 503
IS 7476
BP 381
EP +
DI 10.1038/nature12767
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 254KG
UT WOS:000327163200037
PM 24172898
DA 2026-03-09
ER

PT J
AU Ray, D
   Kazan, H
   Cook, KB
   Weirauch, MT
   Najafabadi, HS
   Li, X
   Gueroussov, S
   Albu, M
   Zheng, H
   Yang, A
   Na, H
   Irimia, M
   Matzat, LH
   Dale, RK
   Smith, SA
   Yarosh, CA
   Kelly, SM
   Nabet, B
   Mecenas, D
   Li, WM
   Laishram, RS
   Qiao, M
   Lipshitz, HD
   Piano, F
   Corbett, AH
   Carstens, RP
   Frey, BJ
   Anderson, RA
   Lynch, KW
   Penalva, LOF
   Lei, EP
   Fraser, AG
   Blencowe, BJ
   Morris, QD
   Hughes, TR
AF Ray, Debashish
   Kazan, Hilal
   Cook, Kate B.
   Weirauch, Matthew T.
   Najafabadi, Hamed S.
   Li, Xiao
   Gueroussov, Serge
   Albu, Mihai
   Zheng, Hong
   Yang, Ally
   Na, Hong
   Irimia, Manuel
   Matzat, Leah H.
   Dale, Ryan K.
   Smith, Sarah A.
   Yarosh, Christopher A.
   Kelly, Seth M.
   Nabet, Behnam
   Mecenas, Desirea
   Li, Weimin
   Laishram, Rakesh S.
   Qiao, Mei
   Lipshitz, Howard D.
   Piano, Fabio
   Corbett, Anita H.
   Carstens, Russ P.
   Frey, Brendan J.
   Anderson, Richard A.
   Lynch, Kristen W.
   Penalva, Luiz O. F.
   Lei, Elissa P.
   Fraser, Andrew G.
   Blencowe, Benjamin J.
   Morris, Quaid D.
   Hughes, Timothy R.
TI A compendium of RNA-binding motifs for decoding gene regulation
SO NATURE
LA English
DT Article
ID pre-messenger-rna; genome-wide analysis; transcription factors; splicing regulator; proteins; specificity; recognition; reveals; family; code
AB RNA-binding proteins are key regulators of gene expression, yet only a small fraction have been functionally characterized. Here we report a systematic analysis of the RNA motifs recognized by RNA-binding proteins, encompassing 205 distinct genes from 24 diverse eukaryotes. The sequence specificities of RNA-binding proteins display deep evolutionary conservation, and the recognition preferences for a large fraction of metazoan RNA-binding proteins can thus be inferred from their RNA-binding domain sequence. The motifs that we identify in vitro correlate well with in vivo RNA-binding data. Moreover, we can associate them with distinct functional roles in diverse types of post-transcriptional regulation, enabling new insights into the functions of RNA-binding proteins both in normal physiology and in human disease. These data provide an unprecedented overview of RNA-binding proteins and their targets, and constitute an invaluable resource for determining post-transcriptional regulatory mechanisms in eukaryotes.
C1 [Ray, Debashish; Weirauch, Matthew T.; Najafabadi, Hamed S.; Albu, Mihai; Zheng, Hong; Yang, Ally; Na, Hong; Irimia, Manuel; Fraser, Andrew G.; Blencowe, Benjamin J.; Morris, Quaid D.; Hughes, Timothy R.] Univ Toronto, Donnelly Ctr, Toronto, ON M5S 3E1, Canada.
   [Kazan, Hilal; Morris, Quaid D.] Univ Toronto, Dept Comp Sci, Toronto, ON M5S 2E4, Canada.
   [Cook, Kate B.; Li, Xiao; Gueroussov, Serge; Lipshitz, Howard D.; Fraser, Andrew G.; Blencowe, Benjamin J.; Morris, Quaid D.; Hughes, Timothy R.] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A8, Canada.
   [Najafabadi, Hamed S.; Frey, Brendan J.; Morris, Quaid D.] Univ Toronto, Dept Elect & Comp Engn, Toronto, ON M5S 3G4, Canada.
   [Matzat, Leah H.; Dale, Ryan K.; Lei, Elissa P.] NIDDK, Lab Cellular & Dev Biol, NIH, Bethesda, MD 20892 USA.
   [Smith, Sarah A.; Yarosh, Christopher A.; Nabet, Behnam; Carstens, Russ P.; Lynch, Kristen W.] Univ Penn, Perelman Sch Med, Dept Med, Philadelphia, PA 19104 USA.
   [Kelly, Seth M.; Corbett, Anita H.] Emory Univ, Sch Med, Dept Biochem, Atlanta, GA 30322 USA.
   [Mecenas, Desirea; Piano, Fabio] NYU, Dept Biol, New York, NY 10003 USA.
   [Mecenas, Desirea; Piano, Fabio] NYU, Ctr Genom & Syst Biol, New York, NY 10003 USA.
   [Li, Weimin; Laishram, Rakesh S.; Anderson, Richard A.] Univ Wisconsin, Sch Med & Publ Hlth, Mol & Cellular Pharmacol Program, Madison, WI 53706 USA.
   [Qiao, Mei; Penalva, Luiz O. F.] UTHSCSA, Childrens Canc Res Inst, San Antonio, TX 78229 USA.
C3 University of Toronto; University of Toronto; University of Toronto; University of Toronto; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK); University of Pennsylvania; Emory University; New York University; New York University; University of Wisconsin System; University of Wisconsin Madison; University of Texas System; University of Texas at San Antonio
RP Hughes, TR (corresponding author), Univ Toronto, Donnelly Ctr, Toronto, ON M5S 3E1, Canada.
EM quaid.morris@utoronto.ca; t.hughes@utoronto.ca
FU NIH [1R01HG00570, R01GM084034]; CIHR [MOP-49451, MOP-93671, MOP-125894, MOP-67011, MOP-14409]; Intramural Program of the NIDDK [DK015602-05]; NSERC Alexander Graham Bell Canada Graduate Scholarships; CIHR; CIFAR; Charles H. Best Fellowship; HFSP LT Fellowship; National Cancer Institute [P30CA014520] Funding Source: NIH RePORTER; National Institute of Diabetes and Digestive and Kidney Diseases [ZIADK015602] Funding Source: NIH RePORTER; National Institute of General Medical Sciences [T32GM008061] Funding Source: NIH RePORTER
NR 47
TC 1145
Z9 1429
U1 2
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 JUL 11
PY 2013
VL 499
IS 7457
BP 172
EP 177
DI 10.1038/nature12311
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 179YA
UT WOS:000321557600054
PM 23846655
DA 2026-03-09
ER

PT J
AU Geim, AK
   Grigorieva, IV
AF Geim, A. K.
   Grigorieva, I. V.
TI Van der Waals heterostructures
SO NATURE
LA English
DT Article
ID hexagonal boron-nitride; graphene films; valley polarization; monolayer mos2; dirac fermions; high-quality; large-area; h-bn; growth; superconductivity
AB Research on graphene and other two-dimensional atomic crystals is intense and is likely to remain one of the leading topics in condensed matter physics and materials science for many years. Looking beyond this field, isolated atomic planes can also be reassembled into designer heterostructures made layer by layer in a precisely chosen sequence. The first, already remarkably complex, such heterostructures (often referred to as 'van der Waals') have recently been fabricated and investigated, revealing unusual properties and new phenomena. Here we review this emerging research area and identify possible future directions. With steady improvement in fabrication techniques and using graphene's springboard, van der Waals heterostructures should develop into a large field of their own.
C1 [Geim, A. K.; Grigorieva, I. V.] Univ Manchester, Sch Phys & Astron, Manchester M13 9PL, Lancs, England.
   [Geim, A. K.] Univ Manchester, Ctr Mesosci & Nanotechnol, Manchester M13 9PL, Lancs, England.
C3 University of Manchester; University of Manchester
RP Grigorieva, IV (corresponding author), Univ Manchester, Sch Phys & Astron, Manchester M13 9PL, Lancs, England.
EM irina.grigorieva@man.ac.uk
FU Royal Society; European Research Council; Korber Foundation; Office of Naval Research; Air Force Office of Scientific Research; Engineering and Physical Sciences Research Council [EP/G02491X/1, EP/G035954/1, EP/K005014/1] Funding Source: researchfish; EPSRC [EP/G02491X/1, EP/G035954/1, EP/K005014/1] Funding Source: UKRI
NR 92
TC 9393
Z9 10662
U1 113
U2 6337
PU NATURE PORTFOLIO
PI BERLIN
PA HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 25
PY 2013
VL 499
IS 7459
BP 419
EP 425
DI 10.1038/nature12385
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 187YP
UT WOS:000322157900029
PM 23887427
DA 2026-03-09
ER

PT J
AU Lee, K
   Kim, SW
   Toda, Y
   Matsuishi, S
   Hosono, H
AF Lee, Kimoon
   Kim, Sung Wng
   Toda, Yoshitake
   Matsuishi, Satoru
   Hosono, Hideo
TI Dicalcium nitride as a two-dimensional electride with an anionic electron layer
SO NATURE
LA English
DT Article
ID temperature stable electride; room-temperature; work function; aluminum; surface; ca2n
AB Recent studies suggest that electrides-ionic crystals in which electrons serve as anions-are not exceptional materials but rather a generalized form, particularly under high pressure(1-3). The topology of the cavities confining anionic electrons determines their physical.properties(4). At present, reported confining sites consist only of zero-dimensional cavities or weakly linked channels(4). Here we report a layered-structure electride of dicalcium nitride, Ca2N, which possesses two-dimensionally confined anionic electrons whose concentration agrees well with that for the chemical formula of [Ca2N](+).e(-). Two-dimensional transport characteristics are demonstrated by a high electron mobility (520 cm(2) V-1 s(-1)) and long mean scattering time (0.6 picoseconds) with a mean free path of 0.12 micrometres. The quadratic temperature dependence of the resistivity up to 120 Kelvin indicates the presence of an electron-electron interaction. A striking anisotropic magnetoresistance behaviour with respect to the direction of magnetic field (negative for the field perpendicular to the conducting plane and positive for the field parallel to it) is observed, confirming diffusive two-dimensional transport in dense electron layers. Additionally, band calculations support confinement of anionic electrons within the interlayer space, and photoemission measurements confirm anisotropic low work functions of 3.5 and 2.6 electronvolts, revealing the loosely bound nature of the anionic electrons. We conclude that Ca2N is a two-dimensional electride in terms of [Ca2N](+).e(-).
C1 [Lee, Kimoon; Kim, Sung Wng; Toda, Yoshitake; Hosono, Hideo] Tokyo Inst Technol, Frontier Res Ctr, Midori Ku, Yokohama, Kanagawa 2268503, Japan.
   [Kim, Sung Wng] Sungkyunkwan Univ, Dept Energy Sci, Suwon 440746, Gyeonggi Do, South Korea.
   [Matsuishi, Satoru; Hosono, Hideo] Tokyo Inst Technol, Mat & Struct Lab, Midori Ku, Yokohama, Kanagawa 2268503, Japan.
C3 Institute of Science Tokyo; Tokyo Institute of Technology; Sungkyunkwan University (SKKU); Institute of Science Tokyo; Tokyo Institute of Technology
RP Hosono, H (corresponding author), Tokyo Inst Technol, Frontier Res Ctr, Midori Ku, 4259 Nagatsuta, Yokohama, Kanagawa 2268503, Japan.
EM hosono@msl.titech.ac.jp
FU Funding Program for World-Leading Innovative R&D On Science and Technology (FIRST); JSPS; Element Strategy Initiative Project, MEXT, Japan
NR 30
TC 467
Z9 519
U1 2
U2 528
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 21
PY 2013
VL 494
IS 7437
BP 336
EP 340
DI 10.1038/nature11812
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 095CS
UT WOS:000315312900034
PM 23364689
DA 2026-03-09
ER

PT J
AU Florian, MC
   Nattamai, KJ
   Dörr, K
   Marka, G
   Überle, B
   Vas, V
   Eckl, C
   Andrä, I
   Schiemann, M
   Oostendorp, RAJ
   Scharffetter-Kochanek, K
   Kestler, HA
   Zheng, Y
   Geiger, H
AF Florian, Maria Carolina
   Nattamai, Kalpana J.
   Doerr, Karin
   Marka, Gina
   Ueberle, Bettina
   Vas, Virag
   Eckl, Christina
   Andrae, Immanuel
   Schiemann, Matthias
   Oostendorp, Robert A. J.
   Scharffetter-Kochanek, Karin
   Kestler, Hans Armin
   Zheng, Yi
   Geiger, Hartmut
TI A canonical to non-canonical Wnt signalling switch in haematopoietic stem-cell ageing
SO NATURE
LA English
DT Article
ID progenitor cells; tumor-suppressor; pathways; cdc42; proliferation; rejuvenation; cooperate; muscle; notch; fate
AB Many organs with a high cell turnover (for example, skin, intestine and blood) are composed of short-lived cells that require continuous replenishment by somatic stem cells(1,2). Ageing results in the inability of these tissues to maintain homeostasis and it is believed that somatic stem-cell ageing is one underlying cause of tissue attrition with age or age-related diseases. Ageing of haematopoietic stem cells (HSCs) is associated with impaired haematopoiesis in the elderly(3-6). Despite a large amount of data describing the decline of HSC function on ageing, the molecular mechanisms of this process remain largely unknown, which precludes rational approaches to attenuate stem-cell ageing. Here we report an unexpected shift from canonical to non-canonical Wnt signalling in mice due to elevated expression of Wnt5a in aged HSCs, which causes stem-cell ageing. Wnt5a treatment of young HSCs induces ageing-associated stem-cell apolarity, reduction of regenerative capacity and an ageing-like myeloid-lymphoid differentiation skewing via activation of the small Rho GTPase Cdc42. Conversely, Wnt5a haploinsufficiency attenuates HSC ageing, whereas stem-cell-intrinsic reduction of Wnt5a expression results in functionally rejuvenated aged HSCs. Our data demonstrate a critical role for stem-cell-intrinsic non-canonical Wnt5a signalling in HSC ageing.
C1 [Florian, Maria Carolina; Doerr, Karin; Marka, Gina; Ueberle, Bettina; Vas, Virag; Scharffetter-Kochanek, Karin; Geiger, Hartmut] Univ Ulm, Dept Dermatol & Allerg Dis, D-89091 Ulm, Germany.
   [Nattamai, Kalpana J.; Zheng, Yi; Geiger, Hartmut] Cincinnati Childrens Hosp Med Ctr, Div Expt Hematol & Canc Biol, Cincinnati, OH 45229 USA.
   [Nattamai, Kalpana J.; Zheng, Yi; Geiger, Hartmut] Univ Cincinnati, Cincinnati, OH 45229 USA.
   [Eckl, Christina; Oostendorp, Robert A. J.] Tech Univ Munich, Klinikum Rechts Isar, Dept Internal Med 3, D-81675 Munich, Germany.
   [Andrae, Immanuel; Schiemann, Matthias] Tech Univ Munich, Inst Med Microbiol Immunol & Hyg, D-81675 Munich, Germany.
   [Kestler, Hans Armin] Univ Ulm, Dept Bioinformat & Syst Biol, Inst Neuroinformat, D-89091 Ulm, Germany.
C3 Ulm University; Cincinnati Children's Hospital Medical Center; University System of Ohio; University of Cincinnati; Technical University of Munich; University of Munich; Technical University of Munich; Ulm University
RP Geiger, H (corresponding author), Univ Ulm, Dept Dermatol & Allerg Dis, D-89091 Ulm, Germany.
EM hartmut.geiger@uni-ulm.de
FU Deutsche Forschungsgemeinschaft [KFO 142, GE2063/1, SFB 1074]; German Federal Ministry of Education and Research; Excellence program of the Baden-Wurttemberg Foundation; National Institute of Health [HL076604, DK077762, AG040118]; Edward P. Evans foundation; European Commission (FP7 Marie Curie Initial Training Network MARRIAGE); Department of Medicine of Ulm University
NR 31
TC 239
Z9 280
U1 0
U2 57
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD NOV 21
PY 2013
VL 503
IS 7476
BP 392
EP +
DI 10.1038/nature12631
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 254KG
UT WOS:000327163200040
PM 24141946
DA 2026-03-09
ER

PT J
AU Sun, J
   Timurdogan, E
   Yaacobi, A
   Hosseini, ES
   Watts, MR
AF Sun, Jie
   Timurdogan, Erman
   Yaacobi, Ami
   Hosseini, Ehsan Shah
   Watts, Michael R.
TI Large-scale nanophotonic phased array
SO NATURE
LA English
DT Article
ID light; antenna
AB Electromagnetic phased arrays at radio frequencies are well known and have enabled applications ranging from communications to radar, broadcasting and astronomy(1). The ability to generate arbitrary radiation patterns with large-scale phased arrays has long been pursued. Although it is extremely expensive and cumbersome to deploy large-scale radiofrequency phased arrays(2), optical phased arrays have a unique advantage in that the much shorter optical wavelength holds promise for large-scale integration(3). However, the short optical wavelength also imposes stringent requirements on fabrication. As a consequence, although optical phased arrays have been studied with various platforms(4-8) and recently with chip-scale nanophotonics(9-12), all of the demonstrations so far are restricted to one-dimensional or small-scale two-dimensional arrays. Here we report the demonstration of a large-scale two-dimensional nanophotonic phased array (NPA), in which 64 x 64 (4,096) optical nanoantennas are densely integrated on a silicon chip within a footprint of 576 mu m x 576 mu m with all of the nanoantennas precisely balanced in power and aligned in phase to generate a designed, sophisticated radiation pattern in the far field. We also show that active phase tunability can be realized in the proposed NPA by demonstrating dynamic beam steering and shaping with an 8 x 8 array. This work demonstrates that a robust design, together with state-of-the-art complementary metal-oxide-semiconductor technology, allows large-scale NPAs to be implemented on compact and inexpensive nanophotonic chips. In turn, this enables arbitrary radiation pattern generation using NPAs and therefore extends the functionalities of phased arrays beyond conventional beam focusing and steering, opening up possibilities for large-scale deployment in applications such as communication, laser detection and ranging, three-dimensional holography and biomedical sciences, to name just a few.
C1 [Sun, Jie; Timurdogan, Erman; Yaacobi, Ami; Hosseini, Ehsan Shah; Watts, Michael R.] MIT, Elect Res Lab, Cambridge, MA 02139 USA.
C3 Massachusetts Institute of Technology (MIT)
RP Watts, MR (corresponding author), MIT, Elect Res Lab, Cambridge, MA 02139 USA.
EM mwatts@mit.edu
FU Defense Advanced Research Projects Agency (DARPA) of the United States [HR0011-12-2-0007]; DARPA POEM [HR0011-11-C-0100]
NR 29
TC 1088
Z9 1408
U1 18
U2 794
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 10
PY 2013
VL 493
IS 7431
BP 195
EP 199
DI 10.1038/nature11727
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 066YY
UT WOS:000313259600034
PM 23302859
DA 2026-03-09
ER

PT J
AU Rao, S
   Chun, C
   Fan, JQ
   Kofron, JM
   Yang, MB
   Hegde, RS
   Ferrara, N
   Copenhagen, DR
   Lang, RA
AF Rao, Sujata
   Chun, Christina
   Fan, Jieqing
   Kofron, J. Matthew
   Yang, Michael B.
   Hegde, Rashmi S.
   Ferrara, Napoleone
   Copenhagen, David R.
   Lang, Richard A.
TI A direct and melanopsin-dependent fetal light response regulates mouse eye development
SO NATURE
LA English
DT Article
ID vegf; apoptosis; vessel; opsin; cells
AB Vascular patterning is critical for organ function. In the eye, there is simultaneous regression of embryonic hyaloid vasculature(1) (important to clear the optical path) and formation of the retinal vasculature (important for the high metabolic demands of retinal neurons). These events occur postnatally in the mouse. Here we have identified a light-response pathway that regulates both processes. We show that when mice are mutated in the gene (Opn4) for the atypical opsin melanopsin(3-5), or are dark-reared from late gestation, the hyaloid vessels are persistent at 8 days post-partum and the retinal vasculature overgrows. We provide evidence that these vascular anomalies are explained by a light-response pathway that suppresses retinal neuron number, limits hypoxia and, as a consequence, holds local expression of vascular endothelial growth factor (VEGFA) in check. We also show that the light response for this pathway occurs in late gestation at about embryonic day 16 and requires the photopigment in the fetus and not the mother. Measurements show that visceral cavity photon flux is probably sufficient to activate melanopsin-expressing retinal ganglion cells in the mouse fetus. These data thus show that light the stimulus for function of the mature eye is also critical in preparing the eye for vision by regulating retinal neuron number and initiating a series of events that ultimately pattern the ocular blood vessels.
C1 [Rao, Sujata; Fan, Jieqing; Yang, Michael B.; Lang, Richard A.] Cincinnati Childrens Hosp Med Ctr, Div Pediat Ophthalmol, Abrahamson Pediat Eye Inst, Visual Syst Grp, Cincinnati, OH 45229 USA.
   [Chun, Christina; Copenhagen, David R.] Univ Calif San Francisco, Dept Ophthalmol, San Francisco, CA 94158 USA.
   [Chun, Christina; Copenhagen, David R.] Univ Calif San Francisco, Dept Physiol, San Francisco, CA 94158 USA.
   [Kofron, J. Matthew; Hegde, Rashmi S.; Lang, Richard A.] Cincinnati Childrens Hosp Med Ctr, Div Dev Biol, Cincinnati, OH 45229 USA.
   [Yang, Michael B.; Lang, Richard A.] Univ Cincinnati, Coll Med, Dept Ophthalmol, Cincinnati, OH 45229 USA.
   [Ferrara, Napoleone] Genentech Inc, San Francisco, CA 94080 USA.
C3 Cincinnati Children's Hospital Medical Center; University of California System; University of California San Francisco; University of California System; University of California San Francisco; Cincinnati Children's Hospital Medical Center; University System of Ohio; University of Cincinnati; Roche Holding; Roche Holding USA; Genentech
RP Lang, RA (corresponding author), Cincinnati Childrens Hosp Med Ctr, Div Pediat Ophthalmol, Abrahamson Pediat Eye Inst, Visual Syst Grp, Cincinnati, OH 45229 USA.
EM cope@phy.ucsf.edu; richard.lang@cchmc.org
FU NIH [AR-47363]; Abrahamson Pediatric Eye Institute of CCHMC; That Man May See at UCSF; Research to Prevent Blindness; March of Dimes
NR 25
TC 175
Z9 215
U1 0
U2 33
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 14
PY 2013
VL 494
IS 7436
BP 243
EP 246
DI 10.1038/nature11823
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 092QS
UT WOS:000315137700041
PM 23334418
DA 2026-03-09
ER

PT J
AU Civril, F
   Deimling, T
   Mann, CCD
   Ablasser, A
   Moldt, M
   Witte, G
   Hornung, V
   Hopfner, KP
AF Civril, Filiz
   Deimling, Tobias
   Mann, Carina C. de Oliveira
   Ablasser, Andrea
   Moldt, Manuela
   Witte, Gregor
   Hornung, Veit
   Hopfner, Karl-Peter
TI Structural mechanism of cytosolic DNA sensing by cGAS
SO NATURE
LA English
DT Article
ID cyclic gmp-amp; innate immune sensor; i interferon; recognition receptors; 2nd-messenger; inflammasome; surveillance; helicase; adapter
AB Cytosolic DNA arising from intracellular bacterial or viral infections is a powerful pathogen-associated molecular pattern (PAMP) that leads to innate immune host defence by the production of type I interferon and inflammatory cytokines. Recognition of cytosolic DNA by the recently discovered cyclic-GMP-AMP (cGAMP) synthase (cGAS) induces the production of cGAMP to activate the stimulator of interferon genes (STING). Here we report the crystal structure of cGAS alone and in complex with DNA, ATP and GTP along with functional studies. Our results explain the broad DNA sensing specificity of cGAS, show how cGAS catalyses dinucleotide formation and indicate activation by a DNA-induced structural switch. cGAS possesses a remarkable structural similarity to the antiviral cytosolic double-stranded RNA sensor 2'-5'oligoadenylate synthase (OAS1), but contains a unique zinc thumb that recognizes B-form double-stranded DNA. Our results mechanistically unify dsRNA and dsDNA innate immune sensing by OAS1 and cGAS nucleotidyl transferases.
C1 [Civril, Filiz; Deimling, Tobias; Mann, Carina C. de Oliveira; Moldt, Manuela; Witte, Gregor; Hopfner, Karl-Peter] Univ Munich, Dept Biochem, D-81377 Munich, Germany.
   [Civril, Filiz; Deimling, Tobias; Mann, Carina C. de Oliveira; Moldt, Manuela; Witte, Gregor; Hopfner, Karl-Peter] Univ Munich, Gene Ctr, D-81377 Munich, Germany.
   [Ablasser, Andrea; Hornung, Veit] Univ Bonn, Univ Hosp, Unit Clin Biochem, Inst Clin Chem & Clin Pharmacol, D-53127 Bonn, Germany.
   [Hopfner, Karl-Peter] Ctr Integrated Prot Sci, D-81377 Munich, Germany.
C3 University of Munich; University of Munich; University of Bonn; University of Munich
RP Hopfner, KP (corresponding author), Univ Munich, Dept Biochem, Marchioninistr 15, D-81377 Munich, Germany.
EM hopfner@genzentrum.lmu.de
FU National Institutes of Health [U19AI083025]; European Research Council [322869]; Center for Integrated Protein Science Munich (CIPSM); DFG [3717/2-1, SFB670]; ERC [243046];  [GRK1721]; European Research Council (ERC) [243046, 322869] Funding Source: European Research Council (ERC)
NR 42
TC 731
Z9 881
U1 10
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 JUN 20
PY 2013
VL 498
IS 7454
BP 332
EP +
DI 10.1038/nature12305
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 166XI
UT WOS:000320592900033
PM 23722159
DA 2026-03-09
ER

PT J
AU Shalek, AK
   Satija, R
   Adiconis, X
   Gertner, RS
   Gaublomme, JT
   Raychowdhury, R
   Schwartz, S
   Yosef, N
   Malboeuf, C
   Lu, DN
   Trombetta, JJ
   Gennert, D
   Gnirke, A
   Goren, A
   Hacohen, N
   Levin, JZ
   Park, H
   Regev, A
AF Shalek, Alex K.
   Satija, Rahul
   Adiconis, Xian
   Gertner, Rona S.
   Gaublomme, Jellert T.
   Raychowdhury, Raktima
   Schwartz, Schraga
   Yosef, Nir
   Malboeuf, Christine
   Lu, Diana
   Trombetta, John J.
   Gennert, Dave
   Gnirke, Andreas
   Goren, Alon
   Hacohen, Nir
   Levin, Joshua Z.
   Park, Hongkun
   Regev, Aviv
TI Single-cell transcriptomics reveals bimodality in expression and splicing in immune cells
SO NATURE
LA English
DT Article
ID messenger-rna-seq; pathway; level
AB Recent molecular studies have shown that, even when derived from a seemingly homogenous population, individual cells can exhibit substantial differences in gene expression, protein levels and phenotypic output(1-5), with important functional consequences(4,5). Existing studies of cellular heterogeneity, however, have typically measured only a few pre-selected RNAs1,2 or proteins(5,6) simultaneously, because genomic profiling methods(3) could not be applied to single cells until very recently(7-10). Here we use single-cell RNA sequencing to investigate heterogeneity in the response of mouse bone-marrow-derived dendritic cells (BMDCs) to lipopolysaccharide. We find extensive, and previously unobserved, bimodal variation in messenger RNA abundance and splicing patterns, which we validate by RNA-fluorescence in situ hybridization for select transcripts. In particular, hundreds of key immune genes are bimodally expressed across cells, surprisingly even for genes that are very highly expressed at the population average. Moreover, splicing patterns demonstrate previously unobserved levels of heterogeneity between cells. Some of the observed bimodality can be attributed to closely related, yet distinct, known maturity states of BMDCs; other portions reflect differences in the usage of key regulatory circuits. For example, we identify a module of 137 highly variable, yet co-regulated, antiviral response genes. Using cells from knockout mice, we show that variability in this module may be propagated through an interferon feedback circuit, involving the transcriptional regulators Stat2 and Irf7. Our study demonstrates the power and promise of single-cell genomics in uncovering functional diversity between cells and in deciphering cell states and circuits.
C1 [Shalek, Alex K.; Gertner, Rona S.; Gaublomme, Jellert T.; Park, Hongkun] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA.
   [Shalek, Alex K.; Gertner, Rona S.; Gaublomme, Jellert T.; Park, Hongkun] Harvard Univ, Dept Phys, Cambridge, MA 02138 USA.
   [Satija, Rahul; Adiconis, Xian; Raychowdhury, Raktima; Schwartz, Schraga; Yosef, Nir; Malboeuf, Christine; Lu, Diana; Trombetta, John J.; Gennert, Dave; Gnirke, Andreas; Goren, Alon; Hacohen, Nir; Levin, Joshua Z.; Park, Hongkun; Regev, Aviv] Broad Inst MIT & Harvard, Cambridge Ctr 7, Cambridge, MA 02142 USA.
   [Goren, Alon] Massachusetts Gen Hosp, Dept Pathol, Charlestown, MA 02129 USA.
   [Goren, Alon] Massachusetts Gen Hosp, Ctr Syst Biol, Charlestown, MA 02129 USA.
   [Goren, Alon] Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA 02129 USA.
   [Hacohen, Nir] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Charlestown, MA 02129 USA.
   [Hacohen, Nir] Massachusetts Gen Hosp, Dept Med, Charlestown, MA 02129 USA.
   [Regev, Aviv] MIT, Howard Hughes Med Inst, Dept Biol, Cambridge, MA 02140 USA.
C3 Harvard University; Harvard University; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; 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 University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Howard Hughes Medical Institute; Massachusetts Institute of Technology (MIT)
RP Park, H (corresponding author), Harvard Univ, Dept Chem & Chem Biol, 12 Oxford St, Cambridge, MA 02138 USA.
EM Hongkun_Park@harvard.edu; aregev@broad.mit.edu
FU National Institutes of Health (NIH) [1F32HD075541-01, U54 AI057159, DP2 OD002230, 5DP1OD003893-03, DP1OD003958-01]; Charles H. Hood Foundation; NIH CEGS Award [1P50HG006193-01]; Broad Institute; HHMI; Klarman Cell Observatory at the Broad Institute
NR 30
TC 896
Z9 1257
U1 0
U2 308
PU NATURE PUBLISHING 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 13
PY 2013
VL 498
IS 7453
BP 236
EP 240
DI 10.1038/nature12172
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 162RR
UT WOS:000320283400050
PM 23685454
DA 2026-03-09
ER

